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Crispr

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51UiMG9M0FL._SY344_BO1,204,203,200_ A few days ago The New York Times published a piece with the headline, A Scientific Ethical Divide Between China and West. My instinct as to what the piece was going to be focusing on was totally off. Whereas my own assumption was that it would focus on perceptions of widespread corner cutting, and sometimes fraud, in Chinese science, it was mostly about CRISPR and genetically engineering humans. As you probably know I find some of this a bit much. I take those who are worried about misapplication of “gene drive” technologies more seriously than those worried about germline edits in humans, because the latter are likely to happen, but be few and far between. In the wide world of human rights concerns CRISPR edited fetuses are very low on my list. Though CRISPR is much better than most older genetic engineering techniques in terms of specificity, for the near term future it is unlikely to be good enough that you’d want to “perfect” your child.

Then there’s this post over at Quartz, Why China won’t listen to Western scientists about genetically modifying the human embryo, which focuses a lot on cultural differences. It concludes with this: “Inside China, there are people who are opposed to international standards, citing cultural differences. This force is actually quite powerful sometimes.” Actually, I have cultural differences with many people who are averse to genetic engineering. I agree with Alex Tabarrok, if the risk/reward proposition for CRISPR in the context of humans shifts enough, I don’t have any hesitation of allowing it on an individual basis (i.e., it shouldn’t be mandatory obviously!). In fact, for adults who want to take the risk the time table for elective genetic engineering is probably much closer.

But this section of the Quartz piece jumped out at me:

“Confucian thinking says that someone becomes a person after they are born. That is different from the United States or other countries with a Christian influence, where because of religion they may feel research on embryos is not ok,” Deng Rui, a medical ethicist at Shanxi Medical University, told the New York Times.

Two East Asian nations have large numbers of Catholics, Protestants, Buddhists, and those who are irreligious, in The World Values Survey. There is a question which asks, “is abortion ever justifiable?” The respondents are given a 1 t o 10 scale. 10 is “always justifiable,” and “1″ is “never justifiable.” Below are the results (Poland is a “control”).

Abortion is….
Singapore No Religion Buddhist Protestant Catholic
Never justifiable 19.4 20.0 33.3 24.6
2 5.0 10.4 10.4 13.8
3 9.0 12.0 16.6 11.0
4 11.7 13.5 8.4 9.7
5 28.5 26.2 20.9 25.5
6 10.6 6.9 4.5 4.6
7 7.0 6.9 3.9 7.6
8 5.7 3.1 0.8 2.5
9 0.9 0.6 0.9 0.7
Always justifiable 2.2 0.4 0.4 0
N 349 579 197 120
South Korea None Buddhist Protestant Catholic
Never justifiable 31.8 41.0 38.6 41.1
2 5.5 6.0 7.8 9.6
3 9.4 17.0 13.4 7.9
4 11.1 6.6 9.6 11.9
5 21.4 14.9 14.1 14.9
6 9.5 3.7 8.1 3.3
7 5.5 5.2 3.8 6.2
8 4.3 3.2 1.0 3.4
9 0.7 1.2 3.4 1.3
Always justifiable 0.8 1.1 0.2 0.4
N 493 244 252 188
Poland None Catholic
Never justifiable 13.2 48.4
2 4.0 10.1
3 8.3 8.0
4 4.1 3.8
5 27.2 14.0
6 14.7 5.0
7 5.9 3.9
8 9.3 3.0
9 2.1 1.3
Always justifiable 11.2 2.5
N 45 844

What’s this telling us? In South Korea there really isn’t much of a difference between the religions, and the gap between religious and irreligious is modest. South Korea has historically been the most Confucian nation in the world. But there is a lot of ambivalence about abortion. The results for Poland show that the irreligious are very different from Catholics. Singapore shows that Buddhists and those with no religion cluster together, but Catholics are not particularly anti-abortion, but Protestants are.

For all the talk about culture, I think old fashioned Marxism and nationalism can explain the Chinese pushing the envelope. There are material rewards to scientists who publish high impact and notable findings. And, there are glories which accrue to the nation as a whole. If China wants to “catch up” with the West in science, then it’s going to push into areas that the West is not focusing on.

