Are doctors allowed to use gene therapy in life or death conditions now? In the trial for fixing OTC deficiency that Jesse Gelsinger died in they only administered the trial to people who were capable of living with the disease as opposed to the babies that were going to die in their first year without it. The idea was that a parent faced with the possibility of their child dying painfully couldn't possibly refuse the treatment and therefore couldn't give informed consent.
> On 13 September 1999, Gelsinger was injected with an adenoviral vector carrying a corrected gene to test the safety of the procedure
> Doctors removed his bone marrow - the part of the body that makes blood. They then genetically altered it in a lab to compensate for the defect in his DNA that caused the disease. ...
> A virus was used to infect the bone marrow with new, correct instructions.
> The corrected bone marrow was then put back into the patient.
This was a self transfusion in the lab rather than an injection of a virus. After the virus infected the bone marrow, it would then have been tested to make sure that there are no immune responses with the material and that it is safe to return to the patient.
Well ... I get the idea, but I am not sure this is rational. If I have the choice between pizza and no pizza, and of course everyone would choose the pizza, my choice is not uninformed, just because it is too good of a deal.
People aren't very good at comparing a terrible known condition A, to a merely potentially terrible known condition B.
It angers me that a misguided and stringent sense of ethics might slow the deployment of one of the most beneficial technologies ever conceived.
However, any significant lag could spell the end of American economic dominance. For this reason, I intend to start investing more in Korean firms in the next few decades.
The gist of it is, in 1970 someone asked a director of NASA why billions of dollars were being spent on exploring space when millions of children were still dying on Earth. The response in part explained that NASA's R&D was paving the way for satellites with better weather forecasting, better communications, and better equipment that was making its way into people's everyday lives. While a bit morbid to say, the advancements made by NASA have arguably saved many more lives in the long run.
It's hard to see the point in investing in experimental technology whose payoff is unknown, especially when we have definite problems with feasible solutions. That doesn't mean we shouldn't try. The possible payoffs - cancer cures, age prolongation, enhanced food production, disease and sickness prevention - that can come from investing in gene therapies are just too great to ignore.
As a side-thought, the technological singularity is thought of as the point at which we create an AI smarter than us, triggering a run-away effect of self-improvement. What if we end up doing it to our own race first through intelligence-improving gene modification? Can you imagine the implications of applying that intelligence to solving the rest of our problems?
As to Flint that does seem to be finally over now, though goodness knows it went on for a distressingly long time.
Um, do we know that? Unless I've missed some very interesting research that sounds like an extremely untested hypothesis.
However, there are some pretty strong reasons to think it would work, at least if we're just talking about improving within the typical range of human ability. Going to the extremes of existing ability and beyond is probably possible too, but there are more unexpected problems that could exist.
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.
What hasn't been said, but is equally true, is that people as capable in physics as Einstein as currently working as waitresses in No Where, Idahoe. Or they're slaving away as bit-actors in Hollywood because that's what they love.
Or they're sitting behind a computer, typing away on HN, never to know that they're potentially amazing theoretical physicists simply because their 7th grade teacher turned them off to the idea of physics in general so they studied computer science instead.
Until there's some kind of test that tells you your aptitudes at very subject, you'll always have people pick suboptimal paths to excellency and something other than what they absolutely theoretically could have been best at.
We will have super smart burger flippers?
The ethnicity is virtually the same so that is being as close to a controlled parameter as it realistically can be without doing unethical things.
I wonder which types of crime they'll optimize?
Looks at the first Reddit comment on any interesting new technology. There's always someone dismissing the whole idea due to some outlandish risk.
CRISPR is better but not there yet, I believe. Let's get all the way to being able to do the equivalent of sed to our germline cells before we start editing.
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 the changes to their offspring.
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 that the method used here goes not really support germ transfer (that requires the gene change to happen in vitro)
This is how a trait that is so dangerous when expressed has managed to spread; in regions with endemic malaria, carriers have better survival chances and the difference is sufficient to make up for those who express it and end up dying young.
It is recessive - you need to inherit it from both parents to express it. So it is in fact entirely safe for this man to have children provided he has children with someone who is not a carrier, or ensure appropriate tests are taken during pregnancy.
Most people who carry this trait in developed countries today know about it, because the mechanism is very clear and they will usually know whether or not any of their family expressed the trait, and will have been tested to see if they inherited it. E.g. we had our son tested because his mother is a carrier, but because I am not we knew he could not have sickle cell disease.
My son is a carrier, but all that means is that like the guy in this article, he will want to make sure his partner is tested before having children, and to ensure to decide in advance what to do if both are carriers or if his partner has the disease (such as whether to have an abortion if tests show the child has the disease).
We can expect the number of people with this gene to drop over time because it is now so easy to avoid. But in the meantime a treatment would make a massive difference for those with the disease.
In order to have the disease you need to inherit bad genes from both parents. 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".
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...
 Lentivirus: https://en.wikipedia.org/wiki/Lentivirus
 The 'updated' hemoglobin: https://serotiny.bio/notes/proteins/hbb/
CRISPR (more specifically, Cas9) is another protein machine that locates particular DNA sequences . It can help take over from the lentivirus with respect to the 'insert into dna' capability. But you're right, we still have no better way to get it into the cell than to use a (lenti)-virus's own 'insert-into-cell' machinery. So a lentivirus might be used along with CRIPSR in order to just get CRISPR machinery into the cell.
This is further muddled by the fact that sometimes you actually want the dna that encodes for your CRISPR system to itself be inserted into the genome, and in that case you might keep both the lentivirus's 'insert-into-dna' machinery AND the CRISPR's own 'insert-into-dna' capability.
At the end of the day, lentivirus's capability to insert into DNA is not predictable, and therefore a bit dangerous (if it inserts its payload in the middle of an oncogene in a predisposed cell you could get cancer). CRISPR is a device which promises to bring specificity to the command, making it 'insert-into-dna-AT'. And in that way it could replace the job of lentivirus in the above gene editing technique.
 Cas9: https://serotiny.bio/notes/proteins/cas9/
The actual sequence and mutation HBB [T87Q] protein:
A short little writeup I did about the mutation:
A very detailed presentation about Bluebird Bio's therapy (called LentiGlobin BB305) provided to the government:
I like that language so much more than, than the increasing THIS IS AMAZING, SO AWESOME, WHAT WE GREAT GUYS ACCOMPLISHED!!!
even though it would fit here much more, than in the usual context people use it fore ...
Yes, he could run at the same pace as someone with a better heart, but he was predisposed to arrhythmias even at a normal level of effort.