(Disclaimer- I am an engineer and not a microbiologist/doctor)
Mutations and wrong copying of genome happens all the time in the body and some enzyme has the job of correcting the mutated genes so it doesn’t get into the system. Level 2 defence is T cells killing it as identified as foreign body.
Thing that baffles me is that I see most work happening to eliminate tumor. To me it sounds a tough problem given the permutation and combination of mutation— roughly few trillions.
But I was curious if there is working happening on L1 defence — fixing the enzyme that fixes the wrong copy paste mechanism. Or making the enzyme get more efficient and powerful. Is that line of thought even valid?
The immune system is pretty good too, which means any given improvement to the replication system is, all else being equal, probably going to prevent mutations the T cells would already handle. If you need to do the research to figure out what's getting past the immune system anyways, and improving the immune system is lower hanging fruit, it's the logical place to start.
Or is it the second layer that works better for them?
But there is much more to it. This is a nice paper for an overview: Hallmarks of Cancer (tng) [0]. It (among others) adds the very important and for years underestimated role of the immune system to the original 2000 paper.
OTOH our L2 isn't that good, mammals in general (with some notable exceptions such as bats, whales and naked mole rats) are prone to cancer in their older age. There probably is a lot of relatively low-hanging fruit there.
If you think about it - individual cells aren't very precious and if some of them gets FUBARed by something (a virus, radiation or chemical insult), it is better to whack it and reuse the proteins to build a new one, if possible, instead of wasting time and resources on reconstruction of a total wreck.
Which also means that some research into replenishment of stem cells is necessary - and this is, IMHO, the really underfunded part of the whole thing. We lose a lot of stem cells as we age. Maybe we don't have to.
Most cell types have systems to safely manage replication. Broadly, there are gas pedals (oncogenes) and brakes (tumor suppressors). A classic oncogene is something like RAS, which activates a signaling cascacde and stimulates progression through the cell cycle. A canonical tumor suppressor is something like TP53, the most frequently mutated gene in cancer, which senses various cellular stresses and induces apoptosis or senescence.
Most cancer genomes are more complicated than individual point mutations (SNPs), insertions, or deletions. There are copy number alterations, where you have > or < 2 copies of a genomic region or chromosome, large scale genomic rearrangements, metabolism changes, and extrachromosomal DNA. There is a series on the hallmarks of cancer which is a useful overview [1].
All of the mechanisms that intrinsically regulate cell growth would fall under your "L1 defense". Unfortunately, the idea of reversing somatic point mutations is likely to be a challenging approach to treating cancer given the current state of technology.
First, for the reasons above, cancer is often multifactorial and it would be difficult to identify a single driver that would effectively cure the disease if corrected. Second, we don't have currently delivery or in vivo base editing technology that is sensitive or specific enough to cure cancer by this means. There are gene therapies like zolgensma[2] which act to introduce a working episomal (not replacing the damaged version in the genome) copy of the gene responsible for SMA. There are also in vivo cell therapies like CAR T which attempt to introduce a transgene that encodes for an anti-cancer effector on T cells. These sorts of approaches may give some insight into the current state of art in this field.
Edit: also I should note that the genes involved in DNA repair (PARP, BRACA1/2, MSH2, MLH1, etc) are frequently mutated in cancers and therapeutically relevant. There are drugs that target them, sometimes rather successfully (e.g. PARP inhibitors). But the mechanisms of action for these therapies are more complicated than outright correcting the somatic mutations.
1. https://aacrjournals.org/cancerdiscovery/article/12/1/31/675... 2. https://en.wikipedia.org/wiki/Onasemnogene_abeparvovec
There are some basic, well-known nutritional interventions that are generally important/critical for DNA repair processes. The 2 main ones are Vitamin D and Magnesium. Ensuring adequate amount of these tend to be helpful (most folks aren't getting enough sun and greens).
Other than that, a steady and adequate source of the substrates seems to be important: ie protein (nitrogen), and phosphates.
One of the interesting bits about some cancer cells is that while they simply haven't gone through apoptosis, physical sheer stress incurred from physical activity (exercise) can cause cancer cells that travel beyond the tumor point (before it becomes metastatic) to finally self destruct.
It seems important to me that the best strategy for cancer is the compounding of many different strategies that optimize the body's innate defenses to run optimally.
