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November 28, 2018

Welcome to our brave new 21st century

Filed under: Crispr,Genetic Engineering,Genetics,science — Razib Khan @ 4:44 pm

Sometimes you know something is going to happen. But you don’t know when it’s going to happen. It’s inevitable, but you don’t know when that inevitability is going to realize itself. In a way, death is like that for most of us.

And so it is with genetic engineering in the 21st century. This week MIT Technology Review broke the story that a researcher in China, He Jankui, used the CRISPR/Cas9 system to modify the genes of twin girls. His goal was to have them be were born with a deletion in the CCR5 gene, which would confer resistance to infection with HIV (about ~10% of Northern Europeans carry the deletion). These are the two first human beings born with genetic modifications that were directed by human beings.

Additionally, these are the first genetically modified human beings who will pass that modification to their children (unlike adults who might be targeted by genetic engineering, where their sex cells would not transmit the modification).

Humans have begun to direct their own evolution!

The science, or perhaps more precisely, the engineering, behind CRISPR/Cas9 is well outlined by this video:

There are many scientific and ethical details that go into the unpacking of the story of the gene edited children. But it is important to take a step back, evaluate the present, and consider prospects for the future. The CRISPR/Cas9 system for gene editing has been in use since 2012. In contrast, genetic engineering more broadly has been part of the scientific toolkit for nearly 50 years.

Asilomar, CA

In 1975 140 individuals from a range of disciplines came together in Asilomar, California, and agreed on rough guidelines for the use of the then-nascent technology of recombinant DNA.

This was the technology which brought the idea of genetic engineering to the public, with its first big success being the development of synthetic insulin, which has transformed the lives of millions of people who suffer from diabetes. The private sector biotechnology industry was birthed by the revolution triggered by recombinant DNA techniques in the second half of the 20th century.

For decades after 1975 genetic engineering occupied a prominent spot in science and popular culture. From genetically modified corn to transgenic mice, genetic engineering had widespread uses in both industrial and academic science.

So why is CRISPR/Cas9 such a big deal? In 2012 researchers realized that it was an efficient, cheap, and simple way to do genetic engineering (it had been known earlier as a peculiarity of bacterial defenses against viruses). In less than a decade, it has become even more effective as an editing tool.

In short, CRISPR/Cas9 democratized genetic engineering, so that small labs with few resources could perform experiments and trials. Previously, only laboratories with extensive experience and funding, or industrial scale corporations, could enter into genetic engineering projects. Within a few months, innumerable laboratories switched from other techniques of genetic engineering, which they had spent decades honing, to CRISPR/Cas9.

The nature of the transformation is obvious when you think about what has surfaced in the media in previous decades. One reason that you have heard about genetic engineering in the context of maize, “corn”, is that this is a crop with enormous economic implications. With older and more expensive technologies, genetic engineering could only be justified by a huge economic upside. Because of its cheapness and effectiveness, CRISPR/Cas9 methods have been applied to stem cells, plant and animal breeding, as well as public health. It may help in curing the most common form of muscular dystrophy, ushering in the era of curing of most Mendelian diseases.

Within the last six years, CRISPR/Cas9 has transformed whole sciences, opening up avenues of basic research which were previously not practical. Experimentation has taken over in the realm of experimentation! The plain truth of it is is that what happened in China may appeal to the love of the sensational, but it absolutely marginal to what CRISPR/Cas9 means to most scientists in their working life today. But, it reflects the fact that genetics is now an international discipline with hundreds of thousands of practitioners.

The times when 140 individuals could come together and agree on rules which industry and academia should follow, will follow, are likely long behind us. When scientists would talk about an “international consensus” in 1975, they meant North America, Western Europe, and Japan. Today that consensus has to extend to China, which is now the home to a great deal of cutting-edge biological science. But the cultural and social chasm between China and the developed world is large. And CRISPR/Cas9 is so simple and cheap that its use will likely spread to less developed countries, even less integrated into the community of science than China.

Though He, the researcher behind the “CRISPR babies”, may get the entry in Wikipedia he mentioned offhand to the media, the reality is that the scientific impact of his work is murky at best. Rather, his brazen contravention of the norms of international science presages the new era of the genetic engineering democracy, as the tools to modify the very stuff of life are now accessible to the many, rather than restricted to the few.

Interested in learning where your ancestors came from? Check out Regional Ancestry by Insitome to discover various regional migration stories and more!

