Forum

Chain

JosHUA LEDERBERG

In 1900, infectious disease was
the leading cause of mortality in
the United States, accounting for
at least 37% of deaths. By 1950,
this had been mitigated to 6.8%,
and again to 2.8% by 1989, with
corresponding improvements in
life expectancy. These numbers of
course must be taken with a grain
of salt, given the eventual preemp-
tive role of infection in chronic
illness and many disorders whose
infectious etiology is still to be
recognized. Further, the relative
importance of sanitation, health
education, and nutrition, in con-
trast to medical interventions like
immunization and antibiotics, has
remained in contentious debate.
Regardless, this achievement is
trumpeted as the conquest of infec-
tious disease, indeed a glorious
tribute to public health and medi-
cal science.

In consequence, health re-
search since 1950 has ever more
emphasized chronic constitutional
afflictions like cancer, cardiovas-
cular disease, and psychiatric dis-
order to the relative neglect of in-
fection. Environmental anxieties
are focused on radiation and chem-
ical toxins rather than arthropod
vectors and airborne contagion.

Qur complacency over the tri-
umph of the human over the mi-
crobial has been shaken by the

 

 

Joshua Lederberg is a university
professor at The Rockefeller Univer-
sity, New York, N.Y., and an editor
of the report by the IOM Task Force
on Emergent Infections. A slightly
different version of this article will
appear in the May 1993 issue of
Trends in Microbiology.

human immunodeficiency virus
(HIV) pandemic. In truth, the ma-
jority of the world’s population has
never been relieved of its load of
malaria, tuberculosis, diarrheal
disease, and a host of parasitoses.
It has taken AIDS to provoke a
new look at the threats to human

Crowded at the Summit: Emergent
Infections and the Global Food

health in the United States from
infections recently thought to be
conquered.

These concerns were taken up
by a recent study of the Institute of
Medicine Task Force on Emergent
Infections. The resulting report
was the product of a broad collec-
tive effort which promptly reached
unanimity that these threats ur-
gently needed to be brought to
public and policy attention. The
report’s recommendations had to
do mainly with (i) the strengthen-
ing of disease (especially virus)
surveillance systems globally, (ii)
wider availability of existing vac-
cines and the removal of legal dis-
incentives to the development of
new ones, (iii) acceleration of the
technology to enable vaccines
against new strains to be devel-
oped on a time scale commensu-
rate with the spread of infection,
(iv) vector control, and (v) public
education. Perhaps the most im-
portant message is that infection
knows no national boundaries,
and we will pay dearly if we ignore
the smoldering of infection any-
where.

No single infectious agent is a
unique target of concern. During
the committee’s deliberations,
multiple-drug-resistant tuberculo-
sis emerged as a major public
health threat in New York City;

 

162

ASM News
 

dare one say this was predictable
from the time of its first appear-
ance a few years ago in immuno-
compromised people with AIDS?
Historically, the influenza of 1918
to 1919 was the most recent previ-
ous pandemic to have a major ef-
fect on U.S. mortality statistics.
Many believe a recurrence of such
a lethal reassortment strain, en-
tering a now-naive human herd, is
all but inevitable. At the moment,
HIV is evolving towards greater
serodiversity (potentially frustrat-
ing proposed vaccines) and occa-
sional azidothymidine resistance.
But its fundamental biological
properties happily have not
evolved towards easier spread; to
the contrary, there are hints of the
appearance of strains with a
longer latent period or perhaps as-
sociated with very limited patho-
genicity. On the other hand, sim-
lan virus strains have evolved
with aggressive and acute lethal-
ity. There is no way to guarantee
that the same cannot occur with
HIV in the human population, and
the potentials for genetic recombi-
nation with related lentiviruses
have scarcely been thought about.
A multitude of other zoonoses fos-
ter scary outbreaks and importa-
tions of Lassa, Marburg, and Eb-
ola viruses. Changing vector
distributions, ill heeded, open the
way to a family of encephalitides.

Economic and technical ad-
vances confer many defenses
against infection. Nevertheless,
the sheer increase of the global
population, its local density in
conurbations, and the scale and
ease of rapid transoceanic travel
are discontinuities in the human
condition that aggravate our vul-
nerability to emergent infections.
Some of these are new genetic
variants; many others are diseases
all too common in their historic
habitats which now have new op-
portunities to spread. Agricultural
and residential encroachments on
forested lands augment the risk of
human contact with arborviruses
and borreliae. Other vectors and
pests accompany the movement of
people and goods. And microbial
populations have their own dy-

namic of evolutionary change con-
nected with their rapid replica-
tion, vast numbers, and inhergnt
inStabilities—especially on the
part of RNA viruses. That the hu-
man species has survived so well is
a tribute to its evolution of biolog-
ical immunity and a modest. de-
gree of intelligent self-defense.

“The human occupation of
planet Earth has left us with a
conceit that our species is at the
very top of the food chain, preda-
tory on all others, rapidly destroy-
ing their habitats, and diminish-
ing the genetic diversity of
domesticated species.. Carnivores
that once terrorized human bands
have been all but exterminated.
Rodents abound and threaten
some food stores, but they can be
contained with concrete and war-
farin. Our agricultural surpluses
are nibbled by insects; but at their
worst, swarms of locusts will be
regional, not global, pests. Barring
genosuicide, the human dominion
is challenged only by the patho-
genic microbes, the predator for
whom we remain the prey.

Our task is then to foresee the
future of this coevolutionary rela-
tionship, our habitation of earth in
company with large cohorts of mi-
crobes. We can discern conflicting
trends. Within the infected host,
the selective pressures favor ag-
gressive growth correlated with le-
thality. Endogenous somatic cells
are also potentially in mutual
competition as well, but this com-
petition is tempered by the evolu-
tionary tradition that has resulted
in the multicellular organism. The
invaders are bereft of that tradi-
tion. But the host rapidly de-
stroyed is a Pyrrhic victory for the
parasite, so efficient transmissibil-
ity from host to host is correlated
with delayed mortality. Our most
effective parasites have entered
into our own genome: every hu-
man carries these integrated ret-
roviruses and is hardly aware of
them, even of their possible sym-
biotic benefits.

The future of this relationship
is incalculable. At the extreme,
the global extermination of our
species by disease is hypotheti-

cally possible, most likely in con-
currence with the stresses of war
and famine. But we need not
search far for historic precedents
of continental decimation of many
plant and animal species and once
every century or so of the human.
At stake is a level of sickness and
death manyfold higher than that
caused by the highly publicized
accidents of industrial pollution.
Yet we continue to neglect the
most elementary precautions.

We have had one wonderful
success in the global eradication of
smallpox. More problematically,
we might accomplish close to the
same with polio and perhaps a few
other viral diseases. We certainly
cannot aspire to decontaminate
the earth with respect to all poten-
tial microbial rivals. These heroic
projects deserve our attention, but
in keeping with renewed vigilance
and a stockpile of knowledge and
developmental capacity to cope
with an unpredictable variety of
emergent pathogens.

Our most important need is a
well-informed consciousness about
these contingencies. Research
workers at the front line will add
more than any top-down line of
command in the generation of new
insights. And for operational pro-
grams of surveillance and of im-
munization, the working authori-
ties will do better at designing
what is feasible than outside con-
sultants. But none of this will hap-
pen without a well-informed, in-
ternalized scientific and moral
perspective and public under-
standing and political leadership
to allocate the resources needed.

 

 

VOL. 59, NO. 4, 1993

163