6 ms·

This is a follow up post to a previous post on mine on how we might look for a natural attenuated (mild) strain of SARS-CoV-2 by genome sequencing [0]. While th

This is a follow up post to a previous post on mine on how we might look for a natural attenuated (mild) strain of SARS-CoV-2 by genome sequencing [0]. While the COG-UK has not been looking directly for such a strain, their data does show that strains with the right type of mutations do exists. 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]. 0. https://www.tillett.info/2020/04/05/a-solution-to-covid-19/ https://www.tillett.info/2020/04/05/a-solution-to-covid-19/ 1. 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...

cocoa19 6y ago
Can downvoters provide some input? It seems contradictory article author is in front page, but at the same time author's comments are downvoted.
- new299 6y ago
  I recommend reading the previous thread to understand some of the issues: https://news.ycombinator.com/item?id=22830320 https://news.ycombinator.com/item?id=22830320 There are a number of issues with the approaches suggested by the author. In particular they’ve suggested an attenuated strain be spread by something similar to Pox Parties. Many might find these suggestions misguided and dangerous...
  - danieltillett 6y ago
    I have not suggested that "pox party" spread would be a good idea, just that it would be hard to stop if a natural attenuated strain was found and that this would influence the way the regulatory agencies viewed its licensing. This is not really relevant to the idea of using an attenuated strain to accelerate the development of other vaccines. This would be done under controlled conditions where the attenuated strain would not spread.
- lvs 6y ago
  Yes, the input I'd provide is that the writer doesn't have a particularly good grasp of virology, but people in this community are upvoting as if this is authoritative. People who write authoritative blog posts without expertise right now should consider themselves part of the disinfo problem. I'll be concrete: the expected correlation between the cited deletions and pathogencity should be considered to approach zero. No evidence supports the hypothesis that single codon or single nucleotide deletions correlate with attenuation of strains. Furthermore, a basic understanding of molecular biology is all that's needed to dismiss the notion of a generalized correlation between observing deletions (or even insertions! or any general mutation!) and the pathologic outcome of infection with a virus. Biology doesn't support general claims of this nature. This is not a well-informed line of reasoning. Even the title of the post is wrong! These are not "gene deletions." These are single codon deletions or deletions of a few nucleotides. No genes have been deleted!!
  - war1025 6y ago
    His "About me" page states: """ I have been a tenured academic (Senior Lecturer) within the School of Pharmacy and Applied Science at La Trobe University, Australia teaching and researching in the areas of phage therapy (bacterial virology), pharmacy, environmental microbiology, bioinformatics and cancer. """ Since that seems easy enough to look up and call him out on if he were lying, I am inclined to believe that it's true. I am inclined to believe his take on things over yours, given that the only info I can see immediately about you is your info blurb stating, "Damn kids, get off my lawn." That said, I don't think anyone is treating what he says as gospel. But it's an interesting perspective.
    - entee 6y ago
      At the risk of starting a flame war, lvs is mostly correct. These are NOT whole gene deletions, they are nucleotide deletions. Genes are usually longer than 33 nucleotides, by my count the largest deletion he sees. For reference, that’s 11 amino acids, rule of thumb for an average protein length is about 200 amino acids. The author highlights that many of these deletions are not codon aligned, which means that if you make this mutation, the resulting protein is highly unlikely to be translated properly. This is true, however devoid of context. Most of the mutations are very rare. The highest frequency one occurs 400 or so out of at minimum 10,000 examples. Next one is 36/10,000. It’s possible these matter, it’s also possible these viral sequences are just low quality and the mutations are an artifact. It’s also possible that these mutations don’t actually matter to viral function for whatever reason. For example, if the mutation is at the end of a protein, it could screw up everything downstream but the protein before the mutation works just fine, i.e. mutation doesn’t matter. It’s just hard to tell with