FDA approves first test of CRISPR for genetic defect causing sickle cell disease
news.berkeley.edu
news.berkeley.edu
I don't really understand the delivery method.
"...some of the patient’s hematopoietic stem cells... [are] harvested for gene editing outside the body. After these cells are removed, the remaining bone marrow is destroyed with chemotherapy to allow space for the repaired and reinfused stem cells to grow."
EDIT: This is apparently the same procedure as conventional bone marrow transplants in SCA patients. CRISPR is just slotted into that workflow to synthesize a transplant, without needing to find a donor.
I suppose in this instance, the patients wouldn’t need immunosuppressants after their treatment, as I’d expect standard care patients currently need for life?
Besides GVHD, it is like you said. BMT patients are one of the few transplant types that can eventually come off of immuno-suppressants with a successful transplant. The patient's original bone marrow is supposed to be wiped out by chemotherapy (and sometimes some radiation) to make room for the new marrow transplant.
Using "something" to manipulate the donor cells has also been done for these autologous HSCTs. I know of "CAR T cell therapy", but there are likely others. ( https://www.cancer.gov/about-cancer/treatment/research/car-t... )
I think some small number of autologous HSCT recipients require immunosuppressants, but from what I remember the number is very very small. (Allogenic HSCT recipients, who receive cells from a different person, are _much_ more likely to require lifetime immunosuppressants.)
It's super cool that they're able to treat genetic diseases this way!
All of the hard CRISPR stuff is likely in vitro.
However, I don’t know anything about what the specific plans are though, this is just speculation.
So you remove bone marrow from the patient, modify the cells, put them back in. The modified cells produce fHb at a high enough level that symptoms of Sickle Cell go away.
Not that different than the already approved CAR-T therapies (with the exception they don't use CRISPR for the genetic modification).
Easier than trying to fix the cells in a solid organ.
[0]: https://www.scientificamerican.com/article/crispr-edited-cel...
This means that you can use CRISPR to selectively kill these cells only since they would be the only ones that easily accept and express the CRISPR modifications. This could be ground breaking if it is not already tried.
This trial is inserting/editing a gene.
You turning this positive into a negative is distasteful.
Not as far as it looks. Honestly, it looks closer, than real self driving cars.
> You turning this positive into a negative is distasteful.
I'm incredibly happy that we, as humanity, are advancing with science - the mRNA vaccines are also incredible. The part that is not incredible is that we, as society, are in most cases still behave like we did in the stone age: greedy, selfish, narcissistic. Because of this tech that should be used to help those in need is most commonly used to "help" those with enough funds or means.
Cheering for science advancements that are far out of reach for the majority leaves a bitter taste.
EDIT BTW, Gattaca is a temporary time. Once it's passed - one whole generation, so say ~80 years - that world would be wonderful, but that limbo time, when the movie plays out, is the nasty part.
Yes. Damn that new fancy tech of farming that only the rich can afford!
Seriously. Think about what you're saying for a second. Tech that is only for the rich becomes affordable for the masses faster and faster every year. Computers were for nation states in my parents life time. Today there are computers more powerful than the first computers in cheap toys.
We cheer for tech that only the rich can use now because it will be for the masses soon. Tech that never exists for the rich, will not exist for anyone ever.
Check your logic.
Realistically however, this kind of area falls squarely in the healthcare field which is increasingly becoming a thing for the rich and indentured servitude for the rest.
You cheer for a world full of Anton's, calculating that it isn't possible to make it to the other side, deciding not to try.
People vastly overestimate our understanding and ability to produce reliable phenotypic changes. Being able to change the tiny percent of diseases that have a straightforward and simple genetic connection is a far cry from designer humans. I think Richard Dawkins said it well.
