The Future of Genomics

The Future of Genomics

Statement of Francis S. Collins, M.D., Ph.D.

Director
National Human Genome Research Institute
National Institutes of Health
Department of Health and Human Services

Testimony
Before the Subcommittee on Health
Committee on Energy and Commerce
United States House of Representatives

Thursday, May 22, 2003

Mr. Chairman and Members of the Committee:

It is a pleasure to appear before you at this historic moment when we have just completed all of the goals of the Human Genome Project (HGP). I look forward to discussing with you the future of genomics at the National Institutes of Health (NIH), as well as the rest of the broader scientific community. I will start by giving a brief history of the HGP, highlighting our recent success. I will then discuss the National Human Genome Research Institute's (NHGRI) efforts to coordinate our work with other federal agencies, other governments, and the private sector. I will also describe our new vision for the future of genomics, as well as some new initiatives already under way. I hope to make clear that while we have just sequenced the 3 billion letters of the human DNA code, our work is really just beginning. The successful conclusion of the HGP heralds the true dawning of the genomic era. There is an ongoing vital role for the federal government in enabling the future of genomics, and especially in applying it to benefit human health.

Summary of the Human Genome Project

U.S. National Academy of Science Study on the Human Genome Project

The main goals of the HGP were first articulated in 1988 by a special committee of the U.S. National Academy of Sciences (NAS), and later adopted through a detailed series of five-year plans jointly written by the NIH and the Department of Energy (DOE). In 1988 Dr. James D. Watson, who won the Nobel Prize along with Francis Crick for discovering the structure of DNA, was appointed to head the then Office of Human Genome Research, which has grown into the National Human Genome Research Institute that I now have the privilege of directing. As of April 14, 2003, the principal goals laid out by the NAS have all been achieved more than two years ahead of schedule and $400 million dollars under budget, including the essential completion of a high-quality version of the human sequence. Other goals included the creation of physical and genetic maps of the human genome, which provided a necessary lower resolution view of the genome and have major value to research in their own right. The HGP also accomplished the mapping and sequencing of a set of five model organisms, including the mouse. That information generally empowers the ability to interpret the human genome, rather like the Rosetta stone allowed the decryption of the ancient languages. The NAS study also recommended that, "access to all sequence and materials generated by these publicly funded projects should and even must be made freely available [to all]." We have adhered to that noble standard throughout the last 13 years.

Congressional and Administrative Interest

Neither the NAS study nor the HGP would have occurred without the visionary leadership and determination of the Administration and the Congress. At the outset, many in the scientific community did not think that the HGP could be completed in a timely fashion or for an affordable cost. But the Administration and key members of the Congress felt that it was essential the United State government play a leading role in this project, and they correctly predicted that the project could be completed without taking resources from other important science. With the support of the Administration and the Congress, the recent doubling of the NIH budget allowed a dramatic increase in the pace of the HGP.

Last month, we were able to observe a major anniversary, the fiftieth anniversary of the discovery of the double helix structure of DNA by Drs. Watson and Crick, while simultaneously celebrating the completion of the DNA sequence of the human genome. In June 2000, the NHGRI and its partners in the International Human Genome Sequencing Consortium had already completed a "working draft" of the human genome sequence; at that same time, Celera Genomics, under Dr. Craig Venter's leadership, released its own draft version of the human genome and participated with us in a joint announcement at the White House. Since then the federally funded sequencing centers and our international partners have been working to correct all the remaining spelling errors and fill in the gaps in the draft sequence, leading to the public release of the essentially complete sequence on April 14, 2003. This is the reference sequence we will be using for all time. The availability of the 3 billion letters of the human instruction book could be said to mark the starting point of the genomic era in biology and medicine. There is now much important work to do to deliver on the promise that these advances in genomics offer for human health.

Coordination with Federal Agencies, other Governments, and the private sector

The HGP would have been impossible without an outstanding partnership between federal agencies, international organizations, and the private sector. From the inception of this project, the NIH has worked very closely with the DOE, and especially its Office of Science. In particular, I have had the great privilege of working with Dr. Aristides Patrinos, who has skillfully managed the DOE's efforts in this regard. We have also worked very closely with the governments and genome sequencing centers of five other countries: the United Kingdom, France, Germany, Japan, and China. In the United States the three main sequencing centers funded by the NHGRI are at the Baylor College of Medicine, Washington University in Saint Louis, and the Whitehead Institute of the Massachusetts Institute of Technology. Dr. Robert Waterston will be describing for you in a moment his work as the former Director of the sequencing center at Washington University.

