Egon and Ann Diczfalusy Foundation

Egon Diczfalusy’s life can best be described as comprehending five major epochs:

• Growing in his native Hungary and moving from the far north, to the far south of the Country.
• Moving to Stockholm and transforming the Hormone Laboratory of the Karolinska Institute and Hospital in a world renown research Center.
• Initiating a great scientific adventure by founding at the World Health Organization in Geneva, the first and still largest research program ever launched by the Organization. Today this has developed into the UNDP, UNICEF, UNFPA, WHO, World Bank, Special Program of Research in Human Reproduction.
• Moving into a very active retirement dedicated to the needs of an ageing humanity.
• Creating the Egon and Ann Diczfalusy Foundation (nicknamed ‘ED phone home’), for the support of scientific work conducted in the field of Reproductive Health.

First epoch

The first epoch of ED life started in Miskolc where he was born on 19 September 1920 in a family with a military tradition. His father was a high ranking army officer in the newly independent Hungary. Like several members of his family, Egon, while studying, joined the military as part of the compulsory service, as shown in Figure 2. It was the time in between the two World Wars, a special period for Hungary, marked by independence from the Habsburg Empire and two revolutions in 2 years. When Egon was a teenager, the family moved to Szeged, where he grew-up and eventually graduated in Medicine.

In an autobiographic lecture given in 1978 (the sir Henry Dale lecture) [1], he provided an interesting picture of his second decades: “How did I become a reproductive endocrinologist? By the Hungarian approach. As a second year medical student at the University of Szeged, I was working in the Department of Pathology and Bacteriology of Professor György Ivánovics and my first task was to repeat a study by the Nobel laureate Prof. Hans von Euler and his co-workers in Stockholm, who found transaminase activity in suspensions of yeast and E. Coli bacilli”. He went on explaining:

“I just could not confirm their findings and my Professor felt that I must publish this. This negative report [2] was my first publication; it was probably instrumental in bringing me to Stockholm after the war, when I had the privilege of working as professor Hans von Euler’s assistant during the years 1946-1947”.

Second epoch

This is how, described by his own words, the second and most productive epoch of his life started. Moving to Stockholm and going to work at the Institute for Organic- Chemical Research directed by Professor Hans von Euler, was no small achievement, since in 1929 he had won the Nobel Prize in Chemistry with Arthur Harden for their investigations on alcoholic fermentation of carbohydrates and the role of enzymes. Together they published on the resistance to streptomycin induced in vitro [3]. While working in Stockholm, ED still collaborated with his alma Mater in Szeged, as shown by an article published in 1948 [4]. Von Euler soon retired and ED accepted an offer by Professor Axel Westman, the head of the Department of Obstetrics and Gynecology at the Karolinska University Hospital and a second father to Egon. He was his mentor, guiding him in the world of research and asking him to create a Laboratory in his Department dedicated to hormones. Axel Westman was famous for his studies on tubal motility in rabbits; he created a small glass window into the abdomen and registered the tubal movements during 24 hours or longer [5]. As ED recounted, he was also his master in teaching him the real Swedish way of drinking both folkconjac (the cheap variant) and genuine Martell. Professor Westman died prematurely in 1960 and Egon was on its own.

By 1948, ED published his first paper in the field that would become the cornerstone of his scientific life: an investigation on the effect of gonadotrophin stimulation of rabbit ovaries [6]. In fact, his early work was on gonadotrophins and his doctorate thesis was on “Chorionic gonadotrophin and oestrogens in the placenta” [7]. Within ten years ED had become an authority in reproductive endocrinology and PubMed lists 55 articles written by him and his collaborators in the decennium 1950–9.

The nineteen sixties have represented the most productive years in ED life. Thanks to a system he designed to perfuse human fetuses from mid-trimester abortions (during those times this was legal and permissible in Sweeden, which is not the case now) and under his leadership, the Hormonlaboratoriet became one of the leading institutions in the area of steroid hormone biogenesis and metabolism [8]. This new field of investigation had been opened at the beginning of the XX century, possibly by Halban, who investigated the inner secretions of the ovary and the placenta [9]. During the first half of the XX century a now classic concept was developed; it postulated that, stating from the beginning of the second trimester of pregnancy, a “temporary endocrine organ”, the placenta, carried out most of the greatly increased steroid biosynthesis at mid-gestation. However, it was Diczfalusy who discovered the close inter- relationship between the fetus and the placenta [10, 11]. He was the first to understand that certain steroids present in the urine of pregnant women were in fact mainly metabolites of placental origin, whereas others seemed mainly of maternal production. Starting from these premises, Diczfalusy and his group developed a new concept: the creation during pregnancy of a functional unit made-up of an incomplete steroidogenetic organ (the placenta), interposed between a complete steroid metabolic system (the maternal organism) and a second incomplete system (the fetus). The unique characteristic of the latter is its ability to compensate for the deficiencies of placental enzyme systems [12].

