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Andrzej Viktor "Andrew" Schally was born in Wilno, Poland, now known as Vilnius, Lithuania, in 1926. Living his early life during World War 2, Schally lived in a Jewish-Polish community in Romania. He moved to England in 1945, where he joined the National Institute of Medical Research¹. He then moved to Canada where he worked and studied at McGill University¹. At McGill, he studied endocrinology. He researched in a lab devoted to adrenal cortical steroids and ACTH. In 1955, he helped demonstrate the presence of corticotropin-releasing factors in the hypothalamic and neurohypophysial hormones, regulating pituitary function¹. In 1962, he became a citizen of the United States¹. Here, he led research in a VA laboratory devoted to the hypothalamus. After six months, he became the Chief of the Endocrine and Polypeptide Laboratories at the VA in New Orleans¹. In this lab, he eventually discovered the structure of certain key hormones such as thyrotropin-releasing hormones, luteinizing hormone-releasing hormones, and follicle-stimulation hormones². These discoveries led to the understanding that the hypothalamus was the controlling factor of the pituitary gland². As a result, he became a Nobel Laureate for Medicine or Physiology in 1977². This work opened the door to new research in contraception, diabetes, abnormal growth, and other mental disorders².

Sources:

1. https://www.nobelprize.org/prizes/medicine/1977/schally/biographical/

2. https://libguides.tulane.edu/famousalumni/AVSchally#:~:text=or%20Physiology%2C%201977-,Dr.,hormones%20and%20follicle%2Dstimulating%20hormones.

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The Fischer peptide synthesis is what is presented here. It shows how to artificially synthesize peptides for experimentation. Emil Fischer discovered peptides at the beginning of the 20th century. Fischer wanted to understand protein synthesis. He contributed to the knowledge of proteins by separating and identifying individual amino acids¹. He discovered peptides such as glycogen by reacting different proteins together. To do so, Fischer produced phenylhydrazine, a base that helped reveal sugar molecules' structures which allowed him to produce several sugars artificially and map the structure of their molecules². Additionally, Fischer discovered the method the peptide synthesis by elongating a peptide through a reaction of amino acids and then removing a reversible protecting group². This discovery of peptides was the foundation of protein synthesis. It inspired further research on protein synthesis and peptide formation, leading to a better understanding of how the human body works and neurotransmission as well. Without Fischer's discovery, Schally wouldn't have been able to explore the role of peptides in the nervous system.

Sources:

1. https://www.nobelprize.org/prizes/chemistry/1902/fischer/biographical/

2. https://www.ias.ac.in/article/fulltext/reso/016/07/0640-0647#:~:text=Emil%20Fischer%20is%20considered%20to,a%20protein%20would%20be%20synthesized.

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The De Usu Partium is a collection of works written by Galen between 165 CE and 175 CE in Rome. In this work of anatomy and physiology, Galen describes different body parts and their function¹. He reveals basic medical concepts and anatomical details¹. Roman laws didn't allow people to dissect animals². He found these anatomical structures and learned physiology through his live dissections called vivisections on animals². These animals include pigs and dogs². In De Usu Partium, Galen describes the hypothalamic infundibulum and the pituitary gland as the draining route and receptacle for mucus passing from the brain ventricular structures to the nasopharynx 3. Even though he was wrong, Galen's contributions to anatomy inspired generations of scientists to further research the human body. Moreover, his discovery of the hypothalamus and pituitary gland inspired heavy research on the brain.

1. https://watermark.silverchair.com/jama_207_12_036.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAz8wggM7BgkqhkiG9w0BBwagggMsMIIDKAIBADCCAyEGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMSlvlOfojbgwrsy3pAgEQgIIC8i7G_6SKviFrn-gBlxnEJaDWCnjxUYCEjbHpEMGoso7JIDLWBXtkJ5cuk3iTCSJ56mHecbCZSqERyFPCU_KHYNKh2UvHF7KdDBTVpZzBDd530iFjTaGaHLScDxAxwYsJ3T-zl-jsPKdIrt3-79SZlofKkWZv-hRx8rx2MzuVuutupfhvi3WzM8XogrsXVG74IrXBMBxHnTWJp87PLYoVavuy09ZzxD6gSOyg9iSyNsJvJQ3aD-4P4fNdJEmTQq07ANvcQxCs0aLXyNfZRZyB4xY7XdSmc1E2XgK0IelyeuBcVjgjRsPCq8iaFjcuLK_iIbhSprlFifvT_Px0VIFZcdcFmSeGtlqRycVvhhyNnvSeMIigKbepm0m9Sp30R0T6RVtxq1A4IN6kMfZecJUnXb7R7r0fwcJPcSKUIjR29Yn6cyKd3FdpKTvqWgqBoljCwpasGVPPqjbBC7Lb3qtrzb1yvJVFAPgI5RYUGGtUiscs9Vbm5mJuivgOgJqAxZ1I-P8C0XxVlY5_I3xDhjfASLt0tlmCR8siNOCATlw85HG-cv_Y5KLEnVpmd_dC4VjD367Wyj8y1P2L4-dka24irBerDwKvFo2Gf_oWQR627BBNtYa1xEgjMMk-66ktlaSCA39g0jH3JvKfj_u_47uDNRjMD5lXDBBvVXvMtWqcz1QmL0vCjv_FsgxRuhfavtkhqxuJ2OmpPslLQRZxHec62MmejqvjGMVBnjnNfSF9EH82CYxpX5aEuXg7wElanzJ9RKhn6gpYf11ITKJWz6Q2zQID0m7WTh4BORbgKp1eph_qQgdtP0_7uKDp9XC23CIYYV1VBfJJ5MQ7rNSyvsj2chxzJ4OJifMriyCKK7jO7pwRFqnioXNN3vY8Qi-CYM0nzCyKe0dziKGc88A86egHzxISTH1xMEi8nKgFMLhBEsTOBpZSgNCGM17sS8izEzasuNMussSGI3zxaeeUpXN0Hsi6A_qafZ0ViKPiXlr-DNW7ZKo

