- Email: [email protected]
In memoriam Paul Boulanger
Biochimie { 1998) 80, 3-6 O Sociel6 h'an~'aisede biochimie c~ biologic mot6culairc / Elsevier, Paris ]in m e m o r i a m
Paul B o u l a n g e r 21 November 1905-16 June 1996)
It was in 2927, at the beginning of his fburth year of medical studies, and his first year as an intern, that Paul Boulanger entered my father's laboratory, to study biochemistry. Rapidly, the teacher-pupil relationship took on the hues of true filial af|bction and my father looked upon him as a son, by associating him in his research and teaching. I saw him as an elder brother, an example, a guide and a support, for which I feel a profound gratitude. If one seeks the origin of Mr Boulanger's qualities, it seems obvious that he harmoniously combined his family's genes, the factors of his environment and his own personality. Paul Boulanger was born on the 21st of November 1905, in Roubaix. His childhood was marked by the 1914-1918 war and the German occupation which probably contributed to developing his patriotism, which was to manifest itself during the 1939-1945 war, through his active participation in the Resistance, as an inIbrmation agent, qb be born on Flemish hind is to benefit from a climate and setting conductive to work; it is to acquire those human qualities we like to attribute to people from the north of France; conscientiousness, courage arid h)y o alty, His father was a primary school teacher and went on to teach English at the Roubaix secondary school. It was him, who through the strict and demanding upbringing he gave his son, made his son in turn a hardoworking and demanding ma.~ter. Apparently, he wished his sons to be first in everything, and these wishes were more than granted in t!~c excellent pupil his son Paul became. After brilliant studies at the Lyc6e of rlburcoing, he attained his Philosophy Baccalaureat with merit. He was first in the PCN exam in 1924; first in his medicine exam in 1925; first in the house doctor exams in 1927 at the end of his third year of medicine. The Lille Faculty of Medicine annually awarded an end-of-year prize, which Paul Boulanger received in 1925, 1926, and 1929. He became a doctor of Medicine in 1930, with a prize Ior his thesis on urinary ammonia, a thesi~ which he had begun in 1927, on entering the laboratory of biochemistry under my fi~ther's, Michel Polonovski, direction, which had already given rise to a dozen publications (10 of which for the Biology Society!). He also passed his Science Degree exams in 1932, with credit, and he obtained the title of first class pharmacist in 194 I. Paul Boulanger spent his entire career at the Lille Faculty of Medicine. "Che/" de Clinique" of the Medical Clinic in 1930, he became biochemistry assistant in 1931, then "Che[de travaux pralique,C in 1934, whilst waiting to receive his agr@ation in 1939. But at this time posts were rare, and biochemistry had not yet been recognised as an important discipline by university boards. There were only three ~)r four professors of biochemistry in science faculties, and chairs in medical chemistry in faculties of medicine were named according to the needs of the moment. When Michel Polonovski was nominated
to succeed Professor Alexandre Desgrez in Paris in 193b, Andr6 Giberton was nominated to Alger, and replaced for a year by Michel Macheboeuf, who was to leave Lille for Bordeaux in 19.37. The chair of Medical Chemistry disappeared for 14 years! It was only recreated in 195 i, at the birth of the new faculty and its installation at the hospital complex. The chair of Medical Chemistry had been transfornled into the chair ~f Pharmaceutical Chemistry in this mixed faculty, and was given to Professor Albert Lespagnol• whilst Paul Boulanger was assigned to the post of permanem accredited Medical Biology teacher for medical students. Two years later, he succeeded in the Clult'oul':~ d Agregatun, and a post having been created in Lille, he took up this post in 1940. But the faculty had only given him a small 30 square meter laboratory with an office. Fortunately, thanks to his work• he had obtained a laboratory in 1939 from the institute of Cancer Research. In 1942. he succeeded Professor ValiSe, in the chair of Mineral Chemistry, which allowed him |o extend his laboratory and to teach his ~tudents there. But it was not until 1951 that he finally acceded to this chair, known as the Bmloglcal Chemistry Posm( n , and whose name was to be modified in 1962 to "Medical Biology'. Paul Boulanger was thus initiated to and trained for research by Michel Polonovski. Hc had a further master, in the person of Professor Richard Kuhn