Milk from a Hucow

May 2011

Image from Wikimedia Commons

In ancient China, the emperor and empress could drink human milk throughout their lives. This was believed to be the height of opulence.

In modern China, despite the massive economic growth and industrial expansion, the gap between the rich and poor is widening. The answer sought is in biotechnology: the country seems to have set its sights on making human milk available to all, babies, children and adults. The catch is that this 'human' milk will come from a cow.

In March, China held an exhibition to showcase its major technological achievements during the 'Five-Year Plan' of 2005-10. Among the wonders on display were photographs of a herd of more than 200 cows that had been genetically transformed to produce 'humanised' milk.

The actual genes, the techniques used to produce the herd, the health of the herd, and the quality of milk obtained are shrouded in mystery and hype, not helped by the need to translate or interpret all the information from Chinese.

However, the lead researcher Li Ning who has produced the GM herd confidently predicts that his GM milk will be as safe to drink as that of the ordinary cows, and that “Within 10 years, people will be able to pick up these human-milk-like products at the supermarket”, ensuring that “healthy protein contained in human milk is affordable to ordinary consumers”.

At this stage, the claim that milk from transgenic animals will be safe is scientifically indefensible, but the UK still managed to trot out a British professor to say “Genetically modified animals and plants are not going to be harmful unless you deliberately put in a gene that is going to be poisonous. Why would anyone do that in a food?” (Comment. The good professor obviously has not read about the GM soya with a non-toxic Brazil nut gene nor about the GM peas with a non-toxic bean gene, both of which would have been killers if they had made it into our food chain.)

What we do know is that to develop the gene technology, make it work in cows (which are not usual laboratory animals), check out the results at every stage, and achieve a herd of over 200 beasts takes a considerable investment of expertise, time and money. China has clearly been on the case for a long time.

So, what sort novel genes do these GM cows actually have? What sort of novel milk do they produce?

Judging from the previous papers published by Li's team, the novel cows have been given human look-alike genes for either α-lactalbumin, lysozyme, lactoferrin, or any combination of these three (see information box). Each of these proteins is abundant in human milk but present at very low levels in cows' milk. Transgenic forms of each of these proteins have been produced by cows in Chinese laboratories in the past.

The likely method of creating these cows would involve constructing the desired artificial DNA in a test tube, multiplying it up in a bacterium, injecting the DNA into bovine foetal cells grown in culture, removing the transformed nucleus and using it to replace the nucleus in an egg removed from a cow, inducing the egg to divide into an early embryo, and finally implanting the embryo into a surrogate mother cow for development into a calf (if you've been counting, that's spare parts from two adult cows and one foetus). The likely artificial DNA would include copies of human genes, marker genes, and any extra sequences needed to make the whole thing operate in a cow's mammary
gland.

This all sounds very clever, but the GM milk is being declared as safe to drink as that of ordinary cows without saying anything about the complexities of testing it. The necessary clinical trials will have to be much more extensive in the case of this staple, variable food destined to be consumed by all sectors of the population, than they would be for the testing of a drug which has a highly controlled dosage.

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Recombinant proteins produced by transgenic cows:

• α-lactalbumin comprises 25-35% of the protein in human milk compared with 2-5% in cows' milk. It seems to have a role in the production of lactose (milk sugar), in providing dietary essential amino acids, in stimulation of metabolism, and in preventing gastro-intestinal infection.
• Lysozyme is an enzyme widely present in human body fluids, such as tears and saliva. In human milk, it can be present in concentrations ranging from 3 to 3000μg/l but typically 200-400 μg/l compared with trace amounts of 0.05-0.22 μg/l in cows' milk. It has anti-bacterial, anti-fungal, anti-viral, immune-system boosting and anti-inflammatory properties.
• Lactoferrin is widely present in human body fluids, such as tears, saliva, sexual secretions, and blood. In human milk, it can comprise up to 15% of whey proteins compared with 0.5-1.0% in cows' milk. It seems to have a role in the absorption of iron in the gut, in defense against bacteria, fungi, protozoa, and viruses, in inflammatory responses, and in bone growth.

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So, what could go wrong?

Judging from the scant information available in the published papers, the DNA in these GM cows may includes copies of human-, cow-, goat-, chicken-, jellyfish- and bacterial-DNA. How 'human' is the protein created by that cosmopolitan concoction? Each of these carries it's own risk of introducing immune-reactive qualities, and of altering the microbial flora exposed to it.

All these recombinant proteins are known to be highly biologically active, multifunctional, and able to assume a variety of chemical formats; we probably don't yet know the full range of these attributes. The scope for subtle differences in protein structure to result in inappropriate activity, or even a completely novel activity, is huge.

