Science (pg. 1680)  [Printer-friendly version]
June 13, 2003


By Floyd E. Bloom

A growing problem of major proportions has been staring us in
the face for many decades. Until solved, this long-neglected
problem presents a gigantic obstacle to the application of the
discoveries flowing from biomedical research into deliverable
standards of medical practice that could benefit all of
society, both in the United States and globally. This problem
is the imminent collapse of the American health system. Unless
steps are taken soon to undertake a comprehensive restoration
of our system, the profound advances in biomedical research so
rapidly accruing today may never be effectively transformed
into meaningful advances in health care for society.

Today's term for such evolutions of discovery into application
has been dubbed "translational research" (1). The appealing
notion that research advances travel from bench to bedside is
laudable, but conceptually flawed. Even though the U.S.
Congress fully anticipates that funding to the National
Institutes of Health (NIH) will result in advances in clinical
medicine and that other forces, presumably nongovernmental (2,
3), will translate the latest in exciting science into health
technologies, under the systems of health care we have today,
this advancement is not likely to happen.

The Delusions of Success

I have been reflecting on the decisions that led me to abandon
my incomplete training as a physician for the exciting vistas
of what has now become the field of neuroscience. My goals as a
student and resident physician were to learn enough about
diseases to help others by treatment and prevention of
diseases. My introduction to clinical neuroscience research in
the setting of the National Institute of Mental Health's
Clinical Neuropharmacology Research Center at St. Elizabeth's
Hospital in Washington, DC, a massive federal hospital for the
mentally ill, allowed me to focus on understanding the
pathophysiological mechanisms of depression and schizophrenia.
It was my good fortune to be present at the dawning of
psychopharmacology, and to work in one of its principal centers
of discovery, the NIH Intramural Research Program. In that era,
we were thrilled when recognition of the common emotional
responses to drugs affecting brain chemistry in humans and
experimental animals led to testable hypotheses of depression
(4); when studies of the adopted-away children of patients
diagnosed as schizophrenic helped to sort out the genetic
influences in that disease (5, 6); and by the initial efforts
to image the brain's blood flow and infer regional changes in
underlying neuronal activity (7). How little we knew about how
much there was to learn.

Genomic Aspirations

Now fast-forward 40 years to the announcements of the initial
compilations of the human genome (8-10), a monumental
coordinated achievement, outstripping any other prior
biological knowledge base by orders of magnitude. This deluge
of data clearly has enormous implications for medical science
(11, 12). The pages of Science and other learned journals have
been loaded with anticipations of postgenomic medicine (12-15).
These vistas predict a time when we will be able to recognize
an individual's vulnerabilities to inheritable, disease-causing
factors and when we will be able to help those individuals
prevent the onset of their diseases. Even though most human
heritable diseases are not the result of single dominant or
recessive genetic mutations, the studies of strongly
inheritable diseases have provided solid clues to help
understand sporadic and complex, multigenic diseases such as
cardiovascular, metabolic (16), and brain diseases.

Nevertheless, even diseases whose genetic origins have been
fully defined are not always easily treated. Two that continue
to baffle modern medicine are Huntington's disease (17) and
Lesch-Nyhan syndrome (18). Although the dysfunctional proteins
of the mutant genes are known, the causes of their unique
neuropathologies and behavioral outcomes remain unknown after
decades of study. Tellingly, expression of the mutant genes in
mouse models or its knockout fails to replicate the human
neuropathology (19).

Complex Genetic Diseases of the Brain

In many of the most prevalent human brain diseases, genetic
vulnerability arises from multiple interactive inheritable
factors. Scholars of Alzheimer's disease, for example,
recognize that at least four different genetic mutations can
render members of some families at high risk to the disease
(20-25). Mutations of the gene encoding amyloid precursor
protein (APP), a protein of unknown function, on human
chromosome 21, and of two alleles (alternative genetic forms)
of the apoliprotein E gene on chromosome 19 create conditions
that greatly increase risk for the disease, especially at
younger ages. Treatments aimed at preventing the inferred
consequences of these mutations are currently hoped to be new
strategies for the treatment of Alzheimer's. They range from
vaccines for absorbing the bad fragments of APP (26, 27) to
enzymes to block the abnormal proteolysis, a possible function
of the two presenilin vulnerability genes on chromosomes 1 and
14 (22, 28-30). A surprising clue may come from the reduction
in risk for Alzheimer's disease seen in patients who are taking
the lipid-lowering statin medications, an effect that occurs
for reasons that are not yet clear (28, 31). A treatment for
Alzheimer's disease no longer seems hopeless, but converting
today's clues into tomorrow's medications will require
considerably more effort.

