Gursaran Talwar (India) After 20 years of research, Gursaran has developed the world's first family-planning vaccine. It is a safe, long-lasting, reversible vaccine that will be of interest and benefit to the South and North alike. The scientific and research challenges have been considerable, and he also had to face the usual skepticism concerning Third World scientists. "For a scientist in a developing country to make an original contribution, he or she has to work five times harder."

by Usha Rai

TWENTY YEARS IS QUITE A LONG TIME TO DEVOTE to a single research project, but this is how long it has taken Dr Gursaran Talwar to arrive at a remarkable achievement: a safe, long-lasting, reversible vaccine to prevent pregnancy in women.

Along the way, Talwar has had to battle scientific challenges and the disbelief of many foreign colleagues. "People felt it was a fantasy," he said of the reaction in the early 1970s to his idea of a birth-control vaccine. "Vaccines are traditionally made for diseases, pestilence, viruses, and bacteria — not birth control." He also faced the usual skepticism concerning Third World scientists. "For a scientist in a developing country to make an original contribution, he or she has to work five times harder," he said.

The idea of doing research for a contraceptive vaccine came to Talwar in the early 1970s when he was working as an executive council member of Banaras Hindu University in the state of Uttar Pradesh. Shuttling between Delhi and Banaras, he observed that most of the people were physically stunted from lack of proper nutrition. He learned that this was due to the small land-holdings in these communities. A full 63 percent of India's farmers have less than 0.6 hectares of land. Because family size remains large (seven or eight children), land-holdings become fragmented as they are passed from father to sons. Small land-holdings cannot produce enough food to keep the families nourished. Forty percent of India's population lives below the poverty line.

Talwar's colleagues in the Department of Social and Preventive Medicine pointed out that, although it was not in the interest of Indians to have large families, there was not a wide choice of effective contraceptives. Vasectomy and tubectomy, offered to them through the official family planning programs, were terminal (nonreversible) methods. Intrauterine devices (IUDs) tended to cause excessive bleeding, which, in a population of women who already suffer from mass anemia, is not sustainable. Pills and condoms call for a high level of daily motivation.

So Talwar had an almost missionary zeal to work on a contraceptive that would have the following characteristics: not call for daily motivation; not have the risk of user failure; be reversible; and not disturb the menstrual cycle or cause bleeding. At the same time, the contraceptive should enable the woman to retain her privacy.

There is also a personal dimension to Talwar's motivation to work in this field. In India, where the majority of babies are born at home with the help of a birth assistant, tetanus is a major killer of young mothers. Talwar was born at home and his mother died 8 days after his birth. Although no one knows precisely what killed her, it could very well have been tetanus. The vaccine developed by Talwar is double-barreled in that it enables the generation of antibodies against human chorionic gonadotropin (hCG) and simultaneously raises antibodies against tetanus, giving women and newborns added protection.

Talwar began this research in 1975 as Professor of Biochemistry at the All India Institute of Medical Sciences, relying on financial support initially from the Family Planning Foundation of India and IDRC. His objectives called for a method radically different from previous attempts at birth control. Talwar's concept of the vaccine matched those objectives. It neither stops ovulation nor alters the menstrual cycle. Also, it does not require the motivation of taking a daily medication. Nor does it involve a doctor having to insert an IUD, which can cause irregular bleeding. Finally, it is reversible and allows women to retain their privacy.

The vaccine works by inducing the production in the body of antibodies to hCG, a hormone normally produced by the embryo to help prepare the uterus to accept implantation of the embryo. By increasing the production of antibodies that are able to inactivate hCG, this hormonal action is blocked and implantation of the embryo does not occur. Therefore, rather than trigger an abortion, the vaccine operates by helping to prevent the onset of pregnancy. In doing so, it simply heightens a natural process: about one-quarter of detectable conceptions fail because the embryo does not become implanted in the uterus. The vaccine induces the production of antibodies to hCG to a point where all embryos fail to become implanted.

Women who take the vaccine for the first time must have it administered once a month for 3 months, during which time they must use other forms of contraception. Dr Talwar is trying to develop a contraceptive for use during this period based on a natural product — the purified extract of the neem tree. Eventually, Talwar would like to refine the administration of the vaccine, so that a woman only has to visit a family-planning service once instead of three times. He is also working on formulations of the vaccine that will last for 6 months, 1 year, or 2 years.

Vaccinated women who later wish to become pregnant simply have to discontinue booster injections. The antibodies will disappear, hCG will no longer be neutralized, and an embryo will have a normal chance of implanting in the uterus.

