Introduction
Charles Thibault was born in Paris on 14th July, 1919, the only child in a family of modest background. There were none of the advantages associated with having relatives in the academic world or traditional professions, but the father clearly had creative talents. He was a designer of car body shapes in the flourishing Renault enterprise, and his activities in this sphere doubtless prompted the son's life-long fascination with Renault motor cars and loyal ownership thereof.
Education
Thibault, hereafter referred to as CT, was exposed to a conventional curriculum at his Paris Lycée and, although steeped in French literature and history and becoming reasonably fluent in German not English, he found himself more and more attracted towards the sciences. It has not been possible to establish whether any particular teacher inspired him in this direction but, as noted below, it formed the background to his life-long endeavours. After a satisfactory if not distinguished performance at the Lycée, he proceeded to the University of Paris (the Sorbonne as it was in those days) and enrolled in the Biological Section, with additional courses in Chemistry and Physics. In his biological studies, he soon came under the influence of Professor P.-P. Grassé, the teacher who was to stimulate his future research activities. It was the beginning of a long-term academic relationship. What seems remarkable at this stage of his studies, still aged only 20 and about to commit himself to advanced course work in biology, is that CT found the time and energy also to teach in a primary school and thereby contribute to the national effort. It was the fateful year of 1939.
Within the university, his studies had progressed well and, being possessed of an enquiring and analytical mind, he soon expressed the wish to engage in research. Initially, this was to involve a project entitled: ‘Vision of colour by fish’, which led to the publication of his first thesis. Next, and more specifically influenced by Grassé, he turned to the field of fertilization in mammals, one that was to become a life-long interest. Here his experimental work was principally with the rabbit and was assembled under the title of ‘Parthenogenesis in mammals’; it demonstrated diverse forms of activation of a secondary oocyte. The thesis submitted in 1949 came to be recognised as a key publication and has been widely cited down the years, although scarcely mentioned in contemporary articles. His knowledge and authority in this domain of artificial activation were to prove invaluable as various groups began to pursue the goal of in vitro fertilization (IVF) of mammalian eggs. Prompted by the conditions of culture, so-called spontaneous activation and the early stages of parthenogenetic development were frequently encountered in studies during the 1950s and 1960s.
The seemingly belated publication of this doctoral thesis may serve to remind the reader of the disaster of the Second World War (1939–1945) and the far-from-favourable conditions in Paris for concentrated study and systematic laboratory work. The city itself was not liberated from German occupation until 1944. CT's studies had been interrupted by military service and, as an exceptionally strong and fit young man, he was to serve with the famous Chasseurs Alpins, being based after initial training first at Marseilles and then in the Alpes de Haute Provence at Digne.
Returning from military service, his first foot on the career ladder was appointment during 1944–1946 as Attaché de Recherche in the Centre National de la Recherche Scientifique (CNRS) followed by that of Assistant in Biology at the University of Paris (1946–1948). These posts sustained him during his substantial thesis work referred to above but they also involved duties, not least responsibilities within the laboratory and some formal teaching. Both duties increased during 1949 with his promotion to Chef de Travaux within the Physics, Chemistry and Biology department of the Sorbonne. His special gifts and abundant energies had already been noted, and he was now being groomed for greater responsibilities. In the event, these were not to be within the university with which he was so familiar, but rather in the state-funded Institut National de la Recherche Agronomique (INRA), still in its infancy.
Stability and sustenance during this remarkable career development were provided by his marriage to Odette Parent, herself a distinguished student in biological sciences. They had two gifted sons, both of whom enjoyed professional careers.
