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284  A Scientist's Perspective.  Biotechnology: Implications for
     Public Policy pp 19-24.  Conference at Brookings Institution,
     January 15-16, 1985, Washington.

     I am presenting a general overview of the subject of
biotechnology.  My difficulty is to extract a few salient points.

     Cells are the basic architectural constituents of all biological
life, including human beings.  The important point is that there is
a vast variety of cells.  Yet the biochemical basis of all of these
cells is the same.  This is known as the unity of biochemistry.

     Curiously in science, sometimes more is known about a detailed
biochemical process than about the organization of chemicals into
the structures found in cells.  It is remarkable that the accurate
identification of the chromosome set in the human was not known until
1955.  And yet at that time, scientists were already presuming
that advances would occur in research in human development and in
genetics.  Those hopes came because the structure of DNA -- the 
essential chemical constituent of the chromosome that embodies
information -- was already known in its physical and chemical detail.
Understanding how DNA encodes information dates to 1953, when James
D. Watson and Francis Crick published their very famous double helix
structural model for DNA.

     DNA has two functions in the cell.  One is to replicate itself
faithfully.  In replication, the problems are (1) transmission of
information from generation to generation and (2) how to ensure
that every cell in the body has an appropriate quota of genetic
information.

     DNA's second function is to influence the structure and character
of the cell and the organism.  This is done through the medium of
another form of nucleic acid called ribonucleic acid (RNA).  RNA
acts as the messengers of the blueprints of the cell that is present
in DNA.  This process of selecting parts of the DNA blueprint and
putting them into RNA is called transcription.  The RNA messengers
then move to a structure called the ribosome, where they direct the
process of protein synthesis.  This process is called translation.
The type and function of proteins manufactured on ribosomes provide
the unique characterization of any cell.  In short, DNA and RNA form
a coding mechanism.  The DNA is transcribed into an RNA copy, and
the information in the RNA then directs the assembly of the amino
acids into protein on the ribosome.

     Proteins are chemically composed of twenty different amino acids.
Proteins differ in the number of amino acids and their order in the
protein chain.  Consequently, after the protein chain is released
from the ribosome, it has a built-in propensity to fold up into a
very specific, three-dimensional shape.  The linear sequence of
information, which in itself is a reflection of the linear sequence
of information in the RNA, then results in objects that have
well-defined shapes and well-defined distributions of specific amino
acids.  Some of the amino acids will have charges on them; some will
repel  water, some will attract water; and the shapes themselves 
will permit attachment to external substances.

     The relationship of DNA structure to the structure of proteins
is reasonably well understood.  Somewhat less is known about the
details of how and why proteins fold up, but that they do fold into
very well-defined and predetermined kinds of three-dimensional 
conformations is apparent.  When they do so, proteins can perform
biological functions.  If the proteins attach to one another, they 
become structural elements like skin or collagen, (for example, hair).
If they have chemical specificities, they can function as enzymes
that catalyze metabolic reactions.  By virtue of their very specific
shapes, they can attach to specific molecules in the environment and
function as antibodies; or grab onto cholesterol and transport that
through the body, and so on and so forth.  These relationships
concerning the transfer of DNA information to protein structure are
the underpinnings of biotechnology.  One can take advantage of this
knowledge for further analysis of how cells work and how they produce
various products.

     A gene can be thought of as the segment of DNA that is
responsible for the characterization of some particular protein.  An
average protein is a chain of one hundred amino acids.  Knowing this,
one can calculate that, in principle, there can be about 10 million
genes in the human organism.  To a rough approximation, using our
alphabet to match the genetic alphabet, a set or a dozen sets of
the Encyclopedia Britannica would be required in order to inscribe
that much information.  Therefore, if one is to understand the
complexity of the human organism, one is going to have to unravel
the identities of at least a hundred thousand different gene products.
And then the fun begins.  Each one of those gene products is worth
a chapter, if not volumes, of further investigation.  This provides
a philosophical perspective that is one of the most important
contributions of molecular biology.  Human nature is a mechanism
of such complexity that it is necessary to be very humble, indeed,
about the ability to even understand small parts.  Today there is
only a glimmer of 1 percent of the knowledge of what the protein
constituents of the human body do.  Of the thousands of proteins
inferred to be present, only a few have been isolated and definitely
characterized.  In large measure, these are known because of the
power of the new tools of biotechnology.  Today, there would not be
materials like interferon or interleukin-2 if it were not for the
intervention of biotechnology as a means of production.

     What about biotechnology?  In the early 1970s, besides the
fundamental understanding of the structure of DNA, a set of tools
for handling DNA was developed and allowed science to move into 
technology.  The contributions of many investigators provided the
tools to allow the cleavage of DNA at certain selected places in the
DNA sequence.  These tools are enzymes that are called restriction
endonucleases.  They function like a search routine in a word
processor.  The enzymes generate pieces of DNA, whose ends are
of a specific nucleotide sequence, and that will form "complementary"
pairs with other pieces of DNA generated by the same enzyme.  The
unity of biochemistry shows that the same rules of DNA structure are
shared by bacteria, plants, yeast, algae, other animals, mammals,
insects, and so on.  So, by using restriction enzymes, a piece of DNA
can be removed from one source of DNA and inserted into another.

