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AS THE RECENTLY APPOINTED SECOND DEPUTY DIRECTOR OF THE NATIONAL HUMAN GENOME RESEARCH INSTITUTE,THE INSTITUTION RESPONSIBLE FOR LEADING THE HUMAN GENOME PROJECT, DR.ALAN GUTTMACHER’S EXTENSIVE CLINICAL GENETICS BACKGROUND WILL BE INVALUABLE AT A TIME WHEN RESEARCHERS ARE BEGINNING TO TRANSLATE THE INFORMATION CONTAINED IN THE NEARLY COMPLETED HUMAN GENOME SEQUENCE INTO MEDICAL ADVANCES.
In the genes
BY KIM RIBBINK
ALAN Guttmacher PharmaVOICE O One might conclude that Dr. Guttmacher’s penchant for medicine was genetically pre determined — both of his parents are physi cians, as are his siblings, and the uncle for whom he is named. The irony of his eventual career choice is not lost on Dr. Guttmacher, who explored a variety of interwoven paths before becoming a renowned geneticist and physician. “When I entered college I thought I was going to be a criminologist, I was very inter ested in social psychology and social rela tions,” he recalls. “I even did an internship at a local correctional facility. For various reasons, however, I decided that was really not what I wanted to do with my life.” After graduating with a degree in social relations, Dr. Guttmacher pursued a number of avenues, including politics, working on a farm, and teaching middle school for a couple of years. Teaching caught his interest, and eventually became one of his life’s passions — a pursuit he holds dear to this day. Teaching also helped form the framework for his future expertise in genetics research. “I decided that I wanted to do something that had a broad impact,” he says. “I applied to and was accepted to attend graduate school to pursue a career in public health. However, my older brother talked me into going to medical school first. Having only taken one science course as an undergraduate, I spent a year and a half taking premed courses. Then I spent a year before med school working in rural health administration because I thought I might like to practice primary care in a rural health envi ronment. Once in med school I decided to spe cialize in pediatrics for a couple of reasons.” His interest in pediatrics was piqued by his experiences in teaching middle school, where he developed an interest in learning disorders. “I became convinced, perhaps in error, that ALAN Guttmacher PharmaVOICE R A the folks who really had knowledge of learning disorders were not so much the educators, but the researchers who were publishing scientifi cally rigorous and valid findings in pediatric literature. I wanted to work more effectively with kids who had learning disorders. “I also wanted to be involved in an area of medicine that allowed me to interact, on a reg ular basis, with both with kids and adults,” he says. “Pediatrics allowed for both. Intellectual ly, I find pediatric illnesses interesting. I also enjoyed working with pediatricians — they are a nice bunch of people.” The plan, according to Dr. Guttmacher, was to pursue primarycare pediatrics for a number of years, then hone in on one specialty. Not sur prisingly, with a keen interest in human behav ior, that specialty became genetics. As fate would have it, Dr. Guttmacher’s longterm goal quickly became a reality. “I owed time to the National Service Corp. to pay back my med school loan, and I ended up doing a genetics scholarship right away,” he says. “I picked genetics because I had an intellectual interest in the way genetic factors work, I also liked dealing with families in clinical genetic settings.” Dr. Guttmacher’s diverse background allowed him to pursue a variety of assignments throughout his career. During his tenure at the University of Ver mont College of Medicine — first as an asso ciate professor of pediatrics and later as the founding director of both the Vermont Human Genetics Institute and the university’s Familial Cancer Program, Vermont Cancer Center — he juggled his time between clini cal genetics, teaching, administrative work, research, seeing patients in genetic clinics, as well as being the founding director of the first pediatric intensivecare unit in Vermont. Reading the Tea Leaves For Dr. Guttmacher the area of genetics held the greatest promise, which at the time — back in the early 1980s — was a specialty relatively in its infancy. “Of all the areas of medicine, it seemed to me that genetics was the one that was going to change the most and be the most exciting dur ing my professional lifetime,” he says. “And of all the decisions I have made, this is the one decision I tap myself on the back about. I real ly read the tea leaves correctly back then.” Dr. Guttmacher believed that genetics would provide him an opportunity to pursue exciting research and make contributions to medicine that would have a broad impact. “We are just launching into an era when a genomic approach to medicine is not only going to change the way we look at healthcare in gen eral, but enable us to really make a difference in people’s lives in terms of their own health,” he says. “This is a wonder fully exciting time.” As the new