It does seem that ketogenic diets may have adjuvant properties, but there is yet to be a clinical trial that demonstrates it, so it's basically stuck in paper and R&D stages as to whether being in a ketogenic state can be one of the last areas that may help cancer patients extend lifetime from say 1 year to 2 years.
You are right. There is a very good explanation in this comic https://phdcomics.com/comics.php?f=1162
If steroids worked, everyone would be constantly injecting them. It would be like drinking coffee.
And that is the reason why steroid injections are harmful. If there is a free lunch, the human body will simply produce the optimal amount of steroids on its own until the Pareto frontier is reached and a tradeoff needs to be made.
Where does the body get the materials to form the steroids? From your diet. So the primary intervention is always a healthy diet and an active lifestyle. You know, the boring things that parents drill into their children.
It's valid but "medicine" that has only upsides and no downsides isn't medicine, it's diet.
There definitely are efforts to correct enzymes involved in tumor-suppression (p53 is probably the best known tumor suppressor protein). e.g., here's a study on a small molecule designed to correct mutated p53 https://pmc.ncbi.nlm.nih.gov/articles/PMC8099409/
Also not a doctor or microbiologist, but just wanted to share my layman’s guess on why fixing enzymes will not completely solve the issue: there’s 2 strands of DNA and to fix the broken (mutated) strand you need to have one correct template strand intact so you know what it should be fixed into. It could be the nucleotides swapped places between strands or are deleted completely or otherwise both mutated, which would mean any repair will not revert the sequence to what it used to be.
The other comments so far are probably more informed.
You’d also have to ‘fix’ DNA: unless we can re-engineer a bunch of key enzymes and then re-encode the entire genome (or maybe key parts) with forward error correction without breaking everything else, it might work. You might also break evolution to some degree by making random point mutations less likely.
But what I learned so far is that as soon as you’d attempt something like this in bacteria, the fitness advantage from an evolutionary standpoint is negligible compared to the efficiency loss introduced by FEC, so your colony would get outcompeted by other bacteria unless there is a niche your resistant bacteria survive in (high radiation environments?). The efficiency loss induced ‘disadvantages’ would probably be less pronounced in mammals though - If (big if) you manage to not also break anything essential in the wonderful yet surprisingly efficient Rube Goldberg machine that is life.
Thought experiment, again as a layman, was to see if these genes responsible for error correction at the base level can be fixed or bolstered and that will act like a cancer vaccine. But looks like from other comments that this is even more harder!
The DNA fidelity issues contribute to only some cancers. Many are caused by mutations due to environmental damage and some are caused by viruses. The point is, there's a huge variety of reasons for developing cancer. So you cover more cases by developing treatments that are more "universal".
If we had the tools to easily do that we’d practically be gods.
Mutations in general are not the defining quality of cancer. It's mutations in these very L1 safeguards. There are several such safeguards and a cell needs several mutations in those to become malignant. Eg. https://en.wikipedia.org/wiki/P53
Correcting genes only works in certain conditions (e.g. limited single strand breaks), in a narrow time frame during cell division, safeguards rather trigger cell suicide, or if that fails they mark the cell for destruction by immune cells. A cell can't fix DNA which made it through cell division once, because it got nothing to proof-read against.
After the safeguards are gone, everything goes and genetic diversity increases quickly within each tumor. This diversity is what's making cancer treatment hard. At some point there won't be a shared vulnerability in all malignant cells. The repair mechanisms are working in favor of the cancer now. For example, with radiation therapy you preferably want to induce DNA double strand breaks, because cancer cells can't repair those. Otherwise you need to increase the radical burden enough to overwhelm repair, but migrating radicals may damage distant cells, too.
I presume you could hypothetically inject mRNA of a working safeguard gene (eg. P53) into all cells (at some point cancer cells can't be selected exclusively, since they lost identifying marks and present as stem cells), so the functional enzyme or transcription factor is forced to be built inside. I am sure people are trying this right now. However, the inner workings of cells on a molecular level are insanely complex and our understanding is only scratching the surface. As with P53, you have a transcription factor, which means it's modifying gene expressions elsewhere. It's only a small part of a complex regulatory cascade. I doubt there is a safeguard target, which can easily be injected without considering the precise timing and environment within that safeguard cascade in the cell. Of course, the rest of the safeguard system needs to be present in the cell to begin with. Mind you, you don't want to cause cell suicide in healthy cells, so you want to restore the function of whole selective complex.
