Abdul Hamood and Kendra Rumbaugh of Texas Tech University in Lubbock and
colleagues studied Pseudomonas aeruginosa, which can infect wounds and
kill patients with severe burns. If anaesthetised mice with small scald wounds
are infected with P. aeruginosa, 95 per cent of them die within 48
hours. But when the team inoculated animals’ wounds with bacteria in which
communication genes had been knocked out, the mortality rate fell to 6 per cent.
The bacteria also failed to spread.

The genes involved produce enzymes that churn out molecules called
autoinducers. When enough bacteria are present, the concentration of
autoinducers passes a threshold level that causes the bacteria to switch on
virulence genes, allowing them to spread through the host.

This allows bacteria to build a bridgehead before running riot, says Barbara
Iglewski of the University of Rochester, New York, who collaborated on the
project. In doing so, they may avoid attracting the attention of the immune
system.

Hamood hopes it will be possible to find drugs that block bacterial
communication. “This approach does not kill cells, it blinds them,” he says.
“There is no pressure for mutant bacteria to become resistant to treatment.”

To reproduce, bacteria first copy their DNA with an enzyme called polymerase III. But pol III stops copying when it encounters bases that have been damaged, for example by ultraviolet light or free radicals.

Now Myron Goodman, a biochemist at the University of Southern California in Los Angeles, and colleagues have discovered that a group of proteins previously thought to shepherd pol III across damage, actually take over the copying when pol III gets stuck (Proceedings of the National Academy of Sciences, vol 96, p 8919).

But pol V only gets through the crippled region by doing a sloppier job, Goodman says. It is far more likely than pol III to make mistakes. “Pol III is the good bricklayer that gets stuck and walks away from the job,” Goodman says. “Pol V is a bricklayer that can lay any brick because it’s so promiscuous.” After pol V copies for a short stretch, pol III gets back on the strand and continues. Goodman says that a similar error-prone polymerase probably exists in plants and animals as well, including humans.

Hypericin, the active ingredient in St John’s wort, reacts with visible and ultraviolet light to produce free radicals. In laboratory experiments, Joan Roberts of Fordham University in New York and her colleagues showed that this reaction can damage proteins in the eye that give the lens its transparency. “If the proteins are damaged, they precipitate out of solution and make the lens cloudy,” says Roberts. “That’s what a cataract is.”

However, hypericin did not cause any protein damage when kept in the dark, the researchers reported at a meeting of the American Society for Photobiology. Roberts recommends that those taking St John’s wort should wear hats and wraparound sunglasses. “If this product is consumed, one should avoid exposure to bright light to prevent damage to the eye,” she says.

The side effect may be a particular problem for any sufferers of seasonal affective disorder (SAD), who combine St John’s wort with light-box therapy. “Certainly never take this drug and use light therapy,” says Roberts. But she cautions that all users should be warned of the risks, particularly if taking the herbal treatment at the beach or while skiing.

Ivor Roots, a clinical pharmacologist at Humboldt University in Berlin, agrees that people must exercise caution when using the herb. “One should not assume that herbal drugs are not without potential side effects,” he says. “In Germany, it is recommended to avoid tanning beds while taking St John’s wort.”

Cows grazing on St John’s wort flowers are known to suffer from extreme photosensitivity that can prove fatal, according to Roots. When exposed to bright sunlight for long periods, the animals develop inflamed and swollen tissues that make swallowing and breathing difficult.

David Wheatley, a psychiatrist at the Charter Chelsea Clinic in London, says he has had no complaints from his patients about side effects while taking St John’s wort. “It works extremely well for people with mild to moderate depression,” he says.

But Geoffrey Bove, a neurophysiologist at Harvard Medical School, has treated a patient who developed intense pain in areas exposed to the sun while taking St John’s wort (The Lancet, vol 352, p 1121). Bove believes that free radicals generated by hypericin resulted in the damage to the patient’s nerve cells.

There may be a silver lining lurking in the herb’s side effect, however. Hypericin’s strong reaction with light is currently being investigated as a treatment for some skin cancers. “Its side effect is being used as a potential therapy for killing cancer cells,” says Roberts.

More than 600 women with HIV took part in the trial. All were given an
antiviral drug during labour, and their babies were treated with the same drug.
Half the mothers and infants were given AZT, the other half a newer drug called
nevirapine. Both interfere with the enzyme reverse transcriptase, without which
HIV cannot replicate.

“We were hoping nevirapine would be as good as AZT, but it turned out to be
better,” says Anthony Fauci, director of the National Institute for Allergy and
Infectious Diseases (NIAID) near Washington DC, which sponsored the trial. In
sub-Saharan Africa, between 25 and 35 per cent of babies born to women with HIV
themselves become infected. In the group receiving AZT, 25.1 per cent were
infected at around 15 weeks. But in the nevirapine group, the figure was just
13.1 per cent.

Nevirapine also has the advantage that it crosses the placenta readily and
breaks down slowly, so can be given in small doses. In the Ugandan trial, the
women received a single dose of nevirapine during labour, and their babies were
given another dose within three days of birth. AZT had to be given several times
over several hours during labour, and twice a day to the infants for one
week.

These modest doses mean that developing countries should be able to afford
nevirapine. In Europe and North America, AZT is often given to pregnant women
with HIV over a period of months, cutting the rate of transmission to less than
10 per cent. But this costs more than $800.

At just $4 per mother and child, the nevirapine treatment should be
within the reach of countries that until now have had to give up on protecting
their infants from HIV. And the NIAID is now even suggesting that the nevirapine
treatment is so cheap that it could be given routinely to women in labour in
developing countries experiencing severe HIV epidemics.

