Andrew V. SCHALLY
CONVERSATION WITH ANDREW VICTOR SCHALLY
from The Roots Are Polish
by Aleksandra Ziólkowska-Boehm
Professor Schally and His Analogues.
I visited Professor Schaly at his laboratory on the 7th floor of the Medical Center in New Orleans in 1991. His office walls were decorated with carefully regimented framed awards. A multitude of folders and other medical literature were stacked up on the table. Professor Schally is of medium height; he looks at me attentively.
- I hope I will be able to answer your questions which will allow you to present a picture of what I do and to what I dedicated my life.
The culminating moment of Professor Andrew Schally's distinguished career came in December 1977 when he received the Nobel Prize in medicine and physiology for "having isolated determined the structure and synthesized the first three hormones of the hypothalamus causing the release from the pituitary gland of hormones regulating the activity of the thyroid, the sex glands and body growth".
The Nobel Prize was shared with Professor Roger Guillemin, his rival for over 20 years. During that time both men directed their separate teams of researchers in research on tons of animal hypothalami to isolate just a few milligrams of the necessary hormones.
It has long been held that the pituitary gland was the "master gland" of the hormonal system. Andrew Schally was the first to prove that the pituitary gland is controlled by hormones produced in the hypothalamus. Moreover, he examined the function of these three neurohormones: TRH - controlling the activity of the thyroid, LH/FSH-RH regulating the hormonal balance of the sex glands and a somatostatin a hormone regulating the processes of growth and influencing the entire digestive system. He also produced these hormones synthetically in the laboratory.
The Nobel Prize brought him additional renown and satisfac-tion, but that was a long time ago, as he says. It did not make him change his lifestyle or his pace of work.A scientist of passion an love, working 12 hours a day, he is persistently hopeful making new directions. Using the phrase of the American journalist, Douglas Stein, "Schally has a good chance of getting a second Nobel Prize, this time though just by himself".
I read in the Biographical Dictionary of the Nobel Prize Winners published by H.W.Wilson in the United States: "American biochemist Andrew Victor Schally was born on November 30, 1926 in Vilna, Poland (now Vilnius, Lithuania), the son of Casimir Peter Schally, a soldier, and Maria Lacka. When the World War II broke out, Schally's Father joined the army"....
The quoted statement has several mistakes. At first, Professor Schally is an endocrinologist. His father was a general of Polish army.
"The way I look at life is influenced by a harsh childhood I spent in Nazi-occupied Eastern Europe". I continue to read in the same dictionary a direct quote made by Professor himself.
It is through our conversation that I found out about his childhood he spent in Warsaw. actually growing up in the so-called Tinroof Palace (Palac pod Blach_), where his father. General Casimir Peter Schally, held a position as head of Military Cabinet for the President of the Polish Republic. His mother, Maria L_cka was a daughter of Helena L_cka and Karol L_cki, an officer.
His last recollection of Warsaw for the then 13 year old Andrew Schally (he changed his name to Andrew in England) is the 1939 bombardment of the city. Together with his mother and sister Halina, he fled the country to sojourn in Romania, Italy, France and Scotland, respectively.
In 1946, he graduated from the Bridge Allen School, a Scottish high school and then, studied chemistry at the University of London until 1950. Over the next two years, he worked as a junior research scientist at the National Institute of Medical Research in London. This is where his love for scientific research found particularly favorable conditions. "It was very happy to have the opportunity to study at the best British research institute. At that time, Britain was making a significant contribution to the development of medicine. This is where penicillin was first discovered. I loved the environment, the area where I lived and worked. I got the "bug" for research and also for the field.
He recalls having studied with some future Nobel laureates, the atmosphere of his university days and the scientific work in London that left lasting life-long impressions.
In 1952 Schally left for Canada, entered McGill University in Montreal, Quebec, to study endocrinology under D.L.Thompson. At the same time he was responsible for laboratory research projects at the Allan Memorial Institute of Psychiatry. In 1955 he received a master degree and in 1957 his doctorate in biochemistry, both from McGill University (McGill didn't offer degrees in endocrinology).