Other exciting genetic leads may point to new approaches to
understanding the origins of schizophrenia and depression,
diseases that have been recognized for centuries but were
considered untreatable until the last 40 years. One recent
study (32) has applied powerful genetic sequencing methods to
study a segment of chromosome 13 in several hundred adults in
France diagnosed with schizophrenia, yielding highly suggestive
support for one of the hypothetical neurochemical
intermediaries of schizophrenia (33, 34), namely, the NMDA
(N-methyl-D-aspartate) glutamate receptor (35, 36). These
findings, enabled by the power of high-throughput sequencing,
make this intervention target even more promising [see (34) for
review]. Other genetic and cellular abnormalities in
schizophrenia are being hotly pursued [see (37) for review, and
(38-45) for recent examples of ongoing studies]. Leads are
emerging for factors that predict treatment successes with
serotonin selective reuptake inhibitors (46, 47), and
vulnerability to depression (48) and suicide (49). Clearly, we
are only now beginning to know what we didn't know (50).

Behavioral Steps in Health Promotion

These examples illustrate that taken at its best, there has
been enormous progress in the biomedical understanding of
disease mechanisms, and the consequences for health promotion
have been equally enormous. These sorts of advances have
resulted in reductions in cardiovascular illness and in deaths
from cardiac causes through scientific insight into the biology
of vascular endothelial cells, blood-borne lipids, the early
warning signs of ischemic heart disease, and the multiple ways
to open and keep open the coronary arteries. Today,
lipid-lowering drugs are among the most widely prescribed drugs
in the United States.

Times Have Changed

Most medically oriented scientists who were trained in the
golden age of academic medicine, that is, before 1965 (2), have
believed (if they have been healthy) that the health care
delivery system would implement their discoveries when the
weight of evidence was sufficient to merit clinical
application. We recall a time when the indigent ill were
welcomed into our academic medical centers (they were not yet
termed "health" centers) and their affiliated municipal
hospitals of the city and county governments. In return for
allowing young physicians to learn responsible diagnostic and
therapeutic problem-solving methods, these generally willing
patients were able to receive the best treatments available for
little or no out-of-pocket expenses. Our faculty taught us the
art of taking a medical history and of performing a physical
examination, and took the time to help us analyze and hone our
problem-solving skills, which we in turn passed on to still
more inexperienced student physicians in shoulder-to-shoulder
service at the bedside (2). Those of us who took a turn away
from the bedside to pursue opportunities at the research bench
made the assumption that our clinical experience would always
be a foundation to which we could return through our research.
Regrettably, we were wrong!

The Crisis in Medical Care Cannot be Ignored

As numerous strong reports from the Institute of Medicine over
the past 4 years have repeatedly pointed out, the U.S. health
system is failing in front of our eyes (51-53), despite
consuming a very significant and growing percentage of the
gross domestic product, and representing the biggest employer
in many communities (54). The president has recently reacted to
some of these concerns by proposing new legislation limiting
the malpractice awards to patients suing their physicians for
errors leading to major pain and suffering. Yet capping awards
will not end the pain and suffering from errors committed in a
system that is no longer able to cope with the pressures of
daily practice. This failure is not due to incompetent
practitioners, but rather to the systemic failures among
physicians, patients, and nursing staffs to communicate rapidly
and effectively. Several states have previously enacted similar
legislation, which does seem to have held malpractice rate
increases in check. Yet even those states are experiencing
consistent annually rising rates of health care cost coverage.

