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.

The promise of the field of synbio as a whole is that scientists will be able to employ this type of genome synthesis to create customized life forms for a wide array of purposes. The peril is exactly the same as the promise.

Rising to this demanding task, committee chair Amy Gutmann, president of the University of Pennsylvania, led a constructive conversation by asking pointed questions and periodically distilling the major points of contention and agreement among the various discussants. Drew Endy of Stanford University, a pioneer of synthetic biology, praised the meeting as the best conversation on synthetic biology that he has ever seen. The reason, he said, was that the most striking development over the course of the two-day conversation was its shift from simply avoiding the risks of synthetic biology to carefully harnessing its benefits in a way that is attuned to broader global challenges.

Jim Thomas of the ETC Group, a Canadian green civil society organization, prompted this major turn in the conversation towards synbio’s global socio-economic implications by emphasizing the economic displacement that takes place when a new technology like synthetic biology enters the global economy. For instance, a synbio technology that allows an industry to grow an organic product in a vat for a lower cost than it could on the land would destroy the livelihood of thousands of farmers the world over. Thomas’s position was distinctly green and scientifically prohibitionist since he advocated a moratorium on the commercial or environmental release of synthetic biology products.

Indeed, upon further questioning by the commission, it seemed as if he were advocating more of a ban than a moratorium since he could not arrive at a concrete “bottom line” for the safety and equity standards that synbio would have to meet for the moratorium to be lifted. He suggested the creation of new “social technologies” for assessing the social and economic impacts of technology and building democratic consensus among global populations. He noted that there is currently no democratic way of allowing the release of synbio technology, to which Dr. Gutmann retorted that there is no democratic way of banning it either.

The dialogue prompted Allen Buchanan of Duke University to provide a more tech-positive counterpoint to Thomas’s claims about the vulnerability of the global environment. Buchanan argued that objections about “playing god,”  “interfering with nature,” or “altering human nature” are often used to smuggle in assumptions about nature being inherently harmonious, stable, or balanced.  He explained that nature is in a constant state of flux and that evolution is an imperfect process that “at most…fleetingly approximates maximal biological fitness.”

Assumptions about nature being benign or harmonious automatically stack the deck against any biotechnologies. Since risk can never be completely eliminated, Buchanan encouraged the commission to educate the public about risk management, its costs, and the importance of institutional designs that create the incentives for accurate risk management. And he did agree with Jim Thomas’s suggestion that effective institutions will require the development of new “social technologies.”An emphasis on social technologies seemed to appeal to the commission and many of the presenters as a new frontier for promoting scientific innovation in a way that is safe, responsible, and democratically accountable without over-relying on top-down regulation.

More controversially, Buchanan clarified the meaning of “dual use” by subdividing it into two types. The more commonly understood form of dual use is the possibility that terrorist groups or rogue states could misuse a technology like synbio, but Buchanan also proposed that “good” actors or states could use synthetic biology for offensive purposes in the name of defending themselves. As an example, he pointed to the grossly unethical human radiation experiments perfumed by the U.S. government from 1944 to 1973.

Buchanan concluded by encouraging the commission to focus on these concrete risks and benefits and not get bogged down with more intrinsic unanswerable questions about human nature, the meaning of life, or the implications of biological materialism for human moral agency. He was clearly asking for the commission to be decisively pragmatic in its recommendations for managing the risks and benefits of synbio without completely ignoring various theoretical views and approaches.

During the audience Q & A period, Gerald Epstein of American Association for the Advancement of Science reminded the commission that synbio will only be one component of much larger issues that humanity faces and that and it should try to analyze the implications of synbio for social justice, human security, or the environment “as a whole.” These discussions moved the conversation toward an emphasis on concrete risks and benefits of synbio for a diverse and complex global environment.

The second day of the meeting continued to place synthetic biology in this broader context. Paul Wolpe of Emory University reminded the commission that humans create technology that then goes on to recreate human existence—examples of this range from the plow, to the car, to the Internet. He speculated on the numerous effects that synbio can have on human lifestyles and humankind’s conception of itself, but he eventually zeroed in on the contrast between the value that humans place on speed and the human impulse to respond to technology incrementally.

Synbio will increase the speed of various biological processes, but humans will only come to understand it incrementally, not realizing the transformative potential of the technology until it has actually transformed our lives. It is this fear of incremental steps toward an irrevocable transformation of human existence that has underpinned some of the behavior-based religious systems and even the “playing god” objection. Wolpe recommended that the commission address synbio in “a positive way by creating goals and incentives rather than trying to stop things.”

He also cautioned that this positive view of synbio’s capabilities be tempered with a wisdom that avoids fetishizing science by over-relying on arguments based on utopian visions or a hyperbolic sense of urgency. So, not only must the commission focus on managing concrete risks and benefits in a global environment, it must understand those risks and benefits in terms of the diverse cultural and religious values held by many of the world’s populations. The commission must also be humble enough to understand that common beliefs about the beneficent power of science and society’s ability to grapple with its implications as possessing their own biases and limitations.

This line of discussion made the meeting as a whole very productive. It elucidated many of the most compelling arguments for a positive, risk management-based, globally-contextualized, culturally self-aware, and pragmatic approach. By coupling this approach to the specific safety and oversight concerns of scientists, business leaders, government officials, and everyday citizens, the commission can find a way to be open to various views of scientific progress while also being critical of them as it makes concrete recommendations. This is what a bioethics commission should be doing, paving a confident path through the ethical forest while respecting the great variety of the trees.

Michael Rugnetta is a Research Assistant to Jonathan Moreno for the Center for American Progress’s Progressive Bioethics Initiative and Science Progress.

23andMe, a personal genomics company co-founded in 2006 with investment from Google, Inc., just published its first genome-wide association study in the online journal PLoS Genetics. The decision by the journal’s editors to proceed with publication brings to light some of the more overlooked controversies surrounding direct-to-consumer, or DTC, genetic tests involving the methods of data collection and concerns about consumer privacy.

The study comes out of 23andMe’s participant-driven research program, 23andWe, which looks for genetic correlations for traits such as curly hair, freckles, photic sneeze reflex (the tendency to sneeze when entering bright light), and asparagus anosmia (the inability to smell asparagus metabolites in urine). 23andMe analyzed the data of 10,000 of their “whole-genome scan” customers who also filled out a survey about their health and physical traits, or phenotypes. Some are heralding this as a new paradigm for genetic research where scientists look for patterns in huge datasets rather than forming small, tailored studies to test specific, narrow hypotheses.

Indeed, these large genetic datasets have the potential to reveal powerful knowledge about public and personal health. Yet there is serious concern about how private companies will generate revenue from this data and whether the government will seek access to this data in the case of public health, public safety, or national security emergencies. Although the Genetic Information Non-Discrimination Act of 2008 prohibits employers and health insurance companies from accessing an individual’s genetic information, there are no uniform rules about other third parties acquiring genetic data from private companies like 23andMe. Long-term care, disability, and life insurance companies can still discriminate based on genetic information since they are not covered by the new law.

The editors of PLoS Genetics took these concerns seriously. They held up publication of the paper for six months to debate ethical concerns such as institutional review, participant consent, and data access. Ultimately, the journal’s editors were satisfied once they were able to ascertain that no participants had been coerced and all were aware that their samples would be used for research. The editors, Greg Gibson and Gregory P. Copenhaver, authored an accompanying editorial explaining this rationale.

Concern was originally raised when PLoS found that the manuscript was submitted without any institutional review board documents, which are customary with what is known as “human subjects research.” 23andMe later submitted a report from an accredited, independent review company, which affirmed that the 23andMe study did not fall into the category of “human subjects research.” This was based on two criteria: that the researchers did not have any direct contact with the study participants, and there was no way for the researchers to associate the data with individual participants since the data seen by the researchers was made anonymous.

PLoS also scrutinized the consent forms that participants were given when they signed up to be a part of 23andMe’s research efforts. 23andMe supplies a lengthy document detailing the potential risks of “unanticipated self-knowledge,” and the curious disclaimer that their services are “not designed to diagnose disease or intended to provide medical advice.” PLoS determined that if 23andMe had an independent review board review their document beforehand, there might have been significant changes to it, but accepted it because the document nevertheless met minimal legal requirements and any post hoc changes would require re-consent of thousands of participants.

PLoS noted, however, that for future research when “a study does not meet the aforementioned [human subjects research] criteria but obtaining a consent form would still be desirable, there are no guidelines or policy with regard to how such a consent form should be developed and reviewed in an ethically responsible manner.” PloS editors Gibson and Copenhaver then called for a review of the institutional review board consent process for genome-wide associated studies. They anticipate that new standards will and should evolve for GWAS research since institutional review boards are not always staffed by experts in genetics who would be more aware of the full implications of this research for subjects.

For consumers of personal genomics tests, this means researchers will need to be more transparent about:

• The conclusions reached from analyzing genetic data
• The potential health benefits or risks to the consumer
• The possibility of new cures or treatments that arise from analyzing one’s data
• The protocols surrounding the transfer of data to third parties

This last point is especially important from a public policy perspective as it becomes easier for scientists to mathematically determine the presence of an individual’s genome in an otherwise anonymous dataset.

Even though 23andMe does have a policy of not turning over individual-level genetic information to third parties without follow-up consent from their customers, 23andMe could still give it up if “required by law.” One can only speculate as to the circumstances under which the government would demand access to 23andMe’s genetic data by law, but it could be for any number of national security, public safety, or public health reasons. These policies are still quite ambiguous since the federal government so far has yet to establish uniform rules for how the various state FBI offices can obtain and utilize genetic data from criminal suspects, as Science Progress detailed last year in an article by Natalie Ram.

Personal genomics holds great promise, and the federal government has already taken measured but important steps toward ensuring that genetic tests are reliable. The National Institutes of Health recently announced the formation of a voluntary genetic test registry where companies can post the scientific data supporting the claims made by their tests so that physicians and consumers can make comparisons. And the Food and Drug Administration announced that it will hold a meeting next month to discuss the regulation of lab-developed tests for genetics, over which the FDA has heretofore not exercised its jurisdiction. Both of these policies were recommended in a 2008 CAP report, “Genetic Non-Discrimination.”

Additionally, with the passing of health care reform and the stimulus act in 2009 the Department of Health and Human Services is making great strides in setting up a new infrastructure for health information technology. This holds great potential for making medical record-keeping much more efficient and also providing patients and care providers with the latest data on tests and treatments at the point of care.

Of course, there are enormous privacy issues, and the Health IT Policy and Standards Committees are currently working on this. In the Science Progress report, “Paving the Way for Personalized Medicine,” we highlight the appropriate roles of these various government bodies for ushering in an era of personalized medicine, where physicians have the best science available at the point of care to get the right treatment to the right patient at the right time. In the report, we also recommend that a high-level office in HHS undertake an initiative to coordinate personalized medicine-related activities across the agency. The Genomics and Personalized Medicine Act of 2010, HR 5440, which was introduced last month by Rep. Patrick Kennedy (D-RI), actually goes so far as to create an entirely new Office of Personalized Healthcare.

All of these public policy initiatives will touch upon genetic testing as it relates Information privacy, scientific validity, and medical utility—all cornerstones of this new personalized medicine approach to health care. 23andMe’s article is only the beginning of a new era of subject recruitment, data collection, and research output. The federal government will definitely need to keep up with the private sector.

Michael Rugnetta is a Research Assistant to Jonathan Moreno for the Center for American Progress’s Progressive Bioethics Initiative and Science Progress.

The leader of the study is UCI’s Hans Keirstead. Using a differentiation technique, whereby human embryonic stem cells can be instructed to become particular types of cells, Keirstaed and his team were able to engineer this early stage retina. Retinal engineering could be an important part of a therapy for the millions of Americans who suffer from macular degeneration and other retina diseases.

Keirstead’s work demonstrates the value of embryonic stem cell research. Embryonic stem cells are unique because of their ability to differentiate into any of the 200-plus different types of human cells, which makes them the “gold standard” for conducting research on the mechanics of cell development and the generation of new therapies.