the data in this article. The concept that maybe there are attenuated strains isn’t completely bogus, there is some thought a Singapore strain (with a massive deletion of 380 nucleotides, or 10x what we see here [1]) might be less infective. This is speculation and we don’t know yet, but that sounds maybe possible to me as a PhD Biochemist (if we’re gonna get all credential-spreading here). However saying “The really interesting deletion mutations are those in the non-structural accessory genes. These are the genes that are likely to play an important role in pathogenicity and it would be expected that some of these mutations may make the virus less dangerous (attenuated).” Is really pushing it. I don’t know of any science to believe this one way or another, viruses are pathogenic for a variety of reasons, both accessory and core (whatever that means) proteins matter. In short, given the uncertainty, we can hope there’s a less infectious strain out there, but this article provides precious little evidence to that effect. 1.) https://www.biorxiv.org/content/10.1101/2020.03.11.987222v1.full.pdf https://www.biorxiv.org/content/10.1101/2020.03.11.987222v1....
dehrmann 6y ago
If you find a safe enough strain, it might as well be a vaccine.
- alkonaut 6y ago
  And to test it and establish that it’s that mild safe will take as long as making any other vaccine. That’s the catch.
  - danieltillett 6y ago
    Maybe, but the idea here is not to use any strain found as a vaccine directly, but as a tool to test other vaccines. Instead of running a large Phase III field trial where we wait for people to get infected, we could use the safer strain to do a challenge trial where we deliberately try to infect the volunteers with the attenuated strain. This will give us an answer much sooner and avoid exposing many people to a vaccine that maybe doesn’t work.
    - alkonaut 6y ago
      The problem I think is that the step where people are infected with a (supposedly!) less harmful virus is just like testing a vaccine. It’s another substance to be tested on healthy individuals. You can’t know the long term effects on the attenuated virus in a large group so the same caution and slow pace would have to be used to test that. First! All you did was go from testing one thing to testing two things (an attenuated virus and the vaccine). If the attenuated virus could somehow (quickly) be deemed harmless in humans then I agree it could be a shortcut, but is that really possible?
      - danieltillett 6y ago
        Yes. The whole idea of looking for a natural attenuated strain is we can use the natural spread of this strain to prove it is safe. This is explored in a lot more detail in the other recent posts on my blog. Yes it is possible, but the only way we will know is if we look. I am arguing we should look.
irjustin 6y ago
> 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 6y 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 6y 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 6y 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.
mirimir 6y ago
Thanks for pointing to the data. I'm not sure about the idea of using any particular strain as the basis for a vaccine. But the severity data for various strains might well be helpful in vaccine development. I'm guessing that this is a riff on using cowpox as a vaccine for smallpox. However, modern vaccines often use inactive virus, separated viral components, unrelated viruses for delivery, etc. And now, I've read, mRNA to drive host synthesis of antigenic viral components. Edit: OK, I see that you propose using less dangerous strains for testing vaccine effectiveness. Good idea!
- danieltillett 6y ago
  The idea in this post is not to use any safer strain as a vaccine, but to use it as a tool to speed up the development of other vaccines. If we can find a safer strain then we may be able to use it in a challenge trial which we can’t do with the normal dangerous strain for ethical reasons. This is explored in more detail in my [1] reference above.
musiciangames 6y ago
Hi Daniel, When you first put up the idea, it seemed like your emphasis was on using the attenuated strain directly as a vaccine (and benefiting from its ability to propagate itself). This post suggests more to help test a conventional vaccine. Could you comment on reasons for the change of approach?
- danieltillett 6y ago
  Yes that is right. While the idea of using such a strain as a vaccine directly was the focus of my first post, this was controversial. Even if you think it is too risky to use a natural attenuated strain as a vaccine, such as strain would be very useful as a tool to accelerate other vaccines. As I said in my first post how to use any such strain is not up to me, but if it can be used to get us to a vaccine sooner it is worth looking into. If we are going consider doing a challenge trial we should at first make the effort to see if we can find a safer strain to use.
