Day: 11th March 2011

 Human microbiota could be behind why deficient diets leave only some children seriously ill.

in the gut could be linked to the swollen bellies caused by condition known as kwashiorkor in malnourished children.MAURO FERMARIELLO / SCIENCE PHOTO LIBRARY

A study transplanting gut bacteria from human twins into mice could help to explain why some malnourished children develop kwashiorkor — a condition that triggers swelling in the belly, fatigue and vulnerability to disease. Researchers hope the work will point the way to better emergency rations for sick children.

The study, presented yesterday by Michelle Smith, a postdoc at Washington University in Saint Louis, Missouri, at the International Human Microbiome congress in Vancouver, Canada, looked at kwashiorkor in children in Malawi. The condition affects tens of thousands of children in Malawi alone and is fatal in up to 15% of cases. Although poor diet is clearly a factor, no one knows why some children are afflicted and others, living under the same conditions, are not. In tracking 317 pairs of twins in Malawi for the first three years of their lives, the group found that kwashiorkor affected both twins in a pair in only 7% of cases, and in 50% of of cases, only one of the twins.

“It’s so odd, because they’re living together,” says Smith.

One possible explanation for why only some malnourished children fall prey to kwashiorkor is that differences in gut bacteria might affect how susceptible people are. Gut bacteria can change how people absorb iron, zinc and vitamins from their food, and have been linked to obesity.

To investigate, Smith’s team, working in Jeff Gordon’s microbe genomics lab at Washington University, took faecal samples from some of the Malawian twins and used them to create a set of gut bacteria for mice raised in a completely clean, germ-free environment. Through this they made a near-perfect mimic of the children’s gut bacteria, allowing the researchers to see how those bacteria react to changes in diet, and to do other experiments, such as faecal transplants, that would be difficult or impossible with the children themselves. “People think their faeces is just waste — but it’s really useful stuff,” says Smith.

In preliminary results presented at the conference, Smith showed how mice with gut bacteria from one set of twins reacted to a series of timed diet regimes. First the mice had three weeks on a typical Malawian diet, consisting of 90% maize (corn) flour and water, and 10% vegetables; then two weeks on a diet of ‘ready-to-use therapeutic food’, a high-calorie peanut-butter-based food often given to malnourished children in developing countries; and finally two weeks back on the Malawian diet.

The mice with gut bacteria from the sibling with kwashiorkor were found to lose more weight on the maize-and-vegetable diet typical for Malawi, and gain more on the peanut-butter diet, than the mice with gut bacteria from the ‘healthy’ sibling.

Riding dietary wobbles

One possible conclusion is that the gut bacteria of the sick twin make it hard for the child to absorb the already limited nutrients and calories available in a meagre diet. The ‘sick’ bacteria were also much more susceptible to change — some species flourished, while others died down, altering the overall composition of the population. The ‘healthy’ gut bacteria, on the other hand, were relatively stable throughout the dietary wobble.

 This doesn’t prove that gut bacteria composition is the key to why some children get sick and others don’t. “I don’t think it’s not involved. But I can’t say it is, yet,” says Smith. James Kinross, a clinical researcher at Imperial College London, who was also at the meeting, wonders whether parasitic infections might also be a contributing cause.

But the results point the way to further studies that could help pin down the role of gut bacteria in kwashiorkor, and how they might be harnessed to help sick children. One idea is to transplant ‘healthy’ gut bacteria into the mice with ‘sick’ bacteria, and see if this makes a difference. “Their work is very important for developing countries,” says Martin Blaser, a microbiologist at New York University, who was also present at Smith’s talk. Their method, he adds, could be used to determine the microbiota that help people extract the maximum possible value from food.

Ultimately, Smith would like to identify a bacterium or set of bacteria that protects children from kwashiorkor, and add it to the emergency rations handed out to starving children, or give it to them beforehand. “Maybe we can do earlier interventions — before they suffer,” she says. 

The destruction of an embryo means procedures based on embryonic stem cells cannot be patented, according to the European Court of Justice.David Scharf/Science Faction/Corbis

The European Court of Justice today issued a preliminary opinion that procedures involving established human embryonic stem (hES) cell lines are not patentable.

