GNRH2011: 50 years of the human clinical use of gonadotrophins

Salzburg, 8 February 2011

In 1961 the first baby was born after being treated by Professor Bruno Lunenfeld with Pergonal, the first human gonadotrophin drug that enabled ovulation to take place.  Until then the many causes of infertility were not fully understood, and there was little that could be done for women unable to conceive.

Professor Bruno Lunenfeld at the 10th GnRH symposium in Salzburg, February 2011

Fifty years later assisted reproductive technologies are today common place thanks to Professor Lunenfeld. He was part of the team which, in the 1950s, unraveled the workings of gonadotrophins and consequently paved the way for their use in the treatment of infertility, including therapies facilitating IVF to this day.

The 50th anniversary of this clinical breakthrough in the field of fertility was celebrated at the 10th International Symposium on GnRH, in Salzburg, in early February.

Any regrets?

It was my privilege to speak with Professor Lunenfeld at the meeting and, rather than asking him to reflect on his long and distinguished career, I chose to enquire if there was anything – looking back – that he would have done differently or, indeed, felt he could have done better?

“Yes, most probably there was”, responded Lunenfeld. “Professor MC Shelesnyak, who was at the Weizmann Institute, invited me to join him there, whilst I was still in the army. He was working on implantation and had just discovered a very interesting situation that with Ergocornine and Ergocryptine he could inhibit implantation in rats and mice and had started to think about how to work on this in humans. So I joined the Weizmann Institute in 1957 and we started working on this, but my interest was still also, on one hand, on gonadotrophins, so we developed an anti-serum to hCG and thought this was a good idea because with this we could again influence  implantation”, said Lunenfeld.

A change of direction

“As I continued to work with  Professor Shelesnyak” continued Lunenfeld “suddenly Professor Harel, the head of endocrinology at the Sheba Medical Centre, was appointed as the Israeli Ambassador to Romania, and I was offered the position to replace him at the hospital. I quickly deduced that someone who gets to be an ambassador will never return as a head of a hospital department, if anything he’d return as head of the hospital itself.

“So, I accepted the appointment even though the scientists at the Weizmann Institute called me a prostitute accusing me of leaving basic research for this silly clinical work. But I did it, and that is how I stopped my work on implantation and continued my work very rapidly on gonadotrophins. The latter moved forward with the help of grants from the Population Council, the Ford Foundation, and the NIH. This enabled us to develop human menopausal gonadotrophins together with Piero Donini from the R&D department of Serono, finally helping so very many infertile women – and of course our work has, directly and indirectly, resulted in the birth of more than four million babies.

“But today I am very sorry that I didn’t continue the work on implantation because, as I told Professor Shelesnyak back in 1958, I wasn’t working on implantation only to prevent pregnancies; I also wanted to study implantation because I wanted to prevent metastasis implanting anywhere in the body”, said Lunenfeld.

Six years later in Chicago when he met Professor Melvyn Cohen, who was doing the first laparoscopies and showed him endometriotic tissue in the pelvis, Lunenfeld commented:

“Listen! This is a very interesting thing, maybe we should work on implantation and then  we could probably prevent implantation of endometriosis wherever it comes from?”

But no one took up to baton.

Any chance of going back to work?

It was too tempting not to ask this energetic professor what is now stopping him from returning to the work of implantation, a question which he responded to in good humour.

“You know, at my age today at 84, I don’t think that anybody would ever give me any funds to work in a laboratory, so I can only use my brain to analyse data, which is coming out and give advice to other people who do research. But personally, unfortunately, my research period in the lab, on the bench, has ended.  However, I think there are enough good people around, and I am always happy to discuss things and I talk to those who wish to discuss science since it is an intellectual exercise for me.  But whereas I would be delighted to help anywhere I can, I think younger people should go do these things themselves and my generation should only act as advisors or consultants”, responded Lunenfeld.

So, what about endometriosis?

This website is about endometriosis, so the obvious question to the professor was: “what do you see as the the single most important thing that has happened in the field of endometriosis in last 50 years?”

Professor Lunenfeld didn’t hesitate with his response:

“Since the discovery of modern laparoscopy and laparoscopic surgery I think that nothing much new has happened, unfortunately. We still do not know enough about this disease. We still do not know how it develops and even when it starts. You know there are the three theories, which probably all have some kind of validity. There is retro-implantation of menstrual blood. There is a more logical theory, the genetic theory, as well as an environmental theory. I think that all of these have something to do together but the entire story of course we do not know yet. I am sure that working on factors which can control angiogenesis and factors which can prevent implantation have a future. We are learning to control pain through certain progestogen agents and GnRH analogues, as we have also heard during this meeting, but for the time being the only thing that we really have, and which really works, is surgical removal of the disease. Through laparoscopy you can diagnose and treat at the same time, removing lesions as good as you can.  But it is still surgery and I only hope in the very near future endometriosis can be treated medically”.

Where are we going?

It was irresistible not to ask an 84-year old trail brazer if he has any idea of what life is all about and where we are going and what we are here for ….and, before I can finish my ramblings he interrupts me and states quite firmly that: “This is very interesting, because for me adult life started at the age of 11 when I was forced to leave  home. My father gave me five pieces of advice:

  1. Never underestimate anyone;
  2. Respect everyone;
  3. Keep your dignity at all times;
  4. Do not expect anything from others – don’t ever ask what others can do for you, but what you can do for others (just like JF Kennedy said it, except my father said it long ago before to me!);
  5. Try to be as honest as possible.

“I took these five messages with me all my life and I tried to live by them. This was my youth. When I became older and a student I was influenced by Jean Paul Sartre, of course, and learned that we had to live for today because we do not know what tomorrow brings. This again influenced my way of life and how I look at life. I am thankful every morning that I am alive and I try to enjoy my current situation.

“Finally, I was influenced by Professor De Watteville, who was my chief and boss, and who really showed me how to think onwards; but, in the end, it is all about what my mother always told me. In German you say Der Mensch denkt und Gott lenkt (man thinks but God decides). Whatever you call God – or whether it is: god, destination, nature, whatever… – I think this is the way we have to look at life.  For me this means continuing to live in good health and with dignity. That is all”, concluded Professor Lunenfeld.

Who can argue with wisdom like this?
Anyone ready to catch – and carry on – the baton?

Further reading

Baby boomer” article by Bernard Dichek for Israel21c, 8 February 2011

Lunenfeld B. Historical perspectives in gonadotrophin therapy. Hum Reprod Update 2004;10(6):453-67.

In celebration: 50 years of the clinical use of human gonadotrophins. RBM Online 2011;22 Supplement 1

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