Institut National De La Recherche Agronomique
Establishment of Physiologie Animale
Stepping across from a strict university background and the specific discipline of mammalian fertilization, the challenge of joining INRA in 1950 must have been considerable. However, with a profound wish to help in the post-war recovery of France, CT was well able to appreciate the value of research aimed at improving animal productivity. Together with senior colleagues, especially Monsieur R. Fevrier, his first crucial tasks were: (a) locating a suitable terrain close to Paris on which a major centre of research could be established; and (b) building up a team of young chercheurs. An estate belonging to a well known banking family was purchased at Jouy-en-Josas. This estate was the Domaine de Vilvert in the beautiful valley of the Bièvre, some 15 km southwest of the centre of Paris and only 5 km from Versailles, and this new centre for animal research developed rapidly. It became known as the Centre National de Recherche Zootechnique (CNRZ), Jouy-en-Josas. The adopted discipline of CT would be animal physiology and the foundation staff appointments slowly but progressively gained national and then international reputations, the latter aspect being extremely important to the psychological health of post-war France. Brief mention can be made here of the key activities of these initial appointments, the vanguard soon to be housed together in a prominent new building known as Physiologie Animale.
Sperm production, ovarian function, fertilization
Bearing in mind the overall remit of increasing animal productivity, and developments elsewhere in the world on artificial insemination, superovulation and egg transfer, it is not surprising that the first research projects were similarly concerned with these various spheres of fertility.
Robert Ortavant was recruited to lead studies on spermatogenesis and sperm production in farm animals, using sheep as his model species. Future developments in artificial insemination were always a backcloth. Louis Dauzier joined CT to work on problems of fertilization, both in vivo and in vitro, and was soon ably supported by Suzanne Wintenberger (to become Mme Wintenberger-Torres). She subsequently established an independent reputation studying progression of newly ovulated eggs in relation to contractile activity of the oviducts. Also notable amongst the early appointments were Pierre Mauléon and Francois du Mesnil du Buisson. Although Mauléon was to develop interests in oogenesis and ovarian folliculogenesis, his first tasks were to examine ovarian responses to gonadotrophic injections, not least with the objective of controlling ovulation and inducing superovulation in cattle.
Du Mesnil was charged with the full sphere of reproduction in pigs, both fundamental and applied. In the former, such as the role of pituitary hormones in maintenance of the corpora lutea and establishment of pregnancy, he was assisted during the late 1950s and early 1960s by the medically trained P.C. Léglise. This recruitment to the staff of Physiologie Animale was an inspired move by CT, and some of the attributes of this gifted surgeon have been noted elsewhere (Hunter, Reference Hunter2005). Development of artificial insemination in pigs was always a practical component of Du Mesnil's work.
Lactation
A group devoted to studies on lactation had been formed within Physiologie Animale under the leadership of Robert Denamur, and he was closely supported by a veterinary surgeon, Jacques Martinet. Without overlooking key studies by Denamur's group on lactation and on milk proteins – developed progressively by G. Petrissant, P Gaye and Michèle Bousquet – the involvement of pituitary hormones in maintenance of the sheep corpus luteum also intrigued Denamur and Martinet. Guided by Léglise, they themselves conducted sophisticated hypophysectomy studies and were joined in the 1960s by a young veterinary surgeon, Guy Kann, who concentrated on the diverse roles of prolactin. Yet another young veterinary surgeon, Jacques Martal, was soon appointed and he in turn focused on uterine proteins and their involvement in regulating corpus luteum lifespan. A major tragedy in the consolidation of the lactation group was the sudden death of Denamur in 1973, still a relatively young man whose influence was already prominent on the international stage.
Steroid hormones and gonadotrophins
Classical endocrinology was, of course, appreciated to be of prime importance in reproductive events and a group concentrating on steroid hormones was formed under the leadership of P. Rombauts. It was soon joined by J. Fevre and later by M. Terqui. Although this group had its own special research interests, not least in adreno-cortical function, it also provided steroid hormone assays for colleagues working on the corpus luteum and placental physiology. Gonadotrophin assays were developed by J. Pelletier.
Animal behaviour
Whilst procedures of artificial insemination in pigs were being developed, accurate detection of the onset of oestrus as a guide to the time of ovulation began to receive attention. Interactions between boars and sows approaching the phase of oestrus were deemed critical and a specialist in animal behaviour, J.P. Signoret, was appointed to work alongside Du Mesnil. Their joint studies were widely appreciated by the expanding French pig industry, and their demonstration that the sight, smell and sound of a boar were together important in eliciting the standing (mating) reflex at oestrus had major practical implications. This message was brought home in a specialist documentary film, and a potent aerosol to mimic boar odour became available commercially for use at the time of insemination, to be sprayed on the sow's nose.