     Other enzymes, called ligases, seal up the chemical bond which
is formed when two pieces of DNA form complementary pairs.  The final
result is that the original DNA, and a piece of DNA that was cut from
another source, are joined together.  This new, chimeric DNA can then
be taken up by bacteria.  These bacteria can now be fooled into
allowing the indefinite promulgation of foreign DNA.  Of course,
there are tricks about getting the bacterium to also perform the tasks
of transcription and translation, which are needed to get a protein
product.

     That is the technical base of the recombinant DNA piece of
biotechnology.  It is important to remember what is easy and what
is difficult.  It is easy to take DNA from any source and manipulate
it so that in a population of 100 billion bacteria, each bacterium
will have one each of the various stretches of DNA that were in the
DNA source.  This is a totally random process. This is relatively
easy.  What is more difficult is to first pick out that one bacterium
that has picked up the particular DNA wanted.  The second difficult
task is to get that bacterium to produce the protein wanted.  Third,
and hardest of all, is to find something really useful to do with
the product that has been made.

     The discussion to this point has focused on recombinant DNA.  But
that is not all of biotechnology.  Biotechnology has a long history
that goes back to the primitive selection of plants for crops.  The
largest part of the world's food supply is still derived from the
choices that our neolithic ancestors made seven, eight, nine thousand
years ago.  No really important new crops to date have been invented
since that time.

     Our staples are still rice and wheat.  There have been geographic
discoveries: the discovery of the New World brought the Irish potato
to Ireland from Peru, the tomato from Mexico and a wide variety of
others that have been of indigenous origin.  Our ancestors were
uncanny in their ability to select and develop plant resources for
that purpose.

     Much the same has happened in the domestication of animals.  The
cat, the dog, the cow, the horse, and the goat, have been subjected to
extensive, although informal and not scientifically sophisticated,
patterns of breeding to achieve specific purposes. The current advances
are part of a continuing progressive understanding, and there are
many other technologies that are involved in biotechnology.

     There is one technology about which there is some misunderstand-
ding.  The term genetic information is not at all the alteration of
germinal information (which dictates the transmission of characteristics
to an offspring), but rather the modification of cells in the
body of the individual.  In this respect, genetic therapy is not very
different from vaccination.  For example, with live polio virus 
vaccination , one introduces genetic information from a foreign  source
into humans in an attempt to modify the behavior with a desired end.
In this case, the desired end is the production of antibodies to polio
virus.  It is very important that already sensitive issues are not
confounded by failing to make important distinctions.  Germ cell 
alteration is something that would deserve the most critical attention.

     I was asked to say a few words about what the issues are.  I am a
little loathe to do so, because I am an interested party.  I cannot
pretend to have a disinterest in the outcome of decisions about the
continuation of modern biological science.  As a scientist very much
involved in laying some of the underpinnings of biotechnology, I have
a commitment to engendering more understanding, and I am eager to see
positive uses.  I am also eager for there not to be any human disasters
as a result of this research.  I also have a financial interest in
these outcomes.  It is very important that I am not perceived as a
disinterested party.

     What are the issues? One very important aspect is to enhance the
scientific  quality of biomedical research.  Biotechnology is framed
much too narrowly.  The glamour of recombinant DNA has made many forget
the many steps requiring hard work in the development of pharmaceutical
products.  After learning how to produce a product, it is hard to
figure out what to do with it.  The testing, validation, and
discovery of a drug's side effects includes many more disciplines than
recombinant DNA.  This country is still not doing a very good job in
this area.  The laboratories of molecular biology are by and large not
in sufficiently good contact with their clinical colleagues for the
development of applications of molecular biology research.

     I think it is of the utmost importance that biotechnology be 
directed to the most important human ends.  One important human end is 
the application of molecular genetics to the problems of parasitic
disease.  Malaria is the world's most important disease, and there are
very significant, exciting, provocative ways in which to attack that
by using the most advanced of our present technologies.  However,
currently, it is very difficult to find support for research in this
area, from either federal or commercial sources.  In agriculture, the
situation is similar.  There is little motivation for trying to do
what would be of the greatest importance in terms of global welfare.

     Opportunities exist for applications of biotechnology that may
lead to a better understanding of environmental toxicity.  Perhaps
this country can establish a rational basis for decisions about
environmental " clean-up."  These priorities must be founded on 
scientific knowledge of how environmental chemicals relate to genetic
structures.

    Social consequence of success in this new field must be anticipated.
Realities are sliding right by that have enormous implications for
the future.  The success of programs in biomedical investigation
will have the most important consequences.  Biomedical research can
contribute to the alleviation of disease.  The conquest of heart 
disease and of cancer is already wreaking a change in our demographic
structure, in the relationship of old to young, and in the interval of
progressive disability.  Those are the important consequences of 
biomedical advance.  Biotechnology cannot be isolated from the whole
framework of biomedical application.  The same is true for agriculture.
The success of programs in enhancing the efficiency of food
production key to the economies of the developed world is very likely
to cause major disruption in world agricultural markets that must be
thought about very seriously.  Otherwise, United States may discover 
that it has the technology and the land, that it can produce all the 
world's food, and nobody else can afford to do it because others
cannot compete with this country.  What a terrible situation that
would be in a global economy.  Yet society seems to be heading there
like an express train. 
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