The practice of infecting human subjects with disease under controlled circumstances to better understand how the body reacts to a new treatment is arguably as old as medical science itself. The reason its not common in India is because of ethical and legal concerns. If we can find our way past that this could be a useful approach.

This is a link-enhanced version of an article that first appeared in the Mint. You can read the original here.

Controlled human infection studies, also known as challenge trials, involve a process by which test subjects are intentionally infected with diseases under controlled circumstances to test a new vaccine or pharmaceutical drug to see if it can successfully achieve its medical aims.

New Wine. Old Bottle.

If intentionally infecting humans sounds awful, this is, by no means, a new technique. During the 19th and early 20th century, many such experiments were carried out to find a cure for a number of vector-borne diseases, and it is thanks to one such experiment—conducted in 1898 by Battista Grassi in Italy—that we were able to confirm that malaria was transmitted to humans by mosquitoes.

Over the second half of the 20th and early 21st century, human challenge studies contributed to the development of vaccines for as many as 15 major pathogens and the treatment of various diseases like cholera, typhoid and seasonal flu.

Challenge trials can be particularly efficacious in India, where infectious diseases contribute to as much as 30% of the country’s disease burden. Since many of the currently available treatment protocols for these ailments have their origins in Western science, they may not be ideally suited to the requirements of the local population—given how they may not adequately take into account relevant environmental factors that could have a bearing on treatment.

Controlled human infection studies carried out in endemic settings are far more likely to uncover immunity patterns, associated co-infections, existing pharmacogenomic data and other relevant factors such as nutrition, etc, that could help deliver more effective treatments.

Causing Harm

The problem is that since the very premise of this approach involves causing harm to another person, if not conducted ethically, challenge trials can have deeply disturbing consequences. During World War II, Germany and Japan used these scientific techniques as weapons, purposely infecting prisoners with a variety of pathogens—from anthrax and chlamydia to cholera, dysentery, and tuberculosis—so that they could observe from close quarters the effect they had on human subjects.

For similar reasons, prisoners at Stateville Penitentiary in the US were infected with malaria, while elsewhere in the country, at Willowbrook School, mentally challenged children were purposely infected with viral hepatitis. While each of these studies were eventually condemned, the opprobrium was directed not so much at the fact that people were being intentionally infected, but the fact that these experiments had been carried out on vulnerable populations without informed consent.

It is largely for these reasons that the medical community in India has refrained from conducting controlled human infection studies in the country, despite the benefits they clearly offer. There is a genuine concern that even if conducted with the highest degree of care and attention, given the economic and social disparities in the country, it will be impossible to completely eliminate the risk that vulnerable sections of the population will end up being exploited. That even if we insist on informed consent being obtained before volunteers take part in these trials, given the levels of poverty in the country, it would be impossible to categorically rule out the chance that some of them might have been induced to participate for monetary benefit.

Ethical Questions

Apart from this, there are a number of ethical and legal concerns that also need to be addressed. Given that each of these experiments necessarily involves the intentional exposure of healthy volunteers to disease-causing microbes, there are ethical concerns around the fact that even if conducted in a controlled environment, it remains a process designed to deliberately cause harm to another human being. As a result, it is possible that the scientists involved in these trials could, despite all the precautions they might have taken, face legal prosecution and personal liability if any participants are harmed during the conduct of the trial.

Personally speaking, I have always believed that this risk is worth the reward, particularly where the study has been carefully designed and limited to diseases that are generally well understood. Which is why I was particularly pleased to learn of the consensus policy statement issued by the Indian Council of Medical Research approving the conduct of controlled human infection studies in India.

Green Signal

Not only does the document offer a way forward when it comes to conducting tests like this in India, it also lays out the steps and precautions that need to be taken.

For instance, it stipulates that only healthy participants can be selected, and that too only if it can be confirmed that they are participating for altruistic reasons only—and not for monetary gains. To ensure that volunteers have the capacity required to properly appreciate the risks, it recommends that only graduates be allowed to participate and expressly prohibits the conduct of these experiments on children. To ensure informed consent, it recommends that it be obtained in an audio-visual format and stipulates that volunteers be clearly informed that they are going to be deliberately infected as part of the process.

I hope that this document provides the medical community with the assurance they need to conduct challenge trials for new treatments. And that the process results in an improvement in the oversight of all clinical research.

I, for one, would happily sign up.