March 3, 2014

Crispr for genetic engineering

From the New York Times:
A Powerful New Way to Edit DNA
By ANDREW POLLACK    MARCH 3, 2014

... In the past year or so, researchers have discovered that the bacterial system can be harnessed to make precise changes to the DNA of humans, as well as other animals and plants. 
This means a genome can be edited, much as a writer might change words or fix spelling errors. It allows “customizing the genome of any cell or any species at will,” said Charles Gersbach, an assistant professor of biomedical engineering at Duke University. 
Already the molecular system, known as Crispr, is being used to make genetically engineered laboratory animals more easily than could be done before, with changes in multiple genes. Scientists in China recently made monkeys with changes in two genes. 
Scientists hope Crispr might also be used for genomic surgery, as it were, to correct errant genes that cause disease. Working in a laboratory — not, as yet, in actual humans — researchers at the Hubrecht Institute in the Netherlands showed they could fix a mutation that causes cystic fibrosis. 
But even as it is stirring excitement, Crispr is raising profound questions. Like other technologies that once wowed scientists — like gene therapy, stem cells and RNA interference — it will undoubtedly encounter setbacks before it can be used to help patients. 
It is already known, for instance, that Crispr can sometimes change genes other than the intended ones. That could lead to unwanted side effects.
The technique is also raising ethical issues. The ease of creating genetically altered monkeys and rodents could lead to more animal experimentation. And the technique of altering genes in their embryos could conceivably work with human embryos as well, raising the specter of so-called designer babies.

This is a big deal, but a couple of cautions:

-- Nothing moves very fast anymore in human medicine, so  don't expect huge changes real soon now.

-- This could be very useful for fixing one bad gene problems, but positive traits tend to be the results of lots of genes interacting, which raises all sorts of questions.

22 comments:

Reg C├Žsar said...

The crisper is the dirtiest part of the fridge. I think I'll pass…

Shouting Thomas said...

Frankenstein lives!

Anonymous said...

Steve, did you ever read the Esquire profile from a few years back of the computational biologist Eric Schadt? You might be interested -- the guy is a brilliant scientist who flunked his way outta high school and, if not for an injury sustained in the military, would have slipped through the cracks.

Anonymous said...

"Hubrecht Institute in the Netherlands" I thought the reason we paid more for drugs and medical care than any other nation was so that all the medical research would be done in the US. What gives?

Unknown said...

Sure, it's a big deal and a really tiny step at the same time. I'd love to see more coverage of avenues to pursue. Sure, changing more complex traits won't be trivially easy, we can start with the easy fixes, and science will probably have to go one step at a time.

Big Bill said...

What is the delivery vehicle? E. Coli?

And is there any way to check for the existence of certain alleles before releasing the payload?

Karen said...

Can this work on trisomy 21 and 13?

Anonymous said...

Steve,

Why did it take so long for news of Crispr to be reported in the U.S. media when it was making headlines in Britain 6 months ago or more?

Steve Sailer said...

I don't know. I was kind of waiting around for it get more press here. Presumably that it hasn't been debunked in that half year of delay suggests that it is the real deal.

Anonymous said...

How far off is this from some of Greg Cochran's theories regarding pathogens and genes?

I ask this because Tim Wise just gave a lecture at my old law school alma mater invited by the alumni assoc. and, though I didn't find time for the lecture, I had the temptation to go and ask why Greg Cochran had never been invited to share his views before this group on the subject of race and privilege. Apparently, Wise's presentation was on the so-called 'backpack of white privilege.' I mention Cochran because I notice he and Wise got into it about a decade ago on the question of whether races were a real thing, and I thought it would be interesting to remind Wise of the exchange and see whether he'd defend or back-peddle from his earlier position.

Anonymous said...

"Hubrecht Institute in the Netherlands" I thought the reason we paid more for drugs and medical care than any other nation was so that all the medical research would be done in the US. What gives?

