Myriad Genetics, Inc., the owner of the patents, brought the case to Federal Court of Appeals, which overturned the lower court’s decision on July 29 in a 2-1 ruling that has, at least for the time being, reaffirmed the patentability of human genes. Notably, the Obama Administrations Justice Department broke with the Patent and Trademark Office, a co-defendant in the case, in filing an amicus brief in support of the plaintiffs claim that the genes should not be patentable.

The Appeals Court also upheld Myriad’s patents on procedures for therapeutic research on BRCA 1 and 2, but agreed with the lower court that Myriad’s processes for “analyzing” and “comparing” the genes are not patentable. Despite this small concession, it does not seem likely that this will make it easier for scientists who are unaffiliated with Myriad to conduct significant research on BRCA 1 and 2.

“[Myriad’s] short sequence claims [on BRCA 1 and 2] will continue to pose problems,” said Arti Rai, the Elvin R. Latty Professor of Law at Duke Law School and an expert in patent law and innovation policy, in an interview with Science Progress. “I’m not sure that the plaintiffs at the end of the day are in a better position,” she said, noting that they will probably run into many of the same patent infringement issues that they have in the past.

Though the full effects of this ruling on the biotechnology industry and the cancer research community remain to be seen, it is by no means the last word on the issue of gene patents. The plaintiffs, a coalition of doctors, patients, breast cancer researchers, research institutions, and medical associations, are expected to ask for an en banc rehearing—in which all of the justices in the court of appeals would sit for the case, instead of a panel of only three—or appeal the case to the Supreme Court. The Supreme Court can let the appeals court decision stand, or take up the case and issue its own ruling.

Why were genes patentable in the first place?

Patents for biological materials have long been a contentious issue, and decades of Supreme Court cases have interpreted U.S. patent law, which was written over 200 years ago, to fit the complexities of property in modern biotechnology. Currently, the United States Patent and Trademark Office, or USPTO, can issue patents for genes, animals, bacteria, and plants—as long as they are, according to the Patent Act of 1790, “any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof.”

Patents for biological materials must also fit the “product of nature doctrine,” a standard that excludes entities that occur in nature from patent eligibility. The doctrine was first used in ex Parte Latimer (1889) when the U.S. Patent Commissioner rejected a patent application for isolated pine needle fibers. It was further developed in Funk Bros. Seed Company vs. Kalo Inoculant Co. (1948) when the Supreme Court ruled that natural phenomena and processes are “free to all men and reserved exclusively to none,” and rejected a patent application for a novel mixture of bacteria and soil.

Genes, bacteria, and animals seem like they should fall in the “product of nature” category, but later Supreme Court decisions have shown that sufficient modification of a naturally occurring entity can make it enough of a “new manufacture or composition of matter” to be eligible for a patent. In Diamond v. Chakrabarty (1980), the Supreme Court permitted a patent for a genetically engineered bacterium. In 1984, the USPTO granted a patent to the creators of the “oncomouse,” a mouse that was engineered to express cancer genes in every cell in its body.

Thanks to the precedents set by these and other cases, the USPTO has issued over 40,000 gene patents to date. Myriad Genetics justified their own gene patents via the argument that isolated forms of BRCA 1 and 2 do not occur in nature, and that such isolation results in the formation of different chemical bond structures within the molecules.

In 2010, the New York district court invalidated the BRCA 1 and 2 patents on the basis that the genes, even when isolated, have not acquired any changes to the fundamental nature of its DNA sequence or the genetic information they contain. The majority opinions of the recent federal appeals court ruling, on the contrary, agreed with Myriad Genetics’ original justification for the patent. They also noted that isolated BRCA 1 and 2 can be modified in the lab to form cDNAs, which can then be used to develop genetic probes and markers—a process for which BRCA 1 and 2 are only useful if they are isolated. The dissenting opinion by Justice William Bryson, however, held that the BRCA 1 and 2 genes on their own should not be patentable because Myriad did not discover the genes or use any novel techniques to isolate them. However, he held that the cDNAs, since they are modified by researchers, are patentable.

Gene patents and scientific progress

While the technicalities of what constitutes a “product of nature” or a “manufacture” seem to spark disagreement in the case of isolated genes, the stakes are high for a decision on gene patentability.  According to the U.S. Constitution, patents are supposed to “promote the Progress of Science and useful Arts” by giving inventors the exclusive right to exploit their inventions for a limited period of time.

This is true much of the time, as patents encourage innovation and scientific progress by ensuring that inventors can reap the benefits of their work. Plus, a ruling that would invalidate all existing gene patents could potentially have far-reaching negative effects on patent holders and the biotechnology industry in general.

But the plaintiffs in the Myriad case disagree, and argue that gene patents significantly impede, rather than promote, scientific progress. Researchers from Oncormed and the University of Pennsylvania Genetic Diagnostic Laboratory, or GDL, who are plaintiffs in the case, were already conducting research on and offering their own diagnostic genetic testing services for BRCA 1 and 2 when Myriad acquired its patents on the genes and associated research and testing processes. However, these researchers were forced to stop conducting diagnostic testing and therapeutic research in the late 1990s after Myriad sent them cease and desist orders for patent infringement.

Myriad’s vigorous enforcement of their BRCA patents has rendered them the sole provider of genetic testing for BRCA 1 and 2 in the United States. As a result, women who wish to learn of their genetic risk for breast and ovarian cancer cannot turn to other diagnostics providers for confirmatory tests. Nor can patients seek cheaper alternatives to Myriad’s services, whose BRCA tests cost between $250 and $4,000.

In addition to limiting the competition among diagnostic test providers, Myriad’s monopoly on BRCA also allows them to control the progress of BRCA research. Other scientists cannot research potential improvements for BRCA therapeutics or expand scientific understanding of high-risk BRCA gene mutations without infringing Myriad’s patents.

An issue of authority

The federal appeals court opinions acknowledge the question of whether gene patents promote or impede scientific progress, but instead of answering it outright, they defer it to Congress and do not deal with the case beyond the scope of patent law. “If the law is to be changed, and DNA inventions excluded from the broad scope of [patent law] contrary to the settled expectation of the inventing community, the decision must come not from the courts, but from Congress,” wrote Judge Lourie in the court opinion.

While Congress might be in a better position than the judicial system to consider social, economic, and scientific implications of gene patents, they have never been particularly successful in passing legislation concerning patentable subject matter. “These are policy issues to be decided by Congress, but the fact is that Congress is unlikely to act in this area,” said Rai.

If Congress doesn’t speak out on the issue, the Supreme Court has the authority to make its own decision on the patentability of genes. “For better or for worse,” said Rai, “a court decision in this area may end up being the final word.”

As such, the federal appeals court ruling is just another step in what has been, and what will continue to be, a long process of sorting out property in the genome. The final outcome for the genetic research community and gene patent holders remains to be seen.

Michelle Spektor recently completed her internship at Science Progress and will complete her bachelor’s degree at Cornell University this year.

The case comes on the heels of a scientific discovery last December, when two research teams independently reported that they could reconstruct fetal DNA taken from the mother’s blood. Analyzing this DNA would allow testing for a range of genetic conditions, including one of the most common chromosomal disorders, Down syndrome, earlier in pregnancy than ever before. Additionally, the simple blood draw would evade the risk of miscarriage that comes with current methods of prenatal screening, including amniocentesis (which involves sticking a needle through the abdomen and into the uterus) and chorionic villus sampling (done either by a needle through the abdomen or by prodding a tube through the vagina and cervix). An early, noninvasive test could in theory become an option for all pregnant women, not just those who carry a high risk of genetic disease.

Due to the earlier testing methods, Down syndrome births decreased 11 percent between 1989 and 2006. Currently, over 80 percent of fetuses diagnosed with Down syndrome are aborted in the United States. These figures hit 91 to 93 percent in the United Kingdom and other parts of Europe. Learning a prenatal diagnosis at nine weeks, in contrast to the 10 to 12 weeks typical for chorionic villus sampling and 15 to 20 weeks for amniocentesis, could alleviate some of the physical and emotional burdens that accompany later abortions, causing these numbers to spike even higher.

A scroll through the online comments to the news stories reveals that the reaction in New Zealand was not unique. “Where do we draw the line?” one user asks. “Screen for autism? Screen for ADD? Abort those kids? How about just screen for anyone with an IQ <100? This notion of ‘designer babies’ is just appalling!” Another laments, “Welcome to the world of ‘Gattaca,’ designer babies and a new ‘master race.’” And yet another: “Anybody who aborts a child with a disability will never know what they are missing, and it is truly your loss, and the world’s loss. I weep for all those unborn babies who never will be able to share their gifts … an unspeakable tragedy.”

Hold that thought.

The Internet critics are right to make the point, as Marcy Darnovsky at Science Progress and many others have, that new developments in the laboratory necessitate profound moral reflection outside of it. But how much of these fears are justified? Is this really eugenics by abortion?

Like it or not, we are afforded a lot of liberty when it comes to reproductive decision-making. Parents may choose how to use their reproductive capacities, what kinds of children they want, and how to raise them according to their own standards of what they believe is best, free from government interference “unless the state could show compelling justification for the restriction,” writes bioethicist John Robertson. This freedom has a legal backing too, with the Supreme Court long protecting the rights of people to make their own decisions with regard to marriage, procreation, motherhood, family, and child rearing. If it’s “designer babies” we are worried about, we are already there. Women can now seek egg donors with criteria as specific as ethnicity and minimum height and SAT scores. Preimplantation genetic diagnosis involves screening for genetic blemishes in embryos created through in vitro fertilization and cherry-picking only the healthy ones to implant.

There is also the freedom not to have kids at all. Regardless of one’s personal opinion on the matter, abortion is legally permitted in this country. Moreover, a woman does not have to disclose her reasons for that choice. If we say yes to abortion for no reason at all, it seems illogical to forbid it for a well-defined reason, such as genetic disease.

So what’s the problem? Answering that means figuring out whether prenatal genetic testing is categorically different—or different only in degree—from what is accepted and established.

Bioethicists have spilt a lot of ink doing just that, and many of their arguments have converged on a similar sentiment. We live in a society in which we nobly aim to promote acceptance of diverse groups. Genetic testing undermines that aim, the argument goes, for it sends an intrinsically offensive message that the lives of people with disabilities are less valuable. As bioethicist Adrienne Asch opined, “As with discrimination more generally, with prenatal diagnosis, a single trait stands in for the whole…. The test sends the message that there’s no need to find out about the rest.” More recently, the New Zealand claimants agree: “The screening programme… devalues children with Down syndrome and is offensive to parents.” Allowing or even encouraging selective abortion based on a single “undesirable” trait is discriminatory, and it should be condemned when directed toward a fetus just as it is when targeting those who have already been born.

Genetic counselors have apparently done little to ease this concern. Counselors and the disability community have a “tenuous relationship,” claims one recent article, in which counselors often hold more negative perspectives on disability than those who are directly affected. These attitudes influence how counselors communicate with patients about prenatal decisions, causing disabled people to feel judged in clinical settings. Adding to the shaky trust is the fact that the National Society of Genetic Counselors, which represents the profession in the United States, has publicly connected itself more with abortion service providers than with disease advocacy organizations.

Doctors are not sporting spotless images either. One analysis concluded that written materials about prenatal screening are often insufficient, and the limitations of testing are not adequately explained. The latter shortcoming is especially problematic in genetics, where testing is probabilistic by nature and thus demands a nuanced explanation to be accurate. Unfortunately, a whopping 45 percent of obstetric fellows say their training on how to deliver a prenatal diagnosis is “barely adequate” or “nonexistent.”

Still, the critique of discrimination relies on an assumption: an attitude toward a diagnosis in a fetus, particularly one’s own fetus, represents an attitude toward an existing person. And social science research shows this may not be true. One discerning study surveyed 197 pregnant women about their beliefs on testing for Down syndrome in their own fetuses along with their attitudes toward the Down syndrome community at large. While unfavorable attitudes toward people with Down syndrome did indeed correlate with the women’s intentions to screen, favorable attitudes toward people with Down syndrome could not predict whether screening would be used. That is, many women who expressed positive attitudes toward the Down syndrome community still wanted to test their own prospective children.

The authors explain this result by pointing to previous research showing that people often make clear mental distinctions between people with a disability who are already born and those yet to be born. As a result, it is perfectly compatible to respect those with Down syndrome while hoping to have a baby without it. One sociologist has dubbed this two-fold position “important to test, important to support.”

Which brings up another big flaw in the testing-is-discrimination rebuke: it puts extraordinary pressure on any given person. Who doesn’t want a healthy baby? A parent’s priority is cultivating the best possible life and opportunities for their children. Asking her to forgo valuable disease testing for the sake of expressing a socially appealing message is making a child into a sacrificial lamb. Some take this argument even farther, saying that prenatal disease testing is not just something parents should do, but rather an ethical obligation. It would be negligent not to screen for genetic diseases if the opportunity to do so existed.

A similar case can be made for nonmedical traits. Want to screen for height genes? For whatever reason, studies have shown that taller people in both genders reach more leadership positions and make more money—an extra $1,000 a year or so—even after factoring out experience and education. And who says it has to end there? We could then open ourselves to the really contentious issue of favoring males because of the regrettable realities of a sexist world. The bottom line being: You can hardly fault a parent for wanting to optimize her child’s social lot. Don’t hate the player; hate the game.

But that doesn’t render the original grievance invalid. Live in a world where everyone acts in his own best interest, and the result could be the so-called “tragedy of the commons” situation, where the group as a whole loses. A powerful example is the selective abortion of female fetuses in India and China, which has caused a noticeably skewed gender ratio leading to a surplus of bachelors unable to find brides. In societies that value marriage as a staple of social acceptance, officials fear an increase in crime by the new male “outcast” group, greater use of the sex industry, and even an increase in the kidnapping of women. Extreme cases like this demonstrate that it can’t be on the shoulders of individuals to do the right thing for society at large. It becomes the law’s responsibility to step in and regulate whatever it is that would damage things for all of us.

This clash in priorities, with the competing interests of parental freedom on one hand and our antipathy toward intolerance (with a worst case scenario of dangerous social ills) on the other, is where the debate often comes to a halt. Both are important values, and saying one overrides the other is a matter of personal inclination.

But maybe there’s a way around taking a blanket stance to support either side. It involves acknowledging that that not all traits are created equal—at least not for prenatal testing purposes. Screening is morally acceptable for some but not others. A clever idea for making that distinction comes from Sara Goering, who uses the values of philosopher John Rawls to distinguish between morally acceptable and objectionable forms of genetic engineering (actually manipulating a fetus’s genome to give it preferred traits, rather than simply testing for what is already there). Some traits are inherently good, she says, regardless of environment. Other traits are only deemed valuable because of subjective prejudices that vary based on your time and place in the world. She gives the examples of cystic fibrosis and Tay-Sachs disease as belonging to the first category and race, height, and sexual preference in the second. Using science to our benefit while rejecting discrimination would involve engineering only those qualities in the first group, she argues. Otherwise, we would be exacerbating arbitrary bias, making us complicit in an unjust system.

An obvious interpretation of Goering’s ideas with regard to testing is drawing the line between medical and nonmedical traits. Based on the unfortunate mental and physical confines of disease, good health can be seen as an objective way of having a better life. In contrast, tallness as better is a societal construct. There is no intrinsic benefit of being tall (maybe they can reach higher things; but they also are worse at escaping notice). Rather than yielding to these prejudices, we should be striving to rectify the existing injustices.

Of course, this is not a perfect science. There is bound to be enormous disagreement over objective versus subjective good. Just look at the dispute over deafness. While most people view hearing loss as a disability, there are those in deaf community who see it as a lifestyle that they want to share with their children.

Realistically, much of this theoretical handwringing may prove moot. Are our prejudices so overpowering that we’d pick abortion over a child with the “wrong” height or eye color? Some people would undoubtedly favor testing without even considering abortion, but rather to prepare better for the baby. Others would opt not to know at all. Characterizing these preferences would require further empirical investigations, and there would surely be very different considerations in societies where biases are more engrained. But intuitively, at least in the United States, it is hard to picture large masses of people opting for prenatal testing of traits like eye color as the deciding factor for whether their child should be born.

This is a passionate issue. People have begun to speak out, whether through semianonymous Internet comments or an official complaint to the International Criminal Court. The concerns are legitimate. Detractors do not need “what if?” slippery slope arguments, often accompanied by references to science fiction, to vindicate their objections. They also do not need emotionally charged analogies to heinous past crimes of eugenics to grant them credibility. There are issues in science that have become so entwined with politics—where people split along predictable party lines, and a presumed clash of values automatically demonizes any opposing view—that open discourse is vetoed before it can begin. Making moral headway in prenatal testing requires that it doesn’t join those ranks.

There is something to be said for following our moral intuitions. There is even more to be said for a rational analysis of their validity, for an informed and respectful exchange of ideas.

Ilana Yurkiewicz holds a B.S. from Yale University and was a staff writer at The News & Observer. Currently an intern with the Presidential Commission for the Study of Bioethical Issues, she will matriculate at Harvard Medical School in the fall.

Download the introduction and summary in pdf here, or read on.

The human genome sequence has been fully completed for a decade now and the price of full genome sequencing is dropping precipitously. Many believe that with these developments, a new era of personalized medicine is about to hit full speed. Personalized medicine is essentially “the use of genetic susceptibility or pharmacogenetic testing to tailor an individual’s preventive care or drug therapy,” although some definitions also include the development of patient outcomes research, health information technology, and care delivery models. Put more simply, it means the development of  medicines and therapies tailored to patients’ unique genetic traits and risks.

The field is evolving rapidly but many hurdles still remain. Individually tailored drugs based on a patient’s genetic makeup are far off, and the cost of developing drugs for genetic subpopulations with largely similar genetic traits for one or more diseases hinders developments in this arena. Similarly, the lack of standards surrounding direct-to-consumer genetic tests and the lack of robust, large-scale genomic data for many diseases and conditions are additional hurdles.

Nevertheless, personalized medicine is making its way into the mainstream. Estimates by PricewaterhouseCoopers indicate that the market for personalized medicine, currently a $232 billion  industry, will grow at a rate of 11 percent annually. Personalized medicine is also making serious strides in the pharmaceutical industry with drugs like the colon cancer drug Erbitux, which is most effective in patients with a certain genetic mutation.

Personalized medicine also has the potential to rein in rising health care costs. For instance, physicians can better prevent adverse drug reactions by using genetic information to calibrate the ideal dosage of the blood-thinning drug Warfarin for an individual patient. This alone could prevent 85,000 serious bleeding cases and 17,000 strokes, and save the health care system $1.1 billion annually.

But the health care and scientific communities will still have to answer important questions about who will have access to these new medical advancements as they develop. Health disparities persist between different groups for various reasons including access to care, lifestyle factors, socioeconomic status, and genetics. Studies indicate that minorities have less access to health care and generally receive a lower quality of care. Studies show that African Americans have lower incidence of breast cancer than white women, for example, but suffer greater mortality. Heart disease is widespread among minorities and a leading killer in the African-American community.

Personalized medicine can potentially alleviate these discrepancies since it could allow physicians to prescribe medication that treats the disease more effectively. African- American women suffer from a more aggressive form of breast cancer that tends to be estrogen resistant, for example. Profiling the genes of the tumor and the genes of the patient could allow a doctor to prescribe the most effective drug regimen.

Yet certain issues regarding racial and ethnic health disparities need to be addressed in order for personalized medicine to offer the greatest benefit to all. This paper examines these issues in detail and then offers some ethical guidelines for policymakers to consider, among them:

• There must be a frank discussion of the social and methodological appropriateness of using race or ethnicity as disease proxies.
• Genetic variation research and clinical trials must systematically incorporate such discussions into their individual study designs and the research itself.
• We cannot ignore structural inequalities in access to health care and in fact should seek to reduce them through research that looks at social, environmental, and behavioral contributions to health status as well as research on the outcomes of different care delivery models for different populations.

In the pages of this report we will demonstrate why these proposed ethical guidelines are
essential to the development of personalized medicine in our country.

Read the full report in pdf here.

Amid the bitter and protracted negotiations over this fiscal year’s federal budget, U.S. investments in science and innovation were largely spared from the deepest cuts some federal programs faced. But they may not be safe for long as Congress considers making further spending cuts in the fiscal year 2012 budget beginning in October against the backdrop of debate this summer over raising the national debt ceiling.

That’s why it is critically important that members of Congress on both sides of the aisle distinguish between federal “spending” and “investments.” What many fiscally conservative lawmakers omit in their zeal to slash spending is that many federal programs actually have positive rates of return, meaning they bring in more revenue—to the government, economy, or both—than they cost the taxpayer. To put it another way, some federal investments are profitable to the public balance sheet and save the taxpayers money in the long run.

Need proof? Look no farther than two reports released last week, which looked at the economic benefits and return on investment in the Human Genome Project, and the National Institutes of Health, respectively, and showed that both federal programs have had a tremendously positive economic impact. Let’s examine each in turn.

The National Institutes of Health and economic growth

The first report “An Economic Engine: NIH Research, Employment, and the Future of the Medical Innovation Sector,” published last week by a consortium of science and research medical organizations, looked at the consequences of the public investment in the NIH on employment and economic output. The study, authored by Dr. Everett Ehrlich, a leading business economist and former Clinton-era undersecretary of commerce, found that the NIH directly and indirectly supported nearly 488,000 public and private sector jobs, and generated $68 billion in new economic activity in 2010 alone. Meanwhile, NIH research grants in FY 2010 cost the taxpayers only $26.6 billion. This would represent a 150 percent single-year return on public investment, counting total economic output from the research as revenue.

The economic activity and jobs supported by the NIH are not limited just to the NIH’s Bethesda campus outside Washington, D.C. They are spread across every state and territory in the country. In 2010 NIH research awards supported 12,000 public and private sector jobs in Georgia, 5,300 in Iowa, 1,300 in Alaska, and 31,000 in Texas, just to name a few.

In California, a company called Syntouch LLC is developing synthetic tactile sensors for prosthetics thanks to NIH-funded research. In Alabama, a company called DiscoveryBioMed, Inc. is using principles discovered by NIH-funded research to identify new therapeutic compounds for respiratory, metabolic, inflammatory, and hyperinflammatory diseases. West Virginia-based Protea Bioscience, Inc. is developing technology based on NIH research that improves the quality, reproducibility, and speed of processing protein samples, a technique that will aide with drug development across the board. See the map below for the number of jobs supported in each state by NIH federal research awards.

Source: Map by Science Progress with data from United for Medical Research

Critics of federal investment in R&D programs often argue that public programs like the NIH crowd out private investment. But a recent study conducted by the National Bureau of Economic Research found that the opposite is in fact true for the NIH. Each dollar of federal investment leads to a 32-cent increase in private medical research investment as discoveries diffuse out of academia and filter into the market. Another study found that NIH-sponsored research was more likely to be considered “advanced,” “novel,” or be related to “orphan diseases” than entirely privately funded drug research. This means that the NIH not only supports an ecosystem of business and innovative companies, but the innovation that comes out of this research is more likely to be novel and substantial.

The evidence in this report contradicts an oft-repeated fiscal conservative argument that public investments cannot create jobs. To quote the report, “simply put, NIH—and the research, jobs, technology, and businesses surrounding it—is nothing less than…an economic engine.”

The Human Genome Projects’ incredible return on investment

The second report, published by the Battelle Memorial Institute, is even more stunning. The report looked specifically at the economic impact and return on the federal investment of the Human Genome Project, an iconic federal science research program begun in the late 1980s.

The findings of the study speak for themselves: the public investment of $3.8 billion spread between1988 and 2003 yielded $796 billion (three-quarters of a trillion dollars), in economic output, and created nearly 4 million job-years over the 23-year period between 1988 and 2010. In 2010 alone, while it costing the government nothing, this farsighted, bipartisan investment in genomics research added $67 billion to U.S. gross domestic product, created $20 billion in personal income for American families, and sustained 310,000 public and private sector jobs.

If looking at these public investments from the point of view of a business, these numbers would represent phenomenal growth and profitability. If the total public investment in the Human Genome Project were a private investment fund, and the total public benefits thought of as revenue, the investments made in it would be said to have a return on investment, or ROI, of 14,000 percent over the 23-year period. A return like that would be enough to make any investor drool. Or, to look at it another way, imagine a family that put just $1,000 of their savings into the Human Genome Project in 1988. Today, they would have $140,000.

These figures are remarkable in and of themselves, but they don’t even take into account the intangible fact that these investments lead to innovation in medical treatments, medicines, and technologies that save lives and improve our public health. NIH research made possible the implementation of the Human Genome Project and genetic sequencing. It has also led to new cardiovascular treatments, neurotransmitters, and monoclonal antibodies, which were a component in 5 of the top 20 best selling drugs in 2010, generating worldwide revenue of $35 billion.

The project also had a tremendous impact not just on economic growth and job creation, but on innovation that is helping save lives. This research has helped launch an entirely new industry around personalized medicine and direct-to-consumer genetic testing, both making it easier to target specific medicines and treatments to patients’ needs. A 2009 study showed that 15 percent of healthcare providers reported at least one patient brought them results from a direct-to-consumer genetic test in the previous year, and 75 percent said they changed some aspect of the patient’s care based on the information. This new technology and the fast-growing industry around it were made possible entirely thanks to the research directly funded and indirectly catalyzed by the federal investment in the Human Genome Project.

The takeaway is that while these public investments have led to jobs, growth, and new technologies, more important is that the product of all this is new medical knowledge that benefits the public good. In the words of Greg Lucier, the chief executive officer of Life Technologies, whose foundation sponsored the Battelle analysis:

“From a simple return on investment, the financial stake made in mapping the entire human genome is clearly one of the best uses of taxpayer dollars the U.S. government has ever made. This project has been, and will continue to be, the kind of investment the government should foster…one with tangible returns.

“The initial dollar investment has already been returned [12 times over] to the government via $49 billion paid in taxes. Now we sit at the dawn of the ‘Genomics Revolution’ and all humankind will reap the benefits as we transfer what we now know about the human genome into major breakthroughs including: new forms of ‘personalized medicine’ and genetics therapy better suited to solving the problems we all care so much about, such as cures for cancer, cardiovascular diseases, Alzheimer’s, HIV/AIDS, and many more terrifying diseases. These major advancements are rapidly creating multiple new industries and companies and those companies are creating quality jobs for thousands of people. Life will be even better for all of us thanks to the HGP.”

Conclusion

When times are tough and budgets are tight, everyone—families, businesses, and yes, even the government—must make difficult choices and prioritize the things they really need while giving up some of the things they don’t. This process of economic recalibration, while painful, is a necessary and healthy step in making our economy more efficient in the long run.

But advocating cuts to government investments that bring in more revenue throughout the economy than they cost to run is self-defeating in terms of both deficit reduction and job creation. Cuts to these high-performing programs would be like a business cutting its best-selling product lines in the name of cost reduction. McDonalds doesn’t cut french fries from its menu just to save a buck. They know their french fries are profitable and draw customers to their restaurants. Such cuts would make McDonalds’ balance sheet worse—not better.

