Two recent controversies over “brain-dead” patients have obviously flustered some medical ethicists. Writing in a commentary in the New England Journal of Medicine, David C. Magnus, Benjamin S. Wilfond, and Art Caplan insist that the definition of death as brain death must be maintained.
In Fort Worth, Texas, the relatives of 33-year-old Marlise Muñoz, a woman who was 14 weeks pregnant, wanted her to be taken off life support after they learned in November that she was brain-dead. But her hospital refused, believing that it would be breaking a Texas law which mandated life support of pregnant women to save the life of a foetus.
At the other side of the country, in Oakland, California, 13-year-old Jahi McMath was declared brain-dead in December and the hospital recommended that she be taken off life support. Her relatives refused.
How should such stand-offs be resolved?
The authors insist that the medical profession and the law must draw a line at brain death. On one side of that line, patients are alive. On the other, they are dead. Too much is at stake, they argue.
The determination of death is a highly significant social boundary. It determines who is recognized as a person with constitutional rights, who deserves legal entitlements and benefits, and when last wills and testaments become effective. Sound public policy requires bright lines backed up by agreed-on criteria, protocols, and tests when the issue is the determination of death. The law and ethics have long recognized that deferring to medical expertise regarding the diagnosis of brain death is the most reasonable way to manage the process of dying. Nothing in these two cases ought to change that stance.
What about grieving families? Should they have a say in the matter?
Not really, say the authors. A brain-dead person is a dead person. The feelings of the family must be taken into account and it is only humane and politic to give them a few days for the truth to sink in. But in the end, the family is clearly wrong about the facts of the case.
“Proponents of allowing family members to determine death threaten to undermine decades of law, medicine, and ethics… Families often need time to accept death, and that can be particularly complicated in cases of brain death. For the family's benefit, a short-term accommodation can be ethically justified. But these psychological realities do not undermine the important social construction of death when the brain has ceased all meaningful activity.
Will articles like this settle the question? Perhaps not. Magnus, Wilfond and Caplan frame their argument in terms of good public policy, rather than proving that brain death is death. In fact, they imply that patients in a permanent vegetative state could be also “defined” as dead. “Although one could conceivably draw the line somewhere else, such as loss of cognitive functioning, the reliability and social consensus that has emerged around brain death as death is reflected in the broad legal agreement under which brain death is recognized in every state.”
Note: an earlier edition of BioEdge misrepresented a "written declaration" which originated in the Parliamentary Assembly of the Council of Europe. This is a petition signed by 61 representative, substitute and observer members of PACE, not a vote by PACE itself. This body has 321 representative members, 321 substitute members and 18 observer members. It is confusing and we got it wrong. Sorry.
Belgium’s Parliament is expected to pass a controversial law permitting the voluntary euthanasia of children as early as next Thursday. The bill will allow minors to ask for a lethal injection if they are terminally ill, if they are in great pain and if there is no effective treatment. Their request has to be approved by the medical team and their parents. Supporters claim that there will only be about 10 to 15 cases a year.
The vote comes much earlier than previously expected. After the Senate passed the bill, the media predicted that a vote would take place in May.
With stem cell technology constantly advancing, the dream of artificial (or synthetic) gametes comes ever closer. Last September Maastricht University, in the Netherlands, hosted a conference on “Artificial Gametes: Science and Ethics” (no papers available at the moment).
The creation of artificial gametes would represent the triumph of technology over the limitations of natural reproduction. Now that it seems feasible to coax adult cells into reverting to a pluripotent state, women could make sperm and men could make eggs. Eventually it might be possible to make bespoke gametes from any tissue samples.
The latest contribution to this simmering debate is a paper in the Journal of Medical Ethics by Timothy F Murphy, of the University of Illinois College of Medicine at Chicago. He argues that artificial gametes are ideally suited for gay and lesbian couples. If they existed, one of the principal arguments against homosexual parenting disappears: that the children are not related to at least one of their parents. “Synthetic gametes do raise questions of ethics in regard to parenthood for gay men and lesbians,” he writes, “but these are largely questions of access and equity, not questions of parental fitness and/or child welfare.”
