Beller, George A.

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President’s Page:
The Human Genome Project:
Implications for Cardiologists and Their Patients
George A. Beller, MD, FACC
President, American College of Cardiology
Fast-forward 10 years, perhaps even as few as five or six, and
the practice of medicine in general and cardiology in
particular may look very different. Today’s physicians may
well be standing precisely on the edge of a major shift in the
medical paradigm.
The National Institutes of Health, along with the ge-
nome centers of many countries and numerous private
enterprises, have been leading the way toward this paradig-
matic shift for some time, and they may unveil the impetus
for this change within only months. Soon, their endeavor—
the Human Genome Project—will provide the scientific
community (as well as the rest of the world) with a map of
the entire collection of 100,000 or more human genes and
three billion letters of deoxyribonucleic acid (DNA) encod-
ing these genes (1). The availability of this map will in many
ways change patients’ expectations of health care and
physicians’ responsibilities, and society will find itself grap-
pling with a whole new set of ethical, legal, and moral issues.
After the human genome is sequenced, the function of
these genes and how they are regulated in health and disease
will have to be ascertained. Dr. Robert Roberts, Chief of
Cardiology and Director of the Bugher Foundation Center
for Molecular Biology in the Cardiovascular System at
Baylor College of Medicine, stated,
“Hundreds, if not thousands, of genes that relate to cardio-
vascular disorders will be available by the year 2000. We as
physicians must now prepare for the onslaught and all of its
potential therapeutic and ethical implications. In addition to
identification of genes and of mutations responsible for
familial cardiovascular diseases, such as the lipid disorders,
cardiomyopathies, and others, there will also be an abun-
dance of genes that play a major role as risk factors for
disorders, such as atherosclerosis and coronary thrombosis,
other than the conventional, well-recognized lipid genetic
influence.” (2).
Many genes associated with cardiac diseases have already
been identified (3). Cardiac diseases with an identified
genetic locus or gene include hypertrophic cardiomyopathy,
dilated cardiomyopathy, arrhythmogenic right ventricular
dysplasia, long QT syndrome, familial heart block, Holt-
Oram syndrome, DiGeorge syndrome, and Noonan syn-
drome (3). In areas other than cardiology, genetic screening
can be used to predict, in many instances, who will have an
increased risk of developing Huntington disease, cystic
fibrosis, and Tay-Sachs disease. Shaywitz and Ausiello (4)
predict that within the next five to 10 years, it will be
possible to anticipate who might be most vulnerable to
illnesses like diabetes, Alzheimer’s disease, and many types
of cancer.
IMPLICATIONS OF MOLECULAR GENETICS: A NEW
PARADIGM FOR MEDICINE
As Dr. Francis S. Collins, Director of the Human Genome
Project, pointed out last year at the American College of
Cardiology 48th Annual Scientific Session (ACC ’99) in
New Orleans, every disease is in some way genetically
related, and each person is in some way flawed (1). The
fields of molecular genetics and genetic epidemiology are in
many ways still in their infancy, but as they grow, they may
provide a new taxonomy for the definition of disease (5).
This new way of defining diseases—by their biochemical
mechanisms instead of their pathogenesis—is going to
dramatically alter the way physicians and researchers cate-
gorize patients, diagnose conditions, prescribe medications,
choose treatments, and counsel patients about prevention
and care.
Within the next decade, genetic testing may be used to
inform a patient of a high risk for developing hypertension
many years before a rise in blood pressure is detected. This
“genetic prediagnosis” may lead to a specific therapy aimed
at preventing hypertension in such a patient, and a phar-
maceutic agent used to prevent hypertension arising from
this patient’s individual molecular genetic make-up will
most likely be available.
Look ahead a decade or less:
A 47-year-old man comes to see you, his cardiologist,
because he has one sister and one brother who died in their
twenties and thirties, respectively. He is diagnosed with
familial hypertrophic cardiomyopathy with nonobstructive
hypertrophy on echocardiography. He is asymptomatic. The
family history indicates that he has two children, and upon
learning that his condition is an inherited disease, he wants
his children to be tested and evaluated. The father and son
are tested, and both have the mutation Arg403Gln in the
beta-MHC gene. The average life span is 28 years, and
death is primarily from premature sudden cardiac death.
