After a 40 Year Battle, Is Male Birth Control Finally Coming?
Meet the man who never gave up on bringing it to market.
Professor Sujoy K. Guha is undeniably stylish. A short, slender man, he is among the select few who can pull off a pair of sneakers with formal shirts and trousers. At 76, he is deceptively brisk, guiding me around the Indian Institute of Technology (IIT) Kharagpur campus to show off his new projects: an artificial heart modeled on the 13-chamber heart of the cockroach; a road transport system to lower vehicular pollution. Guha is cheerful and poised with a birdlike quaver in his voice, not at all how I expected a man who has waited 37 years for his work to be introduced to the world.
In 1979, Guha published a paper in the scientific journal Contraception laying out the idea for his original drug molecule Risug, a non-hormonal, reversible male contraceptive. His idea is simple: All particles carry an electric charge and can be defused by the opposing charge. Sperm are negatively charged and can be defused by the positive ions of the Risug drug polymer. This polymer is inserted with a single injection to the scrotum, which forms an indissoluble film inside the vas deferens—the duct connecting the testes to the penis. The drug formulation for this injection is styrene maleic acid anhydride with dimethyl sulfoxide (SMA+DMSO).
A male contraceptive is an unusual thing. Almost the entire range of contraceptive methods available target the female body. The UK's National Health Service website sums up this state of affairs well: out of 16 choices listed for 'methods of contraception', 13 are female. The options for men are condoms (a method whose effect is very limited-term), vasectomy (whose effect is irreversible) and withdrawal.
In October of 2016, there was news that the clinical trial of a hormonal male contraceptive, in development for several years, was being stopped on account of side-effects experienced by trial subjects. As of this moment, Risug is possibly the only long-term, reversible male contraceptive in development in the world. (And it's non-hormonal and cheap to boot.)
Two years ago, Motherboard wondered why Risug wasn't on the market yet. The average time for a drug to go from idea to market is 10 to 15 years (presumably in the developed world). Now, half of Guha's life later, the word from the Indian Council of Medical Research is that Risug is finally on the cusp of approval.
Testing has been completed on 282 subjects across ten hospitals, and the results are nothing short of miraculous—Risug has shown complete effectiveness with zero side effects. A 2011 report by the Ministry of Health and Family Welfare mentioned finding no side effects for the drug in the long-term (a period of nine to ten years), as well as full efficacy. When the 300th volunteer is tested, the Indian Council of Medical Research will formally submit the application for approval to the Central Drugs Standard Control Organization, which is similar to the American FDA.
An original drug molecule devised by an Indian individual is a very rare thing. Only two Indians have been credited with such an accomplishment—Dr. U.N. Brahmachari introduced Urea Stibamine to treat Kala Zar, a deadly tropical diseases carried through sand flies; and Dr. Amiyo B. Kar for Centchroman, a nonsteroidal female contraceptive. Guha will be the third.
"I have shortlisted two sites for production in Delhi. The knowhow is ready, we just have to scale up from my lab workshop. The sale of my flat is almost finalized," Guha told me. "I am not waiting for a company any longer. I am a scientist, not a marketing man."
The professor has been at this juncture before. Fourteen years ago, the then Union Health minister, who oversees public health programs, had announced the imminent availability of Risug in the market, and the news was published in leading national dailies. Just before this, the Ministry of Health and Family Welfare had announced an extension of the clinical trials in support of the drug's imminent production.
Then, someone in the Indian Council of Medical Research (ICMR) raised an alarm that Risug led to higher levels of albumin in urine. Guha countered with evidence that albumin levels in men increased across the hot, thirsty months of the Indian summer, when the heat robs bodies of vital nutrients.
There was also another problem. In the early 2000s, the Indian government set about tightening the rules for drug approvals among other intellectual property (IP) rights requirements. The timeline granted under the defining Trade-Related Aspects of Intellectual Property Rights (TRIPs) agreement of the World Trade Organisation (WTO), framed in 1995 by the WTO's former avatar known as the General Agreement on Tariffs and Trade, was drawing to a close. The ICMR decided to adopt a set of Good Manufacturing Practices (GMP) and Good Laboratory Practices (GLP) for clinical drug trials.
Even if there had been a case for allowing Risug to be tested in the older framework of rules, the drug had been discredited. Everything had to start over.
At that time, Guha approached then Indian President Abdul Kalam for help. Kalam is a famous orator, known as a man of science himself, having spent his life working for the Indian national program on nuclear weapons. "He told me, 'Sujoy, you know this is not a scientific block. You have to solve this in other ways'," Guha said.
Rejection. Anger. Mellowing. Acceptance. "Sir used to say that every invention takes its maker through four stages," said Dr. Sohini Roy, a biologist who did her PhD under Guha and is now a postdoctoral fellow at UCLA. "He prepared us well for life."