Spermatogenesis and epididymal transit
As the scope of artificial insemination coupled with storage of semen expanded, fundamental studies on spermatogenesis needed to be further developed and Ortavant's group was joined by M. Courot and then by Marie-Therèse Hochereau de Reviers. Their work soon came to be recognised as meticulous basic science while, at the same time, there were practical implications. For example, the depletion of epididymal sperm reserves and the duration of sperm displacement along the epididymal duct and whether these could be related to the frequency of mating or semen collection. Underlying both of these processes was the rate of spermatogenesis.
Fish, fleece and fur production
Although not widely viewed as a mainstream agricultural activity, commercial fish production had become an important fresh-water development in France, and a pioneer research group on fish reproduction was established at Jouy-en-Josas under the leadership of R. Billard and later joined by B. Jalabert and B. Breton. Likewise, fleece and fur production from domesticated or semi-domesticated mammals was not considered as a major component of the agricultural industry in France, yet a research group specifically interested in pelage (fur and fleece coating) was formed under the leadership of J. Rougeot. Small species of wildlife that were a target of the hunting community (La Chasse) were not overlooked, and Mme Lise Martinet was appointed to lead work in this sphere. The hare became her model species.
Electron microscopy
As the above studies of reproductive processes progressed, CT was soon to appreciate that expertise in the relatively new field of electron microscopy would become invaluable. A Unit was created within Physiologie Animale and a well trained young specialist brought up from the University in Lyon. He was Jacques Fléchon who not only provided a service in supporting colleagues but also developed his own studies on sperm cells. Although, with genuine modesty, he did not contribute to the literature for several years, in due course he published high quality work and gained international notice. Similarly, his wife, Bernadette Fléchon, who had initially been his assistant, developed expertise in scanning electron microscopy and also published high quality images.
Moving on to the technique of freeze-fracture, the Fléchons explored features of the sperm head membranes with a particular interest in acrosomal modifications during the events of sperm maturation and the beginning of fertilization. Also noteworthy, the Fléchons established fruitful links with research groups in the Czech Republic and studied protein components of oocytes and young embryonic cells using fluorescent antibody techniques. CT was genuinely proud of their work, and he himself participated enthusiastically in the Franco-Czech workshops organised by the Fléchons.
Already mentioned as a member of the lactation group, Michèle Bousquet (Mme Olivier) became much involved in ultrastructural studies of mammary tissues.
Oocyte organelles, remodelling of nucleus, cloning
One further personality in electron microscopy from the early 1970s was Daniel Szollosi. He first visited Jouy-en-Josas on sabbatical from the University of Washington, Seattle, USA and then moved permanently to France in 1972. He was specifically interested in the evolution and arrangement of organelles within maturing mammalian oocytes, and was joined in this work in the mid 1980s by Mme Marina Soltynska from Professor A. Tarkowski's laboratory in Warsaw. Together they examined the developmental potential of nuclei transplanted at different stages of the cell cycle and into different stages of maturing oocyte or early embryonic development. One of their favourite experimental systems was the remodelling of thymocyte nuclei in oocyte cytoplasm at different stages after resumption of meiosis. Such work led to a series of elegant publications.
Although not recorded in print, these fundamental studies by members of CT's laboratory had a strong and significant bearing on subsequent history, not least as thoughts of eventual cloning were widely discussed by Szollosi and CT at this time. From the late 1970s onwards, Szollosi gave freely of all his experimental observations, thoughts and insights concerning nuclear remodelling in maturing oocytes to Ian Wilmut and members of his Roslin laboratory. Szollosi's work was to prove invaluable in guiding the subsequent experiments with sheep eggs at Roslin. It is certainly worth noting that, in marked contrast to the openness of Szollosi and French colleagues, there was a complete refusal by Wilmut as late as August 1995 to divulge any of the related Roslin work. As a gifted multilingual contributor to diverse intellectual circles and as a man of principle, Szollosi was to remain profoundly shocked by this disagreeable feature of modern science, as was very much true of CT. Needless to say, Szollosi's name is omitted from the immodestly entitled book on Dolly the sheep.