The father and son undergo genetic counseling and agree to
have the triple helix therapy, which will prevent expression
Journal of the American College of Cardiology Vol. 36, No. 1, 2000
© 2000 by the American College of Cardiology ISSN 0735-1097/00/$20.00
Published by Elsevier Science Inc. PII S0735-1097(00)00784-1
of the abnormal beta-MHC gene, while expression of the
normal gene continues. The half-life of the human heart is
about three weeks, and so it is expected that the heart will
return to normal in ;15 weeks. He will return monthly for
magnetic resonance imaging studies to assess his progress.
Both have an indwelling defibrillator until restorative biol-
ogy is complete.
Benefits for patients. As this scenario illustrates, the po-
tential for changes in patient care is enormous. Although
the Human Genome Project is not yet completed, already
there are more than 24 genetic tests at physicians’ disposal.
It may be only a matter of time before genetic tests are as
common and easily administered as those in today’s arsenal,
such as cholesterol screening (6). A 1998 survey by the
American Medical Association (AMA) indicated that 59%
of Americans believe they are at least somewhat likely to
take advantage of genetic testing (7).
Perhaps the most exciting opportunity associated with
genetic screening will be a renewed and strengthened
outlook on preventive medicine. Molecular genetics will
open up a whole new world of “risk factors.” As Dr. Collins
suggested in his ACC ’99 convocation lecture (1), by the
end of this decade, it may be possible to couple taking a
history and doing a physical examination with predictive
genetic screening. The results of this screening would enable
each patient’s physician to identify whether that particular
patient has genetic susceptibility to any of numerous con-
ditions defined at the molecular level (1). Physicians may be
able to move away from what have generally been “one-size-
fits-all” prevention efforts (e.g., don’t smoke, exercise aero-
bically at least three times a week, follow a diet low in
cholesterol and fats) and move toward counseling patients
about their specific, genetically evidenced risks. Genetic
testing for screening purposes is predicted to become
straightforward and less expensive than it is at present, with
the emergence of DNA microchip-array technology.
Clearly, the availability of these predictive tests will
provide great benefits to patients. As Kinmonth et al. (8)
point out, there are likely to be better tests for uncommon
conditions, new tests for rare cases of common conditions,
and new tests for common genetic contributions to common
conditions. In addition to new efforts in prevention, these
scientific advances will yield new means to risk-stratify
patients and, therefore, better ways to predict the clinical
course of disease and choose optimal treatments.
Additional targeted pharmaceutical choices will probably
be one of the first results of the genetics revolution. Dr. John
Bell has noted that many pharmaceutical companies have
already introduced genotyping into clinical trials. New
genetic information will not only lead to the discovery and
development of new drugs based on a new understanding of
disease mechanisms but it will also help physicians to avoid
prescribing certain drugs to patients with genetic potential
to experience severe side effects or even toxicity (5). As Dr.
Philip Leder stated, “We will treat Patient A for breast
cancer with this particular cocktail, for example, because we
will have genetically determined that this form of therapy is
appropriate for her.” (9).
New requirements of physicians. As the era of genetic
medicine unfolds, physicians will be required to take on a
wide variety of new responsibilities. For starters, physicians
will need to understand the evolving new taxonomy of
disease, which will be quite different from the one most
mastered in medical school. This understanding will need to
encompass the kinds of tests that are available, in whom
each test is most applicable, how to interpret the results, and
how to implement quality care on the basis of those results.
The last aspect alone will mean staying abreast of what will
no doubt be rapid advances and fluctuations in the whole
new field of pharmacogenetics/pharmacogenomics. (Al-
ready, the genetics revolution has added new terms to our
dictionary.)
Little time will pass before there will be a pressing need
to integrate genetic risk assessment into medical practice.
Primary care physicians are likely to feel this need—or
demand, as Kinmonth et al. (8) have aptly suggested—first,
but certainly patients will expect their cardiologists and
other specialists to explain and, in many cases, administer
tests for this type of risk assessment. In some cases, this may
require knowing when to introduce the unique expertise of
a genetic specialist, but the AMA survey revealed that two
years ago, 72% of patients believed that their primary care
physician would be able to interpret the results of genetic
testing (7). This expectation is likely to grow, along with
public awareness of screening potential. Unfortunately, in a
recent study, physicians misinterpreted nearly one third of
predictive test results for colon cancer, and fewer than 20%
of patients received appropriate genetic counseling (10).