Moreover, all of these recombinant proteins are capable of negative effects on living cells. For example α-lactalbumin is known to have a folding variant which can induce cell death. Lysozyme's main known action is to disrupt living cells. Lactoferrin has a number of unusual properties: it's effects on the immune system are very specific to the individual; it can depress cancer cells but also stimulate the growth of intestinal cells; it can promote micro-organisms but also depress them; it binds DNA and RNA (a related molecule) to regulate gene expression; it can both bind and release iron to regulate iron metabolism. In the right place at the right time in the right form, α-lactalbumin, lysozyme and lactoferrin all promote health: they also have the potential to be damaging.

There are 25 recognised allergens in natural cows' milk. This suggests a huge potential for increased allergenicity induced by unexpected gene products. Since there is no animal which can adequately model humans to test for human allergy, we can only find this out the hard way.

Much of the experimental transgenic milk tested for quality has another intrinsically unnatural feature: it was obtained from young calves given artificial hormones to induce lactation. Milk produced by a mature cow lactating naturally may well be significantly different.

Some forms of the recombinant proteins are destroyed (or changed?) by sterilization, while others survive. The outcome of processing GM milk might be quite unexpected.

In summary, the 'human' qualities added genetically to 'humanise' the milk might be very 'non-human' in the final product.

OUR COMMENT

Every stage of the likely method of production of the GM cows described above can induce mutations or cause other abnormal cell development. The reported 'success' rate in terms of the number of GM cows achieved from the number of donor eggs removed for “reconstruction” seems to be around 1 per cent. One-third of the calves died within 6 months of birth.

Another consideration is how 'human' will the GM cows' milk ever be? The fat composition, the sugar content and the mineral content of human milk are very different from cows' milk, as is the protein profile and concentration. All of these milk constituents interact in the nutrition of the infant. Inducing the over-production of three proteins will not make the two milks more than superficially similar: extensive further genetic changes would be necessary to make cows' milk anything like a realistic substitute for human. Is it really possible to create healthy human milk by tinkering with a cows' DNA? Is it really possible to create a healthy cow which can produce milk with this huge degree of unnatural alteration?

The question of what weird and wonderful pathogens might be generated in human-goat-chicken-bacterial-jellyfish-cows' milk does not bear thinking about.

Why is China so intent on going down this danger-fraught path? In 2008, 40,000 Chinese babies needed medical treatment, a further 13,000 were hospitalised, 104 became seriously ill and four died after poisoning by formula milk derived from deliberately adulterated cows' milk (see FOOD ADULTERATION - LESSONS FROM CHINA - GMFS News archive, October 2008). This tragedy should have highlighted the danger of using man-made milk-substitutes for a vulnerable sector of the population, plus the risk to infants from the declining rate of breast feeding in China. Transgenic cows seem to be the Chinese answer to both problems. But, as one food editor described it, the novel cows are “an unnecessarily complicated solution to a problem that could instead be tackled through greater support for and awareness of the benefits of breast-feeding itself”.

You're not likely to find human milk from a cow in European supermarkets any time soon. However, once the GM juggernaut starts moving it can be very difficult to stop. If you get a chance to put the brakes on before anyone tries to feed you milk from a humanised GM cow, don't let it go.

SOURCES

• Richard Gray, Genetically modified cows produce 'human' milk, Telegraph, 2.04.11
• Cheng Yingqi, GM 'human milk' predicted to be on shelf, China Daily, 22.03.11
• Nicola Twilley, Food Editor, Genetically Modified Cows Produce “Human” Milk, www.good.is, 24.03.11
• Human Milk from Cloned Transgenic Cattle, Institute of Science in Society Report, 26.04.11
• Biogas for China's New Socialist Countryside, Science in Society 49, Spring 2011
• J. Wang et al., 2008, Expression and Characterization of bioactive Recombinant Human α-Lactalbumin in the Milk of Transgenic Cloned Cows, Journal of Dairy Science 91
• Bin Yang et al., 2011, Characterization of bioactive recombinant Human Lysozyme Expressed in Milk of Clone Cattle, PLoS ONE, 6:3
• Penghua Yang et al.,2008, Cattle Mammary Bioreactor Generated by a Novel Procedure of Transgenic Cloning for Large-Scale Production of Junctional Human Lactoferrin, PloS ONE, 3:10
• J. Nordlee et al., 1996, Identification of a Brazil-nut allergen in transgenic soybeans, New England Journal of Medicine, 24.03.96
• V. E. Prescott, et al., 2005, Transgenic Expression of Bean α-Amylase Inhibitor in Pease Results in Altered Structure and Immunogenicity, Journal of Agriculture and- Food Chemistry, 63(23, 15.10.05
• Harold Eddleman, Composition of Human, Cow, and Goat Milks, www.disknet.com, 6.02.09
• Human lactoferrin 'grown' in rice plants?, Dairy Reporter, 2.05.02
• Will Brink, Lactoferrin: The Bioactive Peptide that Fights Disease, Life Extension Magazine, October 2000