G Model
ARTICLE IN PRESS
JRI-2280; No. of Pages 4
Journal of Reproductive Immunology xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Journal of Reproductive Immunology journal homepage: www.elsevier.com/locate/jreprimm
Origins and evolution of reproductive immunology: a personal perspective W. David Billington ∗ School of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK
a r t i c l e
i n f o
Article history: Received 7 September 2014 Received in revised form 13 October 2014 Accepted 21 October 2014
a b s t r a c t This is a brief personal assessment of the origins and development of the field of reproductive immunology from the 19th century to the present day, with special reference to the founding of the Journal of Reproductive Immunology in 1979. © 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: History Reproductive immunology
1. Early beginnings Following the generous brief afforded me by the conference organisers, this is a short and personal assessment of the origins and evolution of the field that we now know as reproductive immunology, and that have been the mainstay of my professional academic career for over 40 years. Although everyone will likely have their own views on the origins of most specialist subjects, for me the landmark studies leading to the emergence of enquiries into the immunology of reproductive processes are those pursued by the Russian biologist Ilya Mechnikov (1845–1916) and later by the Austrian biologist and physician Karl Landsteiner (1868–1943). For his work on phagocytosis, showing the engulfment and destruction of bacteria by white blood cells, Mechnikov was awarded the Nobel Prize in 1908. These findings eventually led to the recognition of Fc receptor-dependent uptake by macrophages. Landsteiner classified the ABO blood groups by identifying the presence of agglutinins, and later also identified the rhesus
∗ Tel.: +44 1275372329. E-mail address: [email protected]
factor. He was awarded the Nobel Prize in 1930. His work thus laid the foundation for arguably the most important clinical contribution that reproductive immunology has ever made, the recognition of rhesus haemolytic disease of the foetus and newborn and its treatment by injection of anti-D antibody.
2. Anti-sperm antibodies and infertility Although spermatozoal immunogenicity was first recognised by Mechnikov as long ago as 1899, only very sporadic confirmatory studies were reported in widely scattered literature during the early decades of the 20th century. The relationship between antisperm antibodies and infertility was first established in domestic animals (heifers) by Bratanov et al. (1949). The detailed studies of Guy Voisin and his colleagues in the early 1950s demonstrated the experimental induction of autoimmune aspermatogenesis in guinea pigs, and the existence of several spermatozoal autoantigens. In 1959, Rumke reported the association between the presence of anti-spermatozoal antibodies and clinical infertility in human males. These early studies provided the foundation for an explosion of
http://dx.doi.org/10.1016/j.jri.2014.10.003 0165-0378/© 2014 Elsevier Ireland Ltd. All rights reserved.
Please cite this article in press as: Billington, W.D., Origins and evolution of reproductive immunology: a personal perspective. J. Reprod. Immunol. (2014), http://dx.doi.org/10.1016/j.jri.2014.10.003
G Model JRI-2280; No. of Pages 4
ARTICLE IN PRESS W.D. Billington / Journal of Reproductive Immunology xxx (2014) xxx–xxx
2
interest in the identification of the molecular structure of sperm surface antigens and their precise role in the induction of infertility in both males and females, and as potential candidates for immunocontraceptive vaccines. Isojima et al. (1968) were pre-eminent from an early stage in this extensive search. It is, however, a cause of disappointment that after so many decades these goals have still not been satisfactorily achieved. Much less is known about female gamete antigens and their relevance in fertility and infertility.