 
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crispr

Nature has a nice overview of the excitement over CRISPR. The plot above shows Google Trends, and it illustrates what’s been going on. Friends of mine who were working with Talens and Zinc-finger methods are now switching to CRISPR. For a generation genetic engineering has been an idea, CRISPR brings that idea to life. As suggested in the article a lot of the concern with how much more feasible CRISPR has made useful genetic engineering. The cost and effectiveness have gone in reverse directions; down and up respectively.

One thing to note though is that it seems ridiculous to worry about the sheer number of modifications. Conventional genetic engineering techniques and even old fashioned breeding actually produces far more mutants than CRISPR, which has more specificity. Rather, it’s the fact that CRISPR makes genetic engineering feasible for many more labs, and at a more rapid clip. With the ability to do good comes the ability to do bad. As I’ve mentioned before I’m not too worried about CRISPR being used to create genetically engineered superman. Though far better than older forms of genetic engineering, the downside risk of CRISPR is going to be too great for parents to be comfortable engaging in proactive gene editing in the near future (rather, it will be probably first be used in the case of adults with very terminal illnesses, likely of the Mendelian sort). In the Nature piece there’s an analogy to gene therapy. I think that’s a weak one, because gene therapy always had a biomedical focus and massive downsides for misfires (even then, I think there’s been an overreaction, but that’s another post). Rather, CRISPR has more general applications in areas such as GMO.

Finally, there’s the issue of “gene drive.” Basically we’re talking about distortion of Mendelian segregation, so that an allele spreads through the population via intragenomic competition. Instead of a 50% chance of transmission, it could bias it so that the transmission rate is ~100%. Segregation distorters are found in nature, and can cause problems. They could be a foreseeable path toward eliminating pests. But, there are other concerns. From the piece:

But many researchers are deeply worried that altering an entire population, or eliminating it altogether, could have drastic and unknown consequences for an ecosystem: it might mean that other pests emerge, for example, or it could affect predators higher up the food chain. And researchers are also mindful that a guide RNA could mutate over time such that it targets a different part of the genome. This mutation could then race through the population, with unpredictable effects.

This is a legitimate worry obviously. Prominent evolutionary population geneticists take this issue seriously. But, others do not. In the specific concerns above, my reaction is basically echoed below:

The issue is not black and white. Micky Eubanks, an insect ecologist at Texas A&M University in College Station, says that the idea of gene drives shocked him at first. “My initial gut reaction was ‘Oh my god, this is terrible. It’s so scary’,” he says. “But when you give it more thought and weigh it against the environmental changes that we have already made and continue to make, it would be a drop in the ocean.

Genes are not magic. We need to separate the distinctive and particular dangers inherit in genetic engineering, and CRISPR technology specifically, from the broader suite of ills and concerns which plague us. Nature is not at a perfect equilibrium, but dynamic, In addition, we are reshaping the world around us constantly, so concerns of out of control gene drive needs to be kept in perspective.

Finally, I do understand that scientists such as George Church are influential, and their concerns carry great weight. But if CRISPR is so democratizing, does anyone really think that the entire rest of the world will wait? And by the “rest of the world” I guess I kind of mean China….

For God doth know that in the day ye eat thereof, then your eyes shall be opened, and ye shall be as gods, knowing good and evil.

 
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Drakas_cover Everyone and their mother has heard of the story about the CRISPRed embryos by now. If you haven’t, the original paper is open access. Second, Carl Zimmer’s primer is excellent, Editing Human Embryos: So This Happened. For those who are overly alarmed by the non-ethical aspects, I think this is key:

Just because this experiment came out poorly doesn’t mean that future experiments will. There’s nothing in this study that’s a conceptual deal-breaker for CRISPR. It’s worth recalling the early days of cloning research. Cloned embryos often failed to develop, and animals that were born successfully often ended up with serious health problems. Cloning is much better now, and it’s even getting to be a business in the world of livestock and pets. We still don’t clone people, though–not because we can’t, but because we choose not to. We may need to make the same choice about editing embryos before too long.