hazeii 6y ago
Isn't there still a big question over how long immunity will last? (can you get a feel for this from the structure of the proposed attenuated strain?).
- GTP 6y ago
  He talks about this here: https://www.tillett.info/2020/04/05/a-solution-to-covid-19/ https://www.tillett.info/2020/04/05/a-solution-to-covid-19/
tinus_hn 6y ago
I suspect if that is done it’ll be just one more argument for infinite delays, because well we tested it with this inactive virus but how can we be sure it works the same with the real one? Let’s just test a bit more for a few months.
dstroot 6y ago
I wonder why everyone believes so strongly we will create a viable vaccine. The FDA has never approved a vaccine for humans that is effective against any member of the coronavirus family, which includes SARS, MERS, and several that cause the common cold. If political pressure/regulatory relaxation allows a vaccine to enter the market I would be suspicious of its efficacy.
- CyanLite4 6y ago
  Not exactly true. Moderna, and several others who are leading the vaccine race right now are out front because they had viable SARS and MERS vaccines but no where to test it other than in animal models. Coronaviruses are easy to vaccinate against. They mutate very slowly. There’s just not a viable business model for them when the symptoms are so mild and treatments are available cheaply over-the-counter.
  - gridlockd 6y ago
    > Coronaviruses are easy to vaccinate against. From what I've read, creating a sufficiently safe vaccine has been quite a challenge.
  - aledalgrande 6y ago
    > Coronaviruses are easy to vaccinate against. They mutate very slowly. Wait can you expand on that? I thought RNA viruses mutate very quickly?
    - totony 6y ago
      From what I understand, covid is a relatively small rna strand vs e.g. the flu which makes significant mutation way more rare
      - rotexo 6y ago
        SARS-CoV-2 genome size is ~30 kb [1], influenza A genome size is ~14 kb [2]. A protein encoded in the SARS-CoV-2 genome is predicted to have exonuclease proofreading activity, which would result in a lower mutation rate [3]. [1] https://mra.asm.org/content/9/11/e00169-20 https://mra.asm.org/content/9/11/e00169-20 [2] https://en.m.wikipedia.org/wiki/Influenza_A_virus#Structure_and_genetics https://en.m.wikipedia.org/wiki/Influenza_A_virus#Structure_... [3] https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-020-02344-6 https://translational-medicine.biomedcentral.com/articles/10...
IdoRA 6y ago
Assuming that one located a naturally mild strain of virus (which I personally remain bearish on), for it to produce useful (in the regulatory sense) information a challenge trial, you would need to establish that the response of individuals to the mild strain (which by definition differs from the more lethal strain) is representative of the response to the more lethal strain of virus.
- danieltillett 6y ago
  Yes, but that is where you use epidemiology. If you track down each person in the local area infected with the mutant strain and follow their clinical course you can work this out. You can also do serology to make sure the immune response is similar, etc. There will always be the possibility that the attenuated strain varies is some major but subtle way from the non-attenuated strains, but this is not something ever seen before with other viruses. If you demand to know everything and the answers to all possible risks up front medical science doesn’t advance.
  - IdoRA 6y ago
    I demand to know enough information to be able to give proper informed consent to study volunteers. I think your ideas are possible, but the likelihood of success is quite low and the effort required to do the proper studies is far greater than you estimate. Our resources are better spent on much more developed programs with better defined odds of success. My helpful closing suggestion is to speak with some epidemiologists and clinical researchers to see if you can get some budgetary efforts for what you propose, or failing that, try to locate a review article or two. Good luck.
    - danieltillett 6y ago
      How have you determined the likelihood of success and the effort required? With the economic cost to the USA alone running at $500 billion a month are we really constrained by resources? I have spoken to many scientists and clinicians about this. There is a great deal of activity going on to put this into action.