In states where no caps exist on malpractice claims, the
accelerating pace of insurance coverage premiums, combined with
loss of practice profits as third-party payers set rates for
service provision, is forcing physicians out of practice, a
concern especially onerous for radiologists, neurosurgeons, and
emergency care physicians. Furthermore, intrusions into the
traditional physician-patient relationship by increasing
regulatory compliance requirements and third-party payers
deciding issues of clinical practice are not simply onerous,
but have soured the joys of practice and further reduced the
time available for doctors to spend with their patients and to
teach the next generations of physicians.

There is now a serious shortage of medical expertise,
particularly in those states with the highest rates of
malpractice insurance, such as New Jersey, Pennsylvania, and
Nevada. Not only are we experiencing shortages in
physician-specialists as care becomes more and more
sophisticated, but the health system has an even greater
shortage of career nurses and nursing educators. The system has
more than a million fewer nurses than are currently needed for
adequate hospital care; the more patients assigned to a nurse,
the lower the expectations for patient survival (55).

The current economic downturn has given profit-strapped
employers cause to pass a rising fraction of health costs to
employees. When employees opt to conserve their funds, more
people lose medical insurance coverage. This year, owing to the
budget deficits facing states with obligatorily balanced
budgets, many states may be unable to provide their share of
Medicaid Insurance for the indigent and unemployed, or those
employed who are unable to reduce their assets sufficiently to
qualify. Furthermore, in border states of the South and West,
the cost of caring for indigent foreigners coming to emergency
and urgent care facilities has added further unbudgeted
expenses to already overburdened operations.

Further expected changes in the demographics of our population
and the diseases they face will almost certainly compound
today's problems. Thanks to past gains in the treatment of
acute cardiovascular and infectious disease emergencies, more
adults are living well beyond the previous generations'
expected lifetimes. As the population ages, the diseases from
which the elderly and not-so-elderly suffer are becoming
chronic illnesses, more demanding of care and treatment

Patients loudly express their unhappiness with the lack of
choices in physicians, tests, and treatments, and the lack of
information to make decisions about their own lives. With
multiple unconnected caregivers seeing the same elderly or
chronically ill subjects, each for separate conditions,
complex, potentially adverse medication interactions will go
unchecked. These adverse reactions resulting from
miscommunication lead to medical errors, and the spiral into
worse and worse care continues.

Everyone has a suggested problem for a part of the crisis. But
despite all of the reports and outraged statements by leaders
and consumers, no one has offered even partial solutions to the
continually rising costs among the employer or private
providers, the lack of trained personnel, the rise of the
uninsured, and the insatiable hunger for more and more health
services. The United States, like Canada and the United
Kingdom, has recognized for years that unless we act to
implement better programs of individual life-style education
for health promotion, we can only expect the costs of fixing
preventable health problems to continue to rise (3).

Lastly, young physicians are carrying extreme burdens of debt
accumulated during their medical education, while managed care
has imposed time constraints on the provision of medical
education for students (2), residents, and fellows [at a time
when resident hours are severely reduced (56)]. Those concerns
and the recognition that nursing personnel are at an all-time
low (55) tell me that the prospects for receiving good medical
care have never looked more worrisome.

How Did We Get into This Mess?

We can trace the origins of today's health dilemmas to 1909,
when President Theodore Roosevelt endorsed the enactment of
workman's compensation insurance to protect workers in an
increasingly mechanized industrial society (54).

During the 1930s, in part based on experiences of large
military battlefield efficiencies, and the rise of major
hospital technology, such as radiology, anesthesiology, and
pathology, community and private hospitals became the bastions
of health technology, and private physicians deferred to these
settings for their access to expensive technology. At the same
time, communities saw the rise of Blue Cross and Blue Shield
Insurance plans as a means to pay in advance for hospital and
physician services. Such "third party" health subscription or
insurance plan systems allowed our U.S. hospitals to retain
their private, nongovernmental, and independent status (54).