with unexpected opportunities early on. The similarity of our surnames, together with the fact that he had previously worked in the same Oxford department as myself, and in a similar area of research, led to invitations for me to attend and participate in some conferences and symposia that were intended by the organisers to benefit from Bill’s presence! He was greatly amused by this mistaken identity and most generous to me in his later recognition of these missed occasions. 2.2. New technologies
2.1. Immunology of pregnancy A defining moment in the evolution of the field of reproductive immunology came in 1953, when Peter Medawar published the text of his invited lecture to the British Society for Experimental Biology, in which he identified the truly paradoxical nature of the immunological relationship between the pregnant mother and her antigenically foreign foetus. Although Medawar later won the Nobel Prize for his pioneering work establishing the laws of transplantation immunology, he never followed up by experimentation his insightful suggestions as to how the semi-allograft of the foetus and placenta might be able to circumvent the expected recognition and rejection reactions of the immunologically competent pregnant female. Interestingly, it was one of his Oxford graduate students, Rupert (Bill) Billingham, who was, from the next decade onwards, to make significant contributions to an understanding of this problem (see below). My own entry into this field was in 1960, when I was offered the opportunity to begin a graduate studentship with Professor Rogers Brambell, whose group was principally involved in studying the transmission of passive immunity from mother to young, indicating that the mechanism for the selective transport of immunoglobulins resided in the presence of specific receptors for the Fc region of the molecules on the surface of the transmission site, be it neonatal gut, yolk sac or placenta, depending upon the species. My own project was in a different direction, examining the effect of genetic disparity between mother and foetus on the development and growth of the murine placenta. This led to the publication of my first paper in 1964. It was submitted to the journal Nature, had no reference list, and was reviewed, accepted and published in little more than three weeks. I assumed at the time that this was quite normal. How wrong I was! I then joined David Kirby in Oxford to begin a most fruitful and enjoyable collaboration, extending our studies into a variety of topics on the immunology of pregnancy, with special interest in the trophoblast. During this period in the 1960s I became acquainted with, and enjoyed the friendship of, Bill Billingham. He had by then moved to the United States and established a most successful group in Dallas, investigating, inter alia, the uterus as an immunologically privileged site. Together with his colleague, Alan Beer, and others, he made many important advances in several immunological aspects of reproduction, and published one of the earliest and most successful books in this field. He was unquestionably a leading figure right up to the time of his retirement. His international fame also provided me
Throughout the 1960s and into the 1970s the techniques available to experimental immunologists were extremely limited compared with what the present day researcher expects to have at his or her disposal. This is highlighted by the following dates of the potential availability (not the time of discovery) of innovative technologies: • • • • • • • •
Flow cytometry (FACS) – 1974/1978 Monoclonal antibodies – 1975 Personal computers – 1980s Transgenic animals (mice) – 1982 PCR techniques – 1983 Knock-out animals (mice) – 1989 2G mobile phones – 1993 E-mail communication – 1990s
Progress depends heavily upon the tools available for investigation, and scrutiny of the papers published in the later years of the 20th century clearly reflects this relationship. 3. The appearance of the Journal of Reproductive Immunology In 1972 I had the opportunity to move to the Medical School at the University of Bristol in order to set up a research unit for reproductive immunology. This was the first unit to be so named, as hitherto the field had been referred to as “immunology of reproduction” or the “immunobiology of reproduction”. In the late 1970s, I was approached by two major international publishing houses to establish a new journal in this emerging field. After due consideration, I agreed a contract as Editor-in-Chief with Elsevier/North-Holland. Justification for a new publication was provided in the following extract from the editorial of the 1979 launch issue of the Journal of Reproductive Immunology: “Reproductive immunology has unquestionably been one of the most rapidly expanding areas of scientific enquiry in recent years. Its multiple origins have very largely been rooted in independent basic reproductive physiology and immunology and the increasing volume of information has, perhaps not surprisingly, been disseminated in a very wide range of journals. There can be few, if any, disciplines of comparable impact that do not have a central vehicle for the publication of their research material.” The enthusiastic support of Alan Beer (Dallas, Texas) as Associate Editor and the recruitment of a strong,
