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I feel like this type of medicine is more like a research study waiting for a perfect match patient than it is highly personalized treatment...

Is this technique broadly applicable? Or limited to very specific cases

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It looks to me like a somewhat unique opportunity to risk it because without this treatment, she was dead anyway and in fairly short order. So it was a means for them to learn something with very little potential downside. Worst case scenario: The treatment kills her. And she was dying anyway.

From the article:

In Alyssa's therapy, each of the base edits involved breaking a section of genetic code so it no longer worked. But there are more nuanced applications where instead of switching an instruction off you can fix a defective one. Sickle-cell anaemia, for example, is caused by just one base change that could be corrected.

And I already quoted (in my previous comment) the next paragraph that indicates they are already doing trials. This is potentially a big deal and they seem to be pursuing it in a very reasonable and conservative fashion, which is always something that concerns me with this type thing. There's a lot of potential for terrible and horrifying abuse and that is not what I am seeing described here.

Yeah, those are valuable opportunities. You have to take risks to learn, but human life is to valuable to risk.

I remember looking into the state of the art around in utero and neonatal health when we got pregnant. I was astonished at how limited the knowledge is. I quickly realized the big gaps are just because it’s too risky to study. You can’t morally experiment on pregnant people and infants.

Seems like this particular version of gene editing only works with blood/marrow disorders? If someone had a single mutation affecting their colon or eye, would the same technique be appropriate?

Blood/bone marrow is relatively easy as you have a very clear delivery vehicle for your modified genes. Actually getting to the colon cells or retina is a lot harder, can’t just inject it into the blood and expect it to end up in the right place.

A "problem" with this treatment is that, for most patients, the current standard of care works. To the extent that this treatment is effective, it is likely effective for most leukaemia patients, including those who would respond well to current treatments. It is very plausible that this treatment (or a refined version of it) will eventually be shown to be superior to the current standard of care, in which case it would become the standard of care, and the current treatment will be relegated to the niche patient that does not respond to gene edited t-cells.

More broadly, the technique of precisely editing DNA of select cells to perform specific engineered tasks is very broadly applicable. But that is a technique for developing treatments, not a treatment itself.

Remember what "works" means in this case. Chemotherapy, or for other cancers, radiation, surgery that removes large, healthy parts of organs that might have a tumor. Chemotherapy has hosts of side effects, of course (hair loss, nausea, ruined immunity, CIPN, etc) some permanent for some people. It "works" when you look at what KPIs oncologists like, very reductionist things like "5-year overall survival" whilst you ignore things like quality of life both in the short term and long term.

We should be moving away from chemotherapy. It really is poison (cytotoxin) that has "treatment" of cancer as a side effect, just because it will readily kill cancer cells more than healthy cells whilst also taking a lot of the healthy cells with it. But, it's the "established" standard of care, which many doctors built their careers on, so I suppose it won't go away soon.

Surgery to remove part of an organ, followed by chemotherapy gave my mother a few more years of life. Are you suggesting there is some other alternative, currently accepted and understood, that would've worked better? Because while those side effects are terrible they are usually more temporary than the extension of life that they afford people. Face the question, would you rather chemo for a couple months and then live a couple years, or die in a couple weeks?

No, they are suggesting we should strive for better therapies.

Isn’t this treatment simply accomplishing the same thing that the current treatment does but in a targeted way with hopefully much fewer side effects? When you have cancerous T cells the only option is to eradicate all of them and start over with a bone marrow transplant. Normally that would mean frying them with radiation or poisoning with chemo which also effects a lot of other tissue. This treatment is supposed to only kill the T cells.

That's my noob understanding too. This is a more precise form of autologous transplant.

I assume quick adoption of base editing for trickier cases, eg for T-cell acute lymphoblastic leukemia, like this patient had. Note that she had a previous transplant, using the more conventional treatment of her T cells. Just starting with base editing will be much less onerous to future patients.

This is one tough person. Surviving chemo then two transplants is amazing. Just thinking about it crushes my heart.

Source: Had bone marrow transplant 30+ years ago. My then experimental treatment became the default option (as applicable). Don't know much about biology or medicine, but I can repeat what I've heard and read.

> will eventually be shown to be superior to the current standard of care, in which case it would become the standard of care

How does this overturning occur? Do care providers agitate for change? Or is it typically a response to headstrong patients and families?

It starts with researchers convincing their ethical review board that they should be given the opportunity to experiment with the different approach.

That’s why new procedures almost always are done on patients who are as good as dead (gene editing to change one’s hair color won’t soon get past ethical review, for example, but if gene editing gets used in mainstream medicine, enough data may be collected to make a review board say it’s acceptable to give it a try)

The first experiments typically only prove the medicine or procedure works. Long term survival of the patient the exception. From there, it’s step by step towards treating healthier and healthier patients.

If it turns out the approach is better for the typical patient, patient groups (who may even have paid for part of the research) start lobbying for its use. If the new procedure is both better and cheaper, insurers also will lobby for it.

Wiping out your immune system and replacing it has something like a 50/50 survival rate even if you use your own cells. It's a hail Mary than usually either kills or cures.

I knew a guy with cancer that had this done. He survived the process, but unfortunately the cells they restored him with were not cancer free like they thought. He died anyway.

I think increasing the survival rate for these things could be very useful.

Wiping out the recipients immune system and transplanting a donor system is in itself a common (advanced) practice since long, so the new part here is the tweaking of the donor system. Very interesting.

The edited cells did not replace her immune system. They were used to destroy it.

Then after that a bone marrow transplant was done to restore it.

Its coming within the decade for cancer vaccines. The trick is to be able to scale production and lower the turnaround time.

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