The Good Father

He was the first to prescribe a fertility drug called Pergonal for women, although he never thought to apply for a patent. But Prof. Bruno Lunenfeld is not discouraged. On the contrary: He is thinking about launching a new revolution - this time, for men

Prof. Bruno Lunenfeld has two sons and eight grandchildren. He is a warm family man - an enthusiastic grandfather, a loving father and, after five years of marriage, appears head over heels in love with his second wife, Penina Meltzer. When he recalls his first wife, who died 10 years ago - "Shoshana, my first, great love" - his eyes fill with tears. "I am a very emotional person," he apologizes.

But in addition to his own personal offspring, Lunenfeld is also responsible for the birth of "about a million children, a very cautious estimate." None of them would have been born if Lunenfeld had not developed the drug known as Pergonal which, together with its derivatives (Metrodin, Gonal-f, Genetic LH, Puregon, Luveris), also developed by Lunenfeld, serve as the basis for all fertility treatments given to women in the past 40 years.

The first pregnancy in the world that occured as the result of fertility treatments took place in Israel in 1961. Lunenfeld, then a physician at the Sheba Medical Center at Tel Hashomer, tried out the drug he invented on a woman, who until then had been considered completely infertile. He supervised the dispensation of the drug and its dosage on a daily basis and nine months later, she gave birth to a little girl. The next two births - involving two women who until then had also been considered infertile - also came about as a result of treatment with Pergonal at Sheba.

Only after that did the news of the fertility treatments become public, partly due to Lunenfeld's abundant medical connections outside Israel's borders. In the meantime, Instituto Farmacologico Serono, the Italian pharmaceutical company that manufactured Pergonal according to Lunenfeld's research, became the third largest biotechnological company in Europe.

"Within a few years, they made their first billion," recalls Lunenfeld. "I, of course, did not make a penny, but I was very happy."

A fact that adds even more charm to the story of Pergonal is that when Lunenfeld conducted the research that resulted in the drug, he was not yet a qualified doctor and would hop over to Italy for meetings with businessmen and representatives of the Vatican only to rush back to his third-year medical studies at the University of Geneva, where he lived on a scholarship provided by the Jewish Agency.

A staged funeral

Princes and popes, the Holocaust, hard work and world renown all played roles in the life of Lunenfeld, a man with an amazing talent for understatement. At the age of 76, he is still invited to give at least 80 lectures annually.

"I forgo the $30,000 I am offered for each lecture and make do with just having my wife's and my expenses covered, which means flights only in first class with a seat that turns into a bed and good food," he says. "I have concluded that it is more worthwhile this way and I don't really need the money because I have two pensions as a professor, from Tel Hashomer and Bar-Ilan University, as well as a great deal of property belonging to my family in Vienna. And besides, I have modest tastes."

He is also quite a prolific writer. His shelves contain at least 19 books that he has written, in addition to some 400 medical articles. He has citations from numerous governments, obstetric and endocrinological academics, and scientific academies as well as medals, including the German Iron Cross, from a variety of countries. He is also the founding editor of "The Aging Male," a journal published by the International Society for the Study of the Aging Male (ISSAM), which Lunenfeld himself established about five years ago in Geneva and which he has headed ever since. Today, 25 countries and 1,250 researchers from the fields of medicine, sociology, psychology and biology are members of the organization, which is recognized and supported by the World Health Organization.

Bruno Lunenfeld was born in Vienna to a very wealthy family. His father served as legal counsel to the House of Hapsburg, "and because of that, the day the Germans entered Vienna, they immediately arrested my father and his brother, but not as Jews - as monarchists. They took them to Dachau and on the way, shot one of them. I was 11 years old at the time. My grandfather and grandmother were observant Jews, and my mother knew that they would not be able to deal with my father's death if he were not given a Jewish burial. But we never received a body. So my mother organized a funeral and we put on a show for my grandparents as if we were burying my father so that they could properly mourn him by sitting shiva [observing the traditional seven-day mourning period]."

Lunenfeld was sent to England with the help of the Jewish Agency. After a few months, his mother informed him that a postcard had arrived from his father, whom they thought was dead.