Livestock and pets. And plants. I think CRISPR is going to be a big deal. It already is a big deal. But some people are worried now about a profusion of designer babies. We need to get calm here. For something to become a consumer product it needs to get much better in terms of probability of outcomes, and we’re a long long way from that. As Ramez Naam pointed out people are very risk averse with their children.

Rather, the real danger is more one of ethics. Something out of S. M. Stirling’s Draka series where a government or society isn’t bound by normal human ethical standards, and begins to basically treat their population like livestock. As is usually the case the major issues looming are not scientific, but have to do with human volition.

 
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Google Trends Search Results for CRISPR


For God doth know that in the day ye eat thereof, then your eyes shall be opened, and ye shall be as gods, knowing good and evil.

- Genesis, 3:5

413px-Adam_na_restauratie Sometimes science surprises you. Many a time science seems like a slowly sluggish river, inexorable in its progress, but languid nonetheless, beset by turns and twists which delay its progress. Over the last year though I’ve been hearing people whisper in excited tones about something new, something special. And it’s about CRISPR. This may indeed be a world-turned-upside-down moment, and CRISPR may finally cash out the promise that biological science is going to result in a flowering of engineering analogous to what occurred during physics’ ‘atomic age.’

And now the excitement is percolating into the public spaces of the middle-brow media. The New York Times has now finally put CRISPR on the radar of the broader culture, in a rather long article, A Powerful New Way to Edit DNA. As they they, “read the whole thing,” but key in on this quote:

“It just completely changes the landscape,” Dr. Doudna said. Berkeley scientists used to farm out that work to specialized laboratories or companies. Now, she said, “people are able to make mice in their own labs.”

No, it complete creates a landscape. Theory becomes concrete, and the speculations and worries of bioethicists are challenged by the real present, not some vague future. Now a biologist can state, I am become life, creator of worlds. Whereas genetic engineering up to the present has been an almost artisanal act, CRISPR opens up the window into the possibilities of scalable industrialization. No doubt there will be Neo-Luddites demanding we smash the looms, but they will fail, as they always have.

How quickly has this explosion overwhelmed us? According to Google Scholar up until the year 2012 “CRISPR” was in the title of 275 papers. For 2013-2014, 328 results.

 
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220px-David_von_MichelangeloIf you don’t know what CRISPR is, you should. Two words: genetic engineering. And then you have cloning. I was talking to a friend of mine about the possibility of combining these two technologies, CRISPR and cloning. The basic intention here would be to recreate yourself, but superior. Edit out de novo mutations, and genetic load inherited from ancestors more generally. Perhaps substitute well known large effect alleles which have salubrious consequences. This is not totally abstract, as I’ve talked to many people who are interested in the idea of cloning.

For example, the economics blogger and professor Bryan Caplan has confessed that he would like to see what raising a clone would be like. Or as he states, “I want to experience the sublime bond I’m sure we’d share. I’m confident that he’d be delighted, too, because I would love to be raised by me. ” This may be correct. But now imagine that Caplan avails himself of the latest genetic engineering technology, in addition to cloning. Bryan Caplan version 2.0 is taller, better looking, smarter, more socially astute. In fact, from 2.0′s perspective the original Bryan Caplan may simply be an “alpha” version, before he was “perfected.” Perhaps 2.0 would love Caplan 1.0, but I suspect that this love would resemble Christianity’s love of its parent Judaism, which verges into patronizing condescension, as Christians believe their religion is a perfected completion of the Yahweh cult.

More farcically, consider how teenage rebellion would play out between a clone which is superior in every way to the parent. If a parent asks rhetorically “do you think you’re better than me?”, the clone would have to respond honestly, “Yes, and so do you.” The clone would be a better version of the parent, and likely this structural tension in the relationship would persist, as the original copies see themselves as they would wish to be, but never can be.

Addendum: Ted Kosmatka should write a short story based on this idea!

 
• Category: Science • Tags: Cloning, Crispr 
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Razib Khan
About Razib Khan

"I have degrees in biology and biochemistry, a passion for genetics, history, and philosophy, and shrimp is my favorite food. If you want to know more, see the links at http://www.razib.com"