COVID Moonshot - should it be left without saving lives?

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COVID Moonshot - should it be left without saving lives?

Postby ThWuensche » Mon Jan 04, 2021 11:36 pm

Listening to the end-of-year COVID Moonshot presentation https://www.youtube.com/watch?v=fkQwDltGDfU every speaker is explaining what has been done by his/her group - for sure the contributions are fantastic - but in the end for my impression (given the current situation) it stays too much academic. Annette Von Delft is explaining a long route to clinical tests, Frank Von Delft concludes there is no known runway, constitutes problems with project management, missing business models, trouble in funding. Somehow the conclusion is "Ah, we have done a lot and governments should continue that for future pandemics", but conclusions how to save lives now are missing.

While I understand all of that, value the great contributions which have been brought with extreme work hours spent, from my life experience and given the current situation I can't agree with that outcome. I'm now leading a company and that needs to make decisions based on not fully known ground at some times. Back in the early 80s - being a very peaceful person - I went to the army in Germany, became a reserve officer after my experience what the warsaw treaty focused government in eastern Germany aimed at. In such situations you are forced to make decisions not based on long research and with confidence close to 100%, but sometimes at very low confidence levels. However not making a decision could cost more lives than making an only half-way founded decision.

And mankind is in a similar situation now: Worldwide we have about 12000 individuals dying every day, that's about 350 thousand deaths in the month, probably a million more before vaccinations achieve sufficient effect. We have population groups with a risk of death > 20% at the moment they get ill, maybe >50% from the moment the infection gets serious. Unfortunately I'm observing that rather close now. Concluding from the published statistics in the home for older people in the neighbor village from about 100 inhabitants 14 died between December 30 and January 4th. Not much difference in a similar institution in the region right before Christmas.

In that situation - once there is a potentially potent treatment - not making that substance available to people can not be justified. If I have a chance of dying with 50% probability anyhow and if I could take some substance that might help me and has a probability of killing me with less than 10% probability, then I should have that substance available. The risk from what I might die should be my decision and not depend on a two years standard clinical test period. I don't care about pre-clinical and clinical tests if I'm likely to die before those tests are completed. Of course products can always be improved, but in the current situation the question is not what is the best drug, but whether people can get a good-enough drug or not. Being somewhat sarcastic: If somebody is beyond 80 and gets ill with COVID-19, questions about possible negative effects on fertility or damage to the unborn child in pregnancy are not the main concern.

That argument of course is valid only in emergency treatment for persons that are seriously ill. The situation with vaccines is very different: They are given to healthy persons with a risk of dying from COVID-19 lower than 0.1% as of so far accumulated statistics, so there risks from side effects of the vaccination obviously are to be considered and limited with high confidence. But when I'm infected and likely to die from COVID-19 anyhow, I don't care so much about side effects of the preparate on my liver, as long as they're not likely to kill me faster than COVID-19.

That point of view seems to be missing in the discussion considering possible current runways. As soon as there is some confidence that COVID Moonshot results might save lives, there is no justification to deny these results (in form of chemicals a person could take, not paperwork) to persons ill with that disease. This most likely does not fit into standard drug production and distribution schemes. But then on one hand a lot of psychedelic drugs are produced and distributed with much less ethic justification. And on the other hand such situation should justify official, legal procedures beyond lengthy standard therapeutic certification processes. With that in mind, Project Moonshot should consider a minimum set of tests as quick as possible to make sure what has been developed so far is more likely to save the life of somebody in a high-risk group and ill with COVID-19 than take it. That should happen beside further attempts to improve the results and go through lengthy tests.

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Re: COVID Moonshot - should it be left without saving lives?

Postby JimboPalmer » Tue Jan 05, 2021 12:09 am

F@H is not a drug company.

F@H does research and offers it freely and without attribution to all. (Mind you, drug companies are most likely to use that research, but it is free to all)

As I (mis?) read your post, I thought you were expecting F@H to produce drugs themselves. That is not going to happen, most of F@H's researchers are affiliated with an academic institution.
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Re: COVID Moonshot - should it be left without saving lives?

