16 ms·

Variolation

104 points by Cactus2018 6y ago

fab1an 6y ago
Amusingly, this is one of the few cases where - extremely broadly - one general idea of homeopathy works: you're basically just microdosing virus. This is amusing because a lot of anti-vaxxers (at least in Germany) will also be into homeopathy. There's possibly a good pro-vax-comms strategy in here: reframe vaccines as homeopathic viral microdoses (instead of complicated pharmaceutical compounds) and you might save a few kids.
- kevin_b_er 6y ago
  That might increase belief in homeopathy, which is bad too. Homeopathy beliefs are that the stronger the dilution, the more powerful the medication. Homeopathy would be diluting the virus to the point where there's a strong probability of zero virus particles remaining in the "medicine" because of the belief the water has the memory of the virus. This is false, because homeopathy has no effect other than placebo and placebo does not stop covid 19 deaths.
  - DataWorker 6y ago
    Any cite for your claim placebo can’t prevent a covid death? That seems unlikely given how powerful and common the placebo effect seems to be.
- yetihehe 6y ago
  But this has a side effect of supporting homeopathy. I'd prefer we found some better way to educate people.
- PeterStuer 6y ago
  Not really. Homeopathy assumes that which causes likewise symptoms to be a candidate for cure, while here it is the idea of microdosing the disease, which hopefully would not case symptoms like the full blown disease, and the second tenant of homeopathy, the dilutions increase potency, would also hopefully be absent as that would be like the viral load factor, but in reverse.
  - yetihehe 6y ago
    You are using facts. This is not very effective (against antivaxers and homeopathy enthusiasts).
    - cmendel 6y ago
      Facts are very effective against homeopaths, you just have to dilute them 100x first.
    - mistermann 6y ago
      Upon what evidence is this generalized statement based? Did you fact check it? Note: I pose this question not as snark, or as some sort of a "disproof" of the "general truthiness" of your statement (with which I do not disagree, fwiw), but 100% literally.
  - inimino 6y ago
    A tenant is someone who resides in a building, tenet is the word you want.
    - PeterStuer 6y ago
      Thx. Many errors in that post, but beyond an edit now.
- jhbadger 6y ago
  Although vaccines aren't the same thing as variolation, and were developed because of the inherent risks of microdosing a dangerous pathogen. They are called "vaccines" because of the use of cowpox (a virus related to but much less dangerous than smallpox) in Jenner's vaccine and cow is "vacca" in Latin (similar to modern Spanish vaca).
- np_tedious 6y ago
  You're definitely on to something. I couldn't find the original source, but this FB comment has become something of a meme https://twitter.com/Golfergirl2018/status/1216905848179609600?s=19 https://twitter.com/Golfergirl2018/status/121690584817960960... > I am not anti-vax, but I understand why some parents do not want chemicals in their childrens bodies. I think instead of chemical shots, doctors should give a very small amount of the virus so the body can build up immunity.
kh_hk 6y ago
https://en.wikipedia.org/wiki/Balmis_Expedition https://en.wikipedia.org/wiki/Balmis_Expedition
barrald 6y ago
For anyone else watching The Great, Catherine's interest in variolation is apparently a true story: https://smarthistoryblog.com/2016/10/05/catherine-the-great-risked-her-life-for-science/ https://smarthistoryblog.com/2016/10/05/catherine-the-great-...
- 40four 6y ago
  Fascinating. Since I never paid attention in history class, I'll admit The Great did remind me of this practice. It's interesting people were experimenting with techniques likes this so long ago, when their understanding of medical science was so rudimentary compared to today.
- jcroll 6y ago
  It was also done in the HBO John Adams miniseries
OJFord 6y ago
These aren't to me the clearest Wikipedia pages, but I think I now understand that - in modern usage, ignoring origins - vaccination and inoculation are both types of immunisation; the latter using a sample of the thing to immunise against, while a vaccine is actually strictly speaking immunisation through other means, some other substance to the thing that should be immunised against? I suppose I thought they were synonyms, but I certainly thought a vaccine was 'a bit of' the thing to immunised against, despite remembering Jenner and his cow.
- war1025 6y ago
  > certainly thought a vaccine was 'a bit of' the thing to immunised against A lot of the original vaccines were made from deactivated viruses. I don't know how that process works exactly, but your understanding isn't far off at least for how they were originally produced.
  - twic 6y ago
    A lot still are. Sinopharm (the two "Institutes of Biological Products") and Sinovac are both developing inactivated virus vaccines for COVID-19: https://www.who.int/blueprint/priority-diseases/key-action/novel-coronavirus-landscape-ncov.pdf https://www.who.int/blueprint/priority-diseases/key-action/n...