Then there is the question of delivery. Can you deliver eg. the mRNA to every cell without raising suspicion of the immune system? With the COVID vaccine, the enabling breakthrough was the delivery vehicle, not as much the mRNA part. Can you even reach the cancer cells at all? Cancer cells are frequently cloaked, shadowed or cut of by senescent, or necrotic cells, or acquired unique ways of metabolic adaptations. A bit similar to bacterial persistence, like M. tuberculosis, which can evade bodily and chemical defenses for decades.
The take-away: Life is complex beyond comprehension! Despite simplifications taught in schools and reductionist zeitgeist, we actually know very, very little about what's going on in genetics and molecular biology, most medical knowledge is empiric guessing instead of explanatory understanding.
This sounds like world changing news. Can anyone with domain expertise explain the catch, if any?
Also agree that using a PD-L1 mab feels like it’s for show especially considering the cancer model they’re using (Colon-26) was shown to be substantially less responsive to PD-L1 inhibitors…
Not the world’s best paper imo
As they say, "the fame of a mathematician is measured by the number of poor papers", because pioneering works are often awkward, treading completely unknown ground. Maybe the same applies to biology sometimes?
"Tumor-Specific Accumulation Mechanism
E. americana selectively accumulates in tumor tissues with zero colonization in normal organs. This remarkable tumor specificity arises from multiple synergistic mechanisms:
Hypoxic Environment: The characteristic hypoxia of tumor tissues promotes anaerobic bacterial proliferation
Immunosuppressive Environment: CD47 protein expressed by cancer cells creates local immunosuppression, forming a permissive niche for bacterial survival
Abnormal Vascular Structure: Tumor vessels are leaky, facilitating bacterial extravasation
Metabolic Abnormalities: Tumor-specific metabolites support selective bacterial growth
Excellent Safety Profile
Comprehensive safety evaluation revealed that E. americana demonstrates:
Rapid blood clearance (half-life ~1.2 hours, completely undetectable at 24 hours)
Zero bacterial colonization in normal organs including liver, spleen, lung, kidney, and heart
Only transient mild inflammatory responses, normalizing within 72 hours
No chronic toxicity during 60-day extended observation"
Well, I guess Leukemia has been somewhat cured I heard, so that's pretty huge. When I was a kid it was a death sentence IIRC.
Several things trigger my bullshit meter. Quote:
"This dramatically surpasses the therapeutic efficacy of current standard treatments, including immune checkpoint inhibitors (anti-PD-L1 antibody) and liposomal doxorubicin (chemotherapy agents)"
PD-L1 monoclonal antibodies are only effective against cancers that are, you guessed it, PD-L1 positive. At high percentages, ranging from 1 to 50%. Are these authors even familiar with the state of the art when it comes to cancer medications? Mouse tumors do not equate to people tumors. Many tumor types are not PD-l1 positive.
Doxy is an ancient SOC chemo.
This is a nothing burger.
Give me phase II/III clinical trials, and then let me know what their PFS/OS was after 5 years. and what the medians were at 3- and 5-years. Also, ORR and CR and needed.
CAR-T is ahead of the game, and will be the ultimate winner here as it grows to scale.
Crocodile blood antibiotics hope
Scientists are catching crocodiles and sampling their blood in the hope of finding powerful new drugs to fight human infections.
Even horrific fighting wounds on the animal heal quickly
Murine studies are a dime a dozen and therefore it’s the default assumption when reading research papers. When human trials commence the fact that it’s in humans is a big part of the research and therefore paper titles.
Your link is not even about animal studies. It is about a petri dish.
"This news article links human survival to something taken from amphibians and reptiles. There are conspiracy-theorists who posit the existence of Lizard people. It would be amusing if those humans discovered this news, and claimed it was a plot by Lizard People to make us dependent on them."
So there, I think I explained the joke... which isn't necessarily a good thing. In the words of E.B. White:
> Explaining a joke is like dissecting a frog. You understand it better but the frog dies in the process.
Now, I could work that new amphibian-connection into another joke... But let's face it, it would be "too meta" at this point.
I agree with GP that it is very notable.
I mean if it works on humans, which is not a stretch, colorectal cancer is done. It's huge.
I wonder if anyone has tried to engineer a mouse that lives forever by applying all these life enhancing mouse therapies at once.