"That is how we learned that we had `buried' not Father, but rather my uncle. Then two things happened: Living with me in my room in the dormitory was the son of a senior officer in British intelligence, and my father was at the time in Dachau together with Pastor Niemoller, a very high-level member of the priesthood. Because of my family's connections, they decided to try to free my father. But then the Nazis sent Father to Buchenwald and the British managed only to free Niemoller. Ultimately, [Father] managed to get out of Buchenwald with the help of the British. He returned to Vienna and in August 1939, came to Palestine with my mother. I arrived by ship a few months later, in April 1940."

Lunenfeld was 13 years old when he joined his parents in Tel Aviv. At the age of 15, he joined the Irgun Tzvai Leumi (pre-state underground militia), which sent him to study at the St. George School in Jerusalem, "because all the students there were the children of British officers and the Irgun wanted me to gather intelligence."

After high school, still serving in the Irgun, he studied physics, chemistry and biology for two years at the British Institute of Engineering in England and, in 1947, encouraged by the Jewish Agency, he went to study medicine in Geneva. It was there that he began the research that would become his life's work.

"It was already in my early research there that I discovered the principle that would form the basis of the fertility treatment I later developed. In other words, I found the drug even before I studied medicine."

Nuns' urine

Lunenfeld's research dealt with the function of menopausal gonadotropins (sex hormones), "but what led me to the research was my desire to find a cure for infertility. It was a Zionist thing. I kept thinking to myself that the Jewish people had lost so many people and that the maximum had to be done for internal immigration, in other words - to increase the number of babies born."

In Geneva, he met "Shoshana, my love," who had come from Israel to study translation. "We lived together and became very friendly with a rabbi, who also told me, `the greatest mitzvah [good deed] now to save the Jewish people is to deal with infertility.' Until then, from 1927 to 1942, infertility had been treated by giving women suffering from amenorrhea [complete absence of menstruation] gonadotropins extracted from the urine of pregnant horses. Incidentally, there are still places in the world, perhaps even in Israel, where this is still used" - despite the fact that in 1939, it was discovered that women given these gonadotropins very soon developed what was called "anti-hormones." Not only did they not get pregnant, they became very ill.

"In Geneva, I met a researcher in the endocrinology department named De Vatville, and together with him, I decided that the subject of my research would be women's menopause. I thought that when menstruation suddenly stopped, the body would try to activate the ovaries to stimulate menstruation, and that it would be possible to use the hormones present in the urine of menopausal women for women who lacked these hormones."

Lunenfeld indeed discovered that the pituitary gland is responsible for the production of the gonadotropins, and that they stimulate the ovaries. He wrote his thesis on this subject and submitted it in 1954.

"But even before that," he recalls, "I thought that if we succeeded in extracting this hormone from the urine of menopausal women and gave it to women suffering from amenorrhea caused by the fact that their pituitary gland was not producing the hormones, then we might succeed in bypassing the problem with the hormones and cause the ovaries to produce eggs without the women producing the anti-hormones. At this point, I needed funding for research as well as a way to obtain the urine of menopausal women. We decided to contact a number of other scientists in the world who were also studying gonadotropins and we invited them all to Geneva. To my astonishment, they all came."

At the conference, Lunenfeld established the "G Club," an organization of researchers of gonadotropins, the last meeting of which was held at Tel Hashomer in the 1960s, when he was already the head of the endocrinology institute there. Even before the conference, Lunenfeld needed the urine of menopausal women and he was sent to Rome to speak with Pietro Donino, the owner of the Serono pharmaceutical company. Lunenfeld asked Donino to fund a study that would culminate in the production of a drug to fight infertility and Donino asked Lunenfeld to speak to the company's board of directors.

"I, just a kid, had to stand before the board of directors and ask them to help us find 400 menopausal women that would agree to collect their urine daily. I gave my lecture, they all applauded politely and then the chairman of the board got up and said: Very nice, but we are a drug factory not a urinal factory. I ran out crying."

Donino followed him out along with another person. "Donino said, I'd like you to meet Prince Pacelli, Pope Pius' nephew. The prince told me he wanted me to stay with him in Rome for a few days and that we would try to work out together how to solve the problem. I stayed in Rome for 10 days and on the 10th day, I was invited once again to the board of directors.

"There, Prince Pacelli gave exactly the same speech I had given 10 days earlier, but at the end he added one sentence: `My uncle, Pope Pius, has decided to help us and to ask the nuns in the old-age home to collect urine daily for a sacred cause.' That, of course, convinced the board of directors immediately to help our research project with money and resources. I later discovered that the Vatican owned 25 percent of Serono."