Embryo transfer
Studies on bovine reproduction had been part of Mauléon's remit but, conscious of developments on embryo transfer in the USA, UK and Japan, J. Testart was recruited to examine and develop its potential in cattle. The excellent facilities for this work at Jouy-en-Josas included a specialist operating theatre with hydraulic tilting table for surgical interventions in mature animals. Nevertheless, an approach favoured by Testart was to try to shorten the ‘generation interval’ by inducing ovulation in calves long before puberty. Another initiative was essentially a non-surgical, trans-vaginal approach to by-pass the cervix and introduce embryos directly into the uterus. This would avoid excessive myometrial stimulation and retrograde ejection of the transferred embryos. After some success, Testart changed species and moved in the early 1970s to l'Hôpital Antoine Beclerc at nearby Clamart where his originality was much appreciated in human fertility studies (see below).
Testart's research facilities at Jouy-en-Josas were taken over by a young veterinary surgeon, Y. Heyman who, with J.-P. Renard and J.-P. Ozil working at the cellular level, demonstrated the feasibility of induced twinning and, indeed, cloning in cattle reproduction in France. J.-P. Renard also applied skills in cryopreservation to bovine embryos and, jointly with Testart, achieved success with preservation of human embryos in the mid 1980s.
Related groups on campus
Creation of the INRA campus at Jouy-en-Josas had a remit far wider than animal reproduction. Major research groups with substantial facilities were also established, for example, in Animal Nutrition, Dairying, Poultry Production and Animal Genetics, and their independent buildings and research groups were soon identifiable. However, CT's discipline of animal reproduction was by far the most prominent and before long was to outgrow the very large central building of Physiologie Animale, in which his reproduction teams came of age. Specialist satellite buildings arose in the vicinity.
Much more could be written on developments at Jouy-en-Josas, but a key point in the present memoir is the breadth of vision shown by CT in building up the research teams. Coming from a strict university background with a well defined interest in mammalian fertilization and its anomalies, it is remarkable that he so quickly grasped the scope of the research fields needed for a sustained expansion of animal productivity. He was not, of course, working in a vacuum but rather amongst well informed colleagues; nonetheless, he had to lead, to take key decisions, and to carry overall responsibility.
Library and documentation service
Relevant to the build-up of research teams in post-war France was the establishment of a library of international books and scientific journals across a wide spectrum. Under the guidance of a multilingual lady of Polish lineage, Mme Sophie Strajewska, the library service was developed with a similarly-gifted team of female staff who responded promptly to each and every request. Translations were provided whenever necessary, including from Russian, and weekly Wednesday afternoon meetings of the research teams within Physiologie Animale discussed the latest publications of potential relevance. Despite this comprehensive approach, CT was to require personal assistance by the 1960’s to keep abreast of the fast-expanding reproductive literature. Mlle M.-C. Levasseur was appointed as his documentalist within Physiologie Animale. Not only did she act as an extra pair of eyes but she was soon to be involved in drafting reviews and indeed writing the first versions of research publications on CT's behalf. Without such dedicated and diligent full-time support, it would not have been possible for CT to have contributed so effectively and energetically across so broad a canvas.
Personal research activities
Fertilization: parthenogenesis
C. Thibault's doctoral thesis (1949) centred on the process of fertilization in rabbits and in particular on the induction of parthenogenesis. The notion that apparent fertilization – pseudo-fertilization – could be achieved by artificial activation of an ovulated egg (secondary oocyte) perplexed him, and he employed diverse experimental approaches towards this goal. Resumption of meiosis could certainly be prompted and even the formation of structures resembling pronuclei, but normal cleavage divisions and early embryonic development never followed. These studies were conducted before the advent of phase-contrast microscopy, and preparation of sectioned eggs for histological examination was a time-consuming procedure. On the positive side, however, organelles could be revealed that were not usually seen in the whole mounts subsequently used in phase-contrast microscopy. One such organelle in fertilized rabbit eggs was a so-called ‘sperm aster’, and CT soon appreciated potential parallels with fertilization in invertebrate eggs.
