Charging toward an era of genetically modified humans

April 16, 2015 12:12 AM

The CRISPR Revolution [ungated: 1,2,3] - "Biologists continue to hone their tools for deleting, replacing or otherwise editing DNA and a strategy called CRISPR has quickly become one of the most popular ways to do genome engineering. Utilizing a modified bacterial protein and a RNA that guides it to a specific DNA sequence, the CRISPR system provides unprecedented control over genes in many species, including perhaps humans. This control has allowed many new types of experiments, but also raised questions about what CRISPR can enable."

CRISPR Natural History in Bacteria - "We’ve barely begun to understand how CRISPR works in the natural world. Microbes use it as a sophisticated immune system, allowing them to learn to recognize their enemies. Now scientists are discovering that microbes use CRISPR for other jobs as well. The natural history of CRISPR poses many questions to scientists, for which they don’t have very good answers yet. But it also holds great promise. Doudna and her colleagues harnessed one type of CRISPR, but scientists are finding a vast menagerie of different types. Tapping that diversity could lead to more effective gene editing technology, or open the way to applications no one has thought of yet."

A New Kind of Evolution: Did this mean that CRISPR meets the requirements for Lamarckian inheritance? “In my humble opinion, it does,” said Koonin.

Genome Editing with CRISPR-Cas9: Allowing the creation of transgenic animals with targeted mutations - "This video illustrates how CRISPR and Cas9 can help microbes fight viruses and how researchers might use that system to edit human genes."

Après nous le déluge - "Rumors are rife, presumably from anonymous peer reviewers, that scientists in China have already used CRISPR on human embryos and have submitted papers on their results."

Gene drive - "George Church, a geneticist at Harvard Medical School in Boston who is a leader in the field, believes the new study should not have been published, because it does not include measures to restrain the spread of unintended mutations. 'It is a step too far', he says."

Let’s Hit ‘Pause’ Before Altering Humankind - "Two Nobel laureates on gene technology capable of making changes that are heritable by generations to come."

Scientists Have Created 'DNA Scissors' That Can Alter Your Genes, but Should They Use Them? - "A spectacular discovery made in 2012 has turned human genome research on its head. Careful what you wish for, comes the warning... The genetic code is the software that runs living things, and just as with digital technology, DNA is being upgraded, from a read-only to a read-write medium."

It’s time for the United States to talk about genetics - "After roughly 4 billion years of evolution by natural selection, we are on the verge of taking active control of our evolutionary process."

Derek Lowe on CRISPR, from the comments - "Many of the possibilities that people are most worried about are harder to pin down, though. There’s no single gene for height, for example, or intelligence (or Alzheimer’s or diabetes, for that matter, to stick with the fixing-what’s-broken part of the landscape). Many of the really sticky issues are still a bit downstream, awaiting a better understanding of the human genome, but the big fundamental one is indeed here now: the first deliberate editing of the human genetic inheritance."

The CRISPR revolution seems to be here, is this the coming of eugenics? - "I believe the implications of all this — and its nearness to actual realization — have not yet hit either economics or the world of ideas more generally."

also btw...
-CRISPR Patent Fight Now a Winner-Take-All Match
-Health, ethics, or money: What’s really driving CRISPR debate?
-CRISPR-Cas9 pioneer starts recruiting R&D group in Cambridge hub
-Cellectis Plant Sciences, Inc. Locks Early CRISPR Intellectual Property Uses in Plants

[previously: 1,2,3,4,5]

posted by kliuless (27 comments total)

I want the hacking augs.
posted by GallonOfAlan at 12:30 AM on April 16, 2015 [1 favorite]

CRISPR technology is exciting stuff, along with TALEN and ZFN methods. One drug company is researching ZFN as a means to impart CCR5 delta 32 resistance in T-cells of HIV-infected patients, putting them into remission — effectively a cure for HIV. Our lab is using TALEN to modify the regulatory regions of certain cell types, like cancer and blood lines. We can look at how gene expression changes when the structure of DNA is modified, and compare it with what we'd otherwise expect to see happen with a cancer or blood cell type.

For every banana republic using these technologies to do shady research, there could be numerous drugs that come out of this for the rest of us, that modify vulnerable DNA or impart useful defenses against invaders. By sequencing the genomes of centenarians and supercentenarians, maybe we can one day engineer in genes that offer a better shot at longevity. So many possibilities to improve the human condition.
posted by a lungful of dragon at 1:03 AM on April 16, 2015 [2 favorites]

It's hard to overstate the potential of CRISPR. We've long been able to make genetically modified mice (and a few other organisms), but it is now faster and cheaper do it using CRISPR, and it can be applied to any organism. It can be used to discover pathways of drug and pathogen susceptibility and resistance. It also has potential in gene therapy, provided they can miniaturise the technology.

