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.

With the Human Genome Project complete for over a decade, the benefits of genomic data are now trickling into the business and practice of medicine. The passage of the Genetic Information Non-Discrimination Act in 2008 and the Affordable Care Act in 2010 have set the rules of the road, and made the critical investments necessary to lay the ground work for new advances in American genomics research. In the coming years, as the price of whole-genome scans come down and the medical community enters a new era of personalized medicine, we will have a new set of tools with which to study the origin of diseases affecting specific populations.

Genetics can reveal useful information about an individual’s health status, but they can also reveal unexpected information about group identity. The Latino community is both genetically and culturally diverse; and as gene-based medicine advances, Latinos will need to make sure that new medical technologies serve that diversity.

I believe that to capture the necessary genetic diversity to study the drivers of health disparities, America’s research agenda must include a broad swath of the Latino population. The National Institutes of Health (NIH) has so far committed $61 million to observe more than 16,000 Latinos over six years through the Hispanic Community Health Study, the nation’s largest longitudinal study of Latinos. Yet there is still so much more to be gained by incorporating the study of Latino populations into other research projects. But the research process does not end with research funding decisions. Clinical and biomedical research practices must also be more responsive to patients, who should be empowered to tell researchers and doctors what kinds of questions they want research to answer.

Every step of the biomedical research process — from genetic testing to clinical trials — can be made more inclusive, addressing the broad range of genetic and economic diversity in the U.S. The Latino community will need to work together with research institutions and private companies to overcome the barriers that exist with regards to inclusive biomedical research. These barriers range from economic inequalities and provider biases to lack of awareness, distrust, or cultural and linguistic differences.

Doctors can play a major role in making Latino patients more fully aware of clinical trials or genetic studies by communicating the possible risks and benefits. Doctors should also inform patients of the privacy protections afforded by laws like the Genetic Information Nondiscrimination Act and the Health Insurance Portability and Accountability Act in order to build trust and allay fears of discrimination in employment or insurance. This kind of communication will become a necessity in the future as medical research and clinical care become ever more closely intertwined.

The Department of Health and Human Services has already laid out recommendations for more inclusive research practices in a 2009 report. It recommends the building of a more diverse scientific and health care workforce; outreach to trusted community members who can promote the benefits of research; and the building of cultural awareness surrounding diet, work-life balance and access to resources. The report also elaborated on a research model known as “community-based participatory research,” which would involve the Latino community in the design and conduct of the research, creating a sense of community “ownership” over the results and a greater adherence to the outcomes.

These practices have the potential to create actionable, results-oriented research processes that incorporate the histories, lifestyles and values of Latino patients. The last thing we want is for the research establishment to become overly reliant on a single indicator, measurement or classification that does not account for the needs of individuals in the Latino community and other communities. Only by making sure that every community’s voice is heard, can we be sure that personalized genetic medicine will truly be personalized.

This op-ed is reposted from the Huffington Post. Michael Rugnetta is a former research assistant for Science Progress and author of the new report, “Addressing Race and Genetics: Health Disparities in the Era of Personalized Medicine” .

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.

After all, who transmits such quantities of data? Colossal information shipment is hard to escape notice. “We never found out for sure, but to this day we assume that administrators who monitor Internet traffic somewhere came into work Monday morning, were struck by the amount of data going through the routers, and shut things down,” Flicek said.

Genomics gave new meaning to the phrase “big data.” One person’s genome, for instance, consists of 3 billion base pairs. Spelling out the order of, or sequencing, each pair requires about two bits of computer storage, making the whole genome’s storage size 12 billion bits. This translates to about 1.5 gigabytes of data. A modern machine can sequence more than 500 billion base pairs in a week or just over. That is 167 human genomes and 250 gigabytes—or the equivalent of 63,000 standard song files or 200 movie files. The research bottleneck used to be collecting data. Now, the greatest challenge is making sense of it.

Things weren’t always like this. When genomics first began carving its niche in the scientific world, the path to gene discovery was quite different. Researchers pored through recent literature, honed in on a handful of genes that sounded promising, and then, armed with these candidates, designed experiments to test correlation between them and the traits they were suspected to underlie. Call it a paragon of the traditional scientific method: Ask a question, conduct background reading, formulate a specific hypothesis, test it with an experiment, and draw a conclusion.

Over the past 10 or so years, however, meta-reviews of the literature to trace the success of candidate gene methods have disclosed staggeringly abysmal conclusions. Of hundreds of published papers using this approach, only a tiny fraction of results—6 of 166, to be exact—could be consistently replicated. Gradually, candidate gene techniques waned in favor of tactics that scanned the entire genome without any conjecture about the role of any particular gene.

Flicek’s story involved a massive undertaking called the 1000 Genomes Project, an international effort to catalogue a wide array of human genetic variation by inspecting the full genetic makeup of—you guessed it—1,000 people. What are the scientists looking for? In projects like this, often they won’t know until they find it. What is the hypothesis? In a word: vague. The human genome is laden with diversity, both among and within populations.

This way of tackling a scientific problem marks a significant shift from the time-honored scientific method. Those in the field might call it data-driven research, to be contrasted with standard hypothesis-driven science. Critics are more likely to make charges of fishing expeditions. However couched, the change in approach is this: Instead of designing an experiment to test a defined, preconceived hypothesis, researchers first amass large banks of information and then wade through them with the aid of powerful computers to unearth biologically pertinent findings.

For the maneuver to be mathematically robust, data sets must be big. Accordingly, the emergence of the method was fostered by the coupling of biology and computer science that enabled mammoth data production and storage. The approach plays a central role in disciplines ending with “-omics,” which by definition seek to characterize biology in a big way. (Some familiar examples include genomics, which deals with the complete DNA sequences of organisms; proteomics, or the large-scale study of all the proteins; and metabolomics, which involves all small molecules generated in metabolism).

Drifting research paradigms raise questions of who in the scientific community is adapting, how rapidly, and how they are interacting with their more traditional counterparts. Specifically, are those controlling the purse strings caught up on what is happening at the research bench?

A recent article in Nature lends some unique insight. Author Kendall Powell takes readers behind the scenes inside a funding committee of the American Cancer Society, which has funded 44 Nobel Prize laureates, as committee members deliberate through multiple rounds of scrutiny and elimination. Their discussions and decisions shed light on the cherished criteria that filter the haves of research funding from the have-nots. One proposal was cut for allegedly committing a very telling blunder:

Another outstanding application … runs into trouble because of a lack of scientific details. … [the primary reviewer] can’t see how the applicant will filter the genes that are pulled from the proposed screen. The problem with this particular fishing expedition, says the second reviewer, is that “he didn’t explain how he would sort through all the fish”. This proposal, too, is knocked out of the competitive range.

To understand the reviewers’ reasoning, it helps to take a look at the recent history of research funding and the relevant pressures that have developed. Over the last decade, many government science agencies have faced stagnant budgets that at best have kept up with inflation despite increasing numbers of competitive applications. At the National Institutes of Health, or NIH, the largest public funding source for biomedical research in the United States, just less than 20 percent of grant applications were funded in 2009, compared to 32 percent in 2000.

The result is a notoriously grueling application process. Researchers typically begin writing a grant months before the deadline and the entire pipeline of peer review can take up to a year. Subject to scrutiny are the researcher’s background, equipment and facilities needed, time, and most importantly the projected overall impact of the scientific outcome. Innovative, thought-out work with expected output is a must. In 2002 the National Science Foundation, which funds approximately 20 percent of all federally supported basic science research in universities, announced that proposals must demonstrate broader impacts on society in order to be seriously considered. Committee members become increasingly nitpicky, writes Powell, with reviewers “looking for any excuse not to fund a project.”

A prime choice for such an excuse is the fishing accusation, many researchers gripe. In her blog, one scientist observes that she and her colleagues have all received the fishing remark at some point in their proposal reviews, and it was always intended as derogatory. “This kind of hedge trimming suggests that only the safest, most predictable work should be done,” she writes, “and any exploratory tangents should be lopped off early.” She continued in an email to me, “It’s a problem of overabundance of caution.” Dr. Tim Birkhead, a professor of behavioral ecology at the University of Sheffield, voices similar concerns in an article printed in the Times Higher Education. “The scientific research councils seem to be obsessed by hypothesis testing. Many times I have heard it said by referees rejecting a proposal: ‘But there was no hypothesis.’” The problem with this model, he says, is crippling risk aversion. When scientists “basically have to know what they are going to find before putting in a research application,” research becomes “trivially confirmatory and inherently unlikely to discover anything truly novel.”

Still, reluctance to support fishing is not necessarily an assault on big data. “The success of fishing depends on how good your lure is,” explains Dr. Peter Good, a program director at the National Human Genome Research Institute who manages portfolios of grants involving genomic technology development. To get funded, “you have to lay out your ideas – technology-driven or hypothesis-driven – demonstrate what you’re doing is significant, better than anything else out there, and show reviewers you know what you’re doing.”

Dr. Elizabeth Pisani takes that argument one step further in her article, “Has the internet changed science?” What goes on in the laboratory has never been as neat as what gets written in the scientific paper, she points out. The paper follows a template that frames research as a linear story, aligning with the steps of the classic scientific method. Yet the findings that become published are frequently not the ones that were initially pursued. As information accumulates and trends can be detected, researchers can come up with new, increasingly refined hypotheses. Thus, drawing a sharp distinction between data-driven and hypothesis-driven methods, much less presenting this divide as new, is misleading. The two are not conflicting, but complementary. As Peter Good says, “Data-driven really means hypothesis-generating.” It would be silly for a committee to bias (intentionally) against one or the other side of the same coin.

Here is another way to view it: Hypothesis-driven and data-driven do not represent two opposing and nonoverlapping camps of inquiry but rather a continuum addressing the initial idea’s degree of specificity. Data-driven research then falls on one end of that continuum, with a more flexible starting hypothesis. In genomics lingo, that would mean the difference between “we predict a genetic basis underlying this trait” and “we predict that X specific gene is implicated in this trait.”

Different fields have varied traditions about where they fall on that spectrum. Genomics is one where data-driven methods have now been in play for a while, meaning geneticists who sit on review committees are less likely to take a knee-jerk “But where is the hypothesis?” reaction to grant proposals. But departments are integrating—or ignoring—big data at unequal rates. Things get tricky when a committee comprises researchers from diverse backgrounds who subscribe to distinct conventions of how research ought to be conducted. “Issues can crop up when you send a grant to a study section with no geneticists, and they say, ‘this is a fishing expedition,’” says Dr. Matthew State, an associate professor of genetics at Yale University School of Medicine. “You then say ‘Right!’ and have to explain that empirically, it works here.” Often, however, no side is clearly right or wrong. Chalk it up to a clash of scientific cultures.

The scientific method may not be becoming obsolete but it is evolving to exploit the power of modern information technology. Meanwhile, funding agencies are dealing with changing burdens of their own. Difficult decisions must be made and disagreement is expected. There will likely never be a perfect system that will satisfy everyone. Here’s to the goal that the laboratory and funding worlds evolve in a way that is as synchronized and symbiotic as possible.

Ilana Yurkiewicz holds a B.S. from Yale University and was a staff writer at The News & Observer. Currently a clinical research assistant at Walter Reed Army Medical Center, she will matriculate at Harvard Medical School in the fall.

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.

• advance our understanding of basic biology
• create new vaccines, drugs and diagnostic tools
• repair diseased tissues
• engineer new carbon-neutral energy sources
• provide countermeasures for polluting environmental toxins

Synthetic biology, or “synbio,” is a relatively new laboratory discipline that involves creating or altering new life forms. The basic tools of synbio are standard biological parts—sets of genes and chromosomes with known and specific functions created in modern biology labs—that can be assembled to program cells and control an organism’s functions. The process resembles computer programming in that scientists assemble blocks of genetic “code” into instructions for tiny cellular machines.

“Biobricks” are standard, interoperable pieces of DNA for genetic engineering. They are already widely available from commercial websites and the relevant skills for creating them are known to any reasonably competent biology graduate student. Taking advantage of rapid advances in gene sequencing, even college students are learning the techniques. Engineers use biological parts like genes, proteins, and portions of chromosomes to build new microscopic organisms that behave in certain ways. Synthetic biology is only in its infancy, and it will likely be combined with such other emerging fields as nanotechnology to create entities that blend the mechanical and biological.

Synbio nonetheless raises a wide variety of issues that will need to be addressed through a combination of monitoring and regulatory measures, without inappropriate restrictions that block innovation. These issues include:

• Potential environmental hazards due to the accidental release of man-made organisms that may turn out to be harmful and difficult to eradicate
• The possibility that treatment-resistant bacteria or viruses could be synthesized for use in biological warfare
• The risky combination of portions of genes from a human source with those from a non-human source, whether biological or non-biological

For other reasons individuals across the social and political spectrum may also find synbio intrinsically objectionable. The matters of potential cultural concern are far more complex than those faced in the stem cell debate. Many will not view the creation of new life forms capable of performing specific tasks as morally neutral. Political realignment around “naturalness” is a phenomenon that has become familiar in other areas, such as human cloning and genetically modified organisms. A similar reaction could apply to synthetic biology as its implications enter popular awareness.

These worries need to be addressed with seriousness and candor. Scientists and investors rightly complain that inappropriate regulation can impair the development of a new field, yet the rise and fall of public interest in and support of gene therapy should serve as a cautionary tale. Experience has shown that a single adverse event can have an enormous impact on public perception. Ever since the French Enlightenment, trust in scientists has been a crucial component of public support of scientific and technological innovation.

Governance of biotechnology has several elements. Self-policing by the scientific community is necessary but not sufficient. In this field there is an irreplaceable role for smart government, but authority for oversight and regulation of synbio in the United States is currently at best a partial patchwork. The National Institutes of Health require labs receiving its funds to comply with Recombinant DNA guidelines; the Food and Drug Administration would have to approve a drug created by synbio; and the Department of Agriculture might be responsible for avoiding the environmental release of synthetic organisms. But current regulations may not address unique risks posed by the technology.

Nor will merely domestic arrangements be enough. The context for the scientific and commercial interest in the field is a research and development system that has in the past decade or so become globalized to an unprecedented degree. International cooperation and continued scrutiny at many levels of government will be required, as technology will almost certainly rush ahead of current conventions. Researchers and their supporters should also seek innovative approaches for verifying the character and safety of new life forms created through synbio.

Over the long term, the social and scientific impetus behind synthetic biology will overcome political posturing. The greater danger is that through overreaction and misunderstanding we could miss an early opportunity to engage in careful assessment of the research and the development of improved or new regulatory models to avoid harms and maximize the potential benefits of synbio for the common good.  The industrial platforms that this technology is helping to develop will be key components of prospering national economies and national security systems over the next fifty years. America can and must be among the leading innovators.