2. Amaker, T., Barber, C., Benson, A., Beyerl, Z., Bogdan, K., Crocker, L., Doppelheuer, E., Gonzalez, H., Heal, S., Strong, R., O’Dell, A., O’Haren, D., Pavlish, J., Prus, L., Reese, E., Sasnett, M., Shadinger, J., Smith, A., Todd, S., … Rothemich, K. (2020b, July 29). Galen’s Anatomical Anomalies & Discoveries. Science Technology and Society a Student Led Exploration. https://opentextbooks.clemson.edu/sciencetechnologyandsociety/chapter/ancient-anatomy-galen/

3. https://www.ncbi.nlm.nih.gov/books/NBK279126/#:~:text=Galen%20described%20the%20hypothalamic%20infundibulum,the%20pituitary%20gland%20the%20rete

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Wilhelm His Sr., a pioneer of neuroembryology, defined the modern interpretation of the hypothalamus. His' ideas supported the transversal nature and general comparable dorsoventral patterning of the alar plate¹. His was a Swiss anatomist who invented the microtome². The microtome is a specialized precision cutting instrument that accurately and repeatedly slices sections from a block of embedded tissue². Using these technologies, His could better study the organization and function of tissues and cells under a microscope¹. In doing so, he created this drawing, which models the forebrain subdivisions. The hypothalamus was the V.1 region¹. Without His' discovery, Schally wouldn't have been able to understand the role of the hypothalamus to this extent. His' discovery of the true nature of the hypothalamus contributed to Schally's research on peptide formation in the brain.

1. https://www.frontiersin.org/articles/10.3389/fnana.2015.00027/full#:~:text=Wilhelm%20His%2C%20one%20of%20the,et%20al.%2C%202012b).

2. https://www.sciencedirect.com/topics/neuroscience/microtome#:~:text=A%20microtome%20is%20a%20specialized,to%20section%20frozen%20tissues%20(Fig.

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Marie Jean Pierre Flourens (1794-1869) was a French physiologist who believed that the brain acted as a functional entity where specific parts of the brain controlled specific functions. He used ablation and stimulation methods on mammalian species to discover his findings. Flourens had several significant discoveries related to the nervous system that heavily advanced the field of neuroscience and psychology¹. For example, he believed that the medulla is responsible for many vital functions such as respiration¹. His use of ablation in experimentation led to a better understanding of localized functions in the brain. While his experimentation was crude and rudimentary, it was a byproduct of his time since he didn't have the accurate knowledge or proper equipment to conduct these experiments². Flourens' ablation studies were critical for advancing knowledge on brain localization and function². Moreover, Flourens disproved the pseudoscience practice of phrenology, preventing further neuroscientists from following the wrong path². Flourens' research greatly impacted the future of neuroscientists, leading to a new sector and thought of how the brain functions.

This work presented is Flourens' Du Systeme Nerveux. This works that explain the nervous systems and its several functions.

Sources:

1) Yildirim, F. B., & Sarikcioglu, L. (2007). Marie Jean Pierre Flourens (1794 1867): an extraordinary scientist of his time. Journal of neurology, neurosurgery, and psychiatry, 78(8), 852. https://doi.org/10.1136/jnnp.2007.118380

2) https://karger.com/ene/article/61/5/311/124627/Marie-Jean-Pierre-Flourens-1794-1867-and-Cortical

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Electroshock was introduced by Ugo Cerletti in 1930 as the first modern example a of therapeutic application of brain stimulation for severe psychosis¹. The electric current evoked an epileptic seizure that somewhat remodeled the neural connections, helping patients improve¹. This idea was inspired by the belief that the brain passed messages through only electrical signaling, not with chemical signaling. As a result, many brain stimulation technologies were originally based on electrical stimulation, not chemical stimulation. This viewpoint slowly changed over time as new discoveries were made.