The success of the HGP partnership was cited in a recent PricewaterhouseCoopers report, "Managing 'Big Science': A Case Study of the Human Genome Project," in which the author noted that: "A major implication for the future lies with the partnership model of R&D that HGP's organization revealed. Partnerships across agencies, sectors and nations are likely to be the wave of the future for large-scale public efforts at the frontier of knowledge. As a result of the HGP partnership, the first chapter of the human genome revolution is coming to a successful end, and next steps are underway."

New Vision for the Future of Genomics

This April also witnessed the publication in the journal Nature of a bold vision for the future of genomics research, developed by the NHGRI. This vision, the outcome of almost two years of intense discussions with literally hundreds of scientists and members of the public, has three major areas of focus: Genomics to Biology, Genomics to Health, and Genomics to Society.

Genomics to Biology: The human genome sequence provides foundational information that now will allow development of a comprehensive catalog of all of the genome's components, determination of the function of all human genes, and deciphering of how genes and proteins work together in pathways and networks.

Genomics to Health: Completion of the human genome sequence offers a unique opportunity to understand the role of genetic factors in health and disease, and to apply that understanding rapidly to prevention, diagnosis, and treatment. This opportunity will be realized through such genomics-based approaches as identification of genes and pathways and determining how they interact with environmental factors in health and disease, more precise prediction of disease susceptibility and drug response, early detection of illness, and development of entirely new therapeutic approaches.

Genomics to Society: Just as the HGP has spawned new areas of research in basic biology and in health, it has created new opportunities in exploring the ethical, legal, and social implications (ELSI) of such work. These include defining policy options regarding the use of genomic information in both medical and non-medical settings and analysis of the impact of genomics on such concepts as race, ethnicity, kinship, individual and group identity, health, disease, and "normality" for traits and behaviors.

This vision for the future of genomics is not just about the NHGRI. It encompasses the whole field of genomics, including the work of all the other Institutes and Centers at the NIH and of a number of other federal agencies. All of the NIH Institutes are already taking full advantage of the sequence and will apply its data to the better understanding of both rare and common diseases, almost all of which have a genetic component. A recent example of the way that the HGP and the knowledge and new technologies it has spawned are already facilitating science is the extremely rapid sequencing by groups in Canada and at the Centers for Disease Control and Prevention (CDC) in Atlanta of the genome of the virus that causes Severe Acute Respiratory Syndrome (SARS). The sequencing of the SARS virus genome provides insight into this new and deadly disease at a speed never before possible in science. In turn, this should lead to the rapid development of diagnostic tests and, in time, vaccines and effective treatments.

New NHGRI Initiatives

The NHGRI has already begun several new initiatives, and is planning others, to meet the challenge of realizing this new vision for the future of genomics. Many of these initiatives will be co-funded by other NIH Institutes, other federal and international partners, and the private sector. Some examples of these cutting edge programs include:

The Creation of a Human Haplotype Map

Multiple genetic and environmental factors influence many common diseases, such as diabetes, cancer, stroke, mental illness, heart disease, and arthritis; however, relatively little is known about the details of the genetic basis of such common diseases. Together with international partners, the NHGRI has begun to create a "haplotype map" of the human genome to enable scientists to find the genes that affect common diseases more quickly and efficiently. The power of this map stems from the fact that each DNA variation is not inherited independently; rather, sets of variations tend to be inherited in blocks. The specific pattern of particular genetic variations in a block is called a "haplotype." This new initiative, an international public/private partnership led and managed by NHGRI, will develop a catalog of haplotype blocks, the "HapMap." The HapMap will provide a new tool to identify genetic variations associated with disease risk or response to environmental factors, drugs, or vaccines. It will allow more efficient genomic research and clinical applications, thus making for more economical use of research and health care funds. Ultimately, this powerful tool will lead to more complete understanding of, and improved treatments for, many common diseases.

The ENCODE Project: the ENCyclopedia Of DNA Elements

To utilize fully the information that the human genome sequence contains, a comprehensive encyclopedia of all of its functional elements is needed. The identity and precise location of all transcribed sequences, including both protein-coding and non-protein coding genes, must be determined. The identity of other functional elements encoded in the DNA sequence, including signals that determine whether a gene is "on" or "off", and determinants of chromosome structure and function, also is needed. The NHGRI has developed a public research consortium to carry out a pilot project, focusing on a carefully chosen set of regions of the human genome, to compare existing and new methods for identifying functional genetic elements. This ENCyclopedia Of DNA Elements (ENCODE) consortium, which welcomes all academic, government, and private sector scientists interested in facilitating the comprehensive interpretation of the human genome, will greatly enhance use of the human genome sequence to understand the genetic basis of human health and to stimulate the development of new therapies to prevent and treat disease.

