BENGALURU, INDIA -- The Indian Council of Medical Research (ICMR) has derailed a controversial experiment that would seek to revive brain-dead accident victims. On 11 November, ICMR’s National Institute of Medical Statistics removed the “ReAnima” trial from India’s clinical trial registry.
In May, Himanshu Bansal, an orthopedic surgeon at Anupam Hospital in the north Indian state of Uttarakhand, announced plans to give around 20 brain-dead people a mix of interventions including injections of mesenchymal stem cells and peptides, and transcranial laser stimulation and median nerve stimulation. Transcranial laser stimulation involves shining pulses of near-infrared light into the brain; median nerve stimulation is the electrical stimulation of a major nerve that runs from the neck to the arm. Both techniques have been shown to improve cognition in patients with traumatic brain injury. Bioquark, a biotech firm based in Philadelphia, Pennsylvania, had agreed to supply the trial with peptides that are said to help regenerate brain cells.
In interviews with Indian media in the spring, Bansal described his aim as bringing brain-dead individuals back to a “minimally conscious state” in which patients show flickers of consciousness, such as moving their eyes to track objects. Although there is scant evidence that brain-dead people can recover such function, Bansal says the medical literature describes a significant number of cases of people who have recovered full consciousness from a minimally conscious state.
Other researchers point out that it is improbable that the ReAnima trial -- which hasn’t yet begun -- would achieve its goals. “While there have been numerous demonstrations in recent years that the human brain and nervous system may not be as fixed and irreparable as is typically assumed, the idea that brain death could be easily reversed seems very far-fetched,” Dean Burnett, a neuroscientist at the United Kingdom’s Cardiff University, told The Telegraph. Medical journals have on occasion carried reports of brain-dead individuals on life support returning to a fully functional state, but researchers have argued that such cases are hard to interpret and often lack evidence of brain death such as the apnea test, a measure of whether the person’s brain stem is making an effort to breathe.
Scientists and physicians are also raising concerns about whether the ReAnima trial is ethically justified. One concern is that the mix of interventions has not been tested in animal models. On their own, the treatments the ReAnima trial would use have shown promise in people with traumatic brain injury, says Amar Jesani, editor of the Indian Journal of Medical Ethics Mumbai. “But once brain stem death has taken place, and there is no cognition or consciousness, one cannot rely on a few disconnected studies. Why couldn’t they combine these interventions and do proper animal studies?” And even if the experiment were to succeed, he asserts, bringing a brain-dead person back to a minimally conscious state would traumatize family members.
In a press statement, Bansal argued that there are no good animal models for human brain death. Asked in a June interview for The Wire what he planned to do if patients were brought back to a minimally conscious state but did not regain further function, Bansal responded that his team “had not planned for it” initially, but that he had since purchased an insurance policy to cover the costs of full-time care of such patients. Still, the ReAnima team has struggled to convince family members to allow brain-dead accident victims to be enrolled in the trial, says Ira Pastor, chief executive officer of Bioquark.
ICMR identified several regulatory lapses in the trial, including a failure to seek permission to proceed from the Drug Controller General of India, a requirement for all clinical trials in India. Now that ICMR has deregistered ReAnima, the Drug Controller General of India G. N. Singh must stop the trial immediately, says ICMR Deputy Director General Geeta Jotwani in New Delhi. Bansal told Science “ICMR has nothing to do with the trial,” and says the matter rests with the drug controller. Singh’s office did not respond to questions from Science. Bioquark’s Pastor says that the setback ultimately won’t stop the project, and if necessary the team would pursue the trial outside India. “We are in no major rush, in that it represents a ‘Google Moonshot’-style project,” he says. “Many road blocks, no doubt, will pop up. But the project will go on.”