Interviewer: Dr. Pauling, in the last few years you have become interested in the biochemical
basis of medicine, mental disease, and so on. Could you tell us what led you into
this new work?
Linus Pauling: Well, I think that it was the discovery of sickle cell anemia as a molecular disease
that has led to our present activities on the chemical basis of mental disease. You
see, nobody had thought before that there could be abnormal molecules of proteins
and that they could be responsible for disease.
Genetic diseases have been known. You know that each human being has about, let's
say, a hundred-thousand genes that he has inherited from his father and mother. Half
from his father and half from the mother. These genes are now known to be molecules
of a substance called deoxyribonucleic acid and each of these molecules has a little
code of information on it that permits it to manufacture duplicates of itself to be
handed on, for example, to one's children, and also to manufacture special molecules
such as the molecules of proteins, in which each atom is put in its right place in
this product molecule. Each of these genes sets up an assembly line for manufacturing
protein molecules.
When we began studying hemoglobin - the abnormal hemoglobin that produces sickle cell
anemia - we found a very interesting result. The hemoglobin in the apparatus in which
an electric field operates on the hemoglobin molecules and pulls normal hemoglobin
molecules to one side and the sickle cell anemia hemoglobin molecules to the other
side. We found that if we got a sample of blood from the father or the mother of a
parent - of the patient - and put the hemoglobin of the father in the apparatus, it
split. Half the molecules went one direction and half went the other. And similarly
with the hemoglobin from the mother. Both the father and the mother had in their red
cells a mixture; a fifty-fifty mixture of two kinds of hemoglobin.
Now the explanation of that is simple. A normal individual inherits two molecules
of deoxyribonucleic acid, two genes, each of which manufactures normal hemoglobin
molecules. A sickle cell anemia patient has two abnormal genes that are somewhat different.
Each of these manufactures molecules of sickle cell anemia hemoglobin. The parents
of this patient have one normal gene and one abnormal gene. Each of these genes sets
up its own assembly line and manufactures its own kind of hemoglobin molecules. The
abnormal gene was presumably made by a normal gene many thousands of years ago, probably
by a cosmic ray or some other kind of high energy radiation or some other mutagenic
agent, which damaged the gene in such a way - it made only a small damaged region
in it - in such a way as to convert it into the sickle cell gene. This caused the
sickle cell gene manufactures - a hemoglobin molecule that is almost exactly right,
but it has two little errors in it. Out of six-hundred units that make up the molecule,
two have been changed. And that is all the difference that there is between normal
hemoglobin and sickle cell anemia hemoglobin.
Now here we have the normal gene and the abnormal gene, the good gene and the bad
gene. The bad gene was formed by a mutation, a genetic mutation, some thousands of
years ago. It has spread out so that there are now millions of people in the world
who carry this particular bad gene. We know that geneticists have discovered that
human beings carry a great number of different bad genes, and my associates and I
have been especially interested in checking up on the bad molecules of proteins that
the bad genes manufacture. In particular, in investigating these bad molecules in
relation to disease.
