- The stakes here are high. Any company that wants to work with anything other than microbes will have to license Zhang's patent; royalties could be worth billions of dollars, and the resulting products could be worth billions more.
- In an odd reversal, it’s the scientists who are showing more fear than the civilians. When I ask Church for his most nightmarish Crispr scenario, he mutters something about weapons and then stops short.
Although it is all far off from reality still I found the article to be really interesting, especially the part mentioning things like ethics with genome engineering and embryo engineering. What are your thoughts on genetic engineer and its future?
A few notes: - The patent dispute over CRISPR is doubly complicated by the fact that US patent law changed, from first to discover to first to file, right around the time of these discoveries - Jennifer Doudna was one of the founders of Editas Medicine, but left to form Caribou BioSciences - The CRISPR human embryo experiments were not performed in an optimal manner, and did not follow the protocols that a CRISPR lab would use to reduce the chance of off-target effects Is a complete understatement. Short DNA fragments are dirt cheap to print, so on a lab's budget, you're talking about knocking out every gene in an organism's genome... five times over. So you can start better testing things like which genes affect cancer drug-resistance, what combination therapies work better on parasites, etc. There were ways to do this previously, using RNA interference, but CRISPR-based gene knockouts turn out to be a lot more reproducible and informative.The truth is, most of what scientists want to do with Crispr is not controversial. For example, researchers once had no way to figure out why spiders have the same gene that determines the pattern of veins in the wings of flies. You could sequence the spider and see that the “wing gene” was in its genome, but all you’d know was that it certainly wasn’t designing wings. Now, with less than $100, an ordinary arachnologist can snip the wing gene out of a spider embryo and see what happens when that spider matures. If it’s obvious—maybe its claws fail to form—you’ve learned that the wing gene must have served a different purpose before insects branched off, evolutionarily, from the ancestor they shared with spiders. Pick your creature, pick your gene, and you can bet someone somewhere is giving it a go.
This post is really useful, thanks! I was wondering if, as someone who is obviously WAY more informed on this than I am, you could recommend a good place to start reading up the technology
(The sort of place an undergrad with aspirations to one day work in gene editing might begin)? I'm a total nulle, so sorry if the question is ridiculous!
Umm, from which angle would you be most interested in? There are videos online showing how CRISPR/Cas9+sgRNA does its target recognition, and if you read the primary publications on the protein, they go into a lot more detail about its structure. I don't know if it's made its way into textbooks yet, but the canonical "CRISPR" isn't too hard to understand. I'm not too sure about TALENs and ZFNs, the two older technologies for cutting DNA, but they've been around for a lot longer, and a few clinical trials are using them, so a quick google / pubmed search should find you a few reviews on them. The CRISPR field itself is only like 3 years old, too, so you can read through the most impactful publications in a relatively short amount of time. Then there's homologous-directed repair (HDR) and non-homologous end-joining (NHEJ), which are the two primary mechanisms by which cells repair their genome after it has been cut. If you have a decent molecular biology textbook, it should have a section on DNA repair, which covers those two as well as a number of other pathways to repair damaged / mutated / mismatched / cut DNA. I've heard this topic is currently of interest within the CRISPR field, since people want more reliability / efficiency for the process and that involves better control over which repair pathways are used. Beyond that, people are looking for better ways right now to engineer Cas9, including finding smaller versions of the protein from other species, generating Cas9s with alternate PAMs (The fixed start sequence that must be matched to the target DNA), making Cas9's that are photo-activatable / chemically inducible / "split" (Where the protein is cut into two sequences that bind each other to make a functional protein). There's also research into the efficiency over different protocols, which I mentioned in the parent post, where the nuclease portion of Cas9 is mutated to a nickase / Link / Link / Link / Link, causing it to only cut one side of the DNA backbone. Thus you can have two sgRNAs that each target next to the site you wish to mutate, increasing the specificity of places in the genome that get cut on both sides of the DNA. Another topic that's hot right now are Cas9-activators, where the protein itself is linked to transcriptional activators / epigenetic modifiers, allowing someone to up-regulate their gene of choice without having to modify the DNA. There's also Cas9-inhibitors, that down-regulate gene expression, but I don't think they work too well at the moment... Lastly, there's the burgeoning field of synthetic biology, where people are exploring new ways to construct long sequences of DNA and create "gene circuits", where genes act together to sense, interpret, and respond to a cell's environment in predictable ways. Some of it is a little out there, but it can help to know about things like Gibson Assembly and Golden Gate, which are two useful techniques in assembling large portions of DNA. Past that, knowing the basics of cloning / PCR / biochemistry / molecular biology will take you a long way. If you have a good foundation in molecular biology, you should be able to quickly learn any of the fancy biotechnology that's popular that year. Hopefully that's not all too jargony, I kinda brain spewed there in an effort to get out the door in the morning faster.
thank-you thank-you thank-you!
this was what I was requesting and a million times more. I actually printed out your post and pinned it above my desk, so I can work through it at my s l o w pace :) hope you got out of the door in time?
Np, keep in mind CRISPR isn't my main field, so my knowledge of this stuff is just above a dilettante level. I'd try to keep an open mind, if I were you, and try to start thinking about the topic from whatever angles you've been taught about in classes (i.e. chemical, biophysical, genomic, structural, etc). I'm still surprised at the crazy ways people think of to tinker with existing technologies.
Honestly? I have two things to say. First, we stopped natural selection by protecting the weak. I truly believe that bioengineering (either like this, with genetic modification, or via external improvements like prosthetics) is the next path in the evolution of our species. We boosted our numbers by saving those who would not survive otherwise. Now all we have to do is eliminate their handicaps, then improve even an able body so that we may survive the harshness of space (because, in my opinion, I believe we will never leave the Solar System with our current bodies). Our species is stagnating. We can fix that. No more cancer. No more Downs syndrome, or Parkinsons, or degenerative neuromuscular issues. Second thing, genetic engineering does not only apply to us. Within a generation, with this technology, I am fairly certain that some tasks (small-scale power generation comes to mind) will find themselves integrated with bio-machines - specially made lifeforms that can do what the machine can do, most likely better. And I know there'll be at least someone who will point out that this paves the way to eugenics and other nasty side effects. My opinion on this is that if humans never developed any technology that could enable evil, we would still be animals. Any form of communication has the potential to enable evil. Cars, nuclear power, electricity, steel, all of these can enable evil. Medicine itself was often progressed by evil. There IS no doubt that this technology will be used for evil by some people. But the possible positives vastly outweigh most evils for me.
I wouldn't be so sure. Between the Tom Clancy style mini-biographies (God I hate them) the article mentions that this could be worth billions, and they are right. This means genome research gets done quicker. This means new crops are developed faster. Human genome editing will come much later. The ability to do research that is already being done with more precision is what's important. Money is the great motivator.Although it is all far off from reality still
This is fascinating. I'm not at all sure how far off this is from reality, either - the technology seems to already have come on in leaps and bounds since 2012. Genetic engineering should worry me more than it does.
Maybe I'm just so optimistic about its medical potential that I'm ignoring potential misuse!? Or maybe I watched too much sci-fi as a kid. Or maybe I put too much faith in the moral compass of scientists.
What does worry me is how little of the technology appears to be in the public domain. If start-ups are having to pay enormous fees to the (somewhat sinister-seeming) Zhang, that could hurt innovation - or, at least, push researchers to concentrate on the most lucrative possibilities of the technology, rather than those that might be best for humanity.
I feel like I really want to tinker around with this stuff myself! Maybe it's time to go back to university...