second deputy director of the National Human Genome Research Institute (NHGRI), the institution respon sible for leading the Human Genome Project, Dr. Guttmacher is bringing his extensive clini cal genetics background to the HGP at a time when researchers are beginning to translate the information contained in the nearly completed human genome sequence into medical advances. In his new role at the NHGRI, Dr. Guttmacher is helping to integrate genomics into medical practice, assisting the NHGRI with developing new research tools to trans late the findings of the human genome project into new diagnostic tests and therapies, and overseeing strategic planning for the institute and its impact on the field of genomics. “I’m very excited about the new position,” Dr. Guttmacher says. “It’s an incredible opportunity at this particular place, at this particular point in time, to do a job that can make a difference in the way we answer some important scientific questions. And, to me probably more important, is how we accom plish a new kind of healthcare that will make a real difference in people’s lives.” A Century of Change Genomics, Dr. Guttmacher believes, has the potential to be for healthcare in the 21st YOU SPENT MANYYEARSWORKING IN ACADEMIA ANDHAVEAN EXTENSIVE BACKGROUNDASAN EDUCATOR.HOW AREYOU FINDINGTHETRANSITION FROMACADEMIATOGOVERNMENT? My biggest concern about moving to a governmental role was the amount of bureaucracy I was going to deal with. But I’ve found that, in general, I deal with much less bureaucracy as a government employee than I did when I was in academia. I find I’m given the resources I need to do my job instead of hav ing to spend much of my job wondering how I’m going to get resources and how I am going to function if I spend time on a com mittee, etc.? Although it is very rewarding,at this particular point in time,an aca demic career has a great deal of challenges. I love academia and had planned to stay there forever,and may well goback someday,but now that I’m out of it I can see that there were difficulties involved. Adoublestrand approach IN ANEXCLUSIVE INTERVIEWWITH PHARMAVOICE, ALAN E.GUTTMACHER,M.D.,TALKS ABOUTTHECHALLENGES AND OPPORTUNITIESOFWORKING FORTHENHGRI,ANDWHAT LEDHIMTO THE INSTITUTE. ALAN GUTTMACHER For those in academic medicine it’s not an easy time, because of the challenge of finding the resources to do the job one wants to do. WHATDOYOUMISSMOSTABOUTYOUR ROLES IN ACADEMIA AND CLINICAL PRACTICE? I don’t get to teach students very much anymore,and I don’t have much ALAN Guttmacher PharmaVOICE T century what knowledge of infectious disease was for the last. “The most important advances in health status and care, in the U.S. and globally, in the last century stemmed from our understanding of infectious disease and being able to impact mortality and morbidity,” he says. “The same idea of applying knowledge of genomics to diagnosis, to therapy, to prevention, just as we did for infectious disease, will have the same lasting impact.” This vision to apply genetics research to practical medicine has won him much support and acclaim. “It’s wonderful for NHGRI to have Dr. Guttmacher as its deputy director,” says Fran cis S. Collins, M.D., Ph.D., director of the NHGRI. “Alan is an exceptional medical geneticist and has been a valuable advisor to the institute. His ability to see how genomic medicine can be applied in the clinical setting and his passion as a physician will be a tremen dous asset in taking NHGRI into a new era of applying the fruits of the Human Genome Project to improved human health.” Before joining the National Institutes of Health, Dr. Guttmacher ran a number of geneticsrelated projects in Vermont, investi gating ways to integrate a genomics approach into the state’s healthcare. “When there was an opening in Washing ton to do the same kind of thinking, involving the same kinds of issues in a more national way with people whom I believed I would really enjoy working with, it was a pretty easy decision to make the move,” he says. Having joined the institute just three years ago, Dr. Guttmacher’s rise to second deputy director of the NHGRI has been fairly rapid. His approach to genetics, coming from a clin ical healthcare perspective rather than strictly research, is somewhat unusual in the institute, but undoubtedly this was the linchpin for his appointment. Since his arrival at the institute, Dr. Guttmacher has been focused on finding ways to integrate genomics into the nation’s health care. In addition, he also has served as acting director of the office of Policy, Planning and Communications. The office was formed to look at policy development and analysis relat ed to the ethical, legal, and social implications of human genome research; administer a com munications program aimed at disseminating information about the science and policies of the HGP and the NHGRI’s genetics research programs; track and analyze legislation; and oversee program planning and evaluation. As the institute began to address its future role, Dr. Guttmacher’s background made him an