Although the Obama administration has lowered some barriers to federal funding of embryonic stem cell research, the president also ordered the National Institutes of Health to adopt strict ethics guidelines. The guidelines stipulate that only cells leftover from in vitro fertilization therapy can be used to derive cells for research, donors must provide informed consent and cannot receive any compensation for their cells, and the donors must be provided with other options for the disposition of their cells before they can donate the cells for research.

As stem cell therapies like retinal replacement move from the lab bench to clinical trials, the Food and Drug Administration will need to be cognizant of the new technical and ethical concerns that come with this research. To this end, we proposed in our January 2009 report, A Life Sciences Crucible, an expansion of the Recombinant DNA Advisory Committee, which was formed in 1974 by the NIH. Made up of a diverse set of experts, including scientists, ethicists, patient advocates, representatives from private industry, and so on, the RAC could behave as an oversight panel.

We state in the report that “if the trials involve ‘protocols that raise novel or particularly important scientific, safety, or ethical considerations,’ then the RAC will discuss the research at one of its quarterly public meetings.” The function of the RAC will be to supplement the FDA in its efforts to monitor this new and evolving area of scientific inquiry.

The research conducted at UCI may someday lead to monumental advances in the way we treat illness and injury by allowing us to live longer, healthier lives. But as is always the case when exploring uncharted territory, we must take extra care to ensure that knowledge and innovation are not achieved at the expense of our ethics or our safety. As long as we proceed with an eye to ethics, we may one day soon be able to look back at retinal diseases and spinal cord injuries in much the way we view infectious diseases, as dreadful burdens overcome by human endeavor.

Michael Rugnetta is a Research Assistant with the Progressive Bioethics Initiative at the Center for American Progress.

The president instructed Gutmann that the report should consider the “potential medical, environmental, security, and other benefits of this field of research, as well as any potential health, security or other risks.” He also asked that “the Commission should develop recommendations about any actions the Federal government should take to ensure that America reaps the benefits of this developing field of science while identifying appropriate ethical boundaries and minimizing identified risks.” Finally, he directed the Commission to “consult with a range of constituencies, including scientific and medical communities, faith communities, and business and nonprofit organizations.” The Commission will have six months to deliver its recommendations.

The inquiry should open an inclusive dialogue on the material and ethical implications of the research while emphasizing pragmatic action for the government to take. Eric Meslin, former director of the National Bioethics Advisory Commission under President Clinton, wrote in a recent article for Science Progress that “deliberations must not only be rigorously supported by good science and good ethics, but must also include strategies to translate its recommendations into implementation.” Citing his experience with NBAC in the mid-1990s, he presciently warned that “even when you plan to take a slow and steady approach to developing the commission’s working style, along comes a cloned sheep from Scotland or the unexpected announcement of the isolation and culture of human embryonic stem cells to throw a wrench into existing priorities. The PCSBI should expect the unexpected.”

The announcement of the first organism “booted up” from a synthetic genome is a similarly monumental breakthrough, and an unexpected but welcome opportunity.

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.

There are three major provisions in the new law that promise to bring care-enhancing innovations to patients everywhere. The Cures Acceleration Network, or CAN, will speed new therapies from bench to bedside. The Patient-Centered Outcomes Research Institute will bring develop and disseminate information on the effectiveness of different treatments. And the Qualifying Therapeutic Discovery Project Credit will support small biotech firms investing in new treatments for unmet and chronic care needs.

The goal of the Cures Acceleration Network, introduced by Sen. Arlen Specter (D-PA), is “to accelerate the development of high needs cures,” defined by the legislation as priority treatments “for which incentives of the commercial market are unlikely to result in adequate or timely development.” These therapies may include regenerative medicine treatments that rely on decoding genes and mapping complex biochemical pathways for diseases like Parkinson’s, ALS, or multiple sclerosis.

The new law authorizes $500 million for fiscal year 2010, allocated through grants or contracts that may not exceed $15 million. The contracts are termed “partnership awards” and require the recipient to contribute matching funds of one dollar for every three federal dollars, whereas the “grant awards” do not require a match. The National Institutes of Health director is also given the authority to dispense no more than 20 percent of the appropriated funds at his own discretion for “flexible awards.”

As well, another component of the Cures Acceleration Network mission will be to facilitate Food and Drug Administration review of these high-needs cures. The bill instructs the FDA to coordinate its approval requirements with CAN’s activities and to provide technical assistance in order to expedite product development and approval.

CAN will also promote personalized medicine by supporting the development of diagnostics, preventative therapies, and behavioral therapies, as well as biomarkers that can predict the safety and effectiveness of such therapies for patients based on their individual genetic makeup.

Senators Max Baucus (D-MT) and Kent Conrad (D-ND) originally introduced the Patient Centered Outcomes Research Institute last summer in separate legislation. I explained then that the project was “designed to ramp up medical innovation for the common good by championing a new era of personalized medicine.”

This Institute will be tasked with organizing, funding, aggregating, and disseminating comparative effectiveness research, which looks at two or more treatments side by side to see which produces better health outcomes for a particular group of patients. The version of the Institute enacted in the health reform bill will be established as a non-profit entity that is completely separate from the federal government. A dedicated tax stream will fund the Institute’s trust fund beginning in 2013, but the law also appropriates Treasury funds for the trust fund from 2010 until 2019, when both sources of funding sunset.

Research at the Institute will pay special attention to the needs of subpopulations including “racial and ethnic minorities, women, age, and groups of individuals with different comorbidities, genetic and molecular sub-types, or quality of life preferences.” It will explore the impact of where treatments are in the product development process and the skill level of health professionals administering the treatment to see how those factors impact effectiveness. These are real-world considerations that other forms of research like clinical trials often miss.

Most importantly, the Institute is charged with making its data comprehensible, protecting patient privacy and confidentiality, and explaining the data’s limitations and relevance for subpopulations. The Personalized Medicine Coalition, a non-profit representing a broad array of private, public, non-profit, and academic stakeholders has praised the bill’s establishment of the Institute and its thorough incorporation of personalized medicine.

The law also contains good news for small biotech companies, specifically those with less than 250 employees. These firms will be eligible for a tax credit equal to 50 percent of their investment in any “qualifying therapeutic discovery project.” These can include pre-clinical studies, clinical trials, or other clinical studies conducted for the purpose of winning FDA approval of a treatment, diagnostic, or treatment delivery technology. Companies will need to apply for these tax credits and the total amount may not exceed $1 billion for FYs 2009-2010. The projects must possess certain attributes, such as the potential to treat chronic conditions or ailments in areas of unmet need, reduce long-term health care costs, or contribute to curing cancer. The selected projects must also have “the greatest potential to create and sustain high quality, high-paying jobs.”

Another issue addressed by the law has to do with the biologics industry. Biologics are drugs composed of large, complex molecules that are manufactured through complicated cellular processes, as opposed to small-molecule drugs that are manufactured through simple chemical reactions. Since these drugs are so complex that a firm can create a generic version of an existing drug that is similar enough to fit into the same drug class but different enough to avoiding infringing the patent for the reference drug. These generics are referred to as “biosimilars” or “follow-on biologics.” The health reform law alters the landscape for biologics by establishing a clear FDA regulatory pathway for biosimilar drugs while simultaneously establishing a 12-year period of market exclusivity protection for the companies that create the original biologics. Early reports indicate that the new law seems positive for the biotech industry as a whole.

The legislation also leverages transparency efforts to reduce conflicts of interest within medical research and clinical practice. In 2013, the Department of Health and Human Services will begin tracking the funds and gifts that the medical industry provides to physicians, researchers, and hospitals through reporting requirements. This information will then be made available in a public database.

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

Specifically, the legislation ensures that the cells are procured from embryos that were created through in-vitro fertilization for reproductive therapy, were deemed in excess of the patient’s clinical need, and would otherwise be discarded. The patients must also provide informed consent and must not receive any financial inducements.

These provisions uphold basic values that protect the autonomy of embryo donors and grant special consideration to the moral status of the embryo while also fostering the advancement of scientific knowledge for the common good and the benefit of patients everywhere.

It is encouraging to see legislators championing the intellectually robust research standards that the bioethics community has consistently advocated over years of sincere and informed discussion on the science and ethics of stem cell research.

1) The FDA will hone its regulatory approach to adapt to the emerging science of personalized medicine.

Hamburg described the FDA’s plans to build on previous successes by issuing new draft guidance this month on biomarker identification, which will give therapy developers a better idea of how to submit data on genes and proteins to the FDA so that therapies can be tailored to work on patients with specific biomarker profiles. She also encouraged the development of new clinical trial designs through university Centers of Excellence for regulatory science.

Hamburg touted the personalized medicine success stories of the past few years, such as genetic tests that can help calibrate dosing for the widely used blood thinner warfarin, and the HIV drug abacavir, which requires a genetic test to determine if a patient has a form of the virus that will respond to the drug. She also described the fruitfulness of the FDA’s Voluntary Genomic Data Submission Program. Since its inception in 2005, industry has warmed up surprisingly well to the program by submitting substantial amounts of data on the relationship between drugs and genes.

Hamburg also emphasized that in order to ensure the safety and effectiveness of these new personalized technologies, the FDA must adopt an approach to monitoring the entire “life-cycle” of a product, which necessitates post-market follow-up research. She noted that the FDA plans to devise post-market research protocols and that once they are established, it will also make regulators and businesses more confident about the pre-approval process.

2) The FDA is forming crucial interagency collaborations.

The central argument of our report—the need for interagency collaboration—was another focus of her address. The day before her address to the Personalized Medicine Coalition, Hamburg joined National Institutes of Health Director Francis Collins and Department of Health and Human Services Secretary Kathleen Sebelius to announce a new collaborative effort between the NIH and FDA designed to advance regulatory science.

Hamburg explained as well that there have been discussions between FDA and Agency for Healthcare Research and Quality, on some research topics, although she did not mention any specifically. More controversially, an audience member also questioned Hamburg about the possibility of collaboration between the Centers for Medicare and Medicaid Studies, which determines reimbursement, and the FDA. We discuss this in our report as an important way for the FDA to gather information about the real-world usage of drugs and devices and for companies to have a better idea of the economic viability of their products, as has been done with the genetic tests surrounding the drug warfarin, which are only reimbursed if the patient is part of a clinical trial.

3) FDA is making its processes more transparent

Hamburg acknowledged that coordination between CMS and FDA may raise many concerns because the reimbursement rates determined by CMS heavily influence the profitability of drugs and diagnostics, but she made clear that the FDA will need to clearly explain to the public the scientific evidence and administrative rationale behind the decisions that these agencies make. Along with greater flexibility and collaboration, Hamburg considers the transparent sharing of evidence and explanation of policy rationales as one of the major components of FDA modernization.

One of the more logistically complex issues for the future of personalized medicine is the need for coordination between the genetic test manufacturers, the drug manufacturers, and the health care providers. For instance, Hamburg described the FDA’s “scenario-based” approach to “companion technologies” such as a genetic test that is coupled to a drug whose effectiveness on a patient can be determined by the results of that test. While some drugs and diagnostics will be developed in tandem, others will follow separate paths through different companies. Hamburg acknowledged that this will require some process by which different companies can be made aware of all the data coming into the FDA from different sources that may be relevant to each specific product.

The NIH announced in the Federal Register on Tuesday that it plans to tweak its stem cell guidelines in order to accept a wider array of scientifically promising human embryonic stem cells. Currently, the NIH defines acceptable hESCs as “cells that are derived from the inner cell mass of blastocyst stage human embryos.” This definition excludes stem cells that are cultivated from younger embryos that have yet to reach the 70-100 cell blastocyst stage.

This practical problem with this definition came to light when Massachusetts-based Advanced Cell Technology submitted five lines of pre-blastocyst derived cells for NIH approval [correction: an earlier version of this post erroneous said ACT was Nevada-based]. As a result the NIH reviewed the 40 lines it has already approved and put three of them on hold upon learning that they also came from pre-blastocyst embryos. This hold will remain until the NIH officially changes the regulatory definition to cells derived from embryos “up to and including the blastocyst stage.”

Lana Skirboll, who directs the NIH Office of Science Policy, describes the change in a Nature News article as a “small technical revision.” She also reiterates the NIH commitment to transparency by stating, “If we were going to change a comma in the guidelines we might put out a Federal Register notice.” The notice is open for comments until March 25^th.

