Biomedicine

Clive Cookson

Aids took centre stage at the BIO conference in Atlanta with a powerful performance from Elton John, Aids fundraiser extraordinaire, as the day’s keynote lunch speaker.

There is no denying the draw of celebrity, and half an hour before admission the lines snaked for several hundred metres round the Georgia World Congress Centre. The last speaker to pull in such a big BIO crowd was Bill Clinton in Chicago three years ago.

Several thousand people eventually filed into the lunch venue, a gigantic exhibition hall, and sat around circular tables to eat a salad of rare roast beef on iceberg lettuce followed by lime cheesecake.

The warm-up acts before Elton were standard fare at BIO plenary lunches. Brilliant high school science students and a star teacher won educational awards. A heart-rending film called Saving Roman showed sick children who could be helped through biotech research. The annual Biotechnology Heritage award went to Robert Fraley of Monsanto for work on GM crops. Sunny Perdue, Governor of Georgia, won the Governor of the Year award.

At last Kristine Peterson, group chair of Johnson & Johnson, one of the companies most active in Aids research, introduced Sir Elton (as everyone respectfully called him here) and he bounded up to the podium, wearing an orange-red round-necked shirt under a black suit – and his trademark orange-tinted glasses.

As someone who never seen him live or heard him speak, I was struck by Elton’s lively demeanor and strong, deep voice. He sounds like a successful English stage actor.

But enough of the superficial details. Elton’s message is that Americans have become dangerously complacent about Aids in their own country and worldwide. More than 1m Americans are living with HIV – one third of them under the age of 30 and most from poor and disadvantaged groups.

The lack of good educational materials about Aids is shocking, he said, and so is the refusal of the federal government to fund a clean needle exchange scheme that would reduce the spread of HIV among injecting drug addicts.

“Fewer and fewer Americans identify Aids as a public health priority,” he said. “It frightens me particularly that the number of young people concerned about Aids is plummeting.”

Elton ended with a challenge to the biotech industry to increase its rate of innovation in producing Aids drugs and vaccines.

Sadly Elton declined my request for an interview – and, more importantly, BIO’s request to take part in a press conference after his speech. But BIO, the Biotechnology Industry Organisation, held a media briefing anyway.

“Sir Elton John challenged our industry to address the gap between what we are doing and what we should be doing,” said Jim Greenwood, BIO chief executive. “We are here to accept that challenge.”

Three companies – GeoVax, Argos and Tibotec (a J&J subsidiary) – outlined progress on Aids vaccines and treatments. And Aids activists David Miller and Michael Manganillo, once sworn enemies of an industry they accused of profiting excessively from their disease, were there to give their support.

The Elton John Aids Foundation has raised $150m for community-based Aids project since its foundation in 1992. BIO said it would contribute $150,000 to the foundation and it challenged the “biotech community” to match that with small individual donations.

Clive Cookson

Synthetic biology is one of those futuristic concepts, like nanotechnology and regenerative medicine, which everyone feels is going to be a key technology for the 21st century but few really understand. All are a bit fuzzy in their definition – and practitioners are not clear about how much they are already happening and how much they lie in the future.

In effect, synthetic biology takes genetic engineering beyond the insertion or manipulation of individual genes, which scientists have been doing for 30 years. The idea is to engineer large numbers of genes at the same time to transform micro-organisms – and potentially even create new organisms from scratch – in ways that enable them for example to make previously inaccessible drugs or biofuels.

Britain’s Royal Academy of Engineering draws attention to the potential of synthetic biology in an excellent new report this week. Its message is that a national strategy of research and training in synthetic biology is essential, if the country is not to lose out in the next industrial revolution in the life sciences.

“The UK missed out in the 1970s microchip revolution because the government and decision-makers were not fully informed by experts in the field about its potential,” said Richard Kitney of Imperial College London, lead author of the RAE report, at its launch at the Science Media Centre. “Synthetic biology is destined to become of critical importance to building the nation’s wealth.”