At that time, Schally held a fascination for scientist Geoffrey Harris'theory on the hypothalamic control of the pituitary. As early as 1937, this British anatomist believed that the pituitary gland was regulated by hypothalamic hormones released into the bloodstream in a fine system of blood vessels called the portal system that connects the hypothalamus to anterior pituitary. Harris advanced a theory suggesting that the anterior pituitary gland is controlled by the hypothalamus, a neural structure found un the base of the brain through neurohumoral substances. He believed that every pituitary hormone has its own stimulating agent. There was another physician, Roger A.Guillemin, an endocrinologist from Baylor University, Houston, Texas, who had been influenced by Harris's theory. In 1957, he invited Schally to work as an assistant professor within the Physiology Department at Baylor University College of Medicine in Houston, and later, in the biochemistry department at the same university.
Initially together, and then separately, these two scientists dedicated many years of research to test Geoffrey Harris's theory... that there is a functional interrelationship between the
nervous and hormonal; systems with hypothalamus as its regulatory centre. Their 5 year collaborations, sharing the same laboratory did not turn out any major results. They parted in 1962 after what became according to Schally's phrase a "hysterical rivalry". These were "frustrating years", says Schally; he talks about Guillemin's irritating and autocratic style. Therefore, he was happy to have been offered his own laboratory at the Tulane University Medical School and Veteran Hospital moved to New Orleans and became director of the Endocrine and Polypeptide Laboratory.
The race leading to the historical ground-breaking discoveries turned into a bitter rivalry. It brought about repercussions criticism and malicious comments throughout the American endocrine community. Other investigators, jealous about the research funds received by their two colleagues, were full of sarcasm when talking about that efforts. But soon to be proven wrong.
In 1966, Schally announced the discovery of TRH - the hormone stimulating the secretion of the thyrotropic hormone. Together with his collaborators Cyril Y.Bowers and Tommie W.Reading, they determined the sequence of the amino acid of the peptide TRH which stimulated the secretion of the pituitary hormone TSW. This point was marked with an additional flare-up in his relations with Guillemin: although the two rivals now had scientific results to defend the validity of their research.
"My colleagues skepticism made me work even harder", reminisces Schally, "when some of the greatest specialists understood my research they immediately stopped fighting against me, instead, they acknowledged that I was right and joined me and we became friends". When criticism subsided, Schally, Guillemin and at least four other teams of researchers engaged in quite an intense competition to an effort to isolate the hormone causing the release of the gonadotropic hormones FSH and that influence the production of androgens and estrogen by sex glands. For isolation purposes Schally used large quantities of pigs' brains. He succeeded in obtaining farm meat producer Oscar Mayer, 250.000 samples of the necessary animal tissue. Months later, working around the clock, Schally and his team identified the chemical structure of the peptide LH-RH. The discovery, made in March 1971, was announced in June at the convention of endocrinologists in San Francisco. "This was the happiest moment of my life - the announcement of the solution to a problem that has long fascinated me and others. That hormone LH-RH was a big prize in endocrinology because of its impact on fertility, birth control and reproduction".
Guillemin, defeated scientifically, could do nothing but give him a round if applause. From then on, Schally made additional great strides in his research work which culminated in LH-RH being synthesized. Soon, he determined the chemical relationship between structure and synthesized derivatives of LH-TH. so-called analogues.
The success of Schally and Guillemin who independently discovered the peptic DE+ hypothalamic hormones, revolutionized the understanding of some functions of the brain. Practically speaking, the field of neuroendocrinology started with Schally and Guillemin, although theoretically existed since the ground-braking theory of Geoffrey Harris.
They shared Nobel Prize amounting to $145.000 with Rosalyn Yalow who received it for her work on another discovery - "radio-immunoassays".
"We are all very proud... Schally is a success story which probably happens only once in the lifetime of an organization. We are proud that the Nobel Prize goes to the South of the United States, and we are happy that Schally works in at VA and Tulane:, said A.Threefoot professor of medicine and chief of staff at the Veterans Administrations Hospital in New Orleans.
Besides the 1977 Nobel Prize, Schally has been a recipient of a number of highest awards including Lasker Award, Borden Award No 1 and 2 in USA, Mickle Prize and Gairdner Award in Canada, distinctions and honours including the degrees if Doctor Honoris Causa at nearby 20 universities. The Jagiellonian University, Cracow, Poland presented him with a 600th anniversary medal, the American-Polish Medical Association - with a Doctor's Golden Medal commemorating Poland's millennium. On Professor Rudolf Klimek's request, the title of doctor honoris causa in medicine was bestowed on him by the Medical Academy of Cracow.