Bernard Lo and colleagues made a different policy suggestion concerning the informed consent process in a Science Policy Forum. Currently, the NIH only requires informed consent from the in virto fertilization patients donating excess embryos and not from the people who donated the gametes (sperm or eggs) that created those embryos. In the paper Lo et al. write that, “Using embryos for research without permission of third-party oocyte donors could fail to respect donors as persons, breaching a fundamental principle of bioethics.”

The authors examine the possibility of requiring the gamete donors to provide informed consent along with the IVF patients before the embryos are donated for research, but they deem this too cumbersome a remedy. Currently, gamete donors sign a form giving the IVF patient legal authority to determine the use of embryos created with their gametes after infertility treatment has been completed.  This is known as “dispositional authorization” or the granting of “dispositional authority” to the IVF patients.

The problem with this process is that the gamete donors are not always completely aware of all the possible uses, or dispositions, for the embryos, which are numerous and include hESC research, donation to other patients, or destruction. Gamete donors currently do not give explicit informed consent for any of these dispositions when they grant blanket dispositional authority to the IVF patients.  The problem with requiring the gamete donors to give informed consent for all possible dispositions is that the informed consent process itself has numerous built-in requirements including the provision that the gamete donor incur no loss of benefits if they do not give consent.

To avoid additional complications that might diminish other bioethical protections, the authors argue that hESC research be included as part of a disclosure of information regarding disposition. That is, anyone donating sperm or eggs should be informed that one potential use of their tissue may be to procure human embryonic stem cells for research. This could mean simply that hESC research is listed as a possible use on the dispositional authorization form or that literature regarding hESC research be provided to the gamete donors before authorization. The main point being that under this new policy, an IVF clinic, sperm bank, etc. can confirm that donors received information regarding research as a dispositional option.  Gamete donors can choose to grant restricted or unrestricted dispositional authority and the IVF patients can then choose gamete donors based on the level of dispositional authority that they grant.  Thus, the decisions of the gamete donors do not restrict the decisions of the IVF donors.

The policy they propose the NIH adopt was included in the recommended guidelines of the National Academy of Science and the International Society for Stem Cell Research, and is followed by many Institutional Review Boards, a fact that would make it easier for those institutions to accept NIH approved cells for research if the NIH changes its policy.

The authors recommend that previously approved NIH stem cell lines be grandfathered in as long as dispositional authority was granted by the gamete donors, and that there are strong scientific reasons to use the cells, and that other legal requirements are met.

These recommendations, along with the NIH’s regulatory revision, demonstrate that ethical policymaking in this arena is an ongoing process that preserves core bioethical principles such as personal autonomy, human dignity, free scientific inquiry, and administrative pragmatism through open dialogue and transparency.

Alzheimer’s, after all, affects such a large part of the brain that treating it with injections of cells would almost certainly be futile. (Parkinson’s disease, by contrast, involves a very small area in the brain so has real of hope of being helped by injections of replacement cells there.)

But that doesn’t mean that research involving human embryonic stem cells might never play a crucial role in developing treatments for diseases like Alzheimer’s. The reason: because stem cells can develop into any kind of cell in the body, scientists can potentially use them to grow model tissue samples and test drugs without the need to experiment on a human subject.

Stem cells are powerful tools for developing treatments not just because they can regenerate damaged tissue, but because as they grow, scientists can use them to understand the basic biology of a disease.

Researchers at the University of California San Deigo have recently taken just such a step forward in their ability to understand the development of genetic diseases. The scientists substituted an altered cancer-causing gene and a gene for a rare movement disorder in the genomes of embryonic stem cells. Since embryonic stem cells perpetually renew themselves and can differentiate into any type of cell in the human body, this afforded them the opportunity to study the development and behavior of the diseases. Future research can test new drugs and therapies on these human cell models before moving to a clinical trial, making it possible to develop safe and effective drugs in a cheaper and faster manner.

The researchers note specifically in their article in Cell Stem Cell that these two hESC disease models “will become valuable resources to study human tumorigenesis and develop more effective therapeutic interventions for human cancer.”

For years, scientists have studied human genetic diseases with what are known as “knock-out” mice. In this process, scientists “knock-out” or disrupt a gene of interest in mice so that they can observe the effect of the disease on its cells. Since mouse biology is different from human biology, these models present limitations.

Scientists have also tried to use induced pluripotent stem, or iPS, cells. In this process, a mature body cell, for instance from the skin, that carries a genetic disease is converted into a stem cell by adding a combination of genetic and chemical factors. The problem with these cells is that since they are diseased to begin with, they usually have other genetic defects that complicate the study of the disease in question.

The study was funded by the California Institute for Regenerative Medicine and utilized cells from the lab of Dr. Doug Melton at Harvard. Some of the Harvard lines have recently been approved for NIH funding so we should all stay tuned for more of these revolutionary breakthroughs with hESCs.

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.

This address was part of an awards ceremony for over 100 science teachers and mentors from across the country who have demonstrated outstanding work. President Obama also announced the creation of five new public-private partnerships aimed at raising U.S. students to the top of international math and science rankings in ten years.

These initiatives are the newest component of the administration’s “Educate to Innovate” campaign, which kicked off in November with an initial commitment of $260 million from philanthropic organizations and individuals. The initiative is designed to unite and engage citizens, institutions of higher education, non-profits, and businesses alike in the effort to propel STEM education in the United States. Obama has outlined three goals for the campaign: increasing students’ STEM literacy and critical thinking, improving math and science teaching, and expanding opportunities for groups underrepresented in STEM fields like women and minorities.

The new initiatives total an additional $250 million and include efforts by companies like Intel, Texas Instruments, PBS, and a coalition of 75 presidents of public universities, which has committed to train 10,000 science and math teachers annually by 2015.

As further evidence of the federal government’s commitment to improving STEM education in the United States, the president also cited the “the largest investment in education by the federal government in history” in the American Recovery and Reinvestment Act, as well as specific initiatives such as the Department of Education’s $4.35 billion “Race to the Top” fund, and the Department’s plan to provide $10 million in grants to support innovative teaching and $43 million in grants for 28 Teacher Quality Partnership programs at colleges of education and in high-need school districts.

While the president recognized the government’s responsibility to provide greater support for the recruitment, preparation, and retention of quality teachers to improve the nation’s education in the sciences, he also reaffirmed his challenge to the scientific community to “to think of new and creative ways to engage young people in their fields.” In response to this, the scientists at NASA will organize a multi-year “Summer of Innovation” enrichment program in which NASA scientists and engineers will work with thousands of teachers and students to work on cutting-edge STEM learning opportunities.

Other companies and organizations involved include the Bill and Melinda Gates Foundation and the Carnegie Corporation of New York, which are recruiting private sector leaders to advocate for STEM education in the states; Time Warner Cable, which is running a public service campaign; Sony Computer Entertainment America, which is launching a contest to design the best STEM-related video games for children; and the grassroots “National Lab Day” effort which is committed to working with 10,000 teachers and 1 million students this year.

A team of researchers at the University of Michigan analyzed this limited genetic diversity in a paper published yesterday in the New England Journal of Medicine. They investigated 47 lines including 13 of the 21 Bush-era lines and 22 of the 27 newly approved Harvard lines.

The research team estimates that there are about 700 hESC lines available in the world, but that the 47 they investigated are the most widely used. The authors conducted a genotype analysis for the stem cells, looking at 500,000 single nucleotide polymorphisms along each line’s genome. Each of these represents a point in the DNA sequence where notable variations occur. They then compared the cell line genotypes to those of 2,001 subjects from the HapMap Project and Human Genome Diversity Project, which map human genetic diversity around the world. Two of the Bush-era lines, which came from labs in Singapore, are of East Asian origin, and three others were of mixed Middle Eastern and European origin. According to a University of Michigan press release, “none of the lines were derived from individuals of recent African ancestry, from Pacific Islanders, or from populations indigenous to the Americas.”

This unfortunate reality underscores the need for not only expanded hESC research, but also for more diverse research. The Bush-era policy was clearly inadequate and the new policy fortunately allows for much more freedom in conducting research. But if we really want to realize the promise of stem cells, scientists will need to work with lines from diverse genetic origins. That is the only way to design treatments and therapies that work for all populations. Diseases manifest themselves differently in different populations, whether because of genetics or environment. There are also the problems of side effects and treatment effectiveness that scientists can only properly assess when treatments are tailored to specific populations.

Jonathan Moreno and I recently wrote about this very issue as it concerns the Latino community at the Lationvations website.

Michigan’s new Consortium for Stem Cell Therapies plans to attack this issue of limited genetic diversity in the cells head-on by deriving lines that carry the genes responsible for inherited diseases and by also deriving lines from underrepresented groups like African-Americans.

Harvard submitted 28 lines for review, but one was rejected, as it was derived with a consent form that came during a lapse of the university’s institutional review board. Researchers at the university had been using the lines for various projects without federal dollars, but the consent forms for the lines specifically state that the lines support diabetes research:

These cells will be used to study the embryonic development of endoderm with a focus on pancreatic formation. The long-term goal is to create human pancreatic islets that contain ß cells, the cells that produce insulin, for transplantation into diabetics.

The NIH prudently chose to abide by the consent forms, so researchers will only receive federal funds to work on the lines if they follow those rules. NIH Director Francis Collins made this decision after the Advisory Committee to the Director recommended the rules to him following its December 4^th meeting. The Committee also requested that the NIH issue guidelines regarding the broader use of embryos derived for a specific purpose, but according to Jef Akst at The Scientist, “the NIH has not responded.”

The NIH did however update its FAQ page, explaining to researchers that the NIH stem cell guidelines require informed consent from embryo donors, which is different from the provisions in the “Common Rule” governing most federally funded biomedical research—the Common Rule does not require consent for de-identified human cells. The NIH has also decided to honor any restrictive language in the informed consent forms regarding the scope of the allowed research.

We should commend the NIH for dealing with these nuances and complexities in an ethically consistent manner that respects the wishes of the embryo donors. This process embodies a genuine understanding of how scientific necessity, administrative transparency, and ethical clarity can lead to sound policies.

Eighty-three more lines are pending review, and we look forward to seeing them receive the same level of serious ethical scrutiny.

These new policies implemented President Obama’s March 9^th Executive Order, which marked a much-needed departure from President George W. Bush’s policy. The former president’s ethical guidelines for federally funded human embryonic stem cell research were limited simply to a declaration that no government money could support work on lines derived before August 9, 2001. This left scientists with only 21 lines of low scientific quality and ethically questionable origins.

Eleven of the 13 new cell lines came from Children’s Hospital in Boston and the other two came from Rockefeller University in New York and were approved through the NIH’s normal administrative review process. There are 96 more lines awaiting approval either through the same process or by an alternative process for cell lines derived before the new guidelines went into effect. As part of that alternative process, approximately 20 lines will be reviewed tomorrow by the NIH Advisory Committee to the Director. Now that these 13 lines have been added to the NIH Human Embryonic Stem Cell Registry, research can begin on the 30 hESC research projects that have received over $20 million in NIH grants for 2009. According to the NIH press release:

This group of grants includes research using hESCs for the therapeutic regeneration of diseased or damaged heart muscle cells, developing systems for the production of neural stem cells and different types of neurons from hESCs in culture, and developing a cell culture system for the large scale production and self-renewal of hESCs.

The approval of the lines could not come at a better time. As Ali H. Brivanlou, a researcher at Rockefeller University who had to segregate privately and federally funded research activities under the Bush regime, told The New York Times, “You can imagine what it meant not to be able to carry a pipette from one room to another.…They even had to repaint the walls to ensure no contamination by federal funds.”

Indeed, Science Progress is glad to see that scientists can now do their work uncontaminated by bad bioethics policy.

President Obama said this in the White House press release:

As our nation invests in science and innovation and pursues advances in biomedical research and health care, it’s imperative that we do so in a responsible manner. This new Commission will develop its recommendations through practical and policy-related analyses. I am confident that Amy and Jim will use their decades of experience in both ethics and science to guide the new Commission in this work, and I look forward to listening to their recommendations in the coming months and years.

