After the high tide of enthusiasm comes the ebb tide of scepticism. The new STAP cells discovered by a team of researchers from Japan and Boston are being questioned by stem cell scientists.
In a paper published in Nature in January, the authors claimed that subjecting ordinary cells to stress will make them revert to a state in which they can make any cell in the body. “It’s a startling result that makes you stand up and go, ‘Wow!’” said George Q. Daley, a leading stem cell researcher at the Harvard Stem Cell Institute.
The STAP method and results are illogical and too good to be true.
in 2001 “the STAP team previously reported ‘spore’ stem cells, which to my knowledge have not been independently replicated.”
In 2011, “The team also previously reported adult pluripotent stem cells.”
“Evolution should have selected against a hair trigger for conversion to pluriopotency or totipotency”
“Why the delay to make human STAP cells?” The team succeeded in producing mouse STAP cells in 2011.
However, the debate about the experiment should be settled quickly. As Knoepfler notes, “we’ll know if STAP cells are the real deal within as short as two months because quite a few labs are now trying the technique.
Nobel laureate Shinya Yamanaka also stepped into the debate, swatting away reports that STAP cell were a safer alternative to the stem cell he developed in 2007, induced pluripotent stem cells.
“What hurt us were a lot of reports that concluded STAP cells are safer than iPS cells. The iPS cells announced in 2006 using mice and the iPS cells created now use totally different techniques. I find it quite regrettable that the reports made comparisons with the old technique.”
On February 25 and 26 the US Food and Drug Administration will discuss the possibility of legalising three-parent embryos – or, in scientific lingo, “oocyte modification in assisted reproduction for the prevention of transmission of mitochondrial disease or treatment of infertility”.
This procedure, which involves removing the nucleus from one human egg whose cytoplasm contains defective mitochondria and placing it in an enucleated egg with healthy DNA for subsequent fertilisation, is also being debated in the UK.
The measure is strongly opposed by the Center for Genetics and Society, which is promoting an open letter to the FDA. It claims that mitochondrial transfer is unsafe, is effectively experimentation on unconsenting human subjects, and would only help a handful of women. Most importantly, it constitutes germline modification, a form of eugenics. This is a bright line which no country has ever stepped across.
We strongly believe that clinical trials … should not be permitted because of the profound safety, efficacy, policy and social problems they would pose. We question the ethics of bringing children into existence by experimental techniques that have had developmentally poor outcomes in studies using both animal and human oocytes. We are also concerned about the contravention of widespread prohibitions against human germline genetic modification that approval of clinical trials would represent, and about the possible precedent such approval could set for additional human germline modifications.
A bill permitting euthanasia for children has passed the lower house of the Belgian Parliament by a vote of 86 to 44, with 12 abstentions. The parties gave their members a free vote on the controversial issue.
It will become law when King Philippe gives royal assent. This will make Belgium the only country in the world which allows euthanasia without an age limit. This has come only 12 years after it was first legalised.
Neighbouring Netherlands also allows euthanasia for children, but only up to the age of 12.
Supporters of the bill insist that it is safe and that there will only be a handful of cases each year. The child must be suffering from a terminal illness, with “constant and unbearable suffering”. He or she must demonstrate a “capacity of discernment”.
Can an eight-year-old give informed consent to a lethal injection? Yes, they say, because youngsters in this situation often display a maturity beyond their years.
“This is an act of humanity that allows the doctor to make the most humane course of action for his patient,” said Philippe Mahoux, a doctor and Socialist Party senator who sponsored the legislation. “What is scandalous is the suffering of sick children when they are going to die.”
Opponents are not convinced that children are capable of making a mature decision on such a momentous matter. British barrister Charles Foster commented late last year: “children could easily think, or be actively or unconsciously persuaded, that they should opt for death because their illness causes trouble for their parents.”
The UK government has reaffirmed its commitment to decreasing the use of animals in research but has refused to cap the number of animals used. “Britain is a world leader in science and it has also got a great tradition of concern about the welfare of animals," the minister for universities and science, David Willetts said at a press conference releasing his policy. "What we do in this document is bring these two great traditions together in our delivery plan.”
Recent figures show that in 2012, scientists conducted more than 4.11 million experiments on animals—a rise of 8% over 2011. The rapid growth is due mostly to the massive use of genetically modified animals, so births of animals are counted as “procedures”. But the number of animals in experiments as conventionally understood has remained stable at 2 million for the past 10 years.
The minister refused to set a firm target for the reduction in research. “The commitment is to 'work to reduce the use of animals.' Ultimately the final figure will depend on patterns of scientific advance,” he said.
The report reaffirms the government’s commitment to the 3Rs of animal research: “in every research proposal, animals are replaced with non-animal alternatives wherever possible; that the number of animals used is reduced to the minimum needed to achieve the results sought; and that, for those animals which must be used, procedures are refined as much as possible to minimise their suffering.”
Animal welfare groups were highly critical of the report. The CEO of the British Union for the Abolition of Vivisection said: "This is a whitewash and shows that the Government has in reality given up on what it promised to do and that is to reduce the number of animal experiments. This broken promise is a missed opportunity for the Government to make meaningful and lasting change for the millions of animals that are suffering in UK laboratories."
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.”