Fernand Labrie
Long summary of Dr. Labrie's career
Dr. Fernand Labrie obtained his M.D. in 1962 and his Ph.D. in Endocrinology in 1966, both from Laval University in Quebec City, Canada. From 1966 to 1969, he pursued his postdoctoral training at the University of Cambridge, England, first under the direction of Professor Asher Korner, Department of Biochemistry, before joining the Laboratory of Molecular Biology under the direction of Professor Frederick Sanger, twice Nobel laureate in Medicine. In 1969, after completion of his postdoctoral training, he joined the Department of Physiology at Laval University where he founded the Laboratory of Molecular Endocrinology which has become the largest research group at Laval University and one of the largest and reknown research groups in endocrinology at the international level.
In 1973, he founded the Research Group in Molecular Endocrinology of the Medical Research Council of Canada (MRC), the first group in endocrinology funded in Canada by this national agency. This internationally recognized team now includes over 350 scientists, research professionals and technicians at the cutting edge of this highly competitive field of biomedical research. His research has been supported without interruption by the MRC (now the Canadian Institutes of Health Research) since 1962.
Since 1982, Dr. Labrie has been director of research at the Laval University Medical Center (Le Centre Hospitalier de l'Université Laval, CHUL). With more than 1200 high-technology employees, its 300,000 square feet of research space, its 80 millions $ state-of-the-art equipment and its annual budget of over 65 million $ in grants, awards and research contracts, the CHUL Research Center ranks among the largest Canadian medical research institutes. The last addition to the CHUL Research Center is a 100,000 square feet Genomic Center, thus adding to the already unique expertise of the CHUL Research Center. As director of research at the CHUL Research Center, Dr Labrie has been responsible for five consecutive constructions. Moreover, from 1990 to 2002, he was head of the Department of Anatomy and Physiology of the Faculty of Medicine at Laval University.
His dedication to improve and to promote excellence in health research is also well illustrated by his nomination for 1992-1995 as President of Le Fonds de la Recherche en Santé du Québec (FRSQ). This governmental agency had an annual budget of 50 millions $ to support and develop biomedical research in the Province of Québec.
Dr. Labrie has received many national and international awards and honors, among which the Medal of Le Collège de France as well as the title of Officer of the National Order of Québec and of Officer of the Order of Canada. He received a Doctor Honoris Causa from the Université de Caen, France and from the University of Athens, Greece. He is also fellow of the Royal Society of Canada and of the Academy of Health Sciences of Canada. The Canada Council for the Arts awarded the most prestigious Isaak Walton-Killam Prize to Dr. Labrie in recognition of his exceptional contribution for the advance of health sciences. In 2006, he received the highest honor in science from the Government of Quebec, the Armand-Frappier Award. In 2007, Dr Labrie received the prestigious King Faisal International Prize in medicine for his contribution in the field of prostate cancer. He also received recently The Scientific Career Award of the "Association des Médecins de Langue Française du Canada" and The Canada Gold Medal and Man of the year from The American biographical Institute
Indeed, Dr. Labrie's discoveries are described in more than 1205 scientific publications and have been cited more than 40,000 times by other scientists around the world. Dr. Labrie is the most cited Canadian scientist among all disciplines in the international literature, a clear testimony of the tremendous impact of his scientific accomplishments. The recognition by his peers is also indicated by the fact that he has been invited to present his research data at over 504 national and international scientific meetings.
A first scientific achievement of Dr Labrie was made during his postdoctoral training with Professor Frederick Sanger at the Laboratory of Molecular Biology in Cambridge, UK: he then succeeded the isolation of the first mammalian messenger RNA, namely hemoglobin messenger RNA. Following his return at Laval University in 1969, the discoveries of Dr Labrie having a major impact in clinical medicine have been in the field of prostate cancer. In fact, the standard hormonal therapy of prostate cancer had been orchiectomy (surgical castration) or high dose of estrogens since 1941. The psychological limitations of orchiectomy and the serious cardiovascular side-effects of high dose estrogens had limited the use of hormonal therapy to the advanced stage of the disease with bone metastases, a stage where the benefits of treatment are small.
The first discovery of Dr Labrie applied to the treatment of patients has been complete medical castration or complete inhibition of androgen formation by the testicles achieved with GnRH (gonadotropin-releasing hormone) agonists. It is of interest to mention that before Dr Labrie's unpredictable findings, the GnRH agonists were being developed with the objective of treating infertility or gonadal insufficiency in men and women. In fact, when the structure of GnRH was elucidated by the Nobel laureates Guillemin and Schally in 1971, the immediate efforts of chemists were to develop GnRH superagonists in order to treat ovarian and testicular deficiency. However, this approach was leading only to negative results by all investigators while the discovery by Dr. Labrie's group showed exactly the opposite effect, namely a complete blockade of gonadal functions in both men and women by GnRH agonists.
