Brain

Clive Cookson

Another sign today of stem cell research becoming more commercial: An announcement that Stephen Minger, one of the field’s leading academics, will join GE Healthcare next week as head of Research and Development for Cell Technologies.

Minger, an American, has been in charge of stem cell biology at Guy’s Hospital and King’s College London since moving to the UK in 1996.

As well as being one of the top researchers into human embryonic stem cells in Britain – his lab has derived several hESC lines including ones with genetic mutations for cystic fibrosis and Huntington’s disease – Minger has been a fearless public advocate of stem cell science.

The relatively science-friendly legislative and regulatory framework for embryo research that has emerged in the UK owes something to Minger’s communications skills. He is one of the most open and media-friendly scientists I have come across, in any field.

Stephen Minger

Stephen Minger

“Leading GE Healthcare’s Cell Technologies research and development will allow me to bring many years of academic research in the stem cell field to bear in a commercial environment,” he says. “This is an opportunity for me to play a leading role in the realization of the emerging potential of stem cell technology in drug discovery and therapy, and to help grow a strategic business for GE Healthcare.”

GE Healthcare, part of the giant US General Electric group, is one of the world’s largest and most broadly based medical technology companies. It made clear its corporate ambitions in stem cell research at the end of June when it announced an exclusive alliance with Geron, the leading US stem cell company. Minger will, among other duties, lead the GE side of the Geron partnership. He will be based in the UK.

GE’s role in the commercialisation of stem cells will be to provide a comprehensive range of cells and tools for research and development. It does not intend to produce its own treatments.

Incidentally Geron has commented further on last week’s decision by the US Food and Drug Administration to put “on hold” its application to carry out the world’s first clinical trial of a treatment based on embryonic stem cells.  The product would treat spinal cord injury.

The California-based company says the FDA suspension relates to “microscopic cysts” that appeared on some animals during preclinical testing. Reassuringly, the cysts were not cancerous and had no adverse effects on the animals, so it seems likely that the clinical trial will go ahead soon.

“It is appropriate for the FDA to be particularly cautious about the first clinical trial of embryonic stem cells,” Minger says.

Clive Cookson

Traumatic head injury, which my Hong Kong colleague Justine Lau describes so graphically in Saturday’s FT Magazine, is all too common.

In most industrialised countries the number of people admitted to hospital with a brain injury is similar to the number who suffer a stroke: around 135,000 a year in the UK. Around half a million Britons are living with long-term disabilities from head injuries, according to the charity Headway. Again, the number is similar to those disabled by stroke, except that most injury victims are much younger; half of all deaths in adults under 40 are due to traumatic brain damage.

Justine Lau

Justine Lau

The brain contains about 1.3kg of white matter, with a texture similar to soft blancmange, held together in the skull by several layers of membrane. The effect of a traffic accident such as Justine’s is like vigorously shaking a plate of blancmange. The brain shears and tears, disrupting the connections between neurons (nerve cells), while bony ridges underneath the skull can lacerate the front of the brain. At the same time blood vessels tear and bleed, leading to a dangerous build-up of pressure as clots form within the brain.

While a stroke tends to affect a specific area of the brain, accidental impact usually causes more general damage. Symptoms and outcome vary greatly, of course. The death of actress Natasha Richardson in March, after initially refusing treatment following a skiing accident in Canada, showed that what seems at first to be a relatively minor blow to the head can trigger fatal bleeding. Conversely, some people recover almost completely from horrific initial injuries.

However many patients suffer from a common range of distressing symptoms and Justine’s account illustrates several of them. One is post-traumatic amnesia, the period after the patient emerges from unconsciousness following the accident and appears to be conscious and awake – but is behaving or talking in a bizarre or uncharacteristic manner, and cannot remember what happened a few hours or even a few minutes ago. Justine’s talking and acting like a child is typical of this phase.

Another symptom, which often occurs during the period after the patient has emerged from post-traumatic amnesia and is coming to terms with the accident’s long-term consequences, is severe depression, including suicidal thoughts and actual suicide attempts.

On the positive side, the brain shows remarkable adaptability – plasticity in scientific parlance. Gradually, the neurons re-form broken connections or make new ones to bypass areas that have been permanently damaged.

The best sign of recovery is returning to work. A rule of thumb is that if someone does not get back to work within two years, he or she is unlikely ever to do so. Justine’s return to the FT Hong Kong bureau 10 months after the accident is an excellent sign for her long-term future.