> “Think of the body as a blanket, suspended from the ceiling by 100,000 rubber bands, all tangled and twisted around one another. The shape of the blanket — the body — is determined by the tensions of all these rubber bands taken together. Some of the rubber bands represent genes, others environmental factors. A change in a particular gene corresponds to a lengthening or shortening of one particular rubber band. But any one rubber band is linked to the blanket only indirectly via countless connections amid the welter of other rubber bands. If you cut one rubber band, or tighten it, there will be a distributed shift in tensions, and the effect on the shape of the blanket will be complex and hard to predict. In the same way, possession of a particular gene need not infallibly dictate that an individual will be homosexual. Far more probably the causal influence will be statistical. The effect of genes on bodies and behaviour is like the effect of cigarette smoke on lungs. If you smoke heavily, you increase the statistical odds that you'll get lung cancer. You won't infallibly give yourself lung cancer. Nor does refraining from smoking protect you infallibly from cancer. We live in a statistical world.”
>Cheering for science advancements that are far out of reach for the majority leaves a bitter taste.
Yet a random child born in the slums of Mumbai has a higher life expectancy than the wealthiest people on earth did 100 years ago. Just because the rich have it better than everyone else does not mean that scientific advancement has not led to vastly improved lives all over the world. Yeah, people are still greedy and mean and blah blah, but with 2 extra decades of life to live on average.
>BTW, Gattaca is a temporary time. Once it's passed - one whole generation, so say ~80 years - that world would be wonderful, but that limbo time, when the movie plays out, is the nasty part.
I don’t think you understand the point of the movie. The movie was about how we shouldn’t put total and complete faith in gene editing, because our genes are not the only thing that make us “us”. Jude Law is a genetic phenom but ends up not doing anything with his life of note because of his decisions, bad luck, and his lack of drive and motivation. Ethan Hawk was written off as a loser before he was a day old because of his genes, but he succeeded due to his decisions, good luck, and his drive and motivation. His genes said he had a statistically super high chance of dying because of his heart, but he didn’t, because a statistical likelihood is not a certainty. Ethan Hawk is allowed on the shuttle by the doctor, who’s genetically enhanced son is “not all he would have hoped”.
The message of the movie is that we need to be careful of using genes as a proxy for everything that makes up a person, and how that could lead to a dystopian society where people are pigeon holed based on one thing about them. That taking the shortcut of using a proxy, even one as complex as our genes, for something as complex as “human potential” is folly. The statistical nature of genes, epigenetics, and environmental factors cannot be ignored.
One doesn't need an x-ray vision or flying around to be to have superhuman status.
I understand your optimism because it sounds properly awesome. But we humans always, without exceptions, fuck up everything that is even theoretically fuckable and often even the rest. If you don't see potential for evil with this then I guess you lack a bit of imagination.
For every great discovery to help humanity there is always some powerful idiot thinking how it can we weaponized, used to gain advantage above others, the non-conforming, the unknown, or simply the weak.
Don’t mean to intrude, but it reads rather negative. Maybe you should seek help?
Yet science has allowed us to live longer, healthier, freer of disease, less likely to be poor (and far less likely to be extremely poor). Its easy to complain about how terrible everything is when you’re not dead of tetanus at 5 years old or have gone blind due to lack of vitamin A.
Also consider that since the industrial revolution child mortality in the West has declined tremendously (thankfully), so it's possible that our genomes have accumulated mutations presently unknown which will need to be deleted at some point. Better done via gene-editing tech than via the cruelties of natural selection or eugenics.
I agree with you that to you (and me) in this case there is a difference.
But, who sets the scale & scope?
(I am aware that the box has been opened, it will never be closed.)
Whoever does it, hopefully it is after evidence-based discussions to establish a framework for ethical and safe application. Just because the box can’t be closed doesn’t mean we just throw our hands up and say “well, nothing we can do to steer this in a responsible direction”. We don’t breed humans like dogs to produce super men, even though we theoretically could.
>If this is successfully applied in young patients, it has the potential to prevent irreversible complications of the disease
How young is this going to be, One years old, 1 month old...
Now, compare that to editing human embryos in vitro then implanting them, just because you want to prove it's possible to use a gene editing technique to alter the genome of a person.
Moreover, identifying harmful mutations can't tell you how to build superhumans. So I think the similarity is only superficial.
Helping China to trade is not to build a totalitarian country as well. Just trade.