Similarly, cutting programs such as the NIH that demonstrably create jobs, catalyze private investment, and drive economic growth in excess of their public cost is misguided. As we proceed in the discussion of how best to make our government more efficient, and reduce our mounting foreign debt, our lawmakers need to adopt the same mentality. Investments in innovation—fundamental science and the research, development, and commercialization of new technology—have long been shown to have not only a positive return on investment for the government, but also great spillover benefits for private enterprise, small businesses, consumers, and ultimately for American families. Congress can’t forget this as it debates government investment targets for FY 2012 this fall.

Sean Pool is the Assistant Editor for Science Progress.

The technique being developed analyzes fetal DNA that is collected from women’s blood as early as five weeks into a pregnancy. So-called “noninvasive prenatal diagnosis,” or NIPD, may hit the market as a test for Down syndrome later this year. Soon after, refinements are likely that will allow identification of fetal genes at thousands of sites; two different research groups published papers claiming “proof in principle” of this prospect last December.

Because NIPD would be less invasive, less risky, and less expensive than the kinds of fetal gene tests now available, and because it relies on a simple blood draw so early in pregnancy, it is poised to become a prenatal game changer.

The fetal gene tests now offered are far from a walk in the park. For amniocentesis, a long needle is poked through your abdomen and uterus to extract amniotic fluid when you’re about 15-20 weeks pregnant. Chorionic villus sampling takes a snip of placental tissue, acquired by snaking a catheter through your vagina and cervix at 10-12 weeks. Both procedures carry a 0.5 percent to 1 percent risk of miscarriage.

By contrast, for NIPD you’d simply give a little extra blood at the lab at your first prenatal checkup. There would be no risk at all to you or the fetus. And you’d get the results before you were visibly pregnant, before you’d told your mother or your friends.

Of the 5 million or so pregnancies in the United States each year, only a few percent involve amniocentesis or chorionic villus sampling. Another few thousand fetal gene tests are done on embryos created with in vitro fertilization.

These numbers are relatively small. Even so, the practice of selecting fetuses and embryos with particular genes elicits concerns about the implications for people living with the very disabilities that are often “deselected,” about sex selection, and about parental expectations of a “perfect” child. NIPD could send the yearly number of fetal gene tests skyrocketing into the millions, and the level of concern soaring.

Researchers developing NIPD have already established partnerships with biotech companies eager to commercialize it; San Diego-based Sequenom has announced it will make NIPD for Down syndrome available in the fourth quarter of this year. Detecting hundreds or thousands of genetic variations, as opposed to particular chromosomal configurations, will be more difficult (and, at least initially, far more expensive). But researchers working on NIPD are confident that they’ll soon be able to do just that.

In other words, NIPD might soon be able to present you with the kind of genetic information about your five-week-old fetus that you can get today about yourself by sending a couple hundred dollars and a wad of spit to one of the “direct-to-consumer” gene test companies peddling their wares online. In both cases, you’d get a report that claims to predict risk for scores of common diseases and “conditions.”

But what do such reports mean? Predictions based on genetic testing are often highly misleading. You may learn from your own gene test, for example, that your risk of some condition is 50 percent higher than average—but how important is that if the average risk is only 1 percent? You may be told that you have a genetic variation associated with some disease—but that result may be based on one or a couple of small studies that have since been found wanting. The results look impressive and objective but for the most part their meaning is dubious and their usefulness scant. In fact, an increasing number of medical and genetic experts, and an FDA advisory panel, agree that when it comes to predicting common diseases, gene tests are a waste of money. Responsible medical practice, in this view, would limit gene tests to those that are clinically meaningful and useful.

Of course, some gene test results are helpful and important: If you’re planning children, for example, you may want to know if you’re a carrier for a serious single-gene disorder such as Tay-Sachs; if close relatives have had breast cancer, you may want to learn whether you have the mutation that significantly raises your risk of the rare familial form of the cancer.

But even with genetically imposed risks that are well established—for example, the genetic variation linked to early-onset Alzheimer’s—there are often few if any preventive measures to take. Fetal gene testing, however, is different. It presents an option: terminating a previously wanted pregnancy.

If sequencing large swaths of fetal genomes becomes common, that’s a choice millions might face. But how could pregnant women and their partners possibly interpret the results of tests that claim to predict dozens or hundreds of a future child’s traits? How, for example, could they “balance” a 25 percent increase in one risk against a 15 percent decrease in another? What would any of us do with information like this, even—or especially—if we knew it to be dubious and misleading?

And what of the broader social concerns? How many parents would choose to terminate a pregnancy because their child might be born with a disability—even if it was one with which many people are living full and happy lives? Would health insurers encourage such tests, or even require them, in order to avoid the costs of special-needs children?

It could get worse. Would we see parents using prenatal testing to try for a boy who’d play basketball with Dad or a girl eager to go clothes shopping with Mom? Would we begin to see offers—like the one in 2009 by a Los Angeles fertility clinic—to test fetuses for hair color, eye color, and skin tone?

Two close observers of NIPD’s development, UC Hastings legal scholar Jaime King and Stanford bioethicist Henry Greely, predict NIPD will soon force us to face the “brave new world” questions that “we have been able until now to ignore.” In a January Nature article titled “Get Ready for the Flood of Fetal Gene Screening,” Greely described the pending situation in appropriately dramatic terms: The “spectre of eugenics will loom over the whole discussion,” he noted. And concerns about eugenics “will increase as such testing moves from fatal diseases to less serious medical conditions and then on to nonmedical characteristics.”

Though some will object to NIPD largely because it makes greater numbers of abortions likely, its social and moral implications are not well captured by the abortion debate. Fetal gene testing in ballooned numbers and scope will disquiet reproductive rights advocates, disability rights advocates, and many others. Those of us determined to protect abortion rights will need to find ways to prevent frivolous and medically irrelevant genetic testing that could distort our hard-won reproductive freedoms and carry us into the realm of eugenics.

Marcy Darnovsky, Ph.D., is associate executive director of the Center for Genetics and Society, a public interest organization working for responsible uses and governance of human genetic and reproductive technologies.

The commission has moved quickly since its inception last July to produce a farsighted report on the opportunities and ethics of synthetic biology and emerging technologies in December. In forming the commission the president asked experts to:

• “Review the developing field of synthetic biology
• “Consider the potential medical, environmental, security, and other benefits as well as potential health, security, or other risks
• “Identify appropriate ethical boundaries to maximize public benefits and minimize risks”

Speakers were Nelson Michael, M.D., Ph.D., a member of the commission and director of the Division of Retrovirology at the Walter Reed Army Institute of Research; and Valerie Bonham, J.D., executive director of the commission.

Because of the still emerging nature of this technology, Dr. Michael said, the commission had the “rare and exceptional opportunity to be forward looking instead of reactive,” to “take a deep breath and have a public dialogue.” In other words, it is better to begin to identify where future opportunities and threats may lie as new industries develop rather than to try to address them once entrenched interests have taken root.

Synthetic biology is the application of engineering principles to organisms and biological systems. The president’s formation of the commission was in response to last year’s announcement that Craig C. Venter had rebooted a single celled organism with an entirely synthetic genome. Dr. Michael pointed out that this process cost roughly $40 million and occupied a whole research team, but the feat caught the world by surprise and triggered a national debate.

There is a debate about whether Venter’s achievement specifically—and synthetic biology more broadly—are revolutionary in science, or merely an evolutionary extension of molecular biology and genetic engineering. According to Dr. Michael, “molecular biology was intended to ask questions and interrogate biological systems, whereas synthetic biology takes a different approach…While [it] sits on the shoulders of those that came before,” what is unique about synthetic biology, he continued, is that “synthetic biology seeks to make useful things.”

What kinds of useful things? Some of most promising near-term applications of the technology include more effective and efficient production of vaccines, environmentally friendly biofuels, and improved pharmaceuticals. For example, the chemical Artemisinin is a powerful antimalarial that currently must be extracted laboriously and expensively from the sweet wormwood plant. The hope is that pharmaceutical companies could use synthetic biology to engineer microbes to produce large amounts of this chemical in a form that is easy to refine, leading to a more affordable production technique for the life-saving drug. Similarly, researchers working in energy are hoping to use synthetic biology to engineer fuels from sunlight at the Department of Energy’s energy innovation hub at Lawrence Livermore. Using synthetic biology, researchers are experimenting with the genomes of algae species to produce high quantities of lipids for easy conversion to fuel.

But these possibilities are just the beginning. As with any emerging field of technology, where it will lead is difficult to predict. In one famous example of innovators failing to see the long-term implications of their technologies, Thomas John Watson Sr., the president of IBM Corporation in the 1950s supposedly said he believed there would be a world market for “maybe five computers.” Today there are about a billion computers worldwide. While it is unclear whether Thomas John Watson Sr. ever actually uttered those words, we do know that IBM Corporation suffered for its myopic focus on hardware and for failing to predict the vast and growing market for software that their innovation would create. If there is anything we know about technological innovation, it is that it is unpredictable.

Nonetheless, there are some common questions that we should ask of any new field, even if we do not know what it will look like in five, 10, or 50 years. The commission members and staff at the event on Thursday also noted that the report has implications for assessment of all emerging technologies. The report advocates that for synthetic biology and any emergent field of technology, policy needs to be guided by the principles of public beneficence, responsible stewardship, intellectual freedom and responsibility, democratic deliberation, and justice and fairness.

In investigating these principles for policy on synthetic biology, the commission engaged with leaders from the science, faith-based, legal, and ethics communities to evaluate potential risks, and created 18 principles for maximizing the public good. They also took a number of public comments, according to the commission’s executive director, Valerie H. Bonham, to ensure that they gathered “opinions from broad swath of society, on both technical and scientific issues and ethical concerns.” The results are a sensible balance between the “let science rip” approach—for example, minimal regulation to allow maximum progress, but also maximum risks—and an extremely measured regulatory approach that minimizes risk but also slows progress.

The president’s commission’s active engagement with stakeholders should serve as a model for the assessment of risks and benefits of new technologies.

You can view the event video and summary here, and you can download the commission’s report here.

Jonathan Moreno, Ph.D., is the Editor-In-Chief of Science Progress and a Senior Fellow at the Center for American Progress. Sean Pool is the Assistant Editor of Science Progress.

But even if the genome-wide association studies that form the basis for these genetic profiles are imprecise, don’t consumers still have a right to know about their own genes? Should they expect a certain level of validity for information they’re buying? For the moment DTC genetic testing falls, in Lee’s words, in a “regulatory no-man’s land, with little oversight by federal agencies.” And the question remains, do we need health professionals act as gatekeepers and help interpret this new information?

Lee, a medical anthropologist who works as a senior research scholar at the Stanford Center for Biomedical Ethics, and her colleague LaVera Crawley, examined the expanding DTC industry and its implications for consumer health and privacy in an article that appears in the current issue of the American Journal of Bioethics.

Learning about the genes that give you brown eyes or make you lactose intolerant is one thing, but some services offer the ability to share your data with others through social networking tools. And not all genetic information is personal. “One of the special qualities of genetic information,” explains Lee, “is that it is information about the primary user; but it also information about others who may not have consented or agreed to have that information shared with other individuals.” For instance, a heritable trait increasing risk for breast cancer has implications for the person getting tested, as well as their children and grandchildren.

The Genetic Information Non-discrimination Act passed last year promises to protect citizens who might face unfair treatment on account of their DNA, but Lee warns that it’s also not yet clear how the legislation will treat the data shared through these social networks. And once an individual has made the decision to put information out there, it’s very hard to take it back.

Finally, some of these companies are taking consumer-generated genetic information and building commercial databases for research use. The vendors do require consent for this, but Lee says the process is hard to evaluate because in traditional clinical trials, scientists are required to make explicit all the potential uses of personal information. But because this sort of genetic research is still growing, it’s hard to say just what those future uses might be, so it constitutes what Lee calls a form of “open consent.”

So with these exciting new services comes a blurring of the line between consumer and research participant. This creates a tension, Lee says, between policies that allow people who want to actively participate in research to do so while still protecting people who may become unwitting research subjects. “Finessing this balance will be a central challenge as direct-to-consumer genomics expands,” she says.

And as with any expensive technology, there is a concern that the benefits may only be available to those that can afford it, as DTC tests currently run from a few hundred to a few thousand dollars. Yet the bigger divide, Lee suggests, may not be access to sequence information, but access to educational and interpretive information about genetic risk factors—for patients, consumers, and heath care providers alike.

Andrew Plemmons Pratt is the managing editor of Science Progress.

These recommendations come at a time when the race and genetics conversation is at a fever pitch. Many hope that advances in human biotechnology will yield profound medical, scientific, and social advances. But what often goes unacknowledged is that if we are not extremely careful, commercial and forensic applications utilizing human biotechnology may resuscitate harmful ideas about the significance of genetics to understanding racial difference and the cause of racial disparities. To help mitigate such misunderstandings, policy tools such as race impact assessments should be adopted widely across several regulatory agencies. By facilitating greater engagement between public policy and human biotechnology, race impact assessments can provide a forum for multiple stakeholders to work with government to assess the effect race-specific biotechnologies might have on minority communities.

To understand why public policy must grapple with the impact human biotechnology might have on racial minorities, we must first take a close look at how race has informed these technologies’ development and deployment.

Race and Genetics: From Research to Main Street

One of the Human Genome Project’s most heralded findings was that all humans are over 99.9 percent similar at the molecular level, a discovery that supports the social rather than genetic character of racial categories. (Subsequent research has slightly raised the initial estimate of difference, to around 0.5 percent.[1]) At the time that the HGP’s results became public in 2000, numerous scientists and other observers predicted that its finding of human genetic similarity would finally move society beyond biological theories of racial difference that have fueled centuries of racial strife.[2] The truths of science, some hoped, could promote racial healing. Yet almost as soon as researchers announced this result, several research projects began to focus on mapping the less than 1 percent of human genetic variation onto social categories of race.[3]

Since then, biomedical researchers and companies have become increasingly interested in developing treatments that use race and ancestry (both perceived and self-identified) as proxies for groups’ genetic predispositions. Put differently, these efforts presume that social categories of race reflect medically relevant genetic differences, even when such differences have not been identified. This is better known as race-based medicine: drugs that are developed, approved, and marketed for specified racial groups. Only one of these drugs, BiDil (marketed to treat heart failure in African Americans), has received FDA approval. But others are in development.

Meanwhile, dozens of biotechnology companies are marketing genetic testing services directly to consumers, bypassing physicians and other health care professionals. Combined with the power and reach of the Internet, direct-to-consumer genetic testing offers people the ability to swab their cheeks at home, mail the sample (along with a fee ranging from $100 to $1,000), and receive information a few weeks later.

While much skepticism has accompanied the growth of DTC genetic testing, there has been less public discussion about the significant concerns stemming from genetic tests claiming to reveal information about consumers’ ancestral origins, which are often interpreted as tests of racial purity and mixture. Genetic ancestry tests are gaining popularity, especially among African Americans who often have these tests pitched to them as a way to make an end run around the genealogical dead end produced by the slave trade. But in examining less than 1 percent of a person’s genetic background, these tests often overstate their ability to say anything significant about a person’s heritage, giving the impression that social categories of race and ethnicity are somehow genetically verifiable.

Biotechnology is also making an impact in forensics, a field that uses techniques such as ballistics, fingerprinting, and toxicology to investigate crimes. Two decades ago, the United Kingdom’s Sir Alec Jeffrey’s revolutionized forensics by developing genetic profiling. This capacity to extract unique identifying information from hair or body fluids left at crime scenes has given police a powerful tool to catch suspects.

A good part of DNA forensics’ power now comes from massive databases storing large numbers of genetic profiles. Once a DNA sample is gathered from a crime scene, it can be checked against stored profiles for matches.

But whose DNA winds up in police databases? Typically, it is people who have had previous run-ins with law enforcement. And herein lies the risk for minority communities: given that Blacks and Latinos are disproportionately policed, arrested, and prosecuted, their profiles are likely to be over-represented. This means that the significant civil liberties concerns raised by DNA forensics will disproportionately burden these communities.

Will Human Biotechnology Revive Biological Theories of Race?

Like many scholars, the authors of the Stanford guidelines recognize that there is no scientific basis for the idea that human genetic variation reflects any sort of racial hierarchy and acknowledge that racial categories exist within social and political contexts that shift over time. They discourage researchers from using race as a proxy for biological similarity, and caution against what they term the “naïve leap” to genetic explanations of complex social phenomena such as IQ or propensity for violence. Their guidelines are an important contribution, and should be adopted widely so that research on race and human genetics can proceed responsibly.

But as I argue in my report, “Playing the Gene Card? A Report on Race and Human Biotechnology,” concerns about race and human biotechnologies cannot be limited to individual research agendas or best practices in clinical settings. Instead, it is crucial to consider how these technologies, particularly when taken together, are likely to have a public impact. However laudatory, no set of voluntary guidelines or recommendations can obviate the need for greater public oversight of how racial categories are deployed—in research, in the marketing of the resulting products, and in the public understanding of the research findings.

This point is particularly relevant since the approval of regulatory bodies such as the Food and Drug Administration and the United States Patent and Trademark Office can allow the state to sanction potentially misguided claims about the relationship between race, genetics, and social and health outcomes. Regulatory bodies can play a powerful role in giving misplaced legitimacy to claims that correlate social categories of race with genetic variations when the evidence is not yet robust, effectively putting the cart before the horse.

There is some evidence that social categories of race may be genetically relevant to the extent that they may correlate with geographical origin, broadly defined. This, in turn, may reflect the histories of isolation and evolution experienced by some groups. Yet there is also evidence that today’s applications in biomedicine, genealogy, and forensics have treated race in a somewhat circular fashion; unexamined ideas and assumptions about the genetic relevance of race, often reflecting lay perspectives, can shape research questions and methodologies. This is what Troy Duster and others have called the reification of race: transforming race as a social concept into a specific, definite, concrete, and now presumably genetic category that can feed back into preexisting assumptions about racial difference.

The potential of race-specific medicine, genetic ancestry tests, and DNA forensics to revive biological thinking about race is not necessarily due to any ill intent on the part of researchers working in the area of race and genetics. To the contrary, many scientists have devoted their careers to egalitarian and praiseworthy pursuits such as resolving health disparities and assisting law enforcement. For example, the use of racial categories in biomedical research has been proposed as a way to make biomedicine more inclusive. But even with the best of intentions, commercial and forensic applications of this research can unwittingly create the very difference they seek to find. As in other areas, racial injustice is best understood as a matter of systematic outcomes rather than a question of intentions.

The social, political, and economic dynamics surrounding research concerning race and genetics might allow less-than-robust scientific studies or weak correlations between genetic variations and social categories of race to be marketed as commercially viable genetic tests or biomedicines. Our society’s continued stake in the idea that social categories of race reflect inherent biological differences—even when faced with substantial evidence to the contrary—contributes to the acceptance of these products. And this process might work to reconstitute an inaccurate and unsubstantiated view of racial difference and disparities.

Why We Need Race Impact Assessments

Given the remarkably high stakes involved and the rapid development of biotech products and services that implicate racial categories, it is time for policymakers to take these matters under serious consideration. Responsible regulation and oversight can go a long way towards ensuring that these products and services are based on sound scientific research, and that they do not promote unfounded biological theories of racial difference. Regulators can help protect racial minorities from inappropriate commercial pressures, less than forthright marketing, and the often-unintentional re-articulation of folk notions of biological race. The goal is to create an environment in which research and scientific innovation can move forward while guarding against potentially harmful social outcomes.

How might this work? In order to encourage more forethought in regulatory decision-making and implementation, other fields have adopted the use of impact assessments. One relevant example is the health impact assessment,[4] which is a set of procedures, methods, and tools that, according to the World Health Organization,

…provide a structured framework to map the full range of health consequences of any proposal, whether these are negative or positive. It helps clarify the expected health implications of a given action, and of any alternatives being considered, for the population groups affected by the proposal. It allows health to be considered early in the process of policy development and so helps ensure that health impacts are not overlooked.

Public health researcher John Kemm notes that despite different definitions, two essential characteristics of health impact assessments are that they “seek to predict the future consequences for health of possible decisions; and that [they] seek to inform decision-making.” For example, a health impact assessment of a proposal for a new factory would look at a number of ways it may affect the local population’s health, such as whether emissions from the building are linked to adverse health outcomes and how best to contain them.

Similar regulatory assessments of the possible public impact of an innovation or initiative may be instructive for identifying and mitigating their possible adverse effects for racial minorities. Race impact assessments[5] could encourage shared responsibility among multiple actors—including regulators, researchers, internal review boards, and affected communities and their representatives—in making sure that human biotechnologies are not used to promote unfounded biological understandings of race and that claims made about the relationship between race and genetics are based on sound evidence. Just as health impact assessments aim “to enhance recognition of societal determinants of health and of intersectoral responsibility for health,”[6] race impact assessments could promote recognition of the social construction of race and the social determinants of racial disparities.

What might such race impact assessments look like in the context of human biotechnology? As an example, modifications to the traditional role of the Food and Drug Administration might allow it to convene advisory committees as part of its review process that look beyond safety and efficacy to evaluate whether medicines with race specific indications such as BiDil might reinforce biological understandings of race when no biological or genetic mechanisms have been identified.

The composition of such a committee would have to accurately reflect the demographic makeup of the stakeholders and constituent groups affected by the research. Its assessment would not be limited to reviewing biostatistical evidence from clinical trials. It would also consider the effects race-specific medicines might have on broader commitments to racial justice, specifically in the context of past discrimination based on biological notions of race. This might encourage narrowly tailored mechanisms to ensure that a drug’s beneficiaries have access without prematurely giving legitimacy to biological understandings of racial difference.

A race impact assessment of ancestry tests might lead federal and/or state governments to closely scrutinize marketing claims to ensure that they do not overstate the current state of the science. Such assessments might lead regulators to require genetic testing companies to limit their advertising to scientifically verifiable statements, and to give consumers adequate information about the tests’ limitations.

In the context of DNA forensics, a race impact assessment could shed light on policy shifts that might disproportionately affect certain communities, such as familial searching, the use of molecular photofitting, or including arrestees that have not been convicted in DNA databases. This assessment might encourage refinements and recalibrations that could lessen the burden on those communities while ensuring that law enforcement has the tools it needs.

The overall goal of race impact assessments in human biotechnology would be the same as its counterparts in public health and other realms: to increase dialogue between stakeholders and policymakers so as to balance competing interests though strategic planning that promotes the public good.

Osagie K. Obasogie is an Associate Professor of Law at the University of California, Hastings, a Visiting Scholar at the University of California, San Francisco, and a Senior Fellow at the Center for Genetics and Society. This article is adapted from his recent Center for Genetics and Society report entitled “Playing the Gene Card?: A Report on Race and Human Biotechnology,” available at thegenecard.org.

Notes

^[1] Samuel Levy et. al. write “Comparison with previous reference human genome sequences, which were composites comprising multiple humans, revealed that the majority of genomic alterations are the well-studied class of variants based on single nucleotides (SNPs). However, the results also reveal that lesser studied genomic variants, insertions and deletions, while comprising a minority (22%) of genomic variation events, actually account for almost 74% of variant nucleotides. Inclusion of insertion and deletion genetic variation into our estimates of interchromosomal difference reveals that only 99.5% similarity exists between the two chromosomal copies of an individual and that genetic variation between two individuals is as much as five times higher than previously estimated. … [Therefore] we can, for the first time, make a conservative estimate that a minimum of 0.5% variation exists between two haploid genomes.” Samuel Levy, “The Diploid Genome Sequence of an Individual Human,” PLoS Biology 5:10 2113–44. (Cited passages at 2114 and 2132).

^[2] The New York Times’ Amy Harmon writes that “When scientists first decoded the human genome in 2000, they were quick to portray it as proof of humankind’s remarkable similarity. The DNA of any two people, they emphasized, is at least 99 percent identical. But new research is exploring the remaining fraction to explain differences between people of different continental origins.” Amy Harmon, “In DNA Era, New Worries About Prejudice,” New York Times, November 11, 2007, http://www.nytimes.com/2007/11/11/us/11dna.html?_r=1&hp&oref=slogin.

^[3] Duana Fullwiley, “The Molecularization of Race: Institutionalizing Human Difference in Pharmacogenomic Practice,” 16 Science As Culture 1 (2007).

^[4] While an examination of health impact assessments is most relevant for the purposes of this discussion, it is important to acknowledge that health impact assessments have “much in common with and builds on “environmental impact assessment” and also has less recognized but salient links with the field of “health and human rights” and the concept of “human rights impact assessment.” Nancy Krieger et. al., “Assessing Health Impact Assessment: Multidisciplinary and International Perspectives,” J Epidemiol Community Health 2003;57:659–662.

^[5] Racial impact statements or assessments have been proposed in other contexts such as mitigating sentencing disparities. See e.g., Marc Mauer, “Racial Impact Statements As a Means of Reducing Unwarranted Sentencing Disparities,” 5 Ohio State Journal of Criminal Law 19 (2007).

^[6] Nancy Krieger et. al., “Assessing Health Impact Assessment: Multidisciplinary and International Perspectives,” J Epidemiol Community Health 2003;57:659–662.

Science Progress advisory board member Art Caplan offers a sobering perspective about the gravity of this suit for patent lawyers in his Breaking Bioethics column, even though he thinks a Myriad victory is all but certain. Twenty percent of all human genes are patented, he notes, and most of the worldwide drug industry rests on the legal foundation established by the Myriad patents.

Caplan also explains that patents are a privilege and not a right. Nevertheless, the University of Utah and Myriad invested large sums of money into the research and development of the processes by which the BRCA genes are isolated and purified. The monopoly that the patent provides is intended as a reward for that investment and innovation.

Unfortunately, physicians and researchers cannot reduce the costs of the tests or improve on them by investigating other mutations on the genes. According to the lawsuit, Myriad’s exclusive rights also have “resulted in a disparity in the amount of information known about genetic mutations in BRCA1 and BRCA2 in ethnic groups other than Caucasians.”

The lawsuit also notes that information available from the tests is “critical” in helping patients “decide on a plan of treatment or prevention, including increased surveillance or preventive mastectomies or ovary removal.” Moreover, it notes that, “Patients cannot get second opinions on their test results; and patients whose tests come back with inconclusive results do not have the option to seek additional testing elsewhere.” Filmmaker Joanna Rudnick described the difficulty of these health decisions and the impact they have on entire families in an interview with SP last year.

The New York Times notes that the next generation of genetic tests will assess the presence of variations on multiple genes. A scientist working on a multi-gene test would presumably need to pay licensing fees to all of the potential patent holders. In this sense, it is conceivable that gene patents stifle research, innovation, and competition. However, the NYT also links to a 2006 National Research Council report that found “access to patented inventions or information inputs into biomedical research rarely imposes a significant burden for biomedical researchers.”

The Chronicle of Higher Education points out that one of the plaintiffs joining the ACLU, the Public Patent Foundation of the Benjamin N. Cardozo Law School, also brought a patent challenge in 2006 against the Wisconsin Alumni Research Foundation. WARF holds the patents on the human embry­onic stem cell derivation process that James Thomson of the University of Wisconsin-Madison developed, as well as the cells obtained by that process.