This entry is presented to show the early stages of neurotransmission understanding². Without understanding the purpose of electric potentials in the brain, other understandings of brain signaling and neurotransmission would not have been possible².

1) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3157831/#:~:text=Electroshock%2C%20introduced%20by%20Ugo%20Cerletti,1940%3B%20Kalinowsky%2C%201986).

2) https://qbi.uq.edu.au/brain-basics/brain/brain-physiology/action-potentials-and-synapses#:~:text=Synapses%20can%20be%20thought%20of,into%20or%20out%20of%20the

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In 1933, American chemists successfully isolated cortisol within extracts from the adrenal gland¹. In 1948, the first patient with rheumatoid arthritis was treated with cortisone and then other rheumatologic patients received the same treatment soon after². This started a new investigation into cortisol and corticosteroids². They understood that cortisone stimulates native cortisone production, ACTH. Many researchers started looking into this line, including Schalley when he went to McGill. Schalley's research on cortisone and ACTH inspired him to further his pursuit of endocrinology, leading him to eventually create a lab for the VA and Tulane which led to his Nobel Prize³.

1. https://cortisone-info.com/en/general-information/what-is-its-history/#:~:text=In%201933%2C%20a%20team%20of,issued%20from%20these%20animal's%20glands.

2. https://pubmed.ncbi.nlm.nih.gov/22018177/

3. https://www.nobelprize.org/prizes/medicine/1977/schally/biographical/

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Ergot has always been referenced throughout history¹. Ergot mushrooms have often been known to give people hallucinations, paranoia, twitches, and many more reactions. In the Middle Ages, it was often mixed with flour unintentionally, causing many people to be afflicted by these symptoms¹. It has even been referenced in a tablet from 600 BC. Henry Hallett Dale (1875-1968), an American pharmacologist, discovered that ergot mushrooms had many pharmaceutical properties. With the help of chemists, he was able to extract many amines, such as one similar to adrenalin and acetylcholine². With the help of a chemist, Dale could describe the chemical structure and pharmacological action of drugs that mimicked nerve stimulation in the nervous system². He found that acetylcholine best mimicked stimulation of parasympathetic nerves². By 1936, he confirmed that neurotransmitters were secreted at all peripheral synapses and through leech experimentation, he found that acetylcholine was released at the neuromuscular junction². This led to the discovery that there were possibly chemical interactions in neurotransmission, something with Schalley further explored.

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6640538/

2. https://karger.com/ene/article/60/3/162/123616/Henry-Dale-and-the-Discovery-of-Chemical-Synaptic

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Otto Loewi, a Pharmacology professor in Austria, found evidence that supported the chemical mediation of nerve impulses. He stimulated the vagus and sympathetic fibers to the frog's heart and isolated the two substances that had different effects when applied to a second heart preparation¹. He called Acceleransstoff the substance that stimulated the sympathetic stimulation and Vagustoff the substance that stimulated vagal stimulation¹. Through his experimentation of frog hearts in 1921, Loewi concluded that chemical messengers had to play a part in neurotransmission². Specifically, he found out that acetylcholine was a chemical messenger that played a part in neurotransmission. Through his research, he discovered several components of chemicals and neurotransmission that are still taken into account today². Loewi provided the foundation and evidence for Dale's initial research. His research was instrumental to Schally's understanding of peptides and neurotransmission by setting the foundation that chemical substances affect neurotransmission.

Sources:

1. https://karger.com/ene/article/60/3/162/123616/Henry-Dale-and-the-Discovery-of-Chemical-Synaptic

2. https://www.britannica.com/biography/Henry-Dale

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Schally's primary research was on the hypothalamus and pituitary gland. Starting in 1962, Schally researched Thryotropin-releasing hormone (TRH). It's a hormone produced by neurons in the hypothalamus that is widely distributed in the CNS and regarded as a modulator of neuronal activities in extrahypothalamic regions¹ including the cerebellum. It has an important role in regulating energy homeostasis through its regulation of thyroid hormone levels. Schally specifically was able to isolate TRH and determine the amino acids. His lab was able to determine the correct amino acid sequence and subsequently, the structure. As a result, he was able to synthesize TRH, helping greatly advance studies regarding it.

