1. You were the director of the National Human Genome Research Institute and oversaw the Human Genome Project. How has your background as a geneticist affected the way you approach managing the NIH and developing strategies to address national (and global) health concerns?
Genetics underlies nearly every disease, from rare diseases, such as cystic fibrosis and sickle cell anemia, to more common, chronic conditions, such as cancer, heart disease, and diabetes. In fact, as we learn more about the human genome and how its 3 billion letters vary ever so slightly among individuals, we are learning that genetics even influences susceptibility to many infectious diseases, such as tuberculosis (TB) and acquired immune deficiency syndrome (AIDS).
Consequently, I think my background serves as a strong foundation for leading the efforts of the National Institutes of Health (NIH) to turn scientific discovery into health for all peoples of the world.
The study of the genome also fosters a broad view of human biology. As leader of the National Human Genome Research Institute, I encouraged application of genomic knowledge, tools, and technologies to a wide range of human disorders. So, unlike scientists who have devoted their entire careers to studying a specific disorder or biological pathway, I owe no allegiance to any particular group of diseases.
In scientific research, it is very tempting to stay within your comfort zone. But the Human Genome Project, which was successfully finished under budget and ahead of schedule, is proof of the extraordinary progress that can be made when researchers set bold goals and work together to achieve them. My hope is that, as director of NIH, I can encourage the entire research community to pursue endeavors that push us beyond our comfort zones in ways that benefit humankind.
2. The Obama Administration has announced a Global Health Initiative focused on maternal and child health, family planning and infectious diseases like AIDS/HIV and malaria. What programs and projects do you hope for the NIH to implement in order to address the growing concern over global health disparities, and what do you foresee as the most challenging issues you will have to face?
In recent decades, much of global health research has justifiably been focused on the “big three” diseases: AIDS, TB, and malaria. However, biomedical research must now set its sights on other more-neglected causes of death and disability in low-income nations. That includes non-communicable diseases like cancer, heart disease, and diabetes, which are the fastest growing causes of morbidity and mortality in the developing world. In collaboration with other funding sources, such as the Bill and Melinda Gates Foundation, NIH can play a major role in ramping up the discovery of novel targets that may facilitate the development of new ways to prevent, diagnose, and treat these neglected diseases.
It is also critical to build biomedical research capacity and training opportunities in the developing world. For example, NIH and the Wellcome Trust, a global charity based in London, recently formed a partnership to support population-based studies in Africa of common, chronic disorders, as well as infectious diseases. Called the Human Heredity and Health in Africa (H3Africa) project, the effort will enable African researchers to take advantage of new research approaches to understand both the genetic and non-genetic factors that contribute to the risk of illness. We anticipate that what is learned in Africa about genetic variation and disease will have an impact around the globe.
3. As the development of new technology makes whole genome sequencing faster, cheaper and more feasible for the average person, how do you see genetic data like this being integrated into mainstream healthcare? Do you think we have amassed enough knowledge to correctly interpret the results of whole genome sequencing and use this information to create personalized disease therapies?
Today, one of our biggest goals is to cut the cost of sequencing an entire human genome to $1,000 or less. This advance will pave the way for each person’s genome to be sequenced as part of the standard of care, leading to a revolution in the practice of medicine.
In this new era, the current one-size-fits-all approach to healthcare will give way to personalization. Healthcare providers will use a person’s genomic profile, along with information about his or her lifestyle and environment, to develop individualized strategies for preventing, detecting, and treating disease. Genomic information will also enable doctors to prescribe medications in safer and more effective ways, selecting for each patient the right drug at the right dose at the right time.
Granted, there will be great challenges in interpreting anyone’s complete genome sequence, so it will likely take a while before all of these advances show up in local hospitals and clinics. But I expect that within the next decade or so, most people living in developed nations will have their genomes sequenced as part of their medical record — and I hope it will come even sooner.
4. The passage of GINA (the Genomics Information Nondiscrimination Act) was a major victory for proponents of secure genetic testing. What are your thoughts on the privacy concerns of genetic testing? What genetic testing infrastructure still needs to be improved before privacy is no longer an issue?
The passage of The Genetic Information Nondiscrimination Act of 2008 (GINA) represented a major victory for all Americans. In fact, the late Sen. Edward Kennedy (D-MA), who cosponsored the legislation in the Senate with Sen. Olympia Snow (R-ME), called GINA “the first new major civil rights bill of the new century.”
This federal law protects consumers from discrimination by health insurers and employers on the basis of genetic information. One reason this nationwide level of protection was needed was to reduce Americans’ growing concern that results of genetic testing could be used against them by health insurers and in the workplace. Another motivating force was that patients’ fears of potential discrimination were threatening our ability to conduct the very research we need to understand, treat, and prevent disease.
Despite the protections provided by GINA, the law is not perfect. GINA does not address life insurance, disability insurance, or long-term care insurance. So, we need to thoughtfully evaluate these and other areas of our society in which it may be tempting to use – or misuse — genetic information.
5. Many people believe translational research to be a better funding investment, as it is more directly relevant to clinical medicine than basic science research. How do you see the balance between basic science and translational research evolving in the future?
In the past, critics have complained that NIH is too slow to translate basic discoveries into new advances in the clinic. Some of that criticism may be justified, but often the pathway from molecular insight to therapeutic benefit was just not discernible.
For many disorders, that is now changing. We are experiencing a remarkable deluge of discovery in terms of the causes of disease, much of it coming out of genomics, the ability to pinpoint at the molecular level what pathway has gone awry in causing a particular medical condition. Such information is exciting in itself because it provides new insights into human biology. However, what we really want to do is to take such information and push it forward into clinical benefit.