The eugenics debate is bemusing. We've been modifying human genes for neatly 20 years now to correct genetic disorders. And it has been technically feasible to clone and create transgenic humans for well over a decade. CRISPR's potential (potentially) exceeds that of previous approaches, but in this context we're talking about and an ease and efficiency thing, not a holy-shit-this-was-never-possible-before thing.

So I think that if the emergence of this new technology wasn't also coinciding with China's rising influence in, well, everything, then I'm not sure we'd be seeing such alarmist eugenics articles. I'm as excited as the next person about CRISPR, but there is a reflective sinophobia coming through pretty strongly in the end-is-nigh rhetoric.
posted by kisch mokusch at 4:03 AM on April 16, 2015 [4 favorites]

In livestock, CRISPRs are exciting because you're not introducing genes from other species, which consumers tend to feel uncomfortable about. Think about it -- you can create a clone of a high genetic merit bull, use a CRISPR to knock out the horned gene, and you've got a high genetic merit, polled bull. This great from an animal welfare and consumer preference point-of-view. No transgenics necessary!
posted by wintermind at 5:19 AM on April 16, 2015

There's a lot of fearful conservatism out there. That became clear in the UK when they cleared the way for transfers of mitochondrial DNA. That was a complete no-brainer in my opinion, but lots of people, including the Church of England (shame on you) opposed it out of mere caution. We're not sure it's safe, they said. Actually, we were sure, but in any case the idea that having ghastly inherited diseases somehow represents 'safety' must be bitterly ironic if you've suffered from them directly or indirectly.
posted by Segundus at 5:22 AM on April 16, 2015 [4 favorites]

Actually, we were sure, but in any case the idea that having ghastly inherited diseases somehow represents 'safety' must be bitterly ironic if you've suffered from them directly or indirectly.

First of all, ICSI on its own isn't "safe" by a lot of very reasonable definitions, and there's been enough of it done to be pretty sure about that.

You have no way of assessing the "safety" of a procedure where you're swapping around nuclei or spindles until you've done hundreds of them and watched them grow up for a while. So, no, we're not sure, unless "we" means "people who've decided to ignore major concerns". Whether uncertainty means one should or shouldn't do something is, of course, a separate question.

Second, the alternative isn't necessarily "having ghastly inherited diseases". The alternative may be "accepting that your desire to reproduce doesn't necessarily justify sticking somebody else with a ghastly inherited disease, so maybe you should adopt or something".

I'm a freaking transhumanist and this stuff makes me nervous. If possible, I would much rather do modifications in the soma, on adults, until we're smarter.
posted by Hizonner at 6:50 AM on April 16, 2015 [2 favorites]

First of all, ICSI on its own isn't "safe" by a lot of very reasonable definitions, and there's been enough of it done to be pretty sure about that.

Mitochondrial DNA transfer != ICSI
posted by Mental Wimp at 7:00 AM on April 16, 2015

"I'm looking forward to when bioengineering moves from technology to handicraft: biotech on the other side of necessity, where it enters the realm of nose piercing. People with tiny little goldfish swimming in one eye or feathers growing out of their backs. I'd love to be in a world where women grow penises because it is fashionable, or you can have an eye replacement of a different color or from a different species. All the adults will say, 'Tut, tut, tut, girls never had penises in my day. We used to pierce our noses and lips. Why don't you do that?' And the kids will say, 'Mom, you're so old-fashioned.' All good technology should be used to piss off people's parents."
-Neil Gaiman

(Loved this quote for years, been trying to find the original source for it and I think it's from a WIRED piece from pre-2001, but can't find it online.)
posted by Wretch729 at 7:12 AM on April 16, 2015 [6 favorites]

Mitochondrial DNA transfer != ICSI

That's true, but I bet that ICSI is being used to get the "starting material" for that transfer, since ICSI seems to be the method of choice for IVF these days.

Then you follow it up with something a whole lot more invasive. And then somebody claims to be "sure" it's safe?
posted by Hizonner at 7:14 AM on April 16, 2015

If I could give women anything right now it would be the ability rabbits (and some other mammals I think) have to reabsorb unwanted fetuses at will. A big middle finger to the antichoice types.

But yeah, feathers could be fun too.