cocoa19 6y ago

Can downvoters provide some input? It seems contradictory article author is in front page, but at the same time author's comments are downvoted.

new299 6y ago
I recommend reading the previous thread to understand some of the issues: https://news.ycombinator.com/item?id=22830320 https://news.ycombinator.com/item?id=22830320 There are a number of issues with the approaches suggested by the author. In particular they’ve suggested an attenuated strain be spread by something similar to Pox Parties. Many might find these suggestions misguided and dangerous...
- danieltillett 6y ago
  I have not suggested that "pox party" spread would be a good idea, just that it would be hard to stop if a natural attenuated strain was found and that this would influence the way the regulatory agencies viewed its licensing. This is not really relevant to the idea of using an attenuated strain to accelerate the development of other vaccines. This would be done under controlled conditions where the attenuated strain would not spread.
lvs 6y ago
Yes, the input I'd provide is that the writer doesn't have a particularly good grasp of virology, but people in this community are upvoting as if this is authoritative. People who write authoritative blog posts without expertise right now should consider themselves part of the disinfo problem. I'll be concrete: the expected correlation between the cited deletions and pathogencity should be considered to approach zero. No evidence supports the hypothesis that single codon or single nucleotide deletions correlate with attenuation of strains. Furthermore, a basic understanding of molecular biology is all that's needed to dismiss the notion of a generalized correlation between observing deletions (or even insertions! or any general mutation!) and the pathologic outcome of infection with a virus. Biology doesn't support general claims of this nature. This is not a well-informed line of reasoning. Even the title of the post is wrong! These are not "gene deletions." These are single codon deletions or deletions of a few nucleotides. No genes have been deleted!!
- war1025 6y ago
  His "About me" page states: """ I have been a tenured academic (Senior Lecturer) within the School of Pharmacy and Applied Science at La Trobe University, Australia teaching and researching in the areas of phage therapy (bacterial virology), pharmacy, environmental microbiology, bioinformatics and cancer. """ Since that seems easy enough to look up and call him out on if he were lying, I am inclined to believe that it's true. I am inclined to believe his take on things over yours, given that the only info I can see immediately about you is your info blurb stating, "Damn kids, get off my lawn." That said, I don't think anyone is treating what he says as gospel. But it's an interesting perspective.
  - entee 6y ago
    At the risk of starting a flame war, lvs is mostly correct. These are NOT whole gene deletions, they are nucleotide deletions. Genes are usually longer than 33 nucleotides, by my count the largest deletion he sees. For reference, that’s 11 amino acids, rule of thumb for an average protein length is about 200 amino acids. The author highlights that many of these deletions are not codon aligned, which means that if you make this mutation, the resulting protein is highly unlikely to be translated properly. This is true, however devoid of context. Most of the mutations are very rare. The highest frequency one occurs 400 or so out of at minimum 10,000 examples. Next one is 36/10,000. It’s possible these matter, it’s also possible these viral sequences are just low quality and the mutations are an artifact. It’s also possible that these mutations don’t actually matter to viral function for whatever reason. For example, if the mutation is at the end of a protein, it could screw up everything downstream but the protein before the mutation works just fine, i.e. mutation doesn’t matter. It’s just hard to tell with the data in this article. The concept that maybe there are attenuated strains isn’t completely bogus, there is some thought a Singapore strain (with a massive deletion of 380 nucleotides, or 10x what we see here [1]) might be less infective. This is speculation and we don’t know yet, but that sounds maybe possible to me as a PhD Biochemist (if we’re gonna get all credential-spreading here). However saying “The really interesting deletion mutations are those in the non-structural accessory genes. These are the genes that are likely to play an important role in pathogenicity and it would be expected that some of these mutations may make the virus less dangerous (attenuated).” Is really pushing it. I don’t know of any science to believe this one way or another, viruses are pathogenic for a variety of reasons, both accessory and core (whatever that means) proteins matter. In short, given the uncertainty, we can hope there’s a less infectious strain out there, but this article provides precious little evidence to that effect. 1.) https://www.biorxiv.org/content/10.1101/2020.03.11.987222v1.full.pdf https://www.biorxiv.org/content/10.1101/2020.03.11.987222v1....

dehrmann 6y ago

If you find a safe enough strain, it might as well be a vaccine.

alkonaut 6y ago
And to test it and establish that it’s that mild safe will take as long as making any other vaccine. That’s the catch.
- danieltillett 6y ago
  Maybe, but the idea here is not to use any strain found as a vaccine directly, but as a tool to test other vaccines. Instead of running a large Phase III field trial where we wait for people to get infected, we could use the safer strain to do a challenge trial where we deliberately try to infect the volunteers with the attenuated strain. This will give us an answer much sooner and avoid exposing many people to a vaccine that maybe doesn’t work.
  - alkonaut 6y ago
    The problem I think is that the step where people are infected with a (supposedly!) less harmful virus is just like testing a vaccine. It’s another substance to be tested on healthy individuals. You can’t know the long term effects on the attenuated virus in a large group so the same caution and slow pace would have to be used to test that. First! All you did was go from testing one thing to testing two things (an attenuated virus and the vaccine). If the attenuated virus could somehow (quickly) be deemed harmless in humans then I agree it could be a shortcut, but is that really possible?
    - danieltillett 6y ago
      Yes. The whole idea of looking for a natural attenuated strain is we can use the natural spread of this strain to prove it is safe. This is explored in a lot more detail in the other recent posts on my blog. Yes it is possible, but the only way we will know is if we look. I am arguing we should look.

irjustin 6y ago

> 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 6y 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 6y 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 6y 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.

mirimir 6y ago

Thanks for pointing to the data. I'm not sure about the idea of using any particular strain as the basis for a vaccine. But the severity data for various strains might well be helpful in vaccine development. I'm guessing that this is a riff on using cowpox as a vaccine for smallpox. However, modern vaccines often use inactive virus, separated viral components, unrelated viruses for delivery, etc. And now, I've read, mRNA to drive host synthesis of antigenic viral components. Edit: OK, I see that you propose using less dangerous strains for testing vaccine effectiveness. Good idea!

danieltillett 6y ago
The idea in this post is not to use any safer strain as a vaccine, but to use it as a tool to speed up the development of other vaccines. If we can find a safer strain then we may be able to use it in a challenge trial which we can’t do with the normal dangerous strain for ethical reasons. This is explored in more detail in my [1] reference above.