At Science Progress, we are glad that the president has chosen such distinguished scholars and leaders as Drs. Gutmann and Wagner to chair this commission. The Executive Order provides for a commission comprised of 13 members who will be appointed by the president for renewable periods of two years. We look forward to the announcement of the remaining 11 members.

The commission has been charged with not only identifying and examining important bioethical issues, but also with recommending laws, policies, or regulations. Finally, the EO encourages the commission to engage diverse viewpoints and explore opportunities for international collaboration.

Additionally, the commission is designed so that is will draw members from multiple disciplines ranging from science and bioethics to theology and law. At least one and not more than three of the members will be scientists or bioethicists from the executive branch. Finally, the EO lays out a list of timely, critical issues and ideas that will no doubt change our lives, and many of which staff and contributors have explored in Science Progress:

…the creation of stem cells by novel means; intellectual property issues involving genetic sequencing, biomarkers, and other screening tests used for risk assessment; and the application of neuro- and robotic sciences…the protection of human research participants; scientific integrity and conflicts of interest in research; and the intersection of science and human rights.

Update: The Executive Order establishing the commission is now available in the Federal Register.

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.

But thanks to H.R. 3276, introduced by Rep. Ed Markey (D-MA) with seven co-sponsors, the federal government will now begin to support isotope production here at home. The bill appropriates $163 million for fiscal years 2010 through 2014 to the Department of Energy so that it can support industry and universities in the production of the isotope known as molybdenum-99 (Mo-99), which decays into the medically usable isotope technetium-99m (Tc-99m). Tc-99m is used in tests for cancer, cardiac disease, and kidney function. Some tests determine whether a patient with a coronary blockage needs an angioplasty or a stent. Without it, patients might receive unnecessary surgery. These isotopes also identify the location of tumors in breast and bone cancers.

Medical isotopes can be produced using highly enriched uranium, referred to as HEU, or low-enriched uranium, called LEU. But transportation of HEU represents a national security risk, as it is “weapons-grade” material. Markey noted this in his floor statement: “Shockingly, the United States still allows for nuclear weapons-grade highly enriched uranium to be exported to other countries for medical isotope production. This 1950s-era policy simply does not work in a post-9/11 world.”

Wisely, the bill attempts to curtail the production and export of HEU while also allowing for the usage of HEU for isotope production if it is a feasible and expedient short-term alternative. For the long term, the bill promotes the development of LEU Mo-99 production. Hence, provisions for LEU and HEU Mo-99 production are contained in both the licensing and appropriation sections of the bill.

A National Academies of Science report from January found that eliminating HEU is both technically and economically feasible. Other organizations such as the Society for Nuclear Medicine and the Radiological Society of North America support the elimination of HEU in the long-term but stress the need for short-term solutions to the isotope shortage since the United States cannot get any LEU production sites up and running for approximately five to ten years due to the technical and regulatory hurdles.

Markey emphasized that the bill is technology neutral on his floor statement. “Neither this provision nor the bill as a whole give any preference whatsoever to any technology type,” he said, “The purpose of this provision is to give the Department of Energy the greatest number of options for dealing with the medical isotope crisis while also maintaining the incentive for reactors to convert to low enriched uranium fuel.”

The bill now goes to the Senate Committee on Energy and Natural Resources.

“You probably want to be sure they’re going to work so that your crab claws don’t turn into a complete exoskeleton,” he explained.

But in all seriousness, to design stem cell therapies that are effective and safe, scientists need to understand the full mechanics of the cell from its earliest developmental stages, and therefore must pursue many avenues of research. And that, as we have explained previously at Science Progress, will take time. Earlier this year, James M. Wilson, of the University of Pennsylvania underscored the importance of creating safe, responsible trials for stem cell therapies in an article in Science. Wilson understands first-hand the pitfalls of proceeding too quickly with a novel therapeutic technology, as he was the principal investigator in a gene therapy trial that resulted in the death of 18-year-old Jesse Gelsinger in 1999.

Collins also hit all the right notes in his explanation of personalized medicine, saying that it’s about “getting the right drug, at the right dose, for the right person.” It’s about “doing prevention in an individualized way instead of one-size-fits-all—taking advantage of the fact that we’re all different,” he said.

Just a few weeks ago Collins penned an article for Parade Magazine on the importance of pharmacogenomics and family history in treating cancer. It’s an important field of work, but the orchestra of federal agencies involved in the research and policy of personalized medicine is in need of a conductor, as Whitney Kramer and I explain in our recent report.

Here’s the full interview as Collins Reports to Colbert:

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.

The introduction of the key reprogramming genes cause the adult cells to revert back to a pluripotent or embryonic-like state. From there, both Chinese teams used the same technique, known as “tetraploid complementation.” In this process, two cells of a blastocyst are fused together and the iPS cells are then inserted. Since the chromosomes from each of the host mouse’s diploid blastocyst cells, which contain two copies of each chromosome, have been combined into a single tetraploid cell with four copies of each or twice the normal number of chrosmosomes, it cannot replicate and combine its genetic material with the iPS cell. This was a problem in early experiments that introduced iPS cells into blastocysts with only diploid cells, which produced new chimeric mice that possessed cells from two other genetically distinct mice—the mouse that provided the adult cells reprogrammed into iPS cells, and the mouse that supplied the blastocyst. In the tetraploid blastocyst, the genetic material from the mouse that supplied the blastocyst simply grows into placental tissues and the new embryo only possesses the genes from the iPS cells.

While both teams behind the studies published last week demonstrated that it is possible to grow live mice from reprogrammed cells, the group from the Institute of Zoology in Beijing and Shanghai Jiao Tong University managed better results, with a total of 27 live births. According to Nature News, “With their best cell line and optimal recipe, they were able to get 22 live births from 624 injected embryos, a success rate of 3.5%.” Their research appeared in Nature. The other team, from the National Institute of Biological Sciences in Beijing, published their study in the journal Cell Stem Cell and was able to get two live births from 187 attempts. However, one died in infancy.

Robert Blelloch of the University of California San Francisco’s Broad Center for Regeneration Medicine and Stem Cell Research told the Los Angeles Times that these studies can be characterized as a “brute force effort” since the basic technique was the same as previous unsuccessful attempts, but the teams just tried it over and over again with incremental changes until it worked.

This new research changes the bioethical landscape by demonstrating that, at least in mice, any somatic cell from an organism can be used to clone that organism. This is significant for ethicists who fall anywhere along the political spectrum—despite the fact that no reputable scientists are interested in cloning people, and given the low success rate and high death rate of the cloned mice using the new technique, this is something that would be grossly unethical to try in humans.

SP Editor-in-Chief Jonathan Moreno discussed the unforeseen ethical implications of advances such as this, which render every adult cell in the body a potential embryo in Science Next—a scientific possibility that conservative bioethics might fear even more than embryo destruction. You can read a long excerpt of his analysis here.

Image: Nature

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

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

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

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

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

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

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

As a safeguard, he recommends the National Institutes of Health establish a body like the Recombinant DNA Advisory Committee, which reviews any gene therapy trails funded by NIH, to conduct pre-clinical review of the basic stem cell research. This echoes the recommendation Michael Peroski and I made in our report, “A Life Sciences Crucible.”

Wilson fears that advocates and the media are overselling stem cells in the same way both groups oversold gene therapy in the 1990s. To avoid a similar fate for new therapies, he recommends thorough basic research, better communication of how that research process works, attention to realistic timeframes and scopes for stem cell therapies, and greater preclinical transparency. But similar to our recommendations, Wilson does not want this new board to add another level of bureaucracy to the Food and Drug Administration’s review. Its goal should be to allay public concerns and allow for transparent discussion of novel trial-related issues.

Boosters promoted novel gene therapies during the late 1980s and 1990s. There were over 400 gene therapy clinical trials worldwide by 2000. However, Wilson notes that in a September 2000 review, the FDA concluded that “the hyperbole has exceeded the results” and “little has worked.” Gene therapy did produce some positive clinical results that help curtail hereditary blindness and immune deficiencies. Nevertheless, there were many adverse events such as treatment-induced cancers and Gelsinger’s death.

Even though gene therapy was not burdened by a polarizing ethical debate like embryonic stem cell research, ethical and scientific warning signs went unheeded. In 1995, then-NIH director Harold Varmus convened a panel which issued a report concluding that there were “only a minority” of clinical studies that had been designed in ways that might yield “useful basic information” on gene transfer vectors and host-vector interactions. The panel recommended that more basic research was necessary to develop an understanding of gene transfer in animals. These warnings turned out to be right, since just about “every major unexpected toxicity encountered in gene therapy clinical trials can be attributed to complex interactions between vector and host that were not predicted by, or understood at the time of, preclinical studies,” as Wilson explains.

He assigns blame not only to the scientists but also to an uncritical news media, overeager patient advocates looking for a panacea, and the economic fervor surrounding the biotech bubble before it burst. But he remains slightly more optimistic about stem cell research, since there have been more papers published on the basic biology of stem cells than there were on gene therapy before the latter field’s first clinical trials. He still cautions, however, that researchers must look carefully at the clinical safety and utility of human embryonic stem cells and induced pluripotent stem cells, since “[q]uestions about engraftment, rejection, and toxicity abound.”

In our report, we note that the FDA, while still having ultimate authority, will nevertheless have a steep learning curve to overcome as stem cells enter clinical trials. Regulators, researchers, patients, and ethicists need a place to consider the adverse events, discuss the risks and benefits of the therapies, and issue general guidelines for FDA as it develops its own long-term protocols for clinical trials involving stem cells. Wilson even recommends that the Recombinant DNA Advisory Committee-like body consider whether the clinical guidelines developed by International Society for Stem Cell Research should be codified as NIH guidelines.

As stem cell research proceeds under the responsible and ethical guidelines outlined by the Obama administration, let us heed Wilson’s words of caution: “It would be unfortunate if the field of stem cell research missed this lesson from history” and “no one is served by bypassing the hard work of basic research and experiments in animal models.”

More on stem cells: Timeline: A Brief History of Stem Cell Research

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

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

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

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

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

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

For some time, the dialogue between conservatives and progressives on this issue has consisted of ad hominem charges. Consider John Derbyshire, writing recently at The Corner: “There is terrific social and political pressure on researchers, publishers, and commentators to put forward the most nurturist possible interpretation of every finding.” Some of the better-grounded discussions were able to delve into the empirical, methodological, and value-based assumptions as well as the statistical minutiae behind each side’s claims. (See William Saletan’s earnest, yet flawed, series on race and intelligence published last year in Slate and Stephen Metcalf’s critique of it.) Even though the connection between genes and IQ was subject to numerous caveats, the conservative genetic explanations for race and intelligence never really disappeared. This was due to the reductive appeal of genetic explanations for anything and the unfortunate persistence of educational inequalities.

For many years, it seemed the scientific jury was out and there was enough conflicting evidence to support any ideological bias. (This debate even makes for some strange ideological bedfellows, as it is easy, from the progressive vantage point, to agree with Leon Kass’s criticism of the Bell Curve. In this case, he is actually right about genetic explanations reducing the quality of human ability to mere quantity and the danger it poses to society by reinforcing prejudices.)

Fortunately, there has been a raft of scientific evidence in recent years demonstrating that environment matters much more than genes when it comes to an individual’s brain development and intellectual achievement. More importantly, this evidence has been making its way into the popular press and non-fiction, thus bringing digestible coherence to non-genetic explanations for intelligence. University of Michigan psychologist Richard Nisbett’s new book, Intelligence and How to Get It explains in rich yet accessible detail how myriad environmental stimuli can affect a person’s intelligence and educational achievement. This may seem obvious to many people, but the specific findings put forward by Nisbett and his colleagues demonstrate how policies, educational techniques, or environmental adjustments can improve the achievement of everyone from preschoolers mastering their ABCs to high schoolers taking the SATs. These findings are much more robust than the population-wide blanket correlations of the Bell Curve, which are used to advance the case for conservative “throw-in-the-towel” non-policies.