I know we're (ideally) headed towards near or actual immortality, if we don't off ourselves first, but that sure does make it harder to get rid of assholes. As it is, I hope to have the pleasure of reading Dick Cheney's obituary one day, little as that does to make up for his crimes. Future generations may end up being stuck with their Cheney equivalents. And having to decide whether reproduction is really something you need much of if people hang around forever.

Certainly a lot could go wrong between here and there. I worry about doomsday scenarios (mutations released into the wild endangering us or other species thanks to unforeseen consequences) but also about the thought that some cloned/modified and sentient person or persons might be created and end up living a life full of suffering. Or be created to be a sort of sub-human with no rights. Basically, all your sci-fi dystopian scenarios.
posted by emjaybee at 7:29 AM on April 16, 2015 [5 favorites]

Whenever someone asks me "what is the most realistic science-fiction movie of all time?" (it happens more than you'd think), my reply is invariably "Gattaca." As far as portraying a believable future, it is not only the leader of the movie pack, but far more convincing than the vast majority of science-fiction novels. What I'm trying to say is that, for all the hand-wringing, it seems inevitable that these tools will one day be routinely used on human beings. That's not to say that these kinds of concerns are misplaced, but that nothing is going to stand in the way of prospective parents with the opportunity to give their child all the advantages they can possibly muster.
posted by Edgewise at 8:08 AM on April 16, 2015 [1 favorite]

I look forward to farmers using this technology to create wilt-resistant lettuce. But seriously, this looks like a nice overview of CRISPR/Cas9.
posted by exogenous at 8:10 AM on April 16, 2015 [2 favorites]

What I'm trying to say is that, for all the hand-wringing, it seems inevitable that these tools will one day be routinely used on human beings.

The question is, which human beings? If genetic engineering technologies are presumed to belong, as Jonas Salk said of the polio vaccine, to all mankind, then they really would be a boon. Odds are, however, that they're going act as an accelerant to the inequality bonfire already in progress.
posted by Cash4Lead at 8:38 AM on April 16, 2015 [4 favorites]

Odds are, however, that they're going act as an accelerant to the inequality bonfire already in progress.

In the future, you will not only be jealous of billionaires' yachts, you will also begrudge their feathered, be-penised trophy wives whose eyes are filled with tiny goldfish.
posted by vorpal bunny at 9:21 AM on April 16, 2015 [5 favorites]

That's true, but I bet that ICSI is being used to get the "starting material" for that transfer, since ICSI seems to be the method of choice for IVF these days.

You referenced ICSI responding to a comment about the safety of mitochondrial donation, not ICSI. You may be right that ICSI is dangerous, but you conflated it with mitochondrial donation originally and in your response to my comment.
posted by Mental Wimp at 9:29 AM on April 16, 2015

And having to decide whether reproduction is really something you need much of if people hang around forever.

Well, for some of us, reproduction has its own joys beyond the act of procreation.
posted by Mental Wimp at 9:31 AM on April 16, 2015

In the future, you will not only be jealous of billionaires' yachts, you will also begrudge their feathered, be-penised trophy wives whose eyes are filled with tiny goldfish.

Or you simply will be bio-engineered to happily accept your relatively sorry lot in life.
posted by Atom Eyes at 9:52 AM on April 16, 2015 [1 favorite]

Throwing out accusations of "sinophobia" is a bit rash considering China's historical record vis a vis human rights.
posted by Redgrendel2001 at 10:15 AM on April 16, 2015

like kisch mokusch says, human beings -- and many other lifeforms -- have had the reproductive 'tools' of self-selection for a while now; assortive mating and group selection still entail all the 'fitness' bias that germline editing has. the (revolutionary) difference of course is that horizontal gene transfer can move at the speed of cultural transmission -- lamarckian evolution is more like fashion -- where as freeman dyson has suggested: "the rules of Open Source sharing will be extended from the exchange of software to the exchange of genes. Then the evolution of life will once again be communal, as it was in the good old days before separate species and intellectual property were invented."

so to extend the metaphor and perhaps answer the question 'which human beings?' it'd be those with the knowledge to do it first of all -- witness the scramble to 'lock up' talent/IP currently -- their backers/handlers, people with the resources to gain access and/or to whom it's made available. open source knowledge transmission is the ideal, where everyone has access, but what if gatekeepers deem this (dual-use) technology more like nuclear power than BSD? while "[m]any of the really sticky issues are still a bit downstream, awaiting a better understanding of the human genome," i think it's probably worth discussing now, but without knowing its full capabilities (and costs) any debate will be naturally speculative and provisional.

oh and fwiw, on that note, speaking of realistic science-fiction ramez naam's apex is coming out in may :P
posted by kliuless at 10:24 AM on April 16, 2015 [1 favorite]

The really cool thing about people is that it is possible for us to feel two or more different, conflicting things at the same time and none are wrong (if wrong is even an appropriate word).