o1" the Heidelberg Medical Research Institute. the "Kaiser Wilhelm institute', where he spent a year from 1935 to 1936, having received a grant from the French Institute of Berlin. He look part in the work on llavines, work which was to win Kuhn the Nobel Prize Ik~rChemistry in 1938. Paul Boulanger's life history covers almost precisely that of biochemistry in France in the twentieth century, to which he owed a great deal, and on which he left his mark. He first lived through the i~:~r but glorious 1930s, when the laboratories had neither funds nor equipment, whet) technical staff were practically non-existent, closely resembling those laboratories we can imagine, when seeing those of Pierre and Marie Curie in "Les pahnes de Mr: Shutz'. Talking about this period, Paul Boulanger wrote in 1975, on the occasion of his Faculty's centenary: "Those who did not know the Bitwhemislry Department of the rue Jean-Bart, cannot imagine the difficulties against which the researchers had to fight, the shortage of equipment and basic materials, the insufficient running funds, the total absence of technicians." Yet this period was rich in exciting and promising discoveries, such us that of vitamins, c(~nzymes and hormones. The post-war period, which saw a sspectacular~ ' ' development in medical research, allowed Paul Boulanger to build a modern labt)ra!ory, and to train particularly dynamic and enthusiastic young scientists there. The axis of his work evolved as did that of biochemistry. At the beginning of his calver, a biochemist had fh'~! to he a g~md chemist, whereas today he has It) he a good biologist. lake his lll,~s.¢l,' 't, 's, he Was a gt~t~tl organic chemist and an excellent analvsl, . In hi~ research into derivatives similar to rihtfflavinc, ~l'xv"hlctl he was ~tutlying the toxic properties, he carried out the synthesis of all its ¢onlpouttds hh!)ne!f. At this tinle il was necessary to kllow how Io do everything on,self, because there was no question of buying ready-to-use molecules, or to be h e l ~ d by a laboratory assistant! Scientists deserved h~r more merit in the past titan they do now, The first r~:.-search~, " he carried out with Michel Polonovski bore on the origin of urinary ammonia, and he was also a pioneer in work on the formation of ammonia, its transportation in the blood and its renal excretion, He developed the con"cept of renal ammoniogenesis, which we now know comes from the hyd~lysis of glutamine and the de. ammatlon of amino acids, and he distinguished it l ~ m ammoniophaneresis, which re!~resents.. the excretion in urine of ammonia ions. which'aer• part of the elimination process of the protons resulting from acidosis• This work was carried out in conditions of poverty, which necessitated praiseworthy ingenuity, and the determinations of ammoma were remarkably precise in spite of the antediluvian equipment. He applied his knowledge to the study of the metabolism of ,a mmo • acids. His main results concerns tran. anunatlon, With his student Roger Osteux, he particularly studied desamination and transamination of diamino acids, the metabohsm of lysine and that of series D amino acids. His interest in these "non natural' amino acids had been inspired by the works of F K~gl, who had affirmed that cancer tissues contained non-negligible proportions of them• Using remarkably rigorous ~:hntques, he showed the Dutch biochemist's error, but the results he obtained from his study of the metabolism of these compounds have helped deepen our knowledge of several aspects of nitrt,genous metabolism. His work on the metabolism of lysine led him to the discovery of a transat,fination process ditl~ring farm that of Alexander Braunstein, which concerned the u-amino S
•
'~
•
functions, a process v,'hK'h applies [o the ~'-amino function: hc c~.dk'd tllis "pyridinic c¢~cnz3me
mmsamim~tion'. Effectively, the amino function on the ~-cetogl~aric acid h~tppens in tx~,'osteps, the first using the NADPH form of saccharopi,le and the second carries tile t~vo hydrogens onto the NAD and frees the glut~.mlic acid with the/8-semiaidehyde-~ aminodipate. The progress of biochemistry in isolation and structure of proteins, then :ff nucleic acids. attracted hi|ll to research fields which were opening up and ~vhK:h. although difficult, merjo)ed his curiosity-filled mind as well as those of tile young scientists working with him. It is on the theme of "the biochemistry of proteins' that he created the first INSERM unit in Lille in 1966. With his students, Gdrard Bisert and Michel Dautrevaux, he turned his attention to the chemistry of proteins and polypeptides, Together with Raymoqd Havez and