Presently, he holds honorary doctorates from the Sorbonne,, the universities of Madrid and McGill Montreal, to name just a few. His life work encompasses over 2000 publications. He is a member of editorial committees of the prestigious medical journals in the fields of endocrinology and oncology. As well he works in several countries as a consultant in the area of oncology and neuroendocrinology.
Usually, Schally manages projects of long duration, from 5 to 10 years. His research on endocrinology and cancer covers the fields of medicine, physiology and chemistry. He thinks of himself as an endocrine oncologist which allows him to bring his focus back to the basic research.
Actively supported by his knowledge and experience, as well as constantly advancing new theses Schally, together with his team, launched what he called a "massive offensive" against a variety of tumors relying on the functioning of the hormones-cancer of the prostate, breast, bone, ovary, lungs, kidney, stomach, pancreas, colon and brain tumors. This treatment required patients to receive regular doses of medicine over a prolonged period of time. But now once a month insections are available.
Schally and his team have also been working on hormone GH-RH which releases the growth hormone. This hormone GH-RH may be helpful in treatment of suffering from under-active pituitary gland and geriatric patients.
With his colleagues Schally has been conducting animal research on hormonal mechanisms regulating fertility.
Some analogues of LH-RH do not stimulate the pituitary gland to secrete gonadotropic hormones LH and FSH on the contrary, their use inhibits the release of LH and FSH and hence six steroids. After having discovered this fact, scientists proved that these types of analogues trigger the prostate gland tumor to recede. With his wife Dr Comaru-Schally proceeded to initiate clinical research on the treatment of metastasis of the prostate cancer. Started out in Canada, the research yielded very good results. In patients treated with analogies LH-RH, the tumors had only receded but allowed for a better passage of urine and reduced the pain in bones caused by the spreading cancer. This observations was made in 90 per cent of treated to the presence of sex hormones. In order to treat them, the level of testosterone and estrogen respectively must be lowered. In the past, the only method of treatment of prostate cancer was a removal of the prostate and the use of estrogen therapy led to great deal of acute physiological effects such as for instance, impotence. Currently, prostate cancer is effectively treated using synthetic analogues LH-RH which lower the production of testosterone. The analogue is equally effective in the treatment of premature sexual development in children.
Cancer of the pancreas has been incorporated into Schally's research. He finds the analogue may be helpful in the early stages of the diseases, but he says that the methods need to be improved.
Schally has a son and a daughter from his marriage to Margaret Rachel White. He met his second wife, Ana Maria Comaru, a young doctor, during his lecture tours in Brazil. Two years later, they got married. Dr Comaru-Schally shares the commitment and passion of her husband; she is personally involved in supervising the clinical research of hypothalamic analogues.
He speaks Portuguese with his wife, at work it is English and Spanish, in the earlier days it was French, and Polish in his youth. He no longer speak Polish, he says it has been a long time since he spoke it, that he forgot (his younger sister Halina Schally-Ternynck who lives in Montreal is fluent in Polish). He is inquisitive and full of energy. "Schally is for me a symbol of ascetic knowledge utterly happy with his work. He is a titanic giant of science", wrote Professor Klimek.
Despite his unquestionable talent and hard work, Schally attributes his success to favorable circumstances. "...You have to have curiosity and self-discipline, be a master of systematic work. I am not patient but I am disciplined. What also counts is to be at the right place at the right time. Like Napoleon".
Professor Schally is proud of the discipline he has subjected himself and his physical stamina. He swims every day in his swimming pool in Metairie near New Orleans.
Here are some of the replies to the questions I asked him:
- You called yourself primarily neuroendocrinologist. What does it mean?
Neuroendocrinology encompasses primarily research on hormones originating in the brain. I started cancer research in 1978. My wife and I found out a great deal about tumors although at that time we were not oncologists. We worked long hours, perhaps 12 to 13 hours a day, not as much reading textbooks as doing the actual research - to get the core of the matter. Now I consider myself an endocrine oncologist.
- It is commonly believed that you were inspired by the theories of Geoffrey Harris to do research to isolate the hormones. To what extent is it true?
Harris insisted on the importance of the role of hypothalamus in controlling the secretion of the pituitary gland, but was unable to obtain active substances and prove their biological activity. Guillemin and I were successful is isolating these hormones. Harris did nor prove the existence of hypothalamic hormones. I entered this field as an endocrinologist.
