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> While it might be possible to use a natural attenuated strain as a vaccine directly, the real value of having such a strain may be in using it as a safer test

> While it might be possible to use a natural attenuated strain as a vaccine directly, the real value of having such a strain may be in using it as a safer test strain in a human challenge trial of a conventional vaccine. This could shave many months off us getting an effective vaccine for COVID-19 [1]. Could you explain this further as to why this allows us to shave many months off? My current extremely naive understanding of testing would be, at least one group would be unexposed, unvaccinated trial: 1, vaccine, 2 inject, 3 expose to virus 4, measure If Step 3 is expose, how does a safer strain speed this up?

danieltillett 7y ago
The reason it would be faster is at the moment it is not considered ethical to deliberately expose people to the virus after giving them a vaccine. Because we can’t do the exposing we have to use the large field trial approach and wait for people to get ill on their own (or not). These take a long time. If we had a safe strain of the virus then we could do the exposing. I explain this much more in a previous post on my blog [0]. 0. https://www.tillett.info/2020/04/24/it-is-unethical-to-not-search-for-an-attenuated-sars-cov-2-strain/ https://www.tillett.info/2020/04/24/it-is-unethical-to-not-s...
- irjustin 7y ago
  Got it, my assumption for Step 3 existing is wrong. It simply doesn't! Thanks for this explanation and the series of blog posts.
- tempestn 7y ago
  There are those that argue even without a safer strain it is ethical under certain circumstances to still perform that sort of "challenge trial" though, where people are deliberately exposed. A number of conditions would have to be met, such as all volunteer participation of course, very clear explanation and demonstration of understanding, no financial incentive, etc. But a faster vaccine could save many more lives than would be risked in the trial, and the risk itself could be very low, given the trial participants would be monitored closely and would get excellent medical care. Also obviously it would be restricted to young, healthy people without pre-existing conditions. To me it seems like a solid argument that given all those conditions (and possibly others I haven't thought of or mentioned), such a trial should be allowed. My understanding is that there are many people preemptively volunteering to participate.
  - danieltillett 7y ago
    Even if it is ethical to use a strain we know is dangerous, we would still be amiss to use such a strain just because we were too lazy to look for a safer strain. We should only use a dangerous strain if we try hard and fail to find a safer strain. We haven’t even tried yet.
    - tempestn 7y ago
      Yes, certainly.
- JulianMorrison 7y ago
  In practise they would probably be testing on heavily-exposed people (doctors and nurses etc). But it would speed things up some to be able to do controlled exposure.
credit_guy 7y ago
Not the OP, but allow me to jump in. Two years ago, I ate something perhaps and I had a severe allergic reaction. I went from a perfectly healthy individual to a familiar face in the ER in a matter of days (4 times there in a span of a month). I took prednisone for 6 months. All tests came fine. In the eyes of modern medicine, I was still a perfectly healthy individual. My doctor told me that that is the case with 95% of the people with chronic allergies - we simply don't know what's the root cause of their problem. In other words, the immune system is extraordinarily complex, and if you could avoid messing up with it, you should probably do that. Now, a vaccine does exactly that. It plays some games with the immune system. Sometimes the outcome of the game is weird, just take a look at [1]. Here's a random snippet: "Encephalitis (severe brain reaction), which can lead to permanent brain damage (as many as 1 per 83,000)." Variolation as opposed to vaccination, has the advantage that the only side effect is that you can get the disease itself, but no weird interactions with the immune system. All right, in the case of Covid19, the disease can have such weird interactions, so it's difficult to say it's an obviously better alternative, but still, that's the main idea. [1] https://www.historyofvaccines.org/content/articles/vaccine-side-effects-and-adverse-events https://www.historyofvaccines.org/content/articles/vaccine-s...
- gwd 7y ago
  > Variolation as opposed to vaccination, has the advantage that the only side effect is that you can get the disease itself, but no weird interactions with the immune system. This seems to me to be a bit of a false distinction: all the symptoms are ultimately "weird interactions with the immune system"; and this is especially true for the more deadly responses to the virus, AFAICT. That said, after nearly 3 million confirmed cases, we should have a reasonable sample of how the genes in this virus interact with the immune system; it certainly seems to be introducing fewer variables to delete some of these genes than to try adding something else into the mix.