Sickle Cell is prevalent in some populations because the gene mutation is protective against malaria. (Probably only beneficial if you have one copy, not two.)
I hope they will keep this in mind and work to eradicate malaria hand-in-hand with trying to eradicate the genes that are protective against it when they look to take it global.
We have the technology (gene drive) but scientists just aren't sure if we should do it.
There was an island where they used poison to kill all the mosquitoes because it was a big problem. All the mosquitoes dies and then all the things that ate the mosquitoes died.
And then all the things that ate things that ate mosquitoes died. And it went through a few more layers of this, like some modern day version of the Biblical plagues.
That doesn't mean we shouldn't do it. It just means it is correct to not take the decision lightly.
(Unfortunately, I've never found a good write up of this true story on the internet. I read it long ago back when dinosaurs roamed the earth and I had a bright yellow rotary phone and got information printed on dead trees.)
Including helping people who live in poverty to have better housing and medicine so their less susceptible to Malaria ?
Not to mention the ethical (regarding equity) concerns: disease from mosquitoes affects poverty-stricken areas the most, yet the people with the most access to these bodily modifications or procedures are going to be from wealthy countries.
My understanding is that a lot of the diseases we want to kill mosquitoes for are also more likely to affect people in developing countries.
Of the ones that do, many of are of African origin -- they evolved there along with us (and the diseases they carry). They are thus essentially invasive species in the rest of the world.
The nice thing about potentially using CRISPR-based gene drives to extirpate (e.g.) Aedes aegypti is that it would affect only that species, unlike our current pesticides which tend to kill insects of many different species indiscriminately.
Scientist who are eager to take out mosquitos sound more like kids who are eager to play with their new gene drive rather than consider the actual impacts.
No operation warp speed to help save hundreds of thousands of lives a year. It's almost just like a fun topic to make people feel better about themselves.
I've read more about how transmission of malaria works and basically mosquitoes carry it from biting infected humans then pass it to other humans, it's not that mosquitos are evil, they don't even know what's going on.
I think there is a question of ethics involved personally, that's because if mosquitoes had the power to wipe us out, we wouldn't be that happy if they decided to go ahead with the plan.
Saving lives is generally a strong motivator, so it's worth considering the possibilities.
https://www.cnn.com/2019/07/18/health/asian-tiger-mosquitoes...
The eradication of malaria helped Sardinia improve its public health programs and also paved the way for socio-economic development. But at a huge environmental cost that is incalculable. Some farmers accused the DTT of killing their livestock, bees and also fish.
https://totalsardinia.com/malaria/
Sheepherders, fish farmers, and beekeepers blamed their dead sheep, dead fish, and dead bees on DDT spraying.
https://www.wanderingitaly.com/blog/article/785/sardinia-and...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819864/
Edit: Odds are good I read about it originally in Reader's Digest in the late 1970s or early 1980s if you want to find a dead tree copy at a library.
The citation you provided elsewhere (for Sardinia) was for some DDT spraying - which was obviously not targeted exclusively at mosquitoes, and explains why lots of other things died.
Targeting the very small set of mosquito species (that carry malaria) with something that will wipe them out within a few generations (under 12 months) seems tremendously safe, because a) it's a small subset of the total mosquito population, b) you can test this in isolated (eg. island) environments, and c) by the very nature of this, rollback is easy -- once the species has died out locally, if needed you can quickly & safely re-populate with non-modified specimens.
I'm an environmental studies major and I have a genetic disorder. I'm getting healthier when that is supposed to be impossible and it's in part because I'm an environmental studies major and I think of the body as a complex ecosystem.
You kill one thing or change one thing and there are always myriad knock on effects. Always. Anytime you do anything that's actually at all effective, there is hell to pay.
I am getting better by trading short term costs for long term gains, the exact opposite of what Western medicine typically does. We monetize disease by trading short term gains -- that doctors can claim credit for, justifying their fees -- for long term costs which we politely admit to with multi-page warning materials included with all drugs and then normalize largely ignoring that stuff and taking it anyway. Then when your condition gets worse, they blame it on your genes instead of on the side effects of the harsh drugs they have been poisoning your system with for years and years.