The results of this study suggest another crucial respon-
sibility that will soon fall onto physicians’ shoulders. Phy-
sicians will need the ability to recommend tests to patients,
to explain the possible advantages and the limitations of
these tests, to interpret results in lay terms, and to assist
patients in understanding the implications of the results for
the patients themselves as well as their families. This will be
a multifaceted and daunting undertaking, especially because,
according to Dr. Collins, “Most practicing physicians have
had not a single hour of instruction in this particular field
and are ill prepared [to counsel patients about] the com-
plexities of the molecular analysis of their DNA and the
risks it may convey.” (1). Shaywitz and Ausiello (4) make
the very important point that availability of individual
genetic profiles “will demand a level of intimacy and trust
between doctor and patient that is rarely seen today.” They
go on to say, “After all, it’s one thing for patients to learn
that they have a strep throat or a sprained ankle; it’s another
for them to comprehend the implications of a progressively
more complex genetic risk profile.” They also explain that
this is not the kind of information that can be imparted in
the usual 10-min office visit or a cursory telephone report.
Informing patients of a genetic risk of disease will require
enormous sensitivity and compassion.
296 Beller JACC Vol. 36, No. 1, 2000
President’s Page July 2000:295–8
At least one other responsibility will accompany the
plunge into genetic medicine. There will be a pressing need
to educate the public about genetic screening, and physi-
cians and physician-investigators must be at the helm of
most, if not all, awareness campaigns. If physicians do not
take the lead in informing the public and the media,
misperceptions about both the potential and the limitations
of genetics-based screening, diagnosis, and treatment will
prevail. Gill and Richards (11) have suggested that genetic
researchers have a responsibility to draw attention to these
facts and to foster “balanced media reporting.” Physicians
must weigh in on these matters, too, and to do so, they will
need to be literate in the field.
Societal quandaries. In 1998, a survey suggested that
nearly seven in 10 Americans were somewhat or very
concerned that genetic information might be used against
them by either their employer or a health insurance provider
(12). These concerns are not without merit, as medical
progress of such magnitude certainly has the capacity to be
exploited. Will confidentiality laws be adequate to keep
genetically derived predictions in the hands of those who
will use them for good? Will it be possible to avoid
discrimination if employers and health insurance carriers
have knowledge that will give them insight into how much
care an employee or an enrollee might require? What about
the possibility that higher insurance premiums will be levied
on individuals merely on the basis of genetic risk? As Dr.
Leder states, “When you’re able to define an individual’s
genetic make-up in detail and make reliable predictions
about his or her ultimate fate, that’s enormously powerful
information.” (9). These are just some of the questions,
controversies, and fears that society will have to tackle as
adjuncts to such exciting medical progress.
And, of course, the issues related to cost-effectiveness that
are already facing physicians and their patients in the
current era of managed care will be further complicated by
the availability of predictive tests. Even today, physicians’
orders for tests and procedures can be scrutinized. This
scrutiny is liable to intensify as seemingly healthy people
begin asking for and expecting screening tests that may turn
out to be costly. Will payers defer to physicians’ judgment
about whether to run these tests, seeing that the results may
improve preventive efforts that keep patients healthy instead
of having to be treated when they get sick? Gill and
Richards (11) have rightly predicted a need for rigorous
assessment of both the economic and the psychosocial costs
and benefits of genetic screenings.
PREPARATION FOR THE ERA OF MEDICAL GENETICS
Some would argue that the genetics revolution has already
begun; others might contend that it is just around the corner,
ready to launch when genetic sequencing is completed. Few
would debate that the time remaining to prepare for this new
era is waning. As evidenced by the numerous requirements and
responsibilities likely to fall on physicians, there are steps to be
taken now. Here are just a few:
1. At the very least, physicians should keep their minds
open to the possibilities of molecular genetics. As Dr.
Christine Seidman said during her Bishop Lecture at
ACC 2000,
“I would like to encourage you to embrace this—not to be
afraid of it, not to be intimidated by differences in language
and words we use from a basic science perspective. I want to
show you how relevant molecular genetics is in terms of
diagnosing these interesting conditions, and, ultimately, I
want to convince you that this will improve the manage-
ment of these disorders.” (13).
