November 2, 1962

To the Editor of The New York Times:

A news article in The Times today (Nov. 2) misrepresented my actions at the meeting last night in the Community Church of New York at which both Mr. James P. Warburg and I received the Gandhi Peace Award for Promoting Enduring Peace, Inc.

The heading of the article is "Warburg and Pauling Wrangle Before Nonviolence Advocates." The body of the article contains several statements suggesting that I wrangled with Mr. Warburg.

I did not wrangle with Mr. Warburg. There was some wrangling between Mr. Warburg and people in the audience during his address. After he and the chairman had finished speaking, Mr. Warburg sat down in the chair beside me and spoke to me in a low voice. I told him in a low voice that he was mistaken in saying that I had gathered signatures of scientists in foreign countries to a petition to the U. S. government; the petition was in fact a petition to the United Nations, urging that an international agreement be made to stop the testing of all nuclear weapons. I also said that his statement that I had joined with people from 27 countries to obtain an injunction in the courts to stop U. S. nuclear testing was misleading; in fact, my fellow plaintiffs and I had simultaneously filed essentially identical complaints in the courts of both the U.S. and the U.S.S.R., asking that an injunction be issued to restrain officials in each country from carrying out nuclear tests, with the provision that it become effective only when the similar injunction had been issued in the other country. Mr. Warburg said that this information was not in a news item, on which he relied. I then said that I thought it was wrong for him to make a public attack on me when he was ignorant about what I had done. He then left the room. The New York Times reporter approached me and I told him about our conversation, and he left in search of Mr. Warburg.

I have long admired Mr. Warburg, and I was pleased when I learned I was to receive a Gandhi Peace Award at the same meeting at which he was to receive one. I regret that the occasion was made an unhappy one by an action by Mr. Warburg based upon misinformation.

Linus Pauling

ADDRESS BY PROFESSOR LINUS PAULING

AT THE BANQUET OF THE INTERNATIONAL CONFERENCE

ARRANGED BY THE MANFRED SAKEL FOUNDATION

I was happy when Mrs. Gimbel and Dr. Rinkel invited me to participate in this meeting, and I have been happy to attend the symposium on the chemical basis of mental disease and to be associated with the Manfred Sakel Foundation, which is dedicated to the work of diminishing the amount of human suffering in the world.

The world has during recent decades been changing at a tremendous rate. Technological advances are such that the world is not the same one year as it was the year before. Tremendous weapons of destruction are developed. The stresses under which people live become ever more oppressing. There emanates from the centers of governments a special sort of irrationality. Among the people there is the spirit of rejection of dogma and of revelation, the old principles of conduct. If the world is to survive, we must strive for a fundamental ethical and philosophical principle in accordance with which we can all live together in peace.

I believe that the fundamental ethical principle that everyone should accept is that of striving for the minimization of human suffering. This is not the same as maximizing the amount of happiness in the world.

On a scale of income, we may select a certain value as standard -- one that is just enough for a satisfactory life, different, of course, according to duties and circumstances. An increase of 80 percent in income would give same added happiness -- but the suffering that would be caused by a decrease of 80 percent surely deserves a far greater weight.

The nature of the human race has been changed by our technological development. A man or woman is not truly an organism, in the sense that a rabbit is, or a lion, or a whale. Instead, he is a part of a greater organism, the whole of mankind, into which he is bound by the means of communication -- speaking, writing, telephoning, traveling over long distances -- in the way that the cells of a rabbit are interconnected by nerve fibers and hormonal molecular messengers.

The ethical principle of minimizing human suffering requires that we all work together in overcoming the causes of suffering.

In some parts of the world starvation, malnutrition, and the onslaughts of infectious diseases are the principal causes of human suffering; but everywhere mental disease is an important cause. In the United States half of the hospital beds are occupied by mental patients.

Several years ago I became interested in the question of the chemical basis of mental disease. As a result I have had contact with many psychiatrists. I am grateful to them, even though they do not do a very good job. They do the best that they can, but they are handicapped by ignorance. Sometimes they make use of such crude methods as insulin shock, or electroshock, damaging the human organism in the hope that the changed individual will be improved. They make rather effective use of drugs. These drugs were not discovered through any process of ratiocination, based on the understanding of the nature of mental disease; instead, they were discovered empirically, when it was found that certain chemical substances are helpful for some mental patients. No one knows why these drugs are valuable in treating mental disease -- in general, we are lacking in knowledge about the molecular basis of the therapeutic action of all drugs.