It's possible to make targeted changes to an ecosystem, but it's not easy and even if you get it right, there are costs involved. Managing such change is hard and there tends to be hidden costs that the experts want to disavow responsibility for and they can generally get away with it because cause and effect can be hard or impossible to prove.
I hope they cure Sickle Cell. I hope they eradicate malaria. Parasitic infections are pretty awful.
I hope they do it in a way that doesn't involve millions of Africans being thrown under a bus so Westerners can feel like heroes while hand waving off the human costs for the locals which Westerners have a long history of running rough shod over on the excuse that we imagine we are superior to them or something.
I stand by my earlier claim.
While I acknowledge the potential of unintended consequences, and the often surprising interconnectedness of many elements within an ecosystem, I further dispute the claim that any change necessitates other, exclusively bad, 'hell to pay' changes.
Here I am, in rural Australia, and within a kilometre of me these are the pests that I would be ecstatic to get rid of, and that would have close to zero negative, and myriad positive, knock-on effects:
prickly pear, tiger pear, heliotrope, pattersons curse, foxes, rabbits, several species of med fruit fly & mosquitoes.
Almost all of these are guaranteed to have no negative knock-on effects simply because they were introduced here in the past two centuries.
Though the camel being introduced to Australia seems like something of a silver lining. From what I gather, Australia is now like a haven for the species.
Further afield from my humble abode, yes, Phytophthora, lantana, black rats, blackberry, feral goats / pigs / deer, cane toads, camels, etc.
The reason we can export camels to the middle east is that when we imported them from there, we didn't import the various parasites that are now rampant in that part of the world.
Perversely this gives us an export trade and a massively out of control population of highly destructive and resilient beasts.
If we could remove all wild camels from Australia over the space of 10 years you'd be hard-pressed to identify any net negatives, and certainly it'd be impossible to identify any negatives that were detectable when mapped onto a graph of the positive effects.
They are invasive species that exploded in Australia due to a lack of natural predators. How you can cite their existence as a refutation of anything I've said baffles me.
I've been up excessively long. With any luck, I'll be asleep soon.
Ciao.
I wasn't 'citing their existence', so much as declaring an eagerness to remove them.
The context was you started by saying:
> You kill one thing or change one thing and there are always myriad knock on effects. Always. Anytime you do anything that's actually at all effective, there is hell to pay.
I said that sounded alarmist, as there were plenty of contra examples - such as removing a dozen or so named non-indigenous pests from Australia.
You said:
> Australia is like the poster child for unintended ecological consequences. All those introduced species you cite to refute my opinion I would cite to support it.
I asked how that could sit alongside your claim that 'you kill one thing ... there is hell to pay'.
And here we are.
My point stands -- removing these introduced pests via a terminator gene or similar that targets precisely those organisms would be a fantastic result, and almost definitely have no negative effects, though of course I'd want that to be thoroughly evaluated.
An easy fallback option exists (re-introduction).
Just the first counter examples that comes to my mind: "Western medicine" eradicated smallpox and polio; what was the hell price for those?
"Western medicine" really only means medicine based on the scientific method, and shouldn't be conflated with the profit maximisation mechanisms which are so prevalent in the US medical system.
This is a known phenomenon. It's very well documented.
It's not a reason to keep letting people die, but the transition comes with costs.
That's just reality.
Antibiotics were supposed to be the end of disease. Now we are brewing antibiotic resistant infections.
It's common for diseases to jump species when adequately threatened. Organisms don't like being eradicated and will fight back.
You see more genetic mutations in diseases, fomenting resistance, when they are under pressure.
We've lost some of the medical best practices I grew up with. I have no idea if that's directly related to the eradication of small pox or polio. I haven't specifically studied those cases.
Change comes at a cost. That doesn't mean it isn't worth pursuing. It does mean that cavalier attitudes about how, clearly, this is all upside have a tendency to be dangerous.
Which practices are you referring to here?
At one time, the way we stopped STDs was we took the names of all your recent hookups, contacted them and let them know they had been with someone who had just tested positive for a particular STD and offered them testing and treatment.
