There is still a long way to go before any product reaches the market, but if the fish project is a commercial success many other proteins might be made in this way.

“We have a list of 20 other human therapeutic proteins that could be produced via fish to treat lung disease, liver problems, even tumours,” says Norman Maclean of the University of Southampton in the UK.

Maclean has been working on producing human coagulation factor VII in fish together with AquaGene of Alachua, Florida. Factor VII can be purified directly from human blood, but there is a risk of diseases being transmitted this way.

The only alternative, called NovoSeven, is produced using genetically modified hamster cells. But growing mammalian cells is very expensive, and the cost of a single injection can be as high as $10,000.

Gunshot wounds

Factor VII is used to treat people with a rare form of haemophilia that means they cannot make the protein themselves, and it is often needed to treat other forms of the disease as well.

Many doctors, including US army medical staff in Iraq, are now also using it to stem internal bleeding caused by accidents or gunshot wounds, even though NovoSeven is not approved for this purpose.

AquaGene is hoping to produce a much cheaper rival product using tilapia, a fast-growing freshwater fish widely farmed for food. Maclean has now managed to produce several lines of transgenic tilapia that produce human factor VII.

His team added a genetic switch from the tilapia to the human gene. This ensures that the gene is switched on in the liver of modified fish, and the protein secreted into the blood.

“Each millilitre of human blood has about 500 nanograms of the protein. We were able to match that yield in the blood of our fish,” says Maclean. He hopes to produce tilapia that will make 10 times that level within a year.

Silkworm larvae

The next step will be to convince regulators that the fish-derived protein is the same as the human form, and that it is safe. The researchers have already tested it on samples of blood taken from patients with haemophilia, but many more studies will have to be done.

Other groups are exploring rival ways of producing proteins, from plants and chicken eggs to silkworm larvae and cattle, but Maclean thinks fish are a serious contender.

There is no evidence that any disease can be transmitted from fish to humans, for starters. Transgenic fish are also relatively cheap and easy to make, whereas it can cost millions to produce transgenic cattle.

Because tilapia breed so quickly, production could easily be adjusted to meet demand. “But escape is a concern,” says John Matheson of the US Food and Drug Administration. For commercial production, transgenic tilapia could be grown in contained facilities.

Artemisinin, a compound extracted from sweet wormwood (Artemisia annua), has been used for more than 1500 years in traditional Chinese medicine to treat fevers. Over the past few decades, combinations of artemisinin derivatives such as artesunate and artemether have proved highly effective against malaria.

But in the developing world, where malaria kills more than a million people each year, the natural extracts have serious drawbacks. They are costly to produce, and they quickly degrade, making them difficult to use. And the treatment usually fails if the patient fails to take the extract regularly.

Now, a synthetic drug, with apparently similar properties to artemisinin, has been produced by Jonathan Vennerstrom of the University of Nebraska Medical Center in Omaha, US, and his colleagues. It is cheap to make and is being developed by the pharmaceutical company Ranbaxy of New Delhi, India, and Malaria for Medicines Venture (MMV), a non-profit organisation based in Geneva, Switzerland. The drug is now being tested for safety in humans.

Trojan Horse

“We have tested different doses in more than a dozen healthy volunteers and results have been encouraging,” says Lise Riopel, scientific officer for MMV. Phase II field trials are scheduled for late next year.

The synthetic drug, like the natural product, kills malarial parasites by producing free radicals. It does this by reacting with iron, which is released as the parasite digests the haemoglobin of its human host.

“In some respects this drug can be regarded as a Trojan Horse,” says Paul O’Neill, an expert on synthetic anti-malarial drugs at the University of Liverpool in the UK. Free radicals seem to target several proteins and enzymes that are vital to the parasite’s survival, Vennerstrom says.

