History > 2006 > UK > Health (III)

Scientists turn dead cells

into live tissue

Breakthrough could mean new treatments
for Alzheimer's and Parkinson's
but, instead of defusing opposition,
it is likely to raise new ethical dilemmas

Sunday September 24, 2006
The Observer
Antony Barnett and Robin McKie

Scientists working at a British laboratory have achieved one of the most controversial breakthroughs ever made in the field of stem cell science by taking cells from dead embryos and turning them into living tissue.

The technique could soon be used to create treatments for patients suffering from diseases such as Alzheimer's and Parkinson's, the researchers say. The breakthrough has been hailed by many scientists and ethical experts because it could circumvent opposition to stem cell experiments.

'This should get round opposition to stem cell science because live embryos will no longer need to be used in all experiments,' said Professor Miodrag Stojkovic, the researcher who carried out the experiments at the Centre for Stem Cell Biology at Newcastle University last year.

But other experts last night warned that the use of dead embryo cells could lead to more ethical dilemmas, not fewer. 'How do you know when an embryo is dead?' said Eric Meslin, director of the Indiana University center of bioethics.

Stem cells extracted from embryos are prized by scientists because they are capable of turning into any cell or tissue type in the body. Ultimately they could be used as treatments for heart disease and diabetes and other diseases, researchers argue.

But the technology involves creating and destroying living embryos to extract stem cells. Usually these embryos are made at fertility clinics when couples go for in vitro fertilisation (IVF).

However, Stojkovic's work suggests it may be possible to avoid using live embryos; instead, scientists use those that have died naturally during IVF. It would also mean that many more embryos were available for research and eventual treatment of the diseases, speeding up advancements in the cutting-edge science.

Stojkovic's experiments were carried out while he was working at the Centre for Stem Cell Biology at Newcastle last year. In a paper, published last week online on the website of the journal Stem Cells, Stojkovic reveals he and his colleagues took 13 embryos, created by IVF. All 13 had stopped developing a few days after conception. 'They were in a very early stage of development,' said Stojkovic, now head of Sintocell, the Serbian medical research centre.

The team then waited 24 hours to check that the embryos were no longer dividing before beginning their experiments. 'These were all deemed to be arrested embryos,' said Stojkovic. 'In other words, they were dead. [But] they had the capacity to develop any different type of cell you could think of, including kidney cells, liver cells, and skin cells.'

'I think this is a very important development, although stem cells created this way should not be seen as an alternative to those made from live embryos. They should be seen as an additional source.'

Last night right-to-life campaigners called for caution. 'In theory if an embryo is obtained ethically and a stem cell can be derived after that embryo has died naturally, then that will remove all ethical objections as there is no destruction of a living organism,' said Josephine Quintavalle, of Comment on Reproductive Ethics, a Catholic campaign group. 'We do not have objections to the use of donated tissue and organs in other areas of medicine.'

But Quintavalle warned that the case for the use of dead embryo cells had not been proved. 'There is the critical question of how you know when an embryo is dead or not.'

George Daley, of the Harvard Stem Cell Institute, said the paper's approach raised scientific concerns. 'If there was something wrong with the embryo that made it arrest, isn't there something wrong with these cells? We don't know.'

However, Stojkovic's work was given strong backing by Donald Landry, at the Columbia University Medical Center in New York, who called the work an important addition to the field. 'Regardless of how you feel about personhood for embryos, if the embryo is dead, then the issue of personhood is resolved,' Landry said.

'This then reduces the ethics of human embryonic stem cell generation to the ethics of, say, organ donation. So now you're really saying, "Can we take live cells from dead embryos the way we take live organs from dead patients?"'

What they do

· Embryonic stem cells have the ability to develop into any type of cell in the human body, from brain cells to skin and kidney cells.

· By creating cloned embryos of patients, it might one day be possible to grow their stem cells in the laboratory, say scientists. These could use then be used as transplants.

