The number of children born allergic to peanuts or who become allergic later
has risen dramatically. In the US, the figure has doubled over the past decade.
The condition is by far the most dangerous of the food allergies, and sufferers
spend their lives trying to avoid foods that contain even tiny traces of peanut.
Unlike childhood food allergies such as those to egg and milk, there has been no
documented evidence up to now of anyone outgrowing peanut allergy.

A group led by Gideon Lack of St Mary’s Hospital, London, and Jean Golding of
Bristol University studied 14 210 British children for the first four years of
their lives. One in 200 was allergic to peanuts in infancy, with an average age
at the first reaction of 20.5 months. However, 41 per cent of these children had
outgrown their allergy by the time they were four. The team found that these
children were less likely to suffer from other food allergies, asthma and eczema
than those who did not outgrow their peanut allergy

The second group, headed by Jonathan Hourihane at Great Ormond Street
Hospital in London and John Warner at the University of Southampton, studied 100
children with peanut allergy and found that 15 of them had overcome it by the
age of five. These children also suffered less from asthma and eczema and were
less likely to be allergic to other foods. The results of this study will be
published in the British Medical Journal within the next few weeks.
Both groups are presenting their findings this week at the the meeting of the
American Academy of Allergy, Asthma and Immunology in Washington DC.

Both teams measured the levels of the antibody immunoglobulin E in the
children’s serum to test the extent of their allergic response. But for
confirmation, they had to feed the children peanuts to see how they
reacted—a highly dangerous task that they carried out in a hospital in
case of an adverse reaction. “We started by giving them doses of peanut at tiny
milligram levels and then gradually increasing the amount until we arrived at
eight grams,” says Lack.

Warner says that peanut allergy is only likely to disappear within the first
few years of life. “If they still have the allergy at the age of eight, then it
is very, very unlikely that they will grow out of it.”

The quest is now on to explain why some children outgrow their allergy while
others do not. Warner thinks it could be linked to a major change in how the
immune system operates. Children with allergies are thought to be “atopic”,
activating the more aggressive arm of their immune system, known as the TH2
reaction. Normal children are more likely to activate the milder TH1 arm. Warner
believes that children who outgrow the allergy are switching from a TH2 reaction
to a milder TH1 response. “It is difficult to pin down the cause of the switch,
but childhood infections could play a role,” he says.

Do-it-yourself medicine of all kinds is on the increase. Home kits to test for everything from ovulation to cholesterol and blood glucose are on sale in every high street chemist’s shop. In Britain, you can swish a special solution around your mouth and mail it off to be checked for the cystic fibrosis gene. In the US, you can even find out if you are HIV-positive by sending away for a home testing kit-prick your finger, dab some blood on the specimen card and results will be returned in a week.

But nothing promises to bring medicine to the people like the Internet. As a repository of information, a way of linking up with others suffering the same illness and a method for delivering public health education, the Net is unparalleled. The question is: will cutting out the medical middlemen, wading through Web help services, then diagnosing and treating ourselves actually make us healthier?

Not all doctors like to be confronted by patients carrying a sheaf of papers downloaded from the Internet, or to know that patients might be more up-to-date on a medical condition than they are. But many health professionals accept that they must change with the times. “You know that parents will do anything to help their child,” says Andrew Sharples, a consultant in paediatric intensive care at the Royal Manchester Children’s Hospital. “They will read papers, join patient groups and grab at any straw, so we are quite used to sitting down and discussing new treatments with them.” Consensual medicine, he says, is the way of the future.

Last year, one of Sharples’s patients may actually have been saved thanks to her father’s enthusiasm for the Net. Helaina Stone is one of only a few dozen people in the world suffering from Costello syndrome, a condition that causes skin deformities and mental retardation. When she was admitted for an emergency operation, the anaesthetist needed to know more about her disease before he could proceed. Her father came to the rescue. For years, he had kept a Web page (http://sargon.mmu.ac.uk/helaina.html) detailing all the quirks of her illness-as well as listing references to every medical paper ever published on the subject.