Although there had been much discussion in this country of
going to a government-sponsored plan similar to the British
National Health Plan, which provided access to general
practitioners when it was enacted in 1911, the consensus in the
United States was against compulsory coverage and in favor of
voluntary actions by communities [see (54) for more extensive

In taking the path advocated by community activists, local
employers, and charities--that local hospitals should function
autonomously as community enterprises--important and
far-reaching policy decisions were set in place. One rejected
alternative was for the hospitals to become elements of state
or federal governments as the agencies of health service
provision. A second rejected alternative would have been for
groups of hospitals to organize themselves into regional or
multistate networks that would constitute an additional form of
public, and for-profit, utility. Such health utilities could
have been regulated, as were the rising local electricity, gas,
and water utilities, as a necessary service provided to the
citizens. Instead, the hospital system became the center of the
health system and remained independent, distributed, and
voluntary--with many municipal and charity hospitals providing
care to the indigent (54).

Subsequent steps also seemed well intended. Shortly after the
end of World War II, the United Mine Workers demanded a plan
that would include "full" health benefits in their first new
contract negotiations. In the same year, Congress passed the
Hill-Burton Act to develop community hospitals for populations
of fewer than 10,000, and widespread expansion of the
hospital-based health system began.

In 1965, in the midst of struggles over the priorities of guns
and butter, Congress passed the Medicare Act (part A for
hospital services and part B for physician services) to provide
health coverage for the elderly (above 65) and the Medicaid Act
to cover the indigent and incapacitated. Suddenly, hospitals
that had previously cared for the indigent for little or no
cost in return for a steady base of patients for medical
education were now entitled to bill the federal government for
full reimbursement for those services (2).

Congress developed the Medicare and Medicaid programs out of
earlier legislation under which the federal government had
issued grants to states to cover the cost of care for the
indigent. Upon their implementation, the country experienced a
massive, pent-up hunger for care that unexpectedly led to
enormous cost-overruns, quadrupling the budgetary requirements
for such care within 10 years.

In response to their suddenly lucrative opportunities,
enterprising physician groups in the 1970s formed Health
Maintenance Organizations, that is, groups of specialists
practicing to provide integrated coverage. Many enterprising
Academic Health Centers saw this as a means to enhance the
general levels of care and return some profits to their medical
centers and universities. Within the decade, however,
for-profit hospital corporations and health insurance companies
formed networks of hospitals for greater efficiency and profit,
generally with little or no role played by physician leaders.
By the 1990s the sense of growing dissatisfaction was
unavoidable, and the system was clearly out of control.

Automated Doctor Machines?

As noted by David Kipnis and Jeffrey Gordon of Washington
University in St. Louis, many academic health centers
confronted the economic pressures created when, in the early
1990s, the once-profitable clinical practice plans ceased being
profitable by a reactive focus on the bottom-line as an end in
itself (57). In the 1970s, these "practice plans" had provided
large subsidies for research and teaching, and for the
expansion of faculties. However, as the for-profit systems grew
ever more competitive, and as employers resisted cost
increases, maintaining profitability for many academic centers
became impossible (2). When the only goal of a health care
system is financial solvency or profit through cost control and
increased patient throughput, one can only imagine what the
future might hold.

"Eliza" is a so-called artificial intelligence program written
in the late 1960s by an MIT professor of computer sciences,
Joseph Weizenbaum (58). Although intended to demonstrate how
badly mainframe computers could emulate human conversations,
the results were quite the opposite. Eliza was one of the first
computer applications in which users could communicate with
remote mainframe computers through the use of a teletype-style
input, to which the computer could respond by presenting the
user with texts that it generated.

In the guise of a Rogerian psychoanalyst, Eliza would respond
to banal comments from the user by syntactically shuffling the
words typed on her keyboard and spitting them back out in the
form of an assertion. If you asked Eliza a question, "she"
would usually respond with another question. Occasionally, she
would change directions by focusing on the subject's feelings
about their mother or their job.