Philippe Roussel. he gained renown in the field of the chemistry of glycoprotein. And it is Jean Montreuil who championed tile study of glucidic chains. As his student Gdrard Biserte said: "it is to him that the Nord-Pasde-Calais Region owes its reputation as one of the most important centres oI' medical research. dependent on INSERM." From 1939 his work was carried out at tile Cancer Research Institute. He was always an active supporter of collaboration between scientists and clinicians. For example, tile research on the mucins and tile glycopmteins of bronchial secretions that he carried out with his students R Havez, P Roussel, and P Degand earned the Lille Faculty of Medicine international renown in this domain. The situation of his deparlment in |he heart of the hospital complex led him to collaborate very efficiently in the organisation of the hospital laboratories. Tile school he created attracted many gifted young people. He inspired in them the love of work well-done. His students followed his example and have aivcays considered him as a father-figure. Each one took a different path, either in the Faculty of Medicine or Pharmacy, or the Faculty of Science or the Pasteur Institute. Yet all are proud to belong to Mr Bouhmger's school. The in° fluence of this school has gone far beyond tile limits of tile region, and his students have scattered as far as Montpellier, Nantes, Grenoble, Reims, Amiens, Tours, Nancy, Toulouse and Viilejuif. He also attracted t'oreign researchers, who have retained affectionate memories ol' this 'boss'. they loved, admired and respected. Modest by nature, Patti Boulanger thottghl that a masler should step aside to hns students. And he claimed himself to be over:joyed by their success. He knew how to direct them, advise them and point them in the right direction. G6rard Biserte wrote to him: "in all circumstances, hapl~y or sad. yott always showed tlS a cal,ll and serene face. just and clear-sighted advice." His inlluence has spread over ntt,lle,'ot, s generations of students, wllo,n he t,'ai,led ill bit~chcmical thtmght, firstly through his remarkably ct~nsl,'ucled vc,'hal leaching, but alst~ Ihmugh his boo,ks which have u,ldergo,le ,m, ltiple editions twcr lhe last half centm'y. Through his leaching bt~t~k.,. Paul I-louhmger is knt)wn t~)all tile French I~iochemist,,. tlocto,'s ;.,lid I~harlllacisl,, as well as I~ numerotm foreign students. I wus lucky cnuugh to Imv¢ worked with hin, t,~ the pl'cp~u~,titm ul all his books: "Biochimie Medicale" Ibr which he collabor~Lled with Michel Pohmovski. from the first edition in 194{}, to the fifth edition in 1952. and which was mnplified to Ikmr volumes over the lbllowing years; the "Abr¢;g¢~de Bhwhimie Medh'ah,". which Ik~liowed it and which is ~lt present in its third edition since 1979; these are basic handbooks for studenls. The seven vt~lumes of the three tomes o1' "Biochimie G~;n&'ale". produced in association, which was finished in 1972; "Prob/bmes actueis de Biochimie G&u;rale". imblished in 1972 and written by several of his students and colleagues. The "Expos& ammels de Biochimie M&iicale" to which he contributed over 40 years. "Pathologie Chimique". published in 1951-52 with Michel Polonovski and G Schapira. "Biochimie M&licale" has been translated into German. Italian and Spanish. Patti Bouhmger was a workaholic, thtmghtl'ul, meticumus and vigilant. !ti.~ competence in all the domains of biochemistry earned him recognition from all the Frencll biochemists. The wistlo,n of his judgement and fatherly benevolence he showed to all young people explain the almost unanimous sufl'rage given to his name at all the national University and Research authorities. His options and votes were always l'ull ot' sense and guided by the common good and never determined by partisan or unjust considerations. Out" whole geqeration of biochemists knows what we owe t~ his activities on the Consultative Committee of Universities. the CNRS National Committee. as well as that ot' INSERM. He had a considerable influence on the training and selection of most of the teaching biochemists in the Faculties of Medicine. tte more than deserved the decorations he was awarded: Commander ol' the Order of 'Les Palmes Acad6miques'. Officer of the Order of
Public Health, Commander of the 'L6gion d'Honneur', He was an honorary Doctor at the University of Brussels. and was the laureate of the "Prince Albert of Monaco Grand Prix" in 1965. He was elected correspondent of the Acad~mie Nationale de M6decine in 1947 and non-resident member in 1968, He presided over its eighth section for several years from 1980 to 1984. Jacques Polonovski (from the eulogy delivered the 6th of May 1997 at the AcadEmie Nationale de M6decine)