Jonathan D. Moreno, Ph.D., is the David and Lyn Silfen University Professor of Ethics and Professor of Medical Ethics and of the History and Sociology of Science at the University of Pennsylvania, and the Editor-in-Chief of Science Progress.

More on synthetic biology from Science Progress:

Ribosomes Rising: Synthetic Biology Accelerates
By Jonathan D. Moreno

Synthetic Biology: An Overview and Recommendations for Anticipating and Addressing Emerging Risks
By Denise Caruso

All Together Now: As Emerging Technologies Converge, So Should Ethical Discussions

Interview: David Deamer Explains Synthetic Life: Unpacking the Latest Advance in Biology
Interview by Andrew Plemmons Pratt

According to FDA, Pathway Genomics is in fact selling what appears to be a medical device under section 201(h) of the Federal Food Drug and Cosmetic Act, which defines a medical device as an instrument that is “intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease.” As the Washington Post reported, the tests would scan consumers’ genes “for a propensity for Alzheimer’s disease, breast cancer, diabetes and other ailments.” Up until this point the FDA has exercised its enforcement discretion to refrain from regulating direct-to-consumer genetic tests as medical devices.

Other companies offering these types of tests by mail have maintained that the products they sell are for informational purposes only. Despite repeated calls for FDA to set rules for genetic tests during the Bush administration, the lack of federal attention came into sharp focus in 2008, when California and New York sent “cease and desist” letters to several companies offering direct-to-consumer tests through the mail, including 23andMe and Navigenics. Along with a few others, these companies won approval from the state of California by demonstrating that they used up-to-date genetic research to back up their claims, had physicians and genetic counselors on staff to help customers, and contracted their genetic sequencing out to labs that were state-licensed and certified according to federal standards under the Clinical Laboratory Improvement Act, known as CLIA. Navigenics successfully applied for approval under New York’s licensing board and now markets mostly to physicians, but 23andMe and Pathway are not approved and their test cannot be ordered in New York. In fact, Walgreens did not plan to sell the Pathway test kit in any of its New York stores.

Yet quality of the information in these state-level databases is not the only urgent issue in the field. Natalie Ram presented original research last year indicating widespread variation in state rules for “partial” match searches. A partial match refers two genetic profiles that share some, though not all, of the markers used for connecting a crime-scene sample with a stored profile in the database. A partial match, Ram explains, can implicate a previous offender’s immediate family: “In effect, reporting partial matches implicitly incorporates offenders’ close genetic relatives into existing offender databases, even though these relatives have never been convicted of, or arrested for, an offense qualifying them for database inclusion.” Some states allow these searches, some states prohibit them, and for some it is unclear what the policy is at all.

She goes on to recommend that the federal government create rules for partial match searching, as well as that states make their policies explicit and publicly accessible.

In both cases, the authors argue that improved transparency will lead to better science, more effective law enforcement, and just outcomes.

This dynamic seems to be changing in the field of DNA forensics. Two dozen scientists (along with several other scholars and practitioners) recently published an open letter in the prestigious journal Science that called out the Federal Bureau of Investigation for stonewalling research access to the federal DNA database. This database houses almost eight million DNA profiles used to identify unknown offenders who leave biological materials at crime scenes.

Why are scientists poking this bear with a stick? DNA evidence is particularly compelling because the chance that any two samples match coincidentally is slim to none; experts often express the probability as only one in several million. This is also why DNA is useful in exonerating individuals who are wrongly accused; testing can show that unknown samples either match or do not match any one individual with a high degree of certainty. But things become more complicated when forensic  labs compare unknown samples with thousands or millions of stored profiles in search for a “cold hit”—an attempt to identify suspects solely on the basis that a stored profile matches the unidentified crime scene sample.

When forensic scientists make these comparisons, they examine 13 loci, or regions on a chromosome, to assess their similarity. Matches between two samples at all 13 points are considered a full match. But some experts have argued that 9-point partial matches are enough to identify someone. As a result, it has become increasingly common to prosecute and incarcerate individuals solely on evidence based on DNA database matches—even when exculpatory evidence is available. But these types of DNA database matches may very well stand on shakier ground than the feds would like to admit.

For example, a recent examination of Arizona’s 65,493 database profiles led to a surprising result: 122 pairs matched at 9 loci, 20 pairs matched at 10, and two pairs of siblings matched at 11 and 12. There are also reports that other state databases are experiencing similar oddities. Illinois’ state databases reportedly showed that out of 220,000 profiles, 903 matched at 9 or more loci. And it has also been reported that Maryland’s database had 32 pairs of profiles matching at 9 loci and 3 matched at 13. These figures call into question the motivating claim behind DNA database searches—that profiles are unique and coincidental matches are extremely rare—which opens up the possibility for false convictions.

How is it possible that so many ostensibly unique profiles are substantially similar? Well, it’s not entirely clear. And this is precisely why scientists are flabbergasted by the federal government’s refusal to allow them to take a closer look.  Some explain these figures by the way in which matches were sought in examining these state databases; comparing database profiles to one another is not the same as assessing the probability that a particular profile randomly matches any one person.  The bottom line, some researchers say, is that the one-in-several-million statistic that law enforcement routinely cites to describe the chance that an unknown sample matches a database profile isn’t always the LeBron James slam dunk that they portray it to be.

Part of the problem is that the FBI and other law enforcement officials like to express the probability that an unknown sample matches a database profile in relation to the size of the general population. But doing so can significantly underestimate the likelihood of an erroneous “hit.” When sifting databases for a match, the more relevant figure to express the probability of a coincidental match is the number of profiles in the database. This is why two esteemed committees—one convened by the National Research Council, the other an FBI advisory board—have proposed that database size needs to be taken into account when calculating these probabilities. This suggestion, if implemented, would more accurately express the probabilities for a coincidental match and correct the seemingly astronomical odds often used by prosecutors to convince juries of defendants’ guilt.

But not only has the FBI refused to adopt these recommendations, it has worked against efforts to bring more knowledge and transparency into the process—reportedly going so far as to point out that state forensic labs’ access to the federal DNA database could be rescinded if they cooperate with scientists’ requests to study their databases.

The FBI has offered two main reasons for refusing this access. First, they claim that doing so would jeopardize individuals’ privacy. Second, they argue that granting such access would be administratively burdensome; allowing researchers to rummage through these databases might impede law enforcement’s efforts to solve crimes.

But many scientists find this unconvincing. The government routinely releases similar information to researchers that is de-identified; the privacy threats are commonly thought to be negligible. As for the supposed burden, scientists have argued that the relevant files could probably be made available to them in a few short minutes. Moreover, as Krane et. al. note at the beginning of their Science letter, the legislation creating the federal database permits research access to the profiles so long as personal information is removed.

These less-than-convincing justifications for restricting research access to federal databases coupled with the FBI’s attempts to disincentivize state cooperation with scientists’ requests have raised ire among many in the research community. As University of California, Berkeley population geneticist Montgomery Slatkin notes, “When the government works very hard to hide something, it suggests that they have something to hide.”

In order for criminal justice to be accountable to the public, every aspect of its administration must be transparent. And as genetics and other new technologies become a more central aspect of the criminal justice system—where the science fiction of films such as GATTACA is simply becoming plain science—this sentiment rings ever more true. It’s past time for the FBI to open its DNA databases to scientific scrutiny. Sunlight is not only the best disinfectant, but it is also the cornerstone of any just society.

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 (UCSF), and a Senior Fellow at the Center for Genetics and Society.

The full implications of the surprise decision are not yet clear, but gene patents are a contentious intellectual property issue both because they underpin significant investments in the biotechnology industry and because they might pose barriers to increasingly complex genomic research. The ruling is also noteworthy because it invalidates both the patents on the genes themselves and patents for the methods of analyzing and comparing genes to identify mutations in the genetic material.

Some of the patents in question are for the sequences of DNA that make up the BRCA1 and BRCA2 genes. Mutations on these genes are linked to 3 to 5 percent of breast cancer in the United States and 10 to 15 percent of ovarian cancer, according to the Centers for Disease Control and Prevention. But for women with a family history of cancer, genetic testing can be an important medical decision, as BRCA1 and BRCA2 mutations carry a 60 percent lifetime risk of breast cancer and up to a 40 percent risk of ovarian cancer.

Myriad holds patents on the genes along with the University of Utah Research Foundation. As a result, Myriad is the only company that can market a test for the mutations, and it charges as much as $3,000.

Filmmaker Johanna Rudnick spoke with Science Progress in 2008 about her documentary, In the Family, which chronicles her own discovery at age 27 that she carries a mutation on the BRCA1 gene. “There is no other, cheaper test that you could go get in another laboratory, because they have the exclusive patent,” she explained, adding that Myriad also controls the efficacy of the test—there is no other company to turn to for a second opinion.

There are about 40,000 patents that currently protect some 20 percent of the human genome. Last year, a federal advisory panel recommended exceptions from patent infringement liability for genetic research. The proposal came from the Secretary’s Advisory Committee on Genetics, Health, and Society, known as SACGHS, at the U.S. Department of Health and Human Services. But Timothy Caulfield at the University of Alberta argued here at Science Progress that there is little data to back up the claim the gene patents inhibit reserach. “A 2005 study done for the National Academy of Sciences found only 1 percent of the scientists surveyed reported suffering a project delay of more than 1 month due to patents,” he wrote.

Patents are designed to foster innovation, not stand in the way. That’s why patents are public documents that detail the inner workings of a new invention, exposing the idea for anyone to see and understand. Inventors are protected for the life the patent, currently 20 years, from anyone else copying their idea, but in exchange, they share their technology with the rest of the world, advancing knowledge.

Yet the District Court ruling does not hinge on claims about the impact of the patents on research. It deals instead with whether or not the genes and the processes for analyzing them are patentable in the first place.

An analysis of the ruling posted at Genomics Law Report makes it clear that the decision presents DNA as pure information—whether it is part of a complete genome or isolated in the form protected by Myriad’s patents. From the judgment itself:

DNA represents the physical embodiment of biological information, distinct in its essential characteristics from any other chemical found in nature. It is concluded that DNA’s existence in an ‘isolated’ form alters neither this fundamental quality as it exists in the body not the information it encodes (pp. 3-4).

That is, patents on the chemicals that make up specific sequences of DNA are no different from the information they encode in the human genome. And this naturally occurring information is not eligible for patent protection.

The decision in this trial court for the Southern District of New York is not binding precedent for other trial courts, though it could influence thinking elsewhere. But Myriad has the right to appeal the case the Court of Appeals for the Federal Circuit, and has indicated it will do just that. This process could take more than a year, and ultimately, if the case proceeded to the Supreme Court, the justices there would have the final say on the matter.

The implications for the biotech industry and medical research are uncertain at the moment. “We do not foresee this decision producing any radical changes in commercial, clinical or other activity surrounding Myriad’s BRCA patents, or gene patents more broadly,” write the lawyers at Genomics Law Report. The New York Times quotes Bryan Roberts, a Silicon Valley venture capitalist, who suggests that the work of discovering genes and developing the accompanying diagnostic tests will move to university laboratories: “The government is going to become the funder for content discovery because it’s going to be very hard to justify it outside of academia.”

But the ruling did not merely invalidate the patents on the gene sequences themselves. It went even further and invalidated the method patents on the processes for analyzing the genes. The Supreme Court is currently considering a case involving method patents, and that ruling could have implications for the appeal on yesterday’s decision. The case, referred to as Bilski, focuses on a business method patent on a process for hedging commodities risks.

The current rule for testing method patents laid out by the Federal Circuit in Bilski requires that the process be connected to a particular machine or device or that the process transform an article or piece of matter into something else. In yesterday’s ruling, Judge Sweet found that the Myriad patents fail this test, writing, “because the claimed comparisons of DNA sequences are abstract mental processes, they also constitute unpatentable subject matter” (p. 4).

The Supreme Court’s decision could uphold the test or propose a new set of rules that would become the legal precedent. This, in turn, could shape not just Myriad’s appeal, but future decisions on intellectual property involving innovative biotech processes.

Andrew Plemmons Pratt is the managing editor for Science Progress.

SACGHS has formed a task force to address the clinical utility of genetic testing—that is,.the usefulness of genetic tests for helping doctors choose more effective interventions for their patients. Assessing clinical utility is an important component of both personalized medicine and comparative effectiveness research, which analyzes interventions head-to-head to see which work better for different patients. The goal is to improve comparative effectiveness research by incorporating genetic tests, which would allow physicians to tailor treatments to individual patients based on their own DNA.

The Personalized Medicine Coalition held a conference last fall to promote the alignment of comparative effectiveness research with personalized medicine. This alignment is also a crucial aspect of the recommendations issued by the Institute of Medicine, which promoted research on both “diseases and conditions with the greatest aggregate effect on the health of the U.S. population, but also less common conditions that severely affect individuals in vulnerable subgroups of the population.”

The Center for American Progress has also recognized the importance of ensuring that CER can “accelerate the discovery of approaches to individualized medicine and help providers cater to the specific needs of patients.”  This will move medicine beyond the “one size fits all” therapies that result from the research provided by pharmaceutical companies to the FDA.  SACGHS is taking an important step forward by identifying ways to assess the clinical utility of genetic tests. This was one of several recommendations CAP has made not just for advancing personalized medicine but also for improving the quality of genetic testing in the report, “Genetic Information Non-Discrimination.”

Genetics education and training will also be a major part of the SACGHS meeting agenda. The task force outlined its action plan in July of 2008 and has since set out to identify the needs of healthcare providers, the public health workforce, and the general public for genetic education. The task force also identified various types of case studies that it will use to analyze the current information gaps in genetic testing. This will require exploring the best way to gather and disseminate information about pharmacogenomic testing, newborn screening, diagnosis of single gene disorders, direct-to-consumer testing, and population genetics. The task force plans to release their report in the coming months.  This is an important step, as the public must be “informed and educated about personalized medicine through outreach efforts, opportunities for public comment or input, and most importantly through transparency.”

Data sharing is also a major component of the agenda.  Representatives from government, academia, health care systems, industry, and consumer groups will present different models for sharing genomic information. This will be followed by a discussion of health information technologies that aim to efficiently connect the data among these multiple sectors.  In “Paving the Way for Personalized Medicine,” my co-author and I addressed both the positive developments as well as the missed opportunities on this front.  In particular, we noted that HHS’s Health IT Standards Committee has not properly collaborated with outside networks that are working to devise consistent nomenclature so that genomic data can be utilized through health IT.  We recommended this kind of collaboration so that HHS can leverage the expert resources available for combining cutting-edge genomic science with health IT.

The face of medicine is changing at a breakneck pace and a forum like the SACGHS meeting allows scientists, policymakers, innovators, service providers, and patients to work together to ensure that this new era of medical innovation serves the common good by being safe, effective, efficient, and equitable.