His eminent position in the new discipline was instrumental in receiving one of the largest Ford Foundation Grants in Reproductive Endocrinology of those days: one half million

dollars to study Steroid biogenesis and metabolism in the human fetus, placenta and maternal organism [12]. I had the privilege of being part of the first group of some 75, mostly foreign, scientists who worked with him and mapped steroid metabolism at midterm (Figure 3). In addition, as one of the early foreign scientists, I not only participated in this unique scientific adventure, but even joined ED in summarizing the new knowledge about estriol biogenesis and metabolism [13].

Third epoch

By the beginning of the nineteen seventies, a third epoch in ED life began: he had started to collaborate with a new, small Unit in the World Health Organization in Geneva dedicated to Human Reproduction and, together with its young chief Alex Kessler, he conceived the idea of a Research Program under the WHO’s egis to address the issue of population explosion that, in those days, had taken top priority in the international scene. An initial grant from the Ford Foundation, followed by another grant from the Swedish government, jump-started what became known as the WHO Expanded Program of Research, Development and Research Training in Human Reproduction (HRP). His Laboratory then became one of the WHO Research and Training Centers of the Program; among the achievements of this Center was the holding of the Karolinska Symposia on Research Methods in Reproductive Endocrinology [14], held under a grant from the Ford Foundation. In a Book published in 1997, ED presented in chronological sequence, the full text of 17 of his previously published papers with a brief introduction for each. Collectively, these articles provide a unique review of contraceptive science and practice by a true protagonist of the world effort to control the population explosion [15].

Such an international effort represented a new development in international cooperation and, using ED own words:

“A modern interpretation of history is said to be based on the analysis of the history of ideas. The history of the second part of the 20th century represents an entirely new departure in this respect: for the first time in the history of mankind the policies emerging from World Conferences organised by the various Specialised Agencies of the United Nations broadened views and perceptions”.

HRP was structured in Task Forces and ED was involved in most of them, travelling to the four corners of the world. The Steering Committee of one of these Task Forces is portrayed in Figure 4.

Over the years, the WHO Expanded Program, became the first and best known UN interagency research effort, today known as the “UNDP, UNFPA, UNICEF, WHO, World Bank, Special Program of Research, Development and Research Training in Human Reproduction”. ED was the first to summarize the program’s achievements [16]. In opening the 15th anniversary celebrations he challenged all participants by saying: “I myself represent the future. Yes, you heard right, I said the future. I represent the future of the past. As Paul Valéry puts it: “Are you not the future of all memories stored within you? The future of the past”. Ten years later, to honor its cofounder’s Alma Mater, the 25th anniversary of HRP was celebrated in Szeged, that is also the location of one of the WHO Collaborating Centers in Human Reproduction [17]. A further summary of the achievements of this Program was presented on the occasion of its fortieth anniversary in 2012 [18].

Fourth epoch

Times passed quickly and the fourth epoch of his life approached. When ED turned 75, the WHO Director of Personnel decided that, for bureaucratic reasons, he could no longer serve as a Senior Consultant. So, after some 25 years of service to WHO, ED left the Special Program, but not the Organization, since, instead of retiring to Rönninge, he decided to start a new phase of his life, a decade that I will call “the World Time”, not because he wasn’t in the world arena before; rather, because he truly became the epitome of a world citizen [19]. ED started to collaborate as an Advisor (a bureaucratic definition that carried no age limit) with the WHO Division dealing with ageing and, in a small way, I followed him even in this new endeavor. Together, although he did most of the work, we wrote a chapter for the II World Report on Women’s Health, published by FIGO, the International Federation of Gynecology and Obstetrics [20]. The topic assigned to us was “women’s longevity” and, thanks to his broad vision of the issue, we were able to point out the wide range of disabilities and sicknesses, as well as the very high demands that an ageing population would bring to health systems already stressed in many countries. We described the major landmarks on the road to a greater awareness; this new reality had been brought to the world’s attention when the UN convened a World Assembly on ageing in 1982. The Plan of Action adopted at the end of the Assembly pointed to the fact that “the fundamental and inalienable rights enshrined in the Universal Declaration of Human Rights, apply fully and undiminishedly to the aging” [21].

