Chapter 1 opened with two illustrative clinical scenarios. Although not based on specific patients, these scenarios reflect current medical practice and are typical of thousands of real people who visit American clinics every day.1 Patient 1—an otherwise healthy woman with breast cancer—is a direct beneficiary of the stunning advances in science and medicine that have occurred during recent decades. Her physician knows the molecular details of the pathological processes that threaten her life and has at her command therapies that directly target the aberrant molecular events occurring in Patient 1’s cells. The safety and efficacy of these therapies have been confirmed by randomized clinical trials involving other patients well matched with Patient 1 in the molecular details of their disease. Her prognosis is excellent. With continuing advances in science and medicine, similar patients with this type of breast cancer, whose molecular pathology we are beginning to understand, may expect access to treatments that are even safer, more effective, less expensive, and have fewer side effects.
Patient 2 presents a different story. Contemporary medicine has little to offer him beyond a long-available diagnosis and treatment plan. After 50 years of intensive study, substantial headway has been made in the scientific understanding of diabetes. Unlike many children who have a sudden onset of diabetes early in life, we know that Patient 2 has high levels of circulating insulin. His physician may ultimately consider attempting to control his diabetes with still more insulin, but the fundamental problem in this case—and with millions of
1 In 2010, approximately 1.9 million men and women were diagnosed with diabetes, and approximately 261,100 individuals were diagnosed with breast cancer in the United States. [Source: http://www.diabetes.org/diabetes-basics/diabetes-statistics/ and http://www.breastcancer.org/symptoms/understand_bc/statistics.jsp?gclid=CLeJwq7p76sCFUld5QodLz1TLw, http://www.cancer.org/Cancer/BreastCancer/OverviewGuide/breast-cancer-overview-key-statistics.]
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5 Epilogue Chapter 1 opened with two illustrative clinical scenarios. Although not based on specific patients, these scenarios reflect current medical practice and are typical of thousands of real people who visit American clinics every day.1 Pa- tient 1—an otherwise healthy woman with breast cancer—is a direct beneficiary of the stunning advances in science and medicine that have occurred during recent decades. Her physician knows the molecular details of the pathological processes that threaten her life and has at her command therapies that directly target the aberrant molecular events occurring in Patient 1’s cells. The safety and efficacy of these therapies have been confirmed by randomized clinical tri - als involving other patients well matched with Patient 1 in the molecular details of their disease. Her prognosis is excellent. With continuing advances in science and medicine, similar patients with this type of breast cancer, whose molecular pathology we are beginning to understand, may expect access to treatments that are even safer, more effective, less expensive, and have fewer side effects. Patient 2 presents a different story. Contemporary medicine has little to offer him beyond a long-available diagnosis and treatment plan. After 50 years of intensive study, substantial headway has been made in the scientific under- standing of diabetes. Unlike many children who have a sudden onset of diabetes early in life, we know that Patient 2 has high levels of circulating insulin. His physician may ultimately consider attempting to control his diabetes with still more insulin, but the fundamental problem in this case—and with millions of 1 In 2010, approximately 1.9 million men and women were diagnosed with diabetes, and approxi - mately 261,100 individuals were diagnosed with breast cancer in the United States. [Source: http:// www.diabetes.org/diabetes-basics/diabetes-statistics/ and http://www.breastcancer.org/symptoms/ understand_bc/statistics.jsp?gclid=CLeJwq7p76sCFUld5QodLz1TLw, http://www.cancer.org/ Cancer/BreastCancer/OverviewGuide/breast-cancer-overview-key-statistics.] 75
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76 TOWARD PRECISION MEDICINE other patients with type 2 diabetes—is that his cells respond only weakly to in - sulin. His blood sugar remains abnormally high even as his cells receive a strong signal to take the sugar up and metabolize it. The insidiously toxic effects of high levels of circulating sugar threaten the health of Patient 2’s blood vessels. As they age, many type 2 diabetics suffer severe consequences of a deteriorat - ing vasculature. When minor wounds to their feet fail to heal, they often face amputation. As capillaries in their retinas rupture, many go blind. Responses to drug treatments, which have changed little for decades, are highly variable. Similarly, changes in exercise habits and diet help some patients more than oth- ers. There is a high likelihood that Patient 2 faces a future of escalating medical interventions, declining health, and increasing disability. The human, social, and economic costs associated with patients such as Patient 2 are daunting and distressingly typical of those seen for patients with chronic diseases throughout our aging population. The Committee’s assigned task was to “explore the feasibility and need, and develop a potential framework, for creating a ‘New Taxonomy’ of human diseases based on molecular biology.” While the adjective “new” in the