Even though the U.S. Patent Office upheld the patents in question in the 2006 suit, WARF modified its licensing procedures so that academic researchers could license the processes without paying a fee, but when a company begins selling a technology based on the patented processes, they then owe royalties to the foundation. As I argued in our stem policy report, “A Life Sciences Crucible,” the WARF arrangement strikes a good balance between spurring academic research and protecting private-sector investments.

But the Centers for Medicare and Medicaid Services recently released their “Proposed Decision Memo for Pharmacogenomic Testing for Warfarin Response,” in which they write that genetic testing does not improve “health outcomes in Medicare beneficiaries” when trying to predict responsiveness to the anticoagulant.

However, CMS did decide to pursue a strategy known as “coverage with evidence development,” which is authorized under the Social Security Act. This means that CMS will cover the cost of genetic tests for warfarin responsiveness if they are a part of a “prospective, randomized, controlled clinical trial.” In short, CMS will cover more research on use of the genetic test, but not pay for it in clinical settings.

According to GenomeWeb, private insures such as Aetna have also chosen not to cover the tests and have not been moved by the CMS decision to cover them for clinical trials.

Overall, this is a sensible policy and CMS lays out clear reasoning for it. Out of the six professional societies that provided their positions on pharmacogenomic testing for warfarin dosing, only two, the American Association for Clinical Chemistry and the College of American Pathologists, felt that there was sufficient evidence of effectiveness to warrant coverage. CMS also incorporated five expert opinions into their decision, all of which attested that the evidence regarding real-world health outcomes was insufficient. Michael Brophy of the Department of Veterans Affairs Diagnostic Services wrote that the genetic factors influencing response to the drug did not make a practical difference in clinical situations: “It’s only one of many factors that determine the appropriate dose.”

This decision is likewise important because it answers questions raised at a Medicare Evidence Development and Coverage Advisory Committee meeting in February on diagnostic genetic testing, which tests for diseases or anticipates drug response in patients. Most of the committee members felt that diagnostic genetic testing should be held to similar standards and criteria as other forms of diagnostic testing. The committee also emphasized that in order to assess the impact of diagnostic genetic testing on patient-centered health outcomes, there need to be “methodologically rigorous” evidence gathered on direct patient-centered health outcomes such as “mortality, functional status, and adverse events.”

If anything, these evaluations all to point to the need for robust evidence gathering. Personalized medicine will further require a sophisticated infrastructure for collecting, analyzing, and coordinating clinical and research information, and that necessitates investment in health information technology and comparative effectiveness research to reduce costs and improve health care outcomes.

While genetic information is certainly useful in catching some offenders and exonerating the wrongfully imprisoned, this ramp-up nevertheless raises a host of privacy questions. But the F.B.I. is passing it off as the equivalent of fingerprinting:

Law enforcement officials say that DNA extraction upon arrest is no different than fingerprinting at routine bookings and that states purge profiles after people are cleared of suspicion. In practice, defense lawyers say this is a laborious process that often involves a court order. (The F.B.I. says it has never received a request to purge a profile from its database.)

The story also cites a Congressional Research Service report on the impact of compulsory DNA collection on fourth amendment rights. The report points out that while the FBI creates genetic profiles using “junk DNA,” which was originally assumed to be non-coding, “because it is thought to lack both a biological purpose and indicators of sensitive medical characteristics.” But as genetic research has advanced, it has become clear that DNA once deemed extraneous does in fact play a significant role. Bioethicist Sheri Alpert addressed the issue in a report last year on privacy issues in genomic medicine (sub’s required): “[T]here is likely much more interplay among genes and the noncoding portions of the genome and that each gene must play a role in more proteins, traits, and diseases than previously thought.”

Bottom line: storing genetic information in a database means retaining data that may reveal more about a person that we can even interpret at the present moment. The full privacy implications may not be clear until research advances.

The problem addressed in the commentaries is that these diseases were expected to be promoted by genetic variations that are common in the population. More than 100 genomewide association studies, often involving thousands of patients in several countries, have now been completed for many diseases, and some common variants have been found. But in almost all cases they carry only a modest risk for the disease. Most of the genetic link to disease remains unexplained.

Another issue is the difficulty of making useful clinical recommendations to patients based soley on their personal genetic information. But just as these commentaries on the limitations of genomewide studies appear, the National Human Genome Research Institute has annouced that it is looking to partner with an outside organization for a one-year  outreach campaign to increase public awareness of genomic research, and its medical, ethical, and social impact. The effort is important, but organizers will obviously have their work cut out for them if researchers are still scratching their heads at what to make of all  the information. For more, see Michael Rugnetta’s coverage of NHGRI’s new catalog of genomewide association studies.

Image: flickr.com/ethanhein

Natural laws, once discovered, have been successfully and profitably applied in patented applications to new and useful products and processes. No one would have considered patenting the law of gravity, nor would any patent on gravity serve the purposes of the Patent Act: to encourage innovation in the useful arts. It would, in fact, impede innovation. No one employing the law of gravity in any new device could produce and market their invention without paying whatever fee the patent-holder demands. Similarly, no one would consider patenting hydrogen, or plutonium, nor any element on the periodic table. Yet, parts of nature have now been patented in record numbers. Unmodified genes have been granted patents, and this impedes science. Since the mid 1990s, unmodified gene sequences have been granted patents. Thus, the company that owns the patent for the test for BRCA1 and BRCA2 (related to breast cancer) owns not only the process for detection of the gene (which is inventive and should be patentable), but also the sequence of amino acids in the gene itself. Miami Children’s Hospital owns the patent on the monogenic disease called Canavan’s. These are but two of the more than 8,000 existing gene patents.

Even though the Patent and Trademark Office now requires more “stringent” declared uses for gene patents, the uses need not be truly inventive. All genes have some “use,” but the use was invented by nature, not by man. Genes in their unmodified forms code for proteins, but this is not a “use” in the sense demanded by a patent since nature is non-teleological. That is, claiming a philosophical purpose for a gene only make sense within the framework of Intelligent Design.

Intellectual property laws are bargains between inventors, authors, and the public. We grant to authors and inventors valuable monopolies, limited in time and scope, in the hopes that this will encourage new inventions and art, and benefit us all. When the monopoly expires, the full knowledge that was once monopolized moves back to the public domain. The trick to any bargain, however, is balancing the interests of the bargaining parties, and at some point, a bargain may become “unconscionable” when one party’s benefit far exceeds the perceived benefit to the other party. In contract law, such bargains can be invalidated. In the case of gene patents, the bargain not only contradicts the purposes of patent law, but it is unconscionable.

Patenting unmodified genes rewards discovery, not invention. Would we allow a patent on plutonium? It must be isolated through complex processes (which might, being inventive, be patentable) but patenting plutonium would be as ridiculous as patenting hydrogen or any other element of nature Not only does it contradict a long history of not patenting laws of nature, but it impedes both science and invention. Basic science requires openness. It is the original open-source enterprise. Hypotheses can only be tested if results are published, and scientific progress depends upon rapid and thorough exchange of experimental results and public testing of hypotheses. Patents impede this process, because between filing and granting of a patent, information in the patent remains secret. Furthermore, if granted, patents on unmodified genes complicate the process of discovery for other investigators, requiring patent searches, payments of license fees, or turning away from research on parts of the genome that are patented.

We would not tolerate a patent on any other element or part of nature that is unmodified, non-inventive, and fundamental to basic science. Although Einstein worked in a patent office, he never applied for a patent on the theory of relativity. It wasn’t his invention, after all. Nor are the unmodified genes for which countless patents have already been granted the inventions of the patent holders, although we should be grateful for their discoveries, and some might make useful, patentable inventions based upon these discoveries. It is time to prohibit the process of patenting unmodified genes, and to invalidate, either by legislation or judicial action, all claims to unmodified genes. HR 977, the Genomic Research and Accessibility Act first introduced in 1997 by Rep Xavier Becerra (D-CA) to ban the practice of gene patenting, languishes still in committee, but it’s time to renew this debate. Science demands it.

David Koepsell is the author of Who Owns You: The Corporate Gold Rush to Patent Your Genes (Wiley-Blackwell 2009). He has a law degree and a PhD in philosophy from the University of Buffalo, and teaches Ethics and Technology at the Delft University of Technology in the Netherlands.

According to the website, the data comes from literature searches, media reports, and “and occasional comparisons with an existing database of GWAS literature,” the Human Genome Epidemiology Navigator. HuGE Navigator is a comprehensive site that connects genotypes and phenotypes to the research that demonstrates the links between them. HuGE Navigator also connects to GeneTests, which lists the labs that test for the genes and how effective the tests are. It also links to the Online Medelian Inheritance in Man, or OMIM, database which maps the entire genome, and the Pharmacogenomics Knowledge Base, which links genes to drug interactions.

Of course, all of this data takes some sifting in order to make sense of it. That is why the new GWAS list put up by NHGRI is useful. Not only does it establish connections between some of the genome research databases and interfaces, it distills and clarifies the most robust and statistically significant data.

As we move into an era of personalized medicine, one of the most crucial challenges for the scientific community will be not simply to collect more data but to devise better ways of disseminating it and making it accessible. It will be interesting to see how the federal government’s different research institutes as well as private research entities choose distill, repackage, and repurpose their data for different audiences. Some of the pitfalls that researchers will need to watch out for are inaccurate oversimplifications and misinterpretations. Nevertheless, experimentations with data dissemination should constantly evolve so that the research community and—increasingly—the clinical community can utilize genomic data easily, accurately, and appropriately.

I confess I find the prospect of bringing back lost species fascinating. Did anything make the movie Jurassic Park worth watching except the idea of bringing back dinosaurs? Likewise, the idea of meeting a live Neanderthal is fascinating. And think what we could learn: Could they speak? Could they learn a language? And what’s really so great about Geico car insurance?

At the same time, the prospect of bringing back an extinct human species is forehead-puckering. At the very least, as futuristic as the idea sounds, it’s worth turning the idea a little in the light. And the gauntlet has been thrown down: a genetic scientist I know has said to me, in effect, “All right, you thinkers, what do you have to say about this?”

Unfortunately for me, I am hard pressed to know what to say.

Church apparently told the Times that the way to do the work without running into any ethical problems would be to insert the Neanderthal genome into a chimpanzee cell. The chimp cell would be reprogrammed to an embryonic state, inserted into a chimpanzee’s womb, and brought to term. In a way, the product would be nothing more than a mutant chimpanzee-and we do experiments on chimpanzees all the time, so the work doesn’t raise any moral questions. Right?

But surely there are a variety of questions that have to be worked through.

First, let’s think about species that don’t belong to the human family. Sometimes, recreating an extinct organism purely for scientific purposes seems perfectly acceptable. Studying a live version-say, of the 1918-19 influenza virus-might be particularly useful. It might also just be particularly interesting-we could learn whether the velociraptor had stripes-and science is motivated in part just by curiosity. Church apparently proposed that something like intellectual curiosity would justify bringing back a Neanderthal; it “would satisfy the human desire to communicate with other intelligences.” But in these cases, we don’t care what happens to the organism after we’ve learned about it, we’d keep the organism confined while we were working on it, and we’d probably kill it once we were finished. But we’d have to care about Neanderthals, and we certainly couldn’t kill them afterwards. As we know from the Geico commercials, they might be quite sensitive. And maybe they’d integrate nicely into modern urban life. Or maybe they’d be permanently unhappy, no matter where we put them up. But given these uncertainties, bringing them back to life just to satisfy our own curiosity is not justified.

Sometimes, bringing back an extinct species might be justifiable as a case of ecological restoration. But there would have to be a few caveats. First, “restoration” seems appropriate only if the extinction was caused by humans (as may well have been the case with Neanderthals). Under its usual meaning, “restoration” means that we’re trying to undo some damage we’ve done, not that we’re hoping to turn back the evolutionary or geologic clock. Also, “restoration” seems appropriate only if the recreated species would be returned to its ecological home. Recreating a species only to put it in zoos doesn’t undo damage-the animal is animated, but not “restored” to the world. And recreating a species but introducing it to a new ecological home wouldn’t count either. That would be analogous to moving an extant species from one ecosystem into another, and that’s one of the things that sometimes later makes ecological restoration necessary, because one sometimes ends up with an invasive species.

In any event, the concept of undoing environmental damage is of no help in thinking about recreating Neanderthals. The problem here concerns what we do to sentient creatures, not what we do to nature. The prospect of recreating Neanderthals is more like the “designer baby” scenario, in which we consider whether parents might choose which baby to have on the basis of nonmedical criteria-sex, eye color, or whatever is technically feasible. The difference is that, with Neanderthals, the designer baby would be a caveman.

So what of the arguments that have been offered against creating designer babies? Interestingly enough, some of them don’t apply very cleanly, even assuming they work fine for Homo sapiens sapiens. Would concern about the Neanderthal’s well-being argue against creating it? It’s certainly a concern, but it’s particularly sketchy in this case since, never having met one, we really don’t know what make Neanderthals happy. A Neanderthal alone in a sea of Cro Magnon descendants might be wretched, but also might not care.

The German philosopher Jürgen Habermas has argued that some measure of independence from the creative control of other people is necessary if a person is to feel that she is a full moral agent and a full member of the moral community. A person must feel that who she’ll be and what she’ll be like is ultimately up to her. Parents influence it heavily, by deciding what schools she’ll go to and whether she’ll try to learn an instrument, but when they begin to make adjustments to her brain and body before her birth, they’ve overstepped a line.

But even supposing this makes sense for Cro Magnon descendants, there might be special hitches in applying it to a Neanderthal. A Neanderthal might have a special Neanderthal perspective on morality and community. Maybe feeling like one is one’s own person would not be important to a Neanderthal. Maybe Neanderthal views about acceptable human interaction are not even what we’d recognize as “morality.” After all, one of the reasons it would be interesting to communicate with other “intelligences” is that we might form new views about the connection between intelligence and morality.

The bioethicist Dena Davis has argued that we should be wary about creating designer children because the children brought into the world might not have an “open future.” They would be full members of the moral community, she thinks, but they might not feel that they were adequately in command of their own life trajectories. Depending on various things-what traits were selected, what the parents’ attitudes were-they might feel constrained to become one thing rather than another. But again, who knows how to apply this to Neanderthals? The concept of an open future might be unique to Homo sapiens sapiens-it might even be unique to very modern members of our subspecies. And what would we say about the future of a newly created Neanderthal? In some ways, it might seem closed; in some ways, it might seem wide open-particularly compared to every other Neanderthal who ever lived.

There are other objections to designer babies, but you get the drift. The objections depend variously on claims about how the children would feel, how the parent-child relationship would change, what one can reasonably expect of one’s life, or what reasonable people think about human interaction. They all depend on what Paul Ehrlich called our “human natures”; they depend on the accumulated biological and cultural traits that make us who we are. And if the child in question were a Neanderthal, we can do little more than hazard some guesses. Maybe, in fact, what makes a Neanderthal think that life is worth living would be more like what makes life worthwhile to a chimpanzee than what makes it worthwhile to me.

My instinct is not to do it, in spite of the difficulty of laying out good reasons for feeling that way. We may now know enough technically to do it. But we don’t know enough to do it right.

Gregory E. Kaebnick is the editor of the Hastings Center Report and a participant in a research project led by The Hastings Center and funded by the Alfred P. Sloan Foundation on the ethical issues of synthetic biology.

NIH’s Pharmacogenomics Research Network has compiled data from 5,700 patients across the globe who are being prescribed the widely-used blood-thinning drug. Every year, 2 million Americans with certain heart conditions start taking warfarin, but their doctors often encounter difficulty with prescribing the drug since the optimal dosage for each individual patient varies widely. This usually results in doctors taking a trial-and-error approach to dosing that takes months to perfect and runs the risk of causing harmful side effects in the meantime. Warfarin is especially risky for patients for whom the optimal dosage is either very high or very low.

The patient data collected by the NIH included both the patients’ demographic and clinical information as well as genetic information on two gene variants, CYP2C9 and VKORC1, both of which are known to influence a patient’s ability to metabolize warfarin. The consortium also collected data on the initial and optimized doses of warfarin that the patients were prescribed.

According to an article published by the consortium in the New England Journal of Medicine, the 5,700 subjects were divided into two groups along an 80/20 split. This means the data for 80 percent of the subjects were used to construct a dosing algorithm and the other 20 percent were used as a validation cohort to test the algorithm. After running some statistical analyses, the researchers discovered that the addition of the genetic data to the demographic and clinical data allowed for a better prediction of the optimal dosage than just the demographic and clinical data alone. The genetic data was most helpful for those patients whose optimal doses are outside the average range—either very high or very low. This led an accompanying editorial in NEJM by Janet Woodcock and Lawrence Lesko of the Center for Drug Evaluation and Research at the FDA to argue that for warfarin, the “evidence base for pharmacogenetic testing should be informed by…the characteristics of the outliers.”

The lead investigator for the consortium, Stanford University’s Russ Altman, reported that his team plans to tweak the dosing algorithm through an ongoing study of 100 patients from the San Francisco Bay area and report the data on the PharmGKB website. Altman and the other authors also admitted in the report that research still needs to be done on whether the improved dosing leads to better clinical outcomes. This is where the NIH’s upcoming clinical trial falls right into place.

NIH will now embark on a prospective double-blind clinical trial where approximately 1,200 subjects will be split into two groups, one being prescribed warfarin according to clinical data and one using both clinical and genetic data. GenomeWeb Daily News reports that a European team at Newcastle University and the University of Liverpool are also working on a similar clinical trial that will take place at 13 research centers in seven countries where they expect to enroll 2,700 subjects.

The question of clinical outcomes is an important one since the true potential of pharmacogenomics for improving our nation’s health lies not just in the scientific advancements but in the clinical effectiveness advancements it generates. Indeed, pharmacogemomics-based treatments, like all treatments, need to pass the practicality test if biomedical innovation is to make a constructive contribution to a larger system-based healthcare infrastructure.

Last month, for instance, ScienceDaily reported on an analysis conducted by the University of Cincinnati which found that even though pharmacogenetic-based dosing of warfarin improved outcomes, it did so at very high cost—$170,000 per quality-adjusted life year gained. The current rule governing the interpretation of most cost-effective analyses is $50,000 per quality-adjusted life year gained.

The main focus of the UC research was to determine whether pharmacogenetic-dosing decreased the risk of major bleeds. The analysis was conducted on the combined data of the only three clinical studies of pharmacogenetic-guided warfarin dosing that had been conducted by that time. The researchers also found that there is only a 10 percent chance that the pharmacogenetic-based would be cost effective. The lead investigator, Dr. Mark Eckman, recommended a number of conditions that could make the dosing more cost-effective.

Specifically, it should be used for patients who have a high risk for hemorrhage, prevent more than 32 percent of major bleeding events, be available within 24 hours, and cost less than $200.

He recommended that the upcoming NIH clinical trial “examine the impact of pharmacogenetic-guided dosing on bleeding risk and monitor outcomes long enough to determine the true duration of benefit,” suggesting that patients with a higher risk of bleeding should not be excluded if it is determined that they need warfarin. Eckman summed it all up by saying, “personalized, predictive medicine offers great promise, but we need to carefully examine the benefits and understand the cost-effectiveness of such strategies before we spend a lot of money on very expensive tests.”

Image: AP/ED ANDRIESKI

Documented instances of employer discrimination based on DNA are at the moment rare (details on two cases below), but access to affordable direct-to-consumer genetic testing services not only increases the amount and availability of genetic information, but it increases the possibility that third parties could see it and use it to make discriminatory decisions. GeneTests, a group that provides information on genetic testing, charts the rise in labs offering an expanded array of tests for more and more diseases:

(Source: www.genetests.org, © University of Washington, Seattle)

In their report, “Genetic Non-Discrimination,” Michael Rugnetta, Jonathan Russell, and Jonathan Moreno outline the details of two lawsuits filed on behalf of workers who were discriminated against based on their DNA:

Lawrence Berkeley Laboratory (1999)

• Accused of conducting pre-employment screening for sensitive medical information, testing for genetic traits such as sickle cell trait, and for non-genetic factors such as syphilis and pregnancy
• Charges filed under: Title VII of the Civil Rights Act of 1964, and right to privacy as guaranteed by the U.S. and California Constitutions (also the Americans with Disabilities Act, but this was not affirmed by the courts)
• Company argument: sought to have case dismissed in summary judgment without a trial, claiming that the statute of limitations had run out
• Ruling: The U.S. Court of Appeals for the Ninth Circuit sided with the workers

Burlington Northern Santa Fe Railway Corporation (2002)

• Employees charged that those who had filed for workers compensation for carpel tunnel syndrome—a painful hand and wrist condition caused by repetitive motion—were tested for a genetic marker
  – Tests performed without their knowledge
  – Marker dubiously associated with carpel tunnel syndrome
• Charges filed under: Americans with Disabilities Act of 1990 by the Equal Employment Opportunity Commission
• Company argument: testing necessary to determine cause of injury for 36 employees who claimed to have job-related carpel tunnel syndrome
  – 20 employees were tested before program voluntarily suspended
• Settlement: Company agreed to halt testing and pay $2.2 million

As Weiss points out, this EEOC rule will implement a historic piece of civil rights legislation, but the rules for protections from insurance discrimination, handled under a separate GINA Title, are another complex matter that the relevant agencies have yet to sort through. They should not delay. The amount of personal genetic information available will continue increasing. It should help improve health care and not prevent people from getting access to it.

In part, at least, this process is moving apace. Today, the U.S. Equal Employment Opportunity Commission released a Proposed Rule that describes how that agency intends to implement GINA’s so-called Title II provisions, which deal with genetic discrimination in the workplace. (Title I of the Act deals with the insurance provisions—more about that in a moment.) The public will now have 60 days to offer comments on the employment rules, which EEOC will then consider before crafting final language. By statute, the process must be completed by May 21 and the law will go into effect in November.

You don’t have to be a total wonk to appreciate the groundbreaking nature of this accomplishment: We’re talking about the first significant expansion of workplace discrimination protections since 1990, when the Americans with Disabilities Act added “disability” to the list of factors—age, race, religion, and sex—that cannot be considered in hiring decisions.

Gratifyingly, not only is the EEOC’s work on track to be completed on time but the content appears to reflect virtually all of the elements that progressives had called for in their decade-long battle to get GINA passed. A major goal of the legislation was to ensure that people can take full advantage of the ever-growing power of genetic testing for predictive, diagnostic, and genealogical purposes without having to worry that the information revealed would jeopardize their ability to get or keep a job. Another incentive was that without such protections, people were likely to balk at requests to participate in genetic research, which depends on large-scale participation by diverse populations to make new biomedical discoveries about propensities to diseases and other aspects of inheritance.

“We know that in the past, patients have passed up genetic testing that could benefit their health, and have gone to great lengths to keep genetic information secret—even from their own doctors,” said Susannah Baruch, who directs the law and policy program of the Genetics and Public Policy Center at Johns Hopkins University, speaking last week at an EEOC meeting. “There are many factors an individual may consider in deciding whether to take a genetic test, but the fear of discrimination must not be one of them.”

Under the language proposed by EEOC (shorter summary here), GINA would absolutely, and with no exceptions, prohibit the use of genetic information—including family medical history—in employment decisions. It would create protections for people whose genetic information falls into an employer’s hands by accident. And it would make victims of discrimination by private or government employers eligible for potentially robust remedies, including reinstatement, promotion, back pay, injunctive relief, compensatory damages and, in some cases, additional punitive damages.

Unfortunately, progress toward implementing regulatory language is not as far along for Title I of GINA—the part that aims to prevent gene-based discrimination by health insurance companies. That reflects in part the fact that oversight of this provision cuts across agency lines, so language must be agreed upon by a coalition of regulators representing the departments of Health and Human Services, Labor, and Treasury. It also reflects the reality that anything having to do with the lucrative health insurance industry—which for more than a decade argued that GINA was not needed and should not pass—is politically treacherous. And honestly, there are some tricky issues in this part of the Act.

Consider, for example, that the law generally prohibits insurers from even asking a person to reveal genetic information, including whether any diseases run in a person’s family. But what to do about the growing number of employer-sponsored “wellness programs” that try to prevent the onset of diseases by using health risk assessments? These programs typically include questions about family history and other genetic information to help design personalized plans for staying healthy. Indeed, that is pretty much the basis of how they work. It will take some elegant crafting to implement GINA without undercutting the potential value of wellness programs and other emerging aspects of personalized medicine.

The agencies working on language for Title I need to wrap up their work soon if they are going to make the May 21 deadline. They must resist the temptation to punt—by, say, implementing an interim or temporary rule, as some have quietly begun to talk about. That would only delay final implementation of GINA’s valuable protections.

GINA is an unusually forward-looking package of protections in that it prohibits a class of discrimination that has not yet become widespread. But hundreds of gene tests are now widely available for various purposes and more are being developed every month—including some that are being marketed directly to consumers with only vaguely defined firewalls to keep insurers and other interlopers at bay. If we wait much longer, GINA could go down in history not as a pioneering piece of legislation but as an important but embarrassingly late corrective akin to the Civil Rights Act, righting a wrong that was allowed to go on for too long.

Rick Weiss is a Senior Fellow at the Center for American Progress and Science Progress.

If so their anger is misplaced. The issue here is not reproductive freedom but the responsibilities of the fertility specialists to make judgments about the appropriateness of assisting a woman who already has children and of implanting so many embryos. As our Science Progress advisory board member (and my UPenn colleague) Art Caplan put it in his typically direct way, “With all due respect, the idea that doctors should not set limits on who can use reproductive technology to make babies is ethically bonkers.”

Rather, public anger should be directed at a fertility industry that puts mothers and babies at risk. One good outcome of this episode could be the American Society for Reproductive Medicine’s investigation of whether the physicians followed its guidelines for in vitro fertilization. A strong statement by the ASRM would act as a warning and seems preferable to legislation, which would be exceedingly difficult to write in a way that did not prejudice tougher cases.

As the saga of the octuplets unfolds, we were struck by a Wall Street Journal report that another LA fertility clinic (what is it about those Angelenos anyway?) is planning to offer the service of testing embryos prior to implantation for traits like gender or hair color. Reading this story, thirty years of teaching and writing about bioethics flashed before my (brown) eyes. Using pre-implantation genetic diagnosis to make babies with various skin tones may make for delightful bus stop advertising but distressing public policy. Advances in genetics, such as the copy number variation technologies described previously in SP, appear to be leading in the direction of fairly complex trait selection, if not in the near future then someday not so far away.

Leaving aside the question of whether the genetics is as far along as the clinic believes (perhaps it will offer a money-back guarantee), progressive politics entails respect for differences. Skeptical as we are about casual slippery slope arguments, practices that implement and institutionalize attitudes that reduce persons to pigments should at the very least be discouraged. Societies may justifiably limit technologies that are wholly cosmetic while threatening to do harm to innocent bystanders.

In the final analysis, both of these incidents call for the establishment of international standards for reproductive services that draw a line between procedures that are medically appropriate and scientifically compelling, cosmetic but innocuous, or downright dangerous and divisive.