Welcome to our brave new 21st century was originally published in Insitome on Medium, where people are continuing the conversation by highlighting and responding to this story.

October 23, 2017

The presumption of parental choice in genetics

Filed under: Genetic Engineering,In Virto — Razib Khan @ 6:35 pm

In various forms, I’ve been talking about genetic modification and testing of children for years. As most of you know my older son was whole-genome sequenced before he was born. This was in large part scientific activism. I wanted to show people it could be done, and it’s not scary. Genes are not destiny, they’re information.

In the current year of 2017 we’ve gotten much further than when I first began talking about this sort of stuff. The Washington Post and Stat have two articles on the topic that are relevant, Discounts, guarantees and the search for ‘good’ genes: The booming fertility business and A baby with a disease gene or no baby at all: Genetic testing of embryos creates an ethical morass.

I’m prompted to comment on them for two reasons. A simple one is that Michael Brendan Doughtery wondered if the recourse to “super-male” sperm donors would lead to inadvertent consanguineous marriage. I doubt the math works out there. There are tens of millions of children. Even with 1,000 sperm donors genetic diversity would mostly be retained, and you can find plenty of partners. And of course in the near future with ubiquitous genetic testing, most individuals will immediately detect consanguinuity. This is not a problem practically.

A second, broader issue, is in regards to genetic testing and sperm donation I do not believe we should treat parents who make recourse to these technologies any differently from parents (like myself) who can have children without assistance. Most humans make choices on characteristics of their spouses, and those choices aggregate into assortative mating. To me, this is a difference of degree, not kind, from selecting sperm donors. It simply seems creepy because of the technological aspect. The impulses are the exact same.

I do understand that some people have religious, ethical, and normative objections to these new technologies. Personally, I disagree with this viewpoint, but I think it is healthy for us to have the debate openly and candidly.

For example, a few years ago Radiolab had an episode where a gay Israeli couple went looking for egg donors. More specifically they wanted eggs from someone who was white. Obviously, I don’t prioritize my children looking like me that much even though they are biologically mine, so I have a hard time relating to fixating on this issue (my wife and I discussed this topic and I didn’t care too much whether the kids looked like dad, though other people on playgrounds seem to care way too much for my taste). But at the end of the day, it is a choice. And, it is the same choice that the vast majority of humans make by marrying and having children with people of the same race. In multiracial societies like the United States of America, this choice is explicit and implicit in terms of revealed preferences. People want kids to be the same race as themselves. They want to see themselves physically. The Radiolab episode simply exposed what generally occurs on the down-low.

Perhaps we are uncomfortable with the expense and artifice of assisted reproduction. Perhaps it violates our values. This is reasonable. These are issues and debates we need to hash out. But ultimately many of the same issues apply to assisted reproduction and genetic selection as do with “natural” or unassisted parenthood. I think it is important not to put parents who need assistance to a higher standard than those who don’t.

Addendum: I think the argument is ultimately somewhat low stakes because parents who really want a specific child and don’t want to adopt will spend as much as needed to get what they want. And if these technologies were banned in the United States people would just go abroad for the duration of the pregnancy.

October 29, 2012

Prop 37 and the right to have the government enforce your right to know

Filed under: Genetic Engineering,Genetics — Razib Khan @ 11:08 pm

With the election coming up, California Proposition 37, Mandatory Labeling of Genetically Engineered Food, is on my mind. From Ballotpedia:

If Proposition 37 is approved by voters, it will:

* Require labeling on raw or processed food offered for sale to consumers if the food is made from plants or animals with genetic material changed in specified ways.

* Prohibit labeling or advertising such food as “natural.”

* Exempt from this requirement foods that are “certified organic; unintentionally produced with genetically engineered material; made from animals fed or injected with genetically engineered material but not genetically engineered themselves; processed with or containing only small amounts of genetically engineered ingredients; administered for treatment of medical conditions; sold for immediate consumption such as in a restaurant; or alcoholic beverages.”

James Wheaton, who filed the ballot language for the initiative, refers to it as “The California Right to Know Genetically Engineered Food Act.”

Michael Eisen has two posts up on this which get the meat of the issue for me. I disagree with Prop 37, though on first blush I think the idea of transparency is radically empowering. Before I get to my reasoning, I want to set aside some ancillary considerations. Some are voting for the measure ...