What is genetic testing?

Every person’s unique genetic makeup determines many of his or her individual traits. Some of these traits—like the color of our eyes, hair, and skin—are visible to the naked eye and strongly linked to genes in our DNA. But many genes play a role in determining traits we cannot see, such susceptibility to disease or how our bodies react to various chemicals. Scientists have understood for years the direct link between certain genes and specific diseases, but as our understanding of human genetic variation improves and the cost of genetic testing drops, new possibilities for personalized medicine arise. But along with these opportunities come questions about how to interpret the avalanche of genetic information and how to protect it from improper use.

Genetic testing is not new. Scientists identified the genetic mutation that causes Huntington disease, a progressive and fatal brain disorder, in 1993. In recent years, companies began marketing tests for mutations in the BRCA1 and BRCA2 genes that indicate an increased risk of breast and ovarian cancer. But over the past few years, steep reductions in the cost of gene sequencing technology have allowed companies to offer direct-to-consumer genetic testing. These new companies may help drive the expansion of personalized medicine, but proper oversight is necessary because these new tests raise policy questions about privacy, safety, and their usefulness in clinical decision-making. According to the National Center for Biotechnology Information’s GeneTests website, there are now genetic tests available for over 1,800 diseases.

What are the different uses of genetic tests?

Genetic tests serve a variety purposes. Some diagnose a disease after symptoms have manifested themselves. Some are aimed at predicting the likelihood of a disease. Others predict the likely effectiveness of a drug or treatment based on an individual’s genes—this is known as pharmacogenomics. Tests for carrier status look for disease-related genes that parents may pass on to their children even though the parents do not have the disease. Genetic tests for newborns can determine if they need immediate intervention for a preventable or treatable condition such as phenylketonuria, a metabolic glitch that, if left unaddressed, would result in mental retardation or other serious problems, but that can be completely averted with proper dietary adjustment.

Genetic tests can also be conducted on an embryo created through in vitro fertilization before it is transferred into a uterus. This same process is referred to as preimplantation genetic screening when is used to select embryos that have chromosomal defects that may prevent them from surviving an entire pregnancy. This screening process is referred to as preimplantation genetic diagnosis when it is used to select against an embryo with a disease, condition, or—more controversially—an undesirable physical or mental trait. An IVF clinic in California called the Fertility Institute has even advertised that it can select embryos based on gender, eye color, hair color, and skin tone. But after several weeks of heated reactions to this advertisement, the institute suspended its program.

Direct-to-consumer, or DTC, genetic tests allow patients and consumers to bypass their doctors altogether and obtain a test from a company over the internet. These companies include 23andMe, Navigenics, DeCode (which has recently filed for Chapter 11 bankruptcy), and Pathway Genomics. These companies offer whole-genome scans for a few hundred dollars. Some also offer genetic tests for specific diseases or conditions as well as ancestry testing. Usually, these DTC tests utilize statistical techniques that provide a significant amount of information about a genome by only scanning a few hundred thousand molecular units (or nucleotides) out of the six billion units that comprise the human genome. The company Knome will sequence every nucleotide—or chemical unit of DNA—in an individual’s genome for $100,000. The companies that offer these DTC tests do not consider them medical products. Nevertheless, some have been known to tout their employment of on-staff physicians and genetic counselors to review customer orders.

Some Internet-based companies offer nutrigenomic tests, which purport to determine what kinds of foods you should be eating based on your genome. However, a Government Accountability Office investigation led to a scathing 2006 report on the industry. The report found that many of the tests gave recommendations that were “ambiguous” and “medically unproven.” Some of the tests were also attached to advertisements for ineffective dietary supplements, and some of the supplements had price tags of as much as $1,200 a year.

How will genetic tests change medicine and how are they already changing it?

Many researchers and clinicians anticipate that genetic tests will aid in the development of new drugs and treatments tailored to patients with specific genetic profiles. The government, private industry, and the medical community still have lots of work to do on research, administrative reorganization, and devising new protocols to make personalized medicine a reality and to make the incorporation of genetic information into regular medical decision making safe, meaningful, and effective. The recent report, “Paving the Way for Personalized Medicine,” explains these issues in detail.

According to a recent survey, 15 percent of healthcare providers reported that at least one patient brought them DTC genetic test results in the past year. Of those providers, 75 percent changed some aspect of their patient’s care based on the test results. This reaction by the clinicians demonstrates a disconnect between the clinical community and the research community on the perceived effectiveness of genetic tests. The research community believes that current studies have only found a small fraction of the genetic components of most conditions. Additionally, there is scant evidence that genetic tests lead to changes in treatment that improve health outcomes, also known as clinical utility. At this point, there are multiple views concerning the level of encouragement physicians should be giving their patients about adopting DTC genetic testing as a guide for personal health care. Some feel that physicians should wait until there are more comprehensive studies about the clinical outcomes of genomic medicine. Others argue that physicians should encourage prevention with genetic tests and teach their patients about the science as it develops so that they do not seek information from other and possibly less-reliable sources.

Geneticist J. Craig Venter recommends in a recent Nature article that companies report the proportion of disease risk attributable to genetic markers, focus on diseases and traits with high-risk predictions, and agree on a set of strong-effect genetic markers for specific conditions.

What are the privacy concerns?

Thanks to the passage Genetic Information Nondiscrimination Act of 2008, employers and health insurance companies cannot obtain an individual’s genetic information without his or her consent and cannot use an individual’s genetic information to deny that individual a job, promotion, or health insurance coverage. Unfortunately, these federal protections do not extend to disability insurance, long-term care insurance, and life insurance. However, 16 states regulate the use of genetic information in life insurance; 16 states regulate its use in disability insurance; and 10 states regulate the its use in long-term care insurance. Of course, these policies all vary from state to state.

Many of the companies offering direct-to-consumer genetic testing also compile databases of genetic information that they gather from their customers. This is the second major component of their business model, as the data is valuable for advancing genetic research. But informed consent process for this information raises new, complex issues.

In an interview with Science Progress, Stanford bioethicist Sandra Lee explained the consent processes that some of these companies have adopted for using or selling their customers’ genetic data for research purposes. Some have adopted policies of “open consent” where a customer agrees to allow research on their genetic data for any studies in the future. This marks a break with the traditional rules of informed consent in clinical trials where all potential uses of the subject’s information must be disclosed. Navigenics has adopted a policy of asking customers to opt-in to research and then provide new consent forms to customers every time a new study arises. 23andMe also has a similar consent policy wherein they provide individual data to their research partners.

Most informed consent forms for genetic research indicate that a subject’s genetic information will be de-identified by separating the genetic information from the subject’s name and other personal information. Of course, some studies focus on the links between genes and other identifying information like ethnicity, family history, or disease status; and the informed consent forms tend to vary from study to study.

One of the most common types of genetic studies is the genome wide association study, commonly referred to as a GWAS. In a this type of study, scientists take a group of people who possess a certain phenotype—an observable characteristic or a trait like height, a condition like hypertension, or a disease like cancer—and compare them with a group of people without that phenotype. The scientists look at hundreds of thousands of single units of DNA known as single nucleotide polymorphisms or SNPs. Whichever SNPs are more likely to be present in the people who possess the phenotype and absent in those without it are considered associated SNPs. An associated SNP is not directly responsible for the phenotype, though it does indicate that the genetic sequence that is responsible may lie somewhere nearby on the genome. Scientists will then examine the relevant section of the genome and attempt to identify the exact sequence that is responsible.

The hope of many researchers is that with the passage and enforcement of GINA, more people will volunteer for genomic research. GINA is needed now more than ever since even though researchers remove subject names and other identifiers from the genetic data they collect, researchers demonstrated in 2008 that it is nonetheless possible to work backward from a common pool of de-identified genetic information and identify individuals in a database. As a result, the National Institutes of Health implemented stronger security controls for their GWAS databases.

How do scientists or regulators assess the reliability of genetic tests?

In order for genetic tests to have a meaningful impact on medicine, they need to be rigorously assessed and held to transparent empirical and clinical standards. Not only do the labs and diagnostic manufacturers need to demonstrate that the tests they conduct can reliably find the genes they purport to look for, researchers also need to show that once the genes are detected by a test, they can reliably predict a phenotype and help to inform treatment decisions in a way that improves health. This is a tall order to say the least, but scientists and regulators assess tests according to three criteria: analytical validity, clinical validity, and clinical utility.

• Analytical validity is the ability of a test to find a specific genetic sequence, broadly referred to as the “analyte.” Genes are different from other analytes like proteins, which can be present in varying amounts, since a gene is either present or absent.
• Clinical validity is the probability that you will get a disease if you test positive and that you will not get the disease if you test negative. The probability that a disease will appear if a disease-related gene is found is called the penetrance of the gene.
• Clinical utility is the ability of a genetic test’s results to lead to a course of action or interventions that result in improved health outcomes.

A coalition of researchers has also proposed a fourth criterion called personal utility. Research on this criterion would assess the patient’s or population subgroup’s perception of the advantages of genetic testing and whether it would affect the patient’s behavior and subsequent clinical utility of the genetic test. The social considerations and metrics for this criterion are still under development.

What are the gaps in the oversight of direct-to-consumer genetic tests?

Aside from the federal Clinical Laboratory Improvement Act regulations and limited Food and Drug Administration rules, most lab regulation has been left up to the states. Many policymakers, bioethicists, and representatives from the DTC industry feel that this patchwork of state regulations is not sufficient and that the lack of federal oversight has left a gaping hole in the regulatory framework. Two pieces of legislation that would regulate genetic testing and labs have long been on the Congressional back-burner: the “Genomics and Personalized Medicine Act of 2007” sponsored by then-Senator Obama and the “Laboratory Test Improvement Act of 2007” sponsored by the late Senator Edward Kennedy. Ultimately, whether through legislation or simply new regulatory protocols, this regulatory gap can easily be filled by four measures that will allow for the federal oversight of genetic tests, the labs that conduct them, the transparency of their results, and the advertising of direct-to-consumer genetic tests. The Center for American Progress and the Genetics and Public Policy Center have made these recommendations:

1. Have the Centers for Medicare and Medicaid Services, or CMS, create a “specialty” for genetic testing laboratories.
2. Expand the FDA’s jurisdiction to include the regulation of lab-developed tests in addition to pre-manufactured test “kits” that already fall under its jurisdiction.
3. Create a mandatory genetic test registry so that the clinical validity of all genetic tests is transparent for the public.
4. The FDA and FTC should collaborate on curtailing false or misleading advertising by genetic testing companies in accordance with Section 5 of the FTC Act.

Last year, 23andMe collaborated with Navigenics, de CODE, and the Personalized Medicine Coalition to release a statement outlining the standards they would like to see governing the scientific validity of DTC genetic tests. A recent panel convened by the Centers for Disease Control and Prevention and NIH welcomed their input but also advocated independent assessments from the Depart of Health and Human Services U.S. Preventive Services Task Force or the CDC’s Evaluation of Genomic Applications in Practice and Prevention. Both the governmental and private groups are moving ahead with their standard-setting and assessment efforts, but it remains to be seen rules will materialize.

Michael Rugnetta is a research assistant with the Progressive Bioethics Initiative at the Center for American Progress.

The suit claims that “genes cannot be patented because they exist as naturally occurring products of nature,” an argument David Koepsell made here at Science Progress, writing that “patenting unmodified genes rewards discovery, not invention.”

But Timothy Caulfield argued at SP just last week that despite the claims that gene patents impede upstream basic research, there just isn’t data to back up the charge.

In 2005, Mitch Morrissey, the district attorney in Denver, Colorado, approached the FBI about authorizing states to share information with one another regarding partial DNA matches uncovered in searches of the Combined DNA Index System. CODIS, which includes genetic information collected by all fifty states, the District of Columbia, and the federal government, has long permitted and encouraged states to share information where a database search reveals an exact match between a crime scene sample and an offender sample—indicating that the individual whose DNA matches is likely the perpetrator of a given crime.

A partial match is different. A “partial” match in this context refers to two genetic profiles—one derived from a crime scene sample and the other from CODIS—that share some, but not all, of the thirteen core DNA loci that comprise a CODIS profile. Each locus is a point along an individual’s DNA where scientists look for identifying variants in the genes that make up our genetic code. Each DNA locus in a CODIS profile is made up of two alleles, one inherited from each genetic parent.

This kind of match excludes the offender whose CODIS profile provides the match because that individual’s DNA is demonstrably different from the crime scene sample. But a partial match can implicate an offender’s close genetic relatives as possible perpetrators of a crime because they, like the crime scene sample, share some but not all of the examined loci with the individual whose CODIS profile provided the partial match. In effect, reporting partial matches implicitly incorporates offenders’ close genetic relatives into existing offender databases, even though these relatives have never been convicted of, or arrested for, an offense qualifying them for database inclusion.

The FBI’s CODIS director first refused Morrissey’s 2005 request. But when Morrissey approached the director of the FBI directly, the bureau modified its stance. Under an interim policy issued in July 2006, states are permitted in some instances to release identification information to other states where partial matches are found. The FBI’s interim policy left it up to each state to decide whether it would report to intra-state investigators any partial matches that might turn up in the course of ordinary database searches and, moreover, whether it would deliberately search for such matches.

Since the FBI released its interim policy, states have taken a number of approaches to the issue of partial matches. In April 2008, California’s Attorney General issued a well-publicized memorandum providing not only for the reporting of partial matches, but also for the deliberate search for such matches.^[1] In general, states distinguish between these two practices, identifying the former as partial match reporting, and the latter as familial searching. Shortly thereafter, in May 2008, Maryland enacted a statute prohibiting “search[es] of the statewide DNA data base for the purpose of identification of an offender in connection with a crime for which the offender may be a biological relative of the individual from whom the DNA sample was acquired.”^[2]

Most states, however, have refrained from prescribing rules governing partial match reporting or familial searching in statute, regulation, or well-publicized memoranda. This report represents the first effort to catalog in a comprehensive manner state policies and practices regarding partial match reporting and familial searching.

States that permit partial match reporting or familial searching through written or unwritten laboratory practices undermine efforts to bring these issues into the open. Laboratory policies are hardly known outside the laboratory walls, and so public knowledge about these practices, much less public oversight, is severely hampered. Such policies also lessen the impetus for officials favoring familial identification practices to enact policies authorizing such practices by more public means because many of the benefits of partial match data are already accessible without the need to risk opposing public influences. Although written lab policies are better than unwritten ones, neither is as transparent a means for making policy as the public deserves.

