A drug trial run by an American research company for a German biotech has left six young men seriously ill in London, two of them fighting for their lives. The six were participants in a Phase 1 trial, the first humans to use an experimental leukaemia drug called TGN1412. Minutes after taking it, they became violently ill. One sobbing woman told the press that her swollen, discoloured and unconscious boyfriend looked like "the Elephant Man".
The drug company, TeGenero, is one of a new breed of university spin-offs hunting for miracle cures. Its leading product, TGN1412, is a monoclonal antibody. This is a new and very promising type of drug, a genetically engineered "humanised" protein which binds to a targeted protein. TeGenero engaged Parexel to recruit volunteers and conduct the drug trials. TeGenero says that the calamitous result was "completely unexpected". The UK's Medicines and Healthcare Products Regulatory Authority is investigating what happened, along with Scotland Yard.
Much is still unclear: whether the drug was contaminated, whether the dosage was appropriate, whether proper procedures were followed. Apparently it was tested successfully on monkeys, although two of these had developed swollen glands, but it is far from certain that humanised monoclonal antibodies can be tested adequately with animal trials. A scientist told the London Times that "in animals binding may not occur because the antibody may not recognise any animal tissue at all, or binding may be weaker". TeGenero insists that everything had been done by the book and that it was just an unpredictable and very regrettable incident.
The outcome prompted a flurry of commentary on the ethics of clinical research. Had the participants really given their informed consent even if they had signed a form detailing the risks? As the London Times pointed out, they were paid £2,000 for their time and effort, but they were responding to an advertisement which promised free food... digital TV, pool table, video games, DVD player and now FREE internet access!" Some of the young men were cash-strapped students; one is said to have been a "serial guinea pig" who had earned £60,000 from clinical trials over four years.
American bioethicist Arthur Caplan railed against greedy drug entrepreneurs: "The business of conducting medical research is profitable. Private companies running studies for pharmaceutical and device companies are now a $14 billion industry in the United States alone. The problem with the intense commercialization of research is that it's not clear that contract research organizations... always put subject welfare first. There is plenty of room for conflicts of interest when the person recruiting volunteers for research is being paid to get subjects enrolled and data generated as quickly as possible."
Baroness Julia Neuberger, a Liberal Democrat in the House of Lords who also teaches at Harvard Divinity School, suggested that more studies should be done on animals, especially primates, even if primate studies are viewed as morally wrong by animal welfare activists. (Which raises the question of whether Parexel found it easier to organise testing a dangerous drug on humans than on apes.)
A number of scientists declared that it was too early for human trials with a powerful monoclonal antibody. Apparently a similar drug had produced severe side effects in half of a group of cancer patients in the US. "They should have known they would get a meltdown," Angus Dalgleish, professor of cancer at London University, told the Times. He was surprised that the regulatory agency had not consulted outside specialists before allowing the trial to proceed. ~ London Times, Mar 17,19, Independent, Mar 21; Newsweek, Mar 20
HANDICAPPED BRITISH CHILD SAVED FROM HOSPITAL
A British couple have won a reprieve for their severely handicapped son after his hospital asked to let him die because of his poor quality of life. The parents of the 19-month-old child known only as "MB", thanked the judge for his decision.
MB has a condition called spinal muscular atrophy which leaves him almost totally paralysed. He requires a ventilator to breathe and cannot cry, chew or swallow. All his doctors and the guardian appointed to represent the child's interest in court argued that the burdens of his existence outweighed the benefits.
However, MB's mother told the High Court, in London, that the child was conscious. He responded to cartoon films such as Shrek and Finding Nemo, but did not appear to like the news or the TV soap Eastenders. "It must be assumed that he processes all of those sights and sounds like any child of his age and gains pleasure from them," said Justice Holman. "No court has yet been asked to approve, against the will of parents, the withdrawal of life support with the inevitable and immediate death of a conscious child with sensory awareness and cognition, and no significant evidence of brain damage."
