Thursday, August 9, 2012

Inventing Human Milk Oligosaccharides

"Furthermore, E. Coli is the primary bacterium used in genetic engineering.  Many new genes and combinations of genes were created and amplified and propagated in E. Coli, because the original bacterium was harmless.  In the process, genetic engineers have turned an original harmless bacterium into deadly pathogens."   Dr. Mae-Wan Ho

Who would think that men could engineer a microbe that could make a human milk oligosaccharide?  But, yes, yes we can do this through metabolic engineering.  Say what?  Let's look at what Wikipedia says about metabolic engineering.

"Metabolic engineering is the practice of optimizing genetic and regulatory processes within cells to increase the cells' production of a certain substance."  
Metabolic engineering uses genetic engineering techniques. Various research papers state the use of various pathogens to create human milk oligosaccharides:  Escherichia coli (e. coli), Pichia pastoris, Agrobacterium sp. Corneybacterium ammoniagenes, and Corneybacterium glutamicum.  Yeah, quite the mouthful, not sure I can pronounce any of these pathogens except e.coli.

An interesting paper from the Journal of Biotechnology published in 2008 called, "Genetic engineering of Escherichia coli for the economical production of sialylated  oligosaccharides," by Nicolas Fierfort and Eric Samain states,

"Free sialylated oligosaccharides are found at high concentrations in human milk and are know to have both anti-infective and immunostimulating properties."

"The development of efficient systems for the enzymatic synthesis of sialylated oligosaccharides has been possible through the identification of bacterial sialytransferase genes which are well expressed in Escherichia coli and the design of multiple enzymatic systems for the synthesis of CMP-Neu5Ac."

But wait we have to redesign the system,

"Since the only E. coli strains that naturally produce CMP-Neu5Ac are pathogenic strains that cannot be used in biotechnological processes, a pathway for the synthesis of CMP-Neu5Ac had to be imported into E. coli strain K12 derivatives.."

Yes, restructure that e.coli and hopefully trust that our scientists can create pathways that disable the pathogenic tendencies of e.coli.  This study was about generating this particular human milk oligosaccharide at low cost for the food industry.  Scared.  Ya ought to be.

We have a company in Denmark, called Glycom that is using their "bench chemistry" to create human milk oligosaccharides.  I wonder if bench chemistry is another word for genetic engineering?  I presume that some of their bench chemistry will be placed in infant formulas.  Why because their outstanding partner is the Nestle Group with some of their BOD directors from Nestle.  I was amused to see that their CEO and Director, John Theroux, served as head of the European management consultants, Bain and Company (this company has been making the news in the US).  Not that his service is amusing, just that well "its a small world after all."

Actually my real interest in all this is, of course, a patent entitled, "Human milk oligosaccharides to promote growth of beneficial gut bacteria," patent # 8197872.  The inventors are David A. Mills, Carlito B. Lebrilla, Riccardo LoCascio, Milady Ninonuevo, J.Bruce German, and Samara Freeman.  I believe most of the inventors are from UC Davis, land of biotechnology.  The patent is owned by the Regents of the University of California.

In February 2012 Dr. David Mills of the Foods for Health Institute (UC Davis) received a Gates Foundation Grant.  This grant "will improve the health of infants in developing countries by building the scientific knowledge of how intestinal microbiota affect infant health and by developing probiotics uniquely protective against infection of the gastrointestinal system."

Other researchers at the Foods for Health Institute are Dr. German and Lebrilla.  The Food for Health Institute at UC Davis has quite a few partners.  The California Dairy Research Foundation, Nestle, Prolacta, DSM-maker of DHA/ARA, Abbott, Innovation Center of US Dairy, Unilever, Dairy Management Inc., etc.

Ah, the business of improving infant formula...through genetic engineering?  Is that what their patent is all about?  Yes, this particular patent is about a synthetic prebiotic composition.  Biotechnologist often use the word synthetic when what they really mean is genetically engineered.    Yet, in reading this patent one finds some confusing language.  Claim 1 states:  "A synthetic prebiotic composition comprising a first, second and third purified oligosaccharide each of which naturally occur in human breast milk."  Huh?  The prebiotic is synthetic but the oligosaccharides are derived/purified from breastmilk?  Some of the claims are prebiotics from a bovine milk protein, a soy protein, whey, soybean oil or starch.  One of their claims is for use in infant formula.

The patent does state that Human Milk Oligosaccharides of their invention can be derived from purified pooled human milk.  They describe how this separation can be done through centrifugation, fat removal, addition of ethanol and so forth.  And then they go on to describe other ways to obtain the oligosaccharides.  Frankly, the way it is described one would not know whether you were getting the real component or not.  Although the real component is purified through such a chemical process one could not possible believe it was the real human milk oligosaccharide.

The patent does describe not only prebiotic but probiotic formulations and specifically mentions Gerber--which is now owned by Nestle, and Carnation Good Start.  They do mention that their pooled milk--human milk was provided by the Mother's Milk Bank of San Jose, California and the Mothers Milk Bank of Austin Texas.  

So donor mothers, how does it feel to donate your milk in helping create a better infant formula? Yeah I know I am the only one appalled...obviously these mothers knew this was a possibility and they will be happy to know that some infant formula company is making a better infant formula.   Yeah, I know the improvement of infant formula is the moral imperative of all of us breastfeeding advocates.  Of course, I am a little uncomfortable with the profits these companies make but someone has to make the money.
Copyright 2012 Valerie W. McClain

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