Scientists have genetically modified a cow which now produces milk that is low in beta-lactoglobulin (BLG), a whey protein some babies are allergic to, says a report published in the Proceedings of the National Academy of Sciences (PNAS).

Scientists from AGResearch and the University of Waikato, New Zealand, say this is a world first; a GM (genetically modified) cow which can produce milk which is much less likely to cause allergic reactions.

Approximately 3% of infants are allergic to milk which contains beta-lactoglobulin (BLG), a protein that does not exist in human milk. The vast majority of infants with BLG allergy outgrow their allergy by the time they are three years old. A study found that kids who have severe atopic dermatitis, or eczema, are less likely to outgrow their milk (or egg) allergy.

Parents say that cow’s milk allergy has a significant negative effect on the family unit. As well as having to cope with the consequences of the condition for the child after consuming cow’s milk, which typically includes diarrhea, vomiting, eczema and a failure to thrive, 70% said that the condition makes them feel guilty and distressed. 82% said the situation affected their sleep.

AgResearch Chief Executive, Dr Tom Richardson, said:

“PNAS is one of the top journals in the world, and to be published in it reflects the world-leading quality of the science behind this discovery. This will be one of the top-ranking science publications from New Zealand this year.”

Head scientist, Dr Goetz Laible and team had set out to determine whether they could produce milk with lower levels of a protein known to be allergenic to some people. One of the lead authors of the report, Dr. Stefan Wagner said “We were successful in greatly reducing the amount of beta-lactoglobulin (BLG), a milk whey protein which is not in human breast milk and which can cause allergic reactions. Two to three percent of infants are allergic to cow’s milk, and BLG allergies make up a large part of that percentage.”

Studies had shown that RNAs that were designed for reducing beta lactoglobulin were initially tested in cell culture, which is relatively easy to do. Cell culture tests may give scientists a good indication of a technology’s potential, but it is no guarantee that it can work with animals, or humans.

Producing genetically modified cows is extremely expensive, so the scientists started off experimenting with mice. The mice were genetically engineered to produce the BLG protein found sheep’s milk. They used a technique called RNA interference – two microRNAs were then inserted into the mouse to reduce the expression of sheep BLG. Eventually, they managed to get the mice to produce milk with 96% less sheep BLG protein.

As the mouse experiment demonstrated that the micro RNAs worked, the team felt comfortable to try it out on cows.

They carried out an experiment with a female calf they called “Daisy”. Daisy was genetically engineered to express the same two micro RNAs. However, this time the BLG protein found in cow’s milk was targeted. They then used hormones to induce the calf to lactate. When Daisy produced milk, it had no detectable BLG protein. Surprisingly, they also found that casein protein levels were twice as high as in typical cow’s milk.

The authors stressed that they do not yet know what the nutritional implications of high casein protein levels in milk are; they believe that cheese yields will most probably improve. They also need to determine what milk yields these genetically modified cows will have throughout their lifetimes.

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Producing hypoallergenic milk on a commercial scale is still a long way away, the scientists said

Dr Wagner said:

“People have long looked into reducing this enigmatic protein, or completely knocking it out, because there has been no definitive function able to be assigned to it. So, we developed this scientific model to investigate the effect of knocking BLG protein out on the composition and functional properties of milk, and to determine whether the absence of BLG produces cow’s milk that is hypo-allergenic.

This is the real discovery component to this project, and Daisy provides us with the opportunity to answer a lot of those questions.

To avoid the delay of two years before a natural lactation, the milk we analyzed was from an induced lactation. We only obtained small quantities over a few days for these initial studies. We now want to breed from Daisy and determine the milk composition and yield from a natural lactation. We also want to investigate the origin of Daisy’s taillessness, a rare congenital disease in cows.”

The authors wrote that this breakthrough not only has implications regarding the reduction of milk allergies in children, but also avoids concerns regarding genetically modifying the milk proteins themselves.

The researchers say that the technology they used – designer microRNAs – could be targeted towards other genes and be used to protect livestock from various diseases and conditions.

What about people who are lactose intolerant? – these findings are not related to lactose intolerance, which occurs when the person does not have an enzyme that breaks down the milk sugar lactose. In other words, people who are lactose intolerant will not benefit from drinking milk with reduced beta-lactoglobulin, unless it is also lactose free.

Is this technology too expensive for farming? – the scientists said that it is feasible to engineer dairy cattle so that they produce milk for people who are allergic to BLG. Initially, however, the process is extremely expensive and will be limited to few animals.

The authors say that their next step is to see whether Daisy’s calves can yield BLG-free milk from natural lactation. They will also test this milk to determine how hypoallergenic it is.

No, we don’t. The scientists emphasized that they are still at the discovery stage. A great deal more work is required. According to New Zealand’s current GM legislation, this milk cannot legally be consumed by humans.

Written by Christian Nordqvist