Following the successful operation, Sharples and the anaesthetist returned the favour. They wrote up a case report about the operation and posted it on the Web page. It has already helped at least one other hospital faced with a similar situation, they wrote in a letter to the British Medical Journal (vol 315, p 491).

The Internet may have been invaluable for Chewe and Stone. But plucking medical advice at random from the Net can be dangerous too. Doctors and patients will have to cast a wise eye over much of the information on the Web to make sure they get solid scientific findings. They must be careful they are not being fed medical myths or unfounded claims of miracle drugs, says Tony Delamothe, deputy editor of the BMJand coordinator of the journal’s Web site. Information on the Web is not guaranteed, he points out.

In many respects, the Internet has actually undermined traditional relationships between information authorities, their intermediaries and the public, says Andrew Blau, of the Benton Foundation, a think-tank based in Washington DC. The reliability of sources and intermediaries on the Internet is impossible to gauge, he says. “At the moment, anyone can wear a lab coat on the Net.”

People should be especially careful to find out who sponsors the site, warns Delamothe. He came across one site, sponsored by a major drugs company, that recommended a list of medications for diabetes. “The problem was, that company produced all the drugs.”

The issue gets even more complicated when drugs are offered for sale over the Internet-often contravening national regulations (This Week, 24 May, p11). In May this year, the WHO set up a working group to study the problem. It is expected to report early next year. Martijn Ten Ham, who heads the WHO’s Drug Safety Unit in Geneva is particularly concerned about prescription drugs. “This could particularly undermine the whole philosophy of prescription-only medicines,” he says. Ten Ham is also worried about drugs with popular appeal, such as “smart drugs” that purport to improve cognition.

Last year, BACUP (http://www.cancerbacup.org.uk), a British-based patient support group for cancer victims, received several calls from pharmacists who were being asked for a drug called hydrazine sulphate. A derivative of rocket fuel, it was being widely discussed on the Internet as a means of preventing severe weight loss in the terminal stage of cancer. When refused the drug by their pharmacists-it isn’t licensed in Britain-they ordered it straight from the Web.

But none of three trials carried out by the US National Cancer Institute showed any benefit from the drug in terms of survival, weight gain or quality of life. The confusion over hydrazine sulphate prompted BACUP to launch its own Web site. “We were increasingly worried about the amount of misinformation available on the Net,” says Anne Marie Jones, a spokeswoman for the organisation.

Doctors are also preparing for more accidents. Last month, The New England Journal of Medicine(vol 337, p 825) reported the case of a young man who accidentally poisoned himself by drinking 10 millilitres of oil of wormwood, which he had purchased from the Internet. He had thought it was absinthe liqueur. “Should the medical community brace itself for future cases of Internet-mediated toxic diseases?” the article asks.

But doctors also have much to gain in the Internet information explosion. Sharples, for instance, uses an Internet bulletin board to get quick access to the world’s top paediatric intensive care specialists. “If I have a query about one of my patients-for example, if they suffer from a rare disease-I can put up a notice and get advice from all the leading specialists around the world in the next 24 hours,” he says. In the old days he would spend hours digging out medical journals or trying to reach colleagues in the US or Australia by phone. Doctors also have better access to the established medical journals, such as the BMJ, The Lancet and The New England Journal of Medicine, all of which provide online versions, and search facilities for back numbers.

But there is good news for the lay public too. The rush is now on to package similar information for a nonmedical audience. Last year, the pharmaceuticals giant Glaxo Wellcome invested $500 000 setting up a Web site about HIV and AIDS (http://www.ama-assn.org/special/hiv/hivhome.htm), with the help of the Journal of the American Medical Association.

“The Internet will never supplant the medical profession,” says Chewe’s son. The point is not to replace the doctor, he says, but to arm yourself with knowledge. Then you can ask the right questions, make the right demands and tailor the doctor’s advice to your own circumstances. “It’s a great medical reference.”

Schentag surveyed 100 US hospitals, and found that most prescribe one drug at a time—a strategy which allows bacteria to develop resistance. Schentag has found that a better strategy is to use several antibiotics to wipe out infections before bacteria have a chance to evolve resistance to any one drug.

