The researchers, motivated by the debate over the health risks of breast implants, analysed the medical records of 3500 Swedish women who had had breast implants. They considered only cosmetic operations, excluding women who received implants after breast cancer surgery.

The 3500 women ranged in age from teenagers to pensioners and had the implant operation between 1965 and 1993. In an average group of the same size and age, 59 deaths would be expected, but the researchers found that 85 women had died.

Fifteen had taken their own lives, three times the number expected, and a higher number of deaths from smoking-related diseases like lung cancer were also seen.

“Women who ask for breast implants may have low self-esteem,” suggests Veronica Koot at the University Medical Centre, Utrecht, Netherlands, who led the study. “Similarly, women who smoke may also have low self-esteem.”

Body conscious

Michael Beary, a consultant psychiatrist at the Priory Hospital, London agrees that women with low-self esteem are more body conscious and more likely to have breast implants.

“Quite a lot of women who become depressed will seek plastic surgery as a treatment for depression,” he says. “However, quite often operations go wrong, leading to unsightly scarring, unequal breasts or numb areas, and this can make the depression worse. I have certainly seen suicide attempts in women after surgery who were depressed beforehand.” Similarly, Beary says teenage girls with low-self esteem about their bodies can take up smoking believing it will help them lose weight, making it more likely that women who have breast implants are also smokers.

Rocketing rate

Koot thinks surgeons evaluating candidates for breast implants need to be vigilant for subtle signs of psychiatric problems. “If we first treat the psychiatric problems, then maybe some women will no longer want implants,” she says.

In 2002, nearly seven million people in the US alone underwent cosmetic surgical and non-surgical procedures, according to new figures released on Wednesday. Breast enlargements were chosen by nearly 250,000 American women, the second most popular operation after liposuction.

The American Society for Aesthetic Plastic Surgery says the overall number of cosmetic procedures has rocketed by 228 per cent since 1997. The vast majority of candidates – 88 per cent – are women.

Journal reference: British Medical Journal (vol 326, p 527)

The finding comes soon after work in the US revealed that IVF may be associated with an increased risk of rare birth defects characterised by excessive growth of various tissues.

An increasing number of women are having children via IVF, meaning that any health problems the procedure may lead must be investigated, say doctors.

But the authors of both studies caution that their findings are preliminary and should not scare parents away from undergoing the treatment.

Ovulation-inducing drugs

The eye cancer research was prompted when Dutch doctors diagnosed the disease, called retinoblastoma, in five children within a 15-month period. Normally, one child in 17,000 is expected to develop the disease.

They compared the incidence of the disease in IVF-conceived children with that in the general population. They calculated that the risk in IVF children may be between five and seven times higher, though the disease would still be rare.

Annette Moll, at VU University Medical Centre, led the study, published in The Lancet. She thinks the ovulation-inducing drugs used in IVF treatment could be a possible cause. Other possibilities include a genetic link between infertility and the eye cancer, or a general genetic problem resulting from the egg and sperm being joined in a test tube.

However, it is also possible that there is no link to IVF itself, but that serious disorders are simply diagnosed earlier in IVF children because the receive close medical surveillance.

Suspected association

The second study, published in the January issue of the American Journal of Human Genetics, looked at a national US registry of patients with Beckwith-Wiedemann Syndrome (BWS). Children born with BWS have an increased risk of developing various cancers.

Up to June 2001, four of the 279 BWS patients in the registry were known to have been conceived by IVF. Suspecting an association, the investigators began collecting details about conception methods for new patients entering the registry.

They found that three of the 65 new patients were conceived by IVF. This represents an incidence of 4.6 per cent, nearly six times higher than the 0.8 per cent incidence of assisted births in the general US population. But the researchers caution that, although they did not specifically recruit parents who had used IVF, such parents may have been more likely to participate in the study. And, again, even if their findings are confirmed, BWS would still be very rare even among IVF babies.

Journal references: The Lancet (vol 25, p 273), The American Journal of Human Genetics (vol 72, p 156)

Vitamin A deficiency is common in poorer nations and causes widespread disease, but in rich western nations, food is often fortified with extra vitamin A and vitamin supplements are widely used.

However, the new findings suggest the benefits of this supplementation may be outweighed by the harmful effects of high levels on bones, particularly as people in western countries live longer lives and have an increasing risk of osteoporosis. “The current guidelines for vitamin A should be reassessed,” says Hakan Maelhus, at University Hospital, Uppsala, Sweden, who worked on the study. He adds that the findings may not apply just to middle-aged men, but that these were simply the group studied.

Another study looking at whether diets rich in vitamin A are detrimental to bone health is being funded by the UK Food Standards Agency. It is due to report its conclusions later in 2003.

Hip fracture

The Swedish study analysed vitamin A levels in blood taken 30 years ago from more than 2300 men, who were then between 49 and 51 years old.