When Guha and his co-authors published the first paper on Risug in the international research journal Contraception, he was just 40 years old. He was a professor with both the Indian Institute of Technology Delhi and the All India Institute of Medical Sciences (AIIMS), two of the most renowned institutions in the country, and already had the reputation of a maverick. But he was not a medical doctor, and the ICMR would not consider a drug molecule devised by a non-medically trained individual for clinical trials.
At the age of 41, Guha took the medical entrance examination for Delhi University and passed. He completed his medical degree studies while continuing to teach electrical engineering at IIT and biomedical engineering at All India Institute of Medical Sciences (AIIMS).
When the clinical testing process began, trials on rats and rabbits (smaller animals) and monkeys (larger animals) moved fairly fast and proved successful. Phase-one of the human clinical trials on 17 volunteers was completed in 1993. It went perfectly.
Then, someone photocopied sections from a book called Hazardous Chemicals: Desk Reference and sent them to the national research council. The sections in question listed styrene and maleic anhydride, both part of Risug's formulation, as carcinogens. Guha had to counter again: he argued that substances can be individually toxic in nature but harmless as compounds. He gave the example of pure chlorine, which can melt human flesh on its own, but combined with sodium, it becomes sodium chloride, the basic salt that we consume in our diets.
When trials did not resume by 1996, the professor petitioned the Supreme Court. The court dismissed Guha's petition in five minutes, saying they were not the competent authority to rule on it. But it seemed to have sent a message to the government. Phase-two resumed.
The antagonist in Risug's story is not the Indian government, according to Guha, but the international pharmaceutical lobby. "The government has, in fact, put in a lot of time and money for the clinical trials," he said. "In the first place, there would be no trials without them."
Many of the questions raised about Risug and the resultant delays have been instigated by the National Institutes of Health (NIH) in the US, he contends. For several years, the agency wanted to promote a drug for men that involved regular ingestion like the female pill, Guha said. The first medical practitioner to administer Risug for clinical trials, Dr Gulshanjit Singh, told me a similar thing some years ago. The NIH, he said, was batting for a hormone-based, repeat-use drug developed by a US-based firm. He remembered meetings where a section of the ICMR argued strongly in favour of this American drug, and pointed out problems with Risug. Singh served as the head of the department of surgery in Safdarjung Hospital and Deen Dayal Upadhyay hospital, two prestigious publicly-funded hospitals in New Delhi.
Recent developments seem to support this claim. The drug whose trials were stopped in October 2016 was a hormone-based solution, relying on regular ingestion to control the production of hormones. Regular use implies long-term sales, a steady guarantee of profit. Risug, on the other hand, requires a maximum of two doses--one injection to put the polymer film in place, and another to flush it out of the vas deferens.
"In fact, even in the World Health Organization (WHO), there are people who don't want the drug [Risug] to come through," A.R. Nanda, the Union health secretary from 1999-2002, told me.
Then, in 2002 came the albumin charge that halted Risug trials, and subsequently the ICMR decided to put Risug through the new framework for clinical drug trials. The clock turned back to the start. Soon after 2002, the professor came away to IIT Kharagpur. He had enrolled in the seventh batch of IIT Kharagpur in 1957. It was the first IIT to be established in India--the first child of prime minister Jawaharlal Nehru's technology-centric national project--and when the professor attended, it was still suffused with a romantic sense of national service.
Here in Kharagpur, he established the Risug Center With a new batch of students and researchers. This includes a laboratory, where they produce the drug used in the clinical trials of Risug. When the approval comes through, Guha's team has the knowhow to scale up from the few hundred units they currently produce, to several thousands for market production.
There's also another personal history: his maternal uncle was imprisoned for eight years (in three separate terms) by the British colonial administration at the infamous Hijli detention camp here. But he survived it. "From my mother's side of the family, I get my obstinacy. And my father, I saw him kill himself looking after his patients in Patna [the capital of Bihar]. I learned how to keep a job from him," he said.
Guha is both a good storyteller, frank without being self-deprecating, realistic and philosophical. He rarely answers a question when you ask it; he gives every question thought and more often than not, he decides it's not worth his time to answer. It takes a certain kind of temper to be a scientist in the Third World. To not be worn out by the waiting, and form-filling, and inevitable jealousies--among peers, bureaucrats, and scientists in other countries. Guha knows this. He makes sure to sleep. He jogs every night because it makes him feel like himself. He tucks his shirt in and combs his silver hair carefully.
When I asked Guha if he felt more anxious now than he had in 2002, he walked ahead of me without answering. I thought he wasn't going to answer, but he turned around some seconds later. "One hopes that I have learnt something. I am no longer an angry man."
A longer profile of Prof Guha and Risug was published in The Wire .