Com - mittee’s charge provoked much lively discussion—there were varying opinions as to whether a new disease classification would be likely to differ dramatically in kind from existing taxonomies—there was immediate consensus on the more important point: everyone on the Committee agreed that a better taxonomy is needed and that we have a spectacular opportunity to create one. Moreover, the Committee clearly recognized that developing and implementing a Knowledge Network of Disease has the unique potential to go far beyond classification of disease to act as a catalyst that would help to revolutionize the way research is done and patients are treated. Patient 1 has a high likelihood of overcoming her life-threatening disease and going on to live a long, healthy, and productive life. These prospects are a direct result of a new ability to recognize, based on molecular analyses, the precise type of breast cancer she has and to target a rational therapy to her disease. The Committee believes that the best prospects for creating a similarly bright future for Patient 2 lies in achieving a similarly precise understanding of his disease by creating a Knowledge Network of Dis - ease and an associated New Taxonomy. The Committee recognized two key points about its charge: first, develop - ment of an improved disease taxonomy is only one facet, albeit an important one, of the challenge of leveraging advances in biomedical research to achieve better health outcomes for patients; secondly, no single stream of activity—led by any single segment of the biomedical research community—can tackle even this limited goal on its own. Both these points suggested that we could best ad - dress our charge by framing the “new-taxonomy” challenge broadly. Many of the conclusions and recommendations could apply, as well, to other challenges in “translational research” such as evaluating and refining existing treatments and developing new ones. However, disease classification is inextricably linked
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77 EPILOGUE to all progress in medicine, and the Committee took the view that an ambi- tious initiative to address this challenge—and particularly to modernize the “discovery model” for the needed research—is an excellent place to start. The Committee thinks that the key to success lies in building new relationships that must span the whole spectrum of research and patient-care activities that com - prise American medicine. As discussed in Chapter 2, the Committee thinks that now is a propitious time to confront the challenge of developing a Knowledge Network of Disease and deriving a New Taxonomy from it because of changes that are sweeping across basic and translational research, information technol - ogy, drug development, public attitudes, and the health-care-delivery system. Our recommendations seek to empower stakeholder communities by pro - viding them with informational resources—the Information Commons, the Knowledge Network, and the New Taxonomy itself—that would transform the way they work and make decisions. We make no specific promises about the benefits that would ensue as this transformation occurs but have every con - fidence that this initiative would be a powerful, constructive force for change throughout a large enterprise that plays an increasingly central role in science, technology, the economy, and each of our lives—and one that is notoriously difficult to reform. At the core of the Committee’s optimism is a conviction that dramatic ad- vances in biological knowledge can be coupled more effectively than they are now to the goal of improving the health outcomes of individual patients. Biol - ogy has flourished in the 50+ years since the discovery of the molecular basis of inheritance. Powerfully reinforced by the Human Genome Project, genetics is in a “golden age” of discovery. Sequence similarity between genes studied in fruit flies and those studied in humans allows nearly instant recognition of the potential medical relevance of the most basic advances in biochemistry and cell biology. Increasingly, this process also works in reverse: unusual human patients call attention to molecules and biochemical pathways whose importance in basic biology had been overlooked or was otherwise inaccessible. Indeed, there are already many areas of basic biology in which human studies are leading the way to deep new insights into the way organisms work. A good example is color vision. For the simple reason that one can ask a research subject what she sees when looking at a pattern of light—instead of having to develop a crude behavioral test to find out whether she sees anything at all—we know far more about the molecular details of light reception in humans than we could ever have learned from studying mice. Particularly as biomedical research puts an increasing emphasis on unraveling the molecular underpinnings of behavior, the advantages of starting research studies with humans, rather than model organisms, are likely to grow. Experience tells us that translation of intensifying knowledge of basic biology into clinical advances is a daunting task. Nonethe - less, the many examples of success encourage optimism. Furthermore, the Committee shares the sense that basic biology is at an “inflection point” in