ideal candidate to fill the role of deputy director, which was vacated by Dr. Elke Jordan who retired in July after 30 years of service to NIH. Dr. Jordan secured her place in NIH history as an integral leader of the Human Genome Project. “The institute had been founded primarily to coordinate the Human Genome Project,” Dr. Guttmacher says. “While the institute is clearly going to continue to be involved in basic science, in genomics, in sequencing of other organisms, it also is going to be more involved in areas of translational research, and thinking about how to move genomics into patient care. Since I’d been involved with those issues for the past few years, Dr. Collins decided I might be a good person for this role at this point in time.” Thinking Outside the Box As the NHGRI prepares to move into the next phase of its development, which involves a significant planning process to decide what its contribution to the future of genomics will be, one of Dr. Guttmacher’s role is to help coordinate this process and monitor the insti tute’s progress going forward. “There clearly remain scientific and techni cal challenges in terms of research questions that need to be answered, but there also is the huge challenge of educating health profession als and the general public about this new knowledge base,” he says. Dr. Guttmacher’s penchant for teaching continues to come into play in his role at the NHGRI. “I give about 50 talks a year, the plurality of which are to various professional groups about integrating genetics into medicine,” he says. “That’s part of what I really love doing — to go out and teach people about the possi bilities. “This is particularly important, because there are a number of ways in which genomics can be misapplied and misunderstood, which could lead to ethical consequences,” he says. “There will be a seductive power in that this direct patient contact. I love being a doctor, it’s a wonderful privilege. Intellectually I know I’m able to do things at the NHGRI that will improve more people’s lives more than my individual medical practice. But on a daytoday basis, I do miss the individual patient contact. YOUHAVE BEENTHE RECIPIENT OFMANYAWARDS.CANYOU MENTIONONEORTWOTHATHAVEPARTICULAR SIGNIFICANCE FORYOU? I was elected as a faculty member to Alpha Omega Alpha, which is the medical honorary society. Every year students at the University of Ver mont elect one faculty member to this national honorary society. This movedme because it was about the relationship with students,which is important to me. Another honor was being selected to the Hereditary Hemorrhagic Telangiectasia Foundation International, which is a family support group. Hereditary hemorrhagic telangiectasia is a specific genetic disorder that has been one of my primary research interests. It was an honor to be selected by my patients and research subjects. WHOHAVEBEENYOURMENTORS? My mentors have been primarily my family, and some teachers from high school.Bothmy parents taught mewonderful life lessonsand,since they’re both physicians, professional lessons as well. But particularly life lessons.They’ve been my most important mentors. In medicine there are people whohave,and continue to,serve as role models.When I was younger, I thought at some point in life one doesn’t have mentorsanymore,but I don’t know if that ever happens.No matter what age you are, you still have mentors. AS AMENTORYOURSELF,WHATARETHE MOST IMPORTANT THINGS IN GUIDINGOTHERS? The most important thing is having a genuine interest in their lives and careers. Mentoring is not just teaching people information, but being willing to engage on a personal level. Some aspects of being a role model are conducting your professional life in a way that is good and honorable and effective, but also it’s taking a personal interest in stu dents, maintaining those relationships, and being available for those people. ALAN Guttmacher PharmaVOICE new knowledge base may lead people to think that their genetic makeup completely predicts their future. There is a danger of oversimplify ing the role of genomics. Just because we have the human genome sequence in hand, and that within the next few years we will have a better understanding of the genetic factors involved with disease, doesn’t suddenly make the nongenetic factors, the environmental factors, less important than they were last year. These are just as important as they ever were. “For example, if somebody is shown to have a genetic predispo sition to a certain type of cancer, the most important thing they can do is stop smoking,” he says. “Having genetic knowledge won’t necessarily result in gene therapy. We may know our genetic make up, but disease management will have a lot to do with how we handle our environ ment.” Caution aside, Dr. Guttmach er believes that this is the most exciting time in history to be involved in genetic science. “I marvel at the science and technology involved in the human genome sequence — it’s a real techno logical and scientific tour de force, it’s beauti ful,” Dr. Guttmacher says. “But what