Clive Cookson

Nature, the great British science journal, has offered the animal rights movement a new cause. “Posters that feature an endearing marmoset face peering out of a cage and a caption denouncing experiments will make for an emotionally appealing campaign,” it says in an editorial.

Of course Nature, which publishes papers involving animal research in every issue, does not advocate such a campaign.

But its editorial is warning about the implications of an experiment described in this week’s edition. Japanese scientists have created transgenic marmoset monkeys that glow green in ultraviolet light – and passed the added gene for green fluorescent protein (GFP) on to their offspring.

Although several research teams have tried to produce transgenic monkeys that transmit their new genes to subsequent generations, Erika Sasaki of the Central Institute for Experimental Animals in Kawasaki and Hideyuki Okano of Keio University are the first to report success.

GFP, derived originally from jellyfish, is a standard “marker gene” in molecular biology, which scientists use to demonstrate that genetic engineering has worked.  While glowing green marmosets have little practical application, the experiment shows that transgenic monkeys could be important research tools for investigating human diseases, as transgenic mice already are.

The Japanese researchers transferred 80 transgenic marmoset embryos to surrogate mothers. Five healthy offspring were born, which passed the GFP gene on to their own offspring.

Dr Okano told a media briefing that the next step would be to generate transgenic monkeys that carried genes for brain disorders, starting with Parkinson’s and motor neuron disease. Marmosets would be better vehicles for studying such diseases than mice because their brains are much more like those of humans.

Nature supports such research, as does the FT, so long as it offers sufficient benefits, in the form of more sophisticated “models” of human disease, and the experiments are carried out responsibly.

But the researchers must be ready to deal with the broader ethical questions involved and to be open about their use of animals. As Nature notes, that may not be easy for Japanese scientists, who freely admit their dislike of public confrontation.

E.Sasaki et al 2009

Five transgenic marmosets, with feet glowing green in UV light (inset). (Credit: E.Sasaki et al 2009)

Clive Cookson

Just 10 years ago one of the dogmas of 20th century neuroscience – that adult humans do not make new brain cells – was overthrown. The discovery at the Salk Institute in California of adult neurogenesis, the creation of neurons, gave new hope to those seeking treatments for brain disease and inspired a great wave of neural research.

Leading investigators of neurogenesis discussed their findings at the BIO conference in Atlanta today, in the most fascinating scientific session I have attended here. The focus was on depression, which affects an estimated 15m Americans and hundreds of millions of people worldwide. As Saundra Maass-Robinson, an Atlanta psychiatrist, reminded us, fewer than half the patients treated with the antidepressant drugs available today “achieve remission” – in other words have their depression lifted.

Depression is a focus for neurogenesis research because neuroscientists, led by René Hen of Columbia University, discovered around 2003 that all antidepressant drugs achieve at least some of their effects by stimulating the growth of neurons in a region of the brain called the hippocampus, which is involved in learning and memory.

The conventional explanation for how antidepressants such as Prozac work is that they increase the production of certain neurotransmitters – brain chemicals such as serotonin that carry signals between neurons. But scientists have long been aware of a paradox here: the drugs change neurotransmitter levels very quickly but their clinical benefits only appear after a few weeks.

Hen’s hypothesis, that the delay in antidepressant action reflects the time taken for new cells to generate in hippocampus, has been confirmed by animal studies, brain imaging and postmortem examination of human brains – and is now widely accepted by neuroscientists.

The research led to the formation of BrainCells Inc (BCI), a biotech company in San Diego dedicated to developing new drugs for depression based solely on stimulating neurogenesis rather than neurotransmitters. Two candidate drugs, discovered by screening hundreds of chemicals to find ones that best trigger the proliferation of new cells in laboratory cultures of neurons, are already in early clinical trials and results will be available later this year, says BCI chief scientist Carrolee Barlow.

Of course if neurogenesis can be stimulated without unacceptable side-effects, there could be many other applications beyond depression. For example NeuroNova, a Swedish neurogenesis company targeting Parkinson’s disease and ALS, will be presenting its work here tomorrow.  

To go from a basic biological discovery to clinical trials within a decade is remarkable. As Barlow says, “this is one of the fastest moving fields I have ever seen in science.”

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The science blog is no longer updated but it remains open as an archive.

Clive Cookson, the FT's science editor, picks out the research that everyone should know about, in fields from astronomy to zoology. He also discusses key policy issues, from R&D funding to science education. He'll cover the weird and wonderful, as well as the serious side of science.

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