Transparency for search policies

In the face of this transparency gap, there are a number of bodies that could act, issuing some recommended and some mandatory guidance. The FBI’s CODIS Unit, for example, manages the CODIS program and the National DNA Index System component of CODIS.^[3] In this capacity, the FBI may promulgate binding regulations and guidance authorizing or proscribing certain uses of relevant databases. The interim policy discussed above represents the FBI’s current approach, but the FBI could insist in a new policy document that states make their practices regarding familial identification practices publicly known by means of statutory or formal regulatory instruments, or even that states simply not release familial identification information discovered through CODIS searching. The FBI may be limited, however, in its ability to regulate intra-state practices, especially where those practices include methods of analysis beyond CODIS searching—as where states test regions of DNA not among the thirteen core CODIS loci. Moreover, states are likely to view a federal mandate that they undertake particular legislative or executive action as an encroachment on state sovereignty and federalism values.

Here, recommendations and guidelines from the Scientific Working Group on DNA Analysis Methods may serve a guiding function. SWGDAM is a group of forensic scientists under the guidance of the FBI that, among other things, serves as a general liaison between the FBI and the forensic DNA community. This body has already issued one set of recommendations, identifying circumstances under which it deems partial match reporting or familial matching ethically acceptable.^[4] It should go further to recommend, at the very least, that states make their policies in this arena explicit and easily publicly accessible.

Disparate state policies

The results of the original research conducted for this report reveal a startling lack of transparency in rulemaking. Of the thirty-two responding states that have some policy or practice regarding partial match reporting or familial searching, at least 12 have left these policies unwritten. Most of these states have left unwritten a practice not to conduct targeted familial searches or not to turn over partial match information more broadly. In one sense, we might be unsurprised that such non-practices would remain unwritten. Institutions generally codify policies for the things they prescribe rather than the things they proscribe. Trying to dream up all of things we might do with DNA and then prohibiting most of these might well be an unending exercise.

But states have sometimes been proactive in their regulation of DNA databases to specify not only types of analysis that may be completed, but also types of analysis that may not. As described above, Maryland has codified by statute a prohibition on familial searches. Utah and Rhode Island also include explicit statutory prohibitions on analysis that could predict genetic disease or predisposition to illness.^[5] The failure to address in writing deliberate decisions not to conduct familial searches or disseminate partial match information constitutes a failure of transparency, making it extremely difficult for outside observers—and perhaps even laboratory personnel—to know what exactly the state’s policy is.

Nor is inattention to the issue of partial match reporting and familial searching always the reason that policies are unwritten. In New Mexico, for instance, an unwritten policy not to knowingly report a partial/familial hit was voted and accepted by the state’s DNA Identification System Oversight Committee. This committee is not merely advisory; it wields rulemaking authority. Its partial match reporting policy contains specific, though unwritten, language—prohibiting the knowing reporting of partial match information for familial identification purposes. And the committee chair stated that this policy will remain in place unless and until there is a change in state law either by legislative enactment or court decision clearly authorizing disclosure of familial-identifying information. Yet it seems that the policy is deliberately unwritten.

Moreover, at least four states without written policies have nonetheless reported partial match information to investigators in the past. Most broadly, in North Carolina, while DNA reports note only exact matches—hence a partial match would be designated a non-match—analysts may nonetheless informally discuss partial matches with investigators. In South Carolina, a moderate-stringency candidate match that may indicate a familial relationship between a crime scene sample and an offender profile will trigger additional investigation, and possibly reporting. Two other states, Louisiana and Montana, acknowledged that their labs had turned partial match information over to investigators at least once in the past, but both emphasized the rarity of this occurrence.

These practices indicate that a not-insignificant amount of policymaking surrounding identification of possible family relationships in state forensic DNA databases occurs in a fashion that is nearly impenetrable to public oversight. Unwritten practices of reporting partial match information are particularly disconcerting, considering the genetic privacy interests of individuals who, absent their genetic similarities to individuals properly in the database, would not be identifiable through any database search.

States that have formalized policies in writing, however, are hardly fonts of transparency either. Only two of the sixteen states that confirmed that they have written policies have codified these policies in documents easily accessible to the general public. Again, Maryland has addressed familial searching by means of legislation, and expressly prohibited the practice. California, meanwhile, issued a well-publicized memorandum by the state attorney general that authorizes, under limited circumstances, both partial match reporting and familial searching. The remaining 14 states reporting written policies have memorialized these policies in internal laboratory manuals that are not easily accessible (if accessible at all) to the general public. Ten of these lab manual-based policies permit at least partial match reporting, of which one, Nebraska, reports that it conducts familial searches on a case-by-case basis as well.

Policies placed in internal laboratory manuals are often nearly as inaccessible to the general public as unwritten policies. Indeed, in some instances, state labs were unwilling to share copies of the relevant written policies absent a formal request lodged under the state’s freedom of information act. One state, which was otherwise forthcoming and informative, declined to release a copy of the relevant policy on grounds that the lab documents are subject to outside copyright. Another state, in declining to participate in this survey, expressed concern that any information might become publicly known regarding practices and analyses conducted in the state laboratory. Of course, several states, including Florida, Nebraska, Oregon, Washington, and Wyoming, helpfully excerpted the relevant written state policies in their lab manuals.

In some cases, states in the process of developing policies in this arena have no plans for public engagement in the process. North Dakota reported that it is currently developing a policy to govern both familial searching and partial match reporting. This policy, when written, will appear in the state laboratory’s standard operating procedures/procedure manual, but with no opportunity for public comment or participation. In Colorado, where a familial searching policy is under development, there has been no consideration as to whether this policy might be published by the state Attorney General (as in California) or the Department of Safety, in addition to appearing in the bureau’s procedures manual.

But to their credit, other states presently developing policies have taken different, more public-oriented approaches. New York has regulations that appear to authorize familial searching. At present, the New York Commission on Forensic Science is in the process of drafting regulations that will govern whether and how partial match reporting or familial matching will be conducted. These draft regulations were discussed this September at a commission meeting that was streamed online, and any resulting regulations will be available for public comment prior to codification.

West Virginia is taking the most public route to regulating partial match information. In March 2009, a member of the West Virginia House of Representatives introduced legislation that would permit at least partial match reporting. This bill died in committee, and representatives from the West Virginia State Police are working with legislators to introduce similar legislation in the next session. It is tempting to speculate that the failure of the prior partial matching bill indicates that, when exposed to public opinion and debate, partial match reporting and familial searching generate sufficient discomfort and concern so as to make such practices unacceptable. That the only relevant statute on the books is Maryland’s prohibition of familial searches certainly supports such an interpretation. But the realities of the legislative process indicate that bills fail for all sorts of reasons, and so we should hesitate to draw substantive conclusions about public opinion from non-enactment.

Several states that, by written or unwritten policy, do not report partial match information—and, as a corollary, also do not perform familial searches—have also indicated that they will await definitive, public authorization for such practices before adopting them. Rhode Island reported, for instance, that its policy not to release anything less definitive than an exact match will remain in place until the attorney general or legislature instructs otherwise. Nevada indicated that it would not alter its current non-reporting policy unless meetings with the public to gauge and address concerns regarding genetic privacy were undertaken first. New Mexico, as described above, affirmed that its policy not to reveal familial information knowingly will remain in place unless and until there is a change in state law by either legislative or judicial action. Vermont reported that it would not provide partial match information pursuant to the FBI’s interim policy absent additional input from the legal channels in the state. Michigan, meanwhile, is waiting to see what the FBI will do in terms of both national policy and software tools available for analysis. And Minnesota, despite permitting release of partial match information, recognized in a January 2009 report to the legislature that familial identification raises serious concerns about genetic privacy, and called for the legislature to address such practices through legislation. The state legislature has thus far failed to do so.

The experiences of Maryland, New York, West Virginia teach that public engagement is not incompatible with policymaking in this arena, and state laboratories calling for public consideration of familial identification practices indicate that there is a felt need for public involvement in such policymaking. Indeed, public involvement, along with transparency and accountability in this arena, are vitally important. Every state in the union created its DNA database by means of legislation, and many have expanded by legislative amendment the range of persons subject to inclusion. Partial match reporting and familial searching implicitly expand the range of persons that may be identified through existing databases. Although DNA profiles are often described as genetic “fingerprints,” partial match practices take advantage of the ways in which DNA is utterly unlike a fingerprint—genetic relatives have similar genetic features in predictable ways, and so family members can sometimes be inculpated through partial matches with the DNA of their offender relatives. As with previous expansions of DNA forensic databases, this new expansion should be similarly subjected to public scrutiny and oversight through the legislative process.

Whether we would oppose or support the substance of Maryland’s enacted statute or West Virginia’s draft legislation, we should applaud their process.

Natalie Ram is a Greenwall Fellow in Bioethics and Health Policy at Johns Hopkins and Georgetown Universities. She served as a summer research fellow at the Center for American progress in Summer 2009.

Notes

^[1] Memorandum from Edmund G. Brown, Jr., Att’y Gen. of Cal. to All Cal. Law Enforcement Agencies and District Att’ys Offices, DNA Partial Match (Crime Scene DNA Profile to Offender) Policy (Apr. 25, 2008), available at http://ag.ca.gov/cms_attachments/press/pdfs/n1548_08-bfs-01.pdf.

^[2] MD Code, Public Safety, § 2-506(d).

^[3] Fed. Bureau of Investigation, CODIS, http://www.fbi.gov/hq/lab/html/codis1.htm (last visited Oct. 1, 2009).

^[4] See Ted Staples, Chair, Scientific Working Group on DNA Analysis Methods, Address at the Genetic Info. Working Group (June 24, 2008), available at www.ipad.state.mn.us/docs/geninfo17.pdf (setting forth SWGDAM’s recommendations regarding familial identification practices). SWGDAM recommended that familial identification information be disclosed only where, inter alia, identification involved single-source samples only; investigators searched local databases before larger, more general ones; a match was obtained for a substantial number of core loci (as many as possible); additional testing (Y-STR, mtDNA) was performed and confirmed a possible familial link; and tests for expected match ratio and expected kinship ratio were performed and confirmed a possible familial link. Staples, supra at 33.

^[5] R.I. Stat. 12-1.5-10(5) (DNA samples may never be used for purposes of obtaining info about “physical characteristics, traits or dispositions for disease”); Utah Code Ann. § 53-10-406 (bureau must “ensure that the DNA identification system does not provide information allowing prediction of genetic disease or predisposition to illness”).

On October 9th, the most recent call for change came from the Secretary’s Advisory Committee on Genetics, Health, and Society, known as SACGHS, at the U.S. Department of Health and Human Services. Among other things, the Committee recommended the “creation of an exemption from patent infringement liability for those who use patent-protected genes in the pursuit of research.”

So, why all the fuss? While the concerns associated with gene patents are varied, one has had the most policy traction: the idea that patents on sequences of genetic information hurt research, especially upstream, basic research. The worry is that patents will hurt science by making it difficult to acquire the rights to all necessary research inputs. Research will slow, become more inefficient and expensive—or researchers will simply avoid doing research on patented, yet scientifically valuable, genes.

If it were true that patents impede biomedical research, patents would be cutting against the very reason for their existence, the stimulation of innovation. As such, it makes sense that this concern over the impact of patents on research—called a “patent thicket” or an “anti-commons”—is often the focus of the policy activity. For example, Congressman Xavier Beccera (D-CA) justified his support of the Genomic Research and Accessibility Act on the grounds that “[t]he practice of gene patenting is preventing critical research from advancing because scientists are wary of trespassing patent laws.”

At first blush, all this policy activity seems to make sense: a logical response to a profound social problem. But there is a hitch. There is little evidence that the problem exists. There is lots of social angst, but no good data showing a widespread patent thicket/anti-commons phenomenon. Moreover, the gene patent question may actually distract us from more important problems related to the distorting effects of commercialization on basic biomedical research.

Through all this public dialogue and political debate, the practice of gene patenting has marched forward more or less unabated. There has been some tweaking of patent policy—such as a 2001 tightening of the patent criteria requiring inventors to disclose a clear use to the gene—but, in general, every jurisdiction embraces the practice. You can get a gene patent in Japan, Canada, the United Kingdom, all through continental Europe and, of course, in the United States. Calculations estimate that there are well over 40,000 patents issues covering over 20 percent of the entire human genome.

A large 2007 study by the American Association for the Advancement of Science found “very little evidence of an ‘anticommons problem.’” A 2005 study done for the National Academy of Sciences found only 1 percent of the scientists surveyed reported suffering a project delay of more than 1 month due to patents. My own research on the Canadian genetic research community, published in early 2009, revealed lots of researcher concern about gene patents, but little evidence that they are actually having a detrimental impact on the research environment.

Many others have noted the absence of evidence that gene patents impede research, including law professor Chris Holman, who wrote in a 2007 paper: “The paucity of documented examples in which the fears surrounding gene patents have manifested themselves is striking, particularly when one considers the high level of public concern and the extraordinary nature of the proposed legislative fix.”

Given all this data and commentary, one can only speculate as to why the anti-commons/patent thicket argument continues as the justification for reform. It does have great intuitive appeal, and it seems a logical consequence of the existence of numerous overlapping patents. There have also been a number of high-profile controversies that seem to confirm the concern, most notably when the company Myriad Genetics enforced patents on a gene strongly correlated with dramatic risks of breast cancer. But as all good scientists and clinicians know, anecdotes are not good evidence—especially when there are more systematic data pointing in the opposite direction.

In addition, we should not conflate the issues. The Myriad controversy, which has been the dominant gene patent cautionary tale, is not really an anti-commons/patent thicket story. The Myriad case is more about patient access to tests and the development of downstream technologies. These are tremendously important issues, for sure, but not evidence of a breakdown of the upstream research environment.

I am not some rabid, pro-industry patent supporter. On the contrary, much of my career has been focused on an exploration of the concerns associated with the commercialization of the research environment. In fact, this is one of the reasons I get frustrated with the patent debate. While the apparent disconnect between policy concern and evidence is a significant dilemma on its own, I think there is a bigger problem. By focusing on gene patents, we seem to be downplaying other concerns associated with the commercialization ethos that increasingly permeates the research environment.

There is solid evidence that commercialization pressure and the involvement of industry can:

• adversely affect the collaborative nature of research
• increase data withholding behavior (that is, stop researchers from sharing information)
• lead to the premature implementation of technologies
• distort research results and corrode public trust.

For example, a 2009 study by Hong and Walsh concluded that “commercial linkages and increased pressures from scientific competition” was a predictor of increased data withholding. This study also found that, in the realm of biology, data withholding was not correlated with patenting. Commercialization pressure, not patenting, is the problem.

In many respects, patents are just a tool in the commercialization process. How many of the documented issues associated with commercialization and industry involvement will go away if patents are banned? Might some get worse? If patents are removed and commercialization pressure remains, might scientists become even more secretive and firms more aggressive?