Of course, it is not “natural” to reproduce this way, but Dr Murphy cites the authority of a 2004 article in Science by British utilitarian bioethicist John Harris and Italian stem cell scientist Giuseppe Testa which contends that “there is no a priori reason to prefer the natural, for the natural per se is morally neutral. The whole practice of medicine is a comprehensive attempt to frustrate the course of nature.”
Dr Murphy’s reasoning makes this future seem all but inevitable:
If insurance companies in the USA cover infertility treatments for straight couples, is there any morally compelling reason they should not extend the same benefits to opposite-sex couples, some of whom will be in lawful marriages? Given the historical arc of homosexuality in bioethics, the field may eventually move to embrace these kinds of questions fully, after the novelty of synthetic gametes wears off, and bioethics may yet embrace homosexual men and women as the presumptive equals of everyone else in regard to fitness as parents. The sooner, the better.
In the eyes of doctors and the public, evidence-based medicine is the gold standard of clinic practice. If it’s based on evidence from trials and laboratories, it must be right.
However, evidence-based medicine has its critics, as a bilious outbreak of comment and letters in the BMJ demonstrated recently. Early last month a Glasgow GP, Des Spence, said that the system of EBM had been corrupted. “If we don’t tackle the flaws of EBM there will be a disaster, but I fear it will take a disaster before anyone will listen,” he wrote.
How could anyone fault the notion of treatment based on scientifically validated evidence? No one. But the critics of EBM argue heatedly that the standards for the evidence are often low and tainted by commercial or personal interests. Dr Spence accuses drug companies of manipulating the gold standard to their own benefit. “Today EBM is a loaded gun at clinicians’ heads. ‘You better do as the evidence says,’ it hisses, leaving no room for discretion or judgment. EBM is now the problem, fueling overdiagnosis and overtreatment.”
A number of letters pointed out that, while EBM had its flaws, doctors still need to exercise their clinical judgement. They write the prescriptions, not the drug companies.
Dr Spence was supported by Dr Miran Epstein, a medical ethicist at The London School of Medicine. He writes that “EBM “does not regard polluted information, whether it involves misconduct or not, as a sufficient condition for rendering disclosure inadequate. Thus, it lets informed consent degenerate into a legal fiction and the principle of autonomy into a cynical farce. Worst of all, it is perfectly ethical: being the codified expression of the collective conscience of our medicine, it naturally purports to be moral.”
And he was supported by lawyer and ethicist Charles Foster, writing in the Practical Ethics blog. He believes that the editors of journals need the help of a regulator to sift the wheat from the chaff. “Journals can’t do it all. We need a cynical, skeptical, well-funded, well-staffed and ideologically very left-wing regulator. With huge teeth.”
Twenty years ago, a British statistician complained in the BMJ that much medical research was “seriously flawed through the use of inappropriate designs, unrepresentative samples, small samples, incorrect methods of analysis, and faulty interpretation.”
Today, says the BMJ’s former editor, the influential writer Richard Smith, the only word to be changed in that diagnosis is probably “much”. It should now be “most”. And he complains that the leaders of the medical profession are not interested in changing the situation.
Dr Smith is not the only one to ring warning bells about the quality of the enormous quantity of medical research. The acclaimed statistician John Ioannidis* has estimated that only 1% (1%) of thousands of studies which assert that there is a correlation between a particular gene and a medical condition are correct. Why? Ioannides says candidly, ““Most scientific studies are wrong, and they are wrong because scientists are interested in funding and careers rather than truth.”
Dr Smith lists five reasons for the enormous waste: research fails to answer questions that matter; studies are too small or never replicated; the research is not well managed; much research is never published; and much published research is “biased and unusable”.