I hope that the psychiatrists will not have to work much longer under the terrible handicap of extreme ignorance about the diseases that they are treating and about the mechanisms of their methods of treatment. I have been encouraged by information presented at the Manfred Sakel symposium to believe that the time will come, perhaps in 10 or 20 years, when, if enough effort is made, there will be obtained some significant understanding of the nature of the groups of diseases that we classify as schizophrenia and of other mental diseases, comparable to that which now exists for a few diseases that are called molecular diseases.

I believe that most mental diseases are molecular diseases, the result of a biochemical abnormality in the human body. I think that the mind is a manifestation of the structure of the brain, that it is an electrical oscillation in the brain supported by the material structure of the brain; I think that the mind can be made abnormal by an abnormality in the chemical structure of the brain itself, usually hereditary in character, but sometimes caused by an abnormality in the environment. Pellagra is an example of a disease with mental manifestations, which has been largely conquered because of the discovery of the molecular abnormality that produces it. It is a deficiency disease, due to the lack of a vitamin, nicotinic acid. The discovery of its chemical cause has led to the solution of the pellagra problem in many parts of the world.

Considerable progress is now being made in the understanding of molecular diseases that cause mental deficiency. An example is the disease phenylketonuria. It was identified 30 years age by Dr. Foelling in Oslo, Norway, who studied some mentally deficient children who had an odd smell. He found that there were some unusual substances present in the urine of these children; further investigation by him and other scientists then led to the discovery that these children lack an enzyme in the liver that catalyzes the oxidation of one amino acid, phenylalanine, to another amino acid, tyrosine. In consequence the concentration of phenylalanine in the blood and cerebrospinal fluid increases to such a level as to interfere with the development and function of the brain, leading to mental deficiency. The various proteins that we eat contain about 20 different amino acids. The amount of phenylalanine in the diet is somewhat greater than is needed, and there may be a deficiency in tyrosine. Normal human beings have an enzyme in the liver that catalyzes the oxidation of the excess phenylalanine to tyrosine. This enzyme is manufactured by genes -- most people have two genes of this sort, which have been inherited from their parents. One person in 80 has only one gene that manufactures the enzyme, plus another gene, a mutated one, that does not manufacture the enzyme -- such a person has only half the amount of the enzyme that a normal person has, which is, however, enough to keep him in good health.

If two of the people marry one another, there occurs the great lottery: the child inherits only one of the two genes from the father and one of the two from the mother. On the average, a quarter of the children from such a marriage thus inherit the abnormal gene of the father and also the abnormal gene of the mother, neither of which will manufacture the enzyme. In consequence this child has the disease phenylketonuria.

When the knowledge of the chemical basis of phenylketonuria was obtained, it was found that the disease could be recognized by a chemical test a few weeks after birth, and that the child, if fed on a diet of hydrolyzed protein from which most of the phenylalanine had been removed, would develop in a nearly normal manner.

This disease, which in the past has been responsible for one percent of the institutionalized mentally deficient individuals in the United States, may now be brought under control because of the discovery of its molecular nature.

The possibilities for progress toward understanding mental disease may be indicated by a discussion of another disease, sickle-cell anemia. This disease does not have mental manifestations. It is the first disease to be described as a molecular disease.

In sickle-cell anemia the red cells of the blood are twisted out of shape. It has been found that the deformation of the red cells is due to an abnormality of the hemoglobin molecule, the principal protein inside of these cells. The abnormal hemoglobin molecules seem to be self-complementary, so that they clamp on to one another to form long rods, which they line up side by side to form a long needle-like liquid crystal. As this liquid crystal (tactoid) grows and becomes longer than the diameter of the undistorted red cell, it begins to deform the red cells, which then become sticky, become tangled with one another, and prevent the flow of blood through the capillaries, leading to anoxia and to the various manifestations of the disease.

The abnormality of the sickle-cell-anemia hemoglobin was discovered in our laboratories in Pasadena by Dr. Harvey Itano, Dr. J. S. Singer, and Dr. I. C. Wells. They showed that the molecules of abnormal hemoglobin, from the blood of a patient with the disease, have a positive electric charge, in neutral solution, whereas those of normal hemoglobin have a negative electric charge. Through the efforts of a number of investigators, especially Dr. Vernon Ingram, it has been found that the abnormal hemoglobin of this disease differs from normal hemoglobin only in one amino acid residue out of a total of 300 in the half-molecule.