To be fair, not all the policy reports focus on the “patents hurt research” theme. The recent recommendations by the SACGHS seem more concerned with the downstream impact of patents on access and the development of genetic technologies. And the lack of an observable problem may only be temporary. As technologies move closer to the clinic, patents may become more valuable and, perhaps, litigation and aggressive enforcement more common. But, at the current time, we need to recognize that despite all the noise, there is still no solid evidence that gene patents hurt basic research.

This whole debate also engages the interesting question of how much “evidence” should be required to justify policy change. If patents are viewed as a “right” owed by liberal democratic societies to inventors, the evidentiary hurdle might be quite high. You need to muster lots of evidence if you are going to monkey with a “right.” But if patents are a “privilege”—and I think they are—granted by society for the good of society, the evidentiary hurdle might be lower. Indeed, one could argue that a society should have some flexibility to try different strategies in the hope of maximizing the benefits of the innovation process. But even in this context, arguments for reform must be based on an honest assessment of available evidence—not on assertions that conflict with the facts.

There are, undoubtedly, problems with the current intellectual property system. And there are interesting philosophical arguments about the appropriateness of allowing patents on naturally occurring entities like genes—arguments that the courts in both Canada and the United States have largely rejected. As such, the patent debate seems likely to continue for years to come. And because it is surfacing in other domains such as stem cell research, we need to get our policy arguments in order. We need more methodologically robust research on the true benefits and harms of patents. This will allow for a more informed debate on the fundamental patent tradeoff: that is, the granting of a limited-term monopoly for the benefit of society.

Timothy Caulfield, LLM, FRSC, is the Canada Research Chair in Health Law and Policy, and a Professor in the Faculty of Law and School of Public Health at the University of Alberta.

Much Promise and Many Questions

There are promising developments heralding the arrival of personalized medicine, a new medical field where the results of genetic tests or other biomarker assessments are used to tailor drugs and treatments to individual patients. A year ago, for example, the Food and Drug Administration approved maraviroc, the first drug designed specifically for HIV patients who have a particular genetic mutation of the virus. This was the first time a drug had been approved upon the condition that patients first have a genetic test.[1] Similarly, in July scientists at the Van Andel Research Institute published a paper reporting that high expression of the gene known as MET increases the aggressiveness of certain types of breast cancer. This means that the MET gene can be used as a target for new cancer therapies that may inhibit MET’s expression, thereby slowing down the most aggressive forms of breast cancer.[2]

In spite of this kind of progress on the scientific front, Americans today remain guinea pigs in a “one-size-fits-all” approach to medicine in which clinical trials to test the safety and efficacy of new drugs do not take into account the influence of individual genes on individual health and wellness. In contrast, a personalized medicine approach may well allow (perhaps in the not too distant future) every individual patient to receive the best in tailor-made, evidence-based pharmocogenomic medicine.

Similarly, research, development, and clinical care in our health care system merely ensure that medical treatments will work for most of the population most of the time. In fact, most drugs prescribed today only work in 60 percent of patients or less.[3] Personalized medicine promises that treatments will be tailored to individuals by researching the effects of specifically tailored treatments on genetic subpopulations. Since one size does not fit all, personalized medicine will represent a marked improvement over the current system where patients are left to travel down a winding path of physician-led trial and error.

Compounding the unwieldiness of today’s haphazard clinical approach is the disjointed health care informatics system that prevents scientists and physicians from making the most of our nation’s personalized genomics research data. Our impersonal and uncoordinated approach to care costs lives and squanders billions of dollars that could go towards insuring the 45 million Americans who are without coverage while also bringing down costs.[4]

In short, we are awash in evidence that not all individuals will respond similarly to the same medical treatment. But we have not taken the steps to integrate personalized medicine fully into our health care system in order to benefit individuals and society alike.

Granted, there is still a lot we don’t know, especially when it comes to genetics. Most of the genes that have been discovered only have small effects from a diagnostic perspective.[5] But, the bigger question is how can scientists who are eager to expedite the integration of personalized medicine into clinical practice efficiently gather and disseminate their discoveries? It is because of this question that we should look at personalized medicine as contributing to the ultimate goal of turning medical practice into a total learning environment. This means physicians would be able to apply the most recent findings about the efficacy of available treatments while also sharing the outcomes of their own treatment decisions with others so that all physicians can have better data the next time around. This information will also be available to academic scientists and industry researchers so that they can gear their research and product development in more patient-specific directions.

Of course, given the private interests of all the various stakeholders involved, it should be no surprise that bringing about the era of personalized medicine will be no easy task. Many lingering legal, political, and administrative questions remain about patient privacy and about the ownership, organization, and security of the data. And those are just the tip of the iceberg when one considers the vast technical difficulties that computer programmers and health technologists are trying to overcome.

In April, at the Bio-IT World Conference and Exposition in Boston, for example, Microsoft Corp. announced the coming release of Amalga Life Sciences, which promises to be a single platform for aggregating and modeling data from “basic research, clinical trials, health care delivery, and consumer health information needs.”[6] Amalga will also be linked to Microsoft HealthVault so that patients can import their medical data generated at the hospital into their own personal health file.[7] This is an ambitious project that will need to be watched closely in action to see if it enhances or limits the ability of physicians, researchers, and patients to access the information they need in a way that is useful, understandable, and comfortable for them.

For now, though, the bottom line is that there definitely needs to be a strong public debate about what health information is going to look like and what it is going to do. The most promising way to begin this debate is to not get bogged down in the technical questions just yet. Instead, this is a ripe time for taking stock in what values should guide our vision of personalized medicine; what tools we already have available to bring it about; and how responsibilities should be divided up or combined by public and private stakeholders.

Some federal government entities have already started taking steps to answer these questions by moving ahead with initiatives that better streamline the data, technology, and research efforts that are already available. The National Institutes of Health, for example, announced in February that it is moving forward on a clinical trial that will test the effectiveness of integrating genetic data into the dosing protocol for the blood-thinning drug warfarin. This happened just weeks after then-acting Director of the Food and Drug Administration Frank Torti announced that the FDA created a new position in the Office of the Chief Scientist called Senior Genomics Advisor. This office has been filled by FDA veteran Dr. Liz Mansfield, whose job will be to provide “FDA physicians and scientists with tools and personnel capable of high-level analysis of complex genetic data.”[8]

Taking a broader view, the Personalized Healthcare Initiative in the Department of Health and Human Service’s Office of the Assistant Secretary for Planning and Evaluation has conducted reviews of current federal efforts in order to identify organizational challenges to achieving overarching goals. This PHC initiative highlights the need for connecting clinical records with genomic information, ensuring the integrity and privacy of genetic data, preventing discrimination, ensuring the accuracy and validity of genetic tests, and devising common access protocols for genomic databases.

The PHC initiative also highlights various tasks for many government agencies and programs to ensure that that they do their part to achieve these goals for the ethical and coordinated advancement of personalized healthcare. Some of these tasks include directing other agencies in Health and Human Services to devise ways for sharing their data so that the genomic, clinical, and public health aspects of personalized medicine can mutually reinforce one another rather than remain siloed and even redundant in their research and analyses. The PHC initiative also includes in its review the ethical analyses published by the HHS Secretary’s Advisory Committee for Genetics, Health, and Society, or SACGHS, on large-population genetic studies and the bureaucratic logistics of pharmacogenomic research.[9]

Other principled concerns about personalized medicine have also been addressed in general terms through SACGHS, a permanent group that advises the secretary on, among other things, personalized medicine and occasionally releases reports on the issues at hand.[10] Yet the fine practical details of these concerns still need to be hashed out by multiple collaborators on a case-by-case basis.

These concerns have to do with the inclusion of private entities in data-sharing about the validity, utility, and effectiveness of various technologies. What should private biotech companies, pharmaceutical companies, or diagnostic companies be required to share with the federal government? A recent SACGHS report recommends:

In situations where tests are essential to clinical drug use, HHS should require its
grantees and contractors to participate in FDA’s Voluntary Genomic Data Submission Program during the exploratory phase of drug development and/or the review process
for preinvestigational device exemption.[11]

This FDA program is overseen by a body known as the Interdisciplinary Pharmacogenomics Review Group, which was charged in 2005 with collecting phramacogenomic data about drugs in the developmental stage. This program has made regulators more cognizant of genomics, has influenced discussions on clinical trial design, and has even led to the development of a pilot process for qualification of biomarkers for use in regulatory decisions.[12]

From the standpoint of trying to better integrate pharmacogenomic data into the drug development process, this is a great idea. And personalized medicine would advance even more rapidly if pharmaceutical companies could cost-effectively collect information from large-cohort genetic studies and use that information to design better-targeted and more information-rich clinical trials. But companies are reluctant to invest more money in doing their own large-population-based genetic studies that may or may not help them to make a better product let alone recoup their investment.

So who pays for these large-population genetic studies? Usually, it is the NIH. But how can NIH orient its genetic research toward personalizing the drugs that the private sector is developing? SACGHS recommends that the recipients of NIH grants for research that “will be used to demonstrate safety and efficacy to support a [drug or device’s] premarket review application” to the FDA should consult with FDA “early in the study design phase.”[13] Again, this is a practical idea but there needs to be a concerted effort on the part of HHS to make this cooperation materialize on a case-by-case basis.

As pharmacogenomic research develops methodologically and as further evidence is gathered about the application of pharmacogenomic technologies in clinical practice, the policies and protocols for public/private collaboration will need to develop as well. For instance, the SACGHS report makes recommendations about stratifying subject populations based on their predispositions to adverse reactions as indicated by their biomarkers. These recommendations include having the FDA guide the collection of genetic and biological factors that are better predictors of drug responses than race, ethnicity, or gender; and having post-market follow up to find other biological, social, or environmental factors that influence drug response when there is a racial or ethnic disparity in drug response.[14]

Other examples include the plethora of recommendations that SACGHS makes concerning the increasingly controversial areas of insurance coverage and reimbursement, clinical practice guidelines, professional certification, and drug labeling.[15] What we know so far is that these are all relevant issues that can be dealt with by means of better coordination throughout the entire healthcare system.

Researchers need to be informed of all the relevant data collection initiatives. Regulators need to be better aware of the technologies that are coming down the pike. Corporations need to engage in partnerships with the public sector in order to share data for the public good and develop more personalized drugs. And, the FDA needs to encourage drug and device companies to do post-market follow up and coordinate it with the development of new products.

There also needs to be coordination between the genetic test manufacturers, the drug manufacturers, and the health care providers who need to gather evidence for them as they implement tests and therapies in the clinic. The problem, however, is that we do not have sufficient knowledge—both in terms of biomedical data and real-world policy experience—to set in stone any policies for systemic coordination on personalized medicine just yet.[16] Therefore, the best course of action for the time being is for HHS to emphasize better coordination in general, and to guide various coordinated projects by holding them accountable to the broad goals and values put forth in the SACGHS reports and in the work done by the PHC initiative.

This might be a job for HHS’s Office of the Assistant Secretary for Planning and Evaluation, which could:

• Consult with various agencies, programs, and private entities
• Suggest opportunities for collaboration
• Help to iron the terms on which these entities do collaborate

As various personalized medicine initiatives are implemented, HHS can then look at the protocols and policies that do and do not work in terms of data sharing, research coordination, or product development.

This would create an iterative self-correcting process that would allow us to gather more data on personal genomics and conduct more research into the implementation of personalized medicine. Thus, the United States will rapidly build a knowledge base for the future of personalized medicine while it still takes the time to learn how to develop the right policies for shaping that future.

Indeed, all of the initiatives described above are promising steps toward the development of personalized medicine as a new paradigm for medical practice. Nevertheless, the United States still has a long way to go before personalized genomics becomes a standard part of medical practice. Implementation and evaluation must proceed aggressively in tandem in order for us to not only achieve a personalized medicine revolution speedily, but also achieve it efficiently and ethically. This is the essence of progressive innovation and pragmatic policy making. For personalized medicine to fully come to fruition with the fewest number of bumps in the road, we must learn valuable lessons from the current piece-by-piece process as we ramp up our efforts to build upon it.

About the Authors

Michael Rugnetta is a Research Assistant with the Progressive Bioethics Initiative at the Center for American Progress and Whitney Kramer is an intern working on the Progressive Bioethics Initiative.

Endnotes

[1] “Virus-specific Drug Approved for HIV,” New Scientist, August 11, 2007, available at http://www.newscientist.com/article/dn12456-virusspecific-drug-approved-for-hiv.html.

[2] “Possible Drug Target Found For One Of The Most Aggressive Breast Cancers,” Science Daily, July 9, 2009, available at http://www.sciencedaily.com/releases/2009/07/090708153238.htm.

[3] Federal Coordinating Council for Comparative Effectiveness Research, Report to the President and the Congress, (Health and Human Services, 2009) available at http://www.hhs.gov/recovery/programs/cer/cerannualrpt.pdf.

[4] Paul Ginsberg, “Efficiency and Quality: The Role of Controlling Health Care Cost Growth in Health Care Reform,” (Washington: Center for American Progress, 2009) available at http://www.americanprogress.org/issues/2009/06/payment_reform.html.

[5] Alan M. Garber and Sean R. Tunis, “Does Comparative-Effectiveness Research Threaten Personalized Medicine?” New England Journal of Medicine 360 (19) (2009): 1925-1927.

[6] John Russell, “Microsoft Launches Amalga Life Sciences,” Bio-IT World, April 28, 2009, available at http://www.bio-itworld.com/news/2009/04/28/amalgals.html.

[7] Microsoft, “Microsoft Introduces Next-Generation Amalga Unified Intelligence System,” Press release, April 6, 2009, available at http://www.microsoft.com/presspass/press/2009/apr09/04-06AmalgaUISPR.mspx.

[8] U.S. Food and Drug Administration, “Viewpoint: FDA and Genomics,” February 2, 2009, available at http://www.fda.gov/AboutFDA/CommissionersPage/Viewpoint/Archives/ucm153614.htm.

[9] Health and Human Services, “Personalized Health Care,” available at http://www.hhs.gov/myhealthcare/.

[10] Office of Biotechnology Activities, “Secretary’s Advisory Committee on Genetics, Health, and Society,” available at http://oba.od.nih.gov/sacghs/sacghs_home.html.

[11] Advisory Committee on Genetics, Health, and Society, “Realizing the Potential of Pharmacogenomics: Opportunities and Challenges; A Report of the Secretary’s Advisory Committee on Genetics, Health, and Society,” (Health and Human Services, 2008) p. 24, available at http://oba.od.nih.gov/oba/SACGHS/reports/SACGHS_PGx_report.pdf.

[12] U.S. Food and Drug Administration, “Interdisciplinary Pharmacogenomics Review Group,” available at http://www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm083889.htm.