Ana Maria Comaru-Schally:
Let me tell you something about my husband. Lest us forget for a moment about science. Do you know that my husband gets up every morning at five o'clock, does his exercise for half an hour and every day at six thirty we are at the hospital/ We work twelve hours a day including Saturdays. His medical knowledge is immense, he reads a lot. Professionally, he is honest - in his articles, he would always mention the person involved in research in the area he is writing about. He swims every day and is able to walk for hours without a rest. I think it is incredible! When we come back from a trip, he immediately starts his exercises. He speaks several languages, gives lecture in Spanish and Portuguese in South America. I learned Spanish from him. We met in 1974 when I was working in Rio de Janeiro as an endocrinologist. He likes cooking. He taught me how to cook, his specialty is goulash. We have been together twenty two years. It started off as a romantic affair, I was receiving a lot of letters. We are both very happy being and working together.
But not all wives would be willing to go to the lab every Saturday, get up at six o'clock in the morning and work so many hours each day. To top it all off, my wife ia a beautiful and exceptional woman and an excellent physician. i like her parents, I like her company.
- How important is physical fitness in your life?
Sometimes I play soccer. Swimming as I already said is for me a must. Working so hard - physically and mentally - I need my rest. I need to be in good physical shape. When I come home after six o'clock, I am simply exhausted and probably, would not be able to answer a question about my address or telephone number. But after swimming for twenty minutes, I feel refreshed. I swim a great deal, especially during holidays which we usually spend in Brazil staying with my in-laws. While there, we eat a lot of fruits I like, pineapples, papaya. I also lecture at the local universities.
I have always liked sports except for mountain climbing which I find dangerous and complicated. Why would I want to climb the same mountain? Swimming is simpler, simpler than golf. I do not like skiing. As a spectator I like football and boxing. I listen a lot to classical music and operas. I like the music of Beethoven, List and operas by Verdi.
- Did your success result from co-operation or competition?
It is a fruit of co-operation. Co-operation between gentlemen and intelligent people is a pleasure. What existed between me and Guillemin was a sort of cold war rather then an open hostility. The competition became eventually so intense that all co-operation was no longer possible. On the other hand, I believe that healthy competition stimulates the necessary elements to accelerate creativity.
We are jus different, Guillemin and I in our reactions, characters and behaviour. He, for instance, does not like sports. I did not learn from him anything new. In London I worked with people that eventually became Nobel Prize winners. A.J.P. Martin, for instance. For me, he was a true genius.
I think, I have much more to offer now than at the time I received the Nobel Prize. My brain works in a more effective way to arrive at a proper and right diagnostic. I am able to predict the results of a great deal od experiments at the onset of a study.
- What is the impact of one's ethnic background on temperament?
I am a mixture of ethnic background and professional experience gained in various parts of the world. After the German occupation, when I found myself in England, I thought I was in paradise. However, after five years of inclement weather and high taxes, I left partially looking for more sun. I spent some time in Romania, the summers there were warm.
I think that whatever I accomplished it was due to my British experience and the chance that country gave me when I arrived there. I already mentioned that a great number od scientists educated in England became Nobel Prize winners eventually. They simply received good schooling and training. The British taught me how to think practically and exercise my brain; at the same time they showed me, psychologically speaking, the approach necessary in planning a scientific experiment. What was most required was systematic planning, hard work and a great effort. I am not a patient person but I am disciplined, as I have already mentioned.
You know, I always come up with good ideas, but the trick is to know how among the hundreds of promising ones, to choose the ones pursuing. Medical research, as you know, need adequate funding in the sixties, I did a lot of work on my own, using my own hands, because nobody believed in my ideas on hypothalamus. After I was able to isolate TRH and LHRH, I no longer had a problem. Before that however, I would spend hours perfecting new and difficult techniques. People have always told me that I had good skillful hands. That has not changed except that now I work primarily with my head.
- Did you realize that not isolating the hormone would have meant scientific defeat - a disaster' bluntly speaking?
Man has not yet landed on Mars nor on Venus due to technical limitations. I enjoyed full confidence of some key scientist and administrators and I did not lose it. Criticism did not bother me, I knew I was right, so I just had to learn to live with it. We did our best, conducting the research with funds and equipment available to us. If I mention now that I am Nobel Prize laureate, I do so in order to convince my sponsors; the job I do is serious, and it is necessary to enlist the trust of various organizations and institutions that may be helpful. But I do not live in the past. What counts most for me is the present and the future.