  - Cactus2018 6y ago
    >> were made from deactivated viruses. I don't know how that process works exactly Check out the history of the Rabies vaccine, where the virus was weakened through aging: > derived from the spinal cord of an inoculated rabbit which had died of rabies 15 days earlier. https://en.wikipedia.org/wiki/Rabies_vaccine#History https://en.wikipedia.org/wiki/Rabies_vaccine#History > A vaccine typically contains an agent that resembles a disease-causing microorganism and is often made from weakened or killed forms of the microbe, its toxins, or one of its surface proteins. https://en.wikipedia.org/wiki/Inactivated_vaccine https://en.wikipedia.org/wiki/Inactivated_vaccine > The virus is killed using a method such as heat or formaldehyde. > Whole virus vaccines use the entire virus particle, fully destroyed using heat, chemicals, or radiation. > Split virus vaccines are produced by using a detergent to disrupt the virus. > Subunit vaccines are produced by purifying out the antigens that best stimulate the immune system to mount a response to the virus, while removing other components necessary for the virus to replicate or survive or that can cause adverse reactions
gerland 6y ago
Additional trivia - Benjamin Franklin was a big proponent of inoculation. He tried to spread the awarness and convince people that it's safe and effective. Unfortunately his first son died of smallpox before he could be inoculated. He was 4 and developed some other infection, so BJ decided to wait with inoculation. Before he could perform it, he contracted the disease. It was huge blow to the credibility of BJ claims about inoculation, but he continued his mission nevertheless.
- peterwwillis 6y ago
  Claims about variolation/inoculation, not vaccination. Vaccines were discovered 6 years after Franklin's death.
- ptaipale 6y ago
  I think it is somewhat incorrect to call this vaccination, because the proper term for what was available in Benjamin Franklin's time was variolation, or inoculation.
  - elliekelly 6y ago
    An interesting tidbit about the origin of two terms from Wikipedia: > Until the very early 1800s, inoculation referred only to the practice of variolation, the predecessor to the smallpox vaccine. Edward Jenner introduced the latter in 1798, when it was called cowpox inoculation, or vaccine inoculation (from Latin vacca = cow). Smallpox inoculation continued to be referred to as variolation (from variola = smallpox), whereas cowpox inoculation was referred to as vaccination (from Jenner's use of variolae vaccinae = smallpox of the cow). The article goes on to explain how the meanings of the terms have since expanded: https://en.m.wikipedia.org/wiki/Inoculation https://en.m.wikipedia.org/wiki/Inoculation
    - twic 6y ago
      I suppose the analogue of Jenner's cowpox innoculations would be infecting people with coronaviruses other than SARS-CoV-2 and hoping that the cross-immunity is helpful. There is evidence for such cross-immunity, but not strong enough for this to be a strategy you'd bet on.
peterwwillis 6y ago
Some things to note about variolation wrt Coronavirus: - About a 2% death rate when used with Smallpox (compared to 20-30% without variolation), so we could expect mortalities from variolation with Coronavirus. - You actually get infected with the virus, and are contagious, though the effects are lowered and you gain an immunity to the stronger/regular virus. So you'd still need to self-quarantine and people would need to still wear masks/do social distancing and close places with lots of people.
- zbjornson 6y ago
  There's no reason to expect any parallels between variolation with these two unrelated viruses.
  - ggreer 6y ago
    If you read Robin Hanson's blog post on the topic[1], he found data on other diseases: > The most directly relevant data is on SARS[2] and measles[3], where natural differences in doses were associated with factors of 3 and 14 in death rates, and[4] in[5] smallpox, where in the 1700s low “variolation” doses given on purpose cut death rates by a factor of 10 to 30. It looks like the initial dose size has a huge impact on mortality for a wide range of diseases. 1. http://www.overcomingbias.com/2020/03/variolation-may-cut-covid19-deaths-3-30x.html http://www.overcomingbias.com/2020/03/variolation-may-cut-co... 2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367618/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367618/ 3. https://pubmed.ncbi.nlm.nih.gov/3723239/ https://pubmed.ncbi.nlm.nih.gov/3723239/ 4. https://www.nlm.nih.gov/exhibition/smallpox/sp_variolation.html https://www.nlm.nih.gov/exhibition/smallpox/sp_variolation.h... 5. https://www.npr.org/sections/goatsandsoda/2018/02/01/582370199/whats-the-real-story-about-the-milkmaid-and-the-smallpox-vaccine https://www.npr.org/sections/goatsandsoda/2018/02/01/5823701...
kauffj 6y ago
Robin Hanson has a been a strong proponent of this idea. If you're curious about this subject, this post is a must read: http://www.overcomingbias.com/2020/03/variolation-may-cut-covid19-deaths-3-30x.html http://www.overcomingbias.com/2020/03/variolation-may-cut-co...
