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Scientists Find Form of Crispr Gene Editing with New Capabilities (nytimes.com)
113 points by dnetesn on June 4, 2016 | hide | past | favorite | 34 comments



If you are interested in learning more about CRISPR checkout this article - http://gizmodo.com/everything-you-need-to-know-about-crispr-... .

This podcast by Radiolab also breaks down the idea really well - http://www.radiolab.org/story/antibodies-part-1-crispr/ .

I am currently reading this book - The Gene http://www.amazon.com/Gene-Intimate-History-Siddhartha-Mukhe... to gain a better understanding of what genes are and I have found it to be really well written even for someone who last studied biology over 15 years ago.


This gene editing technology sounds powerful, but also dangerous. Should we be worried?


No. You could eat a jar of it and nothing in your genome would change - you'd just digest it like any other protein. You could sit in a bath of it, again, no problem.

In fact, the downside of crispr is that making changes in mammals is still difficult. Progress is being made on delivery mechanisms, but it fundamentally can't go into a runaway process. You'll always need an injection of some sort, or some deliberate action the part of a doctor.


> but it fundamentally can't go into a runaway process.

https://en.wikipedia.org/wiki/Gene_drive

The basic summary is that you can make a CRISPR construct that will copy itself into the homologous chromosome in a zygote/embryo. Thus, any progeny resulting from mating with an individual with the construct will be homozygous for said construct, a runaway process.

This is being considered as a way to eliminate deadly pathogens, and obviously could be used to wreak immeasurable ecological harm. I still wouldn't worry about it for humans, though, as simple genetic testing and further editing could counteract it.


> I still wouldn't worry about it for humans, though, as simple genetic testing and further editing could counteract it.

It might not show up in genetic testing unless you knew what to look for. And if you found some modification, currently it would not be ethical to try to reverse it in the germline (because these gene editing techniques are not perfect and can introduce potentially deadly errors). I think it is worth thinking more seriously about what we would do to counteract gene drives in humans, whether caused by neo-Nazis, terrorists, or well-meaning parents. Gene drives in other species, wild or domesticated, could are more of a threat in the short term.


Picture a bit of DNA that, during egg formation, shoves chromosomes with certain traits into the polar bodies. (polar bodies discard chromosomes to make the genome haploid) Children thus cannot inherit chromosomes containing the undesired DNA. This aggressive bit of DNA also avoids having itself end up in a polar body, ensuring that it will be inherited.

Suppose you wanted to keep your descendants from having any appearance traits that might lead to discrimination issues, such as with AirBNB. DNA which causes that kind of physical appearance gets kicked out during egg formation, saving your descendants from much difficulty and misery.


Gene drives can't harm us but they could easily wreak havoc on fast reproducing species we depend upon. Bees, are what I'd target if I were inclined to cause apocalypses. And perhaps soil nematodes.


I read a trio of apocalypse short story collections earlier in the year and one of the ones that stuck in my head the most was a trio of stories... "Spore", "Fruiting Bodies", and "Resistance" by Seanan McGuire. It centered around a molecular biologist who worked a lab that accidentally releases a modified strain of a "hardier, healthier, and easier-to-grow bread mold, that was resistant to virtually every fungicide and sterilizing agent we knew"

It becomes a fungal apex predator and is capable of consuming living tissue.

It was one of the most frightening apocalypse scenarios I've ever read because it seemed somewhat plausible. A hardier fungus could change ecosystems dramatically.

About 300 million years ago, fungi evolved the ability to break down lignin. Before then when biomass died, it didn't rot away and slowly got turned into the coal and oil deposits that we now consume. Fallen trees stayed where they fell for thousands of years and got turned into petrified wood.

Since that evolution, everything changed so much that it affected future geology.

Never underestimate the ability of our fuzzy fungi cousins and how they can change the world.


Want to see some rapid speciation? Kill off all the bees* and watch the other insects take over and start to specialize. It's not necessarily an apocalypse event, based on http://www.hortmag.com/plants/fruits-veggies/vegetable-crops... and Wikipedia at https://en.wikipedia.org/wiki/List_of_crop_plants_pollinated... :

"The most essential staple food crops on the planet, like corn, wheat, rice, soybeans and sorghum, need no insect help at all; they are wind-pollinated or self-pollinating. Other staple food crops, like bananas and plantains, are sterile and propagated from cuttings, requiring no pollination of any form, ever. Further, foods such as root vegetables and salad crops will produce a useful food crop without pollination, though they may not set seed;"

*The unknown unknowns about gene drive weapons may or may not be able more powerful than the extreme efficacy of natural selection on r-strategists.


Frankly, you can't say with 100% certainty that an enormously large exposure to crispr protein wouldn't have any effect. After all, many techniques used in transformation have extremely low transformation rates and require a very high concentration/rare event to occur.

Further, there are a long list of unexpected outcomes in biology where somebody said "no, never will happen" and then it happens, at some very low rate, and it turns out to have huge consequences (antibiotic resistance and cancer cells resistant to chemo are two that come to mind.)

That said, I agree, based on the nature of this specific technology, the risk of direct exposure in a non-therapy situation would be unlikely to lead to unexpected/unplanned transformation.


