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Gene Editing: What Could Go Wrong?

Headline: Big Tongues and Extra Vertebrae: The Unintended Consequences of Animal Gene Editing: Unintended consequences have included enlarged rabbit tongues and extra pig vertebrae, as bioethicists warn of hubris

Scientists around the world are editing the genes of livestock to create meatier pigs, cashmere goats with longer hair and cold-weather cows that can thrive in the tropics…

When Chinese researchers deleted a gene that limits muscle growth in mammals so that rabbits would grow leaner, their creations exhibited an unusual characteristic: enlarged tongues. Similar experiments on Chinese pigs led some to develop an additional vertebrae. Gene-edited calves died prematurely in Brazil and New Zealand…

“Humans have a very long history of messing around in nature with all kinds of unintended consequences,” said Lisa Moses, an animal bioethicist at Harvard Medical School’s Center for Bioethics. “It’s really hubris of us to assume that we know what we’re doing and that we can predict what kinds of bad things can happen.”

The belief has spread that scientists know how gene editing works “all the time, under all conditions,” says Odd-Gunnar Wikmark, a researcher at the Norway-based foundation GenOk, which studies the consequences of genetic engineering. “We of course do not.”

Critics say that editing animal DNA could introduce unwanted mutations that pose a threat to human health when consumed, and they fear that mutated genes may spread unchecked as animals breed. Proponents say they are engineering mutations just as traditional crossbreeding does, only faster.

Both the critics and proponents are right. GMOs could cause dangers and engineered beasties are faster to produce than regular breeding. Regular breeding cannot, of course, produce animals that cannot be produced naturally, whereas gene-editing can.

Just as obviously, single or few genes that are thought to control a physical attribute (like muscle) are easier to manipulate than genes thought to regulate, or moderate, behavior. But, as is clear from the examples above, even simple edits can cause freaks. Which is to say, can cause unanticipated or undesired consequences.

And they are unanticipated for the reasons quoted: scientists are too sure of themselves.

Much of the evidence in genetics about outcomes is statistical. A great deal of that is based on wee p-values, so of course it is suspect. Many false beliefs are thus entertained because a wee p screamed “Look at me! Look at me!” Exaggerations, which come free with p-values, are believed as truths.

This is not a huge big important deal when playing around with mice or flies or sheep. If an experiment goes wrong making a new pig, why, a quick trip to the bacon factory solves the problem. But inadvertently make a new mutant baby, as that Chinese scientist is alleged to have done? Well, you can go the Belgian way and kill it (using the euphemism “euthanize it”), but that destroys the souls of the baby and the killer.

It should go without saying, but I’ll say it anyway, that interactions between genes and genes and environment are not well understood—and that’s putting it nicely (I’m such a sweet man). This is particularly so in claims of genes and human behavior. We hear things like “Investigating the genetic basis of altruism: the role of the COMT Val158Met polymorphism.” Now that is hubris to the ninety-fifth degree. As if a complicated behavior like altruism—which I bet if you were pressed, right now, could not define unambiguously—can be “explained” by a polymorphism. Here’s a SNP (that’s a joke, son) from the Abstract:

Findings from twin studies yield heritability estimates of 0.50 for prosocial behaviours like empathy, cooperativeness and altruism….Altruism was assessed by the amount of money donated to a poor child in a developing country, after having earned money by participating in two straining computer experiments. Construct validity of the experimental data was given: the highest correlation between the amount of donations and personality was observed for cooperativeness (r?=?0.32, P?≤?0.001).

Heritability sounds scientific, and that “0.50” makes it seem the science was measured precisely. But as the rest of the abstract proves what we have are cheesy linear correlations based on quantifying questionnaires, all certified by wee p-values. That’s not hard science, but soft guessing.

At least they gave a definition of altruism: the amount of fictional non-money given to fictional non-existent non-poor children in fictional non-existent non-developing countries in some simple computer game. This may not be what you thought altruism was when I asked you to think of it above. But it is a definition. The hubris comes in when assuming this odd definition of altruism maps to the true definition with only negligible or non-interesting differences.

Just wait until rich parents of designer babies sue to get their money back when they discover their test-tube precious with its hand-picked COMT allele did not “cure” the hyperactivity of the child.

6 thoughts on “Gene Editing: What Could Go Wrong? Leave a comment

  1. The most challenging work will be conjuring thick tongues, extra vertebrae, etc. from bugs into features. I’m thinking it will require some sleight-of-hand, a boatload of impenetrable jargon, and more funding.