· Diseases such as diabetes, Alzheimer's and Parkinson's - in which particular organs or pieces of tissue have been destroyed - are thought to be the best candidates for treatments

    Scientists turn dead cells into live tissue, O, 24.9.2006, http://observer.guardian.co.uk/uk_news/story/0,,1879891,00.html

4.30pm

Dead embryos can be used to make new stem cells

Thursday September 21, 2006
Guardian Unlimited
James Randerson, science correspondent

Scientists have created embryonic stem cells using dead embryos, it was revealed today. By avoiding the need to deliberately destroy an embryo, the technique could offer a way of producing embryonic stem cell lines that would be ethically acceptable to pro-life groups.

Embryonic stem cells are capable of turning into any cell or tissue type in the body, and scientists think they offer great potential to treat diseases such as Alzheimer's. But to create a stem cell line scientists have had to destroy an embryo - typically one that is surplus to requirements during IVF treatment.

Now Miodrag Stojkovic at Sintocell in Leskovac, Serbia and his team has shown that it is possible to establish stem cell lines from embryos that have stopped dividing. Some embryos are not implanted during IVF treatment because they have visible defects. The new findings suggest that these could be used to make stem cells lines.

"My purpose was to demonstrate in a scientific manner that these arrested embryos - dead embryos - could be used for scientific purposes," said Dr Stojkovic, who was part of the British team that cloned the first human embryo in 2005. He said he supports the use of living embryos to harvest stem cells, but added that using dead embryos might allow scientists to circumvent restrictions, in countries such as the United States, on using live embryos to create stem cells.

The study, which is published in the journal Stem Cell, used very early embryos that are bundles of between 4 and 24 cells. Out of 13 embryos that stopped dividing at 6 to 7 days old, cells extracted from 5 of these went on to develop structures typical of stem cells. The scientists were able to establish a stem cell line from one of these. By comparison, using living 4-day-old embryos, the team was able to establish 2 new stem cell lines.

However, Helen Watt, director of the catholic Linacre Centre for Healthcare Ethics said ethical concerns remained. "If the aim in waiting for natural death - or what we guess is natural death - is to satisfy legal or political concerns, the death of these embryos may even be intended, not merely foreseen," she said.

Dr Watt added that the Catholic church had "serious moral concerns" about IVF anyway. "Use of IVF embryos - even dead embryos - would normally involve close complicity with IVF practitioners, of a kind which could not be justified."

Robin Lovell-Badge, a leading stem cell scientist at the National Institute for Medical Research in London, said the researchers could not be sure that an embryo was truly dead.

"They have no proof that this embryo, if it had been transferred back into a womb perhaps a day or two days earlier, would not have produced a baby," he said, "You can never answer that question."

The problem, he said, is that conditions in the lab can never be as favorable as they would be in the womb, so an embryo that could have survived there might appear inviable in the petri dish. "The culture conditions are never perfect, and just by slightly mishandling an embryo you can compromise its ability to develop."

But Robert Lanza, a stem cell expert at Advanced Cell Technology in Worcester, Massachusetts, welcomed the study. "We need to pursue all the options open to us," he said. "The question is whether we will be able to convince the politicians that it makes any difference."

In a separate study published in Cloning and Stem Cells, Dr Lanza's team showed that it is possible to repair eye disease in rats using human embryonic stem cells. The rats he used had damage similar to age-related macular degeneration, a disease that afflicts 30 million people worldwide, typically those over 60. The study involved injecting stem cells into the space below the retina.

    Dead embryos can be used to make new stem cells, G, 21.9.2006, http://www.guardian.co.uk/science/story/0,,1878057,00.html

Doctors back mass hospital closures

· 60 departments 'should be closed'
· Europe blamed for NHS overstretch

Sunday September 17, 2006
The Observer
Jo Revill, health editor

The medical establishment has thrown its weight behind controversial plans to close up to 60 hospital departments across the country as the only way to guarantee the highest standards of care for patients.

The Observer can reveal that the heads of the British Medical Association and the Royal College of Physicians have given their support to government plans for a massive 'reconfiguration' of hospital services, affecting every region. This will involve the closure of casualty departments, small midwife-led maternity units and children's centres in smaller hospitals.

Although the £512m deficit facing the NHS is a driving force behind the plans, doctors are fearful that hospitals cannot offer safe services as junior doctors' hours have been slashed in recent years from 72 to 48 a week, and will fall to 40 a week by 2009, leaving many fewer doctors available to be on call, particularly at night.

