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Teenager's sickle cell reversed using a treatment to change his DNA

bbc.com

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Re: Teenager's sickle cell reversed using a treatment to change his DNA

#21

Post by PhantomGremlin »

candiodari wrote: post #13
helloworld wrote: post #5

Earlier quoted context omitted.

It sounds like this research involves somatic gene transfer, in which the change to the genome is not passed on to children: Gene transfer can be targeted to somatic (body) or germ (egg and sperm) cells. In somatic gene transfer the recipient's genome is changed, but the change is not passed on to the next generation. In germline gene transfer, the parents' egg and sperm cells are changed with the goal of passing on…

Isn't that dangerous ? This will allow him to have a normal life, which includes kids, which will need this (potentially very expensive) treatment as well. Wouldn't you, in order to not destroy the gene pool, want to restrict gene changes to both of those ? Either that or sterilize the patient to prevent transmission of lethal genes ? This treatment is VERY unfair to any children this guy fathers. Of course I do get…

This treatment is VERY unfair to any children this guy fathers.

In order to have the disease you need to inherit bad genes from both parents.[1] Consequently there are many more carriers than people who actually have the trait. So any of this guy's children have at most a 50% chance of having the trait if the other parent of the child doesn't have it, and 0% chance if the other parent isn't a carrier.

I'm sure if we sequenced your DNA we would find a number of potentially very problematic diseases for which you are a carrier. That applies to everyone, nobody has perfect DNA.

in order to not destroy the gene pool

There are a lot of morons in this world; many more being born every day. Many of them manage to reproduce before reaching the point where they would be under consideration for a Darwin Award. In the greater scheme of things this one particular genetic defect isn't seriously threatening to "destroy the gene pool".

[1] https://en.wikipedia.org/wiki/Sickle-cell_disease

Re: Teenager's sickle cell reversed using a treatment to change his DNA

#22

Post by yjftsjthsd-h »

Moshe_Silnorin wrote: post #12
deepnotderp wrote: post #10

Earlier quoted context omitted.

A better way to increase iq would be to raise the socioeconomic level...

Nope. Genetic engineering works far, far better. We've already plucked the low hanging fruit of adequate nutrition, early education, salt iodization, and lead reduction. Anyway, those reduce mental retardation, they don't improve the baseline too much. And the Flynn effect looks to be slowing or reversing. 50 IQ points is huge. It's the difference between a burger flipper and a physics professor. The change to the wo…

> Genetic engineering works far, far better.

Um, do we know that? Unless I've missed some very interesting research that sounds like an extremely untested hypothesis.

Re: Teenager's sickle cell reversed using a treatment to change his DNA

#23

Post by texthompson »

Moshe_Silnorin wrote: post #12
deepnotderp wrote: post #10

Earlier quoted context omitted.

A better way to increase iq would be to raise the socioeconomic level...

Nope. Genetic engineering works far, far better. We've already plucked the low hanging fruit of adequate nutrition, early education, salt iodization, and lead reduction. Anyway, those reduce mental retardation, they don't improve the baseline too much. And the Flynn effect looks to be slowing or reversing. 50 IQ points is huge. It's the difference between a burger flipper and a physics professor. The change to the wo…

People in Flint, Michigan still don't have clean water. Lots of other folks in the world also don't have clean water. Doesn't that seem like an easier thing to fix than trying out experimental therapies?

Re: Teenager's sickle cell reversed using a treatment to change his DNA

#24

Post by deepnotderp »

Moshe_Silnorin wrote: post #12
deepnotderp wrote: post #10

Earlier quoted context omitted.

A better way to increase iq would be to raise the socioeconomic level...

Nope. Genetic engineering works far, far better. We've already plucked the low hanging fruit of adequate nutrition, early education, salt iodization, and lead reduction. Anyway, those reduce mental retardation, they don't improve the baseline too much. And the Flynn effect looks to be slowing or reversing. 50 IQ points is huge. It's the difference between a burger flipper and a physics professor. The change to the wo…

I think you're putting too much faith into IQ.

Shockley only had an IQ of ~125 (even though he became an eugenicist...).

More importantly, Feynman used his low IQ score (124 I think) to show how useless the IQ test was as a predictor of intelligence.

Re: Teenager's sickle cell reversed using a treatment to change his DNA

#25

Post by deepnotderp »

Moshe_Silnorin wrote: post #12
deepnotderp wrote: post #10

Earlier quoted context omitted.

A better way to increase iq would be to raise the socioeconomic level...

Nope. Genetic engineering works far, far better. We've already plucked the low hanging fruit of adequate nutrition, early education, salt iodization, and lead reduction. Anyway, those reduce mental retardation, they don't improve the baseline too much. And the Flynn effect looks to be slowing or reversing. 50 IQ points is huge. It's the difference between a burger flipper and a physics professor. The change to the wo…

Oh, and enjoy this one: https://www.sciencedaily.com/releases/2012/02/120214100719.h...

Re: Teenager's sickle cell reversed using a treatment to change his DNA

#26

Post by deepnotderp »

Moshe_Silnorin wrote: post #20
josephagoss wrote: post #16

Earlier quoted context omitted.

Is there any foreseeable way to apply gene editing like this to adults? Could existing adults (us) in the future make use of this type of IQ increase?