However, the judge also set down that if the child's heart stops, the hospital would not be required to resuscitate him or to give antibiotics if he develops serious infections. ~ BBC, Mar 15; Guardian, Mar 16
TWO MORE WOMEN DIE AFTER USING RU-486
Two more American women have died after taking the abortion pill RU- 486, the Food and Drug Administration has announced. It issued an alert warning patients and doctors to follow instructions for using the drug carefully and to report warning signs such as nausea, vomiting, diarrhoea or abdominal pain. The New York manufacturer of the drug, Danco Laboratories, said it was deeply saddened by the deaths and was investigating.
Abortion provider Planned Parenthood has begun telling women to take the drug orally, as recommended by the FDA, instead of vaginally, a common off-label use in the US. It emphasised that only a tiny fraction of American women taking the drug had died. Four of these women, including the latest two, received the abortion pill at clinics affiliated with Planned Parenthood. ~ Baltimore Sun, Mar 18; AP, Mar 17
ITALIAN MINISTER CALLS DUTCH NAZIS OVER CHILD EUTHANASIA
Despite furious protests from the Dutch government, an Italian minister has dug in his heels and refuses to apologise for comparing Dutch euthanasia laws to the Nazi regime. "Nazi legislation and Hitler's ideas are re-emerging in Europe via Dutch euthanasia laws and the debate on how to kill ill children," Parliamentary Affairs Minister Carlo Giovanardi said during an radio debate on euthanasia.
When his opponent called upon Giovanardi to apologise during the program, he refused and repeated his remarks. "I have nothing to apologise for, because I am against murders of ill people," Giovanardi said. "It is the Dutch, who are to explain to Europe their homicidal practices. In the Netherlands it is allowed to put to death gravely ill children starting from the age of 12." Dutch Prime Minister Jan Peter Balkenende denounced the analogy as scandalous and intolerable." and said he would raise the issue with Italian Prime Minister Silvio Berlusconi at an EU meeting next week. Expatica, Mar 17; Itar-Tass, Mar 18
MERCY KILLER WALKS FREE
A 60-year-old Australian man who killed his terminally ill girlfriend by spiking her breakfast cereal with sleeping tablets has walked free from a court in Perth. Terence Turton pleaded guilty to a charge of attempted murder. The case is unusual because Turton admitted that Debbie Johnson, who was in an advanced stage of Huntington's disease and unable to speak, did not ask to be killed. Mr Turton declared, however, that he had no doubt that he was doing what she wanted, based on some past remarks.
Turton received a three-year sentence, but he had already spent a year in remand and the other two years were suspended. It emerged when the sentence was handed down that Turton had a significant criminal record, but the judge was impressed by his unstinting care for the woman with whom he lived for five years. Mr Turton emphasised that he did not want to become a spokesman for a looming euthanasia debate in the state of Western Australia. ~ News.com.au, Mar 16
AMERICANS DEBATE CHILDREN'S "WRONGFUL BIRTHS"
Parents in Ohio can now sue doctors whose misdiagnosis leads to the birth of a disabled child whom they would otherwise have aborted. A 4-3 State Supreme Court ruling earlier this month limits the damages to the costs associated with a pregnancy and the birth of the child. Parents cannot sue for pain and suffering or for repayment of the cost of raising a disabled child.
In a New York Times Magazine review of the ethical morass surrounding "wrongful birth" suits in the US, Elizabeth Weil writes that "the moral quandary we find ourselves in pits the ideal of unconditional love of a child against the reality that most of us would prefer not to have that unconditional-love relationship with a certain subset of kids". Ms Weil, who aborted a disabled child herself, focuses on the painful experience of Anthony and Donna Branca. Their child AJ was born with Wolf-Hirschhorn syndrome, which causes severe retardation and physical disability. Eventually they won a multi-million dollar settlement with her doctor which was put into a trust for their son, after arguing that the misdiagnosis had deprived them of their right to abort AJ.
