The Advance of Medical Research

MR. INWOOD: The civilized world today is waiting to see what will be the next important advance in medical research. Will there be a slow development of our present findings or will we wake up tomorrow to miraculous discoveries of cures for heart disease and cancer such as we did in the discovery of insulin for diabetes in 1921?

To the members of the Empire Club and our radio audience the question will be doubly interesting as we are so close to the heart of research in Canada and in particular the new Charles H. Best Institute on College St., a fitting monument to a great medical scientist.

We are particularly concerned about it right now as the pace of living in cities such as ours is placing a new and intense strain on its people unknown to human beings before.

In our speaker today we are fortunate in having the leading interpreter of the latest advances in medical research. He is the co-discoverer of insulin with the late Dr. F. G. Banting. He initiated the discovery of a new enzymehistaminase, a new dietary factor choline, and the purification of heparin and its use in the prevention of thrombosis. He also initiated the Canadian serum project for the provision of dried human serum for military uses at the outbreak of war in 1939.

Our guest speaker is a scientist holding some 15 honorary degrees conferred upon him from universities around the world and to these are added many distinguished and singular awards, medals, fellowships and honours running into literally pages which time does not permit me to enumerate. It is indeed an honour to present Dr. Charles H. Best to you.

DR. BEST: I shall make no attempt to review today the proud record of this last half century in medical research. For those of you who may be particularly interested, the BRITISH MEDICAL JOURNAL of January, 1951, carries a series of articles evaluating the contributions from all parts of the world and incidentally giving appropriate recognition to those which were made in Canada. The first article of this series was written by the doyen of British medicine, Sir Henry Dale, who was the central figure in the opening of our new Institute on September 15th, of this year.

I have been asked to tell you of the researches which are now going on and which will be intensified and extended in our new Institute.

I may say here that I cannot think of a higher honour, certainly there is none which I would appreciate more, than to have this fine building, which is dedicated to medical research, named for me. In 1938 I had been offered in England a better opportunity than any existing in Canada to conduct and direct research and I had almost decided that my future lay in that country. My friends, Fred Banting, and Gerald Fitzgerald the founder of the Connaught Laboratories and the School of Hygiene, thought otherwise. They approached the Board of Governors of the University with a recommendation that a building, an Institute, be created to provide adequate facilities for the research carried out by the members of my group. This was accepted in principle but the war came shortly thereafter and our attention was, of course, diverted to medical research from the military viewpoint. After the war, a running fight against rising prices was waged. Many building ventures with which you are familiar, had a similar history. We received help from a great many different quarters: the University of Toronto, the City of Toronto, the Province of Ontario, the Dominion Government, and also many private donors. Dr. Phair himself was a very great help to us. One of the largest donations was made by Eli Lilly & Co. (Canada) Ltd. whose representative is here today. Although eventually three times the amount necessary to build and equip the whole building in 1938, became available, this was insufficient to include the fifth story of the new structure and this was abandoned permanently. The wing running east and west was only built one story above the ground. The completion of this wing for medical research and the archway to house the Insulin memorabilia and to connect the new Institute with the Banting Institute will, I am afraid, cost between three and four hundred thousand dollars. The wing will soon be needed for important medical researches. The Insulin Museum has been desirable for many years and some day the original notebooks, apparatus, charts and other records which Banting and I kept will be of considerable historical value.

It was a very busy autumn for many of us with the high point, of course, on September 15th. The International Physiological Congress with 3,000 members and representatives from 48 different countries, met in Montreal in the first week of September. My colleagues in Canada elected me president of that organization. Due largely to the work of the local committee in Montreal, under Professor MacIntosh, it ran smoothly. Many friendships were made and many great discoveries described. If we may judge from the contributions to medical knowledge which have been made by the men who attended, this was by far the greatest medical conference ever held in Canada.

The 48 representatives from the different countries formed a World Federation of National Physiological Societies. The first duty was to elect a Council. I found myself on it and then to my great surprise and consternation, the first President of this International Federation of Physiological Societies. I have tried to avoid administrative appointments and to keep my time for medical research but a certain amount must be devoted to administration of research matters. After the conference in Montreal there was another convened by UNESCO to discuss the future of medical research. This conference was in the Laurentians. After that there was a conference, subsidized by The Macy Foundation in the United States, on liver diseases. I have been acting as chairman of this Conference for the past seven years. But the high point, as I have said, of the interesting month of September, 1953, was our Opening on the 15th.

I will not attempt to describe the ceremonies which made this a red-letter day-certainly for our family--and I hope for all the members of the staff who will find better opportunities for research in this new Institute. I would like to attempt to describe for you the first scientific meeting held in our new lecture room. This was in the nature of a confessional. I had asked seven of the distinguished doctors who were our guests on. this occasion, to answer the question: "Which of your own investigations has given you the most satisfaction and pleasure?"