[13] Advisory Committee on Genetics, Health, and Society, “Realizing the Potential of Pharmacogenomics: Opportunities and Challenges; A Report of the Secretary’s Advisory Committee on Genetics, Health, and Society,” (Health and Human Services, 2008) p. 24, available at http://oba.od.nih.gov/oba/SACGHS/reports/SACGHS_PGx_report.pdf.

[14] Advisory Committee on Genetics, Health, and Society, “Realizing the Potential of Pharmacogenomics: Opportunities and Challenges; A Report of the Secretary’s Advisory Committee on Genetics, Health, and Society,” (Health and Human Services, 2008) p. 43, available at http://oba.od.nih.gov/oba/SACGHS/reports/SACGHS_PGx_report.pdf.

[15] Advisory Committee on Genetics, Health, and Society, “Realizing the Potential of Pharmacogenomics: Opportunities and Challenges; A Report of the Secretary’s Advisory Committee on Genetics, Health, and Society,” (Health and Human Services, 2008) p. 4-8, available at http://oba.od.nih.gov/oba/SACGHS/reports/SACGHS_PGx_report.pdf.

[16] Alan M. Garber and Sean R. Tunis “Does Comparative-Effectiveness Research Threaten Personalized Medicine?” New England Journal of Medicine 360 (19) (2009): 1925-1927.

Jonathan Moreno, Senior Fellow at the Center for American Progress and David and Lyn Silfen University Professor at the University of Pennsylvania, applauds President Barack Obama’s announcement that he intends to nominate Dr. Francis Collins as director of the National Institutes of Health.

Dr. Collins is a world-renowned leader in biomedical research who led the government’s Human Genome Project, which decoded the DNA sequence that forms the basis of human life and opened pathways to understanding how we develop, how genes influence illness, and how medicine can harness genetics to diagnose and cure disease.

“I’ve known Francis for many years and have observed close up his deep understanding that American science needs to be informed by our values,” said Moreno. “No one else possesses the remarkable combination of qualities he brings to this important position.

“His tenure as director of National Human Genome Research Institute was remarkable for its inclusivity and for how as director he went out of his way to make sure that all points of view were represented around the table on important points of science and medicine,” Moreno added. “He was always mindful that his strong personal convictions and faith remained just that—personal—and that science and medical policy reflected the best interests of the public well-being, not a political or religious ideology. I’m confident these same qualities will garner him the goodwill and support of Congress and the confidence of the American people, and will mark his leadership at NIH.”

At the National Human Genome Research Institute, Dr. Collins demonstrated a progressive dedication to our nation’s continued investment in the scientific research and innovation that powers our economy, improves our quality of life and well-being, and expands our knowledge of the natural world. His expertise in genomics will be a key asset as we move into an era of personalized medicine.

Dr. Collins is an outspoken man of science and an outspoken man of faith. His commitment to each framework of human understanding is emblematic of the pluralistic ethos of the United States. Indeed, a recent survey released by the Pew Center for People and the Press indicates that 61 percent of Americans see no conflict between science and their religious beliefs. As a researcher, his work has revealed the genetic basis of ailments ranging from cystic fibrosis to Huntington’s disease. As a citizen, he has worked to educate others about the fact that science and religion are not in opposition.

If confirmed by the Senate, Dr. Collins will no doubt support progressive approaches to research and innovation that embrace both science and ethics.

The proposed registry, which they also explain how to implement, would provide information regarding the reliability of health-related genetic tests; how test results “relate to current and future disease risk”; and how useful results are in informing disease diagnosis, treatment, management, and prevention. All clinical laboratories and distributors that advertise for tests or provide result interpretations that are different from those offered by laboratories should be required to register, with the exception of “providers of tests for ultra-rare disorders,” the authors recommend. They also suggest penalties for laboratories that do not comply.

A genetic testing registry would be an important educational resource for patients, parents, and health care providers. In a recent podcast with Science Progress, bioethicist Sandra Soo-Jin Lee said that lack of access to interpretive information about genetic testing is more pressing than lack of access to the testing itself, and that understanding what the results mean for your health is the most complex and valuable part of the process.

The proposal for a registry that would include so many genetic conditions highlights the questions about patient protection that remain even after the Genetic Information Nondiscrimination Act, known as GINA, became law last year. GINA prohibits the use of information obtained from genetic testing to deny health insurance coverage or employment, but insurers are not required to cover the costs of prevention measures a genetic test indicates would be beneficial, Susannah Baruch explains in a recent SP article.

The authors of the new study also suggest that either the National Institutes of Health or the Food and Drug Administration maintain the test registry. NIH has “extensive expertise in registry development and implementation” and FDA “has significant enforcement capability,” they explain. Despite where the registry, if created, is placed, the paper insists FDA be responsible for enforcement of consequences for non-compliance.

Agricultural innovations through modern biotechnology have delivered significant economic, environmental, health and consumer benefits in recent years, but the full potential is even greater. Producers have embraced these innovations wherever they have had access, and consumers have purchased everything produced. The principal obstacle to additional innovations that will extend and expand benefits even further is ill-considered and scientifically unjustified or illogically implemented regulation. While the United States has had a comparative advantage over many other countries with a regulatory regime more closely anchored in science than most, regulations and implementation have not kept pace with scientific advances and accumulated experience.

The United States is the leading exporter of agricultural products in the world with $82 billion worth of goods exported in 2007, the last year for which complete data are available.^[2] Our nation boasts a $12 billion net positive trade balance in agriculture, and is the world’s second-largest agricultural producer (after China) with an estimated market of value of over $200 billion in 2007. The United States is the world’s leading producer of major products such as maize, soybeans, beef and milk. In recent years, productivity has increased and costs constrained through the use of innovative technologies developed through U.S. investment in agricultural research. Seeds improved through modern biotechnology have made a major contribution to U.S. agriculture; the United States leads the way globally in area planted with genetically engineered crops.^[3]

A major reason for this has been the clear delineation of regulatory requirements and authorities, and a system that (usually) delivers predictable decisions in a timely manner. But regulatory requirements and, even more importantly, their implementation, have not kept pace with increased understanding and experience. All domesticated crops have been extensively genetically modified during millennia of plant breeding and improvement, but breeding methods for the introduction of useful traits into crops have been markedly improved in recent years. Agricultural products derived through modern biotechnology—for the purposes of this paper, in vitro recombinant DNA , or rDNA techniques coupled with transformation^[4]—are now a major and increasing part of global commerce.

The techniques of in vitro gene transfer are faster, more precise, more predictable, and better defined than older methods of catalyzing the genetic modification of crops^[5]. By expanding the selection of genes that can be incorporated into new varieties to include genes from essentially all living organisms, recombinant DNA technology allows researchers to introduce new beneficial traits that would be difficult or impossible to create with any other breeding technology. This has allowed for the development and commercialization of crops with innovative improvements in performance. In the United States today, 86 percent of the cotton harvest, 92 percent of soybeans, and more than 80 percent of the corn harvest consist of varieties improved through biotechnology.^[6]

In a world where global agricultural commodity trade is increasingly competitive, improved qualities, value, and production efficiencies provided through biotechnology have preserved jobs here at home, especially in rural areas, by enabling U.S. farmers to remain powerful players in the global market.^[7] While the number of individuals directly involved in farming continues to decline,^[8] other jobs related to agricultural production are on the rise^[9]—with a portion of the increase coming from high paying jobs in biotechnology and related science fields. And the United States continues to retain a leading global role as agricultural exporter despite dramatic increases in production from other countries, including those with much lower labor costs.^[10]

Although the food and agricultural sector appears secure and profitable, both U.S. and global agriculture face a staggering array of challenges. These include factors as varied as shrinking land and water resources, rising energy costs, the effects of global climate change, and competition between food and industrial (biofuel) uses for agricultural products.^[11] Recent events have shattered the illusion that there is a surplus of food in the world, and world food reserves have recently been at an all time low of 53 days.^[12] Over 850 million people are malnourished, most of them in developing countries, and over 1.2 billion live on less than a dollar a day.^[13] Despite years of international efforts by affluent developed countries led by the United States, after decades of decline the number of poor and hungry in the world is again growing in parallel with increasing population^[14].

The upshot: a simultaneously looming humanitarian crisis and a potential source of great political instability—food and water shortages—will drive future global politics. This approaching catastrophe, however, is not preordained, even though the serious challenges posed by food and water shortages are real and growing. The Obama administration can take concrete steps to stimulate more ambitious and widespread innovation that would unfetter the tools needed to address these challenges. The specific measures proposed in this paper would stimulate the process of innovation in seed improvement. Improved crop varieties resulting from these innovations would enable the production of more food, feed, and fiber with lower inputs, reduced environmental impacts, and greater profitability. Such consequences would be economically beneficial to all players in the chain from farm to fork, but perhaps felt most acutely and directly by agricultural producers themselves, boosting the viability of rural communities. As argued in the following pages, several things are needed:

• A realignment of regulations so that oversight is, in fact, anchored in up-to-date scientific understanding and real world experience, and focused on unknowns that may poses risks in need of management, while reducing the burdens on innovations that have been so widely adopted as now to be accepted as conventional
• A more active program of international diplomacy to share information with other countries on the impacts of biotech improvements to agriculture, and the widely shared economic uplift thus enabled
• A more active and coordinated educational outreach program implemented by regulatory agencies and coordinated by diplomats to illuminate the conditions required to enable the widest dissemination of such innovations and their benefits, including strong intellectual property rights and science-based approaches to regulation and risk management.

In the analysis that follows, this report will detail the role of agricultural biotechnology in the United States and around the globe. It will examine issues inhibiting the application of potentially beneficial technologies, including the effects of scientifically unjustifiable and disproportionate regulation and the malign influence of special interest opposition groups. And it will present specific recommendations to improve an enabling environment in which the best of U.S. science and technology can be applied to the national and global challenges that confront us and will define our future.

Global Adoption of Agricultural Biotechnology

The primary biotechnology crops planted in the world today are insect protected and/or herbicide tolerant varieties of corn, soybeans, cotton, and canola. Brookes & Barfoot show net benefits at the farm level of $6.94 billion in 2006 and $33.8 billion over the prior eleven years.^[15] They also show a 286 million kilogram reduction in pesticide applications leading to a 15.4 percent decrease in the environmental impacts associated with their use. Associated greenhouse gas emissions were reduced during 2006 alone by an amount equivalent to removing 6.56 million cars from the road.

Data compiled by noted agricultural biologist Clive James^[16] shows for 2007 a 12 percent year-on-year increase of global biotech crop area (30 million acres/12.3 million hectares), with the total global area devoted to growing biotech improved crops at 282.4 million acres. These crops are grown by 12 million farmers around the world, of whom 11 million are smallholders in developing countries, thus reaffirming the scale-neutrality of the technology. Biotech improved crops are today grown in 23 countries, including 11 industrial and 12 developing nations.

While these data show rapid adoption and market penetration of products derived from plants improved through biotechnology, similar rapid growth has not been equally evident in animal husbandry and livestock improvement. Indeed, the transgenic animal product closest to wide commercial availability today (approved in the European Union, and in phase III clinical trials in the United States) is ATryn,^[17] an animal-derived drug that helps prevent excessive bleeding during surgical procedures.

The animal product perhaps closest to regulatory approval in the United States is a transgenic “advanced hybrid” salmon that reaches market size in half the usual time on 20 percent less food. This has been in the regulatory pipeline for the better part of a decade or more, and is reportedly nearing approval. Numerous other products and applications are in development but the lack of clear understanding on how these products would be regulated has created a perverse incentive that has discouraged investment.^[18]

Regulatory agencies have grappled with these issues for more than a decade, but a lack of attention by the outgoing Bush administration left proposals languishing in bureaucratic limbo for years, a defect partially remedied in recent weeks by publication of draft guidance by the Food and Drug Administration.^[19] Many uncertainties remain, including questions as to how several federal agencies with different or overlapping authorities will coordinate their responsibilities. But concrete decisions emerging from these agencies are the ultimate test and requirement, and a hurdle that remains to be cleared.

Constraints to Adoption

Dramatic as the advances and benefits from agricultural biotechnology have been to date, they represent only a small fraction of what is possible. While many plants improved through biotechnology have been field-tested,^[20]and at least 22 crops have been approved for food and feed use in the United States,^[21] the majority of the global trade in biotech-improved crops to date has involved only four plants: soybeans, cotton, corn (maize) and canola. The improvements delivered through biotechnology thus far have been primarily insect resistance and herbicide tolerance.

Biotechnology is capable of solving many more of the problems and challenges facing agriculture around the world than this short list suggests^[22]. Why are more of these solutions not available today? There are many contributing factors, but there is also wide agreement as to the major obstacle. James has described the impact of overly burdensome regulatory regimes on developing countries, but the critique is no less relevant to industrial nations:

“The most important constraint to biotech crops… is the lack of appropriate cost-effective and responsible regulation systems that incorporate all the lessons of a dozen years of regulation. Current regulatory systems… are usually unnecessarily cumbersome and in many cases it is impossible to implement the system to approve products which can cost up to US$1 million or more to deregulate… With the accumulated knowledge of the last dozen years it is now possible to design appropriate regulatory systems that are responsible, rigorous and yet not onerous, requiring only modest resources… Today, unnecessary and unjustified stringent standards… are denying… countries timely access to products such as golden rice, whilst millions die unnecessarily in the interim. This is a moral dilemma, where the demands of regulatory systems have become “the end and not the means”, overriding common sense, and where “the regulatory surgery may be successful but the patient died.”[23]

The problem, in fact, is larger than this indicates—a dispassionate review of the global experience to date with field testing and commercial growing of transgenic plants and the underlying science suggests that all existing regulatory regimes apply a level of scrutiny and control that is disproportionate to the risks they seek to manage.[24] Science shows that any regulatory review process that is triggered by the fact that an organism has been modified by in vitro rDNA techniques per se is unjustified. Numerous authoritative analyses have concluded that the potential hazards associated with crops improved through biotechnology are the same as those with which we are familiar from conventional crops.[25] Case in point: The European Commission concluded in 2001 that “the use of more precise technology and the greater regulatory scrutiny probably make (biotech derived foods) even safer than conventional plants and foods.”^[26] This conclusion has recently been reinforced by a study from the Joint Research Center of the European Commission.^[27]

These findings from the epicenter of political opposition to biotechnology in agriculture, the EU, have been confirmed in studies and experience around the world.^[28] Indeed, the only findings in the scientific literature which show significantly different levels of hazard between biotech improved crops and other crops favor biotech crops.[29] It is fair to ask, then, how it is possible to justify, other than through bureaucratic inertia and political pressure manufactured by interest groups,[30] a situation wherein the highest regulatory barriers to market entry are placed in the path of products that are better understood and demonstrably more productive, beneficial, and often safer than competing products?