At the same time, patients are swamping casualty departments with relatively minor conditions instead of going to their GP, which puts smaller hospitals under huge pressure. The plans could involve the closure of some hospitals in towns where they serve populations of less than 250,000, with minor injury units taking the place of full casualty departments. There would be bigger emergency centres in major towns and cities.

The leaders of both the Royal College of Physicians and the British Medical Association are supporting proposals to cut up to 60 different units, provided that it is not done before the right facilities are built up in the community.

Ian Gilmore, president of the RCP, said: 'Leaving aside financial cutbacks, the pressure on medical staff due to reducing junior doctors' hours to comply with the European Working Time Directive has made it increasingly difficult to maintain full emergency services running 24 hours a day in many hospitals.'

Gilmore, a liver specialist, is aware that the question of closure cannot be put off for much longer. Three years ago, the college produced a report identifying 59 units which were vulnerable because they didn't offer services such as intensive care, a cardiac unit, or 24-hour cover by anaesthetists. Gilmore said that the college wanted to use the previous work it has done to advise local health officials about solutions to the problems of finding the right hospitals to close. 'However, it is crucial that the balance of services remaining after reconfiguration does ensure patient safety and high standards of medical care,' Gilmore said yesterday.

David Nicholson, the NHS chief executive, said last week there would be as many as 60 'reconfigurations' of NHS services, affecting every strategic health authority, in order to help improve care by concentrating key services in fewer hospitals. Nicholson said 'tough decisions' would have to be made about A&E, paediatric and maternity services.

It then emerged that the Health Secretary, Patricia Hewitt, had met the Labour Party chairwoman, Hazel Blears, last July to look at political 'heat maps' which show where hospital cutbacks would be most controversial. The Conservatives claimed that they had seen leaked emails showing that the government may be trying to target closures in areas where rival parties have seats - a claim which was denied by Downing Street.

James Johnson, head of the British Medical Association, said: 'We have talked for many years about the need to create large multi-centres which have all the facilities. The thing that has stopped it is political timidity because local politicians are terrified of the potential fallout of their local casualty department going. The public does seem to agree with the broad principle of larger centres and better facilities, but what people also want is an all-singing, all-dancing university teaching hospital at the bottom of the road.' He said that if Labour tried to protect the hospitals in its marginal seats, that would be 'disgraceful'.

But there are concerns that 'stealth cuts' are already being imposed by primary care trusts which have gone hugely over budget, with day centres, wards and community teams across the country now facing closure. Mental health trusts are also bearing much of the burden of the cuts, although many of these trusts did not go over budget last year. Health minister Rosie Winterton told The Observer that it was fair for mental health services to share the cuts, provided they were not disproportionate.

The prospect of a further round of closures has appalled some other healthcare groups. The Royal College of Midwives is alarmed that the plans may see the closure of small midwife-led units, believing there is a secret proposal to move more maternity services, run by consultants, into hospitals. Dame Karlene Davis, general secretary of the RCM, said last week that she was 'dismayed' by David Nicholson's 'prejudiced views' that consultant-led units were better for mothers and their babies.

    Doctors back mass hospital closures, O, 17.9.2006, http://observer.guardian.co.uk/uk_news/story/0,,1874356,00.html

For first time, doctors communicate with patient in persistent vegetative state

Brain scans showed woman was able to imagine playing tennis and walking round her flat

Friday September 8, 2006
Guardian
Ian Sample, science correspondent

A 23-year-old woman who has been in a vegetative state since suffering devastating brain damage in a traffic accident has stunned doctors by performing mental tasks for them. Brain scans revealed that the woman, who has shown no outward signs of awareness since the accident in July last year, could understand people talking to her and was able to imagine playing tennis or walking around her home when asked to by doctors.

The discovery has astounded neuroscientists who believe it could have dramatic implications for life and death decisions over other patients diagnosed as being in a persistent vegetative state (PVS). Last year, an intense legal battle over the life of Terri Schiavo, a woman diagnosed as PVS, was brought to an end when US courts upheld the decision to remove her feeding tube in March. She died 13 days later in a Florida care home.