One of the best explanations Nisbett provides has to do with elucidating the concept of heritability, which many science popularizers misinterpret as the end-all-be-all calculation of nature versus nurture. In reality, heritability is about populations and the variability of the environment for the population being studied. Jim Holt draws attention to this in his review of Nisbett’s book in the New York Times:

Even if genes play some role in determining I.Q. differences within a population, which Nisbett grants, that implies nothing about average differences between populations. The classic example is corn seed planted on two plots of land, one with rich soil and the other with poor soil. Within each plot, differences in the height of the corn plants are completely genetic. Yet the average difference between the two plots is entirely environmental.

These claims are supported by research conducted by Eric Turkheimer of the University of Virginia, who has found that on measures of intelligence, middle-class and wealthy households are very similar; therefore differences within those groups are due more to genes. Poor households can vary widely, thus intelligence differences within that group are due more to the environment.

In a laudatory op-ed, the New York Times’ Nicholas Kristof runs off a list of Nisbett’s best recommendations about raising individual intellectual achievement: “Praise effort more than achievement, teach delayed gratification, limit reprimands and use praise to stimulate curiosity” —and collective intelligence. He goes on: “Professor Nisbett strongly advocates intensive early childhood education because of its proven ability to raise I.Q. and improve long-term outcomes…[and] suggests putting less money into Head Start, which has a mixed record, and more into these intensive childhood programs.” The Center for American Progress supports Head Start, but our education team feels it must be coordinated with high-quality state-supported early childhood programs and other federal and state programs for young children.

In a recent paper published in Proceedings of the National Academy of Sciences, Gary Evans and Michelle Schamberg from Cornell University find that poverty affects the physical and psychological health of poor teens through stress and inadequate nutrition. (The Washington Post and Wired.com both covered the study.) With stress in particular, they were able to associate biological markers such as blood pressure and stress hormones with a decrease in working memory capacity. We employ working memory temporarily for remembering things like a phone number that we are about to dial. In their experiment, Evans and Schamber found that poor teenagers could remember an average of 8.5 items; better-off children could remember an average of 9.44 items. This is a significant difference and the differences remained when they controlled for variables such as parenting styles, maternal education level, birth weight, and parent marital status. The only time the differences were eliminated was when the stress indicators were controlled for.

Science Progress board member and University of Pennsylvania neuroscientist Martha Farah explained to me that greater cognitive stimulation in childhood creates more connections between neurons and that a more nurturing environment prevents abnormal development of the hippocampus, the region of the brain associated with forming long-term memories. These effects of stress on the brain are supported not just by hormonal and behavioral differences, but also by differences in brain shape, as evidenced by fMRI studies, and differences in brain electrical activity, as evidenced in event related potential, or ERP, studies, even when behavioral differences are absent. As detailed in Nisbett’s book, more qualitative social science research has shed light on the actual stress-inducing experiences of children who live in poor households, which can include more residential moving, greater neighborhood turmoil and disruption, or the lower levels of parental nurturance that result from parental stress. Farah mentions in the Washington Post article that for children, factors also include “having fewer trips to museums, having fewer toys, having parents who don’t…read to them or talk to them.”

Finally, it is only fair to mention that there has been some reluctance among progressive social scientists to focus on more than just the political and social aspects of educational achievement and poverty. The fear was that once scientists start to study the immediate environments or the neurobiology of poor people, it could be misconstrued as “blaming the victim” or, even worse, social Darwinism. However, when environmental and biological studies are done right, we see how they shed light on combining a top-down socio-political approach with a bottom-up bio-behavioral approach. This combined approach lies at the heart of evidence-based pragmatic progressivism. Already, the Obama administration has made a commitment of $10 billion to early childhood education, aimed at closing the achievement gap in public schools. The administration’s policy provides large-scale support for educators, community leaders, and parents who want to create a more supportive environment for their children so that they can succeed. Indeed, the science of the mind can further bolster the human-level empirical foundations for society-level public policies. From there, we can figure out how our educational system can both enhance our children’s abilities and point them in a successful direction, regardless of what those abilities might be.

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

Indeed, we’re delighted to see that the new guidelines are similar to the recommendations Science Progress and the Center for American Progress proposed in our paper, “A Life Sciences Crucible: Stem Cell Research and Innovation Done Responsibly and Ethically,” published in January. They include:

• Funding only for lines from embryos remaining after fertility procedures
• Full informed consent from the donors
• No financial inducements to donate
• A demonstrated understanding by the donors that the research will not confer benefits upon them personally
• A strict separation of the privately funded cell-derivation process from the publicly funded cell research.

These proposed guidelines keep the regulation of embryonic stem cell research in line with all existing federal laws, including the so-called Dickey-Wicker amendment, which forbids the use of government funds for the creation, harm, or destruction of embryos for research. Another wise aspect of the guidelines is their encouragement and inclusion of research on so called induced pluripotent stem cells. These adult IPS cells are an integral part of the NIH’s overall regenerative medicine research enterprise alongside embryonic stem cells.

Critically, the NIH will not be funding human-animal hybrid research or other kinds of research that still remains outside the mainstream of ethics and science. The new guidelines prohibit the funding of human-animal hybrid research by the introduction of pluripotent human stem cells into animal blastocysts or germlines, and also forbid funding on pluripotent stem cells derived from embryos created through somatic cell nuclear transfer, a form of cloning, parthenogenesis, or non-reproductive in-vitro fertilization.

Unlike the Bush administration, which issued rules governing stem cell research by executive fiat, the NIH is seeking comment over the next 30 days before President Obama makes his final determination. That is also the wise thing to do regarding stem cell research.

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

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

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

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

Predictably, Obama has run into some political pushback. The complaints have arisen primarily over two issues, neither of which is substantial and both of which deserve to be countered.

For one, some opponents of the research have inferred that because the president himself did not announce in his executive order any preordained limits on the research field, there is no aspect of human embryonic stem cell research that he is not willing to endorse. But anyone who paid attention to Obama’s words during the signing ceremony last Monday would know better than that. He spoke repeatedly about the need for such research to be “legal”—a clear reference to the Dickey-Wicker amendment that Congress has renewed annually for 13 years running, which precludes the use of federal funds for any work that could cause harm to a human embryo—and “responsible,” an even more demanding level of ethical care than that of mere legality. Obama also spoke forcefully against the prospect of human cloning in words that could leave no question in any listener’s mind that the president is not going to let this field of science run amok.

Second, some research opponents are upset that the president turned to the National Institutes of Health to create guidelines that will set limits on embryonic stem cell research. In their eyes, these critics saw that approach as one that puts scientists unilaterally in charge of overseeing science—arguably no better than putting theologians in charge.

But that view ignores the expertise within the NIH in areas such as research ethics, biomedical distributive justice, and other fields of social science that focus on the fair integration of pluralistic American values with the intellectual and humanistic imperative to explore science and reduce suffering. The executive order also charges the NIH with reviewing “existing NIH guidance and other widely recognized guidelines.” This refers to the guidelines put out by organizations such as the National Academies and the International Society for Stem Cell Research, which both include ethical safeguards that ensure responsible conduct of embryonic stem cell research. As the president noted, the point is not to assume that science and ethics are opposed, but to view ethics as inherent in the pursuit of scientific knowledge.

Finally, Obama observed that the stem cell policy issue is only one example of the need for policymakers to have access to the best evidence, an important realization after the last eight years. Reasonable people may disagree, but reason cannot flourish without the facts.

Earlier this year, Science Progress and the Center for American Progress released a report, “A Life Sciences Crucible: Stem Cell Research and Innovation Done Responsibly and Ethically,” in which Michael Rugnetta of CAP and Michael Peroski spell out a basic formula that would lead to a new openness in this research field without overstepping ethical lines. We review some of the key recommendations below in the hope that it will help the NIH and assorted experts find a path to bringing this important field to maturity while addressing the concerns of those who have good questions with this new and promising frontier.

Key recommendations from the report

Currently, federal funding is only available for research on the 21 lines of embryonic stem cells that were derived before August 9, 2001. Once this arbitrary limit is lifted, the National Institutes of Health will be able to issue grants to scientists who wish to research embryonic stem cells in accordance with guidelines for ethically derived cells.

CAP believes that the quickest and best way to open up the stem cell field is to focus first on those areas where there is common ground among a wide array of Americans, by allowing funding for research in which:

• The stem cells come from embryos that were originally created at in vitro fertilization clinics for the purpose of fertility treatment and are now stored at these IVF clinics because more were created than required to fulfill the patient’s clinical need.
• Proper written informed consent is obtained from the donors.
• As part of the informed consent process, the embryo donors determine along with the physician that the embryos will never be implanted in a womb and would otherwise be destroyed.
• There are no financial inducements and the donors understand the purpose of the research is not to eventually confer therapeutic benefits upon the donors.

CAP also recommends that embryonic stem cell research requirements along these lines be codified in legislation by the 111th Congress and become law so that future presidents can not obstruct this research.

Over a period of time the NIH must also address the more contentious issue of deploying federal funds for research on stem cells that have been derived with private funds from embryos created for research.

To enforce ethical guidelines and to ensure that all stem cell research (embryonic or otherwise) is conducted cautiously and responsibly so as not to threaten the safety or autonomy of research subjects or the donors of research materials, the following administrative oversight requirements should be included either in the NIH guidelines that respond to the president’s executive order or in legislation that should be passed in the first session of the 111th Congress:

• The National Institutes of Health should require that all research be conducted under the review of a stem cell research oversight committee that adheres to the standards put forth in the regulations issued by the NIH and the Department of Health and Human Services as informed by the National Academies or the International Society for Stem Cell Research guidelines. Any embryonic stem cells that are not in compliance with these rules, or are derived from embryos that are not in compliance with these rules, will not be eligible for federal funding.
• The one caveat to this requirement is that the 21 cell lines that were approved by the Bush administration should be grandfathered into the new policy because federal funding has already been provided for research that is now well underway.

These policy guidelines will ensure that human embryonic stem cell research is carried out with the highest ethical standards. It will also ensure that U.S. public and private biomedical research laboratories live up to the highest scientific standards.

Jonathan Moreno is a Senior Fellow at the Center for American Progress. Michael Rugnetta is a Research Assistant with the Progressive Bioethics Initiative at the Center for American Progress.

See also:

• Report: A Life Sciences Crucible: Stem Cell Research and Innovation Done Responsibly and Ethically
• Column: Eight Reasons to Applaud Action on Stem Cells
• News: Stem Cell Science Takes an Ambitious Step Forward
• Timeline: A Brief History of Stem Cell Research

Publishing their research in the journal Cell, the group described a method for turning adult human skin cells into pluripotent stem cells and then differentiating them into nerve cells without leaving in the tumor-causing viruses or DNA sequences that are also needed to make the cells pluripotent.

The team was also able to turn the iPS cells into the specific kind of nerve cell that deteriorates in Parkinson’s disease. These are the nerve cells that produce dopamine, which is a neurotransmitter that transports reward signals between nerve cells.

As in previous techniques, Jaenisch’s team utilized three viruses to induce pluripotency, each of which contained one of the three reprogramming genes. The LA Times noted that unlike previous techniques, however, these reprogramming genes had added DNA sequences at each end known as loxP sequences. After the cells had been reprogrammed, the team used enzymes to cut out everything between the loxP sequences. The result was tumor-free dopamine producing nerve cells.

This technique is different from the one used in the study published in the online editions of Nature two weeks ago. Instead of using a virus to deliver the reprogramming genes, that technique attached each reprogramming gene to a delivery gene known as a transposon. That technique also used four reprogramming genes instead of three.

Based on comments from Dr. Anders Bjorklund of Lund University in Sweden, The New York Times notes that there are still several more steps required before these reprogrammed dopamine-producing nerve cells can be made identical to the nerve cells that are found in the brain region called the substantia nigra, which Parkinson’s affects directly. Also, before transplantation is even considered, scientists need to prove that all of the reprogrammed cells are fully mature since there is still a risk of tumor formation with immature cells.

We still have much to learn about the complete molecular and developmental mechanics of the cell. Only then can we work out all of these kinks in the reprogramming process. And for that, we need to research human cells going all the way back to the embryonic stem stage.

