In 2016, Canada became one of the few countries in the world to legalize voluntary euthanasia. Since the passage of the new rules, people living there with a “grievous and irremediable medical condition” can choose to have their lives ended by the administration of a lethal cocktail of drugs. Many medical organizations, including the World Medical Association, are strongly opposed to the practice. But now a further ethical dilemma has emerged: some of the patients seeking physician-assisted death have also expressed their wishes to donate their tissues to science to help researchers treat and cure their illnesses in future generations.
Already, several people with advanced multiple sclerosis (MS) have volunteered to donate brain samples to medical research after undergoing voluntary euthanasia—known formally in Canada as medical assistance in dying. Their tissues have been collected within an hour of their death, a meaningfully short window of time for gathering brain samples, according to researchers: “With a long delay between death and autopsy, the tissue degrades,” says Alexandre Prat, a neuroscientist at the University of Montreal. This makes it almost impossible to establish the activity of genes and proteins inside the brain lesions associated with MS. With what Prat terms “ultra-fresh” brain samples collected shortly after death, researchers can access this information. Doing so, he says, might shed light on the underpinnings of disease and, ultimately, lead to improved treatments.
Whereas the potential scientific benefits are clear, the ethics of the practice are muddier, and they have implications for the patient, their loved ones—and the global medical community.
Research into conditions such as MS has traditionally been made easier by the use of animal models of disease. More recently, three-dimensional brain “organoids” have emerged as a promising new tool for researching MS. But there is no substitute for the kinds of insight made possible by studying tissue samples collected from people with the condition.
“It’s all well and good to say: We saw this biologic response or mechanism of action in a rat model and we assume these are probably relevant in humans,” says Brian Kwon, a neuroscientist and spine surgeon at the University of British Columbia. “It’s quite another thing to have an opportunity to test those assumptions in human patients.”
But collecting brain samples from people with conditions such as MS is challenging, says Prat. The brain does not heal well, which prohibits researchers from taking biopsies from those living with the condition, he says. This means brain samples must be collected after death. There is anecdotal evidence that some people with MS are eager to donate their brains for research. For instance, when the subject was raised in a 2017 article written for the digital publication Multiple Sclerosis News Today, several people with MS left comments below the story expressing an interest in donating their own brains. “I didn’t think MS patients were allowed to donate organs,” wrote one commenter. “I would like to donate my MS brain to help in MS research.”
But if there is a significant delay between the declaration of death and sample collection, the tissue loses its medical value, Prat says. Wait just five or six hours between death and the post-mortem examination and it is only stable proteins that will remain detectable in the samples, he says. “Unstable proteins will be degraded and RNA will be useless. It’s a really big limitation in terms of what we can study at the pathological level.”
After Canada’s new laws allowing assisted dying went into effect, Prat and his colleagues approached a few patients with MS who had elected to undergo medical euthanasia and asked whether they would also consider donating brain samples for research. The way Canada’s laws are written means that people with serious but non-terminal conditions like MS may qualify for medical euthanasia, if their health status is so poor that death is considered “reasonably foreseeable.” Moreover, slightly under half of the people who undergo assisted dying in Canada do so in a hospital setting, which means a post-mortem team can be put on standby in a nearby autopsy room to collect tissue shortly after death is declared.
So far, about half a dozen people who have undergone assisted dying have agreed to donate their tissue to the research led by Prat, he says. Loved ones can remain with the patient for up to an hour after death is declared, for any final goodbyes, then the body is transferred to the autopsy room. The person’s brain is removed and MS-associated lesions are sampled. Some of those samples remain at Prat’s institution; others are immediately shipped to his collaborators as far away as the USA and France. Prat says the teams are using a technique called single-cell RNA-seq to work out the quantity of different forms of RNA in the samples. They also use immunohistology to characterize the tissue within different brain lesions and use flow cytometry to identify particular cell types.
According to Prat, MS is such a heterogeneous disease that there is real value in establishing the exact cellular and molecular features of individual brain lesions. “In MS, the brain has hundreds or thousands of lesions, and each lesion is different,” he says. The data he and his colleagues are collecting will go toward building a database that explores the limits of that variation. It could ultimately lead to better treatment options for MS tailored to the individual patient.
“The shorter the post-mortem delay, the better the quality of the brain tissue,” says Inge Huitinga, a neuroscientist at the Netherlands Institute for Neuroscience in Amsterdam. “Short post-mortem delays allow state-of-the-art analyses of the tissue.”