In my teens, the AIDS crisis hit. In the US, it was mostly associated with gay men and IV drug users. These populations had reasonable concerns about giving a list of contacts to authorities and pushed for drug research and stronger privacy policies.
My understanding is we largely no longer use this proven method of stopping the spread of most STDs.
I can also remember going to a doctor with a sibling and a couple of cousins and all of us getting treated so that the issue wouldn't just go round and round through the family. I feel like that was a fairly common practice at the time and we mostly don't do stuff like that anymore.
Historically, doctors did house calls and were one of the smartest, best educated people in town and towns were relatively small. They could address issues that helped contribute to your medical problem beyond just prescribing drugs and surgeries.
Now we act like human beings are specimens in a petri dish and like their physical health is unrelated to their lifestyle or the fabric of their life.
I think this is a big problem. The phrase "We've thrown out the baby with the bathwater" comes to mind but doesn't quite fit.
What we've done is tossed aside wisdom and context to worship at the alter of ooh shiny diagnostics. The high tech diagnostics are useful but the largely unnoticed loss of wisdom and context is a serious problem and we aren't even trying to solve it because we mostly haven't noticed that it matters.
What's the hellish consequence of eyeglasses?
That's a misreading of my statement that talks about killing a thing in an ecosystem and thereby upsetting the balance of the ecosystem.
What's to stop some random, non-scientist, group of people from just doing this? Mosquitos are pretty evil..
Hopefully whoever decides to just go do it has the sense to only target mosquitoes that preferentially feed on humans. Much less ecosystem impact that way.
These days, introducing a known mutation via a CRISPR gene drive is engineering. The hard part is scaling it so your mutation doesn't die out, testing to ensure that it is actually propagating, etc.
> Hopefully whoever decides to just go do it has the sense to only target mosquitoes that preferentially feed on humans.
You have to repeat a considerable amount work for every single target species. I highly doubt they'd target more than one.
The (many) species of mosquito found in the Arctic do not carry malaria. Malaria is largely a tropical and subtropical disease.
Ecologically, they can normally be replaced by some of the 3460 others.
https://blogs.sciencemag.org/pipeline/archives/2021/03/01/a-...
No one will force people in areas where malaria is endemic to have sickle cell anemia treated, and a treatment for sickle cell anemia won't slow down treatment/eradication of malaria.
There are lots of sources out there. Here are just a couple.
https://en.wikibooks.org/wiki/Professionalism/The_Nestl%C3%A...
https://www.ranker.com/list/nestle-baby-formula-boycott/meli...
I guess medical companies testing the technology might do things to get people to participate in trials, but I'm not real sure people with sickle cell anemia would be mad about having to use modern anti-malarials instead of suffering with sickle cell.
This cure is going to cost much much more. So highly unlikely.
One copy of the gene partially protects you from malaria; two copies of the gene make you very sick.
That's why even in Africa only a small portion of the population has the gene. The gene is an evolutionary advantage as long as the prevalence in the population is low. As soon as the frequency of the gene in the population goes up, it becomes a disadvantage because if both you and your partner have the gene your kid has a 25% chance of getting two copies.
1) Extract bone marrow from patient
2) Use CRISPR to fix broken gene in the extracted bone marrow
3) Use chemo to destroy old bone marrow in patient
4) Transplant fixed bone marrow from step 2 back into the patient
A big downside to this treatment is that as far as I know this kind of chemo can make male patients infertile.
(Before CRISPR, you would use restriction enzymes with a short, fixed recognition sequence, typically 4-6 base pairs [1]. In that case it was a bit tricky to find the right enzyme that cuts the DNA in the right place, and not in an unwanted place. And you couldn't just cut the DNA in any place you want.)
[1]: https://en.wikipedia.org/wiki/List_of_restriction_enzyme_cut...
You extract marrow and CRISPR it to get rid of the problem gene. Then you kill off all of the bone marrow in the patient, and replace it with the new stuff. That's a cure.
Does anyone have an idea how much a treatment like this would cost?