The results were so convincing that people refused to believe
they had been conversing with a computer instead of a skilled
analyst. People looked forward to their time with Eliza. People
who were charged for their time with Eliza gladly paid. Why
would people do this? Because people want to be paid attention
to, and to know that the person with whom they are speaking is
paying attention to them and their complaints. Eliza always
responds with complete sentences. She never just says "Mmmm" or
"un-huh," while writing notes in a chart or shuffling through
missed phone-call memos between beeps from the pager or tweets
from a Palm Pilot.

As noted by Leon Eisenberg, a Harvard social psychiatrist,
encounters between patients and physicians are increasingly
marred by mismatches between what patients want and what
physicians are able to provide (59, 60). Patients want enough
time to tell their story, to be listened to, to be cared for as
individuals. Time and trust are key ingredients of
patient-physician relationships (2). Regrettably, the pressures
of the present version of health care management diminish both
time and trust. Interestingly, a recent survey of physicians
and patients reported that what concerned them most about
today's health care was not medical errors but rather the costs
of malpractice, lawsuits, the cost of health care, and the cost
of prescription drugs (61, 62).

As the executives in charge of the managed health care systems
strive to renew their contracts in the face of this year's 15%
cost increase, and next year's projected 22% cost rise,
something will have to be done. How can they ratchet up the
system's efficiency one more level to see more and more
patients, faster and faster, perhaps faster than human
physicians and even physician's assistants can do on their own?

Given the ability of Pixar and virtual-reality simulators of
the human form (like Lara Croft in Tomb Raider), surely a
computer-generated physician version of Eliza in an Automated
Doctor Machine must be among the very next developments being

This sort of development may not be all bad. Dr. Eliza could
immediately assess your heart rate, blood pressure, and oxygen
saturation with devices already available in most drug stores
and exercise clubs, and probably without the hypertension that
initial doctor visits frequently elicit. Dr. Eliza could listen
to today's chief complaint, compare that problem with your
prior diagnoses in her online records, and reconcile that
history with your known allergies, family history, and current
medications, all of which will have been instantly updated from
authenticated information resources. Any recently reported
adverse interactions and contraindications will be duly noted
and alerts placed in your records automatically. With proper
programming, Eliza will then suggest the proverbial "lie down,
take two aspirins, and come back tomorrow," while nature
triages the course of your problem.

Dr. Eliza could also complete the insurance papers and e-mail
them for reimbursement before the next willing user arrives.
And just like the ubiquitous Automated Teller Machine--the
ATM--Automated Doctor Machines will be everywhere and
gratefully received (when was the last time you remember going
into a bank to do banking business?).

The Information Synthesis Challenge

In all scientific disciplines, the database of the published
literature is growing exponentially and will soon be
unmanageable without intelligent tools to guide us. This is a
problem that scientific publishing has recognized for a long
time (63), but to which clinical practice has generally
remained oblivious.

Synthesis of information can be as important as data itself:
Wisdom and insight today are being lost in a sea of
overwhelming knowledge. The issues are especially important in
clinical medicine (in life-and-death situations, where there is
a need to act without the luxury of time and without burgeoning
new rules) (64). In medicine, for example, there are 10,000
drugs, more than 100,000 diseases and conditions, thousands of
guidelines, and millions of rules governing them. The rules
that should be followed implicitly in practice plans (often
essential to life and limb) lie buried inside a sea of facts
that is constantly being modified by the clinical literature

Document retrieval, even when instantaneous, is not adequate
because the needed answers may be scattered among dozens of
sources. For example, a typical elderly patient may have 10
major medical problems, be taking a dozen medicines, have
numerous allergies and laboratory abnormalities, and have
undergone several surgeries. A start-up company launched in San
Diego called MyOwn.MD (and on whose board of directors I sit)
has created a tool that addresses this problem in a very
powerful way. They have converted literally millions of
clinical rules into machine language to provide answers to the
most complex of medical questions in real time and without
physician effort.