The bar for an acceptable side effect profile in an FDA-approved drug would also be a lot higher than "five genetically near-identical mice did not show evidence of pathology in a single study."
I'm not saying this work is bad (skimming, it seems fine for what it is, though haven't read in detail), but it's quite preliminary if we're talking about developing a medical treatment that could eventually be deployed in humans. There's a reason it ended up in a mid-tier microbiome journal.
I agree with your overall point though; it's a little annoying that every few weeks we hear about a new experiment that seems to indicate that we'll have a radically new and effective form of treatment for cancer only for it to never materialize.
"Chemotherapy" again is a loaded term covering a lot of different drugs, drug combinations, protocols and so on. So yeah, a lot of cancer treatment us "chemo" - but today's chemo is far removed from 2000 chemo.
5 year survivability has increased tremendously over the last decades. We're not talking 0.5% here, breast cancer for example has gone from 72% to 93%. Early detection of prostrate cancer has near 100% survivability.
But you're right, improving survivability doesn't make for sexy headlines. Yes there's a social media appetite for "breakthroughs", but the underlying "boring" stuff is doing well, and getting better all the time. It's just not "news".
* Many breakthroughs from the first research stages never make it into medical application.
* Many breakthroughs are touted as some kind of "novel treatment", but when they get into the hands of the doctor, they talk about it as chemotherapy, because it kills cancer cells. So you might not even notice that you're getting something novel.
* Many breakthroughs take decades until they actually land in mainstream treatment.
* Many breakthroughs are specific to some kinds of cancer.
That said, in most developed countries, survival rates/times for cancer have been steadily improving for decades.
It's a bit like with solar cell and battery tech breakthroughs: you hear about them all the time, but it takes 20 to 30 years until they make it to production. But both have been improving steadily for an impressively long time.
These are not your parents cancer treatments.
As an engineer I think all drugs tested and efficacies studied are on statistically not so significant data points. Given the permutations and combinations far exceed the clinical trials available and hence everything post clinical trial is also just an extended trial.
Wonder How to fix this? I am assuming heLa cells etc are also not the right test setup to have better test results.
This drug has been used in a huge number of patients for more than 11 years; the next gen of drugs is currently being used. I'm sorry for my curt style of writing, but - people like your father have helped pave the way for that next generation of drugs by constraining clinical trial designs.
> Many tumor types are not PD-l1 positive. > Doxy is an ancient SOC chemo. This is a nothing burger.
Meh the research didn’t say those were state of the art, but that they were “common” treatments. In other words a baseline for a presumably cheap and well studied animal surrogate.
> CAR-T is ahead of the game, and will be the ultimate winner here as it grows to scale.
Last I read up on it last year CAR-T treatments struggled with solid mass tumors.
Many cancers don’t have unique proteins for CAR-T to target (similar to the pd-l1 issue).
Then CAR-T struggles getting the modified T cells into the solid mass tumors en masse. Interestingly this approach actually makes use of the tumor environment rather than be hindered by it.
Nice to hear an expert opinion. Let's hope your comment goes back to black. I have a lot of question!
> This is a nothing burger.
Is it enough for a bread-mayo-bread sandwich? Lettuce?
IIUC the bacteria makes the cancer disappear for two weeks, until they end the study and kill the mice. (IIUC this is timeline is usual for very early studies.) They tried other bacterias and one of them made the cancer disappear for a few days, so I'm worried about the long time efficiency of this method.
Is injecting the bacterias a second time as efficient as the first time, or the inmune system kills the bacteria before they hurt the cancer?
What happen in case of metastasis? Each one must be injected with the bacterias or they will jump and make all of them disappear?
Does the bacteria infect other organs and kill you? Is there a good antibiotic in case the bacteria cause problems?
They used cancers that were 200mm3 (i.e. like a sphere of 7mm = 1/4 inch). What happens in bigger cancers? Does bigger cancer have better irrigation and make it more difficult for the bacteria to survive? What happens to tiny hidden metastasis (that probably still have good enough irrigation)?
Mice are good for early tries. The researchers had 9 bacterias and only 1 was successful. Experiments in mice are cheaper and have less ethical problems than experiments in humans.
(Hey! They even injected the cancer cells in mice and waited a week until it grow. Nobody will approve that in humans.)
Therefore there is no good solution for this.