Paul B o u l a n g e r 21 November 1905-16 June 1996)
It was in 2927, at the beginning of his fburth year of medical studies, and his first year as an intern, that Paul Boulanger entered my father's laboratory, to study biochemistry. Rapidly, the teacher-pupil relationship took on the hues of true filial af|bction and my father looked upon him as a son, by associating him in his research and teaching. I saw him as an elder brother, an example, a guide and a support, for which I feel a profound gratitude. If one seeks the origin of Mr Boulanger's qualities, it seems obvious that he harmoniously combined his family's genes, the factors of his environment and his own personality. Paul Boulanger was born on the 21st of November 1905, in Roubaix. His childhood was marked by the 1914-1918 war and the German occupation which probably contributed to developing his patriotism, which was to manifest itself during the 1939-1945 war, through his active participation in the Resistance, as an inIbrmation agent, qb be born on Flemish hind is to benefit from a climate and setting conductive to work; it is to acquire those human qualities we like to attribute to people from the north of France; conscientiousness, courage arid h)y o alty, His father was a primary school teacher and went on to teach English at the Roubaix secondary school. It was him, who through the strict and demanding upbringing he gave his son, made his son in turn a hardoworking and demanding ma.~ter. Apparently, he wished his sons to be first in everything, and these wishes were more than granted in t!~c excellent pupil his son Paul became. After brilliant studies at the Lyc6e of rlburcoing, he attained his Philosophy Baccalaureat with merit. He was first in the PCN exam in 1924; first in his medicine exam in 1925; first in the house doctor exams in 1927 at the end of his third year of medicine. The Lille Faculty of Medicine annually awarded an end-of-year prize, which Paul Boulanger received in 1925, 1926, and 1929. He became a doctor of Medicine in 1930, with a prize Ior his thesis on urinary ammonia, a thesi~ which he had begun in 1927, on entering the laboratory of biochemistry under my fi~ther's, Michel Polonovski, direction, which had already given rise to a dozen publications (10 of which for the Biology Society!). He also passed his Science Degree exams in 1932, with credit, and he obtained the title of first class pharmacist in 194 I. Paul Boulanger spent his entire career at the Lille Faculty of Medicine. "Che/" de Clinique" of the Medical Clinic in 1930, he became biochemistry assistant in 1931, then "Che[de travaux pralique,C in 1934, whilst waiting to receive his agr@ation in 1939. But at this time posts were rare, and biochemistry had not yet been recognised as an important discipline by university boards. There were only three ~)r four professors of biochemistry in science faculties, and chairs in medical chemistry in faculties of medicine were named according to the needs of the moment. When Michel Polonovski was nominated
to succeed Professor Alexandre Desgrez in Paris in 193b, Andr6 Giberton was nominated to Alger, and replaced for a year by Michel Macheboeuf, who was to leave Lille for Bordeaux in 19.37. The chair of Medical Chemistry disappeared for 14 years! It was only recreated in 195 i, at the birth of the new faculty and its installation at the hospital complex. The chair of Medical Chemistry had been transfornled into the chair ~f Pharmaceutical Chemistry in this mixed faculty, and was given to Professor Albert Lespagnol• whilst Paul Boulanger was assigned to the post of permanem accredited Medical Biology teacher for medical students. Two years later, he succeeded in the Clult'oul':~ d Agregatun, and a post having been created in Lille, he took up this post in 1940. But the faculty had only given him a small 30 square meter laboratory with an office. Fortunately, thanks to his work• he had obtained a laboratory in 1939 from the institute of Cancer Research. In 1942. he succeeded Professor ValiSe, in the chair of Mineral Chemistry, which allowed him |o extend his laboratory and to teach his ~tudents there. But it was not until 1951 that he finally acceded to this chair, known as the Bmloglcal Chemistry Posm( n , and whose name was to be modified in 1962 to "Medical Biology'. Paul Boulanger was thus initiated to and trained for research by Michel Polonovski. Hc had a further master, in the person of Professor Richard Kuhn o1" the Heidelberg Medical Research Institute. the "Kaiser Wilhelm institute', where he