Tuesday, April 28, 2015

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Now for something completely different because April 25 is Anzac Day, “the one day of the year” , a solemn commemoration of the 1915 Gallipoli landing, the first (and disastrous) battle fought by an independent Australia. Today is the centenary celebration.

The highlight of every Anzac Day is the Dawn Service, a simple ritual which is held in nearly every town and hamlet throughout the country.

For me, the most memorable of these took place in Hobart a few years ago. I walked with hundreds of others through the dark towards the Cenotaph on a frosty morning. There was complete silence as an elderly Protestant minister gave a short and eloquent address about Australia’s fallen heroes which managed to make everyone, both religious and secular, happy.

However, there was something quite eccentric about his delivery. Every couple of paragraphs there was an pause. It only lasted long enough to remind us how cold we were and how dark it was, but it was slightly embarrassing. Then there was another burst before he lapsed into silence again. Finally, he concluded with an Amen.

In a quavering voice he said that this would be his last Anzac Day service. He was 85 now and had done it for 30-odd years. Time to pass the baton to someone else. And then he apologised for those pauses. “It was so cold,” he said, “I had to blow on my fingers so that I could keep on reading.” Suddenly it dawned on me: the old minister was blind and had been reading his Braille text with his frozen fingers. You find heroism in the most unexpected places…

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Michael Cook
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This week in BioEdge

2015-04-20 11:07 PM
China ignites debate over genetic engineering
by | Apr 25, 2015
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tags: China, CRISPR, genetic engineering

Chinese scientists have been editing the genome of human embryos, a world first which has set off an debate over genetic engineering.

A team led by Junjiu Huang, a gene-function researcher at Sun Yat-sen University in Guangzhou, published its results recently in an on-line journal, Protein & Cell. Their aim was to modify the gene for β-thalassaemia, a potentially lethal blood disorder, with a gene-editing technique known as CRISPR/Cas9. They used non-viable human embryos from IVF clinics. The idea was to eliminate the gene in a one-cell embryo so that it would develop into a child who would not suffer the disease.

From a technical point of view, the results were disappointing and Huang said that the technique is not currently suitable for medical use. The reseachers injected 86 embryos and examined them after 48 hours when they had grown to 8 cells. Of these, 71 survived, 54 were analysed. Only 28 had successfully spliced the target gene, but only a fraction of these contained the correct replacement gene. They also found that there were a number of “off-target” mutations somehow caused by CRISPR/Cas9.

 “If you want to do it in normal embryos, you need to be close to 100%,” Huang told Nature News. “That’s why we stopped. We still think it’s too immature.”

What about the ethics of the technique? Since changes to the embryo genome are heritable, they will be passed on to the next generation. This opens the door to the controversial issues of designer babies and human enhancement.

Some observers were highly critical. “No researcher has the moral warrant to flout the globally widespread policy agreement against altering the human germline,” Marcy Darnovsky, executive director of the non-profit Centre for Genetics and Society in Berkeley, California.

In an editorial in Nature in March, when Huang’s research was only a rumour, several scientists published a call for a moratorium on experiments like theirs:

“In our view, genome editing in human embryos using current technologies could have unpredictable effects on future generations. This makes it dangerous and ethically unacceptable. Such research could be exploited for non-therapeutic modifications. We are concerned that a public outcry about such an ethical breach could hinder a promising area of therapeutic development, namely making genetic changes that cannot be inherited.

“At this early stage, scientists should agree not to modify the DNA of human reproductive cells. Should a truly compelling case ever arise for the therapeutic benefit of germ­line modification, we encourage an open discussion around the appropriate course of action.”

In Britain, it was hard to find scientists who were opposed, let alone alarmed, by the news. “It’s no worse than what happens in IVF all the time, which is that non-viable embryos are discarded," says John Harris, a utilitarian bioethicist at the University of Manchester, UK. “I don’t see any justification for a moratorium on research." 

One of the UK’s leading stem cell researchers, Robin Lovell-Badge, was almost enthusiastic. “I disagree with a moratorium, which is in any case unlikely to work well,” he said. “Indeed I am fully supportive of research being carried out on early human embryos in vitro [in culture/in the lab], especially on embryos that are not required for reproduction and would otherwise be discarded.”