For instance, some studies have demonstrated that certain kinds of malnutrition, i.e. the consumption of inadequate amounts of protein and/or with bad amino-acid profile, inhibited the development of tumors caused by carcinogen agents (in rats and mice). This was not really surprising, because tumors grow faster than the rest of the body so they need to synthesize more proteins. If they are starved, they grow slowly and the immune system has time to react and to eliminate the incipient tumors early enough.
Despite this, starving yourself in the hope to avoid cancer would be a very bad idea. While the probability of cancer is lowered, the probabilities of low resistance to infectious diseases or of muscular weakness leading to falling and breaking some limb, or of cardio-vascular diseases, become higher.
Exercise is good for the immune system, this helps clear cancer, helps stay away from inflammation (ie auto-immune diseases). Where as a sedentary life style a poor diet will promote this.
But indeed for some things/behaviors, the relation the cancer may be complex.
For example - if hela cells can be used for trials — can there be the cultured tissue be used instead of mice as day 1?
Also curious — how did the scientist decide on using a specific cell/protein to be used for checking if this is producing results. Is it a hunch or science ?
There are different cancers, different stages different, different chemos, and of course different people.
Ultimately individual experiences of chemo run the whole gauntlet. At one end it can be little more than a bit of fatigue, at the other end a horrendous nightmare.
Yes, chemo has, as it's goal, a poison function. It sets out to poison you, hopefully killing the cancer first. It's never going to be the "fun" part of treatment.
I'm not a Dr, much less a medical historian. I would be ill equipped to quote specific drugs or dosages. Outcomes however are easily Googled, and those don't seem to be controversial.
I get that improved statistics don't make individual loss any easier.
It's worth noting though that humans also have much higher levels of exposure to many carcinogens than most animals, and we screen for cancers at a much greater rate for humans, so just because a species has lower cancer rates doesn't necessarily mean their cancer defenses are better.
Too big to fail basically
The hypothesis doesn't really resolve Peto's paradox, the observation that cancer rates don't scale directly with the number of cells in an organism. Not only do large organisms like whales get fewer cancers per cell division, small animals like mice get more cancers per cell division, which can not really be explained by a threshold beyond which hypertumors suppress tumors. The actual evidence suggests organisms just evolve whatever level of cancer resistance they need to have low odds of dying of cancer before something else kills them.
That being said, the main observation underpinning Peto's paradox was actually just due to lack of good data. Over the years much more data has been collected from animal autopsies and it turns out that big animals do get cancer and cancer rates actually do scale with body size, just different species have varying levels of cancer protection, with the levels of protection being similar in closely related species of different sizes.
I wouldn't describe it working in humans as "a stretch" per se. I'm not identifying a specific reason it shouldn't work in humans. I'm just saying that's true of thousands and thousands of really great looking treatments (per year!) that, nonetheless, end up not working in humans, or not being convincing enough to even warrant putting them in humans once.
The only thing such a state of affairs clearly indicates is broken is using mice as proto-human test subjects.
Which of course, when you state it like that, is obviously suboptimal. But no one knows what to do about it.
It's useful as a very early test. They used a shotgun approach, they tested 9 bacterias and 1 of them was suspenseful. At least it was suspenseful for 2 weeks, until the study ended. It's very difficult to extrapolate that to the 5 year survival rate in humans.
If that particular bacteria doesn't work in humans it may still trigger a search for a bacteria that does.
Still being optimistic about this :)
Existing quality of treatments - if there are already efficacious drugs on the market - how sure are you that this new therapy will be best in class? Only being as good as the status quo is not an ideal competitive position. Conversely, if there is an unmet need because a disease is so lethal/debilitating, regulatory agencies can give latitude in approvals.
Likelihood patient compliance - if it is the most effective drug in the world, but requires intravenous infusion six times a day - nobody is going to adhere to that. GLP drugs are effective, but there is a needle-phobia that is preventing patients getting on board with the idea. Which is why there is an arms race for the first company to develop an oral version.
Toxicity - all chemicals are poisonous. Yet some have a lower therapeutic window than others. If you drug does what it should, but if you take 2x as much and it gives you a heart arrhythmia that is going to be a tough approval for anything but the most deadly conditions.
If your treatment works, that’s an improvement of what you had before. Once you know that, you can treat all patients. For some, that will be too late, but without your tests, it would be too late for them, too.
If your treatment doesn’t do anything at all, it keeps things the same, but the patients in the test group likely will have had some inconveniences (having to visit a doctor, getting an injection, etc), so you shouldn’t do the test.