    While here, I’d also appreciate a few links detailing the medical breakthroughs and near-miraculous life-saving/altering treatments emerging from embryonic stem cell research.

  2. I did something that Dr. Briggs did not do. I expended an extra 3.5 minutes in skimming through the altruism paper that he critiques. There I found what I expected: Dr. Briggs did not read beyond the title and part of the abstract, and simply made up all the other details. He doesn’t even have the excuse of a paywall, as the paper is free to read.

    I’m not claiming that this research is of any real value. But Dr. Briggs claims that they employed methodologies exactly opposite to those they actually employed. He’s not merely lazy; he knows that his target audience won’t or can’t read and understand the paper, and will assume that he is correct. In other words, the same strategy that he employs in discussing climate science and several other topics.

  3. I’m not sure what you mean by “claims that they employed methodologies exactly opposite to those they actually employed”.

    I read the paper, too. The authors used toy tasks and a visual stimulus lifted from an ad showing a cute kid, told the participants they could donate to the kid, and gave the donated money to the organization that placed the ad. What, in the name of logic and semantics, is the “exact opposite” of that? Doing a real task and donating money to a real person?

    The authors obviously may call this mess “high ecological validity” if they so choose. I call it BS.

  4. Just how many things, experiments, are scientists doing right now that might go so wrong that the whole world would regret it for ever and ever? Somewhere, sometime humanity abandoned, if it ever adopted it, the Precautionary Principal. One should have to prove ahead of time that what one wants to do (like gene removal, then carrying the creature to term) has no chance of ending up uncontrollably, nonlinearly, bad. Going bad is OK. But not uncontrollably bad. Maybe the Trinity test was the moment humans accepted the risk and said goodbye to the Precautionary Principal. Whew, the atmosphere did not catch fire. Maybe Luther’s 96 Theses was when we said goodbye to the Precautionary Principal. But we need it now.

  5. There’s probably far more to worry about regarding the widespread use of antibiotics contributing to the incubation of drug-resistant and even drug-immune bacteria that pose very real, including deadly, human threats. That’s here & now.

    Many doctors already try to ration the use of antibiotics on their human patients (most of us have heard about that), but livestock is both substantial and far more indiscriminate (most of us probably don’t realize how substantial this is, but the data is readily ‘findable’). If worrying is your “thing” then instead of worrying about what gene-splicing or DNA manipulation might create you’d be better off worrying about the unintended consequences of feeding livestock antibiotics for our own good.

    Gene manipulation may be just the tactic needed to offset drug-immune bacteria that may render some of us or our heirs incurable infections or even death — now very real threats, “unintended consequences,” to humanity resulting from the then-heralded discovery of miracle drugs such as penicillin.

    Sure, researchers so involved don’t know much of what they’re doing, or, what all the effects might be. That’s why it’s called “research.”

    Nobody back then foresaw the threat humans would create from using such wonder drugs as penicillin. And its somewhat foolish to jump to the conclusion that today’s forays into gene & DNA tampering will result in anything anyone can foresee either — i.e., that anybody has any basis to act as a regulatory overseer.

    BTW –

    Inquisitive readers with a philosophical bent might like to objectively ponder Briggs’ logic presented in today’s essay …

    … and then… compare that logic to his premise in his essay from nearly a decade ago: http://wmbriggs.com/post/1285/

    Observant readers will note that both essays present [arguably] the same fundamental logic/philosophical value: ‘Potentially dire outcomes should (today), or shouldn’t (2009 essay), be sufficient to deny the act that might lead to the dire outcome.’

    Context matters, as the above two essays illustrate. Philosophical analysis conducted in the abstract and resulting in an abstract conclusion, does not, more often than not, lead to useful practical conclusions. Plato’s Republic, an allegedly Utopian social construct (presuming a benevolent dictatorship of sorts), was the result of pure philosophical reasoning … but it overlooks basic flaws in human nature that always get in the way … and most readers will agree that a benevolent dictatorship would be be doomed to such human foibles to end up as a tyranny.

    This point about context is analogous to the link in yesterday’s post (“Next Time Somebody Asks You “What’s the Probability of X” Say This — Crucial Update”) where nothing has a probability … but things do have a conditional probability. This has been a recurring theme, also expounded upon at http://wmbriggs.com/post/12617/ , for example.

    Which makes one wonder why Briggs, etc., are so disposed to the philosophical … as real-world evidence reveals time & again, philosophically-based reasoning routinely leads to flawed conclusions (or, conclusions that are misapplied/over-extrapolated because limiting conditions implicit in the analysis went unrecognized).

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