I'm pretty sure that people were always aware of antibiotic resistance. See for example Alexander Fleming's Nobel lecture from 1945:

http://www.nobelprize.org/nobel_prizes/medicine/laureates/19...


that observation only came about after the antibiotics were used, and resistance was observed. The discoveries happened in the late 20s and it wasn't until resistance was actually observed that people thought it would happen. If you could find a reliable, historical reference that shows this is not the case I would love to see it.


> No. You could eat a jar of it and nothing in your genome would change

Um, I don't think that is what anyone is worried about, rather what can be done intentionally with it and to what extent we are still humans after a few generations of heavy use on ourselves.


OP below asks about contaminating water supplies.


What are the control mechanisms that prevent (which?) runaway process?


It's just a protein. It evolved in bacteria and archaea to operate in those cells. There's no mechanism for it to exit the cell, or replicate, or evolve, or anything you'd need to get it to from one organism to another on its own.

I am glossing over the concept of gene drives, which is potentially worrisome, but as far as accidents go the risk is literally zero.


Unless someone put it in Rhinovirus.


... asked everyone who ever heard of a new technology.


Yes, but the technology is so simple, there isn't any way to stop someone nefarious. Hope for the best.


Yeah, CRISPR is a quite straight-forward process, so much so that pretty much any intelligent pre-med student can learn the process by reading papers. Given they have the tools, execution is no problem.


How difficult would it be to use this technology to selectively apply gene editing to specific humans based on DNA, or to humans of a specific race? Could this technology spread through food or water supplies? Could it be distributed with a delayed effect? How dangerous is this technology?


Well, in priniciple variant specific application has nothing to do with CRISPR, any genome alternation could be coupled to certain mechanisms that rely on reading out the specific traits of the targeted humans. Of course, the current developments enhance these possebilities with gene drives etc. But on the other hand it also allows the development of defense mechanisms, no technology is the ultimate game changer (though CRISPR is thought to get pretty close).

Spread through food or water supplies is probably possible, given that CRISPR is currently mostly administered via virusses like AAV or lentivirus. But that nothing new, those virus cassets existed before, and can also be used with other methods like zink-finger nucleases or TALENs.

Delayed? I don't know, probably. It really depends on what you want to do. Keep in mind that most current applications affect around 0.5 percent of all hit cells. The effectivness of the process heavily depends on the construct and probably decreases with complexity. But sure, delayed promotors and other regulatory circuits should be possible, though unlikely for now.

The whole technology is dangerous, so dangerous that we probably cannot stop it now and have to form and regulate it. But it also has enourmous benefits associated, and again, can probably defend against itself. You cannot win evolution, only participate.


eli5: what can we potentially do in the near and long term with this technology? play god?


That question can be seen equivalent to asking "How many computers will we need in the future?" in the 1950s. Could be 5 could be the current 5 billion or how many we have to day. Maybe someone more involved can say more about it. In theory possebilities are enourmous like currently healing HIV, personal cancer therapeutics, creating of custom crops (that currently do not necessarily count as GMO, mind you), enhanced model organisms. More down the road are deextinction of species, extinction of invasive species (rodents, zika, mosquitos, tilapia, humans ;). Targeted editing of embryos with herited disease. It has been said that if only 10% of what has been proposed will be feasible, we have a huge game changer.

Whether this is playing god I do not dare to say (Last member of my family was babtised 80 years ago). When people invented the airplane people said that the sky is god place and they should not go there. Craig Venter was dubbed God 2.0 many years ago. Still, its just another new technology. In the 1940/50s antibiotics were a huge improvement, today its just what we are used to. I think I will get along with it, what you think depends on you.


An evil person could do many things, like target ethnic groups based on their genetic haplogroup with an infection similar to the one currently being tested to eliminate mosquitoes, making all of their ancestors infertile in a few generations without their knowledge. In the future we could see something similar to the arms race, a sort of cyborg race with governments rushing to come up with way to make cryptographic DNA or mind transfers to protect their citizens from genetic terrorists.


ooh fascinating.. sounds like a good movie plot


Technically there is only homo sapiens sapiens the only "race" of human.


Correct, there is no way to reliably determine race via genes or any other physical method, and biologically speaking race doesn't exist.

But you can find genes that determine phenotypes that people think are racially relevant (skin color, hair texture, eye shape, etc) and you could imagine a gene drive that could do bad things to people with those genes. Whether those people are always (or even primarily) identified as or identify with a particular race could only be awfully approximate, but the effects could still be really bad.


> Should we be worried?

"Top U.S. Intelligence Official Calls Gene Editing a WMD Threat ( WMD = weapon of mass destruction)

Easy to use. Hard to control. The intelligence community now sees CRISPR as a threat to national safety.

...

The CRISPR technique’s low cost and relative ease of use—the basic ingredients can be bought online for $60—seems to have spooked intelligence agencies. "

https://www.technologyreview.com/s/600774/top-us-intelligenc...


We should be excited first.


People who think strong AI will cause a violent apocalypse are gravely mistaken. CRISPR gene editing is the eminent domain of conscious AI, and a conscious machine would seek to create designer organisms to inhabit other worlds as well as potentially birth humans superior to what we know today to become leaders of our sociological hierarchies. It would take just a few generations to rid our race of things like depression, anxiety and mental illness with this kind of intervention. While providing the opportunity to increase diversity to a level where no two humans would be alike physically.


What's with all the weird unfounded statements about AI?


Pass that shit


+1




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