Tuesday, December 13, 2005

It’s just not so simple

Yet more evidence has now been provided that copying a protein from one organism into another is not always as simple as it might seem, and not the innocuous substitution that the biotech industry might claim.

Researchers found that a protein they copied from beans into peas took on altogether different characteristics immunologically, and unlike the original bean protein, the pea-produced bean protein caused allergic lung damage in mice. In the typically reserved and passive voice of the peer-reviewed research journal, they stated:

“Diversity in translational and post-translational modification pathways between species could potentially lead to discrete changes in the molecular architecture of the expressed protein and subsequent cellular function and antigenicity.”
(2005. Prescott, V.E., et al. Transgenic Expression of Bean-Amylase Inhibitor in Peas Results in Altered Structure and Immunogenicity. J. Agric. Food Chem., 53: 9023-9030.)

The protein in question was intended to function in peas as a natural pesticide directed against weevils, as it does in beans, but when produced by peas, the protein took on a 3-D shape different from that of the original. The researchers confirmed that the pea-produced bean protein’s amino acid sequence (the “building blocks” of protein) was identical to that of the bean’s original protein, but when it was produced by pea cells, sugars were attached to the molecule in a different pattern than those of the original pea protein.

Sugars are attached to proteins during post-translational glycosylation, performed by cellular machinery separately from the DNA sequence that codes for the protein’s amino acid sequence. As a consequence of this variant glycosylation, the pea-produced bean protein has a different shape than the original bean protein, and protein shape is exquisitely important to immune recognition.

What this means is that one cannot expect to predict the production of a given protein conformation based solely on its amino acid sequence, but it is that amino acid sequence that is the basis of all genetically modified organism (GMO) manipulations.

Glycosylation is not the only post-translational modification that proteins undergo in their production, but it is one that has already been observed to produce proteins that are sufficiently different as to confuse and confound the immune system, based as it is on recognition of surface shape and charge. There are other cellular processes that help proteins take on their final shapes as they are being produced, and it would be surprising if there are not similar divergences between species in these processes as well.

The short story is that we cannot expect GMOs to produce proteins as if they are dumb coding machines. We cannot assume that we can insert the code for a protein into the DNA of an organism and that the protein will be produced as we expect.

Furthermore, our regulatory system has not caught up with this reality. GMO foods are not required to be tested for immunological properties, and there are no particular tests that are recommended. This is not the first case of GMOs producing aberrant proteins that cause allergic responses, and will doubtless not be the last.

The larger question has to be: what about subtle differences that are caused but might be missed by whatever tests we have available? There are numerous immune system diseases that have unknown origins; is it possible that we could trigger these, or new, immune diseases through manipulation of the proteins produced by GMOs? How could we possibly assess such potential? Would we even recognize GMOs as the cause when we can’t identify the cause in many diseases that exist today?

This report demonstrates once again that such a phenomenon is possible, and as such, it’s a proverbial canary in a coal mine. The view of DNA coding for a string of amino acids that becomes a given protein has to be recognized as dangerously simplistic. Cells do not work like computers or assembly lines in a linear and predictable manner. And, even if the cells of one member of a species were to produce the protein product desired, that does not assure that all members of that species will do the same.

Slowly, evidence is coming to light that lends credence to my intuitive perception that life is vastly too complex to manipulate in such a clumsy manner and expect to be able to predict the outcome. Over eons of time, evolution has done this sort of tinkering for us, fine-tuning as it goes, leaving its vast number of failures to die in its wake. Yet we in our hubris believe that we know better, and can tinker away to our heart’s content, and can avoid the “mistakes” part of the equation, the failures, the deaths?

It seems to me that hubris is indeed the defining characteristic of our time, in biotech as in all other things. That doesn’t mean I have to buy in, and in the case of GMOs, buy in I won’t. I hope we don’t end up with an unstoppable conflagration of genetic pollution brought on by the agribusiness interests in their blind pursuit of profits, but that does seem to be where we’re headed at the moment. We ignore the canaries at our peril.

2 Comments:

Anonymous Anonymous said...

Kathleen,

I would like to know what you think about crops that have been changed by blasting them with radiation. For instance, more than half of the wheat now grown by farmers--even "organic" farmers--is the result of experimental breeding of radiation-mutated seeds. This is what they did *before* they began engineering crops. Do you like radiation mutation better, and why?

Schiller.

5:49 AM  
Blogger Kathleen said...

Thank you for your comment, Schiller.

Regarding my opinion of the induction of crop plant mutations by radiation: This technique has also produced novel proteins. Some of these novel proteins may well be associated with the documented increase in the prevalence of autoimmune diseases over the same time period, but this would be difficult (if not impossible) to demonstrate, given their ubiquity.

No, I don’t like radiation-induced mutation better, or worse for that matter. With radiation-induced mutation, you expect to generate novel proteins, while genetic engineering has been promoted as a way to more precisely obtain desired proteins. My point was that genetic engineering is not necessarily precise, even when the transfer of a specific coding sequence, and its subsequent translation, is successful.

One of the epidemiological mysteries of the day is why we are seeing so much more autoimmune disease now than in the past, and most researchers see this as a result of “environmental factors,” based upon studies of concordance in monozygotic twins. Our most intimate connection with the environment is the food, water, and air we consume. We can choose to ignore the potential for harm when we alter the life forms upon which we depend, or we can recognize that in such pursuits, unintended consequences are more likely than not.

Kathleen

11:37 AM  

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