And Dr Anna Smajdor, a bioethicist at the University of East Anglia, said: “There is a whiff of hypocrisy about the moral outrage over reports that Chinese scientists have been modifying the DNA of embryos. Here in the UK we have given the go ahead to modifying the DNA of babies who will transmit these changes indefinitely to their offspring. The Chinese have tweaked DNA in embryos never destined to be born.”

In any case, it seems more than likely that this research will continue in China. CRISPRs have become a standard tool in laboratories around the world and the potential for interesting research is enormous. According to Nature, at least four groups are working on genetic engineering of human embryos in China. 

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Keeping ahead of the game
by | Apr 25, 2015
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tags: body transplant, head transplant, Russia

A 30-year-old Russian IT worker with a crippling muscle-wasting disease could become the first person ever to get a body transplant. Valery Spiridonov, from the city of Vladimir near Moscow, says that he is so crippled that he has no other option.

"Am I afraid? Of course, I am. But this is not only scary, but also very exciting," Spiridonov told the Daily Mail. He is putting his trust in an Italian neuroscientist, Sergio Carnavero, who has been talking this procedure up for several years, and who has even given a TED talk about it.

Dr Canavero calls the operation HEAVEN, an acronym for head anastomosis venture. (Anastomosis is the surgical connecting of two parts.) He estimates that it would take a team of surgeons 36 hours and would cost US$11.5 million.

Theoretically, a head transplant may be possible. As early as 1908 an American surgeon grafted a head onto a dog, creating the first two-headed dog. In 1970, neurosurgeon Robert J. White transplanted a monkey’s head with some success, as the monkey was able to see, smell, taste and hear, although the spinal cord was not fused. The animal died after eight days because the body rejected the head.

Dr Canavero still has not examined his volunteer, although they have communicated on Skype. He is enthusiastic, telling the Daily Mail:

“I consider it to be as ethical as the transplant of the heart or kidneys. At some point of time this was considered to be unethical as well. There was much talk about where the human soul is located, and if it's ethical to do the heart transplants, but now doctors do it and save people's lives. I think it's the normal way of technology to evolve. It would be strange to stop at this point when the neurosurgery is ready to take the next step.

“The bodies used for transplant could be those of people whose brain was damaged, let's say in a car crash or motorbike accident, or who are sentenced to capital punishment. But, of course, in future humanity should learn how to grow healthy bodies for the transplants so there will be no shortage of organs and bodies.”

Bioethicist Art Caplan, of Langone Medical Center, at New York University, produced a laundry list of potential problems for CNN: poisoning the body with powerful immunosuppressant drugs, identity problems, and spinal fusion problems. In short, he says, the project is “nuts”.

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Donor dad not the genius he said he was
by | Apr 25, 2015
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tags: sperm donation

A lesbian couple is suing one of America’s leading sperm banks for misleading them about the superior qualifications of their sperm donor. Angela Collins and Margaret Elizabeth Hanson chose Donor 9623 at Xytex’s Atlanta sperm bank because he had an IQ of 160, an undergraduate degree in neuroscience, a Master’s in artificial intelligence, and an impressive health history. His prospectus also said that he was working on a PhD in neuroscience engineering.

The sperm donor’s identity was supposed to be confidential, but Xytex inadvertently revealed his name to the couple. To their dismay they discovered that their  donor had dropped out of college, was a schizophrenic, and had been arrested for burglary. A large mole on his cheek had been Photoshopped off his photo. It appears that 60 babies have been born from his sperm.

Xytex’s president says that the donor’s features "do not reflect the representations provided to Xytex". It appears that the information he provided to the sperm bank was false. However, Xytex insists that the lesbian couple had been was "clearly informed the representations were reported by the donor and were not verified by Xytex".

The couple is seeking punitive damages and other compensation. Their lawyer, Nancy Hersh, says that people who resort to sperm banks are often emotionally fragile. "What I really want to see happen is some regulation and some evidence of a consciousness of the fact that they are dealing with vulnerable people who are relying on them," she told AP.