danieltillett 7y ago

The reason it would be faster is at the moment it is not considered ethical to deliberately expose people to the virus after giving them a vaccine. Because we can’t do the exposing we have to use the large field trial approach and wait for people to get ill on their own (or not). These take a long time. If we had a safe strain of the virus then we could do the exposing. I explain this much more in a previous post on my blog [0]. 0. https://www.tillett.info/2020/04/24/it-is-unethical-to-not-search-for-an-attenuated-sars-cov-2-strain/ https://www.tillett.info/2020/04/24/it-is-unethical-to-not-s...

irjustin 7y ago
Got it, my assumption for Step 3 existing is wrong. It simply doesn't! Thanks for this explanation and the series of blog posts.
tempestn 7y ago
There are those that argue even without a safer strain it is ethical under certain circumstances to still perform that sort of "challenge trial" though, where people are deliberately exposed. A number of conditions would have to be met, such as all volunteer participation of course, very clear explanation and demonstration of understanding, no financial incentive, etc. But a faster vaccine could save many more lives than would be risked in the trial, and the risk itself could be very low, given the trial participants would be monitored closely and would get excellent medical care. Also obviously it would be restricted to young, healthy people without pre-existing conditions. To me it seems like a solid argument that given all those conditions (and possibly others I haven't thought of or mentioned), such a trial should be allowed. My understanding is that there are many people preemptively volunteering to participate.
- danieltillett 7y ago
  Even if it is ethical to use a strain we know is dangerous, we would still be amiss to use such a strain just because we were too lazy to look for a safer strain. We should only use a dangerous strain if we try hard and fail to find a safer strain. We haven’t even tried yet.
  - tempestn 7y ago
    Yes, certainly.
JulianMorrison 7y ago
In practise they would probably be testing on heavily-exposed people (doctors and nurses etc). But it would speed things up some to be able to do controlled exposure.

credit_guy 7y ago

Not the OP, but allow me to jump in. Two years ago, I ate something perhaps and I had a severe allergic reaction. I went from a perfectly healthy individual to a familiar face in the ER in a matter of days (4 times there in a span of a month). I took prednisone for 6 months. All tests came fine. In the eyes of modern medicine, I was still a perfectly healthy individual. My doctor told me that that is the case with 95% of the people with chronic allergies - we simply don't know what's the root cause of their problem. In other words, the immune system is extraordinarily complex, and if you could avoid messing up with it, you should probably do that. Now, a vaccine does exactly that. It plays some games with the immune system. Sometimes the outcome of the game is weird, just take a look at [1]. Here's a random snippet: "Encephalitis (severe brain reaction), which can lead to permanent brain damage (as many as 1 per 83,000)." Variolation as opposed to vaccination, has the advantage that the only side effect is that you can get the disease itself, but no weird interactions with the immune system. All right, in the case of Covid19, the disease can have such weird interactions, so it's difficult to say it's an obviously better alternative, but still, that's the main idea. [1] https://www.historyofvaccines.org/content/articles/vaccine-side-effects-and-adverse-events https://www.historyofvaccines.org/content/articles/vaccine-s...

gwd 7y ago
> Variolation as opposed to vaccination, has the advantage that the only side effect is that you can get the disease itself, but no weird interactions with the immune system. This seems to me to be a bit of a false distinction: all the symptoms are ultimately "weird interactions with the immune system"; and this is especially true for the more deadly responses to the virus, AFAICT. That said, after nearly 3 million confirmed cases, we should have a reasonable sample of how the genes in this virus interact with the immune system; it certainly seems to be introducing fewer variables to delete some of these genes than to try adding something else into the mix.