3/3/14, 5:28 PM


The development of this technology was driven by George Church who is at Harvard and Feng Zhang who is at MIT. Several groups in Boston, California and elsewhere in the US are the leaders in this field. The proof of principle work mentioned is not the big advance.

What is the delivery vehicle? E. Coli?

And is there any way to check for the existence of certain alleles before releasing the payload?

3/3/14, 6:33 PM

It is typically delivered as plasmid DNA which is prepared from E. coli then delivered by zapping holes in the cell membrane in vitro. The allele that is being modified is characterized by DNA sequencing before and after modification. In principle this can apply to say human embryonic stem cells or early embryos.



Anonymous said...
Steve,

Why did it take so long for news of Crispr to be reported in the U.S. media when it was making headlines in Britain 6 months ago or more?

These things are always slow to permeate the public consciousness. The first paper about CRISPR genome editing came out the first week of January 2013.

Anonymous said...

How far off is this from some of Greg Cochran's theories regarding pathogens and genes?

You mean Greg Jockran.

Jason Hops said...

Why do things move so slow in medicine now? That is a major issue.

Anonymous said...

>-- This could be very useful for fixing one bad gene problems, but positive traits tend to be the results of lots of genes interacting, which raises all sorts of questions.

I'm more optimistic. I don't have the link on hand, but if you search for Steve Hsu's presentation at Google on the fancy Chinese eugenics thing he's working on, he said that of the 0.6 of the variation in IQ that genes account for, something like 0.4 of it is due to additive genetic variance, i.e. stuff that isn't due to complicated multiple-gene interactions.

If we can genetically engineer those genes to be more common, we can easily raise IQ by many points.

Anonymous said...

Wake me when they are able cure someone's cystic fibrosis instead of making some weed glow in the dark.

AMac said...

Crispr is a really exciting innovation, but the technology should be put in perspective. This is the third effective approach to targeted genetic manipulation to be achieved in the past few decades.

The first is Zinc Finger Nuclease (ZFN) technology. This is currently in Phase 2 clinical trials for ex vivo manipulation of HIV-infected patients' T cells, to slow the rate of disease progression. Recent Sangamo, Inc. press release on SB-728-T here. Browse the company's list of press releases for other ZFN therapy initiatives.

The second is TALENs, dating from about 2011. Recent review at Nature Reviews, but behind a paywall.

Clinical progress is extremely slow with these gene therapy approaches. Many reasons, but the two big ones are the unanticipated risks (Wikipedia on Jesse Gelsinger), and the risk-averse nature of the FDA and other regulatory bodies.

In the long run, a Draka-style dystopia isn't inconceivable. Neither are cures to complex inherited diseases, or Brave New World improvements* to human breeding stock. Per the list of Sangamo PRs linked above, cures to monogenic diseases are within sight.
.
* "improvements," YMMV.

panjoomby said...

they should've given CRISPR a palindromic name, such as CRSPSRC
(clustered regularly short palindromic systematic repeated chain) or a more imaginative palindrome.

fermi's paradox answered said...

the irs could reprogram tea-partiers.

Toadal said...

And when elites tire of their elitist fun,
They'll sell us genetics, so that everyone,
Can be elite.
Everyone can be super! And when everyone is super ...
No one will be.

Melendwyr said...

No, it wouldn't work on a trisomy, which is the presence of an extra copy of a chromosome.

In theory, I suppose a very early stage of embryonic development could have the chromosome removed. In practice, the embryo would have to be conceived in vitro and the defect noticed very early. Successful chromosomal surgery on multiple cells, without disrupting the ongoing process of development... I don't know if our technology could manage it, or whether biology permits it.

As for developed humans, there is no plausible means by which a trisomy could be changed, and probably even with the magical ability to alter the genome in every cell simultaneously, the physiological defects would be mostly set already. It'd be like closing the barn door after the horse had escaped - entirely pointless.

Anonymous said...

"When everyone is super ..."

This reminds me of a certain Monty Python sketch.

rob said...

ZMG, I think there are easier ways of using CRSPR for assisted reproduction.