Jonathan Moreno is the David and Lyn Silfen University Professor and Professor of Medical Ethics and of the History and Sociology of Science at the University of Pennsylvania. He is a Senior Fellow at the Center for American Progress and Editor-in-chief of Science Progress.

If that seems quick to you (how could a company pass muster just a few weeks after the ground rules were released?) you are right. In fact, by approving the drug without having at least one public meeting devoted to important environmental, animal welfare, and other issues, the agency broke its own promises of how such approvals will be handled. Word on the street was that Atryn’s maker was in need of a positive nod from the FDA to help it get some investor dollars. Well, we wish the company well. But we also hope that the agency gets back on its own track with future applications, which are anticipated to encompass not only medicines made in animals but also gene-altered animals that themselves will be marketed for human consumption.

Image: flickr.com/jb1

Already, the FDA runs the Critical Path Initiative, which aims to enhance the product development process by incorporating new tools for product evaluation. These include biomarker assessments, which aim to correlate the presence of certain genes or proteins to the likelihood that a patient will respond to a new medical product. And just a few months ago, the FDA entered into a partnership with Medco, a pharmaceutical benefits manager for more than one fifth of the American population, which can give the FDA access to a plethora of de-identified patient information on tests, prescriptions, and clinical outcomes. The partnership provides an economical alternative to clinical trials, as Medco can data mine reimbursement claims from very large, diverse, real-world cohorts. From this data, Medco and the FDA can then infer the predictive power of genetic tests and identify dosing trends—knowledge extremely valuable to personalized medicine as a whole, because the FDA can then issue more clinically effective guidelines for drug administration.

Unfortunately, dramatic changes will be necessary before the U.S. healthcare system can fully incorporate personalized medicine into everyday clinical practice. Two major priorities include: adoption of digital health records and a reformed reimbursement process that rewards positive clinical outcomes instead of just additional procedures and tests. Last year the Department of Health and Human Services put together a small group called the Personalized Healthcare Initiative which issued a 300-page report on personalized medicine. Additionally, the Secretary’s Advisory Committee on Genetics, Health, and Society, or SACGHS, at HHS also released a behemoth report on pharmacogenomics. It is time for HHS to start taking comprehensive action and coordinate across relevant agencies: from the Centers for Disease Control and Prevention and the Centers for Medicare and Medicaid Services, to the NIH and the Agency for Healthcare Research and Quality.

Such is the case with the Food and Drug Administration’s handling last week of the nation’s first formal application by a company to market a human medicine produced by genetically engineered farm animals—specifically, a medicine made in the udders of goats.

The medicine is antithrombin III (brand name ATryn), a protein that aims to prevent blood clots in people with a rare but dangerous hereditary propensity to clot when they should not, manufactured by GTC Biotherapeutics of Massachusetts. More to the point, it is manufactured by the company’s transgenic goats, which contain a human gene that directs production of the anti-clotting protein in their milk.

It’s a cool approach. The only antithrombin III approved in the United States today is purified from donated human plasma, an unpredictable source that periodically dries up, leaving American patients scrambling. And compared to conventional means of producing biological drugs, such as gene-altered bacteria grown in vats, goats are stalwart and generous, churning out massive quantities in every glass of the white stuff. “Got Antithrombin III? You betcha!”

GTC’s application is the first of its kind, but others are on deck. The company, along with more than 20 other research teams around the country, anticipates a not-too-distant future in which transgenic farm animals will make many human medicines. Endowed with the right genes, a small herd of lactating goats could squirt out enough malaria medicine for all of Africa faster than you could sing a few verses of “Old MerckDonald had a Pharm.”

Problem is, federal regulators were not fully prepared when the folks at GTC anted up for a fast-track review. As I’ve written, it was not until September that the FDA released a draft version of its Guidance for Industry #187, which would codify how the agency will review applications to approve food or drugs from gene-altered farm animals. The agency accepted public comments through December and has yet to release any final guidance.

That made for an awkward situation on Friday, when an FDA advisory committee was asked to rule on whether the medicine made by GTC’s goats was safe and effective and therefore suitable for sale—without the agency’s veterinary center having even finished writing the rules on what constitutes an acceptable production process in animals.

Also embarrassing, if not plainly disingenuous: Agency officials had promised that its reviews of the first foods and drugs made in gene-altered animals would include public meetings at which they would discuss animal welfare, environmental, and public health issues openly. Yet Friday’s meeting had jurisdiction only over the safety and efficacy of the drug itself. After some hemming and hawing, FDA veterinary officials conceded that no public meeting dedicated to those other important issues was likely to happen for this first approval, in part because of statutory requirements that demand the agency move quickly on applications, such as this one, that have won fast-track designation. (The company’s hurry was not explained. In similar cases the problem has often been a shortage of funds and the need to achieve a key regulatory success in order to attract fresh venture capital.)

Friday’s presenters did divulge a few details about ATryn pharming. Company officials and FDA scientists (who have repeatedly inspected GTC’s operations), described all seven generations of the clot-busting goats as hale and healthy (indeed, the founder goat—the grand patriarch of this valuable line—was repeatedly described using the scientific term “handsome fella”). To prevent escape and ensure that their meat and medicinal milk never find their way onto grocery shelves, the goats are double-fenced and under constant video surveillance. They even have electronic transponders implanted under their skin so scientists can track them, if necessary, through the Massachusetts woods. A shockingly thin (read: single sheet of paper) agency-led “Environmental Assessment” concludes that the herd “is unlikely to result in significant effects on the environment.”

Several observers, including Greg Jaffe, director of biotechnology at the Center for Science in the Public Interest, were rightly unimpressed.

“More information about the risk analysis surrounding the genetically engineered goats needs to be made public and scrutinized by independent experts before any product approvals,” Jaffe told me, calling the FDA’s work to date “a good first step.”

Nina Mak, a research analyst with the American Anti-Vivisection Society, raised animal welfare issues. Typically, she said, hundreds to thousands of animals are engineered before an acceptable founder is created. “Unintended and unexpected problems are frequent, greatly increasing animal suffering.”

Mak said it was “astounding” that the FDA would consider approving a drug from a genetically engineered animal when it has not even decided what the rules for such approvals should be. She is right. The only tempering factor is that a number of FDA officials all but conceded that they, too, were chagrined. “Ordinarily,” said the FDA’s Eric Flamm, “we may want to coordinate the two reviews” of the drug itself and of the engineered animals and their various impacts.

After the advisory committee was told, to some members’ open dismay, that it could consider only whether goat-derived ATryn is safe and effective in patients, it voted yes. A final FDA decision is expected by next month. By then the FDA will presumably have released a more finished document describing the rules for approving drugs from gene-altered animals (I predict a release on Jan. 16, the last government workday of the Bush administration), and agency officials will have declared that GTC’s goats passed muster, though it will be too late for the public to weigh in.

A lot of eyes ought to be watching to see if the agency keeps its promise to do better next time.

Rick Weiss is a Senior Fellow at the Center for American Progress and Science Progress.

As a participant in the Personal Genome Project, Pinker’s complete genome and medical history are available on the Internet for researchers to explore. His own experience poking around his genetic profile and reading about studies correlating specific variations to heritable traits leads him to speculate on what does (and will continue to) motivate people to know themselves by reading their own DNA.

For better or for worse, people will want to know about their genomes. The human mind is prone to essentialism — the intuition that living things house some hidden substance that gives them their form and determines their powers. Over the past century, this essence has become increasingly concrete.

But despite his sense that genomoics plays into this essentialism, Pinker’s explanations of the state of scientific research go a long way towards demonstrating that we are not simply the sum of our genetic parts:

Many of the dystopian fears raised by personal genomics are simply out of touch with the complex and probabilistic nature of genes. Forget about the hyperparents who want to implant math genes in their unborn children, the “Gattaca” corporations that scan people’s DNA to assign them to castes, the employers or suitors who hack into your genome to find out what kind of worker or spouse you’d make. Let them try; they’d be wasting their time.

Considering the social elements of our genomes will only become increasingly important—in part because that desire to know one’s self will drive some of the consumer interest in sequencing and interpretation, along with the business models that enable both. A significant element of the service 23AndMe offers is the ability to social network with others who have submitted their spit vials for testing. For the moment, this is considered “recreational.” But if a drop in cost combined with a policy push to include genetic information with electronic health records puts this sort of data in the hands of large numbers of Americans, it seems reasonable that a significant number of people will be equally curious about who has genes similar to theirs, and what behavioral traits they might share.

Granted that this fantasized exchange is both silly and perhaps too close to legislative reality, it does illustrate the fallacy. Now a Turkish opposition leader has gone one better, accusing President Abdullah Gül of secret Armenian ancestry as the reason for his failure to reject a campaign to apologize for Turkey’s genocidal war against Armenians in the early 20th century. Republican People’s Party Deputy Canan Aritman thinks she’s nailed it. The acid test: Aritman wants Gül to take a DNA test to prove his pure Turkish origins, or disprove his impure Armenian ones.

Whether President Gül is a genetic Armenian or not (whatever that could mean), the notion that such a question is relevant to political discourse evokes ugly associations with National Socialist eugenics. One would think that any Turkish political leader seeking to distance Turks from a holocaust would want to avoid racial biology as an explanation for anything. And that is no ad hominen argument.

The advent of bioinformatics has driven home the point that there’s a wealth of genetic information that humans will never be able to comprehend without the help of computers. Science reports (subscription) from the annual meeting of the American Society of Human Genetics that one of the hottest fields in genomic research leverages computing power to sift through the patterns of copy number variations in gene sequences and determine their connection to phenotype and disease risk.

Copy number variation refers to the fact that the number of copies of a gene, or deletions from sequences within a person’s DNA, along with the placement of those copies or deletions, contributes to his or her inherited characteristics. That is, the copies or deletions are themselves genetic information, like the squeaks and pauses in a string of Morse code. Using sequencing methods, researchers can identify the variation in sequence patterns across a population. Spotting those variations is one challenge, but associating them with observable characteristics is another matter altogether. Jennifer Couzin writes:

The study of CNVs, like any emerging field, is plagued by uncertainty. Often the technology used was not designed to detect CNVs, making results difficult to interpret. And it’s not at all clear which CNVs alter the function of genes or influence disease. Last week, scientists at the meeting described links between CNVs and various cancers, schizophrenia, autism, body mass index, and Crohn’s disease. But in nearly all these cases, questions remain as to whether CNVs are coincidentally present, are linked to another genetic disease driver, or are themselves causing ill health.

We spoke with Nancy Spinner, a professor at the University of Pennsylvania, earlier this year, about this emerging field of research. She pointed out that CNV studies can be be powerful, but there’s a lot more to learn: “The problems that are now facing us are just at the very beginning of a) understanding the variation in the genome, and b) understanding how it relates to health and disease. It is all so new that it is very difficult. The science is just not there yet, to be able to tell us what it means to have something that is extra or missing.”

Weiss’s Notebook

CAP Senior Fellow Rick Weiss covered science and medicine for The Washington Post for 15 years, and now he brings his investigative eye to science policy. From cloning and stem cells to agricultural biotechnology and nanotechnology, Weiss examines the issues at the intersection of cutting edge research and public policy.

As my brother-in-law and I gazed upon the enormous, picture-perfect turkey glistening golden-brown on his cutting board last Thursday, we had the same thought—and blurted it out in near-unison: It looks just like the fake turkey that President George Bush delivered to the troops during that photo-op in Baghdad a few years ago!

Indeed, the big-breasted bird on his kitchen counter was too plump, too perfectly muscled, too marvelous to be true. And as I recalled some of what I’d learned over the years about how the once-wild American turkey came to be the magnificently mutated mass of meat that it is today, I couldn’t help but also think again about the Food and Drug Administration’s pending decision on whether to allow the marketing of foods from gene-altered farm animals.

Turkeys are not made by genetic engineering—not yet, at least. But no one can look at the modern Butterball (or, for that matter, the Amish-market free-range Amazon that my brother-in-law broasted) without facing the fact that the animals we eat today have little in common with their wild predecessors. It’s an argument that proponents of gene-altered food have made repeatedly, and one that is especially difficult to ignore on Thanksgiving: Whether by DNA manipulation or old-fashioned selective breeding, we engineer our food. Get over it.

As I’ve written before, I don’t fully buy it. But to be fair, let’s consider the turkey’s trajectory from sinewy forest fowl to succulent urban uber-bird.
The turkeys of Pilgrim’s pride were bigger than the average avian entrée of the day and so popular for special occasions, but they were small and scrawny by today’s standards. The modern turkey was not born until the 1940s, when scientists in Beltsville, Maryland, used conventional breeding to begat a definitively better bird—one whose feathers were white instead of the traditional camouflage green and brown. That took care of a longstanding aesthetic issue. When turkeys with colored feathers got processed, it turns out, the leftover roots and pigments from those feathers gave the meat a five-o’clock shadow. Understandably, that didn’t sit well with consumers.

The advent of the Beltsville White helped launch a major market for turkey meat, which in turn led to a big push for faster growth and bigger birds. Through a series of intensive breeding efforts that began in earnest in the 1980s, turkeys in the 1990s were achieving weights of about 35 pounds in as little as 20 weeks—a 40 percent improvement in heft compared to a decade earlier. Of course, that’s a trend we’ve seen in humans, too. But in this case we’re not talking about an obesity epidemic. The new birds have extremely efficient metabolisms that quickly convert feed into meat and not fat.

Today, more than a quarter of a turkey’s body weight is muscle, and most of that is breast, to satisfy U.S. consumers’ preference for white meat. The bones are oriented and muscled in ways that allow the birds to remain upright despite their teetering, cantilevered, Dolly Parton-ish proportions.

There was a price to pay, of course—for the turkey, that is. The birds’ internal organs are crammed together in what little space remains in the body cavity, which may help explain why the lifespan of a modern turkey is a fraction of what it used to be, even if it is lucky enough to get a Sarah Palin pardon. And sex is all but physically impossible, which is why virtually every turkey raised in this country today is conceived by means of artificial insemination. (I once met, in Beltsville, the guy whose job it was to get many of the semen samples used in this process. He did so by hand, using a technique that he referred to as “abdominal massage.” Suffice it to say that he did not have to call to the turkeys when he walked into a pen.)

My point is that this massive reengineering of the turkey by old-fashioned breeding is clearly more substantive than any of the changes that we might expect to occur through the insertion of a mere gene or two into a few members of the modern barnyard menagerie, such as the Aqua Bounty farmed salmon (gene-altered to make them grow faster) or the Canadian Enviropigs (gene-altered to make their manure more environmental friendly). So it is understandable, perhaps, that the FDA has taken a stance favoring the marketing of milk and meat from gene-altered animals, at least once they have passed some basic tests for safety.

The agency accepted public comments on the issue until just before Thanksgiving (virtually all of which, visible here, were negative, though for the most part not carefully reasoned), and a final decision is expected soon.

As the agency digests consumer sentiments and weighs them against the economic interests anxious to get their altered animals to market, let me just remind regulators and other readers of a few facts that should temper any decision to commercialize these critters too quickly.

1. Breeding happens slowly. Genetic combinations that result from sexual recombination and that don’t work well tend to get weeded out over time and are unlikely to get to a consumer’s mouth. That safety margin can be compromised when genes are crammed into massive numbers of creatures that are then sent on the fast-track to grocery shelves.
2. Genes can behave differently in foreign species than they do in their home turf. An experiment a few years ago involved the transfer of an ordinary gene from a bean into a pea plant. In the bean, the gene coded for the production of an ordinary, non-allergenic protein. In the foreign genomic environment of the pea plant, however, the innocuous bean protein attracted a coating of other molecules that made the protein potentially dangerous to people with certain food allergies. Such unexpected results in cross-species recombinant DNA experiments undermine the idea that genetic engineering is just like regular breeding but more precise.
3. Eating is intimate. People have emotional relationships to food. Even if the health risks to consumers and the animals themselves are low, producers and regulators would be wise to open the new agricultural approach to some degree of public inspection as a way of fostering all-important consumer trust. In other words, make the approval process more transparent than what the FDA has proposed so far.
4. Remember our far-flung food importers. Even if we in the United States decide we are okay with food from engineered animals, our trading partners around the world may not be. In fact, history has shown many of them to be more than a little queasy on this topic. Whatever cost savings may be had from a faster-growing salmon must be weighed against the potential losses in confidence and, ultimately, sales, caused by our move into what others might see as the realm of phony food.

There is an important future for engineered animals as sources of food, medicines, plastics, high-tech fibers and perhaps even organs for transplantation into people—all applications researchers are now pursuing in an array of U.S. labs. But if companies insist on working through an FDA approval process that, as currently proposed, would allow essential details to be kept under wraps forever as “confidential business information,” then they shouldn’t be surprised if they are lambasted as, well, turkeys.

Rick Weiss is a Senior Fellow at the Center for American Progress and Science Progress.

Weiss’s Notebook

CAP Senior Fellow Rick Weiss covered science and medicine for The Washington Post for 15 years, and now he brings his investigative eye to science policy. From cloning and stem cells to agricultural biotechnology and nanotechnology, Weiss examines the issues at the intersection of cutting edge research and public policy.

“Personalized medicine” is the hot new buzz phrase in medicine. Why settle for diagnostic tests or therapies that were designed for the average patient, the thinking goes, when doctors can use new technology to pinpoint the specific details of your bodily biology and tailor tests and treatments to your exact medical situation?

The idea has potential and may gradually catch on as gene tests and other new technologies become more accurate and affordable. But a candid new report from the Department of Health and Human Services balances those lofty promises with a tally of the daunting challenges that scientists, doctors, patients, and insurers will face as the American healthcare behemoth tries to make the leap to the personalized medicine paradigm.

The issue is gaining importance because healthcare reform is high on the agendas of both Congress and the new president in the coming year. Proponents of personalized medicine want to make sure that whatever reforms are instituted do not undercut progress toward a more personalized future. At the same time, one can’t help but conclude, on the basis of the HHS report, that it is going to be an uphill battle to justify some of the upfront costs of the personalized medicine revolution, given the many technical, political, and educational hurdles that stand between where we are and where we want to get.

Some kind of reform is clearly needed. As HHS Secretary Michael O. Leavitt notes in his introduction to the 299-page report (a follow-up to one published a year ago), U.S. healthcare expenditures amounted to just 4 percent of the nation’s gross domestic product when he was born in 1951 but are now 16 percent of GDP and are projected to hit 20 percent by 2016—a trend he calls “not sustainable.” All told, today’s health expenditures of about $2 trillion are expected to double within less than a decade.

The core of the problem, as described in the report, is that Medicare—by far the nation’s largest healthcare payer and the standard-bearer that other insurers use as a model—bases its payouts on volume rather than on value.

Under this system, there is a positive economic incentive to deliver more care rather than better care since Medicare makes payments made irrespective of quality. Indeed, there is little or no incentive to make a proper diagnosis or choose the best treatment the first time around.

Among the many efficiencies that could be brought to this system, one shines brightest among proponents of personalized medicine: customize treatments based on individuals’ particular situations and especially on the basis of their genetic makeup. By one estimate, simply customizing the doses people get of the blood-thinning drug warfarin could save as much as $1 billion a year. The medicine is one of the most heavily prescribed in the country and can cause serious side effects if not calibrated precisely to a patient’s needs.

But there are a number of difficult hurdles to clear before we can realize that dream.

First, we must create a universally usable electronic health records system capable of managing, in a standardized way, the new kinds of genetic information that will be at the core of personalized medicine.

“At a time when information technology has transformed most other sectors, with particular benefit to the consumer, the health care sector, with its paper files, often inaccessible records, and incomplete patient data, stands out as primitive indeed,” Leavitt laments in the HHS report.

There is, at least, progress on this count. The department proposed standards for embedding genetic data and other family history information into electronic health records in 2008 and is in line to finalize those guidelines in 2009. HHS also set a national goal of getting most Americans switched over to electronic health records within five years, an ambitious if probably unrealistic aim.

But we will need a lot more than electronic records. By one account in the HHS report, patients (who are known in the lingo of personalized medicine as “consumers,” a worrisome shift in nomenclature I will address in a moment) will have to take on more of the job of keeping those records accurate and up to date with the help of “new consumer-friendly tools.”

For the most part we still don’t know when, if ever, medical professionals will understand enough of this information in a way that can really have a positive impact on people’s health or the national health care budget.

Take, for example, the time you generally spend at the beginning of a doctor visit, describing how you’re doing and giving the clues that a trained physician might recognize as medically important. That conversation “unnecessarily consumes precious time from providers,” according to a chapter in the HHS report contributed by Geisinger Health Systems. The solution? Spell out your woes to a touch-screen computer before the doctor comes into the exam room.

As it turns out, this is just one of several ways in which personalized medicine will demand a new (and rather impersonal) level of personal responsibility when it comes to health care. In fact, the hidden bomb in the word “personalized” in this new medical context is that it is going to be very much up to the “person”—that “consumer” we were talking about a moment ago—to decide how to deal with all the incoming information, including how to understand what it means and how to balance it against the economic realities of limited health coverage.

As the group FasterCures notes in the HHS report, a major hurdle for personalized medicine “is a lack of ‘genetic literacy’ among members of the general public. Informed patients are critical to patient-centered care, but as personalized medicine techniques become more sophisticated and information more complex, caregivers will face steeper challenges in communicating effectively with patients of all education levels and backgrounds.”

This education process will get even more dicey as doctors and other caregivers try to convince patents—er, consumers—to upload their personal medical information to giant databases in order to help researchers figure out what all these genetic signals really mean. “Discovery will come more rapidly if large amounts of clinical information are made available to researchers,” the report says. “The largest source of such information is ourselves,” it goes on, noting that this is one of the great advantages of getting people’s information into uniform “interoperable electronic health records”: It’s easier to suck personal data up into a data-crunching combine to speed discovery.

I did find one clause buried in those 299 pages acknowledging that “many issues, including privacy protection,” still need to be addressed.

No kidding.

Patient-consumers (or perhaps impatient consumers, waiting for that automated touch-screen to ask them where it hurts) are not the only ones who may find it difficult to adjust to the brave new world of personalized medicine. There are questions about whether pharmaceutical companies will find any economic incentive to develop medicines that are useful for only small, genetically specialized portions of the population. And then there is the looming question of how many of the countless genetic tests now under development are really going to prove themselves to be valuable at all.

As noted at a Personalized Healthcare Summit held in October, “Genetic and genomic knowledge relating to clinical outcome is missing – does value exist when these markers are used in a real clinical setting? The data don’t exist yet to guide physician action.”

In other words, for the most part we still don’t know when, if ever, medical professionals will understand enough of this information in a way that can really have a positive impact on people’s health or the national healthcare budget.

It doesn’t help that the Food and Drug Administration has opted not to regulate most gene tests, citing a shortage of resources; that HHS has so far resisted calls to create a proficiency testing program that would help ensure that test results are accurate and meaningful; or that the Medicare program for the most part does not reimburse for tests considered “predictive,” which pretty much blows the incentive to create these kinds of tests in the first place.

Health officials can say all they want to convince us “consumers” that it is empowering to take the reins of our own healthcare, but the truth is most people feel totally overwhelmed as it is and will be feeling even more so as health technology advances further. No wonder the HHS report acknowledges that the public may not be ready for personalized medicine.

“Patient education will play a prominent role in the acceptance of personalized healthcare, given that patients will need to become more involved in managing their own health portfolios….”

There’s a lot of work to be done by those designing this revolution before I’ll be waving a red flag at the barricades.

Rick Weiss is a Senior Fellow at the Center for American Progress and Science Progress.

But how and where should the lines be drawn? If drawn too tightly they could constrain valuable medical research. If drawn too loosely they could open the door to a Gattaca-like world of neo-eugenic practices and ideologies.

In the United States serious discussion of these questions has been thwarted for the past eight years by partisanship and polarization, and constructive engagement by the Bush administration at the international level has been effectively nil.

The good news, however, is that during this same period many countries have been developing comprehensive human biotech policies that strike a practicable and socially responsible balance between being overly restrictive and overly permissive. A survey of all 192 countries and eight major intergovernmental organizations suggests that:

• There is widespread support for human embryonic stem cell research involving embryos created but not used in the course of assisted reproductive technology, or ART, procedures.
• There is similarly widespread support for embryo screening to avoid passing serious diseases to one’s offspring.
• There is strong opposition to human reproductive cloning, inheritable genetic modification, and embryo screening for non-medical purposes.
• There is widespread concern about the commercialization of human reproductive activities and about the use of genetic technologies for so-called “enhancement” purposes.

One practice about which there is no clear consensus is the creation of clonal human embryos for research purposes. Most countries that have adopted policies addressing this practice have prohibited it, but more than a quarter explicitly support it.

This map provides an overview of selected human biotechnology policies around the globe [1]:

It is instructive to note that of the thirty member countries of the Organization for Economic Cooperation and Development, which together account for 84 percent of world GDP and have the most fully developed biomedical research sectors, fully twenty-six (87 percent) allow human embryonic stem cell research using ART embryos. At the same time, 97 percent of OECD countries have banned human reproductive cloning; 87 percent have banned inheritable genetic modification; and 80 percent have banned embryo screening for non-medical purposes. None have approved these. And those few OECD countries that don't yet have formal policies appear to be unsupportive of these practices.

In most OECD countries and many others, the policies just noted are part of comprehensive regulatory regimes established at the national level that also address important safety, privacy, consent and other concerns. Several countries have established national regulatory agencies, such as the United Kingdom’s Human Fertility and Embryological Authority and Canada’s Assisted Human Reproductive Agency. These allow valuable medical research to proceed in an accountable and socially responsible manner while taking dangerous or otherwise undesirable applications off the table. They also facilitate public participation in the ongoing review and modification of human biotechnology policies.[2]

It’s important to note, however, that the majority of countries worldwide have not yet adopted any meaningful policies regarding the new human biotechnologies. Recent scandals involving stem cell research in South Korea and Austria should be a wake-up call concerning the need for responsible regulatory oversight if such research is to retain public support.[3] In addition, the current policy deficit is an open invitation to rogue nations and scientists intent on creating genetically enhanced bioweapons or conducting human genetic experiments that cross ethical boundaries.

If the emerging policy consensus is to make good on its promise, all countries will need to be part of it in one manner or another. Little is resolved if 189 countries ban human reproductive cloning while three promote themselves as safe havens for the creation of human clones.