1. https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/thyrotropin-releasing-hormone#:~:text=Thyrotropin%2Dreleasing%20hormone%20(TRH)%2C%20also%20termed%20thyroliberin%2C,hormone%20secretion%20from%20the%20thyroid

2. https://www.nobelprize.org/prizes/medicine/1977/schally/biographical/

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Once he finished his efforts on TRH, Schally focused on Luteinizing hormone-releasing hormone (LH-RH) as he saw its potential in clinical applications. Schally first isolated LH-RH from several hypothalami and proved it as a polypeptide¹. He then completed the structure and confirmed it by synthesis. He found that LH-RH was a physiological hormone and he was able to create synthetic LH-RH readily available¹. Once readily available, he further moved his efforts. However, his research on LH-RH was incredibly important. Through LH-RH testing, we can better predict ovulation cycles and testosterone release to better understand how to support pregnancies². This, along with his research on TRH, helped him win the Nobel Prize in science.

Sources:

1) https://www.nobelprize.org/prizes/medicine/1977/schally/biographical/

2) https://www.ncbi.nlm.nih.gov/books/NBK539692/#:~:text=In%20males%2C%20LH%20stimulates%20testosterone,the%20corpus%20luteum%20%5B8%5D.

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I was born in Wilno, Poland on November 30, 1926, being of Polish, Austro-Hungarian, French and Swedish ancestry. My father, a professional soldier trained in the military academies of Vienna, Austria and St. Cyr, France, had to leave his family when the Second World War broke out to fight with the Allied Forces. My life and outlook were influenced by the harsh childhood which I spent in the Nazi-occupied Eastern Europe, but I was fortunate to survive the holocaust while living among the Jewish-Polish Community in Roumania. I used to speak Polish, Roumanian, Yiddish, Italian and some German and Russian, but I have almost completely forgotten them, and my French in which I used to excel is also now far from fluent. In 1945, I moved via Italy and France to England and Scotland. In spite of post-war economic and nutritional austerity, the United Kingdom seemed like a paradise to me because of the respect for human rights. Since that time, I have always had a profound friendship for the British. I received my high school diploma in Scotland in 1946 and afterwards studied chemistry in London. I adored English and Scottish association football and I even tried out as an inside forward for some English and Scottish football clubs, but since I could not devote enough time to training I never made regular First Division teams. However, since 1946 I have always stayed in excellent physical shape by swimming daily and practicing other sports. "Mens sana in corpore sano" has always truly been my motto. In England I also developed a great liking for classical music, especially Beethoven, Brahms and Liszt.

My interest in medical research started at the age of 23, when I joined the National Institute of Medical Research (NIMR, MRC) Mill Hill, London, England. I was fortunate to work with and be exposed to the stimulating influences of such scientists as Dr. D. F. Elliott, Sir Charles Harington, Dr. R.R. Porter, Dr. A.J.P. Martin, Dr. R. Pitt-Rivers, Dr. J. Gross, Dr. T. S. Work, Dr. H. Fraenkel-Conrat, and Dr. W. Cornforth, several of whom later won Nobel Prizes for chemistry or physiology and medicine. Although my position was very junior at Mill Hill, my work was appreciated and this was a source of tremendous satisfaction for me, inasmuch as this recognition came from scientists of such caliber. I learned much in those 2 1/2 years, not only technical expertise but also the philosophy of research and a systematic approach to scientific investigations. These years of instruction (1950-1952) were decisive in providing inspiration, training, and laboratory discipline and profoundly influenced the course of my career. In fact, it was at NIMR, Mill Hill where I endured my "baptism of fire" in medical research and became addicted to it. In May, 1952, I moved to Montreal, Canada where I was given the opportunity to work and study at McGill University. There I learned endocrinology from the brilliant lectures by Professor D. L. Thomson and from my work with Dr. M. Saffran in the laboratory of experimental therapeutics of the Allan Memorial Institute of Psychiatry headed by Dr. R. A. Cleghorn. The work at this laboratory was devoted to ACTH and adrenal cortical steroids. That period marked the beginning of my interest in the relationship between brain function and endocrine activity, and it was there in 1954 that my involvement in the hypothalamic field began.

In 1955, using in vitro systems, Dr. M. Saffran and I demonstrated the presence of corticotropin releasing factor (CRF) in hypothalamic and neurohypophysial tissue. This was the first experimental proof of the existence of hypothalamic hormones regulating pituitary function postulated with prophetic insight by Dr. G. W. Harris. I obtained my doctorate at McGill University in May, 1957, and in September of the same year I was able to secure a position which enabled me to continue my work on CRF at Baylor University College of Medicine in Houston, Texas, where I was associated with Dr. R. Guillemin. My years in Houston (1957-1962) where I was Assistant Professor of Physiology and a Senior Research Fellow of the U.S. Public Health Service were discouraging and frustrating because of problems with the isolation of CRF. Our failure to obtain enough CRF to determine its structure tended to cast doubt on the initial findings. We encountered much skepticism, but I remained unshaken in my confidence in the correctness of the observations on CRF and in the postulation of other hypothalamic hormones regulating anterior pituitary function.

