[condiment]

To summarize, the problem with gene therapy is simply that it's extremely expensive and the list of qualified clients is extremely small. That's because these therapies have been necessarily targeted towards ultra-rare and assuredly fatal diseases.

That approach developed the technologies, but what if a mass market approach is what is required to create the economies of scale we need to actually benefit from this science long-term? Consider a cure for the common cold. All of the technology exists. We can take a tissue or fluid sample and extract viral genomes, comparing against a database of over 100k viruses. We can develop MRNA vaccines that target specific viral proteins. We can do both of these things using current technology in a timeframe of less than a day.

To me this is the next great leap. Gene therapy is less a technology problem than it is an infrastructure problem, and rare diseases cannot support the infrastructure. But there are plenty of wealthy people who would pay $10k, maybe even $50k, out of pocket to cancel a cold. Rare diseases bootstrapped the tech, common diseases can scale it, and once scaled, everyone benefits.

[bashmelek]

I have been curious if it would be possible to create a business around pet-genetics as a means to improve the underlying technology without having to be overly concerned about the human factor…granted there will still be ethical restraints of a sort

[edge17]

A lot of the technology is regulated by FDA requirements, which apply to humans but not animals. Some of these requirements are challenging engineering problems - like how to do certain type of liquid transfers without exposing the contents of a container to the atmosphere, etc. There are lots of tools for doing liquid transfers that mimic what a human would do, but FDA places a different bar when it comes to developing a controlled manufacturing process.

There's also the question of, who writes the rules. Often it's industry experts that are already working on the process, and have incentives like keeping others out or licensing their own IP.

[michaelbrave]

More likely the profit would then be in dealing with animal husbandry types of modifications instead. Cows/chickens that don't get sick, that kind of thing.

[mandevil]

This is actually a lot harder than you think because we still don't understand gene therapy well enough to be able to be sure that any given treatment works without the really expensive part, the Randomized Control Trial. In 2017 a gene therapy was approved in the US for RPE65-associated Retinitis Pigmentosa, Luxterna, the first in-vivo gene therapy approved by the FDA (yay! List price was a mere 425,000/eye). Just a few months ago J&J announced that their gene therapy targeting a different gene, RPGR, missed its primary end-point, only 22 out of 55 treated patients showed improvements on at least two of the measures in the LUMEOS trial and there was no statistically significant improvement on their primary measure. That result happened even though this was mostly just "take the thing that already worked for Luxterna, and do a different gene." The problem is that the human body is far more complicated than computers, and does not scale the same way.

This is why regulators are very wary of "Right to Try" type stuff, they want to be sure that medical treatments are actually effective before they are available to the broad public. These sorts of RCTs are still quite necessary, and they are the really expensive thing in drug discovery. (Well, it's both that they are expensive to run and also they kill all sorts of drugs that don't actually work.)

[michaelbrave]

I think a lot of our diseases if looked at genetically instead of symptoms-wise that we will probably find out that it's actually multiple conditions that we just group together for manifesting in similar ways. I've felt this in my own life with ADHD things where it seems to me that there are at least 3-4 different types of ADHD and that they respond to treatments/medications differently, and this makes me think that many other conditions might be similar, especially if we start looking at them genetically.

[mandevil]

This is such a deep hole of complexity. (My wife is a pharmacist, I make computers do what I tell them to, and she has convinced me that her field is far more complex than us software people can imagine.)

To pick one story my wife has told me, take the example of Multiple Sclerosis. In the 1970's and 1980's, thanks to the MRI machine, there was finally a good diagnosis tool for MS: can you see the lesions in the scan? If you can congrats, you have MS. If you can't, it might be early MS where the lesions are small enough that we can't see them (generally they are visible several years after initial symptoms). But there were a lot of people who had MS-like symptoms and no lesions, so diagnosis of Chronic Fatigue Syndrome (named just in 1970, in contrast to MS which was identified in the 19th Century) started to rise. Most of those people would have been diagnosed with MS in 1950, but now we can rule that out and so they go into the new bucket instead. What is going on with patients in that CFS bucket? It's a mystery. Is it one thing or many? Who knows! Is it genetic or environmental? Who knows!

And how does one get original flavor MS? It's not fully genetic- comparing identical and fraternal twins we can see that it's not purely genetic but there must be a genetic influence. The current most accepted theory, according to my wife, is basically Long COVID- but for the Epstein-Barr virus (what causes Mononucleosis) instead of COVID-19. So if your immune system is somehow susceptible to this (the genetic component, which we apparently do not understand), and it encounters EBV (and there is a bit of bad luck? Who knows!) then somehow the immune system gets confused and starts attacking your own nervous system.

We computer people are simply attacking much more tractable problems.

[outworlder]

There are multiple brain conditions that are increasingly being suspected of being caused by viruses. They are the ultimate DNA editors. And some can remain dormant for decades before reactivating.

Which is why it was so puzzling to see the response during the last pandemic. More so with people concerned about mRNA vaccines and conflating that with 'DNA changes'. If one is concerned about their DNA, they should avoid viruses and do whatever they can to help their immune system fight them as quickly as possible.

The odds of a virus giving us something beneficial like a placenta are minimal, the drawbacks are just enormous.

[searine]

The issue isn't a technical one with gene-therapy. The issue is ethical.

Editing your DNA can be dangerous or even deadly if it doesn't work. Modern methods have mostly solved this, but there is still a lot of hesitancy due to prior failures/tragic deaths.

It is also ethically foggy. Somatic edits, edits that will die with you and do not change your sperm or eggs, are one thing, but when you start making germline changes, that impacts everyone who may inherit your genes. You may consent to a germline change, but will your children? Or your children's children's children? You may have the money now to make they change, but will they have the money to change it back?

Small genetic changes also have a complex spectrum of phenotype outcomes. If you start making germline changes that are not found in nature or are under-studied, that can have compounding unintended consequences. For example, if you spec into a dozen intelligence SNPs, that may also increase your risk for a pandora's box of mental illnesses.

So no, economies of scale will not solve this. It would be a disaster.

[condiment]

You're conflating gene therapies vs. the human genome with gene therapies vs. viral genomes. In some cases, the illnesses are genetic, but this article is specifically about how gene therapy companies keep going out of business trying to cure rare genetic illnesses! Even if the technology is the same, the uses are very different and regulatory approval is still required for the application of the technology.

That's not to say there aren't additional ethical challenges that would arise if gene therapies were cheap, but the ethics concerns you're raising seem like future concerns, relevant to a world that does not yet exist.

[VirusNewbie]

Well, rare disease certainly gets people to pilot the tech. I'm certainly not going to try some ultra-experimental gene therapy to be immune to the common cold or fix my allergies, I don't know what the side effects might be.

But if I was staring down some awful rare disease, then sure, let's roll the dice.