2. Perhaps most important is for each physician to become
literate in genetics. According to Dr. Collins, the AMA
considers this the greatest revolution in medicine since
antibiotics (1). It will inevitably be the responsibility of
physicians to educate their patients, if not the public, and
doing so will require more than a rudimentary under-
standing of the research under way. Last year, Dr.
Collins urged the ACC to take a significant role in
educating its members in this field. The ACC will
incorporate human molecular genetics into its educa-
tional curriculum so that its members will be prepared for
the revolution in cardiovascular care expected in the
post-genomic area, when routine genetic screening and
new medical therapies at the level of genes and cells will
emerge. A new working group, chaired by Dr. Roberts
and supported by the Fund for the Future, will convene
this summer to accomplish preliminary planning for a
College-wide campaign to educate members about the
implications for their medical practices resulting from
the completion of the Human Genome Project. Titled
“Preparing Cardiologists for the Genetics Revolution,”
the group will propose a curriculum and a timeline as
well as identify educational strategies and formats.
3. Finally, physicians may need to be the voice of reason
and wisdom, as ethical, legal, and moral dilemmas
related to genetic progress come to the fore. Dr. Susan
Pauker (6) has urged physicians to “operationalize the
Golden Rule: Treat the patient as you would wish to be
treated when the Human Genome Project divulges
genetic vulnerability information on all of us.” Physicians
should play key roles in promulgating this idea as well as
applying it.
Acknowledgment
I am grateful to Dr. Robert Roberts, FACC, Chief of
Cardiology, Dan W. Chapman Professor of Medicine,
Professor of Cell Biology, Director of the Bugher Founda-
tion Center for Molecular Biology in the Cardiovascular
System and Director of the Specialized Center for Research
in Heart Failure at the Baylor College of Medicine in
297JACC Vol. 36, No. 1, 2000 Beller
July 2000:295–8 President’s Page
Houston, who provided the case history and kindly reviewed
the entire article.
Reprint requests and correspondence: George A. Beller, MD,
FACC, Cardiovascular Division, Department of Internal Medi-
cine, Health System, University of Virginia, P.O. Box 800158,
Charlottesville, Virginia 22908-0158.
REFERENCES
1. Collins FS. Medical and societal consequences of the Human Genome
Project. Convocation lecture given March 10, 1999, at the 48th
Annual Scientific Session of the American College of Cardiology,
New Orleans, Louisiana.
2. Roberts R. Syllabus. 31st Annual Cardiovascular Conference of the
American College of Cardiology, Snowmass, Colorado.
3. Shah G, Roberts R. Topics in molecular biology: molecular genetics of
cardiomyopathies. J Nucl Cardiol 2000;7:159–70.
4. Shaywitz DA, Ausiello DA. Back to the future: medicine and our
genes. New York Times, April 16, 2000.
5. Bell J. The new genetics in clinical practice. BMJ 1998;316:618–20.
6. Genetics: speed reading the book of life (editorial). Harvard Health
Letter 2000;25(3). (Available at http:www.health.harvard.edu.)
7. Karanjawala ZE, Collins FS. Genetics in the context of medical
practice. JAMA 1998;280:1533–4.
8. Kinmonth AL, Reinhard J, Bobrow M, et al. Implications for clinical
services in Britain and the United States. BMJ 1998;316:767–70.
9. Leder P. Harvard Medical Bulletin, Autumn 1999:28–9.
10. Giardiello FM, Brensinger JD, Petersen GM, et al. The use and
interpretation of commercial APC gene testing for familial adenoma-
tous polyposis. N Engl J Med 1997;336:823–7. (as cited in ref. 7.)
11. Gill M, Richards T. Meeting the challenge of genetic advance
(editorial). BMJ 1998;316:570.
12. Mitka M. Genetics research already touching your practice. American
Medical News, April 6, 1998. (as cited in ref. 7.)
13. Seidman C. Cardiomyopathies: inherited gene defects that remodel
the heart. The 31st Annual Louis F. Bishop Lecture, March 14, 2000,
at the 49th Annual Scientific Session of the American College of
Cardiology, Anaheim, California.
298 Beller JACC Vol. 36, No. 1, 2000
President’s Page July 2000:295–8


President’s page: the human genome project: implications for cardiologists and their patients 

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