I think the reason that this topic is as loaded and painful as it is," comments Adrienne Asch, a bioethicist at Yeshiva University in New York, "is that prospective parents want to think that they are open to loving whoever comes into their families, and they don't want to think that they aren't." ~ AP, Mar 4; NY Times Magazine, Mar 12
EMBRYONIC STEM CELL FUNDING SCARCE
Finding private funding for stem cell treatments is getting no easier, according to reports in the financial magazines Red Herring and Forbes. "I would say the venture [capital] community has more or less abandoned this area over the last five years," says Ralph Snodgrass, CEO of VistaGen Therapeutics, a California company investigating embryonic stem cell technologies. A major obstacle is the continuing debate in legislatures over the ethical issues. Venture capitalists are willing to take financial risks, market risks, management risks, but the one thing they are not happy to do is take political risks," says William M. Caldwell IV, CEO of another embryonic stem cell company in Massachusetts, Advanced Cell Technology.
Although some industry figures predict that human embryonic stem cell treatments will be on the market within 5 to 7 years, a British regulator disagreed. "I think we really need to be responsible when we talk about the time frame of the technologies, such as saying they will be available in five years, because people will use it to discredit you, particularly after what's happened in Korea," says Angela McNab, of the UK Human Fertilisation and Embryology Authority.
Geoffrey Seller, of Forbes, summed up the commercial prospects for this controversial area: "For long-term investors, an investment in any of these companies is like buying a lottery ticket and sticking it in a drawer for the next 10 years... As is the case with most lottery tickets, though, there is a good chance they'll never produce riches." ~ Forbes, Mar 15; Red Herring, Mar 15
DOLLY'S "DAD" DEFENDED BY COLLEAGUES
After a blast of criticism following reports in the British press that he was not the main figure in cloning Dolly the sheep, Professor Ian Wilmut as been defended by fellow scientists. "I have no reason to think Wilmut did anything wrong," Dr Richard Henderson, of the Medical Research Council Laboratory of Molecular Biology in Cambridge told The Scientist. And German scientist Eckhard Wolf, of the University of Munich, noted that first authors do not have to be directly involved in a project. "If the basis of the research was his idea, then there is no reason why he should not be first author," he said. Also, contrary to a report in The Scotsman newspaper, the Frankfurt-based Paul Ehrlich Foundation has denied that it intends to strip Wilmut of a prestigious prize.
Naturally, there were other scientists who still feel that Wilmut should not have taken the lion's share of the credit for the landmark experiment. "Yes, this is common practice in scientific publishing," said prominent embryonic stem cell scientist Miodrag Stojkovic. "But, in my opinion, it is not fair practice." ~ The Scientist, Mar 15
IN BRIEF: Hwang-gate...
Hwang-gate: Hwang Woo-suk, the disgraced Korea stem cell researcher, has been fired from his post at Seoul National University. Six of his colleagues were also disciplined by the university. The Korean government has also revoked Hwang's licence to work in human cloning research. ~ Dong-A Ilbo, Mar 21; Washington Post, Mar 16
Stem cells: Japanese researchers have discovered a rich source of stem cells in menstrual blood. Dr Shunichiro Miyoshi, of Keio University School of Medicine, found that menstrual blood, which originates in the lining of the uterus, appears to have about 30 times more stem cells than bone marrow. He succeeded in culturing them so that they behaved like heart cells. ~ Reuters Health, Mar 13
Men's reproductive rights: A men's rights group is fighting to have a Michigan child support law declared unconstitutional because it violates precedents established in Roe v. Wade. It claims that the lack of reproductive rights for men violates the equal protection clause of the US Constitution. The case revolves around a man whose girlfriend fell pregnant even though she had assured him that it was impossible. Now he has been directed to pay US$475 in child support plus half of his daughter's medical expenses. "It just not fair," says Matt Dubay. "She had options in this. As a man, I have no options and am forced to live with her choices." ~ kaisernetwork.org, Mar 10
Russian tussle: A Russian grandmother is fighting a court battle for custody of a grandson conceived with the frozen sperm of her deceased son. Ekaterina Zakarova, 55, organised a donor egg and a surrogate mother to create the child. However, Russian authorities say that the child has no registered father or mother, does not officially exist and cannot be issued with a birth certificate. Since Mrs Zakarova is too old to adopt the child, the government wants to place him in an orphanage. ~ BMJ, Mar 18
