India being a population that is greater than one billion, considerable time and energy is spent in researching and developing methods of effective population control. While many methods of contraception have been cultivated for women, the only safe and effective ones for men are condoms and vasectomy. Condoms have proven to be largely ineffectual in the rural Indian demographic and vasectomy, which involves the cutting and removal of a section of a tubular structure known as the vas deferens in males, has the disadvantage of being irreversible. Also, the idea of having a healthy part of one’s body removed is one that may not sit comfortably in people’s minds. Of those alternate chemical methods that have been put forward, the Reversible Inhibition of Sperm Under Guidance (RISUG) is amongst the most prominent and is currently in the middle of the third phase of clinical trials. It is the invention of Prof. Sujoy Guha, currently, a professor of our own School of Medical Science and Technology.
An interesting origin
Prof. Guha began working on the drug when he was in Delhi, back in the seventies. He was working to purify water obtained from tube-wells and his team structured a compound that would line the tubing and kill the E. coli bacteria present in the water as it rose through the tube. This is when they were struck by the idea: Could the same compound be used to kill sperm? “Serendipity!” as Dr. Guha puts it.
The science behind the action
The method involves the injection of a drug in the form of a clear polymer gel into the vas deferens, which is an exit passageway for sperm cells. Once introduced, it lines the walls of the tube and begins to introduce a predominantly positive charge in the surrounding region. Research has shown that the heads of sperms are negatively charged. As these cells then pass through the deferens, they are neutralized and their membranes disintegrate, killing the cells. The structure of the molecule has a furan ring that opens up and forms the spoken-of charge distribution. The drug has been modelled to have a backbone of styrene – the strong and stable part, and maleic anhydride – the active part.
One of the scientific breakthroughs achieved is that, analogous to a permanent magnet that can magnetize without losing the magnetic property itself, RISUG develops a bound charge that is retained for long periods of time (upto 10 years!). The longevity is significant, given that the effectiveness of the spermicide is predicated on preserving its state of ionisation in an environment where the predominant compound is water – not an easy task by any standard.
Most importantly, as the name suggests, the action is reversible by a compound that simply neutralizes the charge and hence clears all effects of the drug. Finer research into its capabilities have suggested that it may possess anti-infective properties and have a preventive action with respect to HIV and prostate cancer. Specifically in the case of cancer, RISUG works by generating a ‘nano-drug’ locally that attacks mutant cells.
Testing and commercialization
It is not uncommon to learn of useful compounds being made up of harmful ingredients. As it turns out, the individual components of RISUG (styrene, maleic anhydride, DMSO) are toxic, carcinogenic agents. Due to this reason, the developers of RISUG were met with tremendous opposition initially. Their concept of the application of electric charge to contraception, too, was subject to scepticism. Drugs must go through a long and rigorous series of tests before they are approved for use by the public (see box). Not surprisingly then, the contraceptive has been in the process for some thirty years. RISUG is being tested by the Indian Council of Medical Research (ICMR) and is presently undergoing Phase III trials.
As far as commercialization is concerned, for foreign markets, the distribution will be handled by USA. While the developing team is looking for companies in India to help them on the national scale, as per the government’s suggestion, the group has started its own company and takes care of the manufacturing for the test batches. “It will be affordable”, says Prof. Guha.
Research into RISUG is presently being carried out at five cities in the country (including Kharagpur) and five new centres are to be added soon. Developed entirely indigenously, it is noteworthy that the technology involved in RISUG has been transferred to the USA. Generally, it is the reverse that takes place. With RISUG, Indian scientists have complete knowledge of the underlying chemistry and are comfortable with experimenting with the compound and exploring its possibilities. The successful launch of the contraceptive into the mainstream market could one day revolutionize birth control.
Prof. Sujoy Guha is an eminent figure on the Indian biomedical engineering scene. He holds an MBBS degree from Delhi University in addition to a B.Tech and M.Tech in electrical engineering he obtained from IIT Kharagpur in the early sixties. His other major research involvement is in reliability engineering, where he has worked to enable the blind to perform skilled tasks. He was presented with the Distinguished Alumnus Award at this year’s convocation ceremony.
Clinical trials are conducted in phases. The trials at each phase have a different purpose and help scientists answer different questions:
In Phase I trials, researchers test an experimental drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase II trials, the experiment is conducted with a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase III trials, still larger groups of people (1,000-3,000) are tested on to confirm effectiveness, monitor side effects, compare to commonly used treatments and collect information that will allow the experimental drug or treatment to be used safely.
In Phase IV trials, post marketing studies delineate additional information including the drug’s risks, benefits, and optimal use.