According to Dr Don de Savigny, of IDRC's Health Sciences Division, the vaccine gives women a way to space births. "Ninety-nine percent of global maternal deaths occur in developing countries. This vaccine can help alleviate the problem of insufficient spacing as one of the reasons."

Recent clinical studies show that among 119 women immunized with the vaccine, only one pregnancy occurred over 1 224 menstrual cycles. Without the vaccine, 300 to 400 pregnancies would have been expected in such a group.

Talwar's work has been subjected to rigorous animal trials over a 10-year period. After having established the absence of side effects in animals and obtaining approval of the Drug Regulatory and Ethics Committee, safety trials were conducted in Brazil, Chile, Finland, India, and Sweden by The Population Council of New York. All of these studies confirmed that the vaccine was safe and that the effects were reversible. Subsequent tests, in three major Indian institutions, confirmed the ability of the vaccine to prevent pregnancy.

"We have passed an important milestone and that is to confirm that the vaccine works," says Talwar. Despite this success, however, it will be some time before the vaccine is ready for the public. (Contraceptives require much more lengthy testing periods than those for medications against life-threatening diseases. One reason is that a contraceptive is meant for young, healthy people, who could be taking it over a period of up to 30 years.) "My hope is that by the year 2000 it will be available for public use."

The vaccine will have obvious benefits not just to countries of the South but to the entire world. "Many people want alternatives to current methods of contraception," says Talwar. "There is no dividing line between North and South. The vaccine does not block ovulation and it is usable at all stages of a woman's reproductive life."

Talwar insists on mentioning his gratitude to IDRC for its early support of his research. "Yes, it was a novel idea back then, greeted with skepticism by many in the beginning, but IDRC did not hesitate. It gave a grant to support the idea." Part of the reason may have been the reputation of the individual and his research institute.

Some of the best scientific research institutions in the world are in India, says Dr de Savigny. "Talwar's National Institute of Immunology is a world-class institution. Immunologists from all over the world come to work and study there. In fact, birth-control vaccines being developed in Australia and the United States are not as advanced as Talwar's vaccine."

As word of the revolutionary nature of the research has spread, money has poured in from The Rockefeller Foundation, the Department of Biotechnology of the Government of India, and others. But it was IDRC, Talwar insists, that bolstered support for the research when it was most needed. In India, support came from the late industrialist and visionary J.R.D. Tata, who personally met Talwar and ensured support through the Family Planning Foundation that he set up.

In researching for the hCG vaccine, there have been several spin-off vaccines and creams. Praneem, a purified extract of neem seeds, is currently being tested as a contraceptive vaccine on male monkeys. In tests thus far, despite sperm counts of almost zero, it appears that the male sex hormone, testosterone, is not decreased and libido remains unaffected. Unlike vasectomy, this is expected to be a fully reversible method. The research for a male contraceptive silences criticism that all new contraceptives are targeted exclusively at women.

Another unexpected bonus from the research is a polyherbal formulation that acts as a potent spermicide and against a variety of genital pathogens, including candida, gardenella, chlamydia, and herpes. Made from purified neem extract, reetha, and cinchona bark extract, this spermicide is on clinical trials in India, Brazil, China, the Dominican Republic, Egypt, and Nigeria. Studies in progress also indicate an inhibitory effect on the replication of HIV (human immunodeficiency virus), the virus responsible for AIDS.

"The hCG research has opened up a Pandora's box," says Talwar. Yet another vaccine, which controls the production of sex hormones, is on clinical trial in India and Austria. It has therapeutic qualities and is being used in the treatment of prostate cancer.

Although Talwar's interest lies in the control of fertility in humans and animals, he is also working on a vaccine for leprosy. It is currently in phase-three trials in hospitals in Delhi and in a large rural block in Uttar Pradesh.

Countries such as Mexico are testing the hCG vaccine for yet another purpose — its possible application in human lung-cancer patients for which no effective chemotherapy is currently available.

For a man well into his sixties, Dr Talwar has tremendous drive and energy, perhaps owing to his regular practice of yoga and a habit of climbing stairs rather than taking elevators. His scientific efforts have won him laurels from around the world. Among the many awards and titles, in 1991, he was decorated with the Officier de la Légion d'honneur by the President of France and, in 1992, he was awarded the prestigious Padma Bhushan prize by the President of India.

Recognized and admired in India and by the world at large, Gursaran (Pran) Talwar is a truly remarkable humanitarian whose impressive life's work promises to help improve the lives and futures of millions of people the world over.