Huitinga is director of the Netherlands Brain Bank, which has, since the mid-1980s, accepted autopsy samples from donors with a range of neurological and psychiatric disorders, as well as from people who had healthy brains at their death.
A small number of the brains in the Netherlands Brain Bank came from donors who underwent euthanasia, which has been legal in the Netherlands since 2002. However, Huitinga says that in her experience there is little qualitative difference between these brains and those donated by people who died in other ways. One reason is that more than 80% of those who qualify for euthanasia in the Netherlands choose to undergo the procedure at home. This means that even though the time and date of death can be established in advance, there is still a delay, while the body is transported to the hospital, before the post-mortem examination can begin. “In the end, the average post-mortem delay does not decrease due to medically assisted death in the Netherlands,” she says.
Consequently, Prat’s research appears to be unique. Because half of the people undergoing voluntary euthanasia in Canada do so in a hospital, that country may be the only place where it is often possible to collect brain tissue samples within an hour of the declaration of death. Trevor Stammers, a bioethicist at St Mary’s University in London, UK, who studies the ethics surrounding euthanasia and assisted suicide, is unaware of anyone collecting samples for research in the way Prat and his colleagues are. But Stammers says Prat’s work raises some familiar ethical questions, because in a few countries it is already possible to donate organs (principally the liver and kidneys) for transplant following voluntary euthanasia.
Such procedures have been performed in Belgium and the Netherlands for about a decade, and they are now being performed in Canada. Dirk van Raemdonck, a thoracic surgeon at University Hospitals Leuven in Belgium, says organ donation is made possible because the cocktail of barbiturates, morphine and paralyzing agents used to induce death do not appear to have toxic effects on the organs harvested for donation.
Again, there is a need to begin the autopsy as soon as possible after death so that organs can be collected before they degrade—although in this case there is not quite the same level of urgency as that connected with brain-tissue collection, and a delay of a couple of hours is generally deemed acceptable, says van Raemdonck. But Stammers says even this slightly reduced sense of medical urgency following euthanasia risks disturbing the relatives’ grieving process. He suggests it could even lead to later uncertainly that their loved one is actually dead, if the body is removed before they have had time to be sure for themselves.
Prat’s experience of brain-tissue collection from people with MS suggests this is not the case. Family members are told they can have about 60 minutes alone with their loved one after death has been declared so they can achieve closure, but he says many choose to waive that right so that the autopsy can begin sooner.
Stammers, however, wonders whether family members are truly at peace about this process. He suspects some may worry about letting the doctors down by spending too much time with the body and jeopardizing the medical value of the tissues or organs.
Andreas Rudkjøbing, chair of the Medical Ethics Committee at the World Medical Association and president of the Danish Medical Association, raises another concern. It is always stressed to those who apply for euthanasia that they can, at any time, withdraw their request. But if candidates for euthanasia then also agree to donate tissue to medical research following their death, they may feel they have lost the option to decline going through with euthanasia, again because they worry about letting down the doctors. “It will be harder for the patient to change his or her mind if he or she has promised to participate in research,” he says.
It may be too early to say whether or not these concerns play out in the real world.
But performing MS research on samples obtained from people who have undergone assisted dying raises other ethical complexities. In principle, the research Prat and his collaborators perform could lead to new therapies for MS that benefit people the world over, including those in countries in which voluntary euthanasia is still illegal and might even be considered unethical.
“I think it is worrying,” Rudkjøbing says. “The World Medical Association is firmly opposed to euthanasia and we would be similarly opposed to using the practice of euthanasia to facilitate clinical research.”
Dominic Wilkinson, a medical ethicist at the University of Oxford, takes a different view. He argues that knowledge does not have ethical value in itself. Some researchers might feel uncomfortable about performing research on cell lines obtained from people who have opted for voluntary euthanasia. But Wilkinson says it makes less ethical sense for the researchers to ignore knowledge that others have gained by studying such tissue.
Perhaps the most important concern to bear in mind is how research such as Prat’s is perceived by the general public. There are huge benefits to be had if people are willing to donate their tissues and organs after death—whether that death be natural, accidental or medically assisted. But people may be prepared to become donors only if they feel they can trust the donation process. Stammers fears that if discussions surrounding donation become muddled with discussions around the controversial issue of voluntary euthanasia, some people who would otherwise consider donating tissues for research may decide not to.
“I’m very pro-organ and tissue donation,” Stammers says. “Hence my concern about anything that might jeopardize it and harm the trust that is essential for it to work.”
This article is reproduced with permission and was first published on January 24 2020.