musiciangames 6y ago

Hi Daniel, When you first put up the idea, it seemed like your emphasis was on using the attenuated strain directly as a vaccine (and benefiting from its ability to propagate itself). This post suggests more to help test a conventional vaccine. Could you comment on reasons for the change of approach?

danieltillett 6y ago
Yes that is right. While the idea of using such a strain as a vaccine directly was the focus of my first post, this was controversial. Even if you think it is too risky to use a natural attenuated strain as a vaccine, such as strain would be very useful as a tool to accelerate other vaccines. As I said in my first post how to use any such strain is not up to me, but if it can be used to get us to a vaccine sooner it is worth looking into. If we are going consider doing a challenge trial we should at first make the effort to see if we can find a safer strain to use.

hazeii 6y ago

Isn't there still a big question over how long immunity will last? (can you get a feel for this from the structure of the proposed attenuated strain?).

GTP 6y ago
He talks about this here: https://www.tillett.info/2020/04/05/a-solution-to-covid-19/ https://www.tillett.info/2020/04/05/a-solution-to-covid-19/

tinus_hn 6y ago

I suspect if that is done it’ll be just one more argument for infinite delays, because well we tested it with this inactive virus but how can we be sure it works the same with the real one? Let’s just test a bit more for a few months.

dstroot 6y ago

I wonder why everyone believes so strongly we will create a viable vaccine. The FDA has never approved a vaccine for humans that is effective against any member of the coronavirus family, which includes SARS, MERS, and several that cause the common cold. If political pressure/regulatory relaxation allows a vaccine to enter the market I would be suspicious of its efficacy.

CyanLite4 6y ago
Not exactly true. Moderna, and several others who are leading the vaccine race right now are out front because they had viable SARS and MERS vaccines but no where to test it other than in animal models. Coronaviruses are easy to vaccinate against. They mutate very slowly. There’s just not a viable business model for them when the symptoms are so mild and treatments are available cheaply over-the-counter.
- gridlockd 6y ago
  > Coronaviruses are easy to vaccinate against. From what I've read, creating a sufficiently safe vaccine has been quite a challenge.
- aledalgrande 6y ago
  > Coronaviruses are easy to vaccinate against. They mutate very slowly. Wait can you expand on that? I thought RNA viruses mutate very quickly?
  - totony 6y ago
    From what I understand, covid is a relatively small rna strand vs e.g. the flu which makes significant mutation way more rare
    - rotexo 6y ago
      SARS-CoV-2 genome size is ~30 kb [1], influenza A genome size is ~14 kb [2]. A protein encoded in the SARS-CoV-2 genome is predicted to have exonuclease proofreading activity, which would result in a lower mutation rate [3]. [1] https://mra.asm.org/content/9/11/e00169-20 https://mra.asm.org/content/9/11/e00169-20 [2] https://en.m.wikipedia.org/wiki/Influenza_A_virus#Structure_and_genetics https://en.m.wikipedia.org/wiki/Influenza_A_virus#Structure_... [3] https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-020-02344-6 https://translational-medicine.biomedcentral.com/articles/10...

IdoRA 6y ago

Assuming that one located a naturally mild strain of virus (which I personally remain bearish on), for it to produce useful (in the regulatory sense) information a challenge trial, you would need to establish that the response of individuals to the mild strain (which by definition differs from the more lethal strain) is representative of the response to the more lethal strain of virus.

danieltillett 6y ago
Yes, but that is where you use epidemiology. If you track down each person in the local area infected with the mutant strain and follow their clinical course you can work this out. You can also do serology to make sure the immune response is similar, etc. There will always be the possibility that the attenuated strain varies is some major but subtle way from the non-attenuated strains, but this is not something ever seen before with other viruses. If you demand to know everything and the answers to all possible risks up front medical science doesn’t advance.
- IdoRA 6y ago
  I demand to know enough information to be able to give proper informed consent to study volunteers. I think your ideas are possible, but the likelihood of success is quite low and the effort required to do the proper studies is far greater than you estimate. Our resources are better spent on much more developed programs with better defined odds of success. My helpful closing suggestion is to speak with some epidemiologists and clinical researchers to see if you can get some budgetary efforts for what you propose, or failing that, try to locate a review article or two. Good luck.
  - danieltillett 6y ago
    How have you determined the likelihood of success and the effort required? With the economic cost to the USA alone running at $500 billion a month are we really constrained by resources? I have spoken to many scientists and clinicians about this. There is a great deal of activity going on to put this into action.