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Unintended Effects of Genetic Manipulation
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What Does a Tailless Transgenic Calf Tell Us?
Craig Holdrege

The goal of a recent genetic engineering experiment was to see whether the researchers could stop a lactating cow from producing one particular protein in its milk. This protein (β-lactoglobulin, a whey protein) is not part of human milk and has been suspected to be an allergen for infants who are allergic to cow milk.

The experiment, from the perspective of the intended effect, succeeded. It involved a complex procedure that used cell cultures, genetic engineering of mice, and the subsequent cloning of genetically modified cow embryos. Fifty-seven modified cow embryos were transferred to recipient cows, five pregnancies ensued, and one calf was born. When lactation was hormonally induced, the calf produced no β-lactoglobulin in its milk.

But the intended effect was not the only one. When the milk composition was further investigated, the researchers found that, along with the repression of β-lactoglobulin, the amount of a different whey protein was increased, and there was a great increase in the amounts of casein proteins in the milk (α- and β-casein each increased more than two-fold and κ-casein increased four-fold). Overall the whey-to-casein ration shifted from 21:79 (in controls) to 4:96 in the transgenic calf. This compensatory shift in proteins indicates, in the words of the scientists, “an intricate balance of milk proteins synthesis.” This balance was radically altered through the experiment. In other words, while the experiment has the goal of causing a clearly demarcated effect (no β-lactoglobulin production), it in fact alters the protein composition of milk overall. Whether such global changes might imbue milk with other unintended allergenic characteristics is unknown.

The researchers were astonished that, through the suppression of the whey protein, the production of the casein proteins rose to a degree that is not matched in experiments that target the over-production of casein proteins.

An additional and startling unintended effect of the experiment was that the calf was born without a tail. Whether this was directly related to the genetic manipulation itself was not clear. A mutation could have occurred in the cell-culturing process, and genetically modified cloned embryos have, in other experiments, developed into tailless calves.

Given the propensity of genetic engineers to do what seems doable, I wonder who will pick up on this unintended effect and put it to use in the effort to create tailless dairy cattle, since tails — from a utilitarian point of view — get in the way during milking! We shouldn’t expect that any research group tackling such a task will be concerned about how being tailless might negatively impact a cow’s life. After all, so the thinking goes, someone will come up with a new “solution” to address any unintended effects. It’s strange how little thought is given to the fact that milk proteins do display an “intricate balance,” and that tails are meaningful organs that have served cattle for thousands of years. Maybe before we try to manipulate specific characteristics — and end up changing the whole organism — we should learn something about their significance within the life of the organism.

Source
Jabed, Anower, Stefan Wagnera, Judi McCracken et al. 2012. “Targeted microRNA Expression in Dairy Cattle Directs Production of β-lactoglobulin-free, High-Casein Milk,” PNAS, doi/10.1073/pnas.1210057109. Available online: http://211.144.68.84:9998/91keshi/Public/File/44/109-42/pdf/16811.full.pdf.
This document: http://natureinstitute.org/nontarget/misc/Beta-lactoglobulin.php

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