Elucidation of the mechanisms involved in the antigonadotropic action of GnRH agonists as well as the first clinical data on the pharmacokinetics, dose-effect, route of administration and efficacy of GnRH agonists on prostate cancer were obtained by Fernand Labrie and his group at Laval University. In fact, his observations opened the way to one of the best, if not the greatest success of the pharmaceutical industry which simply developed other similar GnRH agonists. In fact, the worldwide sales of GnRH agonists during the last 15 years have been of the order of 3 billion US$ annually, thus illustrating the wide acceptance of this discovery and its major role in medicine.
Due to their unique efficacy and tolerance, GnRH agonists have rapidly replaced surgical castration and high doses of estrogens worldwide since 1980 for the treatment of prostate cancer. While eliminating the limitations of previous orchiectomy and high doses of estrogens, medical castration with GnRH agonists could then be used for the treatment of not only metastatic disease but, most importantly, for the treatment of localized and locally advanced disease where major benefits on survival could be observed. In fact, a recent metaanalysis of all available data has shown a one-third decrease of prostate cancer deaths using GnRH agonists alone. It should be mentioned that prostate cancer is the most frequently diagnosed cancer and the second cause of cancer death in men.
Soon after the discovery of medical castration with GnRH agonists, Dr. Labrie and his group discovered that castration eliminated only 40% to 60% of androgens in the prostate cancer tissue. In order to take into account this pivotal observation, Dr Labrie then added a pure antiandrogens to castration in order to block at the same time, at start of treatment, the action of the androgens made in the prostate itself from adrenal precursors while the androgens of testicular origin were eliminated by the GnRH agonist. This treatment called combined androgen blockade has been the first treatment demonstrated to prolong life in prostate cancer. This treatment is now the standard treatment of advanced prostate cancer around the world. While combined androgen blockade prolongs life in patients treated at the advanced stage of the cancer by 6 to 12 months, it is very important to indicate that the same combined androgen blockade applied at the localized stage permits cure of the cancer in at least 90% of cases.
In fact, when it was realized in the early 1980s that even the improved treatment of advanced disease that he had developed could not provide a cure of prostate cancer at the advanced stage, Dr Labrie started the first randomized and prospective study of prostate cancer screening in order to be able to diagnose the cancer at a localized and potentially curable stage. The strategy developed and validated during the course of that study permits to detect prostate cancer at a localized stage in 99% of cases, thus practically eliminating the diagnosis of metastatic and non curable disease. This first screening study has also demonstrated that early diagnosis and early treatment of prostate cancer decreases deaths from prostate cancer by two-thirds. With the possibility of diagnosis of prostate cancer at the localized stage in 99% of cases and the availability of combined androgen blockade, death from prostate cancer can now be an exception if proper diagnostic tools are used and proper treatment is administered.
In an even larger context, Dr. Labrie made a discovery having a major impact on the understanding of the physiology of sex steroid hormones in humans. He first observed during his studies in prostate cancer that 40% to 50% of androgens in men are produced directly in peripheral target tissues through the local transformation of the inactive steroid precursor dehydroepiandrosterone (DHEA) and DHEA sulphate secreted by the adrenal glands into active androgens. Dr. Labrie and his group then elucidated the structure and have characterized most of the enzymes involved in sex steroid hormone synthesis as well as several of the enzymes responsible for their inactivation. This new field of biomedical knowledge has been designated intracrinology by Dr. Labrie. This new sector of endocrinology describes the formation of active sex steroids from the inactive adrenal precursor dehydroepiandrosterone (DHEA). These active steroids made locally act in the same cells where synthesis takes place without being released in significant amounts in the general circulation. In postmenopausal women, all estrogens and almost all androgens are made in peripheral tissues by intracrine mechanism. This new scientific discipline has major implications, not only in terms of fundamental endocrinology but most importantly for the improved therapy of hormone-sensitive diseases, especially prostate and breast cancers as well as menopause and osteoporosis.
In the field of breast cancer, based upon a successful fundamental research program, Dr Labrie and his group have discovered and developed acolbifene, the most potent and pure antiestrogen available for the treatment and prevention of breast and uterine cancer. This drug has shown efficacy in phase 2 and 3 international trials in breast cancer progressing after tamoxifen failure, thus indicating its superiority over tamoxifen. It is quite unique that a drug is entirely developed in an academic environment, starting from chemical discovery to the phase 3 clinical trial, or the last step before commercialization.
In view of such outstanding and unique achievements as a basic and clinical scientist, his leadership as member, director and president of numerous local, provincial, national and international scientific institutions, societies and funding agencies in addition to his role as president and chief executive officer of a successful R&D pharmaceutical company, and his deep involvement in sport and social organisations in Quebec City, Dr Labrie was recently chosen among the most influential individuals of the Quebec City area on many occasions.