In vitro fertilization of rabbit eggs
At the time of CT's own studies on fertilization, a colourful figure from the medical fraternity was beginning to attract attention in Paris, especially amongst those interested in embryology. His name was R. Moricard, and he was confidently proclaiming that he had achieved fertilization of mammalian eggs in vitro. On the basis of his illustrated findings, there was considerable scepticism amongst French biologists; with CT, there was complete disbelief. None of Moricard's illustrations persuaded a, by now, highly experienced student of fertilization in rabbit eggs that it was anything other than artificial activation. A heated controversy ensued, and Moricard was soon to resign from his post.
Bearing in mind CT's translation from specialist studies in a university embryology laboratory to the world of a newly-created research centre with its major demands on his time and the need for a broad agricultural perspective, it is intriguing that he never abandoned his fascination with the mammalian egg nor with using the rabbit as an animal model. On the one hand, he was planning and developing facilities and research teams at every conceivable level. On the other hand, he was quietly working towards establishment of a small research group devoted to problems of mammalian fertilization, especially to producing irrefutable evidence of fertilization in vitro. The latter project was brought to fruition in partnership with L. Dauzier and S. Wintenberger (Thibault et al., Reference Thibault, Dauzier and Wintenberger1954), and attracted widespread acclaim.
In the preceding context, it is important to note the enthusiastic support of skilled workshop staff who constructed specialist cell culture rooms and novel apparatus enabling expansion of related projects. Of course, within the setting of INRA, in vitro fertilization of rabbit eggs was never a final objective. Rather, there was always the hope of being able to apply such pilot techniques to in vitro fertilization of cattle eggs and perhaps also to those of sheep, pigs and goats. If and when successful, these would then be coupled with procedures of embryo transfer to a recipient (foster mother).
Capacitation of spermatozoa
During the in vitro fertilization studies on rabbit eggs, and prompted by the publications of Austin (Reference Austin1951) and Chang (Reference Chang1951), it was slowly appreciated that suitable surface ‘washing’ or other forms of treatment of the ejaculated sperm sample used in IVF could have a beneficial influence on sperm ability to penetrate the zona pellucida. Based on their in vitro body of work involving a dynamic culture system, CT and colleagues published an endorsement of these first reports concerned with a sperm maturation process known as capacitation (Dauzier & Thibault, Reference Dauzier and Thibault1956).
Sperm progression in female tract
CT's administrative work and responsibilities grew progressively throughout the 1950s and 1960s, but he always made time for laboratory work. These potentially conflicting activities were side-stepped by means of highly competent secretarial and technical support. Although he would never be divorced from his interest in maturation and fertilization of the mammalian egg, he was conscious of the ever-increasing impact of artificial insemination on cattle breeding in France and beyond. The use of deeper deposition of the sperm suspension than occurs with mating raised fundamental questions, and a systematic study of sperm transport in cattle commenced using a histological approach. Oviduct sections were examined in detail to record the numbers of spermatozoa in different regions of the isthmus and ampulla. The full significance of the observed sperm distribution did not emerge at the time, but a steep reduction in sperm numbers was noted between the uterine extremity and the ovarian end of the oviducts. These studies were undertaken during the 1960s but were only published at a later date (Thibault, Reference Thibault1973; Thibault et al., Reference Thibault, Gérard and Heyman1973).
Pre-ovulatory maturation of oocytes
After these detailed studies on bovine sperm transport which were valued across the broader spheres of INRA, CT returned to questions on maturation of rabbit eggs, but not in a post-ovulatory context. Instead, he focused on the maturation that precedes shedding of a secondary oocyte from the Graafian follicle. Whether CT opted to develop this project in relation to his earlier studies of IVF in rabbit eggs or whether it was prompted by the studies of R.G. Edwards in Cambridge, England, is uncertain. However, the work of Edwards on attempted maturation of human oocytes during the mid to late 1960s had certainly caused unease, for some of the published photomicrographs were not typical of healthy pre-ovulatory oocytes. Studies on maturation of oocytes consumed a major portion of CT's laboratory time for a number of years.