Genome Technology Development

The NHGRI continues to invest in technology development that speeds the applications of genomics. Technical advances have caused the cost of DNA sequencing to decline dramatically, from $10 in 1990 to less than $0.09 per base pair in 2002, but this cost must decline even further for all to benefit from genomic advances. The NHGRI, along with many partners, will actively pursue the development of new technologies to sequence any individual's genome for $1,000 or less. Other areas of technology development are also ripe for expansion, and the NHGRI plans to pursue them vigorously.

Vision of the Future of Genomic Medicine

While it always is somewhat risky to predict the future, I want to leave you with my view of where I believe genomic medicine is headed. In the next ten years, I expect that predictive genetic tests will exist for many common conditions in which interventions can alleviate inherited risk, so that each of us can learn of our individual risks for future illness and practice more effective health maintenance and disease prevention. By the year 2020, gene-based designer drugs are likely to be available for conditions like diabetes, Alzheimer's disease, hypertension, and many other disorders. Cancer treatment will precisely target the molecular fingerprints of particular tumors, genetic information will be used routinely to give patients more appropriate drug therapy, and the diagnosis and treatment of mental illness will be transformed.

Conclusion

This year marks a very exciting transition in the field of genomics, with the full sequencing of the human genome marking the successful achievement of all of the HGP's original goals, and thus the advent of the genomic era. When Congress decided to fund the HGP, it did so with the justifiable belief that this work would lead to improved health for all. Those advances are already occurring all around us, and the ability to accelerate the realization of this vision now lies before us. At the same time, we must be sure that these technological advances can benefit all our citizens in a safe and appropriate manner. It is our sincere belief that the newly created discipline of genomics will make a profound difference to the health and well being of all the people of this world.

While I am very optimistic about the future of genomic medicine, we clearly have a great deal more work to do to realize these lofty goals. The vision for the future of genomic medicine that I have described will require major breakthroughs in technology and scientific knowledge. But I am confident that by supporting our best and brightest scientists to work together with our partners within the government and around the globe, we will meet these challenges. We are profoundly grateful for the support the Congress has given to this endeavor. We would not be where we are today without your vital support. Thank you.

FRANCIS S. COLLINS, M.D., PH.D

Director, National Human Genome Research Institute
April 14, 1950. Staunton, Virginia

Education:

• University of Virginia, 1970 - B.S. (with Highest Honors)
• Yale University, 1972 - M.S.
• Yale University, 1974 - Ph.D.
• University of North Carolina School of Medicine, 1977 - M.D. (with Honors)

Professional History:

• 1977-1981, Intern, Resident, Chief Resident in Medicine, North Carolina Memorial Hospital, Chapel Hill, North Carolina.
• 1981-1984, Fellow in Human Genetics and Pediatrics, Yale University School of Medicine, New Haven, Connecticut.
• 1984-1993, Assistant, Associate and then Full Professor of Internal Medicine and Human Genetics, University of Michigan, Ann Arbor, Michigan.
• 1987-1993 Assistant, Associate, and then Full Investigator, Howard Hughes Medical Institute.
• 1993 to present, Director, National Human Genome Research Institute, NIH, Bethesda, Maryland.

Professional Organizations:

• American Society of Human Genetics;
• American Society for Clinical Investigation;
• Association of American Physicians;
• Institute of Medicine;
• National Academy of Sciences;
• American Academy of Arts and Sciences.

Awards and Honors:

• Morehead Foundation Fellow, 1973-1977;
• Alpha Omega Alpha, elected Junior year, President of UNC chapter, 1976-1977;
• Hartford Foundation Fellowship, 1985-1987;
• Paul di Sant'Agnese Award of the Cystic Fibrosis Foundation, 1989;
• Gairdner Foundation International Award, 1990;
• National Medical Research Award, National Health Council, 1991;
• American Academy of Achievement Golden Plate Award, 1994;
• The Baxter Award for Distinguished Research in Biomedical Sciences, Association of American Medical Colleges, 1994;
• Susan G. Komen Breast Cancer Foundation National Award for Scientific Distinction, 1995;
• Breath of Life Award, Cystic Fibrosis Foundation, 1997;
• Mendel Medal, Villanova University, 1998;
• Champions of Pediatric Research Award, Children's National Medical Center, 1998;
• Shattuck Lecture, Massachusetts Medical Society, 1999;
• Arthur S. Flemming Public Service Award, 1999;
• Association of American Physicians, George M. Kober Lecture Award, 2000;
• Scientist of the Year, National Disease Research Interchange, 2000;
• The Biotechnology Industry Organization and The Chemical Heritage Foundation Third Annual Biotechnology Award, 2001;
• Warren Triennial Prize Lecture, Massachusetts General Hospital, 2002;
• Walker Prize, Museum of Science, Boston, 2003.

Honorary Doctoral Degrees:

Emory University, Mary Baldwin College, Yale University, Mount Sinai School of Medicine, University of North Carolina, George Washington University, University of Pennsylvania, Brown University.