POINT OF VIEW

Joshua Lederberg
Harnessing biomedical
research to health
.needs

Any serious consideration of the contribution
of medical research to world health must take
in the general history of the health sciences
over the past century. The pioneering work of
Pasteur and Koch a hundred years ago revealed
the role of specific infectious agents in com-
municable disease and thus laid the founda-
tions for rational sanitation and hygiene, as
well as the development of preventive vac-
cines, followed by that of therapeutic anti-
biotics. The enormous improvement in public
health in developed countries, culminating in
the 195Os, is directly due to the widespread
application of principles and techniques de-
rived from their research.

Since 1950, a second cycle of health re-
search, mainly government-sponsored, has
helped to bring about a profound under-
standing of cell biology, of microbes, and of
viruses. The work carried out on DNA, the
genetic core of the cell, may stand as its symbol.
It has coincided with a wave of sophisticated
innovations in medical and surgical practice,
like the psychotropic drugs and coronary by-
pass surgery. Until about 1980, links between
these two kinds of medical research-funda-
mental and applied-were relatively few, and
many practical advances originated in empiri-
cal insights, which were then elaborated with
the aid of more fundamental knowledge. In the
third cycle, now in progress, practical advances
are being increasingly combined with DNA-
oriented research on such problems as schi-
zophrenia, heart disease, ulcers, diabetes and
sickle-cell disease.

Infectious disease nevertheless remains the
principal health problem of the developing
countries and hence of most of the world's
population. Most recent health research has
accordingly held little relevance for the least
developed countries, whose main problem,
despite substantial progress, may be viewed as
the application of knowledge already well
established in the 1950s. There has thus been
some skepticism about the role of research in
WHO's program-though in fact, apart from
two or three specially funded programs, re-
search accounts for a relatively small part of the
Organization's budget.

Medical research certainly does have a role
to play in efficiently adapting existing knowl-
edge to the needs of individual countries and
cultures, in dealing with those diseases that are
particularly prevalent in the least developed

Dr Lederberg is President of the Rockefeller University,
New York, NY, USA.

60

countries (notably parasitic diseases), and espe-
cially in exploring the extraordinary opportu-
nities now opened up by modern molecular
biology.

Despite attempts to express the relationship
between science and health in quantitative
terms it is difficult to achieve more than a
rough idea of it. The radical improvement in
child health, of course, has its roots in the
microbiological research carried out since
1880. IMy question confines itself to a narrower
time-span: what part of the medical knowl-
edge scientifically accumulated since 1950 has
been of cardinal importance in world public
health?

The basic principles of vaccination were
established long ago, but a practical means of
producing vaccines for viral afflictions like
poliomyelitis had to await the advances in cell
and tissue culture made during the 1950s. The
most celebrated example, smallpox vaccina-
tion, also has the longest history. Political
determination and operational know-how
played at least as important a part as recent
laboratory investigations in the success of the
worldwide campaign against smallpox. Never-
theless, scientific means of ensuring the effi-
cacy of vaccines in widely varying circum-
stances and of preserving their potency were
indispensable to its success. Of particular im-
portance for any further efforts to eradicate an
infectious disease is an understanding of its
natural history so that the means employed
may be closely attuned to the goal. This will
strain our basic knowledge of the genetics and
evolution of most virus diseases.

The theory of the bacterial toxin was one of
the great conceptual advances made by the
pioneer microbiologists, i.e., the explanation
of virulence by the invading microbe's produc-
tion of a specific toxic chemical. The presence
of a specific lethal toxin explains many dan-
gerous infections, from yesteryear's diphtheria
to today's toxic shock syndrome. For many
years, it also misled many scientists as regards
the devastation caused by cholera. The cholera
vibrio, like the bacteria responsible for the
related and equally dangerous enteric in-
fections of infancy, does indeed produce a
toxin, but it is not demonstrable by the tra-
ditional method of injecting culture broth into
a guinea-pig. Not until the work of Indian
researchers in 1959 did we learn that the cho-
lera toxin is essentially harmless when injected,
for its main effect on the body is to stimulate
secretion of water into the gut. The resultant
diarrhea may be so malignant, nevertheless, as
to turn the blood into a dehydrated sluggish
paste, leaving further terrible symptoms in its
wake. Most cases of cholera can now be treated
by simple rehydration with water plus salt and
sugar. Thus sophisticated research has led to
simple, practical measures that have already

@ World Health Organization 1984


POINT OF VIEW

rescued thousands, if not millions, of lives, in
cholera epidemics throughout the world and in
modern pediatric nurseries in the most ad-
vanced countries.