But James McIntyre, director of the perinatal HIV research unit at the Chris
Hani Baragwanath Hospital in Johannesburg, says this ignores the realities of
health care in poor countries. “Only 50 per cent of women in developing
countries deliver in a health service setting,” he says. McIntyre argues that
health infrastructures need to be improved to offer all pregnant women tests for
HIV so that they can be given the drug during labour if they are infected.

The optimism about nevirapine and mother-to-child transmission of HIV comes
hard on the heels of preliminary results suggesting that a simple drugs cocktail
could provide an affordable treatment for adults with AIDS in developing
countries (This Week, 1 May, p 4). But much work remains to be done. For
instance, about one in seven HIV-free babies born to infected mothers will
acquire the virus from breast milk. The next phase of the Ugandan study will
look at the effectiveness of nevirapine at preventing transmission during
breastfeeding.

Jon Chambers of SmithKline Beecham in Harlow and his team were looking into
the role of a receptor in the brain called SLC-1. It turned out that the
receptor binds to melanin-concentrating hormone (MCH), which regulates appetite
and energy balance in people.

The researchers also showed that this receptor is expressed in parts of rat
brains that are involved in feeding behaviour (Nature, vol 400, p 261).
In earlier experiments, scientists showed that genetically engineered mice
without MCH were leaner and ate less than normal mice.

Olivier Civelli and his colleagues from the University of California at
Irvine report similar results in the same issue of Nature (p 265).
“This opens the door to drug design aimed at the MCH receptor,” says Civelli. He
thinks it may be possible to reduce appetite with drugs that block the MCH
receptor.

Jackson and his colleague Jenny Barajas have designed a test tube that is
sure to raise eyebrows. Instead of having to be held vertically, it lies prone
on the lab bench on its flattened base, eliminating the need for a test-tube
rack. However, the test tube can be clipped into a plastic holder for extra
stability (see Figure).
Its neck slants up at a 45° angle to prevent the contents from spilling.

The novel shape allows the test tube to be placed directly on balances,
hotplates or microscopes, says Jackson, who has formed a company called
Norwind-Cortez, based in Ypsilanti, Michigan. It can also be used vertically
like a conventional tube, and fits standard lab equipment such as racks and
centrifuges.

Jackson has tried to interest chemists at the University of Michigan in Ann
Arbor in his design. So far, however, he admits that the most common response
has been amused scepticism. “New ideas take time to catch on, and the customer
has to be ready,” says Jackson.

Billy Joe Evans, one of the chemists who agreed to look at the tube, doubts
if it will replace the standard design. But he thinks it will prove useful for
certain applications. One of the chief advantages, he says, is that liquid in
the tube has a greater surface area in contact with the air. This minimises the
likelihood of “bumping”—having boiling liquids squirt out of the tube as
air pockets trapped during heating are released.

Other innovators who have tried to introduce novel laboratory glassware say
that they have also encountered resistance from scientists. David Howard,
manager of business development in the science division at Corning in New York,
remembers a less-than-enthusiastic response to the launch of a range of
plastic-coated glassware designed to contain broken glass and corrosive
substances in the event of an accident. “People asked why were we bothering to
do it, even within the company,” he says. Six years later, Corning is selling
tens of thousands of pieces a year, and other firms are copying the idea.”That’s
the best form of flattery,” says Howard.

The technique, intracytoplasmic sperm injection (ICSI), has enabled many men
with very low sperm counts, or whose sperm do not swim normally, to become
fathers. But doctors have warned that ICSI may allow the kind of genetic defects
that cause infertility to be passed on rather than being weeded out of the human
gene pool.

Sherman Silber, director of the Infertility Center of St Louis in Missouri,
and colleagues at the Whitehead Institute for Biomedical Research in Cambridge,
Massachusetts, studied four boys conceived by ICSI. All four inherited a
deletion on the Y chromosome within a region called AFZc, already linked to male
infertility (Human Reproduction, vol 14, p 1722).

Other researchers are reporting similar findings, says Silber. But infertile
couples turning up at his clinic seem unconcerned. “Patients are warned of this
risk but still want their own genetic child anyway,” says Silber. “They seem
relieved that their child will be no worse off than them because the deletion is
no worse.”

Joe Conaghan, director of the IVF laboratory at the University of California,
San Francisco, says that 13 per cent of men with very low sperm counts are
infertile because of deletions on their Y chromosome, and similar heritable
deletions may account for much of the unexplained 87 per cent.

Robert Brackett and colleagues at the University of Georgia and the Georgia
Institute of Technology have devised an optic sensor that can identify the
presence of the bug, notorious for causing food poisoning from undercooked
chicken or contaminated surfaces, in as little as ten minutes. This is a huge
leap from the several hours to a few days that similar devices and current
laboratory methods demand
(This Week, 15 May 1999, p 20).

The device uses two translucent strip-shaped sensors—a test strip
coated with antibodies specific to S. typhimurium, and a reference
strip with a nonspecific antibody. As wash fluid from the chicken passes over
both strips, the organisms are trapped by the antibodies in the test strip but
not the reference strip. A laser beam shone through the strips registers a
pattern of light on an output device. When the bacteria are present and bind to
the test strip, they interfere with the beam path, changing the phase of light
and causing a different output signal compared to the reference strip (
Journal of Food Protection, vol 62, p 431).

According to Mike Doyle, director of the Center for Food Safety and Quality
Enhancement at the University of Georgia, today’s immunological tests take as
little as eight hours, but are not as likely to pick up pathogens as traditional
microbiological methods, which take several days.