Male pronucleus growth factor
Ably was assisted in the laboratory by Mme Micheline Gérard, oocytes aspirated from rabbit follicles were subjected to procedures of in vitro maturation followed by attempted in vitro fertilization. Microscopic examination of the resultant preparations frequently revealed incomplete decondensation of the sperm head within the vitellus. The degree of sperm head swelling and pronuclear formation was seemingly related to the maturity of the oocyte cytoplasm. Hence the involvement was postulated of a male pronucleus growth factor (MPGF) presumed to be synthesised and/or made available during the 10-h phase of rabbit oocyte pre-ovulatory maturation (Thibault & Gérard, Reference Thibault and Gérard1970). This event led CT to caution those working with human oocytes of potential incomplete maturation in vitro and the consequent risks for any zygote so formed.
This interest in MPGF and cytoplasmic (vitelline) incompetence was pursued biochemically with Y. Menezo and at an ultrastructural level with D. Szollosi (Thibault et al., Reference Thibault, Gerard and Menezo1975, Reference Thibault, Szollosi and Gerard1987). Although the finding of incomplete sperm head decondensation was of interest in rabbit oocytes, and had been noted earlier in pig oocytes, it was not reported as a significant problem in human pre-ovulatory oocyte maturation. If sperm penetration of the oocyte occurred during attempted IVF, then formation and evolution of a male pronucleus was the usual sequel. Nonetheless, Menezo was prompted to formulate a physiological culture medium based on analyses of follicular, oviduct and uterine fluids. It has since been widely used in France and beyond.
Oocyte culture in demi-follicles
CT's subsequent approach to oocyte maturation in vitro differed in major respects from that of Edwards and colleagues in Cambridge. The latter used human oocytes aspirated from maturing ovarian follicles, placing those deemed morphologically healthy in culture if surrounded by a cumulus oophorus. By contrast, CT believed that an integrated process of pre-ovulatory oocyte maturation – i.e. resumption of meiosis, molecular changes in the ooplasm and modification of zona pellucida characteristics – all depended on oocytes being in harmony with the encompassing Graafian follicle. Organ culture of whole follicles posed technical problems in terms of gaseous diffusion across the many cell layers of the follicle wall. A novel approach to overcoming this limitation was to culture an oocyte still supported on its own cell layers in a demi-follicle, half of a dissected follicle. In conjunction with an American professor on sabbatical leave at Jouy-en-Josas, progress with this partly in vitro model attracted widespread attention (Foote & Thibault, Reference Foote and Thibault1969).
However, the Cambridge studies of Edwards and colleagues, who continued to work with oocytes liberated from the supporting follicle, had progressed well during the early 1970s and there was confidence in that laboratory fertilizable oocytes were being generated in vitro. Supporting evidence came from a series of IVF trials followed by culture of the resultant embryos and then non-surgical transfer into appropriate patients. Various stages of pregnancy were obtained and the Cambridge work was finally vindicated with the birth of Louise Brown in 1978 (Steptoe & Edwards, Reference Steptoe and Edwards1978). The fact that oocyte maturation could be completed in vitro in a relatively simplistic manner intrigued CT, and he attempted to resolve some of the underlying physiological questions in his Hammond Memorial Lecture entitled: ‘Are follicular maturation and oocyte maturation independent processes?’ (Thibault, Reference Thibault1977).
Background to human IVF in France
One of the first laboratories in France to attempt to follow the success of Edwards and Steptoe was at the Hôpital Antoine Beclerc in Clamart, just a few kilometres from Jouy towards central Paris It was no coincidence that key chercheurs in the IVF team at Clamart, J. Testart and O. Bomsel, were themselves former members of CT's Physiologie Animale group. Ondine Bomsel, in particular, had done hallmark studies on chromosome anomalies in mammalian embryos (Bomsel-Helmreich, Reference Bomsel-Helmreich, Wolstenholme, O'Connor, Ciba Fdn Symposia and Churchill1965). There were frequent exchanges between Clamart and Jouy, and CT gave very freely of his ideas and experience to the clinicians at Clamart. The first IVF success in France leading to a healthy full-term baby was that of J. Testart and colleagues, and Testart was himself more than generous in acknowledging his background and training at Jouy-en-Josas.