Please cite this article in press as: Billington, W.D., Origins and evolution of reproductive immunology: a personal perspective. J. Reprod. Immunol. (2014), http://dx.doi.org/10.1016/j.jri.2014.10.003
G Model JRI-2280; No. of Pages 4
ARTICLE IN PRESS W.D. Billington / Journal of Reproductive Immunology xxx (2014) xxx–xxx
committed group of international Editorial Board members (see below) ensured the early success of the venture. K.D. Bagshawe (London, U.K.), M.G. Baines (Kingston, Canada), M. Edidin (Baltimore, U.S.A.), R.P. Erickson (Ann Arbor, U.S.A.), W.P. Faulk (Charleston, U.S.A.), E.H. Goldberg (Albuquerque, U.S.A.), M.H. Johnson (Cambridge, U.K.), W.R. Jones (Adelaide, Australia), A.R. Sanderson (East Grinstead, U.K.), D.P. Stites (San Francisco, U.S.A.), K.S.K. Tung (Albuquerque, U.S.A.), G.A. Voisin (Paris, France), T.G. Wegmann (Edmonton, Canada), A.E. Wild (Southampton, U.K.). The papers published in this first issue, listed here, reflected the already wide-ranging interests in this field at that time. E.J. Jenkinson and R.F. Searle: Ia antigen expression on the developing mouse embryo and placenta. P.N. Goodfellow et al.: Analysis of anti-sperm sera for T/t locus-specific antibody. P.W. Slobodian et al.: The processing of T-lymphocytes by the gut of the suckling neonate. C. Pavia et al.: Suppression of murine allogeneic cell interactions by sex hormones. J.K. Kelly and H. Fox: The local immunological defence system of the human endometrium. P. Chateaureynaud et al.: Antagonistic maternal immune reactions (rejection and facilitation) to the embryo in the urodele amphibian Salamandra salamandra Lin. D.B. Morton and P.A. McAnulty: The effect on fertility of immunising female sheep with ram sperm acrosin and hyaluronidase. For many years the journal was published with quite a plain front cover. The title was in the dark blue of Oxford and the background was in the light blue of Cambridge. In America it was commonly referred to as “The Blue Journal”. Later issues were upgraded to a larger format and had more attractive and colourful designs. 4. Many old questions: many answers still needed Although the field has expanded enormously in the 35 years since the publication of this first issue of JRI, there are still many unsolved areas of enquiry. Here are some of the old questions: for how many of these do we now have definitive new answers? (1) What are the really essential immunological conditions for the establishment and maintenance of normal pregnancy? To what extent do these include (i) the foetal contributions, such as the regulation of trophoblast gene expression, and immunoregulatory signals to the mother and (ii) the maternal contributions, involving diverse adaptive and innate immunoregulatory mechanisms, especially those relating to the roles of the regulatory T cell populations (Tregs) and the uterine natural killer (uNK) cell populations? How can we distinguish relevant determinant factors from any epiphenomena generated by maternofoetal genetic incompatibilities or by the confusion of the diversity of experimental techniques employed to investigate these factors?
3
(2) Are failures in any of these assumed essential systems directly responsible for pregnancy losses, such as recurrent spontaneous miscarriage (RSM), or disorders such as pre-eclampsia? A common difficulty lies in distinguishing between cause and effect when identifying immunological changes in patients with such pathological conditions. How valid are studies on peripheral blood samples in determining events at the intra-uterine materno-foetal interface? (3) Can any such system failures be overcome by immunebased intervention therapies? The actual rationale for, as well as the safe and effective use of, such treatments as paternal or third-party leucocyte immunisation or immunoglobulin infusion for RSM is controversial to say the least. (4) Can safe and effective (and reversible) contraceptive vaccines be developed for global use against male or female reproductive antigens? Despite enormous investments in time and funding these goals remain elusive. It was in fact as long ago as 1965 that the World Health Organisation (WHO) first indicated the need to develop programmes to investigate this aspect of fertility control. Hopes have been pinned primarily upon vaccines based upon spermatozoal antigens and human chorionic gonadotrophin (hCG), but none has proved acceptable for clinical application.