The 20 per cent of men with highest levels of blood vitamin A were 1.6 times more likely to break a bone and 2.5 times more likely to have a hip fracture than men with average levels.

Another way of boosting vitamin A levels is to take beta-carotene, which the body then converts. But there was no link between blood levels of beta-carotene and fracture risk.

Maelhus says two crucial questions remain unanswered: “We do not know what the men with the highest levels in their blood ate to cause such high amounts, nor do we know whether they had the same high level over the 30 years of the study.”

Fat soluble

Vitamin A weakens bones because it reduces the activity of bone-forming cells, as well as stimulating bone-reabsorbing cells. The vitamin is fat-soluble meaning the body cannot easily dispose of it. Excess amounts are stored in the liver. Levels in the blood also normally increase with age, probably because it takes longer to clear from the body.

The results may explain the high incidence of hip fractures in Scandinavia and the US, countries where vitamin supplements are commonly used, say the authors. Vitamin intake in Scandinavia is six times higher than in southern Europe.

Maelhus believes recommended daily intake (RDI) levels may be too high. He adds that many vitamin supplements provide 100 per cent of the RDI: “So if you eat anything else, you pass the RDI level.”

Journal references: New England Journal Of Medicine (vol 348, p 287)

The discovery could one day lead to a gene therapy treatment for diabetics whose own pancreatic cells do not produce sufficient insulin. This would involve converting part of the liver into replacement pancreatic tissue.

“This is not just re-programming of embryonic development,” says Jonathan Slack at Bath University, UK, who led the study. “The tadpole cells were already on the road to becoming liver.” The process of converting the liver cells into pancreatic cells is called transdifferentiation.

“It is the first step towards what could be a cure for Type 1 diabetes,” says Eleanor Kennedy at Diabetes UK. However, she adds that much more research is needed to see if it would work in humans and to look at how, when and how much insulin would be released.

Super-active gene

To convert the cells, the scientists genetically-modified frog embryos to incorporate a super-active version of a gene that is essential for forming a pancreas during development. The gene, called Pdx1, was then also active in the tadpoles’ liver.

The modified liver cells appeared to produce all the cells normally found in the pancreas, including insulin-producing islet cells and those that secrete enzymes to digest food.

They used a similar gene to convert human liver cancer cells into cells with a pancreatic character, some of which produced insulin. Non-cancerous liver cells cannot easily be grown in the lab, and Slack acknowledges that it may be more difficult to convert normal liver cells.

Few per cent

But he suspects that the amount of liver converted would depend on the dose of the gene delivered. This suggests it might be feasible to convert part of the liver of diabetic patients into pancreas without affecting the organ’s normal functions.

“A few per cent of cells secreting insulin ought to be enough,” Slack told ��è����Ƶ.

The researchers now want to test this idea in adult mice. “We know we can get DNA into the liver of mice simply by injecting it into their bloodstream. And previous work has shown that minced pancreas grafted into a liver can join up with the pancreatic duct. So our goal is to see if we can convert mature adult liver cells of diabetic mice into properly functioning pancreatic cells that will produce enough insulin to cure them,” says Slack.

Journal reference: Current Biology (vol 13, p 105)

In autoimmune diseases, immune cells mistakenly identify the body’s own tissues as foreign and mount an inappropriate attack. But by genetically modifying the cells that make the erroneous identification, scientists at Queensland University, Australia, have been able to stop them misbehaving.

The feat has only been achieved in the test tube so far, but the researchers are now using the approach to try to produce a vaccine against rheumatoid arthritis.

Re-educating the immune system is not a new idea, says Ranjeny Thomas, who led the study. A similar approach has been used to tackle an opposite problem, when the immune system fails to identify cancerous cells.

“What’s different is that this is the first time it has been possible to suppress an existing response, once the immune system has started down a deleterious pathway,” says Ranjeny.

“They are nice pre-clinical experiments,” says rheumatoid arthritis expert Ravinder Nath Maini, at Imperial College London. But he cautions: “We are very far away from any application.”

Engulfed intruders

The immune cells that alert our bodies to foreign material, or mistakenly to our own tissue, are called dendritic cells. Engulfing the intruders sets off a chain of events that enables the dendritic cells to activate another set of immune cells known as T cells. In turn, these generate the immune response, enabling our body to attack the intruder.

However, when the scientists knocked out the gene for one of the dendritic cell’s proteins, called RelB, the dendritic cell was no longer able to put another protein, called CD40, onto its surface. Without CD40 on its surface, the dendritic cells inactivated the T cells instead of activating them, thereby suppressing the immune response.

In rheumatoid arthritis, the immune system misidentifies the joints as foreign proteins and eats away at the cartilage and damages the underlying bone.