What is certainly not correct, as all too strongly suggested in the review of Edwards (Reference Edwards2005), is that CT was out of touch with developments in the field of human IVF. Nothing could be further from the truth, as noted more fully below. But his considered advice remained to proceed with animal experimentation before testing new approaches in human patients (Thibault et al., Reference Thibault, Levasseur and Hunter1993).
Decentralisation of Physiologie Animale. Paris Professorship
During all the years of his laboratory studies, CT's responsibilities as leader of an ever-expanding research group within Physiologie Animale had increased substantially, and the group was now spread across the four centres of Jouy-en-Josas, Nouzilly, Clermont-Ferrand and Montpellier. He made it his business to visit each centre every 3–4 weeks in order to follow the progress of individual chercheurs, not least the younger members. He was particularly diligent in this regard. At the same time, indeed since his 1967 appointment as Professor of Reproduction at the University of Paris VI, his teaching commitments had also increased, as had the duty of training and supervising research students. In one sense, the latter burden was eased by guiding many such post-graduate students towards ongoing research projects at Jouy or Nouzilly (Tours), still comfortably within reach of Paris.
President of the CNRS
Despite these increasing burdens and major committee work in Paris, there was soon to be a quantum leap in his duties and long hours of exceptionally hard work. Under the Presidency of Valéry Giscard d'Estaing, he was appointed in 1979 to lead the major French science research agency, the Centre National de la Recherche Scientifique, with its various centres, numerous highly talented staff and wide-ranging programmes of research. All this responsibility might have been daunting to a conventional individual whose background was in animal physiology and mammalian reproduction, but not to CT. He was a man of vision, wished passionately to guide French research endeavours, and had confidence in his own abilities and judgements. In a brief space of time, he established himself as an inspirational leader of the CNRS and was much valued by a wide range of staff. However, such a commanding personality with his own carefully reasoned ideas gradually became less than fully welcome to Giscard's Minister of Science, one J.P. Chevènement. Tensions between CT and the Minister slowly grew to become substantial difficulties and, in 1981, CT offered his resignation as did the Directeur Général and returned to his former activities at the university and supporting INRA at the highest level.
Fertility and infertility; President of French Society
The 1980s were exciting times for mammalian reproductive biology. At the cellular level, various approaches to cloning were being examined, as were the formation of novel constructs such as sheep × goat hybrids. And, at the molecular level, meaningful contributions were beginning to be made by a new wave of biologists, groups of whom were assembled in an impressive specialist building at Jouy-en-Josas. These included J.-P. Renard who had received advanced training at the Pasteur Institute in Paris. Most of all, however, it was work in the human field that had taken centre stage in the 1980s. Infertility clinics were being set up in many hospitals in Western Europe and more and more studies attempted to follow the pioneering work of Edwards and Steptoe. Human infertility was widely appreciated to be an important medical problem, with as many as 15% or more of couples in a stable relationship being unable to procreate.
After clinical screening, IVF and non-surgical transplantation of an embryo or embryos was considered the way forward. The starting point of a treatment protocol was ovarian stimulation to enable laparoscopic or trans-vaginal aspiration of two or more follicular oocytes for attempted fertilization in vitro. Clearly, all the years of experience at INRA employing gonadotrophin stimulation of sheep, goat, pig and cow ovaries were of relevance, as were the IVF studies in the excellent facilities at Jouy. CT interacted more and more with the medical world and with individual gynaecologists, attending their workshops and conferences and visiting specialist clinics. His advice was frequently sought and he was always generous with his time and with his carefully considered views. He was elected President of the French Society for the Study of Fertility and served in that role from 1986–1989.
There were related initiatives. As from the late 1970s, CT had formed a Discussion Group at Jouy which became called a ‘Fertilization Club’, and every 2 weeks it provided a forum in which to examine the latest developments across a broad field. Young clinicians soon became enthusiastic participants and there was a very free exchange of views between animal physiologists and human gynaecologists. In fact, exchange is probably not the most appropriate word here. Based on many years of experience with observations in domestic animals, the flow of ideas and specific information tended to be from animal experimentation towards the human clinical world. One of the paradoxes to attract much discussion was the relative ease of obtaining sperm penetration of the human zona pellucida compared with the zona pellucida of domestic rodent and farm animal eggs. This contrast still awaits a fully meaningful explanation.