First on the list was Professor Adrian, President of The Royal Society of London and Master of Trinity College, Cambridge. Adrian described in a delightful way, the rather simple set of circumstances that enabled him to discover certain vitally important nerve impulses-impulses going to the brain from the various muscles in the body-impulses which enable us to walk upright, to balance and to achieve normal locomotion. It was a beautiful account of a great discovery, described in a way which I am sure he had never done before.

Adrian was followed by Dr. Detley Bronk, President of John Hopkins University, President of The National Academy of Sciences of the United States and now Director of The Rockefeller Institute for Medical Research. Bronk described the application of certain fundamental knowledge to the safety of aviators flying jet planes. Bronk had worked with Adrian in securing some of this fundamental knowledge but he chose to describe the application of this which enhanced the safety and improved the efficiency of this select group of young men chosen for this exacting and dangerous duty.

The third speaker was Sir Henry Dale, who told of the discovery of what we call the neurohumors--chemical substances formed at the end of nerves, substances which produce the affects commonly associated with the result of passage of impulses along the nerves. This is one of the great advances of medicine rewarded by the Nobel Prize. It always hurts me that this life-saving addition to our knowledge should be prostituted, as it were, by the use of a substance as a war-gas which prevents the normal destruction in the body of this vital normal substance. That is, this war--gas permits the accumulation of the normal substance--it might be insulin--and thus causes rapid destruction of living organisms. Insulin is formed and the excess rapidly destroyed. If the destruction should be prevented by a gas the normal organism making this lifesaving substance would be killed by the self-made overdose. This has NOT been done in the case of insulin but has been done for Acetyl choline, the substance normally liberated by nerves in our bodies. You can find a good description of this development in the ultrasecret files of the defence departments,--or in LIFE MAGAZINE!

The fourth speaker was Dr. B. A. Houssay, courageous upholder of the rights of medical scientists in the Argentine, who described his outstanding work. He also was rewarded with the Nobel Prize. He is the only medical scientist in South America ever to receive the Nobel Prize, and he told us of his brilliant work on the mechanism of causation of diabetes.

Then there was Dr. E. P. Joslin, grand old gentleman of medicine in the United States, dean of those who treat diabetes throughout the world. When I was in Boston ten days ago at the National Academy meeting he had just returned to work at 84 years of age--9 days after removal of his appendix.

The sixth was a Canadian of whom we are all very proud--Dr. Wilder Penfield of the Neurological Institute of Montreal, who held his audience enthralled when he told how, in the search for a part of the brain which might be causing epilepsy in his patient, he stimulated in his conscious subject an area that revived memories which had been forgotten. Every time the stimulation was applied the memory came back. When the stimulus was not made with the little electrode on the brain there was no memory of the event. Let this conjure up for you the nature of the card index system by which we catalogue our experiences in our brains. Let us remember that they may be elicited by abnormal stimulation even though we cannot voluntarily call them to mind.

The last speaker--they were arranged alphabetically--was Sir Lionel Whitby, Master of Downing College and Vice-Chancellor of Cambridge University. He told about the development of one of the great sulfa drugs which enabled him to prolong the life of one of his patients whose name is known to everyone throughout our Commonwealth.

The seven included the ranking scientists of the British Commonwealth. There were present three, of the twenty-four of those who hold the Order of Merit. There were three Nobel Laureates. This Conference was recorded and its message will stimulate and thrill generations of our medical students.

In Canada in medical research we have to select and concentrate in order to make contributions which can hold their place in competition with those made in larger and more wealthy countries. Our research group in the new Institute will be divided into ten sections. Each one will be headed by a mature scientist and will usually be composed of only three or four people. We will spend some of our time on defence research. Some of you may have noted an excavation extending out under the Park, protected by thick walls of concrete. That is to house a source of atomic radiation-not an atomic bomb-but a source of continuous radiation so that we may study methods of protection against it. Canada is expected to be an authority on the medical and scientific aspects of living in cold climates and work will be directed to this end also in the new Institute. Toronto has become a bit of a Mecca for diabetics and for research workers interested in diabetes. There is seldom a time when we do not have guest workers from many different countries in our laboratory. There is a great deal more to be done in the field of insulin and diabetes and Toronto has a continuing responsibility to many millions who live with the help of insulin and perhaps also to the many millions more who would live longer if insulin were available to them. There is scope to make an even better form of insulin, to find out the cause of diabetes, to prevent it and actually to cure it. There is real hope that these goals may be achieved. Most diabetics are middle-aged or old. They still have some cells in their bodies which make insulin. It may be possible to release these from the damaging influences which are exerted on them and to encourage them to produce again enough insulin to support the needs of their bodies.

We have a very active group working on agents which prevent thrombosis. Heparin was first purified and used clinically in the Connaught Laboratories in the Division of which I was then in charge. Dr. Scott who played a large part in its development is here today. Dr. Solandt, who unfortunately is ill today, and I showed that heparin could prevent coronary thrombosis in animals and the wide-spread use of this and other anticoagulants in the prevention of second attacks of coronary thrombosis, stems from this fundamental knowledge.