Many abnormal human hemoglobins have been discovered, since the discovery of sickle-cell-anemia hemoglobins, and these abnormal hemoglobins are responsible for many different diseases. It has now become possible to diagnose the hereditary hemolytic anemias in a far more precise way than was possible before the discovery of the molecular nature of this complex of diseases.

Sickle-cell anemia is found in a patient who has inherited two genes for sickle-cell hemoglobin. A patient who has inherited one gene for sickle-cell hemoglobin and one gene for hemoglobin C has a different disease, which is called sickle-cell: hemoglobin-C disease. A patient who has inherited two genes for hemoglobin C has still another disease, homozygous hemoglobin-C disease.

This example indicates what we might expect to find in schizophrenia -- not that there is a gene for schizophrenia, but rather that there are many genes involved, such that any one of them, when inherited in double dose, or some combinations of several of these genes with one another may produce a quantitative genetic abnormality that leads to mental manifestations classified as schizophrenia. The evidence that was presented to the symposium about the presence of biochemical abnormalities in the blood of schizophrenics is significant in this respect.

If schizophrenia is a complex of diseases, rather than a single disease, it will be difficult to find a treatment. Nevertheless, I believe that a tremendous amount of progress can be made in controlling schizophrenia, and in decreasing the amount of human suffering that it causes, provided that a vigorous effort is made to carry out research on its nature.

We may envisage ways for treating diseases that have not yet been brought into practice. For example, with the progress in our knowledge about the nature of enzymes and about the role of enzyme in relation to disease, especially enzyme deficiencies, it may before long be possible to synthesize artificial enzymes that can be used in a substitution therapy that will permit the patient to lead a satisfactory life.

We have no to recognize the possibility that nucleic acid may be introduced into the cells of a patient, to correct the abnormalities that otherwise would lead to mental disease. There is also the possibility that an understanding of mental disease will be obtained such that drugs of definitely predicted structure can be synthesized that will control the diseases in a specific way.

However, all of these would be palliative measures, which would not constitute a solution of the problem. I am concerned about the degeneration of the pool of human germ plasm, resulting from damage to the genes by natural mutagenic agents, natural radioactivity, and those chemicals and artificial high energy radiation that constitute a part of our modern life.

There is a natural process of purification of the pool of human germ plasm. As abnormal genes, such as those that produce phenylketonuria, continue to be introduced into the pool of human germ plasm through new mutations, the defective genes are also removed by the death without progeny of those children who have inherited the abnormal recessive gene in double dose. This process of purification involves a large amount of human suffering.

I believe that it is possible for us now to begin to carry out the process of purifying the pool of human germ plasm without the suffering that is involved in the birth, and death without progeny, of the defective children. If two parents have a phenylketonuric child, then it is known that both of the parents are carriers of the gene for phenylketonuria, in single dose. It is known that the chance is 25 percent that any future child born to these parents would also have the disease. There are a number of diseases caused by defective genes for which a similar prediction can be made

It is accordingly possible in many cases to say that offspring of a marriage will have a 25 percent chance, for each child, of his being grossly defective. Because of the great amount of human suffering involved as a result of the birth of a grossly defective child, I believe that the chance of 25 percent is too great to permit the prospective parents to be left in ignorance about it.

As our knowledge about the genetic character of human beings increases, it may become possible to identify the carriers of the recessive genes for many serious diseases. It would then be possible for these carriers to marry normal individuals, rather than other carriers of the same defective genes, and then to have a somewhat smaller number of children than normal, one or two children, rather than three or four. In this way the defective genes would be removed from the pool of human germ plasm, without the birth, suffering, and death of defective children. As the years go by, there may be achieved by this method a significant decrease in the incidence of mental disease, as well as of the diseases with somatic manifestations.

I believe that we shall move into a better world in the future, with the scientists, collaborating with the psychiatrists, in doing their part to contribute to the control of mental disease and the decrease in the amount of human suffering. We may have hope that the increase in knowledge about the molecular basis of disease will in the course of time lead to a significant decrease in the amount of human suffering in the world.