If your treatment makes things worse, you of course shouldn’t do the test.
Problem is that you typically only can only know in hindsight which of these applies.
So, you think carefully on whether a treatment could fall in category 3, and, if so, first do it on a group of patients who consent to be Guinea pigs and, often, are already terminally ill, as any negative outcomes will cause less harm to such patients.
Then, as soon as during the test your stats tell the drug does or doesn’t work, you stop the test and either treat all patients or stop treating the test subjects.
So the comparison is between old and new, to ensure the new treatment is better than the current standard one.
Best bad reason: it would cannibalize an inferior drug currently in your portfolio that's still under patent protection.
I think this behavior is at the far "evil" end of the spectrum of behaviors that drug developers systematically engage in (which I believe is far more banal + less evil than what they're accused of), but it does happen and it's a really nasty
Where it gets especially nasty is when companies buy drugs in development or pre-development from other companies in order to squash (or at least delay) a potentially competitive asset before it reaches the market.
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Another great bad reason, but mostly applies to devices/procedures: the device/procedure is fantastic but for various structural reasons outside of the control of the device/procedure developer, there is insufficient incentive for healthcare providers to actually deploy said device/procedure.
A trivial example would be a pacemaker that requires fewer leads than the competitors and has fewer complications. Great for patients, but potentially totally uninteresting to the electrophysiologists who install it and would get paid less due to the less complex procedure.
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Best good reasons all fall under: making a therapy is unfathomably difficult and most efforts are destined to fail OR (separately) proving a therapy works is unfathomably expensive and most efforts can't produce a positive ROI after that process.
Simplest "bad" reasons are the wealth of the patients. Malaria, river blindness, guinea worm, etc are terrible diseases that mostly impact poor people out of sight from Western eyes. Spending $X billion developing a drug for a population that can barely afford to feed themselves is not going to make a financial return on investment.
* Most drug candidates just don't work
* Even among the drug candidates that do, figuring how to safely deliver them to their target is very hard (looks similar to "just doesn't work")
Bad reasons:
* It's too expensive to prove that a drug works
* It's too difficult to differentiate the patients for whom a drug works and the patients for whom it does not
* It is very hard to predict recruitment and to actually recruit patients for clinical trials
* There aren't enough people with the disorder who are also rich enough to afford treatment to justify development
I'm not sure that is necessary a bad reason. You need to factor in a lot of concerns to determine what "too expensive" means.
But if you are going to spend billions of dollars to develop a drug that only treats about 2 people a year it is likely too expensive even if it is 100% effective. That money would be better spent on treatments that have wider applicability.
Of course this is not simple to measure. Costs aren't known upfront and the research may end up proving invaluable to more widely applicable treatments.
So it is a judgment call and not necessarily a bad reason.
In other cases it's a bad reason for failure: it's also incredibly expensive to prove your drug works even if it does work for a lot of people.
That's bad! It'd be better if it were cheaper.
Actually counterintuitively, due to a weird drug approval and payor reimbursement policy arbitrage, pharma companies are highly incentivized to produce drugs for tiny populations.
One of my hobby horses is railing against this specific dynamic.
Other treatments may eventually prove to have too many serious negative side effects. That's a good reason to abandon them.
That patient was hit and killed by a car two days after finishing their treatment.
Along with the CEO's stubborn refusal to give up any more equity in the company, they went under, and the world will never know if that treatment worked.
This isn’t really an obstacle, at least not as much as it’s made out to be.
There are numerous examples of drugs being brought to market at high prices despite having been generic compounds. Even old drugs can be brought back at $1000/month or more at different doses or delivery mechanisms.
One example: Doxepin is an old antidepressant that is extremely cheap. It was recently re-certified for sleep at lower doses and reintroduced at low doses at a much higher price, despite being “off patent”.
This happens all the time. The drug companies aren’t actually abandoning usable treatments due to patent issues as much as journalists have claimed. If they couldn’t, for some reason, find a way to charge for it they could still use it as a basis for finding an improved relayed compound with more targeted effects, better pharmacokinetics, etc.
They’re not just dropping promising treatments anywhere if there’s a market for them.
IIRC it was more about production methods than developing new treatments.
I am a lifelong sufferer of insomnia (though mostly sleep onset) and tried all sorts of increasingly risky things. CBT cured me in ~2 months.