In 1961 I spent about one month at the Institute of Biochemistry in Uppsala with Dr. J. Porath where I gained useful experience in the use of Sephadex and column electrophoresis. I also visited Dr. V. Mutt and the late Professor E. Jorpes in Stockholm, in connection with our collaboration on gastrointestinal hormones, and I was encouraged that they and other astute scientists had confidence in our work and the foresight to appreciate the possible scientific and medical importance of hypothalamic hormones.

I was grateful for the opportunities I was given in the United States, for which I felt a complete allegiance, and in 1962 became a naturalized citizen. When Dr. Joe Meyer, then head of the Veterans Administration (VA) basic research, offered in June, 1962, to set up a VA laboratory devoted to research on the hypothalamus and make me its chief, I accepted since this gave me a clear opportunity to be in complete command of such an effort. The support of a number of individuals, including Dr. E. H. Bresler, then Associate Chief of Staff for Research of the New Orleans VA Hospital, Dr. C. Y. Bowers and Dr. G. Burch of the Department of Medicine of Tulane University School of Medicine, and Dr. W. Locke of the Ochsner Foundation Hospital, was instrumental in helping me establish the laboratory in New Orleans. In December of 1962, I was appointed Chief of the Endocrine and Polypeptide Laboratories at the VA Hospital in New Orleans and Associate Professor of Medicine at Tulane University, and, in 1966, Professor. The earliest members of our 1962 VA-Tulane team were T. W. Redding, W. H. Carter, and M. Tanaka. They have stayed with me all these years, and without their devoted help we could not have resolved the many problems associated with our work on TRH in 1969, LH-RH in 1971, and porcine somatostatin in 1975. Working in a clinical environment, I became more aware of the need for better diagnosis and treatment of patients than I had been before. It occurred to me early that problems with infertility on the one hand and the necessity for population control on the other would make a breakthrough in the control of reproduction particularly desirable from the standpoint of society, and therefore I became especially interested in reproductive endocrinology. To broaden our knowledge of reproductive processes at the brain level, we studied the central effects of contraceptive steroids and clomiphene. In some of the early studies on LH-RH, before its isolation, we collaborated with one of the pioneers of the hypothalamus and the man I always admired deeply, Professor C. H. (Tom) Sawyer and also with Drs. J. Hilliard, D. Holtkamp, A. Parlow and W. F. White.

It was my good fortune that in 1964 Dr. A. J. Kastin and in 1965 Dr. A. Arimura came to join our laboratory. Dr. Abba Kastin was mainly interested in continuing his work on control of release of MSH and in helping us in clinical work on hypothalamic hormones. He quickly became my best friend and a most efficient collaborator. Dr. Akira Arimura was an experienced physiologist and endocrinologist. Because of his great knowledge, enthusiasm and very hard work, he made great contributions in all phases of our program, and also broadened it with many independent ideas, especially in immunology. Other excellent collaborators at that time included Drs. I. Ishida, A. Kuroshima, T. Saito, and S. Sawano from Japan, and Dr. E. E. Muller from Italy.

All during the period since 1962, I had been hard at work on TRH with Cy Bowers and Tom Redding. In 1966, we reported for the first time the isolation of porcine TRH and determined that it contained three amino acids (glutamic acid, histidine, and proline) in equimolar ratio, but did not take full advantage of this original early finding, as we were preoccupied with parallel studies on reproduction and growth hormone-releasing hormone (GH-RH). However, when R. Burgus and R. Guillemin announced at the 1969 Tucson, Arizona, conference that they also found the same three amino acids in ovine TRH, I realized that we had the right substance. The same year I established the correct amino acid sequence of porcine TRH with Dr. R. M. G. Nair in New Orleans. Subsequently, with help from Drs. F. Enzmann and J. Bøler working in K. Folkers laboratory in Austin, Texas, we were able to determine the structure of porcine TRH and synthesize it. We have shared the credit with R. Burgus, W. Vale and R. Guillemin, who elucidated the structure of ovine TRH at about the same time.

The identification of TRH removed the skepticism surrounding the work on the hypothalamus and I realized that many workers would now be attracted to the field. We therefore redoubled our efforts on LH-RH.