Schentag, who is also director of the Clinical Pharmacokinetics Laboratory at the Millard Fillmore Health System, a hospital in Buffalo, claims that existing doses of antibiotics are often inadequate. “Our studies show that dosing is too low to keep blood concentration of the antibiotic at the minimum inhibitory concentration for 80 per cent of the time,” he says. “This will result in resistance.”

Aside from recommending the use of multiple antibiotics, Schentag urges a strategy of “cycling” between different drugs, to make it harder for bacteria to develop resistance. He suggests that the bacteria should be grown in culture and identified, after which the patient could be given drugs which are particularly effective against the microorganism in question. During the three days that it takes to identify the organism, the patient could be given general antibiotics.

To keep costs down, Schentag advises switching from intravenous to oral therapy once the bacterium has been identified. Studies at Millard Fillmore indicate that oral therapy is effective and cheap, he says. Indeed, Schentag argues that his entire strategy is more cost-effective in the long run.

But other researchers who attended the New Orleans meeting are sceptical. “Switching from an intravenous agent to an oral agent might work in some settings—but it needs to be tested,” says David Hooper, an infectious diseases expert at the Massachusetts General Hospital in Boston. He also argues that Schentag’s idea of concentrating on antibiotics that are particularly effective against the bacterium causing an infection may not work. It is known, for instance, that some bacteria become resistant by acquiring new genes from other microorganisms, which might not be wiped out by a narrowly focused antibiotic.

Three years later Cole was to learn that his condition was caused by Lariam,
a relatively new antimalaria drug he had been prescribed for his visit to
Africa. But at the time his illness started no one suspected the drug and in
September 1994, when he had still not fully recovered, a doctor told Cole he was
suffering from stress and should take a holiday. He went to Java in Indonesia,
took another eight Lariam tablets and promptly fell seriously ill again. “I felt
permanently jet lagged and frozen, even though the temperature was 100 °
Farenheit”, he says, “and I was a nervous wreck.” He suffered from anxiety
attacks, loss of balance and was taken to hospital. Back in England his illness
continued. He became catatonic, and one morning woke up unable to move.

It was not until September 1995 that a specialist at the Middlesex Hospital
in London diagnosed Lariam as the cause of Cole’s illness. His experience is far
from exceptional. At least 600 travellers who claim they suffered serious side
effects after taking the drug have obtained legal advice. A Bristol solicitor,
Christiane Goaziou, is planning a group legal action on behalf of 450 people
claiming negligence by Hoffmann-La Roche, the Swiss company which manufactures
Lariam. And last month the Malaria Advisory Committee, made up of about 40 of
Britain’s tropical disease experts, held an emergency meeting about the drug.
The committee will issue new guidelines for its use within a few weeks.

Christine Facer, who works in the department of haematology at the Royal
London Hospital and is a member of the advisory committee, says she has taken
Lariam herself on five occasions without suffering side effects. But having seen
74 letters from Lariam users all with similar symptoms she is now convinced
there is a problem. “In high concentrations this is a nasty drug,” she claims.
While such side effects might be expected with a treatment, they are
unacceptable with a preventive medicine, she says. She reveals that when members
of the advisory committee were asked whether they would personally take Lariam,
they were divided “50:50, down the middle”.

New hope

Lariam, also known by the generic name mefloquine, was developed in the 1970s
from a collaboration between the Walter Reed Army Institute of Research in
Washington DC, Hoffmann-La Roche in Basel and the WHO in Geneva. It was first
licensed in Switzerland in 1985 at a time when the malaria parasite in many
areas of the world had become resistant to chloroquine, the traditional
antimalaria drug. It received a British licence in 1990. The researchers
believed they had at last discovered an effective way of reducing the 2 million
annual deaths worldwide from malaria. Initially it was hoped that the drug would
be used only to treat the disease, so that the parasite would not have a chance
to become resistant to it. But the spread of chloroquine-resistant malaria and
pressure from doctors meant that it also came to be used as a prophylactic.