Neuroscientists at the Medical Research Council's cognition and brain sciences unit at Cambridge and the University of Liege in Belgium used a brain scanning technique called functional magnetic resonance imaging (fMRI) to detect signs of awareness in the woman, the first time scientists have been able to do so in a PVS patient. The technique is now likely to become a standard way of determining how conscious vegetative patients are.

"This is extremely important. It's the difference between life and death. From cases in the UK and the US, we know that end-of-life decisions are of course extremely important and this will definitely change the way we deal with these patients. When you have signs of consciousness, you cannot decide to stop hydration and nutrition," said Steven Laureys, a neurologist at the University of Liege and co-author of the study which appears in the journal Science today.

Researchers led by Adrian Owen at Cambridge University began tests on the woman five months after her accident. Although she had emerged from a coma, she was diagnosed as being in a vegetative state, in which patients enter a cycle of sleeping and waking and even open their eyes, but are completely unresponsive.

Scientists ascertained that the woman could understand speech by playing a variety of sentences. Using the fMRI scanner, which takes snapshots of brain activity every second or two, they spotted different parts of her brain lighting up depending on which sentence she heard.

Previous attempts to spot signs of awareness in PVS patients have been inconclusive because brains can respond to some actions automatically. The uncertainty forced the scientists to come up with a test that would show categorically whether the patient was conscious or not.

Dr Owen said: "We said to her, when you hear the word 'tennis', we want you to imagine being on the centre court of Wimbledon playing a big rally and every time the ball comes to you, you struggle to get it back. Then, we had a second scenario in which we wanted her to imagine going from room to room in her home."

The two scenarios were chosen to trigger activity in different parts of her brain so they would be picked up by the scanner. While thinking about tennis, the scientists hoped to see a part of the brain called the premotor cortex, which governs limb movement, flicker into life. If she thought about walking around her flat, they expected to see a brain region called the parahippocampal gyrus, which handles mental maps of places, light up.

During the scans, the scientists said the words "tennis", "home" or "rest" every 30 seconds and looked for changes in her brain activity. Remarkably, after each word, her brain lit up as expected, suggesting she was responding to the instructions. Further tests showed her brain activity was indistinguishable from that of healthy volunteers doing the same task.

Scientists now have to discover how common it is for others in a vegetative state to be similarly aware of their surroundings. The woman in the study has since been able to follow her own reflection in a mirror, leaving open the possibility the brain scans may simply have picked up very early signs of her recovery.

Dr Owen added that the technique had shortcomings in helping diagnose patients, as some may not hear or understand the questions during a scan. "This gives us one more tool for making those very difficult decisions," he said.

Professor Colin Blakemore, neuroscientist and director of the Medical Research Council, said: "This is very impressive evidence for what continues to function in the brain, but function doesn't mean awareness or even potential for awareness. This is a strong indication that it is worth continuing to find ways of raising conscious awareness in such patients, because this work suggests the brain is still capable of cognitive function."

Explainer: PVS

Persistent vegetative state was first described in 1972 by Scottish and American neurologists and only came to medical attention because of extraordinary advances in keeping severely brain-damaged patients alive for longer.

Neurologically, the condition is a slight improvement on a coma. Patients diagnosed as PVS show no signs of consciousness or awareness, but unlike those in a coma, have periods of sleep and wakefulness and periodically open their eyes.

The condition is a source of huge controversy in medical and legal fields, largely because of the difficulty in proving a patient is unaware and the extreme difficulty in predicting whether a patient will ever recover.

Adults typically have a 50% chance of recovering from a persistent vegetative state within the first six months, but after a year, the chances of recovery drop dramatically. Those who recover after longer periods usually experience serious disabilities.

The mysterious condition continues to confound scientists. In May, a team of British and South African doctors announced they had given sleeping pills to a PVS patient to help calm restless movements at night. The patient woke up 15 minutes later and was able to speak and even tell jokes.

Doctors have kept the patient on the pills, and believe it works by acting on part of the brain that had been shut down in response to the patient's original trauma.

    For first time, doctors communicate with patient in persistent vegetative state, G, 8.9.2006, http://www.guardian.co.uk/science/story/0,,1867596,00.html