Fortunately, discussions about the sorts of instruments that might facilitate meaningful global agreements have been underway for some time. In 2001 legal experts suggested that the 1997 Ottawa Treaty on the prohibition of antipersonnel landmines, and other existing treaties, might serve as models for global agreements addressing the new human biotechnologies.[4] A 2002 proposal by law and bioethics scholars George Annas, Lori Andrews, and Rosario Isasi called for an international “Convention on the Preservation of the Human Species.” It would prohibit reproductive cloning and inheritable genetic modification, and mandate national systems of oversight ensuring that the use of human gametes or embryos for experimental or clinical practices meet consent, safety, and ethical standards.[5]

In 2007 scholars associated with the United Nations University argued that the prohibition of human reproductive cloning may by now have attained the status of customary international law, and that measures to formalize this, perhaps negotiated under the auspices of UNESCO’s International Bioethics Committee, would stand a good chance of success.[6] In early 2008 Asia Society Executive Vice-President Jamie Metzl, who served in the State Department under former President Bill Clinton, proposed a “Genetic Heritage Safeguard Treaty” modeled on the 1970 Nuclear Nonproliferation Treaty. He argued that such a treaty could serve the dual function of encouraging responsible applications of human genetic research and specifying limits on those applications deemed undesirable.[7]

There are other possibilities as well. The Council of Europe’s 1997 Convention on Biomedicine and Human Rights allows countries other than Council members to ratify it, suggesting that well-crafted regional agreements might serve as foundations for global agreements.[8] Alternatively, regional agreements might be crafted that harmonize those provisions having profound implications for humanity as a whole, while allowing other provisions to vary in accordance with regional social and cultural differences.

Development and enforcement of such global agreements will not be easy. For some practices, such as genetic testing and screening, the boundaries between acceptable and unacceptable uses are often unclear, and people are understandably reluctant to forego possible benefits without good reason. Countries may fear that constraints of any sort on biotech research or commerce could leave them at an economic disadvantage. And in a world still rife with nationalist conflict, some countries will want to reserve the option of using these technologies for hostile purposes.

But these challenges can be met. People intuitively understand that the ability to manipulate the human genome holds great potential for abuse. The current global financial crisis has served as a powerful reminder of the need for responsible oversight and regulation in a complex, interdependent world. And the emerging international consensus regarding human biotechnology is remarkably consistent across regions and cultures. Western European countries widely regarded as bastions of secular liberalism, for example, have adopted some of the most comprehensive controls over human genetic technology in the world. This derives from their generally social-democratic political ethos and their first-hand experience in the 20^th century with eugenics, euthanasia, and genocide. Europeans know all too well what can happen when ideologies and policies that valorize the creation of “genetically superior” human beings come to the fore. For different but related reasons, developing countries such as South Africa, Vietnam, and Brazil have likewise established regulatory controls over human biotech research and applications.

There is no reason that the human community cannot come to agreement on where and how to draw lines on the most critically consequential new human biotechnologies. But this will require enlightened and committed social and political leadership, and very soon.

Richard Hayes, PhD, is Executive Director of the Center for Genetics and Society. This article is based on testimony presented at a hearing of the House Foreign Affairs Committee Subcommittee on Terrorism, Nonproliferation and Trade on June 19, 2008.

Acknowledgements: Jesse Reynolds, Jamie D. Brooks and Pete Shanks collected much of the data on which this article draws, and which is displayed in the BioPolicyWiki.

Appendix: Policies Adopted by Intergovernmental Organizations

1. The United Nations

In 2001 France and Germany proposed a binding UN treaty calling for a prohibition on human reproductive cloning. An early procedural vote suggested unanimous support for this measure. A significant number of countries subsequently expressed opposition to banning reproductive cloning without simultaneously banning research cloning. This led to extended controversy, and the debate became, essentially, a debate over the acceptability of research cloning. By 2003 it became clear that a consensus concerning research cloning could not be achieved. In 2005 a non-binding declaration opposing both research cloning and reproductive cloning was brought to a vote. It received a plurality of votes, 46 percent, which under UN rules makes it the official UN position. Both opponents and supporters of research cloning claimed vindication of their positions. Supporters of research cloning noted that as the declaration was non-binding, and as 18 percent of UN member states supported research cloning, the vote was of questionable significance. Opponents of research cloning noted that a larger number of countries had expressed strong opposition to research cloning than had initially been anticipated.[9]

2. UNESCO

The United Nations Educational, Scientific, and Cultural Organization (UNESCO) Bioethics Programme is led by the International Bioethics Committee, or IBC, consisting of 36 outside experts, and the Intergovernmental Bioethics Committee, or IGBC, consisting of representatives from 36 member states. The Bioethics Programme has sponsored three major nonbinding international agreements:[10]

The Universal Declaration on the Human Genome and Human Rights was adopted unanimously by the UNESCO General Conference in 1997 and ratified by the UN General Assembly in 1998. The declaration calls for member states to undertake specific actions, including the prohibition of “practices which are contrary to human dignity, such as reproductive cloning of human beings.” It also calls on the IBC to study “practices that could be contrary to human dignity, such as germline interventions.”

The International Declaration on Human Genetic Data was adopted in 2003. The declaration is intended “to ensure the respect of human dignity and protection of human rights and fundamental freedoms in the collection, processing, use and storage of human genetic and proteomic data, and of the biological samples from which they are derived, in keeping with the requirements of equality, justice and solidarity, while giving due consideration to freedom of thought and expression, including freedom of research.”

The Universal Declaration on Bioethics and Human Rights was adopted in 2005. The
declaration used a human rights framework to establish normative principles in fifteen areas, including human dignity and human rights; equality, justice, and equity; and protecting future generations. These principles cover a wider range of issues than did the previous two bioethics declarations.

UNESCO took the lead in negotiating the International Convention Against Doping in Sports, in collaboration with the World Anti-Doping Agency, which had earlier been established by the International Olympic Committee. It includes language banning the use of genetic technology to enhance athletic performance in official athletic events, referred to as “gene-doping.” The convention entered into force on February 1, 2007, and has been ratified by 86 countries (not including the United States).[11] The earlier Copenhagen Declaration on Anti-Doping in Sport has been signed by 192 countries, including the United States.[12]

3. Council of Europe

The 47-member Council of Europe maintains a Bioethics Division, guided by a Steering Committee on Bioethics. The Council’s Convention on Biomedicine and Human Rights was opened for signatures in 1997 and went into force in 1998. As of March 2008 it has been signed or ratified by 34 countries. It explicitly prohibits inheritable genetic modification, somatic genetic modification for enhancement purposes, social sex selection, and the creation of human embryos solely for research purposes. The Convention is perhaps the single most well-developed intergovernmental agreement extant addressing the new human biotechnologies. Human reproductive cloning was banned by an Additional Protocol on the Prohibition of Cloning Human Beings, which went into force in 1998.[13]

4. European Union

With 27 member states, the European Union and its constituent bodies play a major and growing role in European policy integration. Article 3 of the EU’s Charter of Fundamental Rights, entitled “Rights to the Integrity of the Person,” prohibits human reproductive cloning, “eugenic practices, in particular those aiming at the selection of persons,” and “making the human body and its parts as such a source of financial gain.”[14]

5. African Union

At its 1996 Assembly of Heads of State, the African Union (then called the Organization of African Unity) approved a Resolution on Bioethics that affirmed “the inviolability of the human body and the genetic heritage of the human species” and called for “supervision of research facilities to obviate selective eugenic by-products, particularly those relating to sex considerations.”[15]

6. World Health Organization

In 1997 the WHO called for a global ban on human reproductive cloning.[16] In 1999 a Consultation on Ethical Issues in Genetics, Cloning and Biotechnology was held to help assess future directions for the WHO. The draft guidelines prepared as part of this consultation, Medical Genetics and Biotechnology: Implications for Public Health, called for a global ban on inheritable genetic modification. In 2000 WHO Director-General Gro Harlem Brundtland reiterated opposition to human reproductive cloning.[17] In September 2001 the WHO convened a meeting to review and assess “recent technical developments in medically assisted procreation and their ethical and social implications.” The review covered, among other items, preimplantation genetic diagnosis, intracytoplasmic sperm injection, and cryopreservation of gametes and embryos. In February 2002 the WHO repeated its opposition to human reproductive cloning and cautioned against banning cloning techniques for medical research. In October 2002 the WHO established a Department of Ethics, Equity, Trade, and Human Rights to coordinate activities addressing bioethical issues.[18]

7. Group of Eight

At its June 1997 summit in Denver, Colorado, the G-8 called for a worldwide ban on human reproductive cloning. According to the Final Communique of the Denver Summit of the Eight, the leaders of the G-8 nations agreed “on the need for appropriate domestic measures and close international cooperation to prohibit the use of somatic cell nuclear transfer to create a child.”[19]

Notes

[1] The map displays data available in the BioPolicyWiki as of 28 October 2008. The categories used in the BioPolicyWiki to describe policies are broad ones, and policies are subject to change. Consult the BioPolicyWiki for more background and updates.

[2] The Canadian Assisted Human Reproduction Act (AHRA), approved by the Canadian Parliament in 2004, is exemplary. It grounds its provisions in an explicit statement of principles, prohibits objectionable procedures such as reproductive cloning, and establishes a federal regulatory agency to ensure that permitted procedures are safe and used in an equitable manner. The agency licenses and monitors all private and public fertility clinics, research facilities and other institutions whose activities involve human gametes or embryos. The agency is governed by a 13-member board, half of whose members are encouraged to be women. See more on the AHRA and on the UK’s HFEA in BioPolicyWiki.

Comprehensive regulatory structures for the United States have been proposed by Eric Parens and Laurie Knowles in "Reprogenetics and Public Policy: Reflections and Recommendations," Hastings Center Report, July-August: 2003., http://www.thehastingscenter.org/pdf/reprogenetics_and_public_policy.pdf, and by Francis Fukuyama and Franco Furger in Beyond Bioethics: A Proposal for Modernizing the Regulation of Human Biotechnologies; The Paul H. Nitze School of Advanced International Studies, Washington DC; available at http://www.biotechgov.org/

[3] For Korea, see: “Reflections on South Korea's stem cell scandal,” US News & World Report, 3 Jan 2006, at http://health.usnews.com/usnews/health/articles/060103/3book.htm and “So. Korean scandal rocks stem cell community,” Nat Med. 2006 Jan;12(1):4. For Austria, see “Rector sacked in Austrian stem-cell scandal,” 27 August 2008 | Nature 454, 1041 (2008).

[4] See “Health & Human Rights Leaders Call for Global Ban on Species-Altering Procedures,” Genetic Crossroads, October 2, 2001; available at http://www.geneticsandsociety.org/article.php?id=2809

[5] George J. Annas, Lori B. Andrews and Rosario M. Isasi, “Protecting the Endangered Human: Toward an International Treaty Prohibiting Cloning and Inheritable Alterations,” American Journal of Law & Medicine, Vol. 28, Nos. 2 & 3, pp. 151–178 (2002), available at http://geneticsandsociety.org/downloads/2002_ajlm_annasetal.pdf

[6] Chamundeeswari Kuppuswamy, Darryl Macer, Mihaela Serbulea and Brendan Tobin, Is Human Reproductive Cloning Inevitable: Future Options for UN Governance, United Nations University – Institute of Advanced Studies, Yokohama, Japan, 2007; available at http://www.ias.unu.edu/resource_centre/Cloning_9.20B.pdf

[7] Jamie Metzl, “Brave New World War,” Democracy, Spring 2008; available at http://www.geneticsandsociety.org/article.php?id=3985. Metzl is Executive Vice President of the Asia Society, and served as Director for Multilateral and Humanitarian Affairs for the National Security Council during the Clinton Administration.

[8] Council of Europe, “Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine,” 4 April, 1997; available at http://conventions.coe.int/treaty/en/treaties/html/164.htm

[9] See Center for Genetics and Society, “The United Nations Human Cloning Treaty Debate, 2000–2005,” June 1st, 2006, available at http://www.geneticsandsociety.org/article.php?id=338

[10] See UNESCO, “Bioethics,” at www.unesco.org/shs/bioethics

[11] UNESCO, “International Convention against Doping in Sport 2005,” http://portal.unesco.org/en/ev.php-URL_ID=31037&URL_DO=DO_TOPIC&URL_SECTION=201.html

[12] World Anti-Doping Agency, “Copenhagen Declaration on Anti-Doping in Sport,” 2003, linked from and overview at http://www.wada-ama.org/en/dynamic.ch2?pageCategory.id=272

[13] Council of Europe, “Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine,” 4 April, 1997; available at http://conventions.coe.int/treaty/en/treaties/html/164.htm
“Additional Protocol to the Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine, on the Prohibition of Cloning Human Beings,” 12 January, 1998; available at http://conventions.coe.int/Treaty/EN/Treaties/Html/168.htm

[14] The Charter of Fundamental Rights of the European Union, Article 3, text available from http://www.europarl.europa.eu/charter/default_en.htm

[15] Organization of African Unity, Assembly of Heads of State and Government, 32nd Ordinary Session, Cameroon, July, 1996, “Resolution on Bioethics” (AHG/Res.254[XXXII]), paragraphs 3b and 3f; available at http://www.africa-union.org/root/au/Documents/Decisions/hog/6HoGAssembly1996.pdf

[16] World Health Assembly, Resolution 50.37, on “Ethical, Scientific and Social Implications of Cloning in Human Health,” Geneva, 1997; not currently available on the web. The resolution was reaffirmed in 1998, in Resolution WHA51.10 (same title), available at http://www.who.int/ethics/en/WHA51_10.pdf

[17] Cloning in Human Health: Report by the Director-General, World Health Organization, May 10, 2000; available at http://www.who.int/ethics/en/A53_15.pdf

[18] See “Ethics and Health at WHO,” http://www.who.int/ethics/about/en/

[19] Final Communique of the Denver Summit of the Eight, June 22, 1997; available at http://www.g7.utoronto.ca/summit/1997denver/g8final.htm

In fact, besides people working for the genetic testing industry, not one person interviewed for the story you are reading felt this trend was a good idea. “I see four fundamental problems,” says Ellen Matloff, the Director of Genetic Counseling at Yale Medical School and the Yale Cancer Center. “Have their claims been validated? Who is interpreting these test results? What do you do about it if it turns out you have a genetic disposition for a particular disease? Are these labs regulated?” And while Matloff’s concerns are nowhere near the full list of potential hazards, they are a decent place to start.

The old model was akin to spear fishing: a hunt for variations in a single gene that had been exactingly correlated to rare diseases.

The question of “have their claims been validated?” sits at the forefront of this discussion. Genetic testing has been around for years, but not like the version that’s going on today. The old model was akin to spear fishing: a hunt for variations in a single gene that had been exactingly correlated to rare diseases. Over the years, for things like cystic fibrosis, Down syndrome, and Huntington disease, this method has proved invaluable. The new model, as practiced by companies like GeneticHealth, deCODEme, Navigenics, and 23andMe, is more like drift netting. Using gene arrays—specially designed microchips—these companies comb large swatches of the genome looking for single nucleotide polymorphisms, or SNPs, indicative of a vast assortment of conditions. According to the direct-to-consumer genetic testing companies offering these services, their final reports provide some of the best genetic information science is currently capable of—and while they may not be wrong about this fact, what we’re currently capable of detecting remains an open question.

The issue being that information—in this case genetic data—cannot be confused with interpretation of that data. “SNPs haven’t entered mainstream clinical practice yet because we’re still validating these tests,” says Matloff. “Currently, we don’t have any real notion of what they mean and even less of one about what to do with them.” A great example of this is in David Ewing Duncan’s four part series, done last May for Portfolio.com, in which he personally tested these services and three different companies returned three different answers concerning his apparent risk for heart attack. These confusing results occurred because much of modern genetics relies on looking at genotype, the genetic identity that we cannot observe as physical characteristics, and correlating to phenotype, the traits (or lack thereof) we can readily observe. But correlation is not mechanism and without mechanism many fear what’s left is mere extrapolation. The reason being that for correlation to be accurate a huge sample population is required to provide a convergence of traits. But 23andMe wants to use your DNA to build their genetic database because of a current paucity of such data, which most critics argue is still too small to really determine much of anything.

There are more issues as well. “Almost every genetically rooted abnormality is related to environmental causes,” says Tufts University professor Sheldon Krimsky, author of Biotechnics and Society: The Rise of Industrial Genetics and Vice Chair for the Council for Responsible Genetics, “which means that the entire notion of genes as the master planner is suspect.” Then there’s all the new research in epigenetics—the study of heritable changes in gene expression caused by things besides alterations in DNA sequence—which shows that there are a great many DNA-changing environmental exposures that don’t actually show up as mutations. “At the Washington State University,” continues Krimsky, “they exposed animals to certain chemicals. The genetic effects carried on for two and three generations, but didn’t show up as a mutation on SNP tests.”

All of the above are core issues for companies marketing their products primarily for medical purposes. For example, according to the “About Us” portion of the company’s website: “Navigenics was founded on the premise that by helping people understand what health conditions they are at risk for, before they develop symptoms, we can arm people with the information and support to take the next steps to improve their health outcomes.” 23andMe too provides this information, but they have also expanded on the model. “We take a holistic approach to genetics,” says co-founder Linda Avey, “and give us as much information to our customers as is scientifically appropriate, given the current state of knowledge. Hence, we provide not only information about how genetics may affect your health, but also information about inherited traits (such as eye color, height, lactose intolerance, etc.) and ancestry.” And it is this last bit which causes even more concern, as the genetic basis for disease is far better understood than the genetic basis for ancestry.

While 23andMe does admit this portion of the science is still in its infancy, even the veracity of their claims to be able to tell you if you’re from Asia, Africa or Europe—arguably the simplest genealogical information around—remains very much an open question. “That’s because,” continues Krimsky, “the relationship between ancestry and DNA relies on assumptions about the stability of alleles and that stability has yet to be accurately validated.” Moreover, the current limits on this type of testing allows researchers to trace either the maternal mitochondrial line or the paternal Y chromosome, but not both at the same time. This means you can learn about half of a family tree, but not its entirety. And, again because of the novelty of this science, even that half sits on shaky footing.

The next three of Matloff’s apprehensions tend to dovetail together, but they begin with the question of “who is interpreting these results?” At 23andMe, they offer no genetic counseling, though they will let you talk to their scientists if you have any questions. Unfortunately, knowing enough to have those questions is part of the problem. Genetic testing tells us about potential risk factors for certain conditions, but calculating risk is not a simple process. “Look,” says Matloff, “in the U.S. there’s this notion that more information is really better. But even trained genetic counselors don’t really know what this stuff means, so is more really better?”

And these are not idle concerns. As Stanford University’s Nobel Prize-winning RNA researcher Andy Fire says, “if someone off the street is looking for pointers on how to live a healthier life, there’s nothing these tests will tell you besides basic physician advice like ‘eat right, don’t smoke and get plenty of exercise.’” And even with the more well-regarded tests, like the ones that examine the BRCA 1 and 2 markers for breast cancer—which only account for between 5 and 27 percent (estimates, um, vary) of all breast cancers—identifying risk factors does not always lead to easy treatment options. As University of Pennsylvania bioethicist Arthur Caplan points out, “Say you test positive for a breast cancer disposition—then what are you going to do? The only preventative step you can take is to chop off your breasts.”

So if prevention is not available the only thing left is fear and anxiety. Unfortunately, in the past few decades, there have been hundreds of studies linking stress to everything from immunological disorders to heart disease to periodonitic troubles. So while finding out you may be at risk for Parkinson’s may make you feel informed, that knowledge isn’t going to stop you from developing the disease—but the resulting stress may contribute to a host of other complications.

Also in question is the clinical accuracy (as opposed to analytical accuracy) of these tests, but it’s difficult to assess this without also addressing the last of Matloff’s concerns: whether or not these labs are regulated. The short answer is no. The longer answer is slightly more complicated. According to Gail Javitt, Law and Policy Director for the Johns Hopkins Genetics and Public Policy Center, the only existing nationwide regulations that cover this industry are the 1988 Clinical Laboratory Improvement Amendments, or CLIA—a law that passed because of a spate of false negative results in pap smears—and those regulations are, in her words, “fairly light.” While there have been ongoing attempts to strengthen the genetics portion of CLIA, these have met with much governmental resistance and nothing has been done so far. Without a national system to review quality, there is really no way to assess the accuracy of these tests, but Javitt does mention that in 2006 the Government Accountability Office ran an undercover “sting” operation of direct-to-consumer nutrigenomic tests. “They found that the results of testing appeared to be based on the health information provided rather than a difference is customer’s genetic make up,” says Javitt, “and that the claims made by the companies were misleading and so vague as to be not useful to consumers.”

But even better laboratory regulation may not solve this problem because most direct-to-consumer companies are not actually testing labs. 23andMe uses an “off-the-rack” gene array, a chip built by Illumina which examines 550,000 standard SNPs, and has been further customized to include another 50,000 that 23andMe scientists find useful. Illumina processes the data as well, shipping the results back to 23andMe, which then assembles it into an interactive package that is delivered to the consumer via the web. This makes regulation even trickier because these personalized genetics companies are technically serving as middlemen in the actual operation.

“Most people think that GINA [the 2008 Genetic Information Nondiscrimination Act] goes a lot farther than it does.”

Beyond the question of clinical accuracy lies the entire ethical quagmire of direct-to-consumer marketing for medical technologies in general and genetic testing in particular. The list of issues surrounding this muck have been well-publicized elsewhere, with just about every major journal covering the topic to some extent over the past decade, but a greatest hits summary of potential advertising sins include: misinformation about genetics, an exaggeration of consumer risk, an overstatement of the value of genetic testing, manipulation of behavior by exploiting consumer fears and worries, endorsement of a deterministic relationship between genes and disease, reinforcement of the links between ethnic groups and disease, no pre-market review for the tests themselves, and no advertising content oversight. The Federal Trade Commission is charged with protecting consumers against these kinds of unfair or deceptive trade practices, but while they’ve already staked out genetic testing as their territory, all they’ve done so far is to tell consumers to be skeptical of direct-to-consumer claims and to discuss them with a health care provider. The Food and Drug Administration has some authority here too, but only regulates genetic tests sold as “test kits”—meaning kits used by the labs for this kind of testing—but because most of these labs are designing the tests themselves, they fall outside of the FDA’s jurisdiction and thus go unexamined.

Certainly, there is more than enough uncertainty here to justify the 2003 Journal of Clinical Oncology story entitled: “Direct-to-Consumer Marketing of Genetic Test for Cancer: Buyer Beware” (among many other examples), but the tests and the resulting information make up only one half of this entire picture. The second portion comes down to issues of privacy and discrimination and how safe your data really is. On this matter, let’s just start by saying it wasn’t just the doctors who thought direct-to-consumer genetic testing was a bad idea—the lawyers thought the same thing.

In part, the reasons the lawyers feel as such has to do with speculative fears rather than actual fears. 23andMe claims that the firewall separating your phenotypic information (hair color, weight, ailments, etc.) from your genotypic (DNA) information is invulnerable. And they are not casual about this. They have an in-house security team constantly assessing data security and hire outside consultants to attempt to break in to further augment their system’s robustness, but this doesn’t assuage everyone. “Historically,” says Deven McGraw, Director of the Health and Privacy Project for the Center for Democracy and Technology, “we’re always one step behind the hackers. It seems like if someone really wants this information sooner or later they’ll figure out how to steal it. And once this data gets out there, it’s out there. There’s no way to put that genie back in the bottle.”

McGraw and others point to the recent National Institutes of Health decision, made in September of this year, to pull all their genetic data offline because David Craig, of the Translational Genomics Research Institute in Phoenix, Arizona, devised a statistical algorithm that allows identification of individual DNA profiles from samples comprised of more than a thousand people. While this seems a very separate case from the privacy concerns facing these direct-to-consumer genetic companies, the point is that no one really knows what tomorrow’s technology is going to bring. It could very easily bring a way to identify more and more phenotypic information from less and less genotypic information so perhaps their caution does seem justified.

Caution is also justified because once that information gets out there, Americans are really afforded very scant protection under the law. “Most people think that GINA [the 2008 Genetic Information Nondiscrimination Act] goes a lot farther than it does,” says Mark Rothstein, director of the Bioethics Institute at Louisville School of Medicine. “GINA only covers employment and health insurance discrimination. For employment it only covers people who are asymptomatic. If a genetic test shows you’re at risk for Parkinson’s, you can’t be discriminated against, but if you actually develop the disease then that protection ends and it becomes a question of state law. The health insurance portion is problematic because it’s just health insurance. The protections don’t include life insurance, disability insurance, long term care insurance—and since GINA doesn’t help you once you develop a disease then these other acts are the fallback and they’re outside of the circle of protection.”

This brings us back to the social networking portion of 23andMe’s business model. According to Avey, this feature allows the curious “to compare their genome to those of family and friends who are also 23andMe participants. Customers can also join the 23andMe communities, where they can connect with others, share stories, ask questions about specific traits and ancestry groups and learn more about research studies. They can also actively participate in genetic discoveries, through our research program, 23andWe, by filling out online surveys.” While DNA-based social networking has proven especially popular with 23andMe’s clients, how many of those clients believe it either a harmless pastime or a pastime protected by GINA remains a pertinent question. So while Gawker’s notion that this is a trend that will “destroy the world” is certainly hyperbolic, their concern is not. Which is to say, as Ellen Metloff, Director of Genetic Counseling at Yale Medical School and the Yale Cancer Center, put it, “If you’re really interested in fortune telling than don’t spit in a cup, go get your tarot cards read. It’s cheaper, quicker and safer. Plus, they can probably tell you just as much about what may or may not happen to you in the future as these genetic tests.”

Steven Kotler lives in New Mexico with his wife and too many dogs. His work has appeared in The New York Times Magazine, Wired, Discover, Popular Science, National Geographic, among others. You can find him online at: www.stevenkotler.com

SOURCE: Complete Genomics

Image of a plate of DNA sequence markers.

Earlier this week, Complete Genomics announced that it will offer complete human genome sequencing for the low, low price of $5000. To put this in perspective, Technology Review explains that “with a price tag of $100,000 to $1 million over the past two years, only a handful of human genomes have been sequenced to date.”

Technology Review also offers a detailed description of the sequencing technology, along with a helpful slideshow. The graphical explanation illustrates the bridges between cytogenetics, nanotechnology, and computer science that enable the breakneck pace of this sequencing technology.

The new technique also emphasizes the fact that Complete Genomics is set up not as an instrument company; rather, the company is set up as an information service provider:

Beyond its unique technology, Complete Genomics has also chosen an unusual business model: rather than selling instruments, as most sequencing companies have done, it plans to offer sequencing services through a commercial-scale genome center….The company is now building a massive data center to manage the immense volume of information it expects to generate; it’s planning to have a computer cluster containing 60,000 processors online by 2010.

And unlike sequencing companies like 23andMe and Navigenics, which market their services to consumers (and do not offer complete sequencing), Complete Genomics will not be encouraging Spit Parties.

Over at Genetic Future, there’s a provocative analysis of the near-term future of how companies in this market will likely evolve:

If Complete Genomics does indeed have the edge over its next-generation competitors, you can guarantee it won’t last long – all of the platforms are constantly being tweaked and improved, and there are new competitors on the way…. By focusing on service provision using a single, cutting-edge technology, the company may present an attractive option for pharmaceutical companies and other corporations looking to outsource their sequencing needs.

But here’s the kicker, as Genetic Future again points out—the likely result here is for profits to flow to companies that can offer the best interpretation of genetic information, not just the fastest and cheapest sequencing:

There’s an important message here between the lines: as technology drives the price of sequencing down, massive competition between platforms and service providers will almost certainly drive down the profit margins of sequencing providers. The real money will then be in providing sophisticated, up-to-date and easily understandable genome interpretation services. The best interpretations will come from the companies with the largest databases of genetic information, and with expertise in putting that complex information in the appropriate context for lay consumers. It seems to me that right now deCODEme has an advantage in the former race (given the formidable genomic data-sets assembled by its Icelandic parent company deCODE genetics), while 23andMe is winning the latter – but if 23andMe succeeds in attracting a wave of customers (and particularly disease patients) with its new low low prices, they may well ultimately gain the edge on both counts.

