LONDON - Cartons of milk could one day join slow-ripening tomatoes and frost-resistant strawberries in the genetically modified foods aisle at the supermarket. The milk could come from cows genetically manipulated to produce the enzyme lactase in their milk, ensuring that the milk would be low in the sugar lactose and so more easily digested by people suffering from lactose intolerance.
Research on mice suggests that this scenario, although unlikely to come about in the near future, is indeed a possibility. A team of French researchers has developed transgenic mice that produce milk which has between 50 and 85 percent less lactose than normal. They say the technology could be transferred to dairy cattle, allowing the production of milk that could be consumed by people who cannot digest lactose.
Bernard Jost and colleagues at the Institut National de la Santi et de la Recherche Midicale (INSERM) in Strasbourg, France - together with colleagues from the Institut National de la Recherche Agronomique in Jouy-en-Josas, France, and from the Centre National de la Recherche Scientifique in Strasbourg - report their results in a paper in the February edition of Nature Biotechnology. Its title: "Production of low-lactose milk by ectopic expression of intestinal lactase in the mouse mammary gland."
An estimated 70 percent of adults worldwide have very low levels of the enzyme lactase, which is found in the small intestine. Lactase breaks down lactose, the sugar found in milk, into its constituent monosaccharides, glucose and galactose. Some people suffer severe symptoms after milk ingestion as a result, including bloating, flatulence, diarrhea, weight loss and abdominal pain.
Jost told BioWorld International: "We thought this was a very important nutritional problem. Our method could provide a way of producing milk low in lactose, which could be a cheap foodstuff available to everybody, particularly to people in developing countries, or to poor people in industrialized countries."
The group is currently holding discussions with several biotechnology companies on setting up a partnership to take the work forward.
Jost, working in the laboratory of Jean-Noel Freund at INSERM, and his colleagues constructed transgenic mice that contained the gene for lactase, under the control of a promoter that works specifically in mammary cells. The lactase precursor molecule is 220 kilodaltons (kDa) and is normally processed when it reaches the cells lining the small intestine into a mature enzyme of 130 kDa. This processing did not occur in the mammary gland of the transgenic mice, but previously the researchers had shown that the biological activity of the precursor molecule is similar to that of the truncated mature enzyme.
Further tests showed that the lactose concentration of the milk was reduced by 50 percent in milk collected immediately after removing the suckling mice from their mothers, and that it was reduced by 85 percent in milk which had been left in the mammary glands for eight hours without any suckling being allowed to take place.
Mice fed by transgenic mothers showed a similar growth curve to those fed by normal controls.
Bruce Whitelaw, principal investigator at the Division of Molecular Biology at the Roslin Institute in Roslin, Scotland, said the work by Jost and his colleagues was the first example of an enzyme encoded by a transgene being used to successfully modify the composition of milk. "Up until now, transgenic livestock have been used to produce human pharmaceuticals, which have to be purified out of the milk and can then be given as a drug," he said. "But in this case, the milk itself is the product."
Whitelaw, who wrote an "Analysis" article titled "Toward designer milk" which appeared in the same issue of Nature Biotechnology, added that attempts in the past to produce low-lactose milk by knocking out the lactose gene had failed. The resultant milk was very thick. "More tests are required to establish that the low-lactose milk produced by Jost and his colleagues is physiologically very similar to normal milk, but their experiment has shown that it is feasible to do this," he said.
Will dairy herds all over the world be producing tank loads of transgenic low-lactose milk in a matter of a few years? Will this milk go on sale in the supermarket? Apart from the practical and financial problems of transferring the technology from mice to cows, there is the question of public acceptance.
This is where Jost's paper could make a big impact, Whitelaw said.
"Currently, there is a huge debate in both the U.S. and the U.K. about whether transgenic plants should be allowed to enter the food chain, but there is less emphasis on transgenic animals because there is no product from transgenic animals en route for the food chain at the moment," he said. "All the transgenic animal products are pharmaceuticals for the treatment of disease. But what this paper says is that technology is available to make animals which could become part of the food chain. This paper has a role in rekindling the debate about transgenic animals."