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THE POSSIBILITIES FOR FURTHER PROGRESS
IN MEDICINE THROUGH RESEARCH

By LINUS PAULING

When I was born, in 1901, the electron had been discovered,
but the atomic nucleus had not. In 1912 Rutherford reported his
experiments on the scattering of alpha particles, and his interpre-
tation of them as showing that the mass of an atom is for the most
part concentrated into a very small particle, carrying a positive
electric chargep the nucleus of the atom, about which the electrons
move. Most chemists were confident that the structural formulas
that they wrote for chemical substances bore a close relation to
the actual arrangement of the atoms in the molecule, relative to
one another, but there was little expectation that in a decade or
two it would become possible to determine the structures of molecules
and crystals with great accuracy.

The first measurements of inter/fatomic distances were
made by W. H. and W. L. Bragg, by application of their method of
determining the structure of crystals by X-ray diffraction. This

method was soon supplemented by others: ,analysis of band spectra,

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the electron-diffraction technique for gas molecules, and so on.
By 1940 precise structural information had been gathered for
hundreds of gas molecules and hundreds of crystals.

It then became possible to ask significant questions
about the molecular structure sand the vn Bal basis of disease
and of therapeutic mekkhegs treatments. A few of these questions

have been answered. We have begun to talk about molecular biology

and molecular medicine, and to have the feeling that biology and
O-
medicine are just at the beginning of ee period of extraordinary

development, a Golden Age similar to that through which physics
and chemistry have passed during the last seventy years.

Even though powerful methods of experimental investi-
gation have been developed during recent decades, we must recognize
that the problem of determining the molecular structure of the
human jis an extremely difficult one, and that progress may be slow.
I may illustrate this point by mentioning the substance that
constitutes a larger fraction of the human body than any other
substance -- the substance water. We know a great deal about the
isolated water noleculef, we know that the average distance be-
tween the center of the oxygen atom and the center of each of the
two hydrogen atoms is 0.965 A, and that the H-O-H bond angle has
the value 104° 31'. Also, we know the detailed structure of ice.
But the water molecules in the human body are not present as
isolated water molecules or as ice; they are present as liquid
water, containing various substances in solution. We are still
largely ignorant about the structure of liquid water and the
structure of aqueous solutions in general, We shall continue to
have difficulty in understanding the nature of physiological
processes so long as we have not solved the problem of the nature

of liquid water and of its solutions.//A most striking development

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of recent years has beén the inergage in our knowledge about the
structure of proteins and of aay acids. A number of diseases
are now known to result from a gene mutation that leads to the
substitution of a single amino-acid residue for another in a poly-
peptide chain of some protein in the human body. For example, in

the disease sickle-cell anemia it is known that the two beta chains
of the hemoglobin molecule (rather than the two alpha chains)
carry the abnormality, that the abnormality is in the sixth
position from the free amino end of the beta chain (which con-
tains 146 amino-acid residues), and that it involves the intro-
duction in this position of a valine residue, te this postticn>
in place of the glutamate residue that is found in normal adult
human hemoglobin. Moreover, rapid progress is being made in
the attack on the problem of the nature of the genetic code,
and it is likely that within a year or two it will be possible
to say just what substitution of one nucleotide for another in
the polynucleotide constituting the gene for the synthesis of
the beta chain of hemoglobin has taken place during the mutation

from normal to sickle-cell h lobi
rom no o sickle-ce emoglo a o or twe ducal

We can be confident chat gti Lar information will
become available for hundreds of diseases, and that this infor-
mation will in the course of time lead to improved methods of
prevention and treatment.

There is, moreover, the possibility of a great improve-
ment along another line -- the understanding and control of mental
disease. I estimate that there is a strong hereditary factor in
80% of the cases of mental disease. There is, of course, also in
many cases a significant environmental factor. A human being may
sometimes have a hereditary nature such that he can withstand great
environmental stress, whereas for other human beings theP hereditary
character is such that even the minimum amount of environmental

stress is enough to cause serious mental disease. About half the

hospital beds in the United States are occupied by mental patients.
About 10% of the American people spend some time during their
lives in a mental hospital. I believe that /through reaearch
on the molecular basis of mental diseasef it will be possible
to decrease its incidence significantly.

One way to attack the problem of mental disease is
to carry on research on the structure and function of the brain.
I believe that it will be possible, perhaps within twenty years,
to determine the nature of the electric oscillations in the brain
that constitute consciousness and ephemeral memory, the nature
of the material pattern in the brain that constitutes permanent
memory, and the nature of the interactions between the electric
oscillations and the material pattern. I believe that it will
be possible to discover the important molecules involved in the
process of thinking, to determine their structure, and in the
course of time to discover what the molecular abnormalityxies are
that lead to mental deficiency and to mental illness. Molecular
biology and molecular medicine are new fields of science that
can be greatly developed "4giliwe for the benefit of mankind.

The young man or woman who is now attending medical
school and preparing to be a physician is faced with a problem
that will be with him throughout his life. The nature of medical
practice is going to change, more and more, during the next few
decades, as the result of discoveries that are made about the
human bodyk, the vectors of disease, and the molecular basis of
drug action. It will be important that the physician understands
these changes that are brought about by the new discoveries. To
prepare himself to follow the progress of medical research in the

future, the student of medicine can do nothing better than to

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participate in research himself. I am accordingly pleased that
I can be associated with some of the University of Toronto medical
students who have been carrying on research and are publishing

yEmEX accounts of their work in the Research Issue of the University

of Toronto Medical Journal.

Linus Pauling