Although it is not known what molecule the dendritic cells are recognising, there are a number of candidates, says Thomas. She is now testing them with her manipulated dendritic cells to see if she can develop a vaccine that will prevent rheumatoid arthritis.

For a vaccine, dendritic cells taken from a person’s blood would be modified by knocking out RelB and then exposing them to the molecule triggering the autoimmune disease. This would specifically prime the cells to that disease and stop them from activating the immune response.

“Past vaccines for arthritis failed because they were not targeting the correct pathway,” she says. “But this is a very potent form of suppression and we could have a vaccine within five to 10 years.”

Journal reference: Immunity (vol 18, p 155)

“To ease anxiety, we often joke to women experiencing problems or prolonged labour that ‘it must be a boy’ – we wanted to see if there was any truth in this,” says Maeve Eogan, at the National Maternity Hospital in Dublin.

The study compared 8000 babies born at the hospital between 1997 and 2000 and only included women who had spontaneously gone into labour at full term.

Boys were 20 per cent more likely to require instrument-assisted deliveries and 50 per cent more likely to need caesarean sections. They were also more likely to be distressed, needing blood sampling to check for a lack of oxygen. And mothers delivering boys were more frequently given oxytocin, a hormone that stimulates contractions.

Big headedness

“However, we don’t want to scare women because 71 per cent of male infants still had a normal delivery,” says Eogan, compared to 76 per cent of female infants.

Eogan speculates that there is an “inherent vulnerability” in males that makes them less able to stand the stresses of labour. This could be a larger head size.

But while this may be a factor in prolonged labours and where forceps or Caesareans are needed for delivery, she adds that it does not explain the greater occurrence of fetal distress in boys.

“At least when we joke there is a difference between boys and girls, we can say there is a sound scientific basis to it and that we’re not just bad mouthing the men,” says Eogan.

Journal reference: British Medical Journal (vol 326, p 137)

The tiny Caenorhabditis elegans was the first animal to have its genome sequenced. However, identifying all its genes does not tell scientists how they control the animal’s development or behaviour.

So to reveal their function, biologists used the sequence information along with a technique called RNA-mediated interference (RNAi) to temporarily inactivate each of nearly 17,000 of the worm’s genes.

“It’s a tour de force of molecular genetics and a wonderful use of the full genome sequence,” says Paul Sternberg, at Caltech, California.

“The power of the technique is incredible. It is the first time anybody has looked at the function of nearly every gene in an animal,” says Julie Ahringer at Cambridge University, UK, who led the study. She told ��è����Ƶ if the functions can be found for all the genes an animal has, the complex process of how they work together can be understood.

Furthermore, half the worm genes have human counterparts, so discovering the function of the worm’s genes will help explore what human genes do.

Bugs for dinner

In nature, RNAi acts as a defence mechanism to protect cells against retroviruses, but it has been cleverly adapted by researchers. The technique involves designing double-stranded RNA molecules that match a sequence in the RNA produced by the gene you want to inactivate. The molecules attach to the latter, targeting its destruction and thereby blocking the genes activity.

A quirk of the physiology of C. elegans means that such gene inactivation can occur simply if the RNAi molecule is eaten by the worm. And luckily for the researchers, the preferred diet of this little worm is the bug that for decades has been used in thousands of lab experiments – the bacterium E coli. Simply inserting the RNAi sequences into E coli and allowing the worms to feed resulted in the chosen gene being knocked out.

The technique is remarkably fast. “It used to take a year to knock out a gene, now with RNAi one person can knock-out every gene in just a few months,” says Ahringer.

Fluorescent fat

The data gathered can now be used to investigate particular biological processes, such as ageing or, as Gary Ruvkun at Harvard Medical School, Boston, and colleagues have now done, body fat storage.

Along with the RNAi molecules, the researchers included a fluorescent dye in the worm’s bug diet. This enables fat droplets in the intestinal cells of living worms to be visualised.

They then scoured the 17,000 inactivated genes to find those involved in regulating body fat. Over 300 genes were found that reduced the amount of body fat upon inactivation, and over 100 were identified that increased it. About 200 have human counterparts that may represent new targets for anti-obesity drugs.

“Mapping in the human genome is like navigating along the seashore and we have just placed 200 lighthouses. Human geneticists should take note,” says Ruvkun.

Journal reference: Nature (vol 421, p 231, 268)

The French trial is testing a treatment for “bubble boy” disease, or X-SCID (X-chromosome-linked Severe Combined Immunodeficiency). The initial results of the trial were hailed one of the first great successes for gene therapy.

But the trial was halted in October 2002 following the first diagnosis of leukaemia in one of the boys. Three similar US gene therapy trials were suspended at the same time. A similar trial in the UK was not halted, as British doctors argued that without the treatment many of patients would certainly die. Cure rates for childhood leukaemia can be 90 per cent, but boys with SCID almost always die within a year without a bone marrow transplant.