Significant advances have clearly been made in recent decades in our understanding of the mechanisms involved in immunological aspects of male and female normal and pathological reproductive processes. Much, however, remains to be resolved. It is encouraging that so many researchers worldwide are tackling these problems. But their efforts have not been helped by the persistent increase in the bureaucracy imposed by their institutions and funding agencies, demanding frequent reports, reviews, research assessment exercises and increasing the publication pressures. It may just be of small comfort to recognise that this is not at all a recent phenomenon. The following quotation from the German physician and statesman, Rudolph Virchow, in 1865, succinctly encapsulates the issue: “In the past year we have been so extensively authorised, inspected, approved, renovated, evaluated, visited, consulted, circularised, informed; and have completed so many forms, orders, questionnaires and reports that no medical progress has been made.” To paraphrase what our French friends would say: “The more things change, the more they stay the same.” Nevertheless, despite this, significant progress in the field of reproductive immunology will surely continue with the combined efforts of dedicated researchers on the international platform.
Conflict of interest The author declares that there is no conflict of interest.
Please cite this article in press as: Billington, W.D., Origins and evolution of reproductive immunology: a personal perspective. J. Reprod. Immunol. (2014), http://dx.doi.org/10.1016/j.jri.2014.10.003
G Model JRI-2280; No. of Pages 4
ARTICLE IN PRESS W.D. Billington / Journal of Reproductive Immunology xxx (2014) xxx–xxx
4
References Bratanov, K., et al., 1949. Sur la formation des spermoanticorps dans l’organisme des animaux domestiques. Ann. Acad. Rurale “G. Dimitrov,” Fal. Med. Vet. 26, 321–334 (Bulg. Res. Fr.). Isojima, S., et al., 1968. Immunologic analysis of sperm-immobilizing factor found in sera of women with unexplained sterility. Am. J. Obstet. Gynecol. 101, 677–683.
Mechnikov, I., 1899. Etudes sur la resorption des cellules. Ann. Inst. Pasteur 13, 737–769. Medawar, P.B., 1953. Some immunological and endocrinological problems raised by the evolution of viviparity in vertebrates. Symp. Soc. Exp. Biol. 7, 320–338.
Please cite this article in press as: Billington, W.D., Origins and evolution of reproductive immunology: a personal perspective. J. Reprod. Immunol. (2014), http://dx.doi.org/10.1016/j.jri.2014.10.003
ARTICLE IN PRESS
JRI-2280; No. of Pages 4
Journal of Reproductive Immunology xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Journal of Reproductive Immunology journal homepage: www.elsevier.com/locate/jreprimm
Origins and evolution of reproductive immunology: a personal perspective W. David Billington ∗ School of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK
a r t i c l e
i n f o
Article history: Received 7 September 2014 Received in revised form 13 October 2014 Accepted 21 October 2014
a b s t r a c t This is a brief personal assessment of the origins and development of the field of reproductive immunology from the 19th century to the present day, with special reference to the founding of the Journal of Reproductive Immunology in 1979. © 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: History Reproductive immunology
1. Early beginnings Following the generous brief afforded me by the conference organisers, this is a short and personal assessment of the origins and evolution of the field that we now know as reproductive immunology, and that have been the mainstay of my professional academic career for over 40 years. Although everyone will likely have their own views on the origins of most specialist subjects, for me the landmark studies leading to the emergence of enquiries into the immunology of reproductive processes are those pursued by the Russian biologist Ilya Mechnikov (1845–1916) and later by the Austrian biologist and physician Karl Landsteiner (1868–1943). For his work on phagocytosis, showing the engulfment and destruction of bacteria by white blood cells, Mechnikov was awarded the Nobel Prize in 1908. These findings eventually led to the recognition of Fc receptor-dependent uptake by macrophages. Landsteiner classified the ABO blood groups by identifying the presence of agglutinins, and later also identified the rhesus
∗ Tel.: +44 1275372329. E-mail address: [email protected]
factor. He was awarded the Nobel Prize in 1930. His work thus laid the foundation for arguably the most important clinical contribution that reproductive immunology has ever made, the recognition of rhesus haemolytic disease of the foetus and newborn and its treatment by injection of anti-D antibody.