Image: Neural Cells by flickr.com/neurollero

What the Department of Health and Human Services should do is take the extra step of transparent ethical strategizing. Specifically, the NIH should convene a new working group under its Recombinant DNA Advisory Committee, or RAC. The RAC was created in 1974 to foster public acceptance of basic and clinical recombinant DNA research through open deliberation between the scientific community and the lay public. This new working group would do the same thing but with pluripotent stem cell research. It would recommend the overall ethical approach that the stem cell research community should take when moving pluripotent stem cells from the bench to the bedside. This would ensure that all stem cell research would move ahead ethically and with the best chances for success.

Read the full column here.

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

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

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

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

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

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

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

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

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

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

Image: AP/ED ANDRIESKI

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

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

A boost this significant would go a long way towards stabilizing an agency that has seen flat funding for five years, and a concomitant 13 percent decrease in buying power as a result of inflation.

Hopefully, a new policy on that lifts restrictions on federal funding of human embryonic stem cell research will follow passage of this stimulus. Increased NIH funding will give greater heft and meaning to the new stem cell policy. Indeed, some scientists have expressed skepticism about real change in the research environment if the policy shift opens up new stem cell lines to non-existent federal funding. Paul Basken reports in the Chronicle of Higher Education (subscription): “If Mr. Obama promises a policy reversal without finding significantly more money, ‘it will tend to ring hollow’,” according to Dr. Arnold R. Kriegstein of the University of California at San Francisco.

The article goes on:

A move by Mr. Obama might even bring scientists a counterproductive renewal of attention to the politics of stem cells. For all the attention Mr. Bush attracted with his 2001 order, stem-cell research has largely been redirected rather than blocked.

For more on the positive economic impact of NIH work and biomedical research in general see our recent post: “Data Bank: NIH Funding By the Numbers.”

flickr.com/lizhenry

Originally, the Neuroethics Society expected 50—maybe 80—people to show up for its First Annual Meeting. But over 200 neuroethics devotees assembled last week at the American Academy for the Advancement of Science in Washington, D.C. for the two-day series of presentations, discussions, and poster sessions.

Neuroethics is the subfield of bioethics that studies the ethical, legal, social, cultural, and policy issues that arise from our ability to understand and manipulate the brain through basic, applied, and clinical neuroscience.

Several members of the Science Progress advisory board either spearheaded the effort to get this conference together or participated in the meeting’s discussion panels. Martha Farah led a session on the up-and-coming neurotechnology industry featuring Zach Lynch. Hank Greeley discussed the legal and ethical controversies surrounding neuroscience-based lie-detection technologies. Paul Root Wolpe moderated an unexpectedly agreeable discussion between two neuro-partisans on the ever-prescient issue of brain enhancement. Science Progress Editor-in-Chief Jonathan Moreno spoke on a panel about the ethics of deep brain stimulation research and also led a panel on neuroscience research and the use of neurotechnology by the military and intelligence communities.

The success of the meeting is a clear sign that neuroethics has come a long way in a short period of time. Although not the first person to use the term, New York Times columnist William Safire coined “neuroethics” in its contemporary sense. Safire and others refined the term at the 2002 conference, “Neuroethics: Mapping the Field,” convened by the Dana Foundation. According to its website, the Neuroethics Society itself was founded in May of 2006 after a small meeting in Asilomar, California. Shortly thereafter, in October of 2006, the Society aligned with the International Neuroethics Network in an effort to broaden its scope. Harvard University’s Steve Hyman currently serves as the society’s president.

In these few short years, websites such as neuroethics.upenn.edu, the Neuroethics and Law Blog, and journals such as Neuroethics and AJOB-Neuroscience have sprouted up, adding intellectual heft and scope to the field. In fact, it is the breadth of the field that has made neuroethics so popular. The community sees itself as a big tent and incorporates scholars from the humanities, hard sciences, and social sciences, along with doctors, lawyers, businesspeople, and policy professionals. Indeed, the program agenda from last week’s meeting is a testament to the community’s commitment to breadth, diversity, and interdisciplinary.

The society’s will expand its impact with activities like the First Annual Penn Neuroscience Bootcamp on August 2-12, 2009 at the University of Pennsylvania. The Bootcamp will introduce the methods and findings of neuroscience research to educators, economists, businesspeople, policy professionals, along with anyone else whose work requires them to “understand, predict, or influence human behavior.”

Neuroscience is becoming increasingly relevant in our everyday lives. fMRI brain scan images already flood the science sections—and advertising space—in newspapers and magazines. In order to properly separate the reality of advances in brain technology from the hype, consumers, citizens, and professionals have to get educated on the science and engaged in the ethical conversation.

For more details on the Penn Neuroscience Bootcamp, including application instructions, check out the program website.

The final tally came to 2,520,240 (53 percent) “Yes” votes and 2,271,071 (47 percent) “No” votes.

The Detroit Free Press, which endorsed the proposal, reports on the passage of the Proposal and features comments from voters as well as the spokespersons from Cure Michigan (the pro-research advocates) and MiCAUSE (the anti-research advocates).

Business Innovation Blogger Nathan Bomey at Mlive.com welcomes the amendment but is apprehensive about whether there will be enough funding to create high-tech jobs in light of “Michigan’s crumbling state budget and bleak economic situation.” He does, however, include a proud quote from University of Michigan President Mary Sue Coleman:

“We will now build on our already strong reputation for adult stem cell research with an equally committed approach to embryonic stem cell research. We are proud to be one of the country’s leading research universities, and this endorsement by voters will strengthen our ability not only to improve the health of our communities, but also to boost the intellectual and economic vitality that is critical to the future of our region.”

Finally, the Wall Street Journal’s Market Watch posted a press release from the International Society for Stem Cell Research featuring this from George Q. Daley, ISSCR past-president and associate director of the Stem Cell Program at Children’s Hospital Boston:

“This outcome means that critical medical research can proceed in Michigan without political or ideological interference. The voters saw through the fear and misinformation circulated by opponents of medical research and reaffirmed their commitment to allow physicians and scientists in Michigan to pursue the most promising avenues of discovery.”

You can read our previous content on Proposal 2 here, here, and here.

Professor George believes that life begins at conception and any intentional cessation of an embryo’s development is tantamount to murder. It is difficult to argue with this philosophically consistent, if pragmatically untenable, position. But it is not difficult to dispute the hyperbolic and disingenuous statements that George makes about the efforts of those researchers who support human embryonic stem cell research to ensure any research involving cloned embryos is conducted ethically.

By allowing cloned embryos to survive past the embryonic stage and even be implanted in a womb, he is allowing the embryos to develop into fetuses that will inevitably be miscarried.

George characterizes 2005’s Human Cloning Ban Act as a bill “that would authorize the large-scale industrial production of human embryos for use in biomedical research in which they would be killed.” He argues that the proposed legislation “would effectively require the killing of human beings in the embryonic stage that were produced by cloning. It would make it a federal crime for a woman to save an embryo by agreeing to have the tiny developing human being implanted in her womb so that he or she could be brought to term. This ‘clone and kill’ bill would, if enacted, bring something to America that has heretofore existed only in China—the equivalent of legally mandated abortion. What it bans is not cloning, but allowing the embryonic children produced by cloning to survive.”

Although George’s argument follows logically from his assertion that life begins at conception, the practical implications of his argument result in prospects that are less than life-affirming. By allowing cloned embryos to survive past the embryonic stage and even be implanted in a womb, he is allowing the embryos to develop into fetuses that will inevitably be miscarried. In order to prevent the creation of doomed fetuses and the suffering of possible surrogate mothers under this horrific form of experimentation, human cloning must be banned.

Hence, the intention of the Human Cloning Ban Act of 2005 and the Human Cloning Ban and Stem Cell Research Protection Act of 2007 is to do just what they say—ban human cloning. Yes, they do allow the cloning of human embryos for the purpose of research, but ban human reproductive cloning. There is a world of difference here, both scientifically and ethically.

Human reproductive cloning would occur if a cloned embryo created by nuclear transfer were placed inside a womb and allowed to develop into a cloned baby. This is a universally condemned practice. The implantation and gestation of cloned embryos would undoubtedly lead to miscarriages, birth defects, and severe health consequences for the surrogate mother. That is why the Human Cloning Ban Act defines human cloning as “implanting or attempting to implant the product of nuclear transplantation into a uterus or the functional equivalent of a uterus.”

This is a separate and distinct practice from research conducted on cloned embryos. Indeed, this kind of research would be a useful way of learning how to personalize regenerative medicine. If stem cells are extracted from a cloned embryo, a patient would have access to a supply of genetically matched cells for therapy or transplantation. Additionally, research on cloned embryos would generate valuable information about individual differences in developmental biology.

George, however, calls embryo cloning “large-scale industrial production of human embryos.” This description conjures up images of giant factories where tiny humans are cranked-out by the thousands on conveyor belts. This could not be farther from the truth. Embryos are cloned by the process of somatic cell nuclear transfer. In this process, the patient’s genome is extracted from one of the patient’s somatic cells, such as a skin cell, and is implanted in an egg that has had its DNA removed. The egg is then zapped with electricity and commences cellular division.

So far, this process has had only limited success. Robert Lanza of Advanced Cell Technology was able to get the embryos past the 8-to-16 cell stage and form blastocysts, but no one has been able to extract stem cells from the cloned embryos. Scientists are doing all they can to sustain these clumps of cells for a little while longer so they can extract stem cells or carry out other forms of embryo research. A law against human cloning would be desirable so that researchers would be required to stop short of allowing these cells to develop the first indications of nervous systems— i.e. the first indications of sentient personhood—whether inside or outside the womb.

Indeed, both bills are influenced not just by a fear of human reproductive cloning but also by a 24-year consensus on how to balance the need to conduct life-enhancing research while also protecting nascent human life. In 1984, the British government’s Warnock Committee came up with a “14-day rule” for embryo research. This meant that embryos created through in vitro fertilization could not be kept alive or used for research after they underwent 14 days of cellular division. At that point, the embryo either had to be implanted in a womb or allowed to die naturally—the reason being that after 14 days the embryo begins to form the primitive streak, a band of cells from which the embryo develops a nervous system.

With the formation of the nervous system, the embryo has taken the first step towards becoming a sentient human being. Since it is a violation of human autonomy and freedom to hold a sentient person captive in order to experiment on it without its consent, the embryo must be allowed to die naturally before it becomes sentient or be implanted in a womb so that it can grow as a free sentient person. The United States does not have this type of 14-day rule in place because of its outright ban on federally funded embryo-harming research known as the Dickey-Wicker amendment. The Human Cloning Ban Act, however, is a step toward this type of sensible regulation.

It is important to bear in mind that the Warnock Committee was not considering cloned embryos, but merely embryos created through in vitro fertilization. These embryos could still be implanted in a womb since they would simply lead to a normal pregnancy. The Human Cloning Ban Act of 2005 prohibits the implantation of cloned embryos in a uterus or functional equivalent, which (if research into animal cloning indicates anything) would not lead to a normal pregnancy or the growth of a normal human being. The 2007 bill goes a step further by also explicitly including a 14-day rule as well as other protections for fertilized embryos and their donors without hindering research.

George grossly exaggerates the implications of the Human Cloning Ban Act by saying that it would “require the killing of human beings in the embryonic stage.” The cloned embryo would simply be prevented from developing sentience or being placed inside a woman’s body where it would most likely be miscarried. It is an unfortunate prospect, but what is the alternative? No one would be “saving” the embryo; one would simply be postponing the inevitable, making it more gruesome, and involving another person (the surrogate mother) in the process.

Theoretically, the embryo could be saved if scientists could figure out a way to successfully bring clones to term, but that procedure could only be perfected through many rounds of horrific experimentation. To be against the destruction of cloned embryos before they become sentient is to be in favor of allowing women to become incubators for an indisputably grotesque experiment. Although George maintains his pro-life philosophical consistency by asking scientists to do all they can to keep cloned embryos alive as long as possible, his position becomes pragmatically untenable since he is asking that the clone’s inevitable demise take a more horrific form.

Michael Rugnetta is a research assistant at the Center for American Progress and a contributor to Science Progress.

SOURCE: BBC

Eddie Adcock plays his banjo while undergoing deep brain stimulation.

