A quest to 'reanimate' the brain dead

In the movie Awakenings, the victims of an encephalitis epidemic many years ago have been catatonic ever since. Now a new drug offers the prospect of reviving them.

In the movie Awakenings, the victims of an encephalitis epidemic many years ago have been catatonic ever since. Now a new drug offers the prospect of reviving them.

Published May 31, 2016

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Washington - Ever since Ira Pastor declared his company's intentions to take 20 brain-dead patients and try to “regenerate” their nervous systems, his email box has been overflowing with inquiries from far-flung parts of the world.

Sceptical scientists grilling him about the details of the techniques his team is using. Desperate families, who have been paying for years to keep loved ones on life support, wondering how to enroll. Outraged representatives from every major religion telling him why what he's doing violates the laws of nature.

But the most vociferous challenge, says Pastor, chief executive of Philadelphia-based Bioquark, has been from the “zombie contingent.”

“You wouldn't believe how many people have said, 'Please don't do this. You're going to start the zombie apocalypse',” he says.

Such confusion, hope and fear are not unexpected given the radical nature of the project. But Pastor explains that any changes due to the treatments will probably be subtle, at the cellular level at first, and detectable only by sophisticated blood and spinal fluid testing and MRI imaging. Such work, he says, may have more applications for treating traumatic brain injury, mental illnesses, spinal cord issues and Alzheimer's in the short term rather than disorders of consciousness.

“We are not waking anybody up in this study,” Pastor emphasises. “It is very preliminary.”

Brain death is perhaps the least understood state of the human mind. Most of us - including many scientists - take it for granted that the condition is absolute and final. Pastor argues that's a mistake. He says he believes it is a potentially curable condition and that given the right combination of stem cells, drugs, electrical currents, magnetic fields or other stimuli we haven't thought of yet, the mind may yet have the power to reawaken.

That idea is controversial for many reasons - moral, religious, scientific, economic. If the project finds even a little bit of success, it has the potential to upend our entire health-care system. Hospitals could be forced to keep brain-dead people on life support indefinitely, bankrupting insurers, and the whole organ-donation system, which relies heavily on the altruism of families of brain-dead patients, could come to a standstill.

Sam Parnia, a researcher at Stony Brook Medicine who in 2014 led a groundbreaking study on people's state of mind and consciousness at the time of death, has theorised that death may not be a specific moment but a process that can last hours or even days. If that's the case, he says, efforts such as Bioquark's to intervene and reverse this process hold “a potentially very exciting promise for the future.”

But Parnia emphasised that there is a big difference between being able to reanimate some cells and reanimating a whole brain.

“It may reverse cell damage in some areas but not other critical brain areas, leading to severe and significant disabilities and injuries in people who would have otherwise died,” he said. “At worst, people who would have died will come back but end up in a vegetative state.”

Robert Veatch, a professor emeritus of medical ethics at Georgetown University's Kennedy Institute of Ethics who has written a forthcoming book about how death is defined, is more sceptical. He points out that in all of medical history there has not been a single documented case of a person who met the criteria for brain death and was then revived in any state.

“It is a bizarre stretch of the imagination to think that all of those billions and billions of cells could be somehow fixed,” he said.

At any given time, hundreds of thousands of people in the world are estimated to be trapped in the little-understood place between consciousness and nothingness.

Some of them are in a vegetative state that occurs when the part of the brain that controls thought no longer functions but they sleep, breathing as normal. Others are in a coma where they cannot be awakened and don't respond to light, sound or touch. Those most severely impacted are considered to be brain-dead.

The formal definition comes from a Harvard Medical School committee report from 1968 that described the condition as “irreversible coma” in which people are unaware of external stimuli, unable to move or breathe on their own and have no eye movement and other reflexes. Following the controversy over the “right to die” case of Karen Ann Quinlan in 1976, a number of state legislatures moved to clarify the protocols for how and when doctors can declare a patient brain-dead and to equate that with being deceased. This is the point at which many patients are disconnected from life support.

But science doesn't always work in that kind of black and white, and over the years situations have cropped up that challenged this definition.

