New Zealand scientists have genetically engineered a cow that may be the first in the world to produce hypo-allergenic high-protein milk.

The breakthrough - hailed as internationally "seminal" - had been kept under wraps by AgResearch until this morning and will be published in the prestigious American science journal Proceedings of the National Academy of Sciences.

The AgResearch team, led by Dr Goetz Laible, wanted to discover if they could produce milk which contained less of a particular milk protein known to be allergenic.

"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," said Dr Stefan Wagner, one of the lead authors on the paper.


"Two to three per cent of infants are allergic to cow's milk, and BLG allergies make up a large part of that percentage."

The scientists first tested the process in a mouse model engineered to produce the sheep form of BLG protein in mouse milk.

Employing a technique called RNA interference, two microRNAs (short ribonucleic acid molecules) were then introduced into the mouse to knock-down the expression of the sheep BLG protein, resulting in a 96 per cent reduction in the sheep BLG protein in mouse milk.

They next produced Daisy, a female calf that was genetically engineered to express the same two micro RNAs, this time to target the BLG protein that is also a normal constituent in cow's milk.

They then hormonally induced Daisy to lactate.

The resulting milk collected from Daisy had no detectable BLG protein and, unexpectedly, also had more than twice the level of the casein proteins that also normally occur in cow's milk.

"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," Dr Wagner said.

"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."


Read an AgResearch supplied Q & A here.

Dr Wagner described this as the project's "real discovery component" - and Daisy, now 11-months-old, gave the team many answers.

"To avoid the delay of two years before a natural lactation, the milk we analysed was from an induced lactation," he said.

"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."

In the future, the basic process of using designer microRNAs to target other genes could provide an efficient tool to change additional livestock traits, such as producing animals with enhanced disease resistance or improved lactation performance, he said.

Malaghan Institute research director Professor Graham le Gros praised the discovery.

"This outstanding breakthrough has enormous implications due to its potential to reduce the significant impact milk allergies have on our children and neatly avoids the concerns associated with genetic modification of the milk proteins themselves."

AgResearch was reluctant to go into the project's commercial potential, saying that development was restricted by tight regulations around genetic modification.

Caution urged

Auckland City Hospital immunologist Associate Professor Rohan Ameratunga congratulated the researchers on their innovative technology, but cautioned some people may still be allergic to the milk.

"It should however be noted cow's milk allergy may result from IgE antibodies to a variety of proteins. Our own work has shown Beta lactoglobulin is a major allergen. However many patients with cow's milk allergy generate IgE antibodies to other proteins including alpha lactalbumin, caseins etc.

"The absence of Beta lactoglobulin would therefore not be a guarantee patients with cow's milk allergy could consume this product safely. "

Commercial potential make take some time

Dr Mike Boland, principal scientist and executive officer at the Riddett Institute, said the calf was "scientifically very interesting" but any commercial potential is still some distance away.

"Although the composition of milk from this experimental animal has been shown to be quite unusual, this composition must be viewed with caution, as it was artificially produced (induced by hormones) rather than from natural lactation. It also remains to be seen if this animal is able to breed," Dr Boland said.

"Beta-lactoglobulin has long been regarded as the major allergen in cows' milk and so a niche opportunity must exist for milk such as this, for use in hypoallergenic infant formulas and the like. The absence of beta-lactoglobulin also has the potential to improve some processing properties of milk.

"This protein, however, is the main source of branched-chain amino acids in whey, and these are important for muscle metabolism - which is why whey powders are favoured by sports people and body builders. It is also the source of gelling functionality in whey products. And, of course, most people are not allergic to cows' milk. There is therefore not a case for getting rid of beta-lactoglobulin from all milk."