The historical parallel that springs to mind here is the bet Microsoft made in the late 70s to focus on software rather than hardware. The path to blockbuster success in the computer world didn’t turn out to be making the speediest desktop or the biggest hard drive; hardware costs for those products are still dropping after decades. The money was in the tools that helped people manipulate, interpret, and share information.

The not entirely unintuitive fact that the sweet spot for profits in genomics will be in interpretation services emphasizes the challenge for public policy that balances consumer protections with advancing cures. On the one hand, better genome studies will allow researchers to further understand the tangled relationship between genes, environment, disease, and disability. But as regulators have been sluggish to do their genetic due diligence on what Art Caplan calls “spitomics” companies, you can probably bet that spurious claims from companies offering misleading interpretations to consumers will multiply in the future.

Science, Cultured

Science Progress contributing editor Chris Mooney surveys the interactions between science, politics, and culture from Los Angeles, California. He is author of two previous books, The Republican War on Science and Storm World: Hurricanes, Politics, and the Battle Over Global Warming. He blogs at The Intersection with Sheril Kirshenbaum. (Photo: flickr.com/sarahfelicity)

When I started writing for Science Progress a year ago, I wasn’t sure what kind of publication would materialize. True, I had some idea of the kinds of arguments I myself would contribute—being known, among other matters, for discussing political interference with science and the problem of science communication—but it wasn’t clear where the broader experiment would go.

At its one year anniversary, however, I can honestly say that in my opinion, this site—regularly featuring the work of Rick Weiss, Jonathan Moreno, and numerous other insightful contributors—ranks among the very best sources of timely, rigorous, and intellectually serious science policy thinking on the web.

To see that, let’s peruse some of the important threads that have been pursued here over the last year, to give a sense both of the extensive scope and of the quality of analysis. I want to talk about five themes in particular that have recurred at Science Progress: how to restore science advice to the next president and next administration, including revitalizing the role of science in the federal government; the parallel importance of science in Congress; the challenges facing young scientists in America today, especially in the context of concerns about preserving our scientific competitiveness; the knotty but crucial problem of science communication; and the future of the life sciences.

In the wake of an administration that failed to make science a priority, Science Progress writers have worked to outline a better, healthier course for next president to take. Ranging from my own parsing of the National Academies’ advice for the next administration—most notably, that it must quickly appoint a presidential science adviser who can restore the prominence of this role—to bioethicist Art Caplan’s attempt to put six pressing science policy concerns on the administration’s radar (hint: we have to do far more than simply resolve the stem cell issue), you might say Science Progress has provided a cheat sheet concerning what to do, and what to pay attention to, should you happen to be running a government that actually wants to heed the “reality-based community.” Of foremost importance to that government will be having scientists on hand and allowing them easy access to the president and other top policymakers, not only to advise on the issues of the moment but also to provide foresight—so that the issues of the future, like synthetic biology or geoengineering, won’t take anyone by surprise.

And as with the administration, so with Congress—the House and Senate haven’t exactly been science-friendly places of late, but that can and must change. First, there’s the needed but long-delayed solution of bringing back the Congressional Office of Technology Assessment, discussed in this column by Darlene Cavalier. But there’s also the imperative to get more science-friendly members of Congress elected to begin with, so as to improve the scientific literacy of the body from within. We must pursue multiple strategies simultaneously to increase the resonance of science for the average legislator, so that he or she can see that science underlies many or even most important issues handled in Congress and, indeed, directly affects voters back home.

The advancement of scientific research isn’t the same as progress in scientific outreach and communication, and the science community has traditionally privileged the former and given short shrift to the latter.

Science Progress has also been an important outlet for analysis on what is arguably the most visible issue in science policy today: How to ensure ongoing U.S. competitiveness in the face of challenges from emerging science superpowers like India and China. But while authors writing here certainly wouldn’t argue that such competitiveness concerns should be ignored, they have brought out an important sub-theme that has all too frequently been neglected: Namely, that if we want to compete in the broadest sense of the term, simply producing more scientists isn’t enough. For after all, note Science Progress contributors Sheril Kirshenbaum and Beryl Lieff Benderly, we already have staggering numbers of talented young postdocs stuck in holding patterns, without nearly enough academic jobs awaiting them. There is a constriction of opportunity for the youngest scientists in America, and if we want to remain competitive, that’s just as serious an issue as the total number of scientists and engineers we’re producing.

Another important, related wrinkle has been the argument that international scientific competitiveness, alone, may not be enough. For while the United States must continue to excel in research (and let us not forget that our nation still leads the world in science), it’s entirely possible for laboratory science to thrive even as the influence and relevance of science, in policy and to the average citizen, decline. In other words, the advancement of scientific research isn’t the same as progress in scientific outreach and communication, and the science community has traditionally privileged the former and given short shrift to the latter. And so a recurring theme here has been that scientists must study the modern media, and engage in outreach to other important sectors of society. Moreover, such outreach must go beyond simply lecturing about the facts, and come to include broad public engagement on equal footing with non-scientists—as Rick Borchelt and Kathy Hudson argue—which is the only way to break down the walls between the experts and everybody else, rather than reinforcing them.

Such rapprochement will be particularly critical going forward as we watch science generate a deeper and deeper understanding of ourselves. Today genetic research is bringing us ever closer to a world in which being able to sample each individual’s DNA will trigger personalized medical solutions tailored to a given arrangement of base-pairs; even as burgeoning neuroscience work is explaining more and more about how we actually come to be the creatures we are, from the brain up. Ongoing, rapid progress in such fields will raise a host of new ethical concerns and has great potential to alarm the public by calling into question traditional concepts of identity, free will, morality, and obligations between generations. Once again, Science Progress has become a leader in analyzing the bioethical challenges implicit in these unstoppable new discoveries.

We live in a paradoxical time. One the one hand, it’s one in which science is changing our world more than ever before, and matters to policy and individual lives more than ever. Yet at the same time, it has become increasingly difficult to get science on the radar of politicians, the media, and the public, and to make it resonate. In this context, Science Progress plays a unique role as a connector between scientific research and the policy and public process—a task that’s now more vital than ever, and that will only grow more so in 2008 and beyond.

Chris Mooney is a contributing editor to Science Progress and the author of two books, The Republican War on Science and Storm World: Hurricanes, Politics, and the Battle Over Global Warming. He blogs on The Intersection with Sheril Kirshenbaum.

About two million patients take warfarin, or coumadin, each year to prevent blood clotting during medical procedures. But thousands of these patients experience bleeding complications due to inappropriate dosing of the blood thinner, and many die. From August 4^th through September 3^rd this year, the Centers for Medicare and Medicaid Services of the Department of Health and Human Services invited public commentary on whether Medicare should fund genetic tests to determine a patient’s warfarin response. Genetics, weight, sex, and age factors determine roughly 45-60 percent of the variance in response to warfarin, so these tests could prevent many adverse events. This possible change in policy might save thousands of lives and highlights the need for a more comprehensive approach to the field of personalized medicine.

Determining the appropriate amount of warfarin to administer to a patient is very difficult for physicians because there is a wide variance in response to the medication. The Food and Drug Administration approved a genetic test last year that allows physicians to better gauge how much warfarin to administer by checking two genes. Although the cost of these tests has dropped, the current price is approximately $500, which prohibits many seniors from benefiting from the best available care.

Some research indicates that using this genetic test might result in savings for the healthcare system. For example, Genelex reports, “cost effectiveness will be achieved if 33-47 percent of the anticipated number of bleeding events are avoided.” Doctor Raymond Woosley of the Critical Path Institute told U.S. News and World Report that “this test can save $1.1 billion in health-care costs and 18,000 lives a year.” There are methods for checking how a patient responds to warfarin, but as Wired explained, “In a perfect world, physicians would use both [the genetic tests and handheld devices like the Roche CoaguChek system that allow physicians to constantly monitor a patient’s blood] to aid in their decisions.”

If DHHS approves Medicare to fund this test, it could provide a push for the developing industry of pharmacogenomics. Moreover, this potential application of personalized medicine offers an alternative to conventional trail-and-error techniques by allowing physicians to tailor care to an individual’s unique clinical, genetic, and environmental information. This might well be the next medical frontier, but the field itself is in need of help due to genetic data that may not be ready for clinical application. In a recent Science Progress article discussing genomics, bioinformatics, and proteomics, Arthur Caplan explained:

This rapidly growing sector is riding an ill-grounded wave of hype that makes weak, next-to-useless correlations between gene markers and disease states without really having much idea what to tell its customers to do about the risk information that testing companies find.

To unleash the full potential of pharmacogenomics, the FDA and DHHS will need to make sure that the useful products get to the patients who need it and that the snake oil salesmen do not discredit the whole industry.

The co-chairs of the World Stem Cell Summit recently spoke with Science Progress in a roundtable discussion on the state of research. Bernard Siegel, executive director of Genetics Policy Institute, joined Timothy Kamp and Clive Svendsen, co-directors of University of Wisconsin Stem Cell & Regenerative Medicine Center, and Science Progress Editor-in-Chief Jonathan Moreno. Here are some of the highlights of the discussion.

The summit runs September 22 -23 and is distinctive in that it brings together scientists, patients, advocacy groups, and philanthropists, said Siegel. It is public-facing, interactive, and scientists learn “where their work fits into the world,” said Svendsen.

“We live in our own little shoebox sometimes as scientists,” he said.

Clive Svendsen discusses interactions between scientists and the public:

Although Kamp says it’s unusual to have this kind of interaction, he said he’s excited about the upcoming conversations. Industry and advocacy groups will have their own sessions in addition to the discussions of diseases and treatments.

During the summit, attendees will have a chance to discuss the ethical issues surrounding embryonic stem cell research. Those in favor of President George W. Bush’s restrictions on federal funding for hES cell research hailed Thomson’s work to create induced pluripotent stem cells from adult cells. But scientists and policy experts alike have pointed out in order for research to progress, work with human embryonic stem cells is critical, as they remain the “gold standard” for understanding pluripotency. Also, Svendsen said, studying IPS and hES cells simultaneously will create collaboration between scientists working in both fields.

Moreover, putting all future research eggs in the IPS cell basket is not a sound approach. “Extremism in any area is dangerous,” Svendsen said. “Although [Thomson’s research] is an exciting new technique, relying on any one technique is not the way forward, particularly if you want to bring cells into the clinic as quickly as possible.”

Tim Kamp explains why embryonic stem cells are the “gold standard” for pluripotency:
[audio:http://www.scienceprogress.org/wp-content/uploads/2008/09/kamp1.mp3]

“I think we’re still in the long process of really understanding just how much an induced pluripotent stem cell is like an embryonic stem cell and its ability to grow for prolonged periods of time, [and] its ability to deferentiate into all the different cell types we’re interested in,” Kamp said.

Researchers are discovering new, previously unimagined ways to reverse damage from injury and disease. Svendsen said he believes the first work using stem cells in clinical trials will employ them as helper cells, which modulate the tissue by increasing blood flow to the area, regrowing damaged cells.

Tim Kamp describes clinical work using autologous cells to repair damaged heart tissue:
[audio:http://www.scienceprogress.org/wp-content/uploads/2008/09/kamp2.mp3]

“This is really alchemy; taking lead and turning it into gold,” Svendsen said. “We can take an adult cell and make it pluripotent and make it do what ever we want.”

Clive Svendsen on the exciting new potential of pluripotent cells:
[audio:http://www.scienceprogress.org/wp-content/uploads/2008/09/clive2.mp3]

Addressing possibilities for significant expansion of federal support, Kamp said that the United States has “an incredible pool of researchers,” but to continue that research, the National Institutes of Health needs to increase funding. He even mused about the possibility of creating a stem cell and regenerative research center, much like the Center for Cancer Research.

Siegel pointed out that funding for the NIH has been flat overall and that funding for this field has been neglected. He hopes the next administration will increase federal funding for embryonic stem cell research and the Food and Drug Administration will move swiftly and safely on regulations.

Bernard Siegel stresses how important FDA regulations and federal funding are to stem cell research:
[audio:http://www.scienceprogress.org/wp-content/uploads/2008/09/siegel1.mp3]

“We want to make sure we don’t have a gridlock,” Siegel said “and that we can move all systems forward responsibly but quickly.”

The grassroots advocacy groups are pushing hard for this research, politically and financially. Next Monday and Tuesday, more than 150 corporate sponsors and non-profit partners will show their support at the World Stem Cell Summit. The co-chairs expect the summit, now in its fourth year, to help shape the future of stem cell research in this election year.

“This is a field that’s on the move,” Siegel said. “The political climate is changing for the better. And in the next ten years we’re going to see major advancements.”

Tristan Fowler is an intern at Science Progress and a journalism major at Ithaca College.

Today the FDA released its long-awaited—and in some quarters, long feared—proposed new rules for marketing foods from animals that have been genetically engineered to have particular traits.

Among the gene-altered animals that could come through the pipeline first are salmon endowed with extra growth hormone genes, to make them grow faster. Pigs with bacterial genes that make their manure less environmentally damaging. And cattle with genes that help them fight disease or, a little further down the road, genes for omega-3 fatty acids, which could make filet mignon as healthful as a fillet of trout.

AP/Will Kincaid

One possibility for engineered animals: pigs with bacterial genes that make their manure less environmentally damaging.

The FDA proposal, which is open for public comment for the next 60 days, is sure to raise lots of consumer interest. Thousands weighed in on the agency’s clone ruling, with many expressing disgust over the idea of scarfing down clone-burgers. So wary of clones are our foreign trading partners that the Agriculture Department has asked U.S. farmers to hold off sending their clonal critters to market until the rest of the world gets over its jitters, even though the FDA has declared them safe.

Back then, the FDA and the biotech industry made a big deal about the fact that clones were “just” clones and are not genetically manipulated per se. They are merely conceived in an unusual way that involves just one parent instead of two, we were reminded, which produces an individual genetically identical to that parent. If the government were ever to allow gene-altered animals into the food supply, officials reassured the public, the requirements for approval would be even more stringent than they were for clones.

Well, those rules are out today, with ancillary information from the FDA, and they make for an interesting read.

The good news is that the agency has decided to regulate gene-altered animals under the provisions of its “New Animal Drug” rules rather than through, say, its conventional food safety provisions. That’s good because novel foods for the most part can simply be introduced into the food supply without any restrictions, and enforcement by FDA does not kick in unless something goes wrong, like a lot of people dropping dead. By contrast, under the new animal drug provisions, each new kind of animal produced through genetic engineering will have to get approval from the FDA before it is commercialized. That’s the appropriate approach to something as biologically complex and emotionally charged as gene-altered animal products for the dinner table.

The bad news is that the process of getting such stuff approved is, as is the case with new drugs, extremely secretive. In fact, it would be against the law for the FDA (without permission from the affected company) to reveal that it has even received an application for a new gene-altered food animal until it approves that animal for sale in grocery stores. And once it has given its approval, there is virtually no recourse available to the public if people are not happy with that decision.

There are lots of reasons why the public may want to weigh in on these approvals. Concerns about the welfare of engineered animals. Environmental concerns (what happens when some of those genetically enhanced salmon escape their offshore cages and mate with wild salmon?). Concerns about subtle changes in nutritional values or even economic or ethical issues that the FDA is not really authorized to consider.

In interviews yesterday, FDA and biotech officials made a pretty convincing case that the agency is going to be looking very closely at these applications. The safety of consumers and the welfare of the animals themselves are their twin No. 1 priorities, they said. They also said they intend to make the process as public under the rules as possible, at least at first, to reassure consumers that their interests are being properly handled.

As always, the devils will be in the details: Just how much data the agency demands. How well it coordinates with the USDA and the Environmental Protection Agency, which will share responsibilities for many of the issues raised by engineered animals. But the first test will be how the agency responds to public comments over the next two months. Will it take the time to absorb them, respond to them thoughtfully in a public document, and integrate the best suggestions into a final version of the guidance? Or will it, as some agency-watchers suspect, finalize the proposed guidance very quickly after the 60 days are up, adding it to the bureaucratic bolus being force fed through the Washington policy machine in the waning days of the Bush administration?

Undue delay would be wrong. The nation and the world has been worse off, not better, for lack of guidance on how this next generation of animals is going to be regulated. And importantly, this is about more than just food. Engineered animals are also being made that produce important medicines in their blood, milk, and urine. Others may someday grow organs suitable for transplantation into people. Some animals being made or on various drawing boards are just capricious or quaint, such as the pet fish that glow in the dark and the cats that briefly were being produced under the (questionable) claim that they would not trigger allergies.

There is a world of biological manipulation to be had out there, and while some of it will be offensive a lot of it will be for the better. But the process is important. The FDA has to prove it is really listening, and show in its first few application reviews that it cares about the public interest and the animals themselves as much as it cares about the companies that hope to profit from these living and breathing products.

iStockphoto/SP

The paper describing the identification technique was published in the August 29 issue of PLoS Genetics by a team led by David W. Craig at the Translational Genomics Research Institute, also known as TGen, in Phoenix, AZ. In it, Craig and his team detail a new statistical technique that allows researchers to search through genomic mixtures that contain the DNA of more than 200 individuals and identify the presence of a single person’s DNA—even if that person’s DNA only makes up 0.1 percent of the entire mixture. They were even able to show how, theoretically, they could find an individual’s DNA in a mixture containing over 1,000 people.

This technique would be a helpful to forensics experts who usually find DNA samples at crime scenes that contain trace amounts of many individual’s DNA. Specifically, the technique utilized Single Nucleotide Polymorphism chips, or SNP chips, to detect the presence of tens of thousands of SNPs in a genomic mixture. SNP detection is usually employed to study the prevalence of certain genes and their correlation with certain diseases. Academic researchers have been using SNP chips to compile databases of human genomic variation like the one at the NIH, whereas clinicians and commercial ventures such as 23andMe and deCODEme have been using SNP chips to determine if a particular patient or consumer possesses SNPs that are correlated with certain traits or conditions. In fact, the TGen study utilized SNP chips from the companies Affymetrix and Illumina, the company partnered with 23andMe.

If this method is made more cost effective for crime labs, “it would be an amazing asset,” said Commander Brent Vermeer, director of the Phoenix Police Department crime lab in the TGen press release. For some time, one of the assumptions usually made about forensic DNA tests is that it is impossible to identify individuals from pooled data. Investigators currently utilize techniques that detect about 20 SNPs and cost about $50. The chips used in the TGen study detect tens of thousands of SNPs and cost several hundred dollars.

The TGen press release also notes a bill that was passed in June in the Arizona Senate which “requires police agencies to keep DNA evidence in cases of homicide or felony sexual assault for as long as convicts are in prison or on supervised release, or at least 55 years in unsolved cases. Some like Phoenix keep it indefinitely.”

Vermeer added in the press release, “As technology advances, we need to be prepared to keep evidence that, down the road, could prove again to be useful.”

In an email to GenomeWeb News, GPPC Director Kathy Hudson explained the legal implications: “So, the unlikely but concerning scenario is that law enforcement has a DNA sample from a crime scene, searches an NIH database, finds a match and gets a subpoena to identify what researcher provided the cohort data.”

“While a fairly remote concern, and there are some protections even against subpoena, NIH did the right thing in acting to protect research participants,” she wrote.

The larger privacy concern that led to the NIH’s new database restrictions is that this technique allows anyone with the technology to go into an aggregate genomic database and search for an individual’s particular genetic signature—if, of course you already know what that person’s genetic signature is. There have not been any breaches yet, but the NIH decided to abide by the precautionary principle and make the data available only to researchers who apply for access for a certain period of time. The NIH also confirmed that other groups, including the Wellcome Trust Case Control Consortium, and the Broad Institute of MIT and Harvard, also have removed their aggregate data from public availability.

To allay any other concerns, the NIH told GenomeWeb, “even if an individual’s SNP profile was found within a pooled dataset, all that would be learned is that this profile was contained in the dataset and, thus, it could then be associated with the characteristics of that dataset (e.g., disease or control population).”

Americans get the importance of science and technology.

Because the American people are not dense. Despite all the news stories about the last-ditch efforts to keep creationism in our public schools, Americans know which side their bread is buttered on, and that side is science and technology. They can see on television that science and technology are fueling the economies of Europe and Asia. Science and technology will create the good jobs in the United States and will maintain the country’s preeminence in the 21st century. That is why the fact that our kids are falling behind the rest of the world in science literacy is viewed with alarm and a fair degree of nervous joking—Americans get the importance of science and technology.

The public also understands that solutions to some of the major challenges this nation and the entire world face—affordable fuels, global warming, controlling highly infectious diseases, growing sufficient and nutritious food, reducing pollution, cleaning up the oceans and improving transportation, all depend on science and technology. And while the public may not fully appreciate the fact that there have been breathtaking bursts of knowledge in areas such as genomics and neuroscience resulting from heavy taxpayer-supported government funding, they can easily understand that it would be foolish not to make the resources and incentives available to move this new knowledge into practical application in terms of jobs and better health as rapidly as possible.

So in the spirit of three is about as far as you can get (but cheating a little to cover all the areas I am hoping to get on the next administration’s radar) here are six things: three in health and three in science and technology that the next administration ought to argue for vigorously and fund generously during its first term.

Health

Modest but ethically important reform

Most discussions of our strained health care system focus on proposals for single-payer systems, universal health care, and the value of markets and choice. But consider this: the American health care system accounts for about 17 percent of our gross national product, and this inordinate expense is straining industrial productivity and cannot be justified in terms of what we get for our money.

Healthcare expenses affect every level of U.S. industry. For large corporations health care costs mean higher prices on our products along with massive “legacy costs” to insure retired employees. For small business owners healthcare expenses make it impossible both to hire candidates they would otherwise take or to sufficiently incentivize inefficient workers to move on, damaging productivity. Some economists maintain that as many as 42 million U.S. jobs are “susceptible” to offshoring in a future where technology allows the more efficient transfer of jobs and employee health care costs are far less.

As nearly every politician recognizes, something must be done. But the new administration needs to understand that a drastic overhaul of the gargantuan, money gobbling, bloated mess that passes for American health care is not going to fly. There are just so many stakeholders in the hugely inefficient, highly inequitable, but incredibly lucrative broken system that we now have to change it quickly.

The new president should talk boldly but move slowly. Praise the drive toward some day achieving universal coverage, but accelerate change by focusing political momentum on children—the group most likely to command ethical empathy across the political spectrum. The new administration should come up with a proposed basic package, including dental, hearing and eye care, for every American child. Prenatal and post-natal care for every mom ought be there as well.

Of course we need universal coverage for basic health care, but the place to start in practical terms is with those under eighteen years of age. Millions of American children lack health insurance. Not only do they deserve it, but they are the moral key to insuring the rest of us. Show success with kids and the rest will follow.

Stem cell research is great but…

Way, way too much political energy has gone into the embryonic stem cell issue. Working with embryonic stem cells is a very exciting area of biomedical research but it is hardly the only area; nor is it the one that will have guaranteed practical payoffs any time soon. All the new president needs to do is flip the Bush administration restrictions on federal funding, which are inconsistent and wildly unpopular; gin up a new federal panel at the NIH to make sure that oversight of all stem cell research is comprehensive, including all early animal and human trials public and private, transparent, and standardized among the states; put some Federal money into the pot; and get out of the way. The stem cell scientists—adult, fetal, embryonic, induced, and cloned—will take it from there.

America needs much more funding of basic research in genomics, proteomics, and bioinformatics. The “ics” hold the future in terms of mining the little we now know about a whole lot of genes. Without that investment, we will be stuck with half-witted, premature schemes to map our individual genomes—what we can call spitomics—spit-in–a-cup DNA testing. This rapidly growing sector is riding an ill-grounded wave of hype that makes weak, next-to-useless correlations between gene markers and disease states without really having much idea what to tell its customers to do about the risk information that testing companies find.

Fix public health

Our public health system is a wheezing, uncoordinated, underfunded eyesore. It needs to be rebuilt to face the challenges that 21^st century living poses to health, ranging from asthma, to diabetes, to the flu. City and county health departments need federal help across the board. Proactive public health is a key element of our national security. The next administration should demand that Congress pay for it.

So how are we going to fund all this glorious new research? In reality the price tag is not all that big—we hardly spend very much now as a percentage of gross domestic product on basic research in health, technology, and science, especially if you don’t count defense related research. But for those who want a new idea as to funding, here is a bonus suggestion for the next president: It is time to revisit the National Institutes of Health and National Science Foundation budgets and see whether a twist on the Bayh-Dole Act that gives universities incentives to work with industry makes sense.

The NIH budget does not grow in hard times. Congress won’t go there in times of deficit. Private companies wait to see what tax-payer funded basic research looks promising and then develop that, only to sell it back to the taxpayers (you and me) who originally funded the work at high prices. So why not put a 3 percent tax on all products that are generated from NIH, NSF, or other government-sponsored basic research? Keep the core budget there and adjust it to rise in response to inflation, but let American science and the American people really benefit from breakthroughs. In that way the incentives are there to translate basic research into practical products, while at the same time allowing the NIH budget to grow more rapidly without having to whine for more money from Congress every year. Here is a real incentive to universities, think tanks and academic scientists—make real and useful breakthroughs and watch your budget for future research grow!

Science and Technology

A New Push in Agricultural Research

We need safer, healthier food that has far less of a footprint on the environment. Science and technology can help but we need presidential leadership to get us there. To reduce the burden of chemically based farming that depends on fertilizers, herbicides, pesticides and huge amounts of irrigation, we need to apply the genetic revolution to agriculture. Let’s break the link forged by big agribusiness between the “old” chemically based agriculture and genomics and drive forward with a biology-based agriculture that uses genetic knowledge to screen foods and insure their safety; engineers them to make them heartier, more healthful and less oil and chemically-reliant; and creates the next generation of creative farming in cities, estuaries, empty government lands and national forests. And, for those who see creative possibilities in new forms of organic farming and alternative modes of agriculture— working to achieve the “natural” control of pests, better pollination through diversity and using less water through better soil management—give them a bit of money to let them show what they can do as well.

Clean Water

The president needs to understand that clear, drinkable water is going to be a major political issue both in this nation and worldwide very soon. If we have the technology in place to use less, to get more from the oceans, to recapture more from our current industry and farming uses, and ways to identify, track and get rid of microbial pollutants in lakes, rivers, and oceans, we will hold a key foreign policy card. Nanotechnology, micro-sensing technology, better semiconductor technology, and even improved synthetic biology are the tools to get us where we need to go. We just need a president committed to getting us there. If the new president wants to make fast friends in China, the Middle East, India, and Africa he could do worse then by promising to fund and share the science that will lead to more clean water.