2. Anti-sperm antibodies and infertility Although spermatozoal immunogenicity was first recognised by Mechnikov as long ago as 1899, only very sporadic confirmatory studies were reported in widely scattered literature during the early decades of the 20th century. The relationship between antisperm antibodies and infertility was first established in domestic animals (heifers) by Bratanov et al. (1949). The detailed studies of Guy Voisin and his colleagues in the early 1950s demonstrated the experimental induction of autoimmune aspermatogenesis in guinea pigs, and the existence of several spermatozoal autoantigens. In 1959, Rumke reported the association between the presence of anti-spermatozoal antibodies and clinical infertility in human males. These early studies provided the foundation for an explosion of
http://dx.doi.org/10.1016/j.jri.2014.10.003 0165-0378/© 2014 Elsevier Ireland Ltd. All rights reserved.
Please cite this article in press as: Billington, W.D., Origins and evolution of reproductive immunology: a personal perspective. J. Reprod. Immunol. (2014), http://dx.doi.org/10.1016/j.jri.2014.10.003
G Model JRI-2280; No. of Pages 4
ARTICLE IN PRESS W.D. Billington / Journal of Reproductive Immunology xxx (2014) xxx–xxx
2
interest in the identification of the molecular structure of sperm surface antigens and their precise role in the induction of infertility in both males and females, and as potential candidates for immunocontraceptive vaccines. Isojima et al. (1968) were pre-eminent from an early stage in this extensive search. It is, however, a cause of disappointment that after so many decades these goals have still not been satisfactorily achieved. Much less is known about female gamete antigens and their relevance in fertility and infertility.
with unexpected opportunities early on. The similarity of our surnames, together with the fact that he had previously worked in the same Oxford department as myself, and in a similar area of research, led to invitations for me to attend and participate in some conferences and symposia that were intended by the organisers to benefit from Bill’s presence! He was greatly amused by this mistaken identity and most generous to me in his later recognition of these missed occasions. 2.2. New technologies
2.1. Immunology of pregnancy A defining moment in the evolution of the field of reproductive immunology came in 1953, when Peter Medawar published the text of his invited lecture to the British Society for Experimental Biology, in which he identified the truly paradoxical nature of the immunological relationship between the pregnant mother and her antigenically foreign foetus. Although Medawar later won the Nobel Prize for his pioneering work establishing the laws of transplantation immunology, he never followed up by experimentation his insightful suggestions as to how the semi-allograft of the foetus and placenta might be able to circumvent the expected recognition and rejection reactions of the immunologically competent pregnant female. Interestingly, it was one of his Oxford graduate students, Rupert (Bill) Billingham, who was, from the next decade onwards, to make significant contributions to an understanding of this problem (see below). My own entry into this field was in 1960, when I was offered the opportunity to begin a graduate studentship with Professor Rogers Brambell, whose group was principally involved in studying the transmission of passive immunity from mother to young, indicating that the mechanism for the selective transport of immunoglobulins resided in the presence of specific receptors for the Fc region of the molecules on the surface of the transmission site, be it neonatal gut, yolk sac or placenta, depending upon the species. My own project was in a different direction, examining the effect of genetic disparity between mother and foetus on the development and growth of the murine placenta. This led to the publication of my first paper in 1964. It was submitted to the journal Nature, had no reference list, and was reviewed, accepted and published in little more than three weeks. I assumed at the time that this was quite normal. How wrong I was! I then joined David Kirby in Oxford to begin a most fruitful and enjoyable collaboration, extending our studies into a variety of topics on the immunology of pregnancy, with special interest in the trophoblast. During this period in the 1960s I became acquainted with, and enjoyed the friendship of, Bill Billingham. He had by then moved to the United States and established a most successful group in Dallas, investigating, inter alia, the uterus as an immunologically privileged site. Together with his colleague, Alan Beer, and others, he made many important advances in several immunological aspects of reproduction, and published one of the earliest and most successful books in this field. He was unquestionably a leading figure right up to the time of his retirement. His international fame also provided me