There is a great deal more to be done here too and our groups could be strengthened and the work intensified with profit to the people in Canada, and, I think, to people the world over. There is an active group in the cancer field under Dr. Franks, making direct attacks on the cancer problem.

It so happens that in most fields in which we have worked, insulin, heparin and choline--which I am going to describe in a few minutes--there are aspects of these problems which have their bearing on the phenomenon of aging which has certainly been accepted the world over with too much equanimity. There is a lot to be done about the problem of aging. Nothing succeeds like success and continued advance will come from the countries where people live the longest. Canada has a responsibility when we look at it from that point of view.

We have several active groups working on choline, the new vitamin which was discovered some years ago in our laboratories. It is the only food factor, the absence of which has been shown to produce high blood pressure in animals. It's absence leads also to cirrhosis of the liver and some of these cirrhotic fibrous tissues may turn into cancerous tissues. In the countries-and this applies to more than half the world-where nutrition is grossly inadequate, there are many vital food factors which are lacking. It has been shown that the absence of this one simple substance, choline, from the diet of young growing animals, can produce certain of the characteristic signs of advanced old age within two or three weeks. These are drastic experiments on rodents-not studies on human subjects--but they reveal vital truths which will have their application some day to human problems.

My extra-curricular interest which I have attempted to indulge by trips to various parts of the world-subsidized by various foundations in England and the United States and others--might be labelled very conservatively, "The Health of the World from the Medical Viewpoint." In the pursuit of knowledge relating to this interest, my wife and I have flown some 130,000 miles since the war, and have studied conditions in South America, Africa, Australia, and other countries. My interest in this was aroused when I was adviser in nutrition to The Rockfeller Foundation and our findings in the laboratory here have an intimate and practical application to some of the problems which exist throughout a very large part of the world. One small part of this has been the organization of diabetic patients in many, many countries, so that they can help each other. I have played a role in the formation of the International Federation of Diabetic Associations.

The central problem of the world is nutrition of the people in underdeveloped countries, because you can't educate and guide undernourished people. It seems to me to be at the very centre of the present troubles of this world. Canada has made a fine job of feeding its own people and if we had temporary responsibility for an undernourished area, I am sure that we could put on a grand demonstration of what can be done by nutrition, in improving the public health of a country. We do help, of course, through the Colombo Plan and United Nations activities.

We are now, however, in an excellent position in Canada to intensify our efforts in medical research and to provide more basic knowledge which will be immediately distributed to all parts of the world that can use it.

I would pay tribute here to the several departments of the Dominion Government that have taken leadership in making funds available for more intensive medical research in Canada. The National Research Council of Canada, the Defence Research Board, and the Department of Health and Welfare. Their efforts have brightened tremendously the picture of medical research in Canada but there is more that could be done.

It would be appropriate in view of our devotion to private enterprise, if organized voluntary contributions from businesses and individuals were to supply the need. I have been extremely interested to learn recently that a National Foundation for Medical Research, originating here in Toronto, has already received verbal approval from the Minister of Health of Ontario and from the Minister of Health of the Dominion. I can think of many ways across this country in which this organization can be of tremendous help, not only to ourselves but to all the people of the world. Its efforts must of course be carefully coordinated with those of the Government Departments who have already done so much.

Many people ask us the question: Why do you devote your lives to medical research? What are the rewards? They are certainly not financial. Ethical medical men do not make a penny out of their medical discoveries, and this was the course followed in Toronto. The patents on Insulin were assigned to the University of Toronto; they were given away to every country in the world except where a continuous service was rendered. Some funds from the United States, through the companies which make Insulin, have been used by the University of Toronto to administer matters relating to insulin the world over and to support a testing laboratory which has investigated every lot of insulin made. The residue from these funds was made available for medical research in Canada. This has supplied a part of the budget for the departments which have benefitted from it. If the University of Toronto had been so minded, it could have exploited insulin--legitimately from the business point of view--in all countries in the world and have secured a revenue which would have paid all the expenses of educating the 10,000 students in the University for the life of the patents. That is a conservative statement, they probably could have made more than that. This was not considered an ethical way to handle matters and I believe that the University of Toronto and Canada have profited enormously by not attempting to commercialize this medical discovery. The University would have gained some of the world but would have lost part of its soul. Those of us who go into medical research work and other research activities must have a missionary spirit and we must certainly be dedicated to our work, because what we do must be the main reward that comes from it. Many of us are idealists and believe that, after the basic rights which ensure the dignity of man are provided namely his care in sickness and old age and his need for satisfactory and healthy working conditions, people should be rewarded in proportion to their contribution to the public good. Actually the rewards of productive work come in many different ways: the satisfaction of opening up a new country, of discovering a mine, of growing a new type of food product or a beautiful flower. It comes from opening up new pathways, some of which may lead to immediate cures of disease if the field is medical research, some to better methods of treatment, some merely reveal new truths which certainly will be applied later. I can assert with firm conviction, Mr. President, that the rewards of medical research are very real and very great indeed.

THANKS OF THE MEETING were expressed by Dr. C. C. Goldring, the third Vice-President of the Club.