Synthetic Biology

The next president and his administration can’t let human hubris about how wonderful our bodies and genes are fool them. We love to think that it is the science of human genetics and human biology that holds the key to our better future. But the fact is, microbes are usually easier to work with than human beings, and are just as useful for making gains in human health, well-being, safety, and security. That means the government should put more money into research in synthetic biology aimed at fighting diseases, making synthetic fuels, eating pollutants, cleaning the oceans and our arteries. As HIV and pandemic flu show, you cannot ever underestimate a microbe. By developing the microbial and synthetic biological science to manipulate these tiny critters, the next president can go a long way toward solving a host of our current headaches.

Keep It Real

In health care and in science and technology, the new administration can make a huge difference by keeping its eye both on what is practical and what is likely to provide the greatest return on investment. These have not always been the watchwords of health and biomedical science policy in the past. There is no need for administrations elected on a promise of “change” to let history repeat itself in the future.

Arthur L. Caplan, PhD is an adviser to Science Progress and the Emanuel and Robert Hart Professor of Bioethics, chair of the Department of Medical Ethics, and director of the Center for Bioethics at the University of Pennsylvania.

He doesn’t scare me mortally or physically (although if the FBI does indeed have their man, then he scared me pretty badly back in 2001 in Washington, D.C., when I was terrified to open the mailbox). But dead or alive, guilty or innocent, he scares me because of what he can do for the image of the scientist in popular culture today.

There are very, very few kinds of knowledge that we actually ought to regard as forbidden.

There’s a lengthy tradition, dating back long before Mary Shelley’s Frankenstein to mythological precedents like the story of Prometheus, that depicts the search for knowledge as forbidden, dangerous, and leading disastrous consequences. In this narrative, knowledge leads to the temptation to “play God,” interfere with “nature,” thwart fate to determine who lives and dies. Or as Victor Frankenstein himself puts it in Shelley’s novel: “Learn … by my example, how dangerous is the acquirement of knowledge, and how much happier that man who believes his native town to be the world, than he who aspires to become greater than his nature will allow.”

In modern cinema especially, the Frankenstein myth has fueled the recurring depiction of “mad scientist” characters whose pursuit of knowledge tempts them to pursue forbidden powers as well—a desire that ultimately leads to their downfall (after taking lots of innocent victims along with them). These scientists want to know, and in such narratives to know is often to kill. The paradigmatic example is perhaps E.T., in which the evil scientists, looking like astronauts in their protective gear, want to slice up the cute alien. But there are many other such films, often linked to the biomedical sciences and especially to the subject of cloning. One thinks of films like Godsend and The Island—in which the doctor running the clone complex has a “God complex”—but the same trope appears in flicks ranging from Jurassic Park to Star Wars (especially episodes II and III). Traveling back further in time, we can detect the same mythology in early twentieth century novels like The Island of Dr. Moreau and Brave New World.

Certainly science has had its dark episodes in the past—most notably the eugenics fad in the early part of the twentieth century (which is what works like Moreau and Brave New World were reacting to). But in the modern period, one could argue that most scientists, and biomedical scientists in particular, have shown strong moral consciences. The 1975 Asilomar conference, when scientists gathered to agree upon ethical guidelines for recombinant DNA research, and to ban some particularly troubling experiments, serves as a noteworthy example. So while the Frankenstein myth never dies, it also doesn’t really fit reality today: Far and away most scientists save lives, rather than dooming them. And there are very, very few kinds of knowledge that we actually ought to regard as forbidden.

But now, if we’re to believe the FBI, then we have a case of reality coming around to match fiction. The Bruce Ivins we’re hearing about in the media sounds like a mad scientist straight out of Hollywood’s most feverish fantasies. He had access to forbidden knowledge (anthrax spores and how to use them), and a sly, horrible plan to apply that knowledge to its worst possible end. For a public that has been repeatedly instructed not to trust the responsibility of scientists—because they don’t value life and their quest for understanding is somehow dehumanizing and dangerous—Ivins perfectly reaffirms the dangerous stereotype.

Moreover, in doing so, he plays into a particular political agenda. Recognizing well the potency of the mythological tradition I’ve just described, the foes of various forms of biomedical research and advancement have long sought to exploit it to further their ends. Leon Kass, the conservative first chair of President Bush’s President’s Council on Bioethics, opened the council’s meetings by assigning members to read a Frankenstein-type story, Nathaniel Hawthorne’s “The Birthmark,” whose plot (summarized by someone far more able than myself) involves “a scientist married to a stunningly beautiful woman whose only flaw is a tiny, hand-shaped birthmark on her cheek. The scientist devises a treatment to get rid of the imperfection. The treatment works, but—alas!—kills the wife in the process.”

I used to delight in criticizing or even lampooning Kass, and in pointing out the inapplicability of fictional stereotypes to the sober consideration of modern issues in bioethics and science. Today the mad scientist stereotype remains as unhelpful as ever—but the dominant image of the anthrax killer only strengthens its already mythic power.

Chris Mooney is a contributing editor to Science Progress and the author of two books, The Republican War on Science and Storm World: Hurricanes, Politics, and the Battle Over Global Warming. He blogs on The Intersection with Sheril Kirshenbaum.

Effect Measure goes where few other dare and questions the validity of the Ivins fiasco, not once but twice this week. The evidence is the same as what the mainstream media presents, but the authors arrive at a different conclusion from the FBI’s.

Joe Romm, writing at Science Blog’s Next Generation of Energy Ideas blog, explains that if we don’t stem the flood of carbon pouring out of coal-fired power plants, nothing else we do to stop climate change will matter.

Mira Kolodkin at SEA’s blog covers the FDA’s inability to adequately follow up on illegal uses of drugs and comments on the GAO’s suggestion of a tracking system to help the FDA respond to complaints of violations more efficiently.

Brandon Keim at Wired touches on the bioethical implications of cloning Booger and comments on misconceptions about personhood. He explains that Booger, like people, was more than his genes.

An expert panel at Stanford University has determined that nearly one quarter of the colonies of human embryonic stem cells that the Bush administration had approved as ethically derived and eligible for study with federal funds do not meet Stanford’s ethics standards and should no longer be available to researchers there.

The decision is the first of what is expected to become a string of such moves following the publication in May of a little-noticed report by a University of Wisconsin professor who found serious ethics lapses in the way some of the Bush-approved cells were obtained from embryo donors. Johns Hopkins University has quietly come to a decision similar to Stanford’s, and will undertake case-by-case assessments of the appropriateness of using various cell lines. And at least two University of California campuses, as well as the University of Wisconsin and California’s state-wide stem cell consortium are currently considering similar moves.

The revelations bolster a growing sense among researchers, the public, and representatives on Capitol Hill that the Bush stem cell policy is untenable and in need of a major overhaul. Bush’s policy, announced by the president on August 9, 2001, determines which colonies, or “lines,” of stem cells can be studied with taxpayer dollars—not on the basis of whether those cells were obtained by ethical means but simply on the basis of when they were derived. It says cells that were derived before August 9, 2001 can be studied with federal monies and those derived later cannot.

When Bush announced the policy in 2001, it was touted by administration officials as a moral triumph and a Solomonic compromise between those who flatly opposed the research and those who wanted unfettered funding for research on the cells. The Wisconsin investigation found otherwise.

The administration was adamant that as many cell lines as possible that were derived before the August 9, 2001 deadline be included on the approved list…in the hope that scientists would be mollified.

For some of the Bush-approved cell lines, the Wisconsin report found, consent forms that women signed as they donated their embryos for research promised that cells from the embryos would be used for a single, narrowly defined experiment and then destroyed. But stem cell research is not done this way. The whole point is to grow the cells into tissues for research and possible medical use. And in fact, the cells in question have been kept alive and reproduced repeatedly and distributed to scientists around the world for an apparently unlimited array of stem cell experiments.

For other Bush-approved lines, the informed consent form used by researchers to gain access to fertility patient’s embryos was not a consent form for research at all, but rather was a standard medical consent form to begin fertility treatments. Only one vague sentence toward the end of the several-page form mentions the possibility that cells from some of the women’s embryos might be used for research. By contrast, widely accepted standards of informed consent require a full accounting of what kind of experiments will be done and what the various risks and benefits of participation may be. The Bush policy ignored these standards.

The revelation that many of the Bush-approved cells were obtained without proper informed consent is but the latest evidence that there is less to the Bush plan than meets the eye. When the president announced his long-awaited policy on funding of human embryonic stem cell research on August 9, 2001—in his first televised address to the nation after being elected—he said there were more than 60 lines of cells that qualified under his plan, plenty for scientists to work with. As it turned out, the number was actually 21.

Then it came out that all those lines that were eligible and available had been cultivated with mouse cells and were potentially contaminated with mouse viruses, seriously diminishing their value as therapeutic tools. And more recently it has become clear that some of these older lines have begun to accumulate genetic mutations. Meanwhile, researchers around the world have developed hundreds of new embryonic stem cell lines using scientifically and ethically superior methods, but none of them are available to researchers using federal funds because the Bush plan is all about when instead of what.

Made aware of the informed consent lapses, a special stem cell ethics committee at Stanford recently concluded that all five human embryonic stem cell lines derived by two companies—Celartis of Sweden and BresaGen of Athens, Georgia—did not meet widely accepted ethics standards. That means the number of lines now available to federally funded scientists has shrunk at Stanford to just 16.

Stanford officials said they are discussing whether to implement the committee’s recommendations. Those recommendations came about as a result of research by Robert Streiffer, a professor of bioethics and philosophy at the University of Wisconsin at Madison. Streiffer used the Freedom of Information Act to examine the informed consent forms used by all the various research groups whose cells eventually passed muster with Bush. The Celartis and BresaGen forms were in gross violation of federal and international ethics standards, Streiffer said. The others, while imperfect, he deemed acceptable and he encouraged ongoing use of those cells in research.

The Celartis consent form told donors that the cells “will be destroyed” upon the conclusion of a single (undescribed) experiment, but no such restriction is actually in place for researchers who want to use those cells nor would such a restriction be practical, according to scientists. In the BresaGen forms, which women must sign if they want to get fertility treatments involving in vitro fertilization, the one sentence that mentions research says embryos created through the fertility treatments might be used for research if the embryos “are not developing or living.”

In addition to the form not going into any detail about what kind of research might be done, Streiffer said—a basic requirement of any consent form—the forms are deceptive because there are no accepted tests for whether an embryo in a lab dish is, in fact, developing or alive. “This probably does not count as informed consent for research at all,” Streiffer said of the BresaGen form in his published analysis, which appeared in the May/June issue of the Hastings Center Report, a journal of bioethics.

A representative of Celartis said he could not comment on the issue, and BresaGen did not respond to a query from Science Progress.

In an interview, Streiffer expressed surprise that the National Institutes of Health accepted the BresaGen and Celartis lines as eligible for federal funding, given the obvious lapses in the quality of their informed consent. But NIH insiders, speaking on condition of anonymity, said they had little choice at the time. The administration was adamant that as many cell lines as possible that were derived before the August 9, 2001 deadline be included on the approved list, NIH sources said, in the hope that scientists would be mollified. “We essentially had a gun held to our heads,” one insider said.

It is not clear how many experiments in the United States or abroad may be affected by the new restrictions. At least one experiment had been approved at Stanford using one of the lines, and will now be halted before it begins. Federal documents indicate that at least 90 shipments of cells from the two companies have been sent to researchers since they were first made available.

The new recognition that the Bush cells don’t really inhabit any particular moral high ground could change the dynamics of the stem cell debate going into the election. There has been growing suspense in scientific and political circles as to whether the Republican presidential contender, Sen. John McCain of Arizona, will maintain his support for legislation that would loosen the Bush restrictions. McCain twice voted for bills that would have done so, but has recently been rumored to be considering a reversal given a perceived need to solidify support from what remains of Bush’s conservative base.

Streiffer said it makes no ethical or scientific sense to base a policy on the timing of when cells were derived, as opposed to how they were derived. There have been many technical improvements, he noted, that make more recently derived cells more scientifically useful. In addition, newer lines have largely been derived with the benefit of new ethics guidelines that in recent years have been promulgated by the National Academies and other groups.

“Bush’s policy is getting in the way of us doing it better, scientifically, and ethically,” Streiffer said.

* Update, July 28, 2008: This article indicated that Johns Hopkins University has come to a similar decision to Stanford’s. It has been updated to indicate that Hopkins will undertake case-by-case assessments of the appropriateness of using various cell lines. Other changes reflect Stanford’s ongoing review of its committee’s recommendations.

Rick Weiss is a Senior Fellow at the Center for American Progress and Science Progress.

Effect Measure wonders if the unpublished CDC study reporting that up to 50 percent more Americans have HIV than we thought was just another victim of the administration’s suppression.

Michael Stebbins posted on Scientists and Engineers for America’s blog about the new, searchable OTA archive and included a video of Rush Holt talking about why OTA was awesome.

JR Minkel on Scientific American comments on a study (which is hotly contested by the IMF) that finds a correlation between IMF loans and tuberculosis deaths.

Bioethics.net’s Summer Johnson draws our attention to a particularly undesirable effect of high gas prices: cuts in home health services.

Curtis Brainard at CJR provides a very thorough analysis of the renewed interest in GM crops and their potential to solve the food crisis.

Kaid Benfield at NRDC’s Switchboard chides the environmental movement for failing to be more vocal about obesity and its environmental causes, and later in the week posts about how Google Maps can now help.

Huntington’s is a neurodegenerative genetic disease that typically presents between age 30 and 50, but can have earlier or later onset. Unlike most genetic tests, the test for Huntington’s is highly predictive—a positive result almost always leads to the individual developing the disease.

Candidates already have to disclose quite a bit of private financial data in order to receive federal campaign funds.

Before causing death, Huntington’s disease leads to progressive impairment of important cognitive functions, such as reasoning, planning, and abstract thinking. If it were deemed sufficiently in the public interest for voters to have this information, Congress, through the Federal Election Commission, could require genetic testing for Huntington’s disease as a condition of receiving federal funds.

The constitutionality of such mandatory health screening has never been directly challenged, but we do have some applicable legal doctrines. Candidates already have to disclose quite a bit of private financial data in order to receive federal campaign funds. And the definition of “employee” under many nondiscrimination statutes (including the Genetic Information Non-Discrimination Act) does not include candidates for public office.[1] Voting is inherently discriminatory.

The flip side, however, is detailed in Chandler v. Miller, where the Supreme Court held that mandatory drug testing of gubernatorial candidates was against the Fourth Amendment, as the public interest to be served was not strong enough to counter the warrantless, suspicionless “search” of the candidate’s urine.[2] And finally, the disclosure of a candidate’s health details may be protected even where the information is surreptitiously obtained, as the First Amendment protection on political speech is incredibly strong.

What’s more, if genetic testing companies are allowed to continue marketing their services directly to consumers without involving a physician, then the possibility of a candidate’s genetic information being leaked to the press becomes even more real. Journalists could obtain discarded genetic samples from the candidates, and then have them tested and publish the results without the candidate’s consent.

But none of this answers the question of whether the government should require some form of genetic testing. There are a couple of reasons to argue in favor of testing for neurological conditions such as Huntington’s. First, there may be no signs of impaired cognitive functioning during a presidential campaign. Second, once the candidate is elected, there is little assurance that power will be transferred appropriately if the candidate’s mental or physical health slowly deteriorates. The Twenty-Fifth Amendment provides for the transfer of power to the vice president if the president becomes unable to discharge his duties.[3] But the amendment was written with dramatic (and obvious) gunshot wounds or heart failure in mind. It does not specify what threshold of disability should be met to trigger succession, and as such it has perhaps not been invoked when it ought to have been.

There are also countervailing arguments against the genetic testing of presidential candidates for other devastating diseases. For starters, most genetic disorders such as Alzheimer’s disease are not caused by a single gene and often result from a complex interaction of genetic and environmental factors. In many cases genetic tests can therefore only predict a modest increase in the risk of developing a trait; information that may be interesting to voters, but not very useful for predicting a candidate’s future health. Second, requiring even more intrusion into the candidate’s personal life could make the job so unattractive that only sadists would apply. Third, mandatory genetic testing might reinforce the false notion that candidates need to be in perfect health in order to effectively govern.

And how should we decide what is included in the genetic test? Should the candidate be tested only for Huntington’s disease, or for every possible neurological disorder, regardless of the test’s validity? Should we only test for those diseases that are highly likely to severely affect cognitive function? Wherever the line is drawn, the battery will likely be both under- and over-inclusive.

Another problem with mandatory genetic testing is that the results would affect the candidate’s relatives. Unlike the candidate, his or her children and siblings did not volunteer to be public figures, and they would find something out about their risk of inheriting certain diseases that they might prefer not to know. This is particularly troublesome as the suicide rate among adolescents who possess the Huntington’s gene is alarmingly high.

In the absence of clear procedures for the transfer of power, however, perhaps there ought to be better information shared with voters about the candidates’ health. This may become less problematic as genetic testing becomes more and more common and our public understanding of genetics improves. Regardless, any mandatory disclosure scheme should make sure that the privacy rights of the candidate’s family are protected somehow, and that the information is ultimately disclosed through a panel of bipartisan clinicians.

Or perhaps not. We might decide that an individual’s medical records are categorically different from financial information or religious beliefs. Maybe health information constitutes the last bubble of privacy that as a society we ought not to pierce. But even though the arguments for keeping the status quo are incredibly strong, without mandatory disclosure the candidates will continue to cooperate under this unusual “prisoner’s dilemma” and do what is in their best interest: keep quiet. But in the coming Genetic Age of the 21st century, this precedent may not adequately protect what is in the public interest.

Teneille Brown, JD, is a Postdoctoral Fellow at the Stanford Center for Biomedical Ethics

Notes

[1] 42 U.S.C.A. § 2000ff (2008)

[2] Chandler v. Miller, 520 U.S. 305, 309 (1997)

[3] U.S. Const. amend. XXV, § 1

The technology is undeniably impressive. For as little as $1,000, anybody who can drool into a mailing tube can now find out his or her genetic odds of getting any of 20 or more potentially debilitating diseases, including cancer, heart disease and diabetes. Most of these tests will not lead to a frank diagnosis, as happened with Gulcher. But discovering an inherited propensity toward a particular illness can motivate consumers — or, as they used to be known, patients — to get more frequent checkups, take preventive medicines or make lifestyle changes to try to ward off the specter of disease. At last, we seem to be on the cusp of the long-promised personalized-medicine revolution in which gene tests allow physicians to craft far more individualized and effective ways of keeping us well.

While the top officials from all of the major competing gene testing companies agreed that regulations over the industry must be standardized, Weiss does not believe this measure is enough. He calls upon the Department of Health and Human Services and the Food and Drug Administration take the lead on crafting smart policy. Genetic testing companies should also be more transparent about their technology, test results, privacy, and security systems, and the potential use of client specimens for experimental purposes, he argues.

Weiss will discuss the article online this morning on the Washington Post website at 11 a.m. EST.

UPDATE: Weiss discusses the challenges of direct-to-consumer genetic testing in CAP’s latest installment of the Ask the Expert videos.

According to the research, 90 percent of the African population express two copies of a mutation in DARC called DARC-negative. This mutation effectively removes the Duffy antigen from the surface of red blood cells, where it would normally bind to chemokines, small molecules that contribute to the immune response. Antigens like Duffy are large molecules that help generate antibodies and increase the response of the immune system.

However, the new study suggests that the mutated Duffy antigen that is so common in the African population actually helps the HIV virus attach to red blood cells, and more efficiently infect T cells. T cells are like the police chiefs of the immune system—they activate other cells and tell them to destroy various biological threats, such as cells that have been infected by viruses. Once T cells get infected by HIV, the body’s ability to destroy other cells infected by the virus is severely compromised.

But the DARC mutation is not completely devastating for those at risk of contracting HIV. The study indicates that “DARC-negative… is associated with slower disease progression.” In other words, HIV spreads slower when the body’s immune system is already slightly compromised by the mutation in DARC. So while individuals who are DARC negative are at a greater risk for contracting HIV, the same mutation may also slow the progression of the disease.

This research news comes just after the House and Senate passed bills allocating $50 billion for the global fight against AIDS and other diseases and lifting a travel ban for HIV-positive people that has been in place since 1987. However, this latest work on the mutation suggests that policymakers should also increase their commitment to funding HIV/AIDS research, especially because of further discouragement within the community about the possibilities for the development of a vaccine.

Life expectancy has grown by leaps and bounds in the past century. And to be sure, that success story has been written not by exotic anti-aging creams or wrinkle removers but by hard-won victories over infectious diseases, primarily through public health advances and antibiotics. A century ago, only about 40 percent of babies born in countries where births and deaths were reliably counted could be expected to live past the age of 65. Today, almost 90 percent do so. That’s one reason why in the United States alone, the number of people older than 85 is projected to quadruple by 2050, to 18 million from today’s 4 million.

But how do we keep that progress going in developed countries, now that infectious diseases have largely been tamed? The current approach to extending life, which has garnered some modest success in the past decade or so, has been to focus on curing those chronic diseases of aging that have become the modern era’s major killers, such as heart disease, stroke, cancer, diabetes, and Alzheimer’s disease.

Yet most of these diseases have proven remarkably resistant to treatment. More important, a number of research models have concluded that even if scientists were to score a complete home run by finding a “cure” for any single chronic disease such as cancer or stroke, life spans in developing countries would hardly grow longer. That’s because the other chronic diseases of old age are right there, waiting to kill us anyway at about the same age. You’d have to find cures for virtually all of them, these models suggest, to make any real progress at this point.

That’s where the anti-aging approach comes in. As it turns out, scientists studying the aging process in a wide variety of organisms—from worms to flies to fish to monkeys and people—have been finding that certain genes common to virtually all kinds of life play key roles in the metabolic and genetic processes that together underlie most diseases of aging. Some of these genes are important for repairing DNA damage caused by sunlight, chemicals, or other environmental insults. Others affect the levels of vital hormones. As scientists figure out what these key genes do, it becomes possible to envision developing medicines that mimic their activity, which typically wanes late in life.

Complementing that cross-species work, a number of ongoing research projects promise to clarify some of the most important anti-aging genes in people. In one project, described in this week’s issue of Technology Review, researchers are comparing DNA from two populations: people 80 or older who have never had serious illnesses and those who died of age-related ailments before they hit 80.

Two analyses to be published in the July 19 issue of the British medical journal, BMJ, make the case that such efforts could have big payoffs. Unlike conventional advances in lifespan, which in many cases have added years of disability and suffering to the end of life, the anti-aging approach would add healthy years, according to Colin Farrelly of the University of Waterloo in Canada. “There is a credible scientific basis for believing that we could slow aging in the foreseeable future,” he concludes. “And the amount of public funding we invest into such research will determine the likelihood and timescale of success for aging interventions.”

Others writing in that journal—including Robert Butler (a former head of the federal National Institute on Aging), S. Jay Olshansky (a leader in the field at the University of Chicago), and Daniel Perry (of the Alliance for Aging Research in Washington)—argue that $3 billion, or one percent of the Medicare budget, would be a “prudent” investment in anti-aging research. They make a convincing case that such an investment could pay for itself many times over by delaying not only the fatal diseases of old age but also the many debilitating conditions such as osteoporosis, arthritis, cataracts, and cognitive decline that typically take a big toll on quality of life in people’s final decade or two.

They call that benefit “a longevity dividend,” and it looks to me to have a much higher probable rate of return than most of the other dividends I’ve been counting on for my retirement. Meanwhile, hang in there, ol’ Ponce. Your reputation, if not your bod, may get rehabilitated yet.

Rick Weiss is a Senior Fellow at the Center for American Progress and Science Progress.

We are still learning to what extent our genomes influence our health and we still have lots of gaps to fill in our coverage of genetic privacy. GINA was an important first step, and we are fortunate to be able to draw on European experience to guide future legislation.

They examine studies of seven susceptibility alleles with low penetrance, or a small likelihood of causing a disease that individually play a very small role in increasing a woman’s risk for breast and ovarian cancer, but can have a significant cumulative effect. They do not examine low-frequency, high-penetrance mutations in genes like BRCA1 and 2, which increase the risk of breast and ovarian cancer, or TP53, which suppresses tumor formation. The study focused on an analysis of just how significant the cumulative effect of multiple mutations is and whether it is worth changing screening procedures in order to target women with a higher-than-average level of risk due to genetic predisposition.

This study, along with an increasing number of papers which identify cancer-susceptibility genes and meta-studies which analyze the statistical significance of those genes, focus attention on the question of how knowledge of our genes will shape public health in the future. The Pharoah article discussed several scenarios for screening programs and concluded that it would be possible and cost-effective to genotype every woman in the United Kingdom at all known susceptibility alleles and recommend personalized screening routines regarding what age the women should begin to get mammograms. Based on genetic susceptibility, the study concludes that only 0.1 percent of women in the United Kingdom should begin annual screenings at the age of 40, which is the current recommendation.

This targeted approach to cancer screening might save money, but there are certainly several obstacles to implementation of a measure like this in the United Kingdom, the United States, or anywhere else, including the issue of how to reach every woman in the population and how to insure the privacy promised in the Genetic Information Nondiscrimination Act while still delivering personalized screening recommendations. Nevertheless, our small but steadily increasing understanding of our genome ensures that more tests and treatments in the future will be tailored to our personal genetic makeup. As the Pharoah article concludes, “Policymakers should start to consider how this knowledge could be used to make a polygenic approach to disease prevention a reality.”

For now, British insurers may not require customers to disclose the results of genetic tests for holders of life insurance policies of up to £500,000, critical illness insurance of up to £300,000, and income protection insurance of up to £30,000 a year. Only 3 percent of insurance policies exceed these amounts, and even for policies outside those limits, only government-approved genetic tests may be incorporated into an insurance company’s calculus. So far, the only genetic condition for which the U.K. government’s Genetics and Insurance Committee has approved insurance premium adjustments is Huntington’s disease, for which there exists two tests that can determine with 100 percent certainty that a person will get the disease. According to the GAIC, insurance companies may only adjust life insurance policies of over £500,000 if a policyholder tests positive as a carrier for the Huntington’s gene. GAIC stipulates, however, that, “This decision does not mean that individuals will be asked to have a genetic test for Huntington’s Disease before obtaining insurance but, where individuals have already been tested as part of their medical care, then there is nothing to prevent insurance companies asking for that information.”

These policies from the U.K. government and private sector are keeping pace with the ever-changing area of genetic medicine, where new studies frequently propose links between genetic mutations and disorders.

But Mark Henderson, Science Editor of The Times of London, presents a dissenting view of genetic testing, arguing that allowing insurance to companies to make decisions based on the results of genetic testing is not unfair discrimination. The consensus against genetic discrimination is wrong, he writes: “It breaks with precedent, is unfair to businesses and many consumers, and imagines a threat to equality that is actually rather marginal, because of a misunderstanding of how DNA influences human health.” He argues that family history has been used for years to determine insurance premiums and genetic tests are a more accurate indicator for which family history is just a proxy. He also mentions that genetic testing might clear individuals of presumed genetic risks indicated by family history. For instance, if a person has one parent with Huntington’s, they would be considered 50 percent likely to develop the disease themselves, but a genetic test can tell them with certainty whether or not they actually have it.