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Colombia close to legal euthanasia
by | Apr 25, 2015
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tags: Colombia, euthanasia

Colombia’s Health Ministry has finally drawn up guidelines for voluntary euthanasia, 18 years after the country’s supreme court ruled that it was a constitutional right. Health Minister Alejandro Gaviría told media that only competent adults would be able to request the procedure, that only patients with a terminal illness would be eligible, and that if the patient is unconscious, relatives must present audio, video, or written proof that he wanted to be euthanased. Minors and patients with degenerative diseases will not be able to receive a lethal injection.

Despite the 1997 ruling, Colombian law-makers dragged their heels on the issue and never drafted protocols. As a result, doctors feared that they could be charged with homicide if they helped someone to die.

The Catholic Church, one of the principal opponents of euthanasia in Colombia, was scathing in its comments. It told the Health Ministry that legalisation “is a grave attack against the dignity of the ill and against the sanctity of the basic right to life, enshrined in Article 11 of the Constitution.”

 “It would be good, Mr. Minister,” it said in a letter, “if your ministry, so interested in regulating euthanasia and abortion, put the same effort into finding an effective solution to the crisis in the health-care sector and the needs of the poorest”.

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Non-human rights battle continues
by Xavier Symons | Apr 25, 2015
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tags: animal rights, human exceptionalism, law, personhood, US

A New York State Supreme Court judge has ordered Stony Brook University to justify its detention of two chimpanzees, following a request from an animal rights group, The Nonhuman Rights Project (NhRP).

The court order, issued by Justice Barbara Jaffe on Monday, demands that Stony Brook “show cause” as to why the two chimps, Leo and Hercules, should not be immediately released and transferred to Florida’s Save the Chimps sanctuary (a refuge nominated by NhRP).

The two chimps are being kept in a Stony Brook lab on Long Island and used for biomedical experimentation. 

Animal Rights organisations celebrated the inclusion of phrase ‘habeas corpus’ – a means of redressing the unlawful detention of prisoners – in the writ, though Justice Jaffe later struck the language from the document and emphasized that it was simply a formal way of directing the university to her courtroom to present its case.

Supporters remain emboldened, saying that the issuing of the writ is in itself a very positive step. Natalie K. Prosin, the executive director of NhRP, said she was “grateful for an opportunity to litigate the issue.”

The NhRP has made a number of unsuccessful attempts to have courts recognize chimpanzee “rights”. In 2013 representatives from the group filed three separate suits in New York, in each case claiming that an animal had had its rights denied by his owners. In December last year, a five-member state judicial panel in Albany unanimously ruled against NhRP in its attempt to have an older chimp named Tommy released from captivity.

Critics of the animal rights movement were disappointed at Judge Jaffe’s decision.

“Nonhuman animals do not have legal rights any more than they have legal responsibilities,” said Bob Kohn, a technology lawyer in Manhattan who has filed briefs opposing efforts to secure human rights for chimps and other animals. “For a court to hold otherwise would have tremendous adverse legal and moral implications for mankind.”

Others were pleased to see the writ issued. Lawrence H. Tribe of Harvard Law School believes that the writ habeas corpus should be available for “other beings whose capacities are limited but who are potentially capable of bearing rights”. 

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Primed for resignation
by Xavier Symons | Apr 25, 2015
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tags: professional integrity, science fraud, social priming, social psychology

The scandal-ridden field of social priming research has taken yet another blow. Leading social psychologist Jens Förster has resigned his prestigious Alexander von Humboldt Professorship at Ruhr University Bochum (RUB) after being found responsible for data manipulation.

Förster, formerly a leader in his field, was investigated by a Dutch national research integrity panel in 2014 and found to have manipulated data in a 2012 study about the effect of auditory and olfactory ‘priming’ on cognitive ability.

Förster’s resignation comes following another broader reaching investigation conducted by his former employer, the University of Amsterdam (UvA). The results of that investigation are yet to be published, but a UvA source says that the report is finished and that Förster has been informed of the findings.

Förster denies any wrongdoing and feels like he is “the victim of an incredible witchhunt”. In a blog-post on his personal website following his resignation, he offered a number of philosophical reflections on social science: "I will leave the materialistic and soulless production approach in science” he said. “I changed my approach to life completely. I do not further want to chase after publications as was the rule elsewhere”.

