The latest buzz on DNA research

A queen honey bee is genetically identical to most of her worker sisters. Yet their lives and accomplishments are spectacularly different. The workers have astonishing navigation and foraging skills, wearing themselves out bringing in nectar and pollen for the colony, while the much larger and longer-lived queen is above all a pampered egg-laying machine.

Scientists are only now beginning to understand the biological mechanisms that generate two such different female castes from one bee genome. Their research will shed light on one of the hottest topics in biology – epigenetics, which looks at the way environmental and other factors regulate the activity of genes.

The latest and most illuminating epigenetic study of bees, published last week in the journal PLoS Biology, catalogues for the first time the extensive molecular differences between the brains of genetically identical queens and workers.

The study, by German and Australian scientists, reveals the intricacies of the environmentally influenced chemical “marking” process called DNA methylation, which can alter gene expression without affecting the genetic code.

“This marking determines which genes are to be fine-tuned in the brains of workers and queens to produce their different behaviours,” says Ryszard Maleszka of the Australian National University, the study leader. “This finding is not only crucial but far-reaching, because the enzymes that mark DNA in the bee are the enzymes that mark DNA in human brains.”

More than 550 genes are differentially marked between queen and worker brains. The marking is achieved mainly through their different diets while they are larvae, with future queens raised on royal jelly, a rich combination of lipids, proteins and enzymes.

Maleszka says the study already “represents a giant step in the nature-nurture debate, because it shows how the outside world is linked to DNA via diet”.

“Similar studies are impossible to do on human brains,” he adds, “so the humble honey bees are the pioneers in this fascinating area.”

However, ants – another insect in which genetically identical females play different roles – are making a contribution too. In August, a US research team compared the genomes of two ant species. One species, a carpenter ant, lives in large colonies with a highly specialised social system. The second, a jumping ant, lives in much smaller colonies with less specialised roles. As expected, the study found more epigenetic changes in the species with a more complex organisation.

Both bees and ants, it seems, will make excellent “model organisms” for studying the epigenetic changes so important for human health.

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Hard cell: how antibodies fight on

Scientists at the Medical Research Council Laboratory of Molecular Biology in Cambridge have made a discovery of fundamental importance about the way the immune system fights viral infections.

Leo James and his colleagues at the LMB have discovered that antibodies continue to attack viruses inside infected human cells. Until now immunologists had assumed that the battle between viruses and antibodies took place entirely outside cells.

“This research is not only a leap in our understanding of how and where antibodies work, but more generally in our understanding of immunity and infection,” says Sir Greg Winter at the LMB, one of the world’s leading antibody experts.

The discovery is of more than academic interest, according to James. “These are early days,” he says, “and we don’t yet know whether all viruses are cleared by this mechanism, but we are excited that our discoveries may open multiple avenues for developing new antiviral drugs.”

The discovery of “intracellular immunity” could also lead to better vaccines for viral disease. The LMB scientists have patented the discovery and hope to take it through to clinical trials in the near future.

The LMB experiments show that antibodies, which the immune system sticks on to viruses, remain attached when viruses enter healthy cells. Once inside the cell, the antibodies trigger a response, led by a protein called TRIM21, which pulls the virus into a disposal system used by the cell to get rid of unwanted material.

This process happens within an hour or two – before most viruses have a chance to harm the cell. The scientists have also shown that increasing the amount of TRIM21 protein in cells makes this process even more effective, suggesting an avenue for drug development.

James says the research is most likely to lead to new treatments for “non-enveloped viruses”, such as those that cause common colds, winter vomiting and gastroenteritis.

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Fertility or longevity? Time to count sheep

A weak immune system is less of an evolutionary handicap than you might think, according to a study of wild Soay sheep on a remote Scottish island. It turns out that strong immunity extends life – but at the expense of fertility.

Scientists from Edinburgh and Princeton universities found that animals which are less susceptible to infection tend to live longer but produce lambs less frequently. Those with weaker immune responses reproduce more often, but die sooner. Over a lifetime, sheep with strong and weak immunity tend to produce the same number of offspring on average.

During the 11-year study on the island of Hirta, St Kilda, the researchers tested the sheep’s blood for antibodies, and monitored births each spring. The results were published in the journal Science.

Sheep whose blood contained the most antibodies were more likely to survive harsh winters but produced fewer offspring. Sheep with fewer antibodies had more lambs each year and in the end left just as many descendants.

“We have long suspected that there is a trade-off between life-prolonging immunity and reproductive ability,” says Andrea Graham of Edinburgh’s school of biological sciences. “This trade-off – which is rarely demonstrated – could explain why there is so much variation in the strength of immune responses.”

But scientists do not yet understand the fundamental reasons why better immunity should reduce fertility. CC

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Not quite the placebo effect intended

Scientists have long speculated about the “placebo effect” and how the psychology of giving medical attention to a patient can improve their chances of successful treatment, even if the innocuous pill they receive contains no active pharmaceutical ingredient. But what if the inactive “sugar pill” itself had a pharmacological effect?

In an article in the Annals of Internal Medicine, Beatrice Golomb from the medical school at the University of California, San Diego highlights a lack of both consistency and disclosure of the ingredients of placebos used during clinical trials to test the efficacy and safety of experimental drugs against patients receiving no treatment.

When she and colleagues studied 167 trials reported in four of the most prestigious English language medical journals in 2008-09, she found that only 8 per cent described the contents of placebo pills employed and only just over a quarter of those using placebo injections or other formulations.

That might not matter if all placebos were made to a consistent formula, but they are not. Golomb describes placebos that contain olive or corn oil, which could cause an underestimate of the benefits of experimental cholesterol-lowering drugs; and lactose, which could lead to an overestimate of the benefit of cancer drugs. “Perfection in the placebo is not the aim; rather, we seek to ensure that its composition is disclosed,” she writes.

It might even be that cheap everyday ingredients in some placebos bring about patient benefits almost as great as costly and complex new drugs. Andrew Jack

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Eye of the storm

Scientists will soon be able to forecast hurricanes years in advance. The Met Office Hadley Centre can now predict Atlantic hurricanes using factors such as sea surface temperature.