spent a year from 1935 to 1936, having received a grant from the French Institute of Berlin. He look part in the work on llavines, work which was to win Kuhn the Nobel Prize Ik~rChemistry in 1938. Paul Boulanger's life history covers almost precisely that of biochemistry in France in the twentieth century, to which he owed a great deal, and on which he left his mark. He first lived through the i~:~r but glorious 1930s, when the laboratories had neither funds nor equipment, whet) technical staff were practically non-existent, closely resembling those laboratories we can imagine, when seeing those of Pierre and Marie Curie in "Les pahnes de Mr: Shutz'. Talking about this period, Paul Boulanger wrote in 1975, on the occasion of his Faculty's centenary: "Those who did not know the Bitwhemislry Department of the rue Jean-Bart, cannot imagine the difficulties against which the researchers had to fight, the shortage of equipment and basic materials, the insufficient running funds, the total absence of technicians." Yet this period was rich in exciting and promising discoveries, such us that of vitamins, c(~nzymes and hormones. The post-war period, which saw a sspectacular~ ' ' development in medical research, allowed Paul Boulanger to build a modern labt)ra!ory, and to train particularly dynamic and enthusiastic young scientists there. The axis of his work evolved as did that of biochemistry. At the beginning of his calver, a biochemist had fh'~! to he a g~md chemist, whereas today he has It) he a good biologist. lake his lll,~s.¢l,' 't, 's, he Was a gt~t~tl organic chemist and an excellent analvsl, . In hi~ research into derivatives similar to rihtfflavinc, ~l'xv"hlctl he was ~tutlying the toxic properties, he carried out the synthesis of all its ¢onlpouttds hh!)ne!f. At this tinle il was necessary to kllow how Io do everything on,self, because there was no question of buying ready-to-use molecules, or to be h e l ~ d by a laboratory assistant! Scientists deserved h~r more merit in the past titan they do now, The first r~:.-search~, " he carried out with Michel Polonovski bore on the origin of urinary ammonia, and he was also a pioneer in work on the formation of ammonia, its transportation in the blood and its renal excretion, He developed the con"cept of renal ammoniogenesis, which we now know comes from the hyd~lysis of glutamine and the de. ammatlon of amino acids, and he distinguished it l ~ m ammoniophaneresis, which re!~resents.. the excretion in urine of ammonia ions. which'aer• part of the elimination process of the protons resulting from acidosis• This work was carried out in conditions of poverty, which necessitated praiseworthy ingenuity, and the determinations of ammoma were remarkably precise in spite of the antediluvian equipment. He applied his knowledge to the study of the metabolism of ,a mmo • acids. His main results concerns tran. anunatlon, With his student Roger Osteux, he particularly studied desamination and transamination of diamino acids, the metabohsm of lysine and that of series D amino acids. His interest in these "non natural' amino acids had been inspired by the works of F K~gl, who had affirmed that cancer tissues contained non-negligible proportions of them• Using remarkably rigorous ~:hntques, he showed the Dutch biochemist's error, but the results he obtained from his study of the metabolism of these compounds have helped deepen our knowledge of several aspects of nitrt,genous metabolism. His work on the metabolism of lysine led him to the discovery of a transat,fination process ditl~ring farm that of Alexander Braunstein, which concerned the u-amino S
•
'~
•
functions, a process v,'hK'h applies [o the ~'-amino function: hc c~.dk'd tllis "pyridinic c¢~cnz3me
mmsamim~tion'. Effectively, the amino function on the ~-cetogl~aric acid h~tppens in tx~,'osteps, the first using the NADPH form of saccharopi,le and the second carries tile t~vo hydrogens onto the NAD and frees the glut~.mlic acid with the/8-semiaidehyde-~ aminodipate. The progress of biochemistry in isolation and structure of proteins, then :ff nucleic acids. attracted hi|ll to research fields which were opening up and ~vhK:h. although difficult, merjo)ed his curiosity-filled mind as well as those of tile young scientists working with him. It is on the theme of "the biochemistry of proteins' that he created the first INSERM unit in Lille in 1966. With his students, Gdrard Bisert and Michel Dautrevaux, he turned his attention to the chemistry of proteins and polypeptides, Together with Raymoqd Havez and Philippe Roussel. he gained renown in the field of the chemistry of glycoprotein. And it