The opinion has wrong-footed stem-cell researchers, who had been expecting a less conservative judgment.

“It’s the worst possible outcome,” says Oliver Brüstle, director of the Institute of Reconstructive Neurobiology at the University of Bonn in Germany, whose 1991 patent of a technique to generate nerve cells from established hES cell lines sparked the legal debate. Brüstle hopes that his patented work will eventually lead to the generation of nerve cells that could be used to repair damage to the brain or spinal cord.

The preliminary opinion was prepared by Judge Yves Bot, the court’s advocate general. The case was presented in November 2009 by the German Federal Supreme Court, which had requested clarification of the legal definitions of human embryos in relation to patentability after it had trouble adjudicating a challenge to Brüstle’s patent from the environmental organization Greenpeace, based in Amsterdam. Greenpeace said that the patent was unethical because hES cell lines are derived from human embryos.

European Union guidelines on biotechnology patenting are hazy when it comes to techniques involving cells derived from human embryos. That ambiguity applies to the embryos that provide starting materials for cultured hES cell lines — such as spare embryos from in vitro fertilization procedures — which would have been destined for destruction anyway.

The preliminary opinion will now be considered by the 13 judges in the court’s Grand Chamber, whose final decision is expected within a couple of months. If the Grand Chamber agrees with Bot’s opinion — and few preliminary opinions are reversed, says a spokesperson for the European Court of Justice — it could spell difficulties beyond the issue of patenting for researchers in other European countries.

National rules

Legislation covering hES cell research varies across Europe. Some countries, such as the United Kingdom and Sweden, are relatively liberal and allow research on fresh hES cells that are still totipotent, meaning that they would still have the potential to develop into a human if they were transplanted into a womb. Others are more restrictive: Germany, for example, allows research only on imported hES cell lines created before May 2007. Such cell lines comprise pluripotent cells capable of developing only into defined organs. And some countries, including Ireland, have yet to legislate. They are “quite obviously going to refer to a legal opinion at the European level for guidance”, says Hans Schöler, a stem-cell researcher and director of the Max Planck Institute for Molecular Biomedicine in Münster, Germany.

In his judgment, Bot concludes that pluripotent stem cells cannot be defined as embryos because “they are no longer capable of developing into a complete human being”. However, he adds that the embryonic source of pluripotent cells “cannot be ignored”. Bot argues that techniques involving hES cell lines are not patentable — even if the process in question does not involve the direct destruction of embryos — because they are tantamount to making industrial use of human embryos, which “would be contrary to ethics and public policy”.

Scientists fear that a legal opinion that the embryonic origin of hES cell lines cannot be neglected — however long ago the hES cell lines were established — is likely to encourage vacillating countries to introduce restrictive laws or complete bans. Patent expert Clara Sattler de Sousa e Brito, who is a member of Brustle’s legal team, says that in all patent jurisdictions the scope of a patent is defined by what that patent claims, not by issues that are outside of the claim, as the original source of hES cell lines would be.

The final opinion of the European Court of Justice will not be binding on the Federal Supreme Court in Germany, but it is likely to sway the German decision. “If we are not allowed to protect our inventions in Germany, we won’t be able to compete in the international market for new disease therapies,” says Brüstle.

L’annonce a été faite par le ministre des Finances hier: un groupe étranger veut se lancer dans la production du carburant à partir de la bagasse à Maurice. Pravind Jugnauth a fait cette annonce à St-Pierre lors d’une cérémonie de distribution de lopins de terre aux retraités des ex-sucreries Mon Désert-Alma et Savannah.  Pour le Grand argentier, il faudra d’abord examiner le coût de ce projet. Si le gouvernement le trouve rentable, il ira de l’avant avec ce projet, lequel devrait alors permettre à notre pays de réduire sa facture d’énergie. Pravind Jugnauth estime que dans un tel cas de figure, les consommateurs pourront souffler car c’est la hausse des prix des produits pétroliers qui explique la cherté des prix.