But Henderson misses a key provision of the moratorium. According the ABI’s brochure, “You may choose to tell the insurer about the result of a predictive genetic test that is in your favour in order to override family history information. Insurers may take this voluntarily disclosed information into account. Each case will be assessed individually.”

Henderson also brings up evidence from a Duke University study that patients who test positive for an Alzheimer’s gene are more likely to take out long-term nursing care insurance. This knowledge of a genetic predisposition would give high-risk customers too much of an upper hand and would result in a rise in premiums for all those in the insurance pool just to take care of those who are high-risk. Finally, Henderson makes the point that genetic testing will eventually prove to be a poor basis for determining life insurance premiums because “there is no such thing as a perfect genome.” But the probability that a gene will express a disorder varies. In fact, variable probabilities in multiple genes can cancel each other out in terms of risk conferred to the carrier. It would not be wise for an insurance company to pick and choose genetic predispositions, since it would loose business that way. He concedes, however, that customers with particularly detrimental genetic predispositions, such as Huntington’s, should be taken care of by the government; especially because, for many such diseases, insurance companies don’t need to look at genes and can just raise premiums based on family history.

Most of these are excellent points, but again, Henderson neglects to consider that without the moratorium, insurance companies might jump the gun and start discriminating to gain a slight, if temporary, edge over competitors. Discrimination does not wait for the market to respond.

In the United States, insurers would do well to learn from their British counterparts, where trade associations make voluntary agreements and defer to the government on certain standards. The business community’s support for GINA indicates that there is some promise for such a move on our side of the pond. For example, companies such as IBM and Eli Lilly have added genetic non-discrimination to their employment policies. More importantly the trade group American Health Insurance Plans did not “oppose the bill and agree[d] with its intent.” Nevertheless, with the ABI’s recurring reviews of the moratorium and the GAIC’s approval of genetic tests that are relevant enough for insurance purposes, the United Kingdom’s public and private sectors have proven to be exceptionally diligent in developing policy that keeps up with the ever-developing science of personal genomics.

To grapple with her own choices and to explore the impact of genetic testing for the BRCA mutation on women across the country, Rudnick set out to make a documentary, In the Family. If decisions about prophylactic mastectomies and hysterectomies were not difficult enough, Rudnick must also balance her genetic privacy and medical treatment before the passage of the Genetic Information Nondiscrimination Act. She talks to mothers fearful of passing the mutation on to their daughters. She finds sisters grappling with the choice to get the BRCA test in the first place. And she also finds a strong, supportive community of women brought together by their common battle against cancer.

Now 31, Rudnick spoke with Science Progress about the impacts that genetic medicine and public policies have on the lives of women from all walks of life who face empowering and frightening decisions wrapped in their own genes and family history. This interview has been edited.

Andrew Plemmons Pratt, Science Progress: Can you tell us about when you knew that you needed to make this movie, and why?

Joanna Rudnick: When I was 27 years old, I got tested for both BRCA1 and 2, and found out that, like my mother, I was positive for a mutation on the BRCA1 gene. I received a piece of paper that said I was positive for a “deleterious mutation,” and was stunned by the information and didn’t exactly know how to talk about it with people who were my age, my peers—really anyone. I didn’t know how to talk about breast and ovarian cancer, but I have this incredible predisposition to getting both of these diseases. I felt very stigmatized, and really knew that there needed to be a language where we could talk about this, so we didn’t feel like we were tainted, all of us with genetic mutations, and that we could create a culture where this is something we could talk about without fear of discrimination—without fear of not only discrimination from employers and insurance companies, but discrimination from friends, colleagues, peers. Again, that feeling that you’re tainted or something is wrong with you because you basically inherited faulty DNA.

SP: Was there anything in your experience or training as a science journalist that informed the way you put this movie together?

Rudnick: I made this film at Kartemquin Films, which is a production company that has 40 years of experience of putting a human face on some of these complex social issues. So it went away in a sense from a lot of my science journalism training—which is really focused on helping people understand what genetics means, and taking the science and making it easy to translate—but instead focusing more on the people themselves who are affected by having this information.

We’re really telling the stories of the individuals who are struggling and families that are struggling with this information, and what it means in a psycho-social context to look at yourself as someone, again—who is tainted or has this incredible 80 percent risk of getting breast cancer—and what it means to walk around everyday with that knowledge. We really moved away from including a lot of science in the film. We do have an animation that we use to explain how the BRCA gene works, and how having a BRCA mutation could lead to cancer. But in a sense we really focused on letting the women themselves, and the family themselves, tell the stories, rather than having a lot about future treatments or some of the science of what’s happening with BRCA.

SP: There’s a really interesting moment in the movie with Dr. Mary-Claire King, the geneticist who identified the link between the BRCA gene and increased risks of cancer. She says, “Living with the predisposition is like being a cancer survivor.” Do you feel like that rings true?

Rudnick: I don’t know what it’s like to be a cancer survivor, thankfully, but I think in a sense what she was saying is that you’re always looking over your shoulder. Once you have cancer, you’re always thinking, is it going to come back? Living with BRCA, every time I have a pain in my breast, or I have any kind of feeling of being bloated, or just a fear, it’s constantly in the back of my mind: am I going to get cancer? When am I going to get cancer? Am I going to be able to fight it? Once you know that predisposition is there, it’s very hard not to think about yourself as someone who will eventually get these diseases if you don’t do something about it. So you are constantly looking over your shoulder and pleading not to get these diseases. I think that can be similar to someone who is worried about a recurrence of a disease.

SP: You mentioned privacy; you and the women that you talk with in the film were all tested for the BRCA mutation before the recent passage of the Genetic Information Nondiscrimination Act. Can you talk about the privacy decisions that you made when you got tested, and how GINA going to change those decisions for people in the future?

Rudnick: I’m definitely someone who was impacted by the lack of protections when I got tested. I was very nervous that I could potentially be discriminated against by an insurance company and be dropped, or be charged higher premiums because of this predisposition that I have. As you know, people who have had cancer have difficulty getting insurance coverage. So I thought, “well I have this incredible risk of getting cancer, they’re going to see me as someone who could potentially be extremely expensive and be a liability.” So I did actually test anonymously. And I was fortunate in that I knew what particular mutation I was looking for, so my test was only $250, as compared to the $3000 price tag—or even higher now—I believe, that Myriad Genetics charges for the test. So I did test anonymously and I paid out of pocket, and again, I had the privilege of being able to pay out of pocket—a lot of women don’t.

I kept that information out of my medical records for years. I would go to a doctor and they’d be asking me all these questions, like “Why are you getting this test?” and I would say, “Well I have the BRCA mutation.” They’d go to write it down and I would say “No, no, no, don’t write it down!” because I thought I could potentially lose my insurance, and I realized I was in a sense harming myself by not being able to keep it in my medical records. That was a harmful thing. So I think many of the women, like me, who were living with this information pre-GINA were always worried, again, looking over our shoulders, asking “are we adequately protected?”

It was less that there were actually cases of women being discriminated against because of having BRCA, and more that fear of being discriminated against or the privacy being infringed. I think that fear actually kept a lot of people from testing. That’s what we’re working on now: how do you kind of break down that culture of fear and tell people that this law is there to protect them and their rights? They do have the rights: having faulty DNA doesn’t make you someone who should be discriminated against.

SP: You mentioned being in a position where you could pay out of pocket for these tests, and you knew exactly what you were looking for. While the mutation affects women across ethnicities, that doesn’t necessarily mean that women of various backgrounds are tested with the same consistency. There are disparities. Can you talk a little bit about the impact this has on the health of women of different backgrounds?

Rudnick: That’s a really great point. When BRCA first came out, it was associated with Ashkenazi Jewish women. A lot of the early studies were just done in Ashkenazi Jewish populations, where 1 in 40 individuals does have the mutation, which is extremely high. But the truth is that women of all ethnic backgrounds have BRCA mutations. The estimate is anywhere from 1 in 400 to 1 in 500 people carry BRCA. That’s kind of a contradictory figure; I’ve seen it as high as 1 in 700. But the fact is, it’s common, and it’s common in all populations.

What we found in working on the film, talking to genetic counselors, and looking at the research, is that minority women were less likely to be referred. Part of that is that because this initial research was done on Ashkenazi Jewish women, physicians would not necessarily see a woman who was African American, Hispanic, or Latina and think that even though they had this incredible family history, it could be caused by a BRCA mutation, but, in fact, it absolutely could be.

Martha, one of our characters in the film, tests for something called “a variant of uncertain significance,” which shows you how imperfect our genetics knowledge is right now. It’s a change in the DNA where we don’t know if it’s deleterious—meaning it caused her breast cancer, and she’s a three-time breast cancer survivor—or if it’s not a harmful change at all, just a regular kind of fluke in her DNA that isn’t deleterious. I think because researchers haven’t tested enough African American women, as the genetic counselor says in the film, that’s part of the reason why they haven’t reclassified these mutations that they’re finding in the African American population as either deleterious or benign. That raises a lot of questions about access, and about perceptions about who actually carries these mutations.

SP: Are there projects that you’re aware of that are trying to close that testing gap, and educate women—particularly in the African American community—who might not know about the possibility for testing?

Rudnick: There are people out there who are working on that at universities, and the program that we profile in the film is actually funded by Avon, and that’s a special assistance program in a county hospital in Chicago, to provide genetic testing to women who are underinsured or uninsured, and to make sure that they actually have access to this information that they normally wouldn’t be getting because of the cost of the test. But educating physicians is also important so that they understand that not only Ashkenazi Jewish women are at risk for having a BRCA mutation, but that it is much more common amongst all ethnic groups.

SP: You mentioned a couple of times the cost of the test, and part of that is connected to the fact that there is one company that provides testing for BRCA, Myriad Genetics. Can you talk a little bit about the way gene patenting controls this particular situation, and what people think about the fact that one particular company literally has a patent on the gene?

Rudnick: Like many of the women that I talked to and families in the film, I was very shocked to find out that genes were patented. My first response was, “How can you possibly patent a gene? It’s something that exists in nature.” I think not that many people are aware of the fact that there is a lot of natural material and natural products that are actually patented.

I really wanted to go to Myriad to talk to the founder of the company, and ask about why it’s OK to patent genes, in that sort of pure and simple way. Why is its OK to patent genes, and what are some of the results of patenting genes? When I was there in the interview, you saw that I asked him about research, and does patenting actually impact research? How does it impact the search for a cure? Very importantly, how does it impact the accuracy of the test and the cost of the test? I think those are two things that really come out in the film. By owning the exclusive patent, Myriad does control the cost of the test, and there is no other, cheaper test that you could go get in another laboratory, because they have the exclusive patent. They also control the efficacy of the test. If they are missing mutations, there’s not another test out there that could be a better test, a cheaper test, a quicker test, and even a more accurate test. It’s not just the actual test, which I think people sometimes don’t understand, and it’s not that they only have this one way of testing. They actually have the patent on the gene itself, the composition of that particular gene, because they sequenced it. I think a lot of people are kind of amazed to learn that, so we wanted to bring that up in the film.

SP: Another controversial thing that’s happened with Myriad is that in the fall, the company started an advertising campaign that encourages women with certain hereditary histories to seek out the test, which seems a little strange, to be marketing a test for this predisposition when they are the only company that controls it. Can you talk a little bit about that particular push to advertise the test, and the impact that might have on people?

Rudnick: I can put myself in the position of being a high-risk woman, whose mom had ovarian cancer, whose grandmother had breast cancer, who has kind of one of those classic families. If I was sitting at home one night, watching that television commercial, and I didn’t know what I know now—that I do have this mutation—I would be terrified. I would see that commercial and I would be terrified. And if I didn’t know how to find a genetic counselor, or I didn’t know where to go to get the test, or I couldn’t get to a genetic counselor for some reason, I think that would really create a lot of fear inside of me that for some women may be unnecessary. Everyone is so afraid of breast cancer. It is an epidemic: you look around you, you know someone who has breast cancer. But only 5 to 10 percent of all breast and ovarian cancer is hereditary. Which is not to say this is not a significant population, because we’re disproportionately affected, because we’re affected young. But there are a lot of women out there who may have breast cancer in their family that was caused by a different gene that we haven’t found yet, or that there isn’t a test for, or that was caused by other factors.

So I think that there’s a real responsibility in how we get this information out there. What the film shows you is that it’s not a simple blood test. There are repercussions afterwards, in terms of how it impacts your life, and good genetic counseling is very important. What I’ve heard, is when those commercials came out originally, and they were directly marketing to women, there weren’t enough genetic counselors in those areas to actually field the calls of these women who were very distraught and distressed. And I think that’s a very scary proposition—to be out there, and to have this potentially devastating information, that you don’t know whether or not you’re even appropriate to get the test, and not have the right support system that you need to make the right decisions for yourself. Knowing this population and what we show in the film, you really see how important getting that pretest counseling and that post-test counseling is for these families. This is just straight family dynamics, where sometimes you have one person who wants to know, and one person who doesn’t want to know. Without good counseling, that could create serious rifts in people’s lives.

SP: There’s actually one scene in particular where you are filming at the moment where three sisters who have decided to all get tested learn their results, and they’re speaking with a counselor, learning about their predisposition. Why is it important to show that particular moment, and that particular support? It seemed like a very important part of the movie.

Rudnick: That’s a great question. First of all, I am so grateful to Mary-Claire King and her genetic counselor Jessica Mandell, and those three sisters, for allowing us in, the entire family, on what is such an incredibly personal and sensitive moment—especially when you have three young girls, testing at the same time, and knowing that, most likely, not all of them are going to have the same result.

I think what was so important about showing that is it’s almost impossible to explain to people what it means to actually get that information, and just the reaction in that moment. We also tried to show in the movie is that it’s so much more than that particular moment, the gravity of the information. It was really important for us to show how a genetic counseling session actually happens, to demystify it a little bit. We wanted to provide as much information for individuals thinking about testing as possible, and we thought it was important for them to actually see what that moment looks like and feels like, as much as you possibly can without being those individuals.

As a filmmaker, I think you are just so grateful. And as someone who went through that experience—and to think about a film crew being there at a moment where I was absolutely devastated to find out my results. I was just so grateful that they were open enough to let a camera in there, because they wanted people to understand what it’s like to get this information, and also, I think there are some moments—even without giving away what happened in that session—that you see that this information can be handled in a way that helps the people who are getting it prepare for the future. And that again speaks to good counseling.

SP: Let me close on a fairly personal question: how are you preparing for the future? Part of the movie is you going through a process of learning about your options for how you can deal with the chances that you have, over the course of your lifetime, of developing breast or ovarian cancer. Where are you in that process?

Rudnick: I think you’re asking me about an interesting point. I think in a way the process of making the film was sort of this brilliant distraction, and this was a wonderful way to talk about and tell the story without really thinking as much, even though in the film I’m absolutely thinking about my own life. But now that I’m no longer sitting and making it as a full-time profession, I’m thinking a lot more about my own future, and the choices that I have to make.

It’s getting more frightening to me, that I’m getting closer, I think, to making surgical decisions. I’ve certainly decided that by 40 I have to remove my ovaries, which is absolutely the recommendation. My mom got ovarian cancer at 43, and you learn in this film that every woman has a magic age, and every woman who had a relative—because it can be passed down through a father—it comes unexpectedly. But women who have seen a relative go through breast or ovarian cancer, first degree, that’s what they think of their lives. So I see 43 as a scary age. That’s when my mom was diagnosed. Every year, it becomes more real.

And they’re difficult decisions, you know? I could say that I wish it was easier, and I could just answer this, “I’m going to have the surgery, I’m going to have it on this date.” I’m still struggling.

SP: What should readers understand—those who might be grappling with these decisions on a personal level, and those who are making decisions within the medical or policy community? Is there anything that you think they need to understand about this particular film?

Rudnick: I think that there are a lot of resources out there for women and for families who are going through this. There’s an amazing support group online support group called FORCE, or Facing Our Risk of Cancer Empowered. Their website is facingourrisk.org, where there is tons of information about screening options. One way to go with this is to watch yourself extremely closely. We’re getting better at catching cancer early, and screening, and there’s MRI technology for looking at the breast, which is really a new, wonderful way of trying to detect cancer early. There are also surgical options, and there are women out there who’ve been through and taken both tracks, who are extremely supportive, and are willing to talk very openly. They gave me the courage to come out and talk about it. Part of it is families getting together and talking about this history very openly with each other, and moving away from female cancer, talking about breast and ovarian cancer. But there are some amazing surgical outcomes out there. You see women cut off their breasts, they remove the breast tissue that could become cancerous, and they oftentimes get beautiful reconstructions, and they look great, and they’re still sexy, beautiful. There are really empowering choices out there. So we don’t have everything we want, but I think that there is some very brave decision-making happening, and it is a gift to have this information, to think that you can avoid the fate of your genes and your destiny. You step back from it, that’s a pretty awesome ability to have.

SP: You have some screenings coming up here in the DC area.

Rudnick: Our next screening is July 10^th. We have two screenings at the E Street cinema to celebrate the passage of the Genetic Information Nondiscrimination Act. We hope everyone will come out, and they’re free. You can learn about them through the Genetic Alliance, or on the inthefamilyfilm.com website. Also, we will be airing nationally on public television on the Point Of View series on October 1^st; check your local listings.

It sounds ridiculous, but this is the situation our nation is in for one of the hottest new tools in medicine, genetic tests. Gene tests conducted on a drop of blood can help predict what diseases a person is likely to get, fostering better preventive care and earlier diagnosis. For a growing number of diseases, gene tests can tell a patient which drug will work and which will not.

The moves by California and New York are the clearest evidence yet that a federal leadership gap now threatens to undermine the pending benefits of the genomics revolution.

But despite repeated calls by scientific and patient advocacy groups for the Bush administration to focus on this important emerging specialty, years have gone by without federal leadership. The Food and Drug Administration says it has the authority to regulate these tests—to make sure they give accurate results and provide meaningful information—but has largely steered clear of the complicated arena. The Federal Trade Commission, which has the responsibility for protecting Americans against false claims and consumer fraud, has effectively been AWOL on the gene test front, with the exception of a general “buyer beware” warning it put out in 2006. And despite repeated assurances that gene tests are a top priority, Health and Human Services Secretary Mike Leavitt has barely acknowledged receipt, back in April, of a long-awaited federal advisory report that called for HHS to take the reins on gene tests before this fast-moving specialty gets tainted by bad science and overzealous entrepreneurs.

Yesterday that lack of federal attention came sharply into focus with the revelation that California’s public health department had sent “cease and desist” letters to more than a dozen gene test companies, including several direct-to-consumer companies that have recently begun to offer DNA tests through the mail. Health officials told the ventures they have two weeks to prove that they are in compliance with applicable state rules relating to such things as laboratory licensure and the status of the doctors or other professionals who are ordering and interpreting these pricey tests for clients.

It’s tempting to see California’s move as simply a responsible act by state officials concerned that consumers not get taken for a ride. And to be sure, there is room for concern. The tests offered by these companies—most prominent among them are 23andMe, Inc. of Mountain View, California, and Navigenics, Inc. of Redwood Shores, California—provide predictive information about future disease risks that is, by nature, preliminary, approximate, and difficult to interpret. Since by law consumers in some states cannot order these tests themselves, they are ordered by doctors affiliated with the testing companies, who do not know the clients/patients personally. And test results can be easily misinterpreted by clients if not explained by a trained genetic counselor or other professionals. Moreover, since there are some diseases for which there are no good treatments or preventives, there are questions of medical ethics, such as whether people are being too glibly encouraged to get information they may wish they never got.

At the same time, the gene test industry is the leading edge of a pending revolution in which diagnoses and treatments will, in many cases, be personalized to individuals’ precise biological details. Already, the FDA has begun to approve drugs with gene test requirements or recommendations. In December, for example, the agency oversaw a label change for the drug carbamazepine—which is used to treat epilepsy, bipolar (“manic depressive”) disorder, and nerve pain—to inform people of Asian ancestry that they should get a genetic test before starting therapy with the drug. People with a certain version of a gene, it turns out—a gene that is particularly common in Asians—have a significantly higher risk of developing an otherwise rare, but serious, skin reaction to the drug.

Similarly, researchers reported last month that a lung cancer drug that has otherwise been disappointing appears to be very effective in the ten percent of patients who have a particular gene variant. Such discoveries can mean the difference between life and death for some patients, and can turn a drug that might have been thrown away by its developers into an overnight money-maker.

The problem is that state laws and regulations meant to protect patients and other users of gene tests vary considerably across the nation. Indeed, many of the same companies that got letters from California received similar letters not long ago from health authorities in New York State, which has perhaps the strictest medical test rules in the nation.

Now is the time for a clear guiding hand from the highest levels of the federal health bureaucracy.

The moves by California and New York are the clearest evidence yet that a federal leadership gap now threatens to undermine the pending benefits of the genomics revolution. “I can buy any number of medicines whose safety has been reviewed but I may not be able to get a test to say which drug is better for me,” Kathy Hudson explains with apparent frustration. Hudson is the director of the Genetics and Public Policy Center in Washington D.C., which has produced a chart that shows the wide variation in state laws and regulations regarding gene test oversight.

One thing that this latest twist shows is that it is not enough to assure patients that the information gleaned from gene tests will not be used to discriminate against them in health insurance or employment. Congress secured that important human right this spring when it passed the Genetic Information Non-discrimination Act. But it took a dozen or so years for the legislation to pass, and the pace needs to pick up.

Consider that back in 2005, Secretary Leavitt responded to concerns about oversight of direct-to-consumer gene tests, saying he would “carefully consider” looking into the issue. More than a year ago, Leavitt announced that HHS was reviewing “existing structures for ensuring that genetic tests are accurate, valid and useful.” Last September, he said, “work is moving ahead rapidly to support genomic medicine in particular and Personalized Health Care in general.”

Meanwhile, tired of waiting, a number of gene test companies did their due diligence and launched, hoping that regulators would either ignore them or ultimately agree that they were in compliance with relevant laws and regulations. Washington remained silent.

In April, the Secretary’s Advisory Committee on Genetics, Health and Society sent Leavitt a carefully researched report on oversight of genetic tests. Among other things, it recommended that the FDA use its authority to oversee the full range of genetic tests and that the Centers for Medicare & Medicaid Services, which oversees proficiency testing for various medical specialties, start a program of proficiency testing for gene test labs to make sure these fledgling enterprises really know what they are doing. It also recommended the launch of a variety of federal programs to help individuals know what they are getting into when they decide to get a genetic test.

To the great frustration of many, Leavitt has not even formally acknowledged receipt of the report, much less hinted at how he will respond.

The advisory committee’s recommendations echo a report released by the Center for American Progress in April, “Genetic Non-discrimination: Policy Considerations in the Age of Genetic Medicine.”

If HHS does not act, the CAP report says, then Congress should pass legislation requiring proficiency testing and FDA oversight. Two Senate bills already introduced, S. 976 and S. 736, could accomplish those goals. The CAP report also calls for a public registry of available gene tests to facilitate consumer education and government oversight. And it calls for the FTC and the FDA to collaborate toward creating advertising guidelines for gene testing companies, and for strict enforcement by the FTC of companies that violate those guidelines.

Without attention from the Bush administration, the fledgling field of genetic medicine could deteriorate into a war among companies and state governments, exacerbated by a turf war among doctors, medical geneticists and genetic counselors as they vie for control over this new and potentially profitable piece of the healthcare pie. Representatives of the major gene test companies quickly expressed a willingness yesterday to work with state government officials to draw up ground rules that can protect consumers and not stifle the nascent industry. Now is the time for a clear guiding hand from the highest levels of the federal health bureaucracy.

Rick Weiss is a Senior Fellow at the Center for American Progress.

At the event, Collins sparred with co-panelist, Dr. Jim Evans from UNC-Chapel Hill, about how the medical science community can best use the emerging body of genetic knowledge to make clinical decisions.

Evans emphasized the murkiness of the diabetes-genes link, saying, “It’s relevant, but I’m not sure it will ever be robust.” In contrast, Collins was more optimistic, noting that with a disease like diabetes, there has not been enough clinical research to tell us whether a genetic disorder responds better to a particular type of diet or a to particular type of exercise.

Collins also reminded the audience that even though, “we can’t manipulate genes, we can manipulate environment.” Evans, who explained that he has enough difficulty getting his patients to stop smoking, felt that most people would not be motivated enough to change their diets or exercise habits based on a few percentage points of increased risk. As far as he was concerned, the kind of treatments that patients are waiting for are drugs.

Evans also stressed that the development of effective treatments depends on how many “large effect” genes we find. Collins thinks we will find a lot, and Evans does not. Citing Alzheimer’s disease as an example, Evans noted that the average American has a 12 percent chance of developing the disease, and then posed the question, “But what would 20 percent tell me?”—implying that a mere genetic probability might not be clinically actionable. This led Collins to retort, “Actionable is in the eye of the beholder.”

Citing the Risk Evaluation and Education for Alzheimer’s Disease Study (REVEAL) conducted by the NHGRI and the National Institute on Aging (NIA), Collins explained that after a year, most people in the study who found out they had a high risk of getting Alzheimer’s Disease handled it pretty well. Unfortunately, for most of the general public, misconceptions remain about genes being the primary determinants of one’s fate.

Because of this, Nikolas Rose, a sociologist from the London School of Economics, disagreed with Collins’s use of an “instruction book” as a metaphor for the genome, contending, that “genes don’t tell us who we are,” and that protein formation, environment, and society also comprise a person’s identity. Misha Angrist, a science writer, assistant professor at Duke University, and a subject in the Personal Genome Project (a Harvard University effort to sequence and make public the genomes of 100,000 volunteers), also pointed out the fallacy of genetic determinism by noting that there are over fifty genes which influence height by only one or two inches. But he nevertheless insisted that regardless of what one thinks of genetic tests, “People want this information.”

The group did agree that the recent passage of the Genetic Information Non-discrimination Act was a good thing. Still, Evans expressed concern that the even though GINA applies to heath insurers and employers, it does not apply to long-term care insurance, disability insurance, and life insurance, which are arguably the types of insurance where the lifetime probabilities provided by genetic tests might be most relevant. This sentiment was echoed by Collins, who added that GINA also takes family history into account and that health insurance companies are okay with that as long as it’s off limits to all companies.

Delving into the practical implications of genetic discrimination, the panel moderator, Nobel Prize-Winner and President of Rockefeller University Paul Nurse, posed a question about whether an airline might be justified in denying a job to a pilot who has a genetic predisposal to having a heart attack. This prompted Evans to burst the gene-centric bubble of the conversation by reminding the panel and audience that physiology is the most important diagnostic tool because, “it tells me what’s going on with your heart right now.” Collins quipped that the probability of death for all of us is one, and that half the population has a genomic characteristic that makes them 16 times more likely to commit a crime—it’s called a Y chromosome.

Rose continued to debunk determinism and concluded by noting, “Nothing that we find will transform philosophically or practically whether we have free will.” He even admitted that he agrees with Leon Kass, former chair of the President’s Council on Bioethics for the Bush aministration, on the point that we need to stop thinking, “if only this, if only that, we will relieve all suffering.”