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78 TOWARD PRECISION MEDICINE which there is every reason to expect increasing payoffs from the large invest - ments in basic science that have brought us to this point. However, the grand challenge of coupling basic science more effectively to medicine will require a rethinking of current practices on a scale commensurate with the challenge. The Committee regards the initiative it proposes to develop the tripartite In - formation Commons, Knowledge Network, and New Taxonomy, as having the potential to rise to this level. Information technology is the key contributor to the technological conver- gence the Committee perceives. Information technology, quite simply, has made the rise of data-intensive biology possible: molecular biology, as now practiced, could not exist without modern computing systems. In medicine, information technology offers perhaps the best hope of increasing efficiency and improv - ing our collective learning about what works and what does not. Throughout society, technology is changing attitudes toward information. In a mere 20 years, people have made the transition from regarding most human knowledge as locked away in the dusty backrooms of research libraries to expecting it to be at their finger tips. Understandably, the public is losing patience with bar- riers to the sharing and dissemination of information. The social-networking phenomenon is a particularly dramatic illustration of changing attitudes toward information and associated blurring of the line between the public and private. For all these reasons, the Committee sees powerful forces converging in a way that favors the dismantling of existing barriers—institutional, cultural, eco - nomic, and legal—between the biomedical research environment, the clinic, and the public. The Committee recognizes that some aspects of the world we envision are more readily approachable than others. Even the easiest steps will be challeng - ing. As emphasized throughout this report, there are many impediments to progress along the path we outline. That is the reason the Committee recom - mends pilot projects of increasing scope and scale as the vehicle for moving forward. Although we consider the creation of an improved classification of disease valuable in its own right, we do not recommend a crash program to pursue this goal in isolation from the broader reforms we emphasize. We regard smaller projects on the recommended path as preferable to larger, narrower initiatives that would distract attention and resources from these reforms. We think the impediments can best be overcome and the optimum design of the Information Commons, Knowledge Network, and the New Taxonomy best emerge in the context of pilot projects of increasing scope and scale. Even some stakeholders in the health-care system who find the Commit - tee’s basic vision compelling may ask whether or not a special, organized effort is required to achieve the Committee’s goals. In particular, some might argue that there are already enough examples—many have been cited in this report— in which data-intensive laboratory tests have such clear benefits for patients that the traditional system of test development and insurance reimbursement
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79 EPILOGUE will allow a smooth transition to a new era of molecular medicine. We would caution against this conclusion. Indeed, there is real risk of a backlash against premature claims of the efficacy of genomic medicine (Kolata 2011). The key to avoiding such a backlash is development of a robust system for discovering applications that have real clinical benefits and validating those claims through open processes. The Committee believes that expecting or pressuring payers in the health-care system to bear the costs of integrating data-intensive biology and medicine without clear evidence of the safety, efficacy, and economic feasi - bility of particular applications would fail—indeed, such an effort could easily be counter-productive. On the other hand, as some of the scenarios sketched above indicate, the Committee believes that a well planned public investment in creating the system the Committee envisions would lead relatively quickly to robust public–private partnerships that would allow all stakeholders to build on early successes. Perhaps even more importantly, the Committee believes that its approach offers the most realistic available path to ultimate sustainability of precision medicine. Public investment in research can play an essential role in building a solid foundation for precision medicine, but it cannot sustain its dissemination: precision medicine will only become a routine aspect of health care when it pays its own way. To bring the discussion back to the Committee’s core mission, we close by re-emphasizing our view toward disease taxonomy. Diagnosis is the foundation of medicine. Accurately and precisely defining a patient’s condition does not assure effective treatment, but it is unequivocally the place to start. Hence, in exploiting the convergent forces acting throughout the health-care system, a long-term focus on developing the new informational resources proposed in this report would be a powerful unifying principle for biomedical researchers, physicians, patients, and all stakeholders in this vast enterprise. Whether the payoff from such a commitment would occur in time to help Patient 2, the 40-year-old type II diabetic described at the beginning of this report, is impos - sible to say. However, the Committee believes that implementation of its core recommendations would bring many new allies to the cause of improving this patient’s health prospects and would equip these diverse players with powerful new tools and resources that are unlikely to emerge without an organized effort to create them.
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