Barriers to Trade

Policies adopted by the EU, for example, have created de facto trade barriers that discourage the development and use of transgenic crops. U.S. farmers have been reluctant to plant some biotech improved crops such as wheat, potato, and rice because these crops have not been approved by the EU regulatory system, and out of concern over potential loss of market share. The United States, Argentina, and Canada brought a World Trade Organization case against the EU, which was decided in their favor in 2005[31]. Yet the EU has so far been intransigent in agreeing to any resolution of the judgment against them.

Moreover, the EU has invested hundreds of millions of euros in various trade distorting measures, promoting fear and misinformation, and advancing their approach to regulation as a model for other countries.[32] EU support has been targeted at a variety of measures attempting to ensure that developing nations adhere to the Cartagena Biosafety Protocol by installing biosafety systems but which, in fact, create barriers to the adoption of transgenic crops. Not only is the EU unwilling to approve transgenic crops in a timely manner, but after approval for use transgenic crops are discriminated against by a mandatory labeling regime that requires segregation of transgenic from “conventional” crops, which adds 10 percent-to-20 percent to the cost of these commodities and foods prepared from them.[33]

What’s more, EU policies and EU civil organizations have focused on keeping biotechnology away from developing countries that most need to improve their agriculture.[34] This politicization of regulation has eroded the role of science and experience, leading to counterproductive policies that add enormous costs to the food and feed system, such as regulatory and compliance costs, the cost of segregation and testing, and numerous opportunity costs.

Bruce Ames and Lois Gold (University of California, Berkeley) have described this phenomenon as: “damage by distraction: regulating low hypothetical risks. Putting huge amounts of money into minuscule hypothetical risks has a negative impact on public health by diverting resources and distracting the public from major risks.”[35] The misplaced focus on GMOs also creates damage by diverting regulatory and consumer attention and resources away from real food safety issues, such as food borne pathogens and mycotoxins, which do real harm.

Barriers Created by Existing U.S. Policy & Regulations

In contrast to the EU, the United States relies on regulatory policy more firmly anchored in reliance on science-based risk assessment, in which regulators are directed to base decisions on data and experience rather than political considerations. Existing U.S. policy was set out in 1986,[36] and is widely known as the Coordinated Framework. The scientific consensus that plants improved through recombinant DNA techniques present no novel or unfamiliar risks by comparison with their conventional counterparts justified the use of existing legislative authority granted to the U.S. Department of Agriculture, the Environmental Protection Agency and the Food and Drug Administration.[37] Experience in the intervening years has produced nothing to cast doubt on this consensus. Each of these agencies has put in place regulations, promulgated policies, and adapted them over time, some repeatedly. Indeed, this system has, for the most part, entailed clear regulatory requirements and decisions taken by regulators have generally produced predictable results in a timely manner—affording the United States a comparative advantage over many other countries.

But the U.S. regulatory oversight system as it presently functions, is imperfect in the extent to which its regulatory burdens track credible risks or significant uncertainty. Vast experience has been accumulated under existing regulations, especially at USDA, but proposed updates to these regulations fall significantly short of changes justifiable on the basis of experience to date.[38] The situation is exacerbated by lawsuits and court decisions which appear to be driving USDA in the direction of repairing procedural vulnerabilities at the expense of regulatory reforms that would more closely align oversight with genuine risks and uncertainties.[39]

While a wholesale overhaul is not required, several updates and course corrections are overdue. The problems created by their absence are best seen by examination of some of the concrete innovations possible with modern agricultural biotechnology, and the disproportionate regulatory obstacles they face.

Improved production and quality of fruits and vegetables. There are a great many “minor” crops for which production is constrained by a disease, an insect pest, or another environmental stress or factor for which biotechnology could readily provide one or more solutions. The markets for these products are generally much smaller than those for major commodity crops, making the prospects for recovery of the costs of regulatory approval[40] through amortization of several years of market growth for new biotech varieties much more tenuous.

Improved production of medicines through plant made pharmaceuticals. Field trials of plants modified to become more productive and economical sources of innovative medicines have been burdened with and impeded by measures to impose isolation and containment out of proportion to any reasonable estimate of potential hazard. A classic example in this regard is the use of rice economically to produce lactoferrin as a medication to treat childhood diarrhea. Lactoferrin is a protein found in mothers’ milk. There is no indication its consumption would present any potential for harm, yet permits for field trials have been burdened with onerous requirements to ensure that pollen does not carry the lactoferrin gene beyond the test plots,[41] and absolutely no commingling of the experimental rice is permitted with other rice.

Reduced environmental impacts in large scale commodity crop production through improved weed control/herbicide tolerance. Many crop plants carry innate tolerances for exposure to different herbicides as a natural consequence of plant physiology and genetic variation in nature. Crops produced through biotechnology carrying similar phenotypes are subjected to intense scrutiny while those produced using older less precise methods can be marketed without any regulatory review. Experience with the newer herbicide tolerant crops has generated so robust an affirmation of safety that the burden of evidence should now be on those arguing for scrutiny greater than that applied to herbicide tolerance derived through mutagenesis and conventional breeding. Detailed and duplicative reviews for all biotech herbicide tolerant crops are beyond what can be justified by any data on hazard or experience in the field. Future regulatory reviews of herbicide tolerant crops, however derived, should focus only on any novel risks.

Improved pest control. Many different agricultural crops possess varying degrees of resistance to different potential pests. Crops enhanced through biotechnology to resist herbivorous insects (“plants with pesticidal properties”) are regulated by EPA under the same laws and with generally comparable methods applied to conventional pest control substances. In a dramatic and unprecedented departure, however, plants containing an insecticidal protein derived (through biotechnology) from Bacillus thuringiensis, or Bt, are required by EPA to be planted under a “resistance management plan.” EPA stipulates setting aside an area (usually 20 percent) for growing non-Bt plants as a means of forestalling the inevitable evolution of insect resistance. Integrated pest and resistance management are clearly valuable, but such “refugia” requirements have not before been imposed on other types of insect protected plants, nor have they been applied to use of Bt as a topical pesticide (e.g., as practiced by organic growers, in the only situation to date where, in fact, resistance has been seen to evolve in the field).

Resistance management is an issue of product longevity more than of environmental protection and it can be argued that issues of product longevity are better left to market forces. EPA should encourage innovation and good stewardship in pest management more effectively with a shift towards performance standards and away from rigid prescriptions. This would accelerate the development of pest protected plants incorporating multiple modes of action and other innovative approaches.

Improved cellulosic biomass production. Cellulosic biomass is widely used for myriad purposes: in the construction industry as structural material; throughout business, education, commerce and life through paper products; increasingly of late for energy, either directly or through production of ethanol or other energy storing compounds to concentrate energy and make it more easily transported. Several novel sources of cellulosic biomass (Miscanthus, switchgrass, Eucalyptus and poplars) are being genetically engineered in order to make them suitable for efficient and economical pulp and/or biofuel production. The greatest obstacles limiting their development and adoption are regulatory barriers that treat all biotech crops as a suspect class subject to heightened regulatory scrutiny. Regulatory agencies continue, for example, to impose significant constraints on biotech crops in R&D field trials to eliminate any potential for gene flow, even in cases where no possible harm to humans or the environment could result. It is difficult, for example, to imagine an unfamiliar risk from a plant modified to resist a well characterized herbicide, yet new crops containing resistance to such herbicides due to biotech manipulations are subject to scrutiny while similar crops produced conventionally are not.

Improved livestock production, Recombinant DNA technology can be used to improve livestock and companion animals in many ways—improved feed conversion and nutritional qualities, shortened time to market, resistance to disease, reduced environmental impacts, improved efficiency as sources of human medicines, and more. Although the emergence of policy guidance and regulations from the FDA has been slow, the principle obstacle here has not (yet) been disproportionate regulatory burdens so much as regulatory uncertainty caused by such delays. The primary cause of the delays appears to have been a failure by the White House Office of Management and Budget’s Office of Information and Regulatory Affairs to allow proposed regulatory guidance documents to be published for public comment.

A promising recent development has been the publication of guidance by the FDA[42] detailing how they would regulate transgenic animals and their products. The Agency has assigned responsibility to the Center for Veterinary Medicine to apply regulations governing new animal drugs. It remains to be seen if the resulting oversight will provide scrutiny at levels proportionate to the level of risk and in a timely manner, but it is clear that to unleash this technology and enable it to proceed at a pace dictated by the rate of scientific advance the remedy is simple: the Obama administration should renew the requirement for transparency, and more specifically proportional reviews and timely decisions. Future adaptations of regulations must be delivered through prompt publication of proposed policy documents and regulatory guidance by responsible agencies, accompanied by timely responses and decisions.

Lost opportunities and opportunity costs. Regulatory barriers, trade barriers, and the dissemination of deliberate misinformation about crops produced using modern biotechnology have had a chilling effect on adoption of existing approved varieties, and they have discouraged researchers and corporations from undertaking development projects that utilize rDNA technology. Nowhere has this had more damaging impact than in developing nations that suffer from recurrent food insecurity and hunger, and which desperately need to improve agricultural productivity and sustainability. The magnitude of these lost opportunities is difficult to calculate, however, if the productivity gains and environmental benefits reported for four major crops^[43] were extrapolated to all crops for which biotech solutions have not been adopted, the lost potential would obviously be enormous. This is setting aside the fact that higher yields and nutritionally enhanced crops such as Golden Rice might have saved millions of lives per year.^[44]

Policy Recommendations to Reignite Innovation in Agricultural Biotechnology

Biotechnology applied to agricultural has, for good reason, been described as Promethean.^[45] It promises to re-shape the relationship between humans and our environment in dramatically greener and more sustainable ways than anything that has gone before. Although the technological challenges remain formidable, the science accessible to us today would enable more rapid innovation than we have seen to date, primarily because of regulatory obstacles for which experience has over the past two decades eroded the scientific justification. There are a number of specific steps that could be taken to reduce or eliminate such obstacles.

Reform the US regulatory system. Regulations must be based in science and should be frequently updated to take into account the lessons gained from experience. Judicial decisions based on perceived procedural deficiencies^[46] should not be allowed to drive regulatory action in directions unsupported by science. The system should not seek zero risk as this is unattainable in the real world. Regulatory review should seek to establish that novel products are as safe as others in the marketplace. In making this evaluation regulators must take into account both the harms caused by present practices as well as opportunity costs, the potential benefits that would be lost by non-adoption. The degree of regulation should be commensurate with real risks and harms. Specifically:

• The trigger for regulatory review should be the novelty of the introduced trait (introduced by whatever method) and not the process used to introduce the trait. The degree of scrutiny should depend on the relative risk associated with the phenotype and the host when it can be shown that the methods used do not add to the risk. The system should have clear guidelines that quantitatively specify timely decision-making.
• Exempt phenotypes from regulatory review if they could be accomplished through classical methods. If a phenotype comparable to that under review could be produced by a variety of production methodologies (classical breeding vs. recombinant DNA modifications, for example) then there should be a strong presumption against any review process that would make it more difficult, for example, to see the rDNA product move into the field for R&D or commercial purposes when there is no scientific justification for such discrimination.
• Recognize that gene flow is a natural phenomenon and is not intrinsically hazardous. The potential for gene movement via pollen flow is a natural phenomenon. Regulatory agencies must stop treating gene flow as intrinsically hazardous, and shift their focus to appropriate risk management/mitigation in the rare cases where genes so disseminated could, in fact, present a genuine hazard.
• Shift to phenotype-based regulatory triggers. Agencies should transition from an event-based regulatory process to a phenotype-based process, as the hazard of a phenotype that is stably inherited has more to do with the distinguishing features of the phenotype than with the precise details of the process through which it was produced.
• Enhance effectiveness, adaptability, and public confidence by accelerating regulatory updates and transparency. To unleash this technology and enable it to proceed at a pace dictated by the rate of scientific advance the remedy is simple: the new administration should insist on transparency and require prompt publication of proposed policy documents and regulatory guidance by responsible agencies, which must then be tasked with timely responses to public comment. This will galvanize innovation not only in the animal biotech sector, which has suffered acutely in this regard, but broadly.

Fund outreach and education here and abroad. A program to counter misinformation and offer developing countries regulatory models that will create an enabling climate for biotechnology is essential. Regulators from USDA, FDA, and EPA should be a much more active and visible presence on the international stage and in multilateral fora, sharing the American experience with agricultural biotechnology and correcting misunderstandings fueled by opponents driven by concerns unanchored in data and experience. The Department of State should play a larger leadership and coordinating role focusing these efforts on countries of key strategic importance and global significance.

Make helping developing countries attain sustainable food security a major priority for U.S. foreign aid, open not only to biotechnology but to all technological innovation. Such a policy would be relatively inexpensive (by comparison with the costs of dealing with consequences of the alternatives, including inaction) and yield beneficial results on numerous fronts, including national security. Reversing the past three decades of decline of support, through USAID, for international agricultural research through the CGIAR^[47] would be a good first step.

Maintain strong intellectual property protection as an essential stimulus to investment. Intellectual property contained in the genetics of self-replicating plants is easily infringed. The administration should advocate for patent law and PTO administrative reforms that reward private investment in valuable agricultural innovations.

Conclusion

In summary, biotechnology applied to agriculture has enormous potential to enhance our ability to develop seeds for improved crops and for enhanced livestock to enable us to meet the food, feed and fiber challenges of a growing world and stressed ecosystems in coming years. Significant impediments are created by unwarranted or outdated regulatory burdens that could easily be removed. The resulting, stronger scientific basis for regulatory oversight will increase the efficiency of regulation designed to prevent or manage risks and uncertainties while enabling more rapid development of innovative, safer products. Benefits to human health, the environment, global political stability and national security would follow.

L. Val Giddings, Ph.D, is President, PrometheusAB, Inc. and Bruce M. Chassy, Ph.D., is Professor of Food Microbiology, Department of Food Science and Human Nutrition at the University of Illinois, Urbana.

Endnotes

^[1] Nina Fedoroff & Nancy Marie Brown. 2004. Mendel in the Kitchen: A Scientist’s View of Genetically Modified Foods. Joseph Henry Press, Washington, DC. 370pp. ISBN 0-309-09205-1.

^[2] http://usinfo.state.gov/products/pubs/economy-in-brief/page3.html

^[3] Clive James, 2008. Global Status of Commercialized Biotech/GM Crops, 2007. ISAAA Brief 37-2007: Executive Summary at http://www.isaaa.org/resources/publications/briefs/37/executivesummary/default.html.

^[4] Combining two or more DNA molecules in the laboratory, and then inserting the resulting DNA into the hereditary material of a plant or animal; also sometimes referred to as “transgenics” or (inaccurately) “GMOs” for Genetically Modified Organisms.

^[5] Chrispeels, Maarten & David E. Sadava. 1994. Plants, Genes & Crop Biotechnology (2^nd Edition). Jones & Bartlett, New York. ISBN-13: 9780763715861. also Fedoroff & Brown, 2004 (note 1 above).