And in one stinging paragraph, the authors accuse scientists themselves, not just the economic and administrative systems in which they work, of responsibility for this failure:
Science is not done by paragons of virtue, but by individuals who are as prone to self-interest as anyone else. They can compromise their usually high standards of rigour when involved in commercial or otherwise conflicted relationships. When resources are scarce and competition is fierce they might seek the easiest and quickest—rather than the best—ways forward. They could judge that they would rather be first than be right. When their research hunch turns out to be wrong, many researchers move to the next one rather than going through the painstaking business of reporting negative findings. Finally, they could prefer research that they find interesting rather than research that addresses issues of importance to the users of research. These behaviours are compounded by the complacency and poor craftsmanship of some scientists.
* Apologies. This name was misspelled in the original text.
Dr Stephen Brigham being arrested by Maryland police. Charges were later dropped.
Pro-choice supporters and pro-life supporters have finally found an issue which brings them together: loathing of Dr Stephen Brigham, an abortion provider on the East Coast of the US. A graduate of MIT and an MD from Columbia, Dr Brigham has been opening and closing abortion clinics in Pennsylvania, New Jersey, New York, Maryland, Virginia and Florida since the 1990s. His main company is American Women’s Services (toll-free number 1-800-ABORTION).
RH Reality Check, a pro-choice website which does investigative reporting, profiled Dr Brigham last year. It found:
Since the early 1990s, public records show, Brigham’s patients have suffered emergency hysterectomies, severe bowel injuries, severed ureters, and sweeping lacerations to the uterus. Over a period of two decades, Brigham has been barred from practicing medicine in at least six states, sued by his landlords and business associates, and even served jail time for failing to pay taxes. And yet today, Brigham remains in control of a network of 15 abortion clinics in four states, and there appears little that most state authorities are able—or willing—to do about it.
“You feel completely powerless,” the former chair of the National Abortion Federation and Physicians for Reproductive Health, Suzanne Poppema, told RH Reality Check. “We spend enough of our time trying to beat back harassment, threats, and anti-abortion legislation. The fact that we have to spend time policing someone in our own profession is just depressing.”
A recent issue of The New Yorker also profiled Dr Brigham. It painted a bleak picture of the abortion profession in the US. Because fewer and fewer doctors are willing to do abortions, venal and substandard practitioners step in. “Now you have two types of doctors doing abortions—the doctors who are totally committed to women’s health and are going to do them even if they never get another dime, and the people that just want to take advantage of the situation and milk everything they can out of it,” says Dr LeRoy Carhart, one of the few doctors in the US who does partial-birth abortions.
Pro-life supporters contend that the existence of Dr Brigham and his clinics proves that sub-standard treatment is common in the abortion industry. Pro-choice supporters deny this. They respond that restrictions on abortion providers are the problem. “The more expensive and inaccessible that abortion becomes,” one provider told the New York Times, “the more it creates a space for a Gosnell or a Brigham to operate.”
It’s the ultimate confirmation of the notion that stress is good for you. A team of researchers from Japan and Boston have discovered that subjecting ordinary cells to stress will make them revert to a state in which they can make any cell in the body. It is an astonishingly simple door to the promise of personalised medicine which has obsessed scientists for the last 15 years.
“It’s a startling result that makes you stand up and go, ‘Wow!’” says George Q. Daley, a leading stem cell researcher at the Harvard Stem Cell Institute. “With an equal dose of amazement and skepticism.”
And colleague Douglas Melton, says, “It’s just a wonderful result; it’s almost like alchemy. It says one has found a way to reveal the hidden potential of cells with a relatively straightforward method.”
The bombshell research was published in the journal Nature this week. The researchers claim that their method of reprogramming cells to pluripotent state – which they have dubbed stimulus-triggered acquisition of pluripotency (STAP) bypasses both cloning and the use of chemicals. It has been proven with mouse cells; experiments with human cells are under way.
Stem cell reprogramming is one of the hottest areas of biology and Japanese researcher Shinya Yamanaka won a Nobel Prize in 2012 for discovering “induced pluripotent stem cells”. This discovery, because of its simplicity, could be even more momentous.
Surprisingly the central figure in the discovery, Dr Charles Vacanti, of a tissue engineer at Brigham and Women’s Hospital in Boston, is not even a stem cell scientist. In 2001 he published an article in which he claimed that he had discovered a new type of stem cell which he called a “spore-like cell.” But other scientists were sceptical. “Our lab was pretty ridiculed,” he told the Boston Globe.