Among the most recent was the 2013 case of 13-year-old Jahi McMath, who went into cardiac arrest and was declared brain-dead after what was supposed to be a routine tonsillectomy. After doctors at a hospital in Oakland, California, declared her brain-dead and said they would remove life support, her family ended up moving her to New Jersey, where the laws were more flexible about keeping her on life support, and they have gone to court seeking to have her old death certificate voided.

In March, the family posted pictures on Facebook showing Jahi, now 15, “as healthy and beautiful as ever” even though she has not awakened during those two years.

The more we learn about the brain, the more it has become clear that there's no on-off switch and that there area between consciousness and unconsciousness is a spectrum. There have, for instance, been cases of patients being given anaesthesia who appear to be asleep but are actually conscious of their pain and paralysis. Researchers have also reported the nearly miraculous reawakenings of the near dead after being given, quite paradoxically, the sleep drug Ambien.

Then there's the case of former Israeli prime minister Ariel Sharon. Cared for in a private room at a medical centre with an armed guard outside for eight years, the “sleeping giant,” as he was known, never woke up from his coma, but the scientists caring for him found through scans that when they played the sounds of voices of his family, his brain lit up.

Research on brain-dead patients who are still on life support, however, is rare. The MD Anderson Cancer centre in Houston published results of a ground-breaking study on brain-dead and nearly brain-dead patients in 2002 that some believed would set the stage for further work. The research involved infusing millions of peptides - strings of amino acids that scientists believed may have the potential to block blood vessels feeding tumours - into the patients and then doing a number of invasive biopsies to see what happened. The results, published in Nature Medicine, yielded “a wealth of data,” according to a write-up that year in Science magazine.

At the time, some scientists predicted that the findings would pave the way for an explosion in such research, but it raised so many ethical questions that few other institutions dared to venture into type of work. Jacqueline Glover, writing in the Hastings centre Report, argued that while the research is “undeniably valuable,” there is a slippery slope: “If we start with the already dead patient and move to the nearly dead patient, who will be next?” she wondered.

Now, nearly 15 years later, Bioquark and its India-based partner Revita Life Science hope to build on those findings. Recruitment of study subjects started this month in northern India, a location the company chose partly because it's cheaper but also because the laws surrounding studies of what some call living cadavers are in a gray area. But for a study with such grand ambitions, it is a modest affair - and there is some doubt that the group is in a position to make huge breakthroughs.

Without the backing of any university, major hospital or pharmaceutical company, Bioquark expects to use nearly half the $2 million capital it has raised from family and friends and some angel investors. The lead researcher for the project on the ground is Himanshu Bansal, a doctor whom the Hindu, one of India's largest daily newspapers, described as “a slightly overweight, affable, eager-to-please man in his early forties.” He is an orthopaedician, a specialist who deals with injuries and diseases of the musculoskeletal system, rather than a neuroscientist.

According to the Hindu, Bansal claims that he has been working on comatose patients since 2009 and has had some success with two patients.

“One patient was brain-dead, but after we started our experiments, she started responding to pain stimulus - meaning her blood pressure would change every time she felt pain,” he said. “But I cannot give you more details due to confidentiality agreements with my patients.”

The setting for the study is just as unlikely - the top floor of a three-story medical facility that is flanked by a restaurant on one side and a gym on the other. It is located in Rudrapur, Uttarakhand, a town about 145 miles from New Delhi that the Hindu said is “so inconsequential that it is best known for bad roads.” The researchers are talking to families with loved ones at intensive care units at local hospitals and looking for people who have been declared brain-dead but whose central nervous systems are mostly intact, such as someone who drowned in a pool or flew off a motorcycle with a helmet on.

During the six-week trials (patients will be treated individually as their families sign on), the men and women will be given a continuous infusion into an area around the spinal cord of a biochemical cocktail the company developed through its research on previous regenerative medicine. Stem cells will also be administered every two weeks.

Pastor said that the researchers spent a lot of time figuring out how to communicate their work and expectations to the families in a way that is sensitive to the fact that they may still be grieving. Part of the protocol of the experiment makes it clear that families can opt to drop out at any time if they change their minds.

“We want them to understand this is highly experimental,” Pastor said. “Although it represents a possibility, we don't want to generate false hope.”

Washington Post

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