In 1965, in Mexico City, I met Dr. C. Gual of the National Institute of Nutrition who invited me to collaborate with him in the clinical testing of hypothalamic hormones in Mexico. We took advantage of this invitation and in 1968 demonstrated, with Cy Bowers, that preparations of natural TRH are active in humans. Subsequently, again in collaboration with Carlos Gual, Abba Kastin and I established that highly purified porcine LH-RH unequivocally released LH and FSH in men and women under a variety of conditions. It was clear that LH-RH might be useful clinically and this encouraged us to continue the agonizing effort involved in the isolation of this hormone. Although I consider myself an endocrinologist or neuroendocrinologist, with considerable interest in clinical endocrine research and not a biochemist, I personally carried out the isolation work on TRH, LH-RH, somatostatin, and other hormones. Only a person such as myself with strong faith in the presence of these materials would have the patience to go through the many fastidious steps of the isolation procedure, since the effort required in isolating exceedingly small quantities of gradually purer and purer materials from a crude hypothalamic exctract is so enormous. I was able to isolate a small amount (800 µg) of LH-RH from 160,000 hypothalami and proved it to be a polypeptide. This tiny amount of material was passed to our chemists, Dr. H. Matsuo and Dr. Y. Baba, with suggestions for a structural approach. Since I did not think that amounts of LH-RH on hand would be enough to complete our structural work, I decided to isolate additional amounts of LH-RH. Drs. Matsuo and Baba worked hard and efficiently, and we were able to determine the complete structure of LH-RH with the 800 µg material. After confirming the structure by synthesis, we were in a position to present our findings at the Endocrine Society meeting in San Francisco, California, in June 1971. It was one of the high points in my life to be able to report for the first time the solution to the problem which had preoccupied me and others for so long.

Physiological and subsequently immunological studies with natural and synthetic LH-RH in our laboratory by Drs. A. Arimura, L. Debeljuk, J. Reeves and M. Saito, and with others demonstrated that LH-RH was indeed the physiological hormone. With the synthetic LH-RH readily available, Dr. Kastin and I continued to carry out a variety of clinical studies in Mexico in association with Dr. Gual and later with Drs. A. Zarate and D. Gonzalez-Barcena. I also did parallel clinical tests with Dr. J. Zanartu in Chile and in Argentina with Drs. L. Schwarzstein, N. Aparicio, and the late R. Mancini.

The importance of analogs, particularly with respect to the possibility of developing a new birth control method was uppermost in my mind. I was very fortunate in being able to induce Dr. D. H. Coy, a superb peptide chemist and his wife Esther, also a researcher, to join our laboratory in 1972. More than 300 analogs of LH-RH were synthesized by the Coys with the help of Drs. Y. Hirotsu, K. Nikolics and J. Seprödi in our laboratory between 1972 and 1977. We were particularly interested in stimulatory long-acting superactive analogs for clinical use and in inhibitory analogs which would block LH and FSH release. We were joined in this important work by researchers from many countries. The work of Drs. J. Vilchez from Venezuela, A. de la Cruz from Peru, E. Pedroza from Colombia, and N. Nishi from Japan established in 1976 that the antagonists of LH-RH can indeed completely block ovulation in animals. Very recently with Dr. D. Gonzalez-Barcena in Mexico we showed that these analogs are also active in humans. This of course raises the possibility that such analogs could eventually form the basis of a new birth control method. However, much work is still needed to make my dream of being able to control reproduction at the central level come true.

In 1971, immediately after solving the LH-RH problem, I decided to reinforce our attacks on PIF and GH-RF next, but six years of hard work with Dr. A. Arimura and Drs. J. Sandow from Germany, A. Dupont from Canada and J. Takahara from Japan resulted only in a demonstration that hypothalamic catecholamines and gamma-amino butyric acid (GABA) may be involved in the control of release of prolactin, but did not yet lead to the development of any clinical agents. In our preoccupation with PIF and GH-RH, we did not work on factors inhibiting growth hormone release but after P. Brazeau and collaborators in 1973 announced the isolation and structure of ovine somatostatin, we purified this hormone from porcine hypothalami, determined its structure and synthesized it. We also carried out much physiological and immunological work (some in collaboration with Dr. F. Labrie in Quebec, Canada), as well as clinical work which convinced us of its importance. Particularly important was the establishment of a radioimmunoassay for somatostatin by Dr. Arimura. The clinical work on somatostatin was carried out mainly in England. Brilliant clinicians Professor R. Hall from the Royal Victoria Infirmary in Newcastle-upon-Tyne and Professor G. M. Besser of St. Bartholomew's Hospital in London were our leaders of two clinical teams which also included excellent collaborators such as Drs. A. Gomez-Pan, D. Evered, C. Mortimer, S. R. Bloom, and others. These clinical studies in England (based in part on some of our suggestions) showed that somatostatin inhibits the release of GH, TSH, glucagon, insulin, and gastrin. Basic studies carried out in England in collaboration Dr. A. Gomez-Pan and in Poland with Professor S. Konturek showed that somatostatin also inhibits gastric acid and pepsin secretion, and the release of duodenal hormones, secretin and cholecystokinin. Since the immunological work of Dr. Arimura showed the presence of somatostatin in the pancreas, stomach and intestine, we then suggested that this substance may be involved in the control of secretion not only of the pituitary, but also of the pancreas, stomach and duodenum. Since somatostatin has multiple short-lived effects, Drs. D. H. Coy and C. Meyers are achieving considerable success in the synthesis of long-acting and selective analogs of somatostatin, some of which could be more practical clinical agents.

