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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.

November 25, 2018

The human CRISPR revolution will probably be written in Chinese

Filed under: Crispr — Razib Khan @ 5:32 pm

I am probably biased because of my professional focus, but this may be the biggest story of 2018, Chinese scientists are creating CRISPR babies:

According to Chinese medical documents posted online this month (here and here), a team at the Southern University of Science and Technology, in Shenzhen, has been recruiting couples in an effort to create the first gene-edited babies. They planned to eliminate a gene called CCR5 in order to render the offspring resistant to HIV, smallpox, and cholera.

We knew this was coming. Soon. But now we can confirm it. It confirms my assumption that gene editing in the human context is going to mostly focus on preventing disease in the near future. In a world of low fertility, every expectant parent prays (literally or metaphorically) for a healthy child. After the child is born they can think about other things like how tall they are going to be or how smart they are. But health, that is always the number one concern.

From what I know the United States still has the largest number of top-flight researchers in the basic and applied sciences. American scientific culture, for all its faults, is second to none. But for various reasons, I can’t see America trying to keep up with the Chinese when it comes to gene editing of humans. CRISPR technology will probably be applied to other things, such as in applied plant and animal sciences.

The future is here. We’re just along for the ride….

September 18, 2018

On the whole genomics will not be individually transformative…for now

Filed under: Crispr,Genomics,Personal Genetics,Personal Genome,Personal genomics — Razib Khan @ 4:51 pm

A new piece in The Guardian, ‘Your father’s not your father’: when DNA tests reveal more than you bargained for, is one of the two major genres in writings on personal genomics in the media right now (there are exceptions). First, there is the genre where genetics doesn’t do anything for you. It’s a waste of money! Second, there is the genre where genetics rocks our whole world, and it’s dangerous to one’s own self-identity. And so on. Basically, the two optimum peaks in this field of journalism are between banal and sinister.

In response to this I stated that for most people personal genomics will probably have an impact somewhere in the middle. To be fair, someone reading the headline of the comment I co-authored in Genome Biology, Consumer genomics will change your life, whether you get tested or not, may wonder as the seeming contradiction.

But it’s not really there. On the aggrgate social level genomics is going to have a non-trivial impact on health and lifestyle. This is a large proportion of our GDP. So it’s “kind of a big deal” in that sense. But, for many individuals the outcomes will be quite modest. For a small minority of individuals there will be real and important medical consequences. In these cases the outcomes are a big deal. But for most people genetic dispositions and risks are diffuse, of modest effect, and often backloaded in one’s life. Even though it will impact most of society in the near future, it’s touch will be gentle.

An analogy here can be made with BMI, or body-mass-index. As an individual predictor and statistic it leaves a lot to be desired. But, for public health scientists and officials aggregate BMI distributions are critical to get a sense of the landscape.

Finally, this is focusing on genomics where we read the sequence (or get back genotype results). The next stage that might really be game-changing is the write revolution. CRISPR genetic engineering. In the 2020s I assume that CRISPR applications will mostly be in critical health contexts (e.g., “fixing” Mendelian diseases), or in non-human contexts (e.g., agricultural genetics). Like genomics the ubiquity of genetic engineering will be kind of a big deal economically in the aggregate, but it won’t be a big deal for individuals.

If you are a transhumanist or whatever they call themselves now, one can imagine a scenario where a large portion of the population starts “re-writing” themselves. That would be both a huge aggregate and individual impact. But we’re a long way from that….

January 22, 2018

The rise of Chinese science and CRISPR

Filed under: Crispr — Razib Khan @ 9:52 pm

So as of now China is producing more scientific publications than the United States of America. But there’s quality and there’s quantity. I think most people would still American science is more cutting edge than Chinese science. And for cultural reasons that may stay true for a while longer.

But there is one area where China seems to be forging ahead and likely will make advances earlier than the USA: genetics, and genetic engineering in particular. The Wall Street Journal has a long piece, China, Unhampered by Rules, Races Ahead in Gene-Editing Trials. It turns out that Chinese have been doing human trials since 2015. Meanwhile, in the USA the greenlight has still not been given (though it seems close).

Honestly how quickly the Chinese are moving in human trials is alarming. Then again, this is a country with the highest number of executions in the world (some of this is sheer size, but it’s higher per capita than the USA). So we should keep perspective. There are many worse things that the Chinese are doing in relation to human rights that moving too fast in trials with cancer patients.

In any case, this comment jumped out at me:

In traditional drug development, too, human-trial rules can differ among countries. But China’s foray into human Crispr trials has some Western scientists concerned about the unintended consequences of using the wholly new tool—such as harm to patients—which could set back the field for everyone.

Western scientists the Journal interviewed didn’t suggest America’s stringent requirements should be weakened. Instead, many advocate an international consensus on ethical issues around a science that makes fundamental changes to human DNA yet still isn’t completely understood.

As a descriptive matter, I am highly skeptical of the possibility that “international standards” is going to involve the Chinese adhering to Western standards. If a genuine international consensus is going to emerge there has to be a give and take, which means that the very high threshold set for safety in human trials in the West may not apply in China.

August 2, 2017

But editing embryos is normal science!

Filed under: Crispr — Razib Khan @ 9:44 pm

The media is writing breathless stories about the recent CRISPR “embryo-editing”, In Breakthrough, Scientists Edit a Dangerous Mutation From Genes in Human Embryos.

The paper is out in Nature, Correction of a pathogenic gene mutation in human embryos.

My major confusion is that this is normal science. The breakthrough was the discovery of the power of CRISPR-Cas9. Once the discovery was made there was a literally stampede to use the technique because its power and ease was so manifest. What’s happening now is that the technique is getting more powerful and effective. I think it would surprise people if it didn’t get better.

A major problem for economists in modeling productivity growth is that innovation is unpredictable. But in this case the big innovation has occurred. The next few decades are likely going to see progressive and continuous improvement in the technology. Where that will lead us? Unpredictable….

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