Parasite proteins

Malaria has become much more common over the past 30 years, largely because the malarial parasite has developed resistance to many cheaper drugs such as chloroquine and quinine. But the parasites do not seem to develop resistance to any of the artemisinin family of compounds, probably because they attack several different parasite proteins. However, Brian Greenwood of the London School of Hygiene and Tropical Medicine says it is possible – though unlikely – that the parasite could build a resistance to the synthetic drug.

Laboratory tests suggest that the synthetic drug should remain active in the body for longer than the natural extracts. A three-day course should be sufficient to completely cure malaria, O’Neill says.

The MMV estimates that about 300 to 500 million malaria treatments are needed each year. “If human trials are successful, the new cheap synthetic drug could prove to be a breakthrough in the fight against malaria,” Riopel says.

Journal reference: Nature (vol 430, p 900)

Animals have been shown to have a preference for drugs since early studies in the 1960s. But it was not clear whether the animals simply derived pleasure from the substances or whether they were actually addicted to them.

So Pier Vincenzo Piazza and colleagues at the Bordeaux Institute for Neurosciences, France, set up an experiment in which freely moving rats could obtain traces of cocaine by poking their noses into a hole.

After a three-month period the rats were not only extremely reluctant to cut down on their drug use, they had an unusually high desire for the cocaine and would seek it even when it was accompanied with an electric shock to the foot. “This tells us addiction is not a social phenomenon, but a brain disease,” Piazza told żěè¶ĚĘÓƵ.

Inherent susceptibility

Something else also caught the researchers’ attention. The percentage of rats showing all of the symptoms above – about 17 per cent – is the same as that in human addicts. And like their human counterparts, the addicted rats were also most likely to return to drugs after staying away from it for 30 days.

The researchers concluded that prolonged use of cocaine and inherent susceptibility in some rats turned them into addicts. The researchers do not know what causes the inherent susceptibility, but suspect it is a combination of stress, negative social environments, and genetics.

Terry Robinson, a behavioral neuroscientist at the University of Michigan, Ann Arbor, says: “Though drugs are necessary for abuse, they are not the only condition for addiction”.

Casual to compulsive

In a related study, researchers Louk Vanderschuren and Barry Everitt at the University of Cambridge, UK, showed that rats that had been accessing cocaine for extended periods of time continued to do so even when they received a cue evoking the memory of a past electric shock.

“Translated into human terms, our study shows the progression from casual drug taking – which is flexible, i.e. sensitive to interference – to compulsive drug use -which is inflexible and occurs with considerable cost to the addict,” Vanderschuren told żěè¶ĚĘÓƵ

The rat models now mean researchers can seek a more complete understanding of what addiction entails, at both neurobiological and psychological levels, he says.

“Identifying the changes in the brain that underlie the loss of control of drug use may help to develop treatments that reverse or suppress these changes,” says Vanderschuren. “That would be a therapy that addresses addiction at its core.”

Journal reference: Science (vol 305, p 1014, p 1019)

And people in Cameroon are showing up with symptoms of HIV, but are testing negative for both the virus and its primate equivalent SIV, the virus from which HIV is thought to have evolved. That suggests that new strains of an HIV-like virus are circulating in wild animals and infecting people who eat them, sparking fears that such strains could fuel an already disastrous global HIV pandemic.

The warnings come from experts who gathered this week for the annual meeting of the Society for Conservation Biology at Columbia University, New York. They say that deforestation and the trade in bush meat are creating the ideal conditions for new diseases to emerge, as people have ever closer contact with exotic animals that harbour novel pathogens.

The conference reports follow the discovery earlier in 2004 that simian foamy virus, another disease that infects monkeys, has been found in bush-meat hunters and three different species of primates. As yet, it has not caused ill-effects, but it could mutate into something more insidious.

“Basically, this is a virus looking for a disease,” says William Karesh, director of the Wildlife Conservation Society’s field veterinary programme.

Small game

Despite those concerns, we still do not have a clear idea of how many wild animals are killed and eaten, David Wilkie, co-chair of the Bushmeat Crisis Task Force (BCTF), told the conference. He has carried out the first-ever survey of daily bush-meat consumption by rural communities in Gabon.