  With the reduction of infant mortality (also
linked with spasmodic and geographically dis-
parate improvements in agriculture), most of
the least developed countries have experienced
a relative population explosion, which has in
turn imperilled the possibility of social and
economic advance. Oral and injectable contra-
ceptives, based on the most advanced chemical
and endocrinological principles, have been
important ingredients of the scattered suc-
cesses achieved in countering this threat. That
social and political factors are of prime impor-
tance in deciding the outcome should not
distract attention from the desperate need to
develop contraceptive methods still better
suited to the requirements of particular coun-
tries and free from the disadvantage of possible
side effects. The lack of such methods is often
used as an excuse for not pursuing humane and
sensible programs of family planning and
population control. _

The confusion surrounding the alleged risk
of cancer and other side effects from oral con-
traceptives and the resultant cost to orderly
development are typical of a whole range
of problems that have arisen in the course
of adjustment to  industrial modernization.
These include the effects of cigarette-smoking
on health, the hazards presented by the pesti-
cides used to promote agricultural efficiency
and control disease vectors, and the pollution
created by the air- and waterborne emissions
attendant on factory production and mineral
extraction. In assessing pollution, science has
reached a half-way point, namely in the devel-
opment of exquisitely sensitive analytical
methods that can point to possible risks every-

, where in our man-modified environment. Un-
fortunately we are not very far advanced in the
precise risk-benefit calculations that will be
urgently needed in order to make the right
choices, especially where economic factors are
as serious constraints as they are for the least
developed countries.

Looking now to the future, the gradually
improving health and living standards of the
developing countries are bringing them closer
to the problems and opportunities of the indus-
trial countries. There will be an ever-increas-
ing emphasis on research on their growing
problems of heart disease and cancer, not to
mention psychiatric illness and viral infec-
tions. Of the highest importance in all these
areas is DNA-oriented research, which can, for
example, furnish details on the structure and
regulation of the lipoproteins, the substances
most intimately involved in depositing choles-

terol in the coronary arteries. This work should
lead fairly promptly to more rational dietary
and pharmacological measures to control a
leading cause of death-and to engender the
still more perplexing problem of the welfare of
ever older (though not necessarily more ro-
bust) populations. Current research on the
"oncogene" does not point quite so directly to
specific measures against cancer, and we are
still a long way from understanding the basic
causes of schizophrenia and depression. Never-
theless, there can be little doubt that we are in a
stage of renewed advance comparable only to
the emergence of the scientific investigation of
infectious disease 100 years ago. It is gratifying
to see the renewed attention also being given
to the problems of parasitic disease at every
level, including the emphasis on the applica-
tion of molecular biology, greatly inspired by
WHO's Special Program for Research and
Training in Tropical Diseases.

There are still ominous clouds on the hori-
zon, however. While modern research can
refine health-promoting measures so as to fa-
cilitate their application in the least developed
countries, the best vaccine is useless if there is
neither the will nor the infrastructure to dis-
seminate it. We have yet to see the universal
commitment to health improvement-and to
the most effective forms of research to support
it-that might allow such possibilities to be
realized.

For some years, I have warned that the
microbial world has not ceased to evolve, and
that it would be rash to imagine that the great
pandemics of history can never be repeated.
The current example of AIDS unhappily re-
minds us how quickly new diseases can
emerge, and how limited is our capacity to
understand them promptly and provide a de-
fense against them. In its present form, AIDS
appears to spread very slowly and inefficiently,
and there is every reason to expect that it will
be contained before it dominates the public
health statistics of any country. We have due
warning, however, that our quest for funda-
mental knowledge in virology is not an idle
game but a precondition for ensuring the wel-
fare of the human species everywhere.

With nature's harshness all around us, it is
all the more tragic that calculated man-made
epidemics remain a grave threat. This threat
provided a major incentive for the negotiation
of the Biological Weapons Disarmament Trea-
ty of 1972, in which WHO played an important
role by spelling out the underlying human
necessity. Regrettably many problems remain
in the enforcement of this treaty, so that we
cannot ignore the danger of man-engineered
and man-disseminated disease on top of all the
other plagues that already impose so heavy a
burden on world health.           cl

WORLD HEALTH FORUM VOL. 5 1984

61