In the decade across the two millennia, ED he published essays on broad issues, with a vision of the future that seemed almost impossible for a person of his age. He wrote: “The wind of new realities is blowing with increasing strength. It is up to us to decide whether we prefer protective windscreens or new types of windmills” [22]. For himself. He never cherished protective windscreens, being always out where “the action is” and, being a strong promoter of international collaboration and cooperation, he wrote extensively on the topic. I will quote two sentences summarizing his view on the subject: “A modern interpretation of history is said to be based on the analysis of the history of ideas. The history of the second part of the twentieth century represents an entirely new departure in this respect; for the first time in the history of mankind the policies emerging from World Conferences organized by the various Specialized Agencies of the United Nations broadened the views and perceptions of many Member States (including donor governments) and significantly influenced their policies” [16]. “Our time is the first since the dawn of civilization in which people have dared to think it practicable to make the benefits of civilization available to the whole human race (a quote from A. Toynbee)” [22].

In his later years he had not forgotten the issue so dear to his heart: “The Contraceptive Revolution” [23], but he also became aware of the fact that in Western Countries, ageing was coupled to a fertility below replacement and lectured extensively on the topic. He summarized the new reality with the words:

“Quo vadimus? To many grandparents for too few grandchildren” [24].

Fifth epoch

Paraphrasing a famous movie, I have labeled the fifth epoch and last 15 years of Diczfalusy’s life “ED phone home”, because, after leaving the world of formal work, at age 85, he turned to his Alma Mater in Szeged and wanted to organize a major Conference there. He asked me to help him, but I had a different idea: seek the financial help of all his former students and friends and organize a Foundation in his name and in that of his wife Ann, who had for decades been the “Custodian Angel” of the Globetrotter Egon (Figure 5). After some hesitation, he accepted and decided that he will use for this purpose what his friends and former students had donated together with the money he received in 1996 when he was honoured with the Prince Mahidol Award from the Royal Family of Thailand.

Clearly, his many years in Sweden had not made him forget his Hungarian origin and culture and, being born in 1920, he had direct knowledge of the consequences of the breaking down of the Austro-Hungarian Empire. Hungarians had long dreamed of becoming independent, but what followed was not what many had hoped: they went through many political changes and regimes to several decades of Communist rule.

So, we went to work on a simple, while at the same time revolutionary, idea of ED: breaking the historical barriers existing between the countries of Eastern Europe and in particular those in the region surrounding Hungary. Diczfalusy wanted to bring together the countries of the region around Hungary and I wanted to create a long-lasting legacy for his name, through such an achievement. This is how the Foundation was born.

In 2007, ED visited Szeged and discussed the legal and procedural aspects of the new Foundation with Pál Attila, at the time the Chairman of the Department of Gynecology and Obstetrics at the Albert Szentgyörgyi University, and with Bártfai György, Professor in the Department and a former ED student. The latter was given the task of identifying issues related to creation of the Foundation and to work with the lawyer and Hungarian authorities. Eventually, Pál Attila became the first President and Bártfai György one of the Vice-Presidents.

The Foundation had Egon Diczfalusy’s imprinting. Its Mission Statement reads:

“The Foundation’s mission is to promote Reproductive Health in Central-Eastern Europe by facilitating support for the development of new scientific programs and establishing and supporting opportunities and a Forum for the publication of scientific results and for organizing scientific conferences. In the course of these activities, it aims to create opportunities for internationally acclaimed scientists and young researchers to build fruitful professional relationships and present their latest scientific achievements. In the course of fulfilling its mission, the Foundation specifically supports scientific research in the Central European Region, with a special focus on young scientists”.

The Foundation grants yearly awards to encourage young research fellows doing research in the female healthcare arena and also a lifetime award for senior researchers from all over the world for their achievements on the field. These awards are handed over at the Annual Meeting of the Foundation that is accompanied by a high-level scientific program with top speakers and international participation.

The birth of the Foundation was celebrated by a Symposium attended by well-known scientists from all over the world (Figure 6).

On his 90th birthday, one of the members of the very active “Young Diczfalusy Fellows” section of the Foundation, Cristian Furau, published a Book providing an excellent summary of ED life and achievements [25]

Summaries

I would like to conclude this brief picture of a man who guided three generations of reproductive scientists and forever shaped their approach to research, by mentioning Leonardo da Vinci, one of the greatest genius humanity has known, who said:

“Tristo è quel discepolo che non supera il suo maestro.”
(unworthy is the disciple who does not overtake his master).

Unfortunately, none of his students ever overtook him!

References

Download Full Article

• Giuseppe Benagiano: Egon Diczfalusy on 100^th anniversary of his birth (2020, Journal of Hungarian Obstetricians and Gynaecologists, PDF, 8 pages, English/Hungarian, 2.6MB)