Deep brain stimulation is an experimental technique in which electrodes are implanted into the thalamus to correct the effects of neurodegenration or brain injury. Scientists have used the process to treat essential tremor since 1997 and Parkinson’s disease since 2002. The Neurophilosophy blog reports that doctors have recently used the technique to monitor brain surgery in real time—and in tempo.

Neurosurgeons had their patient, the legendary bluegrass musician Eddie Adcock, play his banjo while he was undergoing deep brain stimulation. According to Neurophilospohy:

Adcock is suffering from essential tremor, a progressive neurological condition characterized by tremors in the arms which appear during voluntary movements and which are thought to occur as a result of degeneration of cerebellar Purkinje cells.

Due to his tremor, Adcock could no longer play the banjo with his characteristic fast-picking style. As the surgeons stimulated Adcock’s brain with electrodes, his banjo-playing became more nimble. By observing the quality of Adcock’s strumming, the surgeons were able to fine-tune the therapy by finding the most effective positions for the electrodes.

The surgery was performed at Vanderbilt University Medical Center in Nashville, Tennessee and video footage of the surgery is available on the BBC’s website, which explains that the electrodes are powered by a pacemaker in Adcock’s chest.

A review article in Nature Medicine (subscription) from earlier this year notes that scientists and clinicians are still unsure about how DBS actually works. It might facilitate, impede, or “overwrite” the information passing through the stimulated neurons. There is some evidence from studies of essential tremor that DBS increases production of the neuromodulator adenosine. This makes neurons less active, reducing the tremor. The charges must administered continuously by the pacemaker, otherwise the tremors resume.

Today, the Detroit Free Press and the Detroit News both endorsed a new policy that will be on the ballot this November in Michigan, and, if passed, will allow significantly more stem cell research.

Michigan has the most restrictive anti-stem cell research laws in the nation, a tragedy which is compounded by the fact that Michigan has one of the most productive biotech R&D infrastructures of any state. Michigan is home to some of the nation’s most prestigious academic research universities and nonprofit institutes as well as 542 private life sciences companies that employ 31,777 workers.

The Detroit News interviewed Doug Engel, head of the cell and developmental biology department at the University of Michigan, about the current law. Engel lamented the fact that the law, which threatens Michigan’s scientists with criminal prosecution if they derive their own embryonic stem cells, has forced his colleagues to order stem cells from out of state, thereby slowing down research. One of his colleagues had to wait seven months for stem cell lines, a situation that Engel calls “not conducive to cutting-edge research.” A situation so non-conducive, in fact, that another of Engel’s colleagues—a top stem cell biologist—eventually left Michigan for California.

Perhaps the greatest irony about the current law is that its intention is to protect embryos, but instead of allowing for leftover embryos from IVF clinics to be used for research, the embryos are simply destroyed.

The proposed new law simply allows researchers to use leftover embryos from IVF clinics as sources of stem cells. The new law also has sensible provisions built into it that prohibit the buying and selling of embryos, as well as the creation of embryos specifically for research. This, of course, would still outlaw therapeutic cloning (or research cloning, otherwise known as somatic cell nuclear transfer, or SCNT) as Michigan’s 1998 prohibition of both reproductive and therapeutic cloning would remain intact. The ballot initiative prohibits the derivation of stem cells from an embryo that has undergone cell division for 14 days or more, and also stipulates that proper informed consent must be obtained from the donors and that the embryos must otherwise not be suitable for implantation. For an interactive explanation of each of the ballot item’s provisions check out Cure Michigan’s website.

Both newspapers do make the concession that the law perhaps goes a tad to far by putting a blanket ban on future regulations. However, they both acknowledge that the legislature could still revise the state Constitution in the future if needed.

Altogether, this is a modest ballot proposal that will repeal the most extreme and counterproductive provision of Michigan’s Constitution.

Jeff Miller/University of Wisconsin-Madison

When James Thomson’s and Shinya Yamanaka’s research teams published their ground-breaking papers last year on induced pluripotent stem cells, or iPS cells, one of the major hurdles to clinical application was the propensity of the cells to cause cancer. In these original methods, genetic factors inserted into somatic cells by way of retroviruses induced both pluripotency and caused tumors.

Now, scientists from Harvard University have successfully introduced the pluripotency-inducing genes into mouse somatic cells by way of adenoviruses, which are less harmful than retroviruses because they do not permanently integrate the genes into the cell’s DNA. The study detailing the work was published online yesterday on the website of Science. In its story on the discovery, the The Washington Post quotes Robert Lanza of Advanced Cell Technology, who explains, “The adenovirus will infect the cells but then will clear themselves from the cells. After a few cell divisions there are no traces of the virus in the cell. You can’t tell the virus was ever there.” However, the Post also quotes Rudolf Jaenisch of the Whitehead Institute, who expressed doubts about the method, saying, “It’s still very inefficient.”

Indeed, according to the article in Science, the efficiency was “extremely low, ranging from less that 0.0001 to 0.001%,” and that “[t]his frequency is lower than that obtained with integrating viruses (~0.01 to 0.1%) and is probably due to the fact that many cells do not maintain viral expression long enough to trigger entry into a state sustained by endogenous pluripotency factors.”

In order to increase the efficiency of this method of inducing adult cells to become pluripotent, scientists may need to supplement the genes with chemical compounds, as has been done with retroviral reprogramming. At the end of the article in Science, author Konrad Hochedlinger and his research team acknowledge, “Before translating these observations into a therapeutic setting, however, it will be important to asses if human iPS cells generated without viral integration are indeed as potent as human ES cells.”

And that’s one more reason that human embryonic stem cells remain the gold standard of pluripotency, and will still be critical to this ongoing research in regenerative medicine, despite conservative naysayers.

iStockphoto/SP

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

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

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

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

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

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

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

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

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

Given recent research advances in regenerative medicine, ethical questions surrounding federally approved stem cell lines, and the likelihood that the next president may change existing rules for research, it’s time for some new thinking on stem cell policy.

In order to streamline research and improve research collaboration, the federal government needs to establish either a national stem cell registry and or a national stem cell bank for all human embryonic stem cell lines. A stem cell registry would be simply a database of all stem cell lines that are available to researchers through an organization such as the National Institutes of Health. The registry would contain all information about the cells, including the date and place of their procurement, the informed consent protocols used to obtain the embryos from which the cells originated, the biological makeup of the culture media used to nourish the cells, and the results of tests performed on the cells. A bank, on the other hand, would provide a central physical location where the cells could be stored so that a research organization could then distribute them to approved scientists who request them.

The National Stem Cell Bank contract expires in September 2009, and needs to be reconsidered, modified, extended, or terminated depending on the utility of the bank and the next administration’s stem cell policy.

Banks and registries are useful because they help to coordinate research and facilitate research collaboration. Indeed, major innovations in the United States are usually driven by research collaboration. A recent study from the Information Technology and Innovation Foundation found that over the past 35 years, America’s most economically significant innovations (as noted by the annual R&D 100 awarded by R&D Magazine) have more and more often come from federally funded research programs (from 14 percent of the top innovations in 1971 to 69 percent in 2006). Nevertheless, total federal levels of R&D spending have been decreasing in real terms since 2003 and the funding efforts for collaborative research have been limited. The report urges the federal government to improve the funding of research collaboration and for the federal government to rein in its decentralization of research funding, which it has recently been carrying to an “unproductive extreme.”

Currently, the NIH maintains a registry of the 21 approved stem cell lines. The NIH also contracts out the maintenance of the National Stem Cell Research Bank to the WiCell Research Institute at the University of Wisconsin-Madison, which was established through a $16 million, four-year contract in 2005. Currently, the bank contains 18 of the 21 lines (another line is held by the University of California, San Francisco and two others by the Swedish/British biotech company Cellartis). The National Stem Cell Bank contract expires in September 2009, and needs to be reconsidered, modified, extended, or terminated depending on the utility of the bank and the next administration’s stem cell policy. Ultimately, it remains the responsibility of Congress and the president to determine whether to continue or expand the national stem cell bank.

Difficulties may arise if federal funding of embryonic stem cell research suddenly opens up and unleashes a deluge of new hES cell lines for banking. Since the current business model has been unable to bank stem cells at economies of scale (at WiCell it cost $16 million to hold 18 lines for 4 years), the NIH and WiCell may not be able to get up to speed on cell banking in a cost-effective manner. We therefore suggest that the NIH explore multiple options and encourage competition among the many institutions across the country that store biological materials, including WiCell. The NIH can then arrange a new contract with the institution, or combination of institutions, that can maintain the most cost-effective bank.

The benefits of a stem cell registry are overwhelming, and even private entities that may be reluctant to bank their cells will still have clear incentives to register them.

Given the difficulty of getting a large and cost-effective stem cell bank up and running, the NIH should focus its initial efforts on expanding their existing stem cell registry and making sure that it is comprehensive. The NIH’s existing hESC registry sets a precedent for a national stem cell registry, but it is woefully incomprehensive. Not only must this registry be expanded to contain all cell lines for which federal funding is approved, the registry should also go beyond compiling the usual and rather basic information that it has maintained thus far. This expanded stem cell registry should be more sophisticated and offer information about the compatibility of lines with one another and with the laws governing embryo procurement in various states, locales, or institutions. This registry would optimize collaboration among research groups, as it would make voluntary registration very easy.

On June 20, 2007, President Bush attempted to expand the NIH’s stem cell registry by changing the name from the “Human Embryonic Stem Cell Registry” to the “Human Pluripotent Stem Cell Registry.” Nearly a year has passed and the NIH has still not settled on a definition of “pluripotent” that would set criteria for whether a given stem cell line would be allowed in the registry. Due to the failure of national-scale efforts like these, we recommend funding for projects intended to stimulate competition among private contractors in order to create a model for a sophisticated national stem cell registry which would then be developed specifically for the NIH.

The benefits of a stem cell registry are overwhelming, and even private entities that may be reluctant to bank their cells will still have clear incentives to register them. For example, listing stem cell lines enables more researchers (and hence potential customers) to know that the lines exist.

When it comes to stem cell banks, however, many for-profit companies may perceive challenges and be more resistant to banking their cells. For example, some for-profit owners of stem cell lines might not want to share their lines with every research group for reasons such as quality control, the amount of time it takes to deposit cells into a bank, and the expectation of payment. However, banking saves costs for companies by providing federally funded stem cell vetting comparisons of lines from multiple institutions. Banking also improves efficiency for researchers by centralizing research-quality stem cells, allowing for the easy scientific comparison of lines, and improving research collaboration. Ultimately, in spite of the initial difficulties that the NIH and other institutions might have in developing a cost-effective business model for stem cell banking, there would nevertheless be long-term payoffs.

Creating both a federally funded stem cell bank and registry would not be redundant, as the registry would catalog the bank’s lines, and the official registry of the bank would be the national registry. If the president and the Congress decide to continue funding and expand the national stem cell bank, it must be linked to the national registry. Carried out in a smart, efficient, and innovative manner, banks and registries will streamline research and foster collaboration by providing researchers with a uniform display of all available cell lines.

Michael Rugnetta is a Fellows Assistant at the Center for American Progress. Michael Peroski is an undergraduate majoring in biochemistry and philosophy at Allegheny College and a former bioethics intern with CAP.

Just last month, a judge in Cole County, MO denied a request from the Missouri Roundtable for Life for a temporary restraining order that would prevent state money from going to the Life Science Research Board for 15 days while the state clarifies the law. The Roundtable fears that the money might go towards abortions, cloning, or embryonic stem cell research since the law is unclear about the restrictions placed on the funds.

The Life Science Research Board was created by state legislation in 2003 and was charged with distributing funds in the Life Sciences Research Trust Fund. According to the law, the trust fund is supposed to receive 25 percent of the money that the state received from the Tobacco Master Settlement Agreeement. The intention of the law was to ensure that the legislature appropriates that 25 percent of that continuous tobacco revenue stream every year starting in FY 2007. The LSRB, however, is just starting to receive applications and will not make any grants until FY 2009.

University of Wisconsin-Madison

Human embryonic stem cells.