Over two years, he documented a flourishing, but previously unrecognised, informal trade in bush meat, where rural communities hunted and ate small game, having already caught most available primates. He thinks official studies of bush meat sold in markets account for only 40 per cent of the total bush meat eaten in the country.

“In the Congo basin alone, between one and five million metric tonnes of bush meat was consumed last year,” says Heather Eves, head of the BCTF, a non-governmental organisation that monitors the trade.

And the dangers of eating such animals are real. The BCTF points out that SIV infection has now been reported in 26 different species of African nonhuman primates, many of which are hunted and sold as food.

Wake-up call

The bush-meat trade is not the only way new diseases could jump into humans. The trade in wildlife, both for agriculture and as pets, is a major global business estimated to be worth billions of dollars. In 2002 alone, for instance, over 38,000 mammals, 365,000 birds, two million reptiles, 49 million amphibians, and 216 million fish were imported into the US.

In 2003, monkeypox jumped from pet prairie dogs to their human masters. That “was just a gentle wake-up call,” says Tonie Rocke, an epidemiologist with the US Geological Survey. Previously the disease had only been known to infect humans after bush-meat hunters ate red colobus monkeys.

The trade in exotic farmed meat also appears to have sparked an unusual outbreak of a common human parasite called Trichinella. In 2004, a farmed crocodile in Papua New Guinea was discovered with Trichinella, which was only thought to infect mammals, after being fed wild pig meat (Emerging Infectious Diseases, vol 10, p 1507).

In 1999, another farmed crocodile in Zimbabwe was similarly infected. “There is a strong chance that infected crocodiles may be in other countries, and could infect humans who eat them,” says Edoardo Pozio, a parasitologist at Rome’s institute of public health. People in Papua New Guinea who eat crocodile meat have already been found to have the parasite, which can cause fever, rashes, and respiratory and neurological problems in humans.

Rocke says there are few safeguards to prevent the spread of diseases through the wildlife trade, and is calling for stricter import and quarantine restrictions.

Brown dwarfs have been an enigma ever since they were discovered in the mid-1990s. The dim bodies are too massive to be called planets – about 10 to 75 times the mass of Jupiter – yet not big enough to ignite hydrogen fusion and glow like a star.

One early theory suggests brown dwarfs form like stars. But the claim is largely circumstantial, based on the fact that they both appear to have dusty discs surrounding them at birth. An alternative theory proposes that small proto-stars forming in a dense gas cloud are ejected before they are big enough to trigger fusion.

Testing these theories is not easy as brown dwarfs are usually very faint, but leftover heat from their birth does allow them to glow for a short while. Using this as a guide to seek out brown dwarfs, Kevin Luhman, from Harvard University, Massachusetts, US, trained the Magellan telescopes at Chile’s Las Campanas Observatory on a star cluster 540 light years away in the Chameleon constellation.

Free floating

He found a dozen new brown dwarfs floating freely, but one pair stood out. “At first I thought the double image was a blur from the telescope but spectroscopy readings confirmed the presence of a binary brown dwarf. It was an accidental find,” says Luhman.

Calculations showed that the two brown dwarfs were orbiting each other at 240 times the distance between the Earth and Sun, a distance 10 times greater than other brown dwarfs pairs.

Since even the slightest tug could upset this fragile balance, Luhman suggests the pair could not have formed from a violent ejection. Instead, they must have formed in a slow gravitational collapse, like stars.

Gibor Basri, an astronomer at the University of California, Berkeley, and one of the early pioneers of brown dwarf research, agrees. “The distance between most other binaries is very small. The extremely large separation in this binary shows that the same process that formed stars extends to bodies of low mass as well.”

The new research was presented at the Cool Stars conference in Hamburg, Germany, on Thursday, and will be published in a future issue of The Astrophysical Journal.