June 28, 2012


Filed under: Anthroplogy,Genetic Engineering,Genetics — Razib Khan @ 10:19 pm

This story in The New York Times, Flavor Is Price of Scarlet Hue of Tomatoes, Study Finds, is pretty cool:

Yes, they are often picked green and shipped long distances. Often they are refrigerated, which destroys their flavor and texture. But now researchers have discovered a genetic reason that diminishes a tomato’s flavor even if the fruit is picked ripe and coddled.

The unexpected culprit is a gene mutation that occurred by chance and that was discovered by tomato breeders. It was deliberately bred into almost all tomatoes because it conferred an advantage: It made them a uniform luscious scarlet when ripe.

Now, in a paper published in the journal Science, researchers report that the very gene that was inactivated by that mutation plays an important role in producing the sugar and aromas that are the essence of a fragrant, flavorful tomato. And these findings provide a road map for plant breeders to make better-tasting, evenly red tomatoes.

The paper, Uniform ripening Encodes a Golden 2-like Transcription Factor Regulating Tomato Fruit Chloroplast Development:

Modern tomato (Solanum lycopersicum) varieties are bred for uniform ripening (u) light green fruit phenotypes to facilitate harvests of evenly ...

August 5, 2011

The social goods of individual actions

Over at Genetic Future Dr. Daniel MacArthur has a measured response to a Nature commentary by David Goldstein, Growth of genome screening needs debate. As Dr. MacArthur notes an excessive portion of Goldstein’s piece is taken up with inferences derived from assuming that the model of rare variants causing most diseases is correct, when that is an issue currently in scientific contention (and this is a debate where Goldstein is a primary player on one side). But the last two paragraphs of the piece is where the real action is, no matter the details of genetic architecture of diseases:

One potential problem with this is that numerous genetic risk factors will have diverse and unexpected effects — sometimes causing disease, sometimes being harmless and sometimes perhaps being associated with behaviours or characteristics that society deems positive. Even for simpler Mendelian diseases, up to 30% of the mutations originally termed pathogenic have turned out to be apparently harmless…Wholesale elimination of variants associated with disease could end up influencing unexpected traits — increasing the vulnerability of populations to infectious diseases, for instance, or depleting people’s creativity.

There are no clear-cut answers to the questions of what should be screened ...

November 8, 2010

Engineering the Messiah

Filed under: Engineering,Genetic Engineering,Genetics — Razib Khan @ 11:37 am

834518In the 1920s the Soviet Union sponsored a “humanzee” breeding program. From what I recall the ultimate rationale for the funding was that the program might create a race of superior warriors, combing the incredible physical strength on a per pound basis of the chimp, with the greater level of intelligence found in human beings. To our knowledge the experiments were failures, though there have long been rumors of successes in these sorts of programs. I suspect the possibility persists because of the transgressive freak-show aspect.

This was a case where the science of the time was simply not up to the ambitions of the scientists, and this sort of engineering for the good-of-society has been the domain of science fiction. Consider the novel Cyteen. In this future history cloning is normal and acceptable, and the heart of the story involves the attempt to replicate a super-genius. There are broader stellar-political implications, as these sorts of minds are driving engines of innovation, and so strategically valuable. A cruder model of this was also explored in the G. I. Joe universe in the form of the villain Serpentor. He was engineered from the genetic material of ancient conquerors.

One of the issues which naturally cropped up in Cyteen is that genius seems to emerge through an intersection of environmental and genetic inputs. So part of the novel focuses on the environmental inputs which are replicated for the copy-genius, and the tensions which arise from this. But even granting this mitigating factor the underlying model is that the genes of geniuses will increase the odds of producing geniuses. We see this with professional athletes; regression toward the mean explains why the offspring of most professional athletes are not good enough to become professionals themselves. But, the odds of one’s child becoming a professional athlete are far above expectation if a parent is a professional athlete. The Bonds and Griffeys illustrate this.

With all that said, we have long been able to “brute force” the existence of clones in theory (at least since Dolly). Combined with the future reboot of gene therapy procedures, as well as the ability to extract and amplify older DNA samples, there is the possibility that with enough capital inputs you could “re-create” Einstein. I’m talking a classic Boys from Brazil scenario. The humanitarian and ethical obstacles to this are clear and present in any liberal society, but what about a totalitarian one? Stalin was in power for about 25 years.

Addendum: And then there’s the famous case of Duncan Idaho.

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