Beyond the UK-oriented call to arms, the report is a good summary of who is doing what in synthetic biology.

The fact that an engineering body has written a report about biology may seem surprising at first – but it turns out that one of the key features of the new field is the application of rigorous engineering principles to the design of biological systems. Moving on from gene replacement on a case-by-case basis, biological engineers are developing standard procedures for designing, modelling, testing and validating methods to make and use synthetic DNA.

No-one will be surprised to learn that the US is well ahead of the rest of the world in both the basic science and the early commercialisation of synthetic biology. The RAE report lists 18 companies active in synthetic biology, of which 14 are based in the US.

Prominent American researchers include Craig Venter, the genomics pioneer, who is on the verge of building a simple microbe from scratch using laboratory chemicals, and Jay Keasling of the University of California Berkeley, who has engineered yeast to make artemisinin, the anti-malarial drug currently extracted from wormwood plants.

Clive Cookson

The flu strain that is spreading from Mexico and causing alarm about a possible pandemic has generally been called “swine flu” by health authorities, including the World Health Organisation.

But pig producers and animal health experts understandably dislike that term. Not only does it give pigs a bad name (and incidentally damage consumer demand for pork products) but also, they say, it is inaccurate.

In fact the H1N1 virus responsible for the outbreak has not been linked directly to pigs, in Mexico or anywhere else. The virus has not been isolated from any animal apart from humans, though virologists surmise that it may have originated in a pig.

Like birds and people, pigs can act as a “mixing vessels” in which different viruses swap genes and produce a new strain. The Mexican virus appears to contain porcine, avian and human genetic components.

The Paris-based animal health organisation OIE proposes calling it “North American flu”, to reflect its geographical origins. After all, the last pandemic, in 1968, was caused by “Hong Kong flu” – and the great 1918-19 pandemic was “Spanish flu”.

For me, North American flu is too much of a mouthful. I’d prefer “Mexican flu”.

Clive Cookson

Embryonic stem cells get all the publicity in stem cell research, good and bad. Their supporters see them as the future of regenerative medicine, producing all manner of new human tissues to treat degenerative diseases. Opponents – mainly from religious groups – hate the fact that they originate with the destruction of an embryo.

No treatment based on human embryonic stem cells has yet been tested on patients, though the US Food and Drug Administration recently told Geron that it could begin a clinical trial of embryonic stem cells to treat spinal injury. Meanwhile, as the UK national stem cell conference in Oxford heard today, universities are making good progress using adult stem cells, derived from the patients themselves, to repair bone and cartilage.

At Southampton University Richard Oreffo is leading a programme to fill holes or gaps in bones caused by accident or disease with a “living composite” material, made of stem cells extracted from the patient’s bone marrow mixed with a biocompatible scaffold.

Four patients have so far received transplants of living composite, says Prof Oreffo. Early signs are encouraging: the material is integrating well with the patients’ own bone and stimulating natural regrowth.

Meanwhile Alicia El Haj of Keele University is working on a 10-year clinical trial at Oswestry Orthopaedic Hospital, using adult stem cells to repair cartilage damaged in accidents. The patients’ stem cells are multiplied outside the body, before being injected back into injured joints.

Although the Oswestry trial uses stem cells on their own, Prof El Haj is also leading a more futuristic research project in which stem cells are linked to microscopic magnetic nanoparticles. “We can then use a magnet to move the stem cells around the body and control what they do there,” she says.

Magnetic control could be far more effective than simply injecting stem cells into the patient. The nanoparticle system has already produced new tissue growth in laboratory mice and is about to be tested in goats, ahead of clinical trials.

While adult stem cells are more readily available than embryonic stem cells – and pose no ethical problems – they are much less versatile. However Prof El Haj said techniques developed for adult stem cells, such as magnetic control, could be adapted to embryonic stem cells or the recently discovered “induced pluripotent stem cells” (which are made by reprogramming adult cells so that they revert to an embryonic state).