we’re about to launch into now is much more engaging and interesting because it has to do with integrating this knowledge into human life, influencing the way people think about health, changing the way they practice pre vention strategies to stay healthy, and design ing drugs to meet these needs.” This type of forward thinking requires the institute to anticipate the future, but, Dr. Guttmacher says, this is nothing new for NHGRI since it was just this type of thinking that led to the sequencing of the human genome. “When the human genome project was started there were many people who thought it wasn’t doable from a technical standpoint, and even when it was feasible, they doubted its worth,” he says. “But the people involved with the project understood that once the basic framework had been created, it would launch other research initiatives that wouldn’t have been undertaken nearly as effectively or effi ciently without it.” Already, the institute is forging ahead with some outofthebox thinking, such as addressing key issues around diversity in rela tion to genomics. “Our institute is keenly interested in diversity issues for a number of reasons,” Dr. Guttmacher says. “Part of the interest comes from the ethical, legal, and social implications of genomics. Clearly genomics plays a part in the relationship between biology and con structs of race and ethnicity, for instance. “We also are keenly aware that individuals from minority populations are significantly SEPTEMBER 2002. Second deputy director of the National Human Genome Research Institute. The NHGRI is the institution responsible for leading the Human Genome Project for the National Institutes of Health 1999–2002. Senior clinical advisor to the director, NHGRI; acting director of the NHGRI Office of Policy, Planning and Communications 19961999. Medical staff, Rutland Regional Medical Center, Rutland, Vt. 19951999. Founding Director, Vermont Human Genetics Initiative, University of Vermont College of Medicine 19931999. Founding Director, Familial Cancer Program, Vermont Cancer Center,University of Vermont College of Medicine 19931996. Associate Professor of Pediatrics with tenure,University of Vermont College of Medicine 1991. Founding Director, Pediatric Intensive Care Unit, Medical Center Hospital of Vermont 19891999.Founding Medical Director,Vermont Newborn Screening Program 19871993. Assistant Professor of Pediatrics, University of Vermont College of Medicine 19871999.Director,Vermont Regional Genetics Center and Pregnancy Risk Information Ser vice, University of Vermont College of Medicine 19871999. Referring consulting staff, Champlain Valley Physicians Hospital,Plattsburgh,N.Y. 19871999. Attending in pediatrics, Medical Center Hospital of Vermont,Burlington,Vt. 19861987. Senior Associate in Pediatrics, Beth Israel Hospital, Boston,MA 19851987. Fellow in Medical Genetics, Children’s Hospital and Harvard Medical School, Boston 19821985. Intern and Resident in Pediatrics, Children’s Hospital, Boston 19811982. Physician, Developmental Pediatrics Clinics, Children’s Hospital,Boston Board Certification 1987.American Board of Medical Genetics,Diplomate and Certification in Clinical Genetics 19891996.American Board of Pediatrics, Diplomate EDUCATION: 19771981. M.D., Harvard University 19751976. Premedical student, Duke University 1975. Premedical student, Johns Hopkins University 19671972. A.B. cum laude in Social Relations, Harvard University AWARDSANDHONORS: 2000. Joseph E. Cannon Award,New England Public Health Association 1999.Honorable Mention,American MedicalWomen’sAssociation Gender Equity Award,Uni versity of Vermont 1996.Volunteer of the Year, Hereditary Hemorrhagic Telangiectasia Foundation International 1990.Alpha Omega Alpha Medical Honorary Society, University of Vermont 1989.Volunteer of the Year,Vermont Chapter,March of Dimes Birth Defects Foundation 19851987. National Research Service Award,U.S.Public Health Service 19851986.Farley Fellowship,Children’s Hospital,Boston 19781981.National Health Service Corps Scholarship,U.S.Public Health Service Career sequencing ALAN E. GUTTMACHER — RESUME Dr. Guttmacher’s passion for education also has led to the formation of a cohesive Internet program at the institute. ALAN Guttmacher PharmaVOICE R under represented in the genomics workforce,” he says. “If genomics is going to be integrated into society in a useful and meaningful way, we need to have people from all populations involved in the decisionmaking process as health professionals and in research. There is an overwhelming importance to honor diver sity and to explore it scientifically, but also to make sure that we are sensitive to cultural issues involving different populations and issues about genetics. By diversity, I’m includ ing the involvement of underrepresented communities, about the scientific and socio cultural relationship between genetics and constructs of race and ethnicity.” For Dr. Guttmacher, this is uncharted ter ritory. And while many questions remain to be answered in terms of how genomic medicine will change healthcare