Scientific `prostitution'

Serono established three centers for urine collection and 600 nuns collected urine daily. Company drivers brought the containers of urine to special laboratories where the desired hormones were extracted from the urine. "When I told my father that I wanted to be a doctor," recalls Lunenfeld, "he told me that it wasn't a good idea. Be a chemist; turn shit into gold. That's what he offered me. So in the end, I became a doctor that turned urine into gold. That is, I made gold for Serono. I never even considered the idea of making any material profit from this story. We had this idealism then which held that to turn science into something commercialized would be a prostitution of science. It naturally never occurred to me to register a patent on the technique we invented to refine the urine and extract the hormones from it."

Lunenfeld developed the technique to extract the hormones in 1953. A year later, he earned his degree in medicine and returned to Israel to serve in the army, because he had been studying abroad during the War of Independence and was required to complete his regular service. He was recruited into the medical corps and served as a brigade physician. In his spare time, he began working in the Weizmann Institute as a visiting scientist.

"But then, too," he recalls with pride, "as a regular soldier, they allowed me to travel twice a year to Geneva to continue the research."

Two years later, he traveled once again to Geneva and, in 1961, he completed his study and Serono began to manufacture Pergonal. Lunenfeld returned to Israel and accepted Prof. Haim Sheba's invitation to replace him as head of the endocrinology department at Tel Hashomer.

"I was the first doctor in the world to come up with a drug for fertility treatment," he says. "Infertile women in a terrible state came to the endocrinology department, which I later turned into an institute. I naturally thought that I had to help them and I also knew how. At that time, there was no Helsinki Treaty to authorize drug experiments, so I asked Prof. Sheba what to do and he allowed me to try out the drug on three women." Of course, no one, including Lunenfeld, knew what dosage of the hormone would stimulate the production of eggs in the ovaries or what side effects could be expected. "The first woman I treated was a new immigrant from South America, a very brave and courageous woman. I began to give her courses of hormones and she received 12 series of treatments, with each involving 14 days of hormonal treatment and daily urine collection and, of course, examinations and all sorts of other things. After 12 such series, she became pregnant and was very happy. We were all very happy.

"This was a woman who previously had been completely infertile. I only treated women suffering from amenorrhea, women who had never gotten their period before and suddenly, she became pregnant and gave birth to a little girl, the first baby in the world born as a result of fertility treatment, but the Israeli press lynched me ethically. They said that it was not ethical to interfere in the workings of nature. After that, another baby girl was born, and then a baby boy and we were all overjoyed. We wanted to start spreading the treatment around when Fabio Bertarelli, who was the big boss at Serono, called me and said, I have already given away 200 doses of gonadotropins to doctors, but I have yet to sell a single dose. So I used my connections with doctors all over the world and between 1962 and 1968, numerous doctors worldwide repeated my experiment and the drug became very popular."

Competition and tragedy

The drug's popularity bred competition - and, in retrospect, tragedy, too. "At the same time as me, [German Prof.] Carl Gensel was extracting gonadotropins from the pituitary gland of cadavers, and naturally that way it is possible to extract far more and cleaner material. I heard about it and that triggered an intellectual competition between us." The competition ended in 1985 in a terrible tragedy.

"We were in New York and staying at the Waldorf-Astoria at the time," recalls Lunenfeld, "and Gensel was staying there, too. Suddenly, I read in The Wall Street Journal that women that were given Gensel's hormone fell ill with Creutzfeldt-Jakob syndrome, the human version of Mad Cow disease, and the babies too, perhaps. A short time later, I saw Gensel, white as a ghost and he said to me, `This is the last day of my career.'"

Lunenfeld also suffered a period of anxiety. "Creutzfeldt-Jakob's syndrome is a disease that is contracted as a result of human tissue being introduced into the body," he explains.

"I also began to fear that perhaps this could happen when materials are extracted from the urine of a living woman. I realized that we had to do two things - first of all, to find an immunological method of refining the substance from urine, and even more important, to start to find a way to manufacture gonadotropins using genetic engineering.