Also among our present projects is the isolation of all the compounds with PIF activity, of PRH, GH-RH, CRF, and other hypothalamic substances. In addition to authoring or co-authoring many publications, I take satisfaction from the fact that I helped Dr. W. Locke write a book for clinical endocrinologists.

Since much work with hypothalamic hormones and their analogs is being carried out in Latin America and Spain, my ability to communicate in Spanish and Portuguese has aided me greatly, and resulted in the formation of many beautiful friendships. However, the greatest reward for learning Spanish and Portuguese came when, in 1974, in the course of my work in Brazil I met a very charming endocrinologist, Ana Maria de Medeiros-Comaru (M.D.). Our friendship soon deepened into love and led to our marriage.

I have had the satisfaction that my work in the hypothalamus was honored by top U.S., Canadian and Spanish awards: Van Meter Prize of the American Thyroid Association; Ayerst-Squibb Award of the U.S. Endocrine Society; William S. Middleton Award, the highest award of the VA; Charles Mickle Award of the University of Toronto; Gairdner Foundation International Award, Canada; Edward T. Tyler Award; Borden Award of the Association of American Medical Colleges; Albert Lasker Basic Medical Research Award, and the Laude Award, Spain. In 1973 I was made a Senior Medical Investigator by the Veterans Administration, an honor reserved for only a few. When I learned about my Nobel Prize, I was too grateful and too moved to be overcome with joy, but that came a few hours later when my friends from all over the world began to phone or wire. However, I do not feel that these prizes will have an adverse effect on my future productivity. I am still as keen as ever to make new discoveries and useful contributions to endocrinology.

This autobiography/biography was written at the time of the award and later published in the book series Les Prix Nobel/ Nobel Lectures/The Nobel Prizes. The information is sometimes updated with an addendum submitted by the Laureate.

Addendum, April 2005

In the years 1972-1978, I developed agonistic analogs of LH-RH (also called GnRH) and in 1981 was the first to show that they inhibit growth of prostate cancer in rats. On this basis, I organized with Dr. George Tolis the first clinical trial with LH-RH agonists in patients with advanced prostate cancer in 1982. This trial demonstrated the clinical efficacy of LH-RH agonists in palliative treatment of androgen-dependent prostate cancer. I then helped develop sustained delivery systems (microcapsules) for agonists of LH-RH and participated in evaluations of their efficacy. Sustained delivery systems of various LH-RH agonists (microcapsules or implants) now provide the preferred method for the treatment of advanced prostate carcinoma. Previous primary endocrine treatment modalities for advanced adenocarcinoma of the prostate based on the work of Charles Huggins (Nobel Prize in Medicine for 1966), used since the 1930s, included orchiectomy or administration of estrogens (DBS). However, surgical castration (bilateral orchiectomy) is associated with psychological impact and estrogens such as DES have serious cardiovascular, hepatic and mammotropic side effects. Treatment with LH-RH agonists is as effective as orchiectomy and offers the advantage of avoiding castration. The therapy with agonists of LH-RH is presently the preferred method of treatment for men with advanced prostate cancer and in about 70% of cases, LH-RH agonists are selected for primary treatment.

I helped Prof. R. Hall and Prof. M. Besser in the first clinical evaluations of somatostatin in normal subjects and patients with neuroendocrine tumors in England and I was profoundly influenced by its effects. Based on this experience, I became one of the pioneers in the development of analogs of somatostatin for oncological uses and demonstrated their antitumor activity in animal models of various tumors. I have been credited with influencing the thinking in the field of oncological applications of somatostatin. Analogs of somatostatin are used now for treatment of acromegaly and endocrine tumors, including carcinoid tumors. The fact that few relevant clinical benefits have been obtained in patients with pancreatic, colorectal, prostatic, breast and other cancers treated with somatostatin analogs is due to a low expression of SST receptor subtypes 2 and 5 in these malignancies that preferentially bind octapeptide somatostatin analogs. However, the expression of these subtypes should be high enough to permit therapy with targeted cytotoxic somatostatin analogs synthesized by my group or somatostatin analogs labeled with various radionuclides developed in the meantime in Europe. Radiolabelled somatostatin analogs pioneered in Holland are now extensively used for tumor localization. Among my other major accomplishments is the development of antagonistic analogs of LH-RH, the demonstration of their antitumor activity in experimental cancer models and with my associates of clinical efficacy of these antagonists in patients with prostate cancer, endometriosis and leiomyomas. My late wife Ana Maria Comaru-Schally also showed that antagonists of LH-RH could be used as a therapy for benign prostatic hyperplasia (BPH).

