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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.]
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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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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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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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