In the 2014 report, the Netherland’s Board of National Research Integrity  found that some of Förster’s reported results were “statistically speaking virtually impossible”, and that “conclusion that research data must have been manipulated is considered unavoidable”. Förster’s 2012 Social Psychological and Personality Science paper has since been retracted.

The field of social priming has been the victim of several high-profile cases of research fraud. After Dietrich Stapel, another  Dutch social priming expert, was exposed in 2012, laureate Daniel Kahneman warned that the lack of integrity threatened the whole field. “I see a train wreck looming,” wrote Nobel in an open email to psychologists who work in social priming: “your field is now the poster child for doubts about the integrity of psychological research”.

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German IVF mum to give birth to quadruplets
by Xavier Symons | Apr 25, 2015
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tags: Germany, IVF, reproductive rights, Ukraine

A 65-year-old German woman has fallen pregnant via IVF to quadruplets, to the surprise of some and the anger of others. 

Annegret Raunigk, a language teacher and mother of 13, travelled to a clinic in the Ukraine to receive IVF – German laws prohibited her from receiving the treatment in her own country. She was implanted with eggs and sperm from donors. Seemingly contrary to the doctor’s expectations, all four of the eggs developed into embryos. The chance of a natural quadruplet pregnancy is otherwise one in 13m.

Raunigk, now her fifth month of pregnancy, said she decided to have more children after her youngest daughter, Lelia, nine, asked her for a sibling.

Significant risks accompany pregnancies like Raunigk’s. The pregnant mother is susceptible to high blood pressure, pregnancy diabetes and pre-eclampsia, all of which impact on each other. Risks for the babies include cerebral bleeding, paralysis, and sight and hearing problems.

Karl Lauterbach, a leading Social Democrat politician in Germany, called Raunigk’s pregnancy “a very questionable case”: “Such a pregnancy cannot be allowed to become an example for anyone to follow,” he told the German newspaper Der Spiegel.

Christian Democrats health expert Jens Spahn, called Raunigk’s decision “negligent”.

Ms Raunigk’s gynaecologist, Kai Hertwig, does not seem concerned. A German television station quoted her as saying that everything was going well, despite the usual strains of a quadruple pregnancy.


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The complexities of brain death
by Xavier Symons | Apr 25, 2015
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tags: brain death, clinical ethics, clinical practice, end of life, organ harvesting

A forthcoming article in the journal Neurology provides insight into the complexities of achieving international consensus on brain death. 

The article by a team of neurologists and medical researchers from clinics and universities around the US catalogues conceptions of brain death in medical institutions around the world. 

The authors found that institutional protocols were absent or poorly understood in a significant number of low-income countries. They also found that “substantial differences in perceptions and practices of brain death exist worldwide” and that “whether a harmonized, uniform standard for brain death worldwide can be achieved remains questionable.”

The study – the first to examine opinions in a broad range of countries – involved an electronic survey which was distributed globally to physicians with expertise in neurocritical care, neurology, or related disciplines who would encounter patients at risk of brain death. Physicians from 91 countries responded.

The results were quite revealing.

Doctors around the world leave different periods of time following initial neurologic deterioration before they declare brain death. The most common waiting period is between 6 and 10 hours, but reported results ranged from less than 5 hours to more than 25 hours. 

“There were several discrepancies regarding the conduct of apnea testing”, the authors report. Views about the import of ancillary testing (EEGs, Dopler ultrasounds etc.) differed significantly between countries.

In their discussion of the results of the study, the authors flagged a need for greater collaboration between medical institutions from different countries:

"To promulgate a unified stance on brain death, valuable for practitioners everywhere, consensus among leading experts in the field is urgently required…[our] findings underscore the importance of international partnerships between institutions to improve medical education and alleviate critical human resource needs in lower-income settings."

In a comment on the article, Dr. James Bernat observed that there is signficant disagreement on brain death even within the US.

“[There is] a surprising degree of practice variation among hospitals in the United States. In contrast to the international circumstance, in which practice disparities arise more because of legal, cultural, or religious differences, those in the United States result more from the biases and ingrained practices of individual physicians.” 
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Michael Cook
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