Some of the benefits could come in the form of prevention, that is, identifying people at highest risk and making sure be sure they are taking the right preventive measures. However, despite our best efforts at prevention, people are still going to get sick. So, we also want to come up with better treatments than what we have now. In the past, the development of drugs has largely been left to the private sector, which used rather broad-brush, empirical approaches to identify compounds that would have the right properties to improve the situation.
Today, informed by a better understanding of what is going on inside a cell and how a disease affects that, researchers in both the private and public sectors have developed more rational strategies for screening very large libraries of chemical compounds in a systematic, high throughput manner to find the one that has the right properties. NIH recently has gotten much more involved in such efforts, helping many academic investigators who are interested in taking their basic discoveries and move it in the direction of therapeutics.
Still, it is one thing to have a compound that works in a Petri dish, and quite another to give it to a patient. There is much work that needs to be done in terms of testing the compound’s toxicity in an animal, as well as assessing its ability to be metabolized and absorbed. All of these steps are long, expensive, and time-consuming processes. It is in this gap between target discovery and human clinical trials where a lot of drug development projects die – a gap that many in the industry refer to as the “Valley of Death.”
NIH is now pushing very hard to bridge that Valley of Death for carefully chosen projects. Make no mistake, we are not trying to compete with the private sector. Instead, we are developing new partnership models, especially for unexplored drug targets or diseases that are relatively less common, and for which there exists little economic incentive to develop therapeutics. For example, NIH’s new Cures Acceleration Network, which was established by the Patient Protection and Affordable Care Act, will make it possible for academic investigators to move their discoveries much further down that pipeline towards a therapeutic. Also, to carry out initial clinical trials to see if the drugs work, NIH has a 240-bed clinical research center on its Bethesda, Md., campus, along with a network of about 60 clinical centers scattered all over the country. In addition, the NIH has established a much stronger relationship with the Food and Drug Administration, trying to ensure that there is a synergism there between the development of new drug compounds and their oversight.
I’m optimistic that, working in partnership with the private sector, we can create a new paradigm that will provide the public with new and more effective treatments far faster than we do now. We simply cannot sit around and wait for the next blockbuster drug. In fact, there are not going to be very many blockbusters. As we increase our molecular understanding, diseases are actually being divided into smaller and smaller subsets, which means that the odds of finding one blockbuster drug that works against all subtypes are growing smaller and smaller. Instead, we likely will need to develop a wide array of drugs, each exquisitely targeted to specific subtype. So, if we want to see true progress in the rational design of therapeutics, NIH-supported science has to play a larger role – and that will be one of my highest priorities during my time as NIH Director.
None of this should be taken as an erosion of NIH support for basic science, however. Basic science is the foundation of all translation, and must continue to be a major component of our research agenda.
6. Judge Royce Lambert recently ruled that the Obama administration’s policy on embryonic stem cell research violated the Dickey-Wicker amendment. How has this ruling affected the NIH? How do you hope to resolve this issue?
The preliminary injunction issued on Aug. 23, 2010 has cast a cloud of uncertainty in the field of human embryonic stem cell research. Young scientists, once excited about careers in stem cell research, are now worried about the future.
If this research is slowed or halted, the greatest loss will be suffered by the millions of Americans with conditions that might be helped by research involving human embryonic stem cells. Such people include those suffering from heart disease, diabetes, liver disease, and vision problems, along with those afflicted by spinal cord injuries and neurodegenerative conditions, such as amyotrophic lateral sclerosis and Parkinson’s disease. While we continue through the legal process, we must keep patients and their families foremost in our thoughts.
7. You earned your PhD in physical chemistry from Yale in 1974. What is your favorite memory of Yale?
While at Yale in 1972, a course in biochemistry changed the course of my life. Taught by Peter Lengyel and Bill Summers, this course sparked my interest in the molecules that hold the blueprint for life: DNA and RNA. It became clear to me that a revolution was coming in molecular biology and genetics. So, I shifted gears and moved away from the orderly logic of physical chemistry and into the wild and “messy” world of biology and medicine.
I enrolled in medical school at the University of North Carolina in Chapel Hill, where I earned an M.D. in 1977. After a residency and chief residency in internal medicine, I returned to New Haven for a postdoctoral fellowship in human genetics at Yale Medical School. Fortunate enough to be mentored by Sherman Weissman, a wonderful advisor who encouraged creativity, I used the opportunity to develop an innovative approach, called chromosome jumping, to cross large strands of DNA to identify genes responsible for inherited disorders.
8. What advice do you have for people interested in scientific research, healthcare and medicine?
Choose important problems to work on. Identify great mentors. Persevere.
Our world urgently needs bright, creative minds if we are to turn discovery into health. Equally important, we need such minds to work together. Our ability to unravel nature’s biggest mysteries and solve medicine’s toughest puzzles will hinge upon assembling complex research teams that meld biological know-how with expertise in computer science, physics, math, clinical research, bioethics, and many other disciplines.
Also, bear in mind that the power of discovery comes with a very serious responsibility — the responsibility of scientists to weigh the ethical, legal, and social implications of their research before embarking upon a project or advocating a new technology. Clearly, we do not yet have the answers to many of these daunting questions. It likely will take years of thoughtful research and vigorous debate among scientists, ethicists, legal scholars, and ordinary citizens to chart the wisest course. And that is where you come in. Whether your journey of discovery takes you to a high-tech laboratory, an inner-city clinic, the courtroom, or some other equally challenging setting, the future depends on you.