Lariam is considered the most effective antimalaria drug on the market and
has been widely prescribed for people travelling to sub-Saharan Africa, Asia and
South America. Hoffmann-La Roche advises people with a history of psychiatric
disturbances or seizures not to take it, warning that it could induce certain
neuropsychiatric side effects—those affecting mental stability or the
nervous system. The company admits that up to 22 per cent of users not in this
“high risk” category may suffer mild side effects, which should wear off within
three weeks of them stopping taking it. Serious side effects—defined as
death, disability or needing hospital treatment—affect only 1 in 10 000,
it claims.

However, doctors believe the true number of Lariam takers who develop serious
side effects is much higher. “The figure of 1 in 10 000 is absolutely absurd,”
says Gordon Cook, a malaria expert at the Hospital for Tropical Diseases in
London. “I’ve had a colossal number of people with memory loss, disorientation,
panic attacks, psychosis and epileptic fits. These people, who had no history of
mental disease, suddenly started fitting.”

In July last year, Cook wrote to the British Medical Journal to
alert other doctors to the dangers of Lariam. His concern precipitated last
month’s emergency meeting of the Malaria Advisory Committee. The committee’s
proposed new guidelines are shrouded in secrecy, but Cook believes GPs should be
advised to stop prescribing Lariam as a malaria prophylactic and go back to the
earlier recommendation of a combination of chloroquine and proguanil. He
concedes that, on paper, Lariam is the best medicine for preventing malaria, but
points out: “If people get side effects they stop taking the drug, and if they
won’t take the drug then it is not effective.”

The first accounts of Lariam takers experiencing neuropsychiatric side
effects appeared in the late 1980s (see This Week, 30 September 1989, p 23). By
1989 the WHO had received 300 such reports. The side effects ranged from extreme
anxiety and dizziness to hallucinations, psychosis, mania, suicidal thoughts and
seizures. The WHO recommended then that airline pilots and other people whose
job required “fine co-ordination” should not take the drug. The Civil Aviation
Authority in Britain heeded the WHO’s warning and told its pilots to use
chloroquine and proguanil instead of Lariam for protection against malaria.
Hoffmann-La Roche, however, stood by its product.

The WHO’s recommendations did not apply to tourists. Up until March 1995,
British guidelines advised that travellers wishing to protect themselves against
malaria should take either a mixture of chloroquine and proguanil, or Lariam.
Then, after the publication of several studies—including one funded by
Hoffmann-La Roche in The Lancet—which claimed that the incidence
of serious side effects with Lariam remained at 1 in 10 000, the guidelines
changed: Lariam became the first choice malaria prophylactic.

Travellers were instructed to take one tablet, containing 250 milligrams of
mefloquine, every week, beginning the week before they left Britain and
finishing five weeks after their return. They were told that if while abroad
they developed flu-like symptoms, often indicative of malaria, they should
“self-treat” by taking two tablets immediately. However, several of those who
developed dizziness—a side effect of Lariam—thought they had
contracted malaria. The self-treatment only made their symptoms worse.

One of these victims, Emma Watts-Lay, returned from Kenya early in 1995 with
dizziness, loss of balance and blackouts. Her doctor was aware of Lariam’s side
effects but said her symptoms should wear off within two to three weeks. Yet
Watts-Lay was still suffering several months later. Hoffmann-La Roche then
admitted to her doctor that mefloquine could remain in her system for up to 7
months. She is still suffering and her doctors are treating her for
“Lariam-induced chronic fatigue syndrome”.

Brain wave

It is unclear why Lariam produces neuropsychological side effects, but
doctors at the University Hospital of Zurich in Switzerland may have uncovered a
clue. In 1994 a patient who was given Lariam for the treatment of malaria became
delirious and eventually had to be put on a life support machine. His doctor,
Rudolf Speich, suspected the drug was interfering with a neurotransmitter in the
brain called acetylcholine. Speich treated the patient with a drug called
physostigmine and he recovered immediately. Speich then called for a trial,
asking for collaboration with other doctors to discover if treatment with this
drug would be successful. He is still waiting for responses.