Postby gunnarre » Tue Jan 05, 2021 1:21 pm

Universities definitely do develop vaccines, cures and new test methods. The NTNU university in Norway has developed a test method using microbeads, which is uses a lot less reactant than other tests - making it possible to test more people. Oxford University in cooperation with the drug company AstraZeneca did develop a vaccine, which is now being administered in the UK. The Oxford vaccine was approved on an accellerated schedule, precisely due to the considerations that you mention here:
ThWuensche wrote:In that situation - once there is a potentially potent treatment - not making that substance available to people can not be justified. If I have a chance of dying with 50% probability anyhow and if I could take some substance that might help me and has a probability of killing me with less than 10% probability, then I should have that substance available.

This is a classic "risk assessment" or "cost/benefit analysis" - the UK has decided that since they have so much infection right now, it is acceptable to take a higher risk for adverse effects due to the benefit. If there had been no active pandemic in the UK, the vaccine would not yet have been approved.

There does have to be some testing of efficacy and safety before it's rolled out though. We've seen serious adverse effects from drugs before, and we shouldn't take unnecessary risks. (Like Lyodura and Thalidomide.)

Basic study of the actual virus has found a location that is a very promising for disabling its camouflage, so that the immune system can destroy it: https://foldingathome.org/2020/12/16/sa ... potential/ This shows that basic research of protein folding also can find promising results. And when you learn about protein folding in muscles or in cancer cells, you might actually discover something that is applicable for a different disease than the one you started studying.

The Covid Moonshot is about as close to applied research as F@H gets, I think, because they're studying candidate compounds that target the Covid-19 virus. Some of the other Covid-19 projects are more about understanding the virus itself, but the Moonshot sprints are about studying actual compounds. Unfortunately, new compounds have to be tested for toxicity and adverse effects before they can start human trials. And even compounds which looked promising in vitro (like Chloroquine and zinc) might turn out to not be effective when they are actually tested in a clinical trial. If the Covid Moonshot finds a compound that it shown to work in an in vitro assay and is safe in animal testing, and can be synthesized in an economical way, then many drug companies can start clinical trials without paying for a patent. It would be ethical to credit the Covid Moonshot if they use the work from it, but they don't have to pay anything.
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Re: COVID Moonshot - should it be left without saving lives?

Postby JimF » Tue Jan 05, 2021 5:11 pm

gunnarre wrote:If the Covid Moonshot finds a compound that it shown to work in an in vitro assay and is safe in animal testing, and can be synthesized in an economical way, then many drug companies can start clinical trials without paying for a patent. It would be ethical to credit the Covid Moonshot if they use the work from it, but they don't have to pay anything.

I am all in favor of Covid Moonshot, and have seven Nvidia cards on it plus to big Ryzens for the CPU work.

However, the common misconception is that patents are holding up the progress of drug delivery to the market. In fact, they facilitate it by allowing companies to make money on their research and testing, which runs into many millions (often billions) of dollars. In fact, the main hindrance to developing more antibiotics that avoid resistance to germs is the lack of profit potential. And the cost of development is not just finding the drugs in the lab, but testing them in animals and eventually humans, which is usually the biggest cost of all.

Fortunately for COVID research, various governments are helping to fund and conduct the trials. It will be necessary for Covid Moonshot to somehow plug into that, since without the potential for patented drugs, they won't find much private money for it. It is not by accident that all the most advanced vaccines (Pfizer BioNTech and Moderna, for example) are privately funded.

By the way, Dr. David Baker of Rosetta/IPD has a rather elegant solution. After doing the public research, he takes advantage of that by setting up companies to commercialize the results. Maybe Covid Moonshot needs something like that.
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Re: COVID Moonshot - should it be left without saving lives?

Postby Jonazz » Wed Jan 06, 2021 6:24 pm

JimF wrote:
gunnarre wrote:If the Covid Moonshot finds a compound that it shown to work in an in vitro assay and is safe in animal testing, and can be synthesized in an economical way, then many drug companies can start clinical trials without paying for a patent. It would be ethical to credit the Covid Moonshot if they use the work from it, but they don't have to pay anything.


By the way, Dr. David Baker of Rosetta/IPD has a rather elegant solution. After doing the public research, he takes advantage of that by setting up companies to commercialize the results. Maybe Covid Moonshot needs something like that.


But IPD's angle is a bit different. They design proteins from scratch, to treat diseases. FAH's research is a bit morde fundamental (protein folding problems and cryptic pocket discovery), but with the moonshot they're also edging more towards drug design

For those interested in IPD spinoff: https://www.neoleukin.com
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