is Jean Montreuil who championed tile study of glucidic chains. As his student Gdrard Biserte said: "it is to him that the Nord-Pasde-Calais Region owes its reputation as one of the most important centres oI' medical research. dependent on INSERM." From 1939 his work was carried out at tile Cancer Research Institute. He was always an active supporter of collaboration between scientists and clinicians. For example, tile research on the mucins and tile glycopmteins of bronchial secretions that he carried out with his students R Havez, P Roussel, and P Degand earned the Lille Faculty of Medicine international renown in this domain. The situation of his deparlment in |he heart of the hospital complex led him to collaborate very efficiently in the organisation of the hospital laboratories. Tile school he created attracted many gifted young people. He inspired in them the love of work well-done. His students followed his example and have aivcays considered him as a father-figure. Each one took a different path, either in the Faculty of Medicine or Pharmacy, or the Faculty of Science or the Pasteur Institute. Yet all are proud to belong to Mr Bouhmger's school. The in° fluence of this school has gone far beyond tile limits of tile region, and his students have scattered as far as Montpellier, Nantes, Grenoble, Reims, Amiens, Tours, Nancy, Toulouse and Viilejuif. He also attracted t'oreign researchers, who have retained affectionate memories ol' this 'boss'. they loved, admired and respected. Modest by nature, Patti Boulanger thottghl that a masler should step aside to hns students. And he claimed himself to be over:joyed by their success. He knew how to direct them, advise them and point them in the right direction. G6rard Biserte wrote to him: "in all circumstances, hapl~y or sad. yott always showed tlS a cal,ll and serene face. just and clear-sighted advice." His inlluence has spread over ntt,lle,'ot, s generations of students, wllo,n he t,'ai,led ill bit~chcmical thtmght, firstly through his remarkably ct~nsl,'ucled vc,'hal leaching, but alst~ Ihmugh his boo,ks which have u,ldergo,le ,m, ltiple editions twcr lhe last half centm'y. Through his leaching bt~t~k.,. Paul I-louhmger is knt)wn t~)all tile French I~iochemist,,. tlocto,'s ;.,lid I~harlllacisl,, as well as I~ numerotm foreign students. I wus lucky cnuugh to Imv¢ worked with hin, t,~ the pl'cp~u~,titm ul all his books: "Biochimie Medicale" Ibr which he collabor~Lled with Michel Pohmovski. from the first edition in 194{}, to the fifth edition in 1952. and which was mnplified to Ikmr volumes over the lbllowing years; the "Abr¢;g¢~de Bhwhimie Medh'ah,". which Ik~liowed it and which is ~lt present in its third edition since 1979; these are basic handbooks for studenls. The seven vt~lumes of the three tomes o1' "Biochimie G~;n&'ale". produced in association, which was finished in 1972; "Prob/bmes actueis de Biochimie G&u;rale". imblished in 1972 and written by several of his students and colleagues. The "Expos& ammels de Biochimie M&iicale" to which he contributed over 40 years. "Pathologie Chimique". published in 1951-52 with Michel Polonovski and G Schapira. "Biochimie M&licale" has been translated into German. Italian and Spanish. Patti Bouhmger was a workaholic, thtmghtl'ul, meticumus and vigilant. !ti.~ competence in all the domains of biochemistry earned him recognition from all the Frencll biochemists. The wistlo,n of his judgement and fatherly benevolence he showed to all young people explain the almost unanimous sufl'rage given to his name at all the national University and Research authorities. His options and votes were always l'ull ot' sense and guided by the common good and never determined by partisan or unjust considerations. Out" whole geqeration of biochemists knows what we owe t~ his activities on the Consultative Committee of Universities. the CNRS National Committee. as well as that ot' INSERM. He had a considerable influence on the training and selection of most of the teaching biochemists in the Faculties of Medicine. tte more than deserved the decorations he was awarded: Commander ol' the Order of 'Les Palmes Acad6miques'. Officer of the Order of
Public Health, Commander of the 'L6gion d'Honneur', He was an honorary Doctor at the University of Brussels. and was the laureate of the "Prince Albert of Monaco Grand Prix" in 1965. He was elected correspondent of the Acad~mie Nationale de M6decine in 1947 and non-resident member in 1968, He presided over its eighth section for several years from 1980 to 1984. Jacques Polonovski (from the eulogy delivered the 6th of May 1997 at the AcadEmie Nationale de M6decine)