in terms of environ mental disparities in the U.S. and in develop ing countries, he is confident that genetic research will make a difference. “This will be one of the most important areas of focus for us over the next few years and will become part of the planning process as we move forward,” he says. To that end, the institute recently hired a senior consultant to look specifically at health disparity issues. Reaching the Masses Dr. Guttmacher’s passion for education also has led to the formation of a cohesive Internet program at the institute. In 1999, Dr. Guttmacher and Dr. Collins founded Genetic Resources On the Web, otherwise known as GROW, which works with organizations sponsoring geneticsrelated Websites to ensure that they contain highquality infor mation. GROW’s membership includes some three dozen organizations, including health profes sional groups, patientsupport groups, federal agencies, foundations, nonprofit agencies, and forprofit companies. “GROW started just as a meeting and has become a semiformal organization of several dozen institutions that have an interest in the Internet as a way to provide genetics informa tion primarily to the general public, in addi tion to healthcare professionals,” Dr. Guttmacher says. Through education, technology, and research, genomics will help answer some very important scientific questions and make a dif ference in how healthcare is approached in the U.S. and the rest of the world. “I feel as though I’ve been struck by light ening to be able to work at the institute and have the opportunity to do things that make a difference in people’s lives,” he says. F PharmaVoice welcomes comments about this article. Email us at email@example.com. Mission accomplished: the NHGRI and the humangenome T The National Human Genome Research Institute (NHGRI) orig inally was established as the National Center for Human Genome Research (NCHGR) in 1989. Its primary mis sion is to lead the National Institutes of Health’s (NIH) contribution to the Human Genome Project — an international research effort to determine the location of all human genes and to read the entire set of genetic instructions encoded in human DNA. The NHGRI carries out this mission by pro viding financial support to scientists at universi ties and other public research laboratories throughout the U.S. In addition to supporting the Human Genome Project, the NHGRI established a Division of Intramural Research in 1993 to develop genome technologies that would accelerate the process of identifying and understanding the molecular basis of human genetic diseases. HUMANGENOMEPROJECT The Human Genome Project (HGP) official ly began in 1990 and is coordinated in the U.S. by the NHGRI and the U.S. Department of Energy. International HGP partners include the U.K., France, Germany, Japan, and China. Once scientists complete the ultimate task of sequenc ing all 3 billion base pairs in the human genome, they will have created a virtual blueprint for a human being. From 1990 to 1994, the activities of the HGP were primarily devoted to developing genetic and physical maps that allow precise localization of genes, and to exploring technolo gies that enable the sequencing of very large amounts of DNAwith high accuracy and low cost. Pilot projects were initiated in 1996 to explore the feasibility of such largescale sequencing of human DNA. These projects were extremely successful and resulted in cre ative laboratory innovations that automated and accelerated the sequencing process. By Septem ber 1997, the pilot projects had sequenced approximately 2% of human DNA. Now, with current technology, HGP centers can sequence 1,000 base pairs per second at a very low cost. Scientific leaders of the HGP also made an important decision in 1996 — to deposit sequence in public databases within 24 hours of its assembly, with no restrictions on its use or redistribution. This defining moment in the HGP made the sequence immediately available to anyone with an Internet connection, ensuring that the sequence would ultimately benefit the public by empowering all the world’s best minds. In June 2000, the International Human Genome Sequencing Consortium announced that a “working draft” sequence of the human genome, nearly 90% complete, had been pro duced. In February 2001, the consortium pub lished this sequence and an initial analysis of the human genome that reported a number of dis coveries. The most surprising of these was that humans have only 30,000 to 35,000 genes, whereas previous predictions had ranged from 80,000 to 150,000 genes. The HGP’s goal of producing a highly accu rate “finished” sequence will be met in 2003 — under budget and two years ahead of the original schedule. As the HGP nears completion, the mission of the NHGRI has expanded to encompass a broad range of studies aimed at understanding the structure and function of the human genome and its role in health and disease. The HGP’s goal of producing a highly accurate “finished” sequence will be met in 2003 — under budget and two years ahead of the original schedule.