Not impossible but much, much, much more plausible with embryos. Modifying billions of neurons is a very, very tall order, and would likely be much less effective after the brain is grown. Embryo selection and modification are almost doable now, we just don't know which alleles to select for or edit in. A gift you can give your children but one you are unlikely to be able to get for yourself.

This is true, as much as I disagree with his ideas. Trying to genetically modify a living adult across many cells is very difficult.

Re: Teenager's sickle cell reversed using a treatment to change his DNA

#28

Post by jfarlow »

candiodari wrote: post #13
helloworld wrote: post #5

Earlier quoted context omitted.

It sounds like this research involves somatic gene transfer, in which the change to the genome is not passed on to children: Gene transfer can be targeted to somatic (body) or germ (egg and sperm) cells. In somatic gene transfer the recipient's genome is changed, but the change is not passed on to the next generation. In germline gene transfer, the parents' egg and sperm cells are changed with the goal of passing on…

Isn't that dangerous ? This will allow him to have a normal life, which includes kids, which will need this (potentially very expensive) treatment as well. Wouldn't you, in order to not destroy the gene pool, want to restrict gene changes to both of those ? Either that or sterilize the patient to prevent transmission of lethal genes ? This treatment is VERY unfair to any children this guy fathers. Of course I do get…

Part of the beauty of these kinds of gene therapies is that the cost can ultimately be lowered to near-zero levels. These are not drugs that must be taken over a lifetime, but can potentially provide 1-time delivery of the instructions to your own body about how to cure itself. Certainly in the near term the R&D must be paid for (and the marketing, and regulatory burden, and everything else). But in the long term the actual material used to change someone's life forever can cost pennies and a one-time delivery.

Re: Teenager's sickle cell reversed using a treatment to change his DNA

#29

Post by abtinf »

deepnotderp wrote: post #24
Moshe_Silnorin wrote: post #12

Earlier quoted context omitted.

Nope. Genetic engineering works far, far better. We've already plucked the low hanging fruit of adequate nutrition, early education, salt iodization, and lead reduction. Anyway, those reduce mental retardation, they don't improve the baseline too much. And the Flynn effect looks to be slowing or reversing. 50 IQ points is huge. It's the difference between a burger flipper and a physics professor. The change to the wo…

I think you're putting too much faith into IQ. Shockley only had an IQ of ~125 (even though he became an eugenicist...). More importantly, Feynman used his low IQ score (124 I think) to show how useless the IQ test was as a predictor of intelligence.

IQ mean is 100 and stddev is 15. He was in the top 5.5% of human intelligence.

Re: Teenager's sickle cell reversed using a treatment to change his DNA

#30

Post by jfarlow »

jasonkolb wrote: post #27

Is this using CRISPR or some other method of editing the DNA?

This treatment does not use CRISPR. It involves the hollowed out and repurposed lentivirus (similar in kind to HIV)[1]. The virus keeps it's own viral 'insert-into-DNA' machinery, but is stripped of its replication machinery as well as the code for its physical shell. The insert-into-DNA machinery is further hijacked so it can insert nothing but the DNA that encodes for the new mutated hemoglobin (HBB [T87Q][2]) that, when the patient's cell reads that new DNA will produce a new version of the protein. That insertion machinery with its new payload is loaded into a viral shell in a lab somewhere (again, its replication machinery and the code for new shells has been gutted).

When this new virus is given to the patients it does indeed infect the patients' cells. It uses its viral machinery to insert itself into the genome of the patient, more or less randomly - and that is not ideal. CRISPR systems are much newer and are being worked on right now, but the technologies you see in use in this article predate CRISPR. CRISPR will only speed up what was here a monumental (and slightly more risky) effort.

Regardless of how the code gets inserted into the genome (lentiviral in this case, CRISPR likely in future therapies), the instruction set to produce the new protein is not only capable of doing the job of the broken hemoglobin, but actually enables the broken hemoglobin to regain some of its function, likely coming very close to actually curing the patient.

In computer terms, someone with sickle-cell disease has a typo in the source code that leads to a buffer overflow error in the oxygen transport module. We found stuxnet can inject live code into a running OS, so we stripped it of its payload, it's ability to replicate but kept its injection capabilities and gave it our hot-fix as its payload. Our patch will be injected into billions of running nodes, inserting a ~500 line patch randomly into the each node's memory stack (yes, that's scary - but if a few of the nodes (cells) go down, it's not a horrible problem, and the current price of doing the patch at all... CRISPR can help here in future versions). That new code provides not only an alternative oxygen transport package, but this new package, so long as its running on >20% of the nodes, actually forces the original code's memory to periodically flush, thus de facto correcting the original typo's overflow bug - allowing both the new package and the old (kinda bug-fixed) package to both now be useful oxygen transport code. No more bug = cure.

The patients had a code regression, and we're applying not just a 1.0 fix, but a very real 1.1 patch on the human hemoglobin instruction set (randomly, into live code, on millions if not billions of cells, using modified HIV technology).

Diagram of the patch's entire injected instruction set (8.5kb): https://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/t...

[1] Lentivirus: https://en.wikipedia.org/wiki/Lentivirus

[2] The 'updated' hemoglobin: https://serotiny.bio/notes/proteins/hbb/

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