"At the time, I had a student named Aliza Eshkol, a wonderful student, and together with [immunologist] Michael Sela of the Weizmann Institute, we developed an immunological method to extract the substance. That, of course, led to Serono offering Aliza the position of chief scientist of the company and she agreed and also led them to the use of this technique."

But Lunenfeld was not yet satisfied. Following the enormous success of Pergonal, physicians began giving the drug to women with other fertility problems, which led to an enormous demand for the urine of menopausal women. And the more urine was needed, the more difficult it became to effectively supervise its quality. Lunenfeld consequently proposed that Serono look for a way to synthesize the hormone: "They began working on genetic engineering and my conscience was clear and I could sleep peacefully."

Did they heed your warning against using the urine?

"Serono began manufacturing synthetic hormones and wherever I was involved, no more hormones from urine were used. But there are places that for irresponsible commercial reasons, hormones taken from living sources are still used, and even in Israel there are still such places. In my view, this is very, very bad. But I have written and spoken out against the practice, and it is no longer in my hands."

Why did it happen?

"It happened of course because the treatments became very widespread and very profitable for doctors, and when doctors only want to succeed and make money as quickly as possible, they aim for a sure thing. They say to themselves that if they succeed in producing multiple-fetus pregnancies, there is a greater chance that at least one of the fetuses will survive, and their patients will be very satisfied. Another thing is, of course, that Pergonal is also being used for in-vitro fertilization as well, and there too there are doctors who believe that if they implant a large number of fertilized eggs, there is a greater chance that the pregnancy will culminate in at least one baby.

"But I say that if things are done properly, there does not have to be so many pregnancies with multiple fetuses, because the goal of the treatment is to end up with one baby each time. How many such failures have there been in Israel, for example?"

Have you yourself conducted many fertility treatments with Pergonal?

"I have done quite a few and have of course been involved in treatments carried out in the endocrinology institute at Tel Hashomer."

Men age badly

In 1967, Lunenfeld founded the Department of Life Sciences at Bar-Ilan University and became a full professor soon afterward. He was 40 years old. Ten years ago, he retired from Sheba Medical Center and today, he continues his work at Bar-Ilan as an associate professor. Somehow, in addition to the two full-time jobs he held over the years, at the hospital and the university, he also managed to serve for two years as chief scientist of the Ministry of Health. He was a visiting scientist at the Weizmann Institute for three years, and naturally continued his research, which expanded to include other areas related to endocrinology.

How does it feel to be the father of a million children?

"It is wonderful to know that because I did something that interests me and caused me so much pleasure, it somehow happened that so many women became mothers and so many babies were born. I have been extremely fortunate that something that happens to give me personal pleasure gives others pleasure, too. That is why I also decided after I left Tel Hashomer that the time has come to do something for men too, especially aging men. Because men age very badly."

How are they different from women?

"Women have a much greater awareness of preventive treatment. They go to their gynecologists when they are healthy and take healthy children to the pediatrician to be inoculated, as preventive treatment. Unlike women, men tend on the one hand to be hypochondriacs, and on the other, to deny their medical problems. And, of course, whatever remains unused, deteriorates. Because with men, the penis, brain and heart all work in exactly the same way as far as the blood circulation is concerned, when problems begin with the circulation to one organ, you can be sure that the other places will also soon suffer. And then men become ill and die far earlier than women.

"Everywhere you go, you see women who are still in good physical and mental condition caring for men who at the same age are already ill and falling asleep in front of the television, whose brains don't function as well either. They are very dependent and drive the women caring for them crazy. So I started to think that something should be done in this area, too.

"I am thinking in the direction of conducting a worldwide survey on the specific processes of aging in males, and to learn from the study how to improve their quality of life - the physical and mental functions of the aging male. In this way, I hope to create a situation in which men will also be able to care for women, not just the other way around. So you see that in this case, too, I have the benefit of women in mind."

Lunenfeld says that it is too early to talk about practical conclusions. He himself, it appears, has solved the problems of his own aging very well. Judging from his own personal example, all that is needed for a man to continue living a life full of awareness and satisfaction, even as he nears 80, is an active love life and a brain that never stops exploring and asking questions for a moment. And it helps to be viewed as the No. 1 expert in a field that interests you in the extreme.

"Or, as they say, my work is my hobby, and my hobby is sex," Lunenfeld sums up in his heavy German accent, hardly altered by the 62 years that have passed since he first set foot in Israel. n