^[6] Economic Research Service, USDA, 2008; see http://www.ers.usda.gov/Data/BiotechCrops/.

^[7] See http://www.ers.usda.gov/Data/FATUS/ .

^[8] See http://www.ers.usda.gov/StateFacts/US.htm.

^[9] See http://www.csrees.usda.gov/newsroom/news/2005news/USDA_05_Report2.pdf.

^[10] See http://web.worldbank.org/WBSITE/EXTERNAL/EXTDEC/EXTDECPROSPECTS/EXTGAT/0,,menuPK:547863~pagePK:64167702~piPK:64167676~theSitePK:547846,00.html and http://www.ers.usda.gov/Briefing/AgTrade/

^[11] See www.fao.org.

^[12] See http://www.discovery.org/a/5601.

^[13] See http://www.unmillenniumproject.org/documents/table_2.gif; and http://www.fao.org/newsroom/en/news/2006/1000433/index.html.

^[14] Evans, L.T. 1998. Feeding the Ten Billion. Cambridge, New York. ISBN 0 521 64685 5.

^[15] Graham Brookes & Peter Barfoot, 2008. Global Impact of Biotech Crops: Socio-Economic and Environmental Effects, 1996-2006. AgBioForum 11(1):21-38 at http://www.pgeconomics.co.uk/pdf/agbioforumpaper2008final.pdf.

^[16] James, 2008.

^[17] Scott Gottlieb & Matthew Wheeler, 2008. Genetically engineered animals and public health: Compelling benefits for health care, nutrition, the environment, and animal welfare. At http://www.bio.org/foodag/animals/ge_animal_benefits.pdf.

^[18] See http://www.bio.org/foodag/animals/ge_animal_benefits.pdf.

^[19] See FDA, 2008 (18 September), “Guidance for Industry 187, Regulation of Genetically Engineered Animals Containing Heritable rDNA Constructs” at http://www.fda.gov/OHRMS/DOCKETS/98fr/FDA-2008-D-0394-gdl.pdf.

^[20] See USDA APHIS data on field trials at http://www.isb.vt.edu/cfdocs/biocharts1.cfm.

^[21] See the US Regulatory Agencies Unified Biotechnology Website at http://usbiotechreg.nbii.gov/database_pub.asp

[22] See, for example, Leonard P. Gianessi, Cressida S. Silvers, Sujatha Sankula, and Janet E. Carpenter, 2002. Plant Biotechnology: Current and Potential Impact for Improving Pest Management in US Agriculture. National Center for Food & Agricultural Policy, at http://www.ncfap.org/biotechcrops.html, and also Gabrielle J. Persley, 1990. Agricultural Biotechnology: Opportunities for International Development. CAB International. Wallingford, UK, 495pp. ISBN 0-85198-643-9.

^[23] James, 2008.

[24] Kalaitzandonakes K, Alston JM, Bradford KJ (2007) Compliance costs for regulatory approval of new biotech crops Nat Biotech 25: 509 – 511.

^[25] One of the earliest such studies was NAS 1987, Introduction of Recombinant-DNA Engineered Organisms Into the Environment; Key Issues. National Academy Press, Washington. 25pp. A more recent corroboration was Charles Kessler & Ioannis Economidis, 2001. EC-sponsored Research on Safety of Genetically Modified Organisms: A Review of Results. European Commission, Brussels. ISBN 92-894-1527-4. Additional authoritative examples are legion.

[26] European Commission, Press Release of 8 October 2001, announcing the release of 15 year study incl 81 projects/70M euros, 400 teams. See (http://ec.europa.eu/research/fp5/eag-gmo.html and http://ec.europa.eu/research/fp5/pdf/eag-gmo.pdf ).

^[27] See http://ec.europa.eu/dgs/jrc/downloads/jrc_20080910_gmo_study_en.pdf.

^[28] See, for example, http://www.nap.edu/openbook.php?record_id=9889.

^[29] See, for example: Munkvold, G. P., Hellmich, R. L., Showers, W. B. 1997. Reduced fusarium ear rot and symptomless infection in kernels of maize genetically engineered for European corn borer resistance. Phytopathology 87:1071-1077; & Munkvold, G. P., Hellmich, R. L., Rice, L. G. 1999. Comparison of fumonisin concentrations in kernels of transgenic Bt maize hybrids and non-transgenic hybrids. Plant Disease 83:130-138. .

^[30] Pressure groups opposed to agricultural biotechnology, such as Friends of the Earth, Greenpeace, and the Soil Association (UK) and a small handful of sister groups have prosecuted major campaigns in opposition to agricultural biotechnology.

^[31] See http://www.wto.org/english/tratop_e/dispu_e/cases_e/ds291_e.htm.

^[32] See http://www.economist.com/world/europe/displaystory.cfm?story_id=9832900 and http://www.foodnavigator.com/Publications/Food-Beverage-Nutrition/NutraIngredients/Regulation/EU-regulations-attract-global-attention/?c=BsQPsnsxVtbvnOzYL7sWTw==

^[33] See http://www.pgeconomics.co.uk/pdf/Global_GM_Market.pdf and Kalaitzandonakes, N., R. Maltsbarger, & J. Barnes, 2001. The costs of identity preservation in the global food system. Canadian Journal of Agricultural Economics 49:605-615.

^[34] Robert Paarlberg, 2008. Starved for Science: How biotechnology is being kept out of Africa. Harvard University Press, 235pp. ISBN-13: 978-0-674-02973-6; also, 2001. The Politics of Precaution. Johns Hopkins University Press. 181pp. ISBN 0-8018-6668-5; and Jon Entine (ed.), 2006. Let Them Eat Precaution. AEI Press, 203pp. ISBN 0-8447-4200-7.

^[35] Bruce N. Ames & Lois Swirsky Gold, 2000. Paracelsus to parascience: the environmental cancer distraction. Mutation Research 447:3-13.

^[36]See Office of Science & Technology Policy, Coordinated framework for regulation of biotechnology; Announcement of Policy and Notice for public Comment. 51 FR 23,392, 26 June, 1986 also at http://usbiotechreg.nbii.gov/ .

^[37] See OECD 1986: Recombinant DNA Safety Considerations – Safety considerations for industrial, agricultural and environmental applications of organisms derived by recombinant DNA techniques. ISBN 92-64-12857-3; and National Research Council, 1989. Field Testing Genetically Modified Organisms: Framework for Decision. Washington, DC, National Academy Press. ISBN

ISBN-10: 0-309-04076-0 ;

^[38] See, for example, USDA proposals and comments to the APHIS Docket at http://www.regulations.gov/fdmspublic/component/main?main=DocketDetail&d=APHIS-2008-0023.

^[39] See, for example, http://www.ca9.uscourts.gov/ca9/newopinions.nsf/4C054C94994E1DB3882574B80059C7B9/$file/0716458.pdf?openelement.

^[40] http://www.pewtrusts.org/news_room_detail.aspx?id=24758

^[41] See, for example, http://www.epa.gov/EPA-IMPACT/2005/May/Day-13/i9606.htm.

^[42] FDA, 2008.

^[43] Brookes & Barfoot, 2008.

^[44] Ingo Potrykus, 2001, “Golden Rice & Beyond: Emotions are the problem, not rational discourse.” Plant Physiology 125:1157-61 at http://www.plantphysiol.org/cgi/content/full/125/3/1157.

^[45] See http://www.worldbank.org/html/cgiar/publications/prometh/pscont.html; also Gabrielle J. Persley, 1990. Beyond Mendel’s Garden: Biotechnology in the Service of World Agriculture. CABI Press, Wallingford, UK. ISBN 0-85198-682-X; and Gordon Conway, 1997. The Doubly Green Revolution – Food for all in the 21^st Century. Comstock Publishing, New York. ISBN -13- 9780801486104.

^[46] See, e.g., Geertson Seed Farms v. Johanns, No. 06-01075, 2007 WL 518624 (N.D. Cal. Feb. 13, 2007).

^[47] The Consultative Group for International Agricultural Research, see http://www.cgiar.org/.

Despite the significant protections offered by GINA, hailed at its passage as “the first civil rights legislation of the 21^st century,” there are no comforting answers to such key questions as: If my genetic test reveals that I need preventive care or early treatment, who will pay for that care? If my health is at risk and I want to protect myself, could my genetic information be used to deny me life insurance, long-term care insurance, or disability insurance? Most patients today undergo genetic testing to learn their health risks, but economic risks also loom large. GINA’s passage has illuminated further the need to create policies that support people once illness strikes. First and foremost, Congress and the White House simply must succeed in current efforts to overhaul our system of health care and health insurance. At least as challenging is the need for an honest look at our country’s systems of disability insurance, long-term care insurance, and life insurance—the public and private support systems for individuals and families dealing with the financial impact of serious illness and death.

What GINA does not do is require insurers to pay for care that a genetic test indicates would clearly be beneficial. Thus, there are no guarantees that patients will be able to access or afford therapies and screenings that could reduce their risks. Without further reform efforts to ensure that preventive strategies are within reach, GINA’s protections from discrimination will ring hollow.

For example, BRCA genetic testing evaluates the risk of developing breast and ovarian cancer. A positive genetic test may lead a doctor to recommend that a patient increase the frequency of early surveillance such as mammography to heighten the chance of early detection, or take preventive drugs such as tamoxifen, or consider prophylactic removal of the breasts or ovaries. However, GINA does not require that insurers pay for the early intervention that genetic testing indicates is necessary. Policymakers must address this gap in protection for patients—made all the more glaring by protections GINA does afford—as part of the comprehensive health insurance reform efforts now underway.

Similarly, GINA doesn’t protect people from health insurance discrimination on the basis of their current health status, even when a patient’s health can be dramatically improved—and health care costs lessened—by early detection, treatment, and disease management. Consider the common genetic disease hemochromotosis: In this disease, iron levels in the blood build up, and, if left untreated, can cause damage to organs and organ failure. The disease often is diagnosed with the help of genetic testing. A classic scenario involves a patient who has no symptoms, but opts for a genetic test to determine his or her risk after a family member develops the disease. The test indicates a mutation in a key disease gene, leading to diagnostic testing which may, in turn, detect increased blood iron levels, the earliest stage of the disease. The good news in this case is that simple blood donation by the patient manages the disease: It’s an easy, cheap solution that prevents the real risk—organ failure—from occurring. The bad news is that some health insurers have balked at covering an individual once there is a “diagnosis,” no matter how early, and how symptom-free the stage. An insurer’s refusal to cover the individual creates incentives against undergoing beneficial testing that can lead to a very early diagnosis and improved health. This too must be fixed through health care reform.

Individuals considering genetic testing typically want to know about their health risks. But genetic information reveals personal financial risk as well. Knowing their chance of future illness allows individuals and families to prepare for the possibility of devastating financial losses due to the inability to work and loss of income from illness or death of a family’s wage-earner.

These are exactly the circumstances under which people may want to seek life insurance, disability insurance, or long-term care insurance policies. Disability insurance protects against loss of income, while long-term care insurance protects against the cost of services including medical care, psychological support, or assistance with daily living. Life insurance typically pays a sum of money upon the insured person’s death. These insurance markets differ in some ways from the health insurance market—in general, observers view these insurance protections as meeting needs that are less fundamental than health insurance. Consequently, they generally leave insurers in these markets alone to set premiums and eligibility as they see fit.

GINA does not prohibit an insurer’s use of genetic information in setting rates for life insurance, long-term care insurance, or disability insurance. But should insurers be allowed to deny people the protections of these forms of insurance based on their genetic risk? It is not a simple question. In recent years, Mark Rothstein of the University of Louisville and Susan Wolf of the University of Minnesota have lead efforts to explore policy approaches to this issue. No consensus has emerged, but a significant body of work has laid the foundation for building solutions.

Some states have begun addressing whether the use of genetic information ought to be permitted. As of this writing, 16 states regulate the use of genetic information in life insurance, 16 states regulate its use in disability insurance, and 10 states regulate the its use in long-term care insurance. Although state approaches vary widely, the number of states acting in this area clearly has increased in recent years and the number is likely to continue to climb.

It makes sense that when people learn of their increased health risks, they may be motivated to buy new insurance in preparing for the future. Insurers are concerned that if individuals set out to purchase insurance on the basis of genetic information that is known to them but cannot be known by or used by insurers, the underwriting process will be corrupted through what is referred to as “adverse selection.” In a 2005 study, Cathleen Zick of the University of Utah and Robert Green of Boston University found that patients who learned they had tested positive for a genetic mutation associated with an increased risk of Alzheimer disease were significantly more likely to purchase long-term care insurance than patients who either tested negative for the mutation or did not learn their genetic testing results. On the other hand, this group was not more likely to purchase disability, life, or health insurance. Alzheimer disease presents a special case in a number of ways: The large number of people affected, the huge costs associated with care, and the relative lack of impact on length of life all point to long-term care insurance as the most likely market affected by adverse selection. Other diseases with variable costs and prognoses are expected to affect purchasing behavior and insurance markets differently.

Regardless of the disease, genetic information (which includes a person’s family history) is very rarely, if ever, a perfect predictor of whether an individual will become sick, how sick they will become, or whether and how they will die. But policymakers are concerned that genetic information may be viewed as magically precise, and as such will be over-valued by insurers, compared with similar health issues or other risks without a known genetic basis. Even if the predictive value of genetic information and the relevance to future claims cost were high, many genetic diseases are treatable and their effects can be mitigated. Protecting people from the threat of having genetic information used against them could bring public health benefits by reassuring patients and encouraging more appropriate health care, prevention, and early treatment, allowing those with diseases and conditions to live productive and happy lives while mitigating the severity and costs of illness.

Of course, underwriting is and always has been built on the complicated process of meticulous risk classification. No doubt experts in these markets could design a system that takes into account genetic test results just as they take into account the imperfect predictive value of a person’s lifestyle or habits.

One possible starting point may be existing unfair trade practice laws in every state, which prohibit unfair discrimination and require actuarial justification for underwriting. However, it is clear that better enforcement of these laws would be necessary to ensure fairness. Ultimately, it is clear that, at this economically precarious time, policymakers must reexamine and improve existing private and public programs that provide support to individuals and families facing the fiscal impact of serious illness and death. These programs, including Social Security Disability Insurance, Supplemental Security Income, Workers Compensation, and a range of employer-based programs, need a fresh look.

In sum, GINA has not solved every issue related to genetic testing and health. But it has highlighted the urgency in finding our way forward. Reform efforts must protect not just genetic information itself, but also access both to the actual care that is critical for prevention, early detection, and treatment, and to the support systems that help individuals care for themselves and their families when serious illness strikes.

Susannah Baruch is the Law and Policy Director at the Genetics and Public Policy Center at Johns Hopkins University.

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.