At present stem cell trials use one-off procedures developed by individual research teams. “We need to move away from bespoke therapy into standard procedures that can be used by [doctors] anywhere,” says Prof El Haj.

Although many scientists and patient groups are impatient for stem cell research to deliver clinical benefits more quickly, Prof Oreffo says it is important not to push ahead too fast: “The last thing we want is a case that goes wrong, because that would set the field back tremendously.”

Clive Cookson

Scientists at Sheffield university have taken an important step towards using stem cells to restore hearing to deaf people.

Their research shows for the first time how embryonic stem cells can be converted into the specialist cells we rely on for hearing. These sensory hair cells and auditory neurons, as they are known, cannot be regenerated in adults using existing medical technology; once they are damaged, hearing loss is permanent.

The long-term aim is to treat deafness by transplanting new auditory cells, generated from stem cells, into people who have lost their own.

“We have found the recipe to persuade embryonic stem cells, which can become any cell in the body, to become auditory cells,” says Marcelo Rivolta, who has led the Sheffield project for the past five years. “Our lab studies have shown that these cells behave and function just like their counterparts in our developing ears.”

The research started by studying cells from the developing ears of aborted human foetuses (around 10 weeks old) and then applied the findings to embryonic stem cells (which originate in early embryos just a few days old). The next step will be to graft the specialist auditory cells into deaf strains of laboratory animals.

The research – funded by the charities Royal National Institute for Deaf People and Deafness Research UK – is published online by the journal Stem Cells and will be discussed at next week’s UK National Stem Cell conference in Oxford.

Ralph Holme, director of biomedical research at RNID, says: “Stem cell therapy for hearing loss is still some years away but this research is incredibly promising and opens up exciting possibilities by bringing us closer to restoring hearing in the future.”

A more immediate application will be for research into deafness. “We have now an experimental system to study genes and drugs in a human context,” says Dr Rivolta, who is originally from Argentina.

“In addition to the future potential for restoring hearing with stem cell therapy, the recent research success means that we may now have better ways to test the efficacy and toxicity of new drugs on auditory cells,” adds Vivienne Michael, chief executive of Deafness Research UK.

Clive Cookson

The controversial all-in-one polypill – a cocktail of drugs to fight heart disease – has come through its biggest clinical trial so far with flying colours.

Two thousand middle-aged and elderly people in India took part in the trial. The results, published online by the Lancet, show that a polypill with five active ingredients works almost as well as the sum of its individual components. And the combination causes no unexpected side-effects.

Salim Yusuf of McMaster University in Canada and his Indian colleagues, who organised the trial, estimate that middle-aged people could roughly halve the chance of suffering a “cardiovascular event” – heart attack or stroke – by taking polypills regularly. For those at high risk, the benefits would be greater.

The polypill used in the Indian study contains a statin (simvastatin) to reduce cholesterol, aspirin to thin the blood and three antihypertensives (atenolol, ramipril and thiazide) to lower blood pressure. It is similar to the polypill originally advocated by two UK professors, Malcolm Law and Nick Wald, in the British Medical Journal in 2003.

Although there is nothing to stop a doctor prescribing the five polypill ingredients individually to patients, there is a strong psychological obstacle to taking so many pills at once every day. Much better to swallow them as a single capsule.

All the ingredients are off-patent, cheap and easy to produce. Indeed Indian generic drug companies are already gearing up to manufacture polypills.

Some experts have been concerned that adverse reactions between the ingredients might seriously reduce their effectiveness or even lead to new side-effects. The Indian study has allayed most of these fears, though more clinical evidence will be required before GPs – and regulators such as the US Food and Drug Administration – are convinced of the merits of the polypill. Issues such as dosing also need to be resolved.

A Lancet commentary by Christopher Cannon of Harvard Medical School, accompanying the research paper, raises another question: “Would the availability of a single magic bullet for the prevention of heart disease lead people to abandon exercise and appropriate diet? Would this make two of the major root causes of heart disease worse?” The medical profession would need to make sure that the answer is No.

The world of research

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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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