The problem that anti-science advocates have is that Amendment 2, which protects embryonic stem cell research in MO, was passed in 2006 and may “loosen” the restrictions on cloning and abortion that were originally put on the funding. That is why there was a major struggle in the state legislature this year regarding the appropriations. The final wording of the appropriations bill stated that the research should be done “exclusively on animal science, plant science, medical devices, biomaterials and composite research, diagnostics, nanotechnology related to drug development and delivery, clinical imaging, and information technology related to human health,” according to the Associated Press. But Amendment 2 has a clause in it that prohibits state officials from withholding research funds for purposes other than stem cell research simply because those officials want to inhibit the conduct of human embryonic stem cell research. In other words, crafters of the legislation did not want scientists or institutions denied funding for other purposes simply because they might have an association with hESC research.

Edward Martin, the Roundtable’s attorney, expressed the group’s concern about the uncertainty surrounding the funds. “We’re asking for the court to say what the law is,” he told the Daily Record and the Kansas City Daily News-Press after the July hearing.

State attorneys, however, denied that the funds would be used for any of the procedures that the Roundtable is concerned about, like human cloning and abortion.

What’s interesting is that Amendment 2 says nothing about abortion and still prohibits human cloning just like the original restrictions put on the LSRB. What the Roundtable is probably concerned about is the contested definition of “cloning,” which Amendment 2 defines as an effort “to implant in a uterus or attempt to implant in a uterus anything other than the product of fertilization of an egg of a human female by a sperm of a human male for the purpose of initiating a pregnancy that could result in the creation of a human fetus, or the birth of a human being.”

Note that this does not ban somatic cell nuclear transfer, or therapeutic cloning, which is a technique that scientists are working on to create stem cells that are a genetic match for a donor. In this process, the blastocyst is not implanted and cannot even have cells removed from it after 14 days. The Roundtable’s hope is that the original LSRB restriction included both therapeutic and reproductive cloning, and that it will take precedent over Amendment 2. This is just the latest in a long line of petty stem cell squabbles.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

At the governmental level, there are a host of questions about safety, privacy, social and political coercion, access to technology and therapy, and the direction of government-funded neuroscience research. Informing these policy questions is “neuroethics”—the field of bioethics that studies the values and principles involved in researching and manipulating the brain. Neruoethics also considers how individuals should conceptualize the brain as an integral part of the human person, especially as individuals attempt to alter or enhance their brains and nervous systems.

Safety

One of the major reasons drugs or devices that affect the brain might seem more dangerous than those that affect other parts of the body is because the brain is a complex system. Tampering with it can be alarming because the mind is inextricably linked to conceptions of who we are as individuals. This makes the side effects of trying to alter or enhance the brain loom large.

For example, although Ritalin has proven to be quite helpful for children, researchers still do not understand its long-term effects, such as whether it might speed up cognitive decline in old age. Memory-enhancement drugs like Donepezil might also prevent those who take them from properly understanding, integrating, and relating information. In fact, it is precisely because of these side effects that the clinical neuroscience community is moving away from drug-based approaches to brain enhancement, which work by trial and error, and is focusing instead on brain stimulation technologies, which deliberately target specific areas of the brain. Regardless of therapy, the FDA must regulate brain enhancement technologies in order to make sure that the benefits outweigh the risks. The analysis that guided the FDA’s July 2005 approval of technology for vagus nerve stimulation for the treatment of depression was insufficient. The technology did not confer a statistically significant benefit, and was approved because the Agency deemed it harmless—but safety alone is an insufficient criterion for therapeutic approval. The FDA needs to be more critical in its evaluation of future enhancement technologies.

Privacy and Mind Reading

Experiments that employ brain-imaging technologies have given scientists a new vision of the brain and its operations—in some cases allowing researchers to build computer programs that understand what people are thinking.

Scientists employ a variety of techniques that allow them to non-invasively peer into the heads of study participants. The most common of these is functional magnetic resonance imaging, or fMRI, which allows observation of oxygen levels in the brain that are associated with neural activity. Other techniques include event-related potentials (ERP), which can detect and average electrical impulses across larger areas of the brain and produce readings on the millisecond scale; and transcranial magnetic stimulation (TMS), which uses strong magnetic impulses to stimulate or inactivate small targeted areas of the brain for research or therapeutic purposes.

Already, fMRI experiments can tell researchers the intentions of a subject presented with the option to add or subtract two numbers. The ERP technique can reveal whether a subject has seen an object before, or—to a certain extent—whether a subject is lying. Scientists at the University of Pennsylvania have even derived an algorithm from fMRI observations of subjects that can tell the difference between a lying brain and a truth-telling brain. There is even evidence that fMRI can decode the brain’s visual cortex and tell us what a subject is looking at. The ethical questions that follow some of these technologies raise serious issues in the legal realm. Could an fMRI scan become admissible in court as evidence of malicious intentions? More ominously, does this so-called “brain-reading” portend a future where the inside of a person’s head is no longer sacrosanct? Could the government exploit this technology for national security purposes? If so, what does that mean for the freedom of human thought?

Although much of this research is benign, aimed simply at better understanding the brain or possibly helping to cure brain disorders, some of the more controversial forms of research—such as memory and lie-detection—have been funded by the Department of Defense through DARPA, and are intended for national security purposes. Since fMRI machines are large and expensive and the scans take time, DARPA has been developing more portable lie and memory-detectors by using wireless near-infrared technology to scan brains from a distance in airports or other secure areas.

Government and Social Coercion

As a result of DARPA’s Augmented Cognition (AugCog) project, U.S. soldiers may eventually carry equipment that integrates directly with their brains. Despite the program’s recent completion, its aims live on in other brain research initiatives. One project monitors soldiers’ brains as they rapidly scan intelligence photos: as many as 10 to 20 a second. Computers can then assess the fluctuations in their attention levels and determine whether the soldier’s brain finds the image relevant before the soldier is even consciously aware of the image. The computer can then store the relevant images for later viewing. Similar technology could also operate in a soldier’s binoculars and induce increased attention in the soldier when his visual system detects a relevant stimulus—again, all before he is even aware of the stimulus and consciously attends to it. Commanders can also assess the stress levels of soldiers in the field and shift tasks to other soldiers so that work is distributed for maximum efficiency. Electrocardiogram (ECG) and electroencephalogram (EEG) sensors in soldiers’ helmets could monitor vitals—or computer chips might even be implanted directly in a soldier’s brain.

Today pharmaceuticals like Adderall can enhance cognition, and others, like Prozac, can enhance mood. Drugs such as Provigil can even keep us awake for extended periods of time. Of course, their stated medical purpose is to help those with neuropsychological disorders—attention deficit disorder, depression, and narcolepsy, respectively. Nevertheless, ambitious college students, academics, and professionals are taking Adderall and Ritalin for enhancement purposes, either through off-label prescriptions or—as is the case with up to 25% of students at some colleges—without prescriptions. The journal Nature recently released the results from a survey of 1,400 of its readers. It found that one-in-five respondents had used drugs for non-medical reasons to enhance focus, concentration, or memory. Of those users, 62% have taken methylphenidate (Ritalin) and 44% have taken modafinil (Provigil).

One perspective is that these pharmaceutical forms of self-improvement should come out of the shadows so that individuals can exercise their freedom to alter their capabilities without stigma. The opposing viewpoint is that these drugs pose a significant problem because the usage and acceptance of brain-enhancement by society at large will pressure even the most enhancement-resistant citizens to finally give in or be left behind in the cognitive dust. And although many people may shudder at the notion of required enhancement in order to keep a job or stay in school, it would be equally coercive to forbid enhancements for all just to protect those who might choose not to take them. Even assuming that brain enhancement is safe and effective, access to cognitive enhancement technologies will likely be distributed no better than current healthcare technologies; but again, this is not necessarily a reason to forbid brain enhancement for all. But if brain-boosting drugs were to further contribute to social stratification, it might provide a rationale for government subsidies for those enhancements through existing healthcare frameworks.

Because school and workplace are obvious situations where required enhancement would raise serious ethical questions, it is likely that the first policies will be formed at the local level with school boards, employers, contractors, unions, and local governments. Will these policies require, forbid, or simply allow pharmaceutical enhancement in these contexts, or will it be some nuanced mixture? Already Connecticut has a statute that prohibits “any school personnel from recommending the use of psychotropic drugs for any child.” The state also has another statute that prohibits children from being taken into state or court custody because their parents or guardians refuse to administer psychotropic drugs to the child.

Most importantly, policies must be sensitive to special populations within society that might be subjected to certain kinds of brain enhancement or brain manipulation coercively: these groups include military personnel, prisoners and detainees, and criminal suspects and witnesses. The military has an obvious interest in enhancing the capabilities of soldiers so they are able to fight for long periods of time without sleeping, and remain alert and attentive. Pharmaceuticals might also make soldiers less sensitive to psychological trauma. This could prevent many soldiers from suffering post-traumatic stress disorder—an obvious benefit. But another conceivable effect of limiting the psychological impacts of warfare might also make military personnel less risk averse or less empathic—effectively turning them into guiltless killing machines. Are these the kind of soldiers that America wants returning from the battlefield? Are these the kind of soldiers that America even wants on the battlefield in the first place?

Coercive brain alteration also raises ethical concerns for the treatment of convicted criminals. Some courts have taken it upon themselves to mete out so-called “therapeutic justice”: both to sex offenders by requiring them to take androgens, to reduce sex drive, and also to violent criminals by requiring them to take drugs known as selective-serotonin reuptake inhibitors (SSRIs), like Prozac, to reduce their impulsiveness.

In the criminal justice system, issues of privacy and coercion merge when considering drugs like oxytoic, which can compel detainees, witnesses, or suspects to tell the truth or act friendlier to their interrogators. This is different from peering into a person’s brain, since the subject is aware that he or she is actively giving up the information—but is it still free will when that will is bent by a drug? Are there circumstances in which authorities should be allowed to slip coercive drugs to detainees without their knowledge?

Limitations of the Technology and Policies for Advancement

These brain-imaging studies have significant limitations with the current technology. For instance, fMRIs only look at the increase in blood oxygen levels associated with brain activity and not the activity itself. Also, in order for experiments to provide us with relevant information, they must be carried out with highly specific designs: conditions must have discreet variables so that precise differences in each metal state are discernible. Complicating this is the fact that some regions of the brain have multiple functions.

The most relevant policy consideration regarding brain imaging is to fund the advancement of the neuroimaging apparatuses. In order to improve these imaging technologies and develop smaller, less expensive imaging machines, biological and physical scientists need to work together to determine how to unlock clear, real-time images from the brain’s electrochemical signals. This kind of research is difficult, given the current structure of scientific funding in this country, which assigns physical science research to the National Science Foundation and biological science research to the National Institutes of Health. Since neuroimaging lies at the intersection of both agencies’ jurisdictions, more joint-funding mechanisms—or even a restructuring of both agencies into one—would make sense.

Another consideration for science-funding policy is that private companies will conduct certain kinds of research that they will not publish or leave open for review. Advertising agencies have already entered into the field of neuromarketing; fMRI research probing how the brain responds to advertisements. Private companies such as Cephos and the aptly named No Lie MRI have also begun to offer fMRI lie-detection services. However, their clients have largely been married couples who suspect each other of cheating. Private companies may conduct less-than-thorough studies and make unsubstantiated claims about neurological research; appropriate oversight will be necessary to protect public interests and health.

Conclusion

Neuroscience research will continue to progress. Whether the research is done by the government or by private companies, in the U.S. or abroad, someone will fund it. Regardless of where the brain-enhancing drugs are made, they will eventually make it into the hands of the people who are willing to pay for them. Funding, marketing, and regulation will shape the impact of neuroscience research on society. These forces will determine what kinds of research are carried out, the purpose of that research, and subjects on which it will be performed. They will determine what institutions or corporations will get access to the technology and innovations that result from that research. Finally, these forces will determine which citizens will have access to the products of neuroscience. Therefore, public policies must ensure rigorous research standards, protect privacy, prevent coercion, and an aim for an equitable distribution of benefits.

Michael Rugnetta is a Fellows Assistant at the Center for American Progress.

The Center for American Progress has a new report on the importance of GINA: “Genetic Non-Discrimination: Policy Considerations in the Age of Genetic Medicine.”