Magnum opus – the big green book
At an age when many senior academics might have considered slowing down, CT increased and diversified his activities, and initiated an overall synthesis of modern mammalian reproductive research. It was to take the form of a major book, written in French by authors working actively in French research institutions and hospitals. Together with Marie-Claire Levasseur, he immersed himself in the project during a period of more than two years. Not only did he guide the content of individual chapters but, in most cases, he suggested substantial revisions to the specialist authors. To contribute specific knowledge across such a broad field and to be able to edit incisively was remarkable and the clearest indication of intellectual stature. In the event, the final draft of each and every chapter was word-processed by CT himself and then reproduced directly by the publisher. The finished text, a substantial volume of 900 pages, was extremely well received in France and was a notable commercial success (Thibault & Levasseur, Reference Thibault and Levasseur1991). A subsequent updated version in English never really secured its place in the reproductive literature. Although the name of C. Thibault was widely recognised in western European circles, the opposite was true in much of North America and beyond, and the book failed to compete with established texts. This was a severe disappointment, not least since the French approach to a research topic usually differed both philosophically and practically from that in North America.
Final years at Jouy-en-Josas and Vélizy
After his several years of commitment to the book, CT continued to give of his time and experience in numerous ways. He remained fascinated by reproductive biology and was well informed about the latest developments, but he did not embark on major new projects in the laboratory. Instead, he wrote carefully-balanced reviews (e.g. Thibault, Reference Thibault1999, Reference Thibault2003) and assisted others in a similar vein. By that stage his achievements had been recognised with various national and international prizes, but undoubtedly being awarded Commander of the Legion of Honour in 1999 would have touched him most deeply.
Now living in nearby Vélizy, his daily routine was the 5 minute drive down to Jouy-en-Josas, working at his desk all morning, lunch with INRA colleagues in the excellent Refectory, and thereby keeping in touch with the most recent findings. He had occupied almost exactly the same rooms in Physiologie Animale since the early 1960s and, surrounded by his personal library and immediately next door to his long-standing documentalist (Marie-Claire Levasseur), he gradually adjusted to a quieter pace of life. There had always been an excellent personal relationship with Marie-Claire Levasseur and, some years after the death of Mme Odette Thibault, CT and Marie-Claire decided to live together. After the lonely widower years in Paris when he was still working ferociously long hours, this new arrangement provided much-needed companionship and a therapeutic social life. Together they enjoyed classical music and they entertained generously and with warmth. The only compulsory aspect for visitors was having to watch television when an important football match was being screened! For such a knowledgeable and influential individual, he had remained wonderfully simple and unspoilt. Despite the contentment of these final years, there was no escaping the march of time and a significant deterioration in his health had occurred. He was stoical in the face of such adversity and died in 2003 at the age of 84. In his honour, a group of French experts in 2015 instigated a ‘Prix Charles Thibault’ to be awarded annually for the best acknowledged contribution in the field of reproductive biology.
Concluding perspective
From a university microscope and rabbit oocyte via development of a major national centre of animal research to the highest councils of state, the sheer range of CT's commitments and responsibilities will leave most readers feeling modest indeed. Few could even begin to contemplate such an amazingly broad canvas.
Declaration and acknowledgements
Apologies to former colleagues who have been overlooked or who feel they have received insufficient mention.
The author was a Chargé de Recherche in Physiologie Animale, Jouy-en-Josas, from 1968–1970, returning there as Visiting Professor from the University of Edinburgh in 1978 and again in 1992. He has an enduring affection for France and its intellectually inspiring milieu.
M. Bernard Thibault and Professor W.R. Allen, CBE, FRCVS, kindly read a draft of this memoir. Jenny Levitt willingly typed my original hand written text, and Julia Chambers MRCVS, generously undertook its submission. I remain grateful to each and all of them.