But by reflecting on his results, Dr Vacanti realised that the stem cells might have emerged as a result of stress, as part of the body’s repair kit, and did not reside in the tissue itself. Together with a Japanese research fellow in anaesthesiology, Haruko Obokata, of the RIKEN Center for Developmental Biology in Kobe, his team pursued this avenue.
They found that after bathing mature cells in acid or growing them in a low-oxygen environment, some of them reverted to a pluripotent state – STAP cells. If they were then placed in a growth medium, they became just like embryonic stem cells -- totipotent. In other words, they can also produce the cells which create the placenta as well as the embryo. The new method is far simpler and quicker than Yamanaka’s method.
However, the results were so counter-intuitive that other scientists refused to believe them until the accumulation of data was overwhelmingly convincing.
For years many stem cell scientists have insisted that ethical barriers to destructive research on embryos had to be dismantled because they are the best source of pluripotent stem cells. Persuaded by their arguments, many governments relaxed legislation on destructive embryo research. But if the STAP cells prove to be viable, both scientists and politicians will be looking rather silly.
Unfortunately, this discovery could give rise to its own ethical debate. New Scientist points out that if STAP cells are totipotent, they could become induced to become embryos. "The word totipotent brings up all kinds of issues," Robert Lanza ,of Advanced Cell Technology, told the magazine. "If these cells are truly totipotent, and they are reproducible in humans then they can implant in a uterus and have the potential to be turned into a human being. At that point you're entering into a right-to-life quagmire"
In other words, the STAP cells could lead to a new debate about cloning. "Clones like Dolly are not actually a perfect copy," says Dr Vacanti. "When you clone a cell using our technique, there is no egg, so there's no additional mitochondrial DNA. There's an embryo and a placenta which is a perfect copy of the original."
Left: Hwang with Snuppy, the first cloned dog (Ahn Young-joon/AP). Right: Hwang today (David Cyranoski)
This year marks the tenth anniversary of what may have been the most spectacular scientific fraud of the last 100 years: Hwang Woo-suk's claim that he had cloned human embryos. It made him a scientific celebrity everywhere, but especially in South Korea. The fraudulent data and ethical lapses, however, soon emerged and his career seemed over, his name a byword for scientific infamy. In January 2006, the president of Seoul National University described the affair as “an unwashable blemish on the whole scientific community as well as our country”.
However, David Cyranoski, a journalist for Nature, reports that Hwang is making a comeback, as a specialist in cloning animals, especially dogs. Outside Seoul he runs the Sooam Biotech Research Foundation, which was launched in 2006 with millions of dollars from supporters. He has 45 staff and delivers about 15 cloned puppies a month. Americans (mostly) are paying US$100,000 to have their pets cloned. His group is publishing in peer-reviewed journals and he has forged ties with the world’s largest sequencing facility, BGI in Shenzhen, China. Half of his budget comes from government grants.
Despite the scepticism of other scientists, in Korea and abroad, Hwang – who is now 61 – is clearly a comeback kid. He is even seeking recognition of his claim that he did clone a human embryo, even if the research was tarnished by misconduct.
Nature's editorial team was shocked when many South Koreans interpreted Cyranoski's profile as recognition of his achievements. A week later they published an editorial in which they insisted that "The evidence suggests that Hwang was not a great scientist… The potential of Hwang’s claimed work was over-hyped even before the work was exposed as fraudulent, especially considering that superior technologies — such as stem cells made from reprogrammed adult cells — were already in the offing."
The best way, they suggest, for Hwang to be accepted as a scientist of integrity is to drop his legal action seeking recognition as the first to clone a human being. "People are asking, can we trust him? Part of the answer lies in how he resolves this issue. If he wants to start again, he should look there."
Texas woman Marlise Muñoz was disconnected from life support last Sunday. All cardiac function ceased within a few minutes. Her body was released to her family, ending a nation-wide debate over reproductive rights, brain death, and advance directives.