The System Must Be Repaired if We Are to Benefit from the
Scientific Advances

Several conclusions can be drawn from this analysis. The health
care system has become more and more automated and rigid in the
pursuit of cost reduction. This evolution has occurred just at
the time when science is revealing the need for a highly
flexible system with a different focus. The transition from
symptom- and disease-driven medicine to a predictive,
preemptive, preventive postgenomic medicine will be slow and
costly. The very skills and time that will be necessary for the
wise clinicians of the future to invest in the study of
individual patterns of disease progression are the very
features that profit-driven, high-throughput care systems
eschew and that insurers will refuse to cover. If predictions
that the medications of the future will be molecularly tailored
to individual needs hold true, the cost of getting such
tailored medications through a drug- approval process that
demands that consumers receive risk-free efficacy will simply
be prohibitive. The current system can scarcely meet today's
needs, let alone the costs of such a transition.

In a recent report, the Institute of Medicine's Clinical
Research Roundtable concluded that "clinical research is
increasingly encumbered by high costs, slow results, lack of
funding, regulatory burdens, fragmented infrastructure,
incompatible databases, a shortage of qualified investigators
and willing participants" (65, 66). According to this latest
analysis, we do not have sufficient capacity to incorporate new
knowledge, let alone new ways of using that knowledge for the
diagnosis or treatment of disease.

The physician-scientists of the past are an endangered species
(67-69). Those who remain the most viable candidates for the
translation of science to health are indeed a vanishing and
fragile resource that must be part of any restorative process
(66). We urgently need to begin the expansion and training of a
new cadre of academic health practitioners to fill the gap
between basic scientific discoveries that inform us about the
unknown elements of the life process, and the practical steps
needed to provide societal benefit from those insights. It is a
form of science termed by the historians Holton and Bonnert
"Jeffersonian Science" (70, 71)--a form of use-inspired
engineering of the kind that delivered transistors and lasers
from the insights provided by physics, and the novel products
provided by modern chemistry.

A Call to Fix It

Scientists must now unite to insist that the system be prepared
for the discoveries of the future and that we fulfill as
quickly as possible the major needs of today's global health
problems. In my view, it is time to seek a New National
Consensus to Restore the American Health System, enabled by a
Commission from the President elected by the 2004 ballot. The
consensus must consider all of the problems noted here:
restoring the incentive to be a physician or nurse; restoring
medical care and treatment affordable by the consumer, the
provider, and the payer; standardizing the best practices for
diagnosis, treatment, and outcome assessment so that systems of
care provision can be compared; reducing the occurrence of
practice errors by implementation of a modern system of
communication; accelerating the recovery from the diverse
published literature of information on clinical issues and
their interactions; and implementing preventive medicine with a
renewed emphasis on public good health in which the consumers
of health services accept responsibility for their own health
maintenance (72). Indeed, to benefit from the discoveries that
have already flourished as the NIH's budget has doubled, we
must create a translational health system in which research
discoveries flow to clinical trials to best-practice standards
to those exceptions that will define the feedback to fuel new
discoveries. We must restore a system that can welcome the new
insights and exploit them.

While AAAS alone cannot drive such reform, our commitment to
advance science and serve society demands that we seek such
reforms and do so promptly. We must gather the full rosters of
stakeholders who can make decisions to go into the why's and
wherefore's of what we are about, what we want our health care
system to provide, and what we are willing to spend and invest
to make that happen. The decisions of the 1930s that made the
hospital systems of America into a self-standing emporium of
then-modern technology may well require reanalysis. Hospitals
were once seen as community-based, charity-based,
teaching-intensive institutions, and yet in their zeal to
become the profit-based vehicle of today, they have degraded,
if not lost, all of these attributes.

If we agree that we must have a system that can provide for the
dissemination of the best of modern medical technology [and
clearly, some communities have been able to do so (73)], then,
as the Institute of Medicine has said, we must be prepared to
pay that price. But what system should that be? One possibility
is that the basic medical system should be available to all who
live in and contribute to our society in the same way that
clean water, gas, and electricity are available, as closely
regulated utilities with profit margins fixed by regulatory
commissions and with charges to the users for the amounts

Perhaps, as Oregon's Governor Kitzhaber (a physician as well as
an elected administrator) has noted (74), we need to turn our
attention back to community responsibility for health
promotion, and to provide individuals with incentives to
maintain their health rather than allowing the expectation of
free care now paid for by federal and state governments and
employers. Richard Mahoney, former CEO and chairman of
Monsanto, has proposed that American business should stop
providing specific health care plan coverages, and move to a
system where the employees, when properly educated, can spend
their own money for the care they deem necessary. Business
would therefore get out of the annual coverage dilemma
decisions that small businesses increasingly cannot afford
(75). Suppose, for example, that in order to qualify for a
basic level of universal coverage, one were required to have
check-ups at various critical life points, the way new
automobiles were required to be inspected in order to maintain
the factory warranty?