There are two trials in progress in Britain on the side effects of Lariam,
both of which are due to be published this year. One, by the Medical Advisory
Service for Travellers Abroad, began in 1993 and is looking at the effects of
Lariam on tourists. It is being coordinated by David Bradley of the London
School of Hygiene and Tropical Medicine, who is chairman of the Malaria Advisory
Committee. The other, concerning the effect of Lariam on soldiers, is being
carried out by the Ministry of Defence. The Lariam Action Group, a support group
set up in February, is concerned that the statistics used in these trials may
not be reliable because, until recently, doctors were unaware of the problems
associated with Lariam, and so would not have reported them.

Meanwhile there is no clear line on what travellers should do to protect
themselves from malaria. Chris Ellis of Birmingham Heartlands Hospital, who also
sits on the Malaria Advisory Committee, says: “My feeling is that if people are
going to sub-Saharan Africa, where malaria resistance is rife, for more than two
weeks, then they should take Lariam. If people are going for shorter periods,
then if they do catch malaria they are likely to be back in this country when
they develop the disease. They could probably take a less effective drug with
fewer side effects.” Ellis points out that British doctors have a good record
for spotting and treating malaria.

The Department of Health says it is “reviewing the evidence” on Lariam, but
will not make a recommendation on its use until it has seen the new guidelines
from the advisory committee. In the meantime Lariam victims will continue to
suffer, and travellers and their doctors will remain confused.

One group of US researchers says that some people avoid infection because
they have cells which are resistant to HIV. Another American team has identified
a range of immune system genes that help determine how long an HIV-positive
patient remains healthy.

William Paxton of the Aaron Diamond Aids Research Center in New York and his
colleagues studied a group of 25 people who had frequently had unprotected sex
with HIV-positive partners, yet remained uninfected. The group included
homosexual men who said that several of their partners had died of AIDS.

HIV infects a group of white blood cells called CD4 T cells. So the
researchers took CD4 cells from the 25 volunteers, cultured them in the
laboratory, and then tried to infect them with HIV. Cells from some of the
volunteers resisted the virus (Nature Medicine, vol 2, p 412). In two
cases, they did so even when the dose was 3000 times the amount normally require
to infect half of the cells in a culture, says Paxton.

But the story has a twist. The cells only resisted viruses taken straight
from the blood cells of an infected patient. They succumbed to laboratory
strains that had been grown for a long time in CD4 cell cultures. “It is
possible that other researchers have not seen [cellular resistance] because they
were using the wrong virus,” says Paxton.

Paxton says that viruses grown for long periods in cell cultures make groups
of CD4 cell fuse together into clumps called syncytia. These syncytia also show
up in many patients with advanced AIDS. But Paxton points out that HIV is
usually passed on by people carrying viruses that do not cause syncytia.

The researchers believe that the cellular resistance they have discovered
gives the immune system time to kick in and eliminate the virus from the body,
so that an infection can never take hold. They are not sure exactly how the
cells fight off HIV, but have found that resistant cells release large amounts
of molecules called chemokines, which are known to inhibit the virus. “It’s
fascinating,” says Mario Clerici of the University of Milan, who also studies
people who have been repeatedly exposed to HIV. Nevertheless, Paxton says it is
too early to tell whether chemokines could be used to protect other people from
infection.

Paxton thinks that the resistance is probably the result of particular genes
carried by a small minority of people. The researchers hope to pinpoint the
genes eventually, but first plan to see if they can find people with resistant
CD4 cells from a random sample of the population

Richard Kaslow at the University of Alabama, Birmingham, and his colleagues
across the US have found that HIV-positive people who have survived for long
periods without developing AIDS tend to have particular genes in their immune
system. The researchers looked at genes that code for major histocompatibilty
complex glycoproteins. These MHC glycoproteins display fragments of viral
proteins on the surface of cells so that the immune system recognises them. We
all have different MHC glycoproteins, and some are better than others at
harnessing an effective immune response.

