122**  NIH funding - testimony  5/20/98
     John Porter H.R. Subcommittee

Statement by Joshua Lederberg
.fi

Very appropriately, most of my colleagues will stress their
analysis of the public benefits that ensue from the overt
products of biomedical research.  It has been the pride of NIH
to have sponsored innumerable discoveries on the biology of the
human organism, and of our microbial predators -- discoveries that
have assisted the ongoing defense against disease.  Despite
setbacks like the HIV epidemic, life expectancy in the US -- one
excellent measure -- has steadily improved throughout this century,
from 47 years in 1900 to 76 at the present.  Pushing up that
expectation is ever harder, as we face the more difficult
challenges of cancer, heart disease, cardiovascular disorder,
neurological deterioration ... but our progress has been steady,
in many areas very exciting especially with the insights derived
from genetic analysis.

But I would assert that equally important is the human capital,
the skills, ideals, imagination and motivation of the scientific
investigators whose work depends absolutely, day by day, on
research support from the NIH.  We have discovered a deep fount
of creativity in the young people we have been training; and they
have spilled over from academia into government and industry.  In
the process they have generated enormous economic advantage for the
nation, most explicitly in biotechnology and pharmaceuticals, where
the U.S. has unquestioned world leadership.  As generous as it has
been, NIH funding has not kept pace either with the scientific
opportunities, nor with the talents that could be cultivated and
brought to bear.  So the prospects of a new acceleration in this
domain are very encouraging, and there can be no doubt that the
investment will be repaid many times over.

The two substantive topics I would put on the table are

1. infectious disease, and
2. aging in its most fundamental aspects.

1.  My own research for 55 years has probed the genetics and
evolution of microbes.  While I have only occasionally worked
directly with pathogens, that background has led to the elucidation
of the role of plasmids, as the means why which "germs" conspire
with one another, and to a particular perspective of how we relate
as a species in relation to these micro-predators.  In fact the
microbes are our only serious competitors, and we know that in the
end they will win ... dust unto dust.  Our destiny is in the
details.  It serves the pathogenic microbe no advantage to kill its
host, that is an almost incidental byproduct of its struggle
against our physiological defenses; and the "smartest" pathogens
are those that keep the host alive - but infected - so that we
continue to serve their needs for food and shelter.  If we could
better understand how that balance is maintained, it would be of
enormous advantage in our unremitting struggle.
     The global pandemic of AIDS has been a poignant reminder
of the need to maintain and strengthen our vigilance about the
evolution and emergence and of microbial threats to our health.
We had another reminder with the episodes of avian influenza in
Hongkong.  These had a very high mortality -- six out of 18 cases
diagnosed as A-H5N1 -- but as events turned out, we were very lucky:
this flu was not readily transmitted from human to human, and what
might have evolved into another 1918-like catastrophe was nipped
in the bud.  This was no accidental circumstance, but the result
of well tuned international collaboration, and energetic response
on the part of the Hongkong health authorities.  In turn they depended
on studies of virus biology and diagnosis that have deep roots in
NIH-funded investigations over the past 30 years.  All authorities
caution that such episodes will recur -- if not flu, then any of
scores of emerging and reemerging infections.  Similar problems
challenge us in the spread of antibiotic resistant microbes, and
the need to understand how these evolve, and how better to approach
the design of new generation drugs.

Coping with new infectious disease has also become a depressing
element in our national security planning.  With the end of the
Cold War, we are no longer locked in a strategy of mutual
deterrence with another superpower.  Instead, rogue states,
guerilla groups and psychopathic individuals have become imbued
with the powers of mass destruction through the use of chemical
and biological weapons.  At a basic level, our long-term strategy
for defense is hardly different from that for protection against
naturally emerging infections: the needs for prompt and accurate
diagnosis, surveillance, and far more powerful vaccines and drugs
to prevent and treat infections from many exotic agents.
Curiously, even the eradication of a disease like smallpox evokes
new vulnerabilities with a population no longer exposed to
immunizing doses -- focussing sharply on the need for agile and
multi-pronged agents for health protection.

NIH does not operate in a vacuum: its research strategy needs to be
and is well
informed both by scientific opportunity and public health priority.
Its creative people and findings must be readily transferred to
the health care sector and to industry.  All this is working quite
well -- and I particularly wish to commend the initiatives to make
medical information universally available through the electronic
media of Medline.

2.  One could pick many areas of challenging promise, but the
biology of aging is one that seems especially ripe for advancement
through the applications of molecular biology.  May I say that I
have had a further impulse to study this field by serving as
principal scientific advisor to the Lawrence J. Ellison medical
foundation, which is working closely with the National Institute of
Aging to find the most creative ways for a private foundation
to complement the excellent work of NIA.
For example, what has been learned about the risk factors and the
biochemical basis of Alzheimer's disease has already transformed
our concepts of "senility", and provide the hope that homing in on
specific disease syndromes can offer substantial enhancement of
healthy life extension well into the 9th and 10th decades.

Prof. Joshua Lederberg       
Raymond and Beverly Sackler Foundation Scholar
The Rockefeller University 
New York, NY   10021-6399  


See: www.fundingfirst.org/comment/07/index.html