Clearly, there is a pressing need for innovative and extensive
reevaluation of the U.S. health care system. To do less would
be tantamount to never having done the research of the last 25
years. Doing nothing is a severe form of doing less. Inaction
will extend the period of nontranslation of the discoveries of
the next decade that the past discoveries have enabled to
flourish. Those of my era simply do not want to see their
lifelong career investments contribute nothing to our global
society's health.

I look forward to hearing your suggestions as to how we can
help a great enterprise restore itself to effectiveness at
reasonable expense and how we can help ourselves learn to
accept responsibility for the decisions we make that can
adversely affect our health. In closing, let me remind you of
some excerpts from last year's Presidential Address by Peter
Raven: "The challenges that we face are enormous and deeply
rooted in relationships neglected for far too long. We must
find new ways to provide for a human society..." (76)--and from
the 2002 Plenary Lecture by Ismael Serageldin: "For science to
realize its full promise and become the primary force for
change in the world, it requires that scientists work to engage
scientific research in the pressing issues of our time" (77).
We must ensure that we have a health system that will be able
to deliver on the important biomedical discoveries of the past
25 years and the bounties to come from postgenomic medicine--we
owe it to our colleagues and to society. Join with the AAAS in
this effort; together, we can do more (78).

References and Notes

[1] D. Nathan, J. Am. Med. Assoc. 287, 2424 (2002).

[2] K. M. Ludmerer, Time to Heal (Oxford Univ. Press, New York, ed. 1,

[3] A. Robins, P. Freeman, Pharos 65, 22 (2002).

[4] J. J. Schildkraut, S. S. Kety, Science 156, 21 (1967).

[5] D. Rosenthal, P. H. Wender, S. S. Kety, J. Welner, F. Schulsinger,
Am. J. Psychiatry 128, 307 (1971).

[6] S. S. Kety, D. Rosenthal, P. H. Wender, F. Schulsinger, Am. J.
Psychiatry 128, 302 (1971).

[7] M. Reivich, J. Jehle, L. Sokoloff, S. S. Kety, J. Appl. Physiol.
27, 296 (1969).

[8] E. S. Lander et al., Nature 409, 860 (2001).

[9] J. D. McPherson et al., Nature 409, 934 (2001).

[10] J. C. Venter et al., Science 291, 1304 (2001).

[11] A. Cravchik, G. Subramanian, S. Broder, J. C. Venter, Arch. Neurol.
58, 1772 (2001).

[12] G. Subramanian, M. D. Adams, J. C. Venter, S. Broder, J. Am. Med.
Assoc. 286, 2296 (2001).

[13] B. Childs, D. Valle, Annu. Rev. Genomics Hum. Genet. 1, 1 (2000).

[14] G. Jimenez-Sanchez, B. Childs, D. Valle, Nature 409, 853 (2001).

[15] F. S. Collins, V. A. McKusick, J. Am. Med. Assoc. 285, 540 (2001).

[16] S. O'Rahilly, Eur. J. Endocrinol. 147, 435 (2002).

[17] A. B. Young, J. Clin. Invest. 111, 299 (Feb. 2003).

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The author is in the Department of Neuro-pharmacology, The
Scripps Research Institute, La Jolla, CA 92037, USA. E-mail: This essay is adapted from his Presidential
Address to the AAAS annual meeting in February 2003; a portion
of these remarks was also presented to the Class of 2002,
University of California-San Diego, School of Medicine, in June
2002. Summary of this Article

Copyright 2003 by The American Association for the Advancement of Science