Kaslow and his colleagues studied the MHC genes of 241 volunteers from two
large studies of HIV-positive people. They found that long-term survivors often
possessed genes called B27, B57, B18, B51,
A32 and A25. The patients who quickly became ill often had
genes called A23, B37 and B49 (Nature
Medicine, vol 2, p 405).

Kaslow warns, however, that the researchers are not yet ready to produce
genetic tests to predict how long an HIV-positive person is likely to live. Many
other genes will be involved, he says. For example, the researchers already know
that another related gene, which codes for a protein called TAP, seems to
modulate the effect of the MHC glycoprotein genes. The TAP protein ferries
pieces of foreign peptides to the MHC glycoproteins.

One intriguing possibility, says Andrew McMichael of the Institute of
Molecular Medicine in Oxford, is that some of the genes identified by Kaslow’s
team could also underlie the cellular resistance discovered by Paxton and his
colleagues. “They could be interrelated,” he says.

It may also be possible to use cell culture infection tests, like those
employed by Paxton and his colleagues, to determine how susceptible people might
be to HIV. Paxton says that one or two people have already asked for this kind
of test. But he is loath to encourage the practice. “I’m kind of scared that
insurance companies might get hold of this,” he says. “These resistant people
are few and far between. If people turn up on the doorstep, then we will test
them, but I usually say I can guarantee you won’t be one of these people.”

Sickle-cell disease is a genetic condition, common among Afro-Caribbeans, in
which red blood cells carry an abnormal form of haemoglobin called
haemoglobin-S. Although the cells are still able to carry oxygen to sites where
it is needed, when the cells give up oxygen their haemoglobin-S molecules link
together. This causes the cells to become dehydrated, distorted and rigid.

“The red blood cell has to be flexible to get through the capillaries, so the
sickle cell tends to get stuck,” says Seth Alper, one of the Harvard team. These
trapped cells can block the capillaries, preventing tissues getting enough
oxygen. Even though sickle-cell anaemia was the first genetic disease to be
characterised, there is still no really effective treatment.

The Harvard researchers were looking for a way to prevent the dehydration
that leads to cell sickling, and were intrigued by research which showed that
clotrimazole blocks a channel that pumps potassium ions out of red blood cells.
These ions drag water out of the cell with them so the researchers realised that
if this channel could be blocked in sickle-cell patients, it might be possible
to delay sickling until the cells have left the capillaries.

They treated five patients with a three-week course of oral clotrimazole and
found that all had fewer dehydrated sickle cells afterwards (Journal of
Clinical Investigation, vol 97, p 1227). “It’s pretty exciting to discover
a new use for an old drug,” says Alper. He adds that clotrimazole is
inexpensive, which is important given that patients may require lifelong
treatment.

Other researchers are interested in the new findings, but cautious. “The
results suggest a clinical effect,” says Sally Davis, a haematologist at the
Central Middlesex Hospital in London. But she wants to see whether the drug will
have benefits if given over long periods.

If oxygenated haemoglobin could be added to the bloodstream directly, rather
than inside blood cells in a transfusion, it could be used as a blood
substitute, and there would be no need to match the blood types of donor and
recipient. But unfortunately this causes the blood vessel into which the
haemoglobin is injected to contract, stopping blood flow.

Jonathan Stamler and his team at Duke University in Durham, North Carolina,
realised that some substance inside red blood cells must prevent this reaction.
They suspected that nitric oxide, which relaxes the muscles that surround blood
vessels, might be involved.

The researchers found that nitric oxide ions (NO⁺) can bind to an amino acid
called cysteine within the haemoglobin molecule (Nature, vol 380, p
226). When haemoglobin combines with oxygen it changes shape, Stamler explains,
exposing the cysteine molecule so that a sulphur atom within the animo acid can
bind to an NO⁺ ion. “No one knew why that cysteine residue was there,” he
says.

When blood cells reach the capillaries, the haemoglobin they contain releases
oxygen. As the molecule flips back to its original shape, the nitric oxide is
also released, relaxing the blood vessels. This in turn improves the delivery of
fresh oxygenated blood cells. By dilating blood vessels, haemoglobin lowers
blood pressure and Stamler argues that red blood cells are in fact the main
players in regulating blood pressure.