Throughout the 1960s and into the 1970s the techniques available to experimental immunologists were extremely limited compared with what the present day researcher expects to have at his or her disposal. This is highlighted by the following dates of the potential availability (not the time of discovery) of innovative technologies: • • • • • • • •
Flow cytometry (FACS) – 1974/1978 Monoclonal antibodies – 1975 Personal computers – 1980s Transgenic animals (mice) – 1982 PCR techniques – 1983 Knock-out animals (mice) – 1989 2G mobile phones – 1993 E-mail communication – 1990s
Progress depends heavily upon the tools available for investigation, and scrutiny of the papers published in the later years of the 20th century clearly reflects this relationship. 3. The appearance of the Journal of Reproductive Immunology In 1972 I had the opportunity to move to the Medical School at the University of Bristol in order to set up a research unit for reproductive immunology. This was the first unit to be so named, as hitherto the field had been referred to as “immunology of reproduction” or the “immunobiology of reproduction”. In the late 1970s, I was approached by two major international publishing houses to establish a new journal in this emerging field. After due consideration, I agreed a contract as Editor-in-Chief with Elsevier/North-Holland. Justification for a new publication was provided in the following extract from the editorial of the 1979 launch issue of the Journal of Reproductive Immunology: “Reproductive immunology has unquestionably been one of the most rapidly expanding areas of scientific enquiry in recent years. Its multiple origins have very largely been rooted in independent basic reproductive physiology and immunology and the increasing volume of information has, perhaps not surprisingly, been disseminated in a very wide range of journals. There can be few, if any, disciplines of comparable impact that do not have a central vehicle for the publication of their research material.” The enthusiastic support of Alan Beer (Dallas, Texas) as Associate Editor and the recruitment of a strong,
Please cite this article in press as: Billington, W.D., Origins and evolution of reproductive immunology: a personal perspective. J. Reprod. Immunol. (2014), http://dx.doi.org/10.1016/j.jri.2014.10.003
G Model JRI-2280; No. of Pages 4
ARTICLE IN PRESS W.D. Billington / Journal of Reproductive Immunology xxx (2014) xxx–xxx
committed group of international Editorial Board members (see below) ensured the early success of the venture. K.D. Bagshawe (London, U.K.), M.G. Baines (Kingston, Canada), M. Edidin (Baltimore, U.S.A.), R.P. Erickson (Ann Arbor, U.S.A.), W.P. Faulk (Charleston, U.S.A.), E.H. Goldberg (Albuquerque, U.S.A.), M.H. Johnson (Cambridge, U.K.), W.R. Jones (Adelaide, Australia), A.R. Sanderson (East Grinstead, U.K.), D.P. Stites (San Francisco, U.S.A.), K.S.K. Tung (Albuquerque, U.S.A.), G.A. Voisin (Paris, France), T.G. Wegmann (Edmonton, Canada), A.E. Wild (Southampton, U.K.). The papers published in this first issue, listed here, reflected the already wide-ranging interests in this field at that time. E.J. Jenkinson and R.F. Searle: Ia antigen expression on the developing mouse embryo and placenta. P.N. Goodfellow et al.: Analysis of anti-sperm sera for T/t locus-specific antibody. P.W. Slobodian et al.: The processing of T-lymphocytes by the gut of the suckling neonate. C. Pavia et al.: Suppression of murine allogeneic cell interactions by sex hormones. J.K. Kelly and H. Fox: The local immunological defence system of the human endometrium. P. Chateaureynaud et al.: Antagonistic maternal immune reactions (rejection and facilitation) to the embryo in the urodele amphibian Salamandra salamandra Lin. D.B. Morton and P.A. McAnulty: The effect on fertility of immunising female sheep with ram sperm acrosin and hyaluronidase. For many years the journal was published with quite a plain front cover. The title was in the dark blue of Oxford and the background was in the light blue of Cambridge. In America it was commonly referred to as “The Blue Journal”. Later issues were upgraded to a larger format and had more attractive and colourful designs. 4. Many old questions: many answers still needed Although the field has expanded enormously in the 35 years since the publication of this first issue of JRI, there are still many unsolved areas of enquiry. Here are some of the old questions: for how many of these do we now have definitive new answers? (1) What are the really essential immunological conditions for the establishment and maintenance of normal pregnancy? To what extent do these include (i) the foetal contributions, such as the regulation of trophoblast gene expression, and immunoregulatory signals to the mother and (ii) the maternal contributions, involving diverse adaptive and innate immunoregulatory mechanisms, especially those relating to the roles of the regulatory T cell populations (Tregs) and the uterine natural killer (uNK) cell populations? How can we distinguish relevant determinant factors from any epiphenomena generated by maternofoetal genetic incompatibilities or by the confusion of the diversity of experimental techniques employed to investigate these factors?