For the 11 kids out of every 10,000 in the united states born with Trisomy 21, can/should offer a method to strip off the surplus chromosome on the 21^st gene? In utero? Post natal?

On the one hand, parenting a child with Down syndrome is difficult. Exceptionally difficult. It doesn't help that my generation and the one before who are the policy makers for today and tomorrow grew up in a eugenics/institution biased world and have been instrumental in making parenting and education more difficult or made it more difficult to get better. It's bone tiring.

On the other hand, my daughter's generation has grown up around her and in a world with hardly any institutionalization and understand her and accept her for who she is. They grew up with inclusion and least restrictive environment and the ADA. In short, they understand the value of diversity and frequently school me by their actions and words.

Making a genetic change such that parenting is easier also feels lazy to me. Why not an exposed pressure point so that a toddler will nap at a touch?

And perhaps the root of the issue is allowing the disability to define the person.
Still, I remain conflicted.
posted by plinth at 1:45 PM on April 16, 2015 [2 favorites]

I am hugely optimistic about genetic modification, but gene drives still scare the willies out of me.
posted by BungaDunga at 3:40 PM on April 16, 2015

I'm not so optimistic about genetic modification for "making smarter humans", although obviously it'll help enormously with medical applications, like treating genetic diseases, understanding risk factors for non-genetic diseases, preventing genetic defects like retardation, etc.

I'm optimistic about education being able to "make people smarter". I'm also optimistic about neural implants actually "make people smarter", both through directly providing computations at which neurons such, and through allowing clusters of human minds linked directly together.
posted by jeffburdges at 4:41 PM on April 16, 2015 [1 favorite]

Khaaaaaaannnnnnnn!!!!!!!!!!
posted by rankfreudlite at 7:44 PM on April 16, 2015

Nature: Chinese scientists genetically modify human embryos

It confirms the rumors of Chinese use of CRISPR, but it sounds like it's not ready for primetime by a long shot:

The team injected 86 embryos and then waited 48 hours, enough time for the CRISPR/Cas9 system and the molecules that replace the missing DNA to act — and for the embryos to grow to about eight cells each. Of the 71 embryos that survived, 54 were genetically tested. This revealed that just 28 were successfully spliced, and that only a fraction of those contained the replacement genetic material. “If you want to do it in normal embryos, you need to be close to 100%,” Huang says. “That’s why we stopped. We still think it’s too immature.”

His team also found a surprising number of ‘off-target’ mutations assumed to be introduced by the CRISPR/Cas9 complex acting on other parts of the genome. This effect is one of the main safety concerns surrounding germline gene editing because these unintended mutations could be harmful. The rates of such mutations were much higher than those observed in gene-editing studies of mouse embryos or human adult cells. And Huang notes that his team likely only detected a subset of the unintended mutations because their study looked only at a portion of the genome, known as the exome. “If we did the whole genome sequence, we would get many more,” he says.
posted by Cash4Lead at 1:26 PM on April 22, 2015 [1 favorite]

CRISPR gene editing startup Caribou Biosciences raises $11M (15/4/2; via) - "This funding will allow us to further accelerate deployment of our advanced genome editing platform, which enables simple, flexible targeting of any site in a given genome, in a number of focus areas including therapeutic research and development, agricultural biotechnology and industrial biotechnology."

In 2014, Caribou co-founded Intellia Therapeutics, which is utilizing Caribou's technology platform in the discovery, development and commercialization of human gene and cell therapies.

Intellia Therapeutics Announces Dr. Jennifer Doudna and Dr. Derrick Rossi to Join Company (15/4/22)
posted by kliuless at 2:46 PM on April 22, 2015

more press, fwiw...
-CRISPR for beginners
-Claims about embryos
-CRISPR edits in human zygotes
-America Needs to Figure Out the Ethics of Gene Editing Now
-Scientists in China have just crossed one of biotechnology's red lines
posted by kliuless at 9:16 AM on April 30, 2015 [1 favorite]

Carl Zimmer's explainer about editing human embryos.
posted by kliuless at 1:23 PM on May 6, 2015