George Whitesides and his team at Harvard University are experimenting with
compounds that could stop the flu virus infecting cells lining the upper part
of the lungs. Before entering a cell, the virus must dock with its membrane
using a protein called haemagglutinin, which coats the surface of the virus
and binds to molecules called sialic acid, carried on the surface of many of
our cells. “Although the surface of the influenza virus is slowly mutating and
avoiding the immune system, the ability of the virus to bind to sialic acid
does not change,” says Mathai Mammen, a member of the team.

The researchers initially experimented with small molecules containing
sialic acid, with only limited success. After several years of research, they
hit upon a more promising molecule, which consists of a backbone made from an
organic polymer called polyacrylamide carrying many sialic acid side chains.
These bind to haemagglutinin, coating the virus with the polymer and
preventing it docking with cell membranes. “If you bring a very large molecule
to the surface of the virus, it blocks out other surfaces,” says Mammen.

The sialic acid side chains on the polymer also bind to a second molecule
carried by the flu virus, an enzyme called neuraminidase. In one experiment,
Whitesides and his colleague added a compound that inhibits this binding, and
found that the polyacrylamide became much better at preventing the flu virus
from docking with cell membranes (Chemistry and Biology, vol 3, p 97).

The researchers say the key to this apparent paradox lies in the molecule’s
polymer backbone. When a few of the sites where the polymer binds to the flu
virus are released, they say, the overall effect is to create large loops of
polymer around the virus. These loops keep the virus well away from its target
cell.

The researchers think the same idea could be applied elsewhere. “Our goal
is to develop a strategy that could be used in many biological systems, for
example antifertilisation between the sperm and egg,” says Mammen.

Although the polymer seems highly effective in blocking the flu virus,
clinical trials are a long way off. The researchers still have to tackle
issues such as toxicity – nobody knows whether it will be safe to give people
such a large molecule. They also have yet to work out how to administer it.
But the researchers hope that the polymer could one day be used either as a
preventative medicine, or to control an active infection.

Heat shock protein 73 normally ensures that other proteins end up where
they are needed, and helps them keep their correct shape. But French
researchers say that HSP73 can also throw a spanner into the works of the
immune system, turning it against the cartilage found in joints.

Since the mid-1970s, biologists have known that people carrying certain
immune system genes are more likely to develop rheumatoid arthritis. These
genes produce molecules called major histocompatibility complex (MHC)
glycoproteins, which usually sit on the surface of certain immune cells
alongside fragments of foreign proteins, and alert the immune system to any
invaders.

MHC glycoproteins contain a highly variable region called the beta 1 chain.
In people with rheumatoid arthritis, this chain often contains one of two
particular sequences of five amino acids. But how these sequences trigger an
autoimmune response has been a mystery.

Immunologists led by Jean Roudier of the Marseille Faculty of Medicine
looked for molecules that would bind to the rogue sequences. They first homed
in on a bacterial protein, HSP70, and then found that the human equivalent,
HSP73, also bound to the sequences (Nature Medicine, vol 2, p 306).

“HSP73 is involved in the transport of proteins within the cells,” says
Roudier. Normally, he says, the proteins that HSP73 interacts with do not
include MHC glycoproteins, but by binding to the rogue sequences, the protein
could interfere with their normal function.

Exactly how this turns the immune system against the body’s joints is still
unclear. One possibility, however, is that the shape of the glycoproteins
changes, prompting the immune system to attack the body’s own tissues, rather
than invading microorganisms. Alternatively, the bound HSP73 may end up being
presented to the immune system by the MHC glycoproteins, and itself gets
attacked as a result.

Although Roudier admits that there is a long way to go before his discovery
translates into an effective treatment, he thinks it provides hope. “There is
an experimental drug called deoxyspergualin that binds to the HSP73 protein,”
he says. If this drug could be used to target HSP73, he suggests, then the
rogue MHC glycoproteins might still function normally.