3
(2) Are failures in any of these assumed essential systems directly responsible for pregnancy losses, such as recurrent spontaneous miscarriage (RSM), or disorders such as pre-eclampsia? A common difficulty lies in distinguishing between cause and effect when identifying immunological changes in patients with such pathological conditions. How valid are studies on peripheral blood samples in determining events at the intra-uterine materno-foetal interface? (3) Can any such system failures be overcome by immunebased intervention therapies? The actual rationale for, as well as the safe and effective use of, such treatments as paternal or third-party leucocyte immunisation or immunoglobulin infusion for RSM is controversial to say the least. (4) Can safe and effective (and reversible) contraceptive vaccines be developed for global use against male or female reproductive antigens? Despite enormous investments in time and funding these goals remain elusive. It was in fact as long ago as 1965 that the World Health Organisation (WHO) first indicated the need to develop programmes to investigate this aspect of fertility control. Hopes have been pinned primarily upon vaccines based upon spermatozoal antigens and human chorionic gonadotrophin (hCG), but none has proved acceptable for clinical application.
Significant advances have clearly been made in recent decades in our understanding of the mechanisms involved in immunological aspects of male and female normal and pathological reproductive processes. Much, however, remains to be resolved. It is encouraging that so many researchers worldwide are tackling these problems. But their efforts have not been helped by the persistent increase in the bureaucracy imposed by their institutions and funding agencies, demanding frequent reports, reviews, research assessment exercises and increasing the publication pressures. It may just be of small comfort to recognise that this is not at all a recent phenomenon. The following quotation from the German physician and statesman, Rudolph Virchow, in 1865, succinctly encapsulates the issue: “In the past year we have been so extensively authorised, inspected, approved, renovated, evaluated, visited, consulted, circularised, informed; and have completed so many forms, orders, questionnaires and reports that no medical progress has been made.” To paraphrase what our French friends would say: “The more things change, the more they stay the same.” Nevertheless, despite this, significant progress in the field of reproductive immunology will surely continue with the combined efforts of dedicated researchers on the international platform.
Conflict of interest The author declares that there is no conflict of interest.
Please cite this article in press as: Billington, W.D., Origins and evolution of reproductive immunology: a personal perspective. J. Reprod. Immunol. (2014), http://dx.doi.org/10.1016/j.jri.2014.10.003
G Model JRI-2280; No. of Pages 4
ARTICLE IN PRESS W.D. Billington / Journal of Reproductive Immunology xxx (2014) xxx–xxx
4
References Bratanov, K., et al., 1949. Sur la formation des spermoanticorps dans l’organisme des animaux domestiques. Ann. Acad. Rurale “G. Dimitrov,” Fal. Med. Vet. 26, 321–334 (Bulg. Res. Fr.). Isojima, S., et al., 1968. Immunologic analysis of sperm-immobilizing factor found in sera of women with unexplained sterility. Am. J. Obstet. Gynecol. 101, 677–683.
Mechnikov, I., 1899. Etudes sur la resorption des cellules. Ann. Inst. Pasteur 13, 737–769. Medawar, P.B., 1953. Some immunological and endocrinological problems raised by the evolution of viviparity in vertebrates. Symp. Soc. Exp. Biol. 7, 320–338.
Please cite this article in press as: Billington, W.D., Origins and evolution of reproductive immunology: a personal perspective. J. Reprod. Immunol. (2014), http://dx.doi.org/10.1016/j.jri.2014.10.003