- What do you think about the availability of research funds?
In the 1970's, I wrote to a leading pharmaceutical companies asking for support and help in the LH-RH testing. Tulane University where I worked received donations for this testing from various sources. Donations ranged from two hundred to two thousand dollars. I knew that the research I was doing with my associates was worth a hundred thousand times more for these donating companies. There are people that receive a great deal of money from pharmaceutical companies, giving nothing in return. This is totally unethical. But once you do it, you loose credibility once and for all. Our laboratory is in a constant need for financial help, however small.
- What do you mean by "small"?
People think that the Nobel Prize and other awards I received make it all simpler. That is not the case. We have 42 laboratories with modern equipment and 28 offices. I have to staff it with dozens of highly qualified specialists. People from a lot of countries would like to work with us. If I had a larger team, cancer research would advance much faster. The cost of research is very high. Modern scientific research is the result of the team effort, the same as in football or soccer. A team's offensive players attack their opponent endeavoring to score goals...the defensive of the same team tackle their opponents to prevent them from scoring goals.
- To continue the sport analogy, do you see yourself more as a team captain or a coach?
Definitely as a team captain, because he is the one who has lots to say about the possible strategy. Certainly not as a coach!
- What is the difference between total dedication to work and an obsession?
An obsession is healthy if it pertains to a healthy idea. If the idea is bad than the obsession may become unhealthy. To work on and describe a good experiment gives me a lot of satisfaction, but it is not an obsession. When someone sticks to a idea and is convinced that he or she is right to me, that is determination, although the dictionary may not agree with me.
I am always curious about new issues. I propose a new study because I have a vision. The study should bear fruit although that is not always the case. I would not call it an obsession: it has always been mu intention to prove the validity of my claims because I have firmly believed in them. Winning a prize has never motivated me. What compels me is a need to prove the validity of my ideas. Should I continue to be such a workaholic? I have received practically all the possible scientific honours available. I can travel, stay at the best hotels, but that is not what gives me satisfaction. I have enormous quantity of mental and physical energy, and yes, an obsession - in the positive, creative sense of this word.
I am pretty happy with myself and my achievements, although I do not think I can measure up, as a scientist, to such giants as Einstein or Darwin.
- Let us talk now about Poland.
Now you are asking me about Poland. I grew in Poland, yet I no longer speak Polish. I have not spoken Polish in many years. My father after the war was engaged in anti-Communist activities. I am not involved in politics. For a long time I id not want to go to Poland. I was afraid I will get implicated by the authorities in some illegal activity: money change on the black market or something else. After having received the Nobel Prize, I went with my wife, my sister and her husband. I saw Warsaw, Cracow, Zakopane, Morskie Oko, Wieliczka.
...it is difficult for me to speak about Poland... The West has never been able to understood her. Maybe there should be more people of the Brzezinski caliber abroad. I highly value the Polish Pope. He has been the best pope in five hundred years. It is my wish to meet him in person.
Ana Maria Comaru-Schally:
I remember how, in 1977, we were invited to Brazil. We went to New Orleans directly from Stockholm where my husband received the Nobel Prize. We changed clothes and went to Brazil. At that time everyone was repeating the name of my husband. A lot of people phoned us. Among them there were also Poles - they wanted to invite us to a special ceremony organized just for us. We turned down most of the invitations. I said to my husband: "let us go to see them, if only for half an hour...". We were greeted in a beautiful residence. They spoke French, English; were sophisticated, educated. What we found most moving though was the fact that in the group there were my husbands father's soldiers. They had recollections of General Casimir Peter Schally whom they greatly valued. They told us how proud they were to find out his son became a Nobel Prize winner.
But it is America that is clearly for me the most important country. I love it end appreciate it and I am 100 % loyal to it. It is America that made my work possible, although my British and
Canadian helped me greatly in training.
I do not know what picture will this conversation provide you with. I would still like to go to Poland, tie it to some lectures. I might be able to do it in the near future?
This chapter appeared in English in “New Horizon”, July 1999, and in the book “THE ROOTS ARE POLISH” (Toronto, second edition 2004) published in Canada under the care and with the support from the Canadian
Aleksandra Ziólkowska-Boehm : Andrew Schally transl. Nina Krygier-Michalak
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