However, the second leukaemia case has prompted the US Food and Drug Administration to suspend other trials that use the same type of virus to shuttle therapeutic genes into blood cells.

“Precautionary measure”

The FDA has no evidence of leukaemia caused by gene therapy in US studies, but says the suspension of trials using retroviruses is a “precautionary measure”. The agency will consider specific requests to allow new patients into gene therapy trials tackling life-threatening disorders for which there are no other treatments.

The UK’s Gene Therapy Advisory Committee says they will maintain their position and not suspend the British X-SCID trial. However, no new patients will be treated until the evidence from the French trial has been looked at, says Stephen Cox, of Great Ormond Street Children’s Hospital where the British patients are being treated. The patients have all been assessed in the last month and none shows any sign of leukaemia.

Norman Nevin, chairperson of GTAC, speculates that the adverse French results may be due to minor differences in the techniques used. “The design of the vector is not quite the same in the UK as in the French study,” he told ��è����Ƶ.

Philip Noguchi, head of gene therapy issues at the FDA, remains optimistic about the overall prospects of gene therapy. “We continue to see gene therapy as a promising therapy for all those who have not benefited from current technologies,” he says.

No resistance

Boys with SCID have no resistance to infection due to a faulty copy of an X-chromosome gene that makes an immune protein called interleukin-2. The gene therapy corrects the genetic defect by shuttling a correct copy of the gene into the patient’s cells using a virus. The treatment appears to have cured a number of boys.

The two boys with leukaemia are now being treated with chemotherapy and are clinically stable. The leukaemia may have been caused by the fact that the injected DNA cannot be targeted to insert into a specific part of a chromosome.

��è����Ƶs suspect the first child developed the cancer because the gene inserted next to an oncogene, called Lmo2, in a single white blood cell. This could have triggered the cell to proliferate uncontrollably, causing the disease.

According to Reuters, gene therapy experts called to an emergency meeting on Friday at the US National Institutes of Health have said that the development of leukaemia could be unique to the SCID gene therapy trial.

Since Saturday, over 70 scientists from Europe, the US and Ethiopia have detonated 19 explosions across and along Ethiopia’s Rift Valley. Project EAGLE is Africa’s largest ever seismic survey, and the world’s biggest ever three-dimensional seismic survey.

Tectonic forces are in the process of slowly pulling the African plate apart. “It is the only place on Earth where molten rock bubbles to the surface and a continental split is actively taking place,” says Peter Maguire, at Leicester University, UK, who is leading the study. A new ocean will form if, in several million years’ time, the continent splits completely.

The seismic waves produced by the explosions will travel tens of kilometres down before being reflected back to the surface and detected by the 1000 instruments deployed. The data collected will help the geophysicists better understand the role earthquakes and volcanic eruptions play in the fundamental tectonic transition from continent to ocean.

However, the work will also bring benefits for one of Africa’s most densely populated countries by mapping the seismic and volcanic hazards in the area. “The Rift Valley is the bread basket of Ethiopia, so a major earthquake or volcano would have a big effect,” says Cindy Ebinger of the Royal Holloway University, London, also an EAGLE participant.

Welling up

“When a continent is breaking apart, it does not just crack and go, but slowly stretches,” says Ebinger. The strain is accommodated by either rocks sliding past one another, causing earthquakes, or by molten rocks welling up from deep underground to fill the opening space, ultimately leading to volcanic eruptions.

In the transitional phase seen in the Rift Valley, “we do not know which of the two processes are more important,” says Ebinger.

Monitoring the seismic waves generated by natural earthquakes has produced some data. But setting off controlled detonations of up to two tonnes of explosive is more informative because the exact time and place of the event is known.

“We can therefore determine the velocities of the waves and so tell the difference between one rock and another and whether or not the rock is molten,” says Ebinger. “Finding mainly molten rock beneath the Valley’s floor would suggest magmatism is the dominant process in the transition.” It would also suggest that the area is at high risk from volcanic eruptions.

Broken segments

The explosions have been detonated in two 400 kilometre long lines, one along the length of the Valley and the other across it. This gives 3D images which may help answer another fundamental question.

Oceanic plates are generally made up of roughly 60-km long broken segments. “Break-up is a 3D process so we need 3D images to be able to ask whether segmentation starts before continental break-up or after,” says Ebinger.

EAGLE is also gathering other geophysical data, including electrical conductivity measurements, which can detect rock type and magma.

“It’s rare in geophysics for a single technique to give an authoritative answer,” says Kathy Whaler, at Edinburgh University, Scotland, who is leaving for Ethiopia on Friday to take the conductivity measurements. “But putting together the data will enable us to test our models.”