My group demonstrated that the receptors for LH-RH, somatostatin and bombesin are present in various tumors, including human prostatic, mammary, endometrial and ovarian cancers. Based on this demonstration of receptors for peptides in various tumors, I started in 1995 the development of modern cytotoxic analogs of LH-RH, bombesin and somatostatin, which can be targeted to peptide receptors on various primary cancers and their metastases. We demonstrated in experimental models of human cancers that these hybrids produce tumor regression or eradication. Because the receptors for these peptides are present on many cancers, targeted chemotherapy based on cytotoxic analogs of these peptides should be more efficacious and less toxic than the currently used systemic chemotherapeutic regimens and might permit dose escalation. My group also developed bombesin antagonists aimed at decreasing EGF receptor levels in tumors and growth hormone-releasing hormone (GH-RH) antagonists, which suppress IGF-I and -II levels and block tumoral receptors for GH-RH and showed that they inhibit a variety of experimental cancers, including androgen-independent prostate cancers, estrogen independent breast cancers, ductal pancreatic cancers, colorectal cancers, lung cancers and brain tumors. My associates and I also demonstrated that GH-RH, which we found in mammary, ovarian, endometrial lung cancers and other tumors, is probably an autocrine growth factor. Our work suggests that cytotoxic somatostatin analog AN-238, cytotoxic LH-RH analogs AN-152 or AN-207 and GH-RH antagonists could be used in the management of patients with advanced prostatic carcinoma who relapsed androgen ablation. Cytotoxic LH-RH analogs or GH-RH antagonists might also be considered for improvement of primary hormonal therapy for prostate cancer.

In September 2004, my wife Ana Maria Comaru-Schally, M.D., F.A.C.P. died suddenly from thyroid cancer. I was profoundly hurt by the unexpected passing of my wife after 28 years of wonderful marriage, which was preceded by 2 years of an exciting and emotional romance. She was an ideal wife, companion, collaborator and my best friend. She will be sorely missed by me and many friends in various countries. Her death was the hardest blow and the biggest tragedy in my life. I am seeking consolation and comfort by continuing my work in cancer research. I believe that this is what she would want me to do.

In conclusion, since receiving the Nobel Prize, I developed the preferred method for treatment of advanced prostate cancer based on LH-RH agonists. My group synthesized several new classes of antitumor peptides such as LH-RH antagonists, somatostatin analogs, bombesin/GRP antagonists, GH-RH antagonists and targeted cytotoxic analogs of LH-RH, bombesin and somatostatin. I then proposed, and with my associates experimentally demonstrated, the efficacy of new approaches to therapy of prostatic, mammary, ovarian, endometrial, renal, pancreatic, colorectal, gastric and lung cancer (SCLC and non-SCLC), osteosarcomas, melanomas, non-Hodgkin's lymphomas and brain tumors based on these antitumor peptides.

I have been credited with extending the concepts of hormone-dependent tumors beyond the pioneering work of the great Charles Huggins. Hormonal therapies that I proposed are based on the peptide analogs of hypothalamic and other hormones and are relatively free of side effects, in contrast to radiation and chemotherapy. I am gratified that my discoveries have led to many practical clinical applications that are widely used and highly effective. It is my hope that the significance of these discoveries and their applications to oncology will increase in the future.

I now have over 2200 publications, more than 1200 of which were published after I received the Nobel Prize.
Copyright © The Nobel Foundation 2005

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MLA style: Andrew V. Schally - Biographical. NobelPrize.org. Nobel Prize Outreach AB 2024. Fri. 23 Feb 2024. <https://www.nobelprize.org/prizes/medicine/1977/schally/biographical/>

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The Nobel Prize in Physiology or Medicine 1977

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The Nobel Prize in Physiology or Medicine 1977 was divided, one half jointly to Roger Guillemin and Andrew V. Schally "for their discoveries concerning the peptide hormone production of the brain" and the other half to Rosalyn Yalow "for the development of radioimmunoassays of peptide hormones"

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Schally's Nobel Prize-winning research inspired many scientists to look into neuropeptides. So far, many researchers have found that neuropeptides modulate the activity of co-released neurotransmitters to increase or decrease the strength of synaptic signaling¹. Neuropeptides function similarly to peptide hormones and modulate nearly all bodily functions¹. Now, people have started to use neuropeptides for several functions. For example, neuropeptide theory has been heavily researched. Neuropeptides help increase various growth factors in the brain and enhance what the brain is naturally capable of doing². Neuropeptide therapy helps with energy, concentration, mood regulation, and much more. Current researchers are trying to see if peptide therapy can help address neurodegenerative diseases such as Alzheimer's and dementia. For example, amino acid modifications and enhancing delivery and pharmacokinetics have drastically improved treatments for neurodegenerative diseases¹. Schally leaves behind a lasting legacy in the neuroscience world as he sets the foundation a new sector of neuroscience and a new set of treatments and preventative measures for neurological diseases.

Sources:

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5424629/#:~:text=Within%20the%20brain%2C%20neuropeptides%20can,modulate%20nearly%20all%20bodily%20functions.

2. https://neurogrove.com/neuropeptides/

3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8961788/