On November 26, 33-year-old Mrs Muñoz collapsed after a clot in her lungs. The John Peter Smith Hospital in Fort Worth diagnosed brain death but also found that she was 14 weeks pregnant. It thereupon refused to remove her from life support, against her husband's wishes. It cited a Texas law which says that “life-sustaining treatment” must be maintained if a patient is pregnant, even if an advance directive exists or her relatives oppose it. The hospital planned to keep Mrs Muñoz on life support until her child was viable, deliver it with a Caesarean section, and then remove her from life support.
But the hospital finally relented when Mr Muñoz filed a lawsuit. "In fact, Marlise cannot possibly be a 'pregnant patient' — Marlise is dead," the suit says. "To further conduct surgical procedures on a deceased body is nothing short of outrageous." Her husband also alleged that the baby was not viable; it was said to be badly deformed and suffering from hydrocephalus.
This complex situation generated a storm of controversy. Was the Texas law unjust? Feminists said Yes. Was the Texas law being misinterpreted? Legal experts differed. Should a woman be used as an incubator? Feminists said, No. Should a dead body be used as an incubator? Her family thought that this did not show respect to Marlise Muñoz. Should a baby's right to life be ignored? Pro-life groups said, No.
Was it possible for the woman to give birth to a healthy baby? Surprisingly, this question was not often posed. If the fate of the baby was mentioned in the media, the focus was on its alleged deformities. However, surprising as it may seem, there have been a small number of documented cases of brain-dead women who have given birth to viable children. A 2010 study by German doctors examined 30 cases of brain-dead pregnant women between 1982 and 2010. Twelve viable children were born and survived infancy.
In fact, at the same time as Americans were debating whether to remove Marlise Muñoz from life support and to allow her child to die, Italians witnessed the birth of a healthy child from a brain-dead mother. Carolina Sepe, 25, was shot in the head by a deranged neighbour when she was 10 weeks pregnant (he killed her father and grandmother). She survived for another 17 weeks and passed away in early January.
The case also raised the thorny question of whether Marlise Muñoz was really dead, even if she fulfilled all the criteria for brain death. A few neurologists say that if the body is functioning as an integrated whole, the person is not dead – because the person is not the brain.
Assertions that euthanasia in Belgium is safe and voluntary have been undermined by a recently-published study in the Journal of Medical Ethics. A survey of end-of-life decisions made by Flemish doctors in 2007 has found that in nearly 80% of cases of terminal sedation, there was no explicit request from the patient. Terminal sedation, or relieving the distress of dying patients by heavily sedating them, accounts for nearly 10% of all deaths in Flanders.
In such a controversial area, precision is important. In many cases of terminal sedation, the intention of the doctor is to make patients as comfortable as possible, not to kill them. It is not necessarily "slow euthanasia".
But it can be. In nearly 22% of terminal sedation cases, the doctor explicitly intended to end the life of the patient. In other words, the patients were euthanased, even if death did not happen immediately. If this is true, the real proportion of euthanasia cases in Flanders nearly trebles, to 3.3%, not just 1.26%, as reported in the study. Or at least that was the figure seven years ago, in 2007.
Even the authors seemed a bit rattled by the fact that in 79.7% of cases of terminal sedation, there was no explicit request from the patient. These were not necessarily unethical. There could have been proper reasons why no consent was given: patients could have been unable to give consent because they were in a coma or demented; relatives may have given consent by proxy; or there may have been a living will.
What concerns the authors is that many Flemish doctors do not understand what palliative sedation is. They conclude by recommending more education so that doctors will act within ethical and legal limits:
"Physicians seem to use ‘palliative or terminal sedation’ as an umbrella term to capture a wide variation of end-of-life practices. … the ambiguity of the use of the term can also be a barrier to a responsible, justifiable and reliable sedation practice in end-of-life care. Better knowledge of palliative sedation, including its procedural and ethical requirements and boundaries, may be necessary and would allow physicians to provide appropriate medical treatment at the end of life."