- beepboopbeep 6y ago
  This man is claiming that staying at home increases deaths... He's also claiming a vaccine could be years away. I also see zero evidence as to why he should be considered a credible source for effective covid treatments. The man is an economist at a university. Am I looking at the wrong Robin Hanson?
  - skosch 6y ago
    You've got the right Robin Hanson. The key argument is that there is lots of uncertainty, but variolation is probably worth trying. And if volunteers can be found, why not? One shouldn't need to be a virologist to credibly make that argument.
    - zbjornson 6y ago
      Well, for one, orthopoxviruses cause skin lesions, replicate in keratinocytes, dermal fibroblasts and other skin cells and evoke strong immune responses there. Coronaviruses don't.
      - pmayrgundter 6y ago
        I've been looking into this.. you might be interested in my work on a Live Virus Skin Vaccine for CoV2. Comments welcome! https://docs.google.com/document/d/1x91Ef7G6xbm77DcRDvjAXbFmkn6jklTf_4-U_aepDbQ/edit https://docs.google.com/document/d/1x91Ef7G6xbm77DcRDvjAXbFm...
    - powersnail 6y ago
      I'm not a medicine professional, so I'm just curious here. Since variolation has basically the same principle as vaccination, it's hardly an alternative to vaccination. Is it really worth trying? To me (with my very crude understanding), proposing variolation as an alternative to vaccination is akin to proposing knife without a handle as an alternative to a regular knife. Is there any case where vaccination fails to work, while variolation succeed?
marcosdumay 6y ago
Isn't discovering a good dosage and application frequency for this just as hard as testing a vaccine?
- acqq 6y ago
  It's actually even harder, as the starting point is much, much worse. That's the reason the modern vaccines were developed: they are much safer from the very start. We simply know much more today than at these times, so we can know (almost) exactly what is going on in the building blocks, and actually use the building blocks and track the effects of the building block without ever having the risk of having to handle and manage the more dangerous thing -- the complete, fully functioning and easy to spread virus -- applying it to every human that we want to "protect". In analogy world for the modern vaccines, imagine a science fiction scenario: the evil aliens look like humans, can and want to easily kill them, but look exactly like humans and we don't know how to recognize them. Variolation is like catching them but them setting them free to go around and kill more in order to train us, expecting that it is possible to set free small enough number of them over and over so that in the fight we will "manage somehow" to win and also learn something while fighting, wheres, producing modern vaccines is like just finding out that the evil aliens look differently in infrared light and just teaching us to use infrared cameras to locate them, completely avoiding the real additional fights among the population "just for training." Variolation, as defined in the article, was the best method that we knew a few centuries ago, but now we simply know much more now. And solving the problem is still complicated enough even with the "better start." We want to minimize false alarms, friendly fire etc. practically, we know what we want and how to measure it and we do all we can to minimize the number of bad outcomes.
- zozbot234 6y ago
  Right, and scaling it up to a large population is just as hard as making vaccines. Not much reason for variolation nowadays.
  - davidw 6y ago
    The 'reason' for variolation is for people like the aforementioned Robin Hanson to get attention by suggesting something controversial.
alkonaut 6y ago
Variolation is a form of vaccination like any other (a treatment given to healthy individuals) so is subject to all the safety requirements of any other vaccine. So its an idea for a vaccine but it's not a magical shortcut compared to all the other vaccines under development (some of which are based on attenuated virus).
ttfkam 6y ago
Epidemiologists and virologists have literally dedicated their lives to effectively containing and dealing with infectious agents. Other medical doctors have focused at least a decade of intense study on the human body and the processes by which human life perpetuates and ends. But by all means, let's all presume that an economist like Robin Hanson—whose primary interest it would seem to be opening up commerce during a pandemic—has somehow come up with an idea that has escaped the notice of that entire segment of the population dedicated to human health. Let's ask Mike Pence about his thoughts on the use of bloom filters as relational database indexes while we're at it. I'm sure he'll point out that mauve seems to have the most RAM. Sure, experts can have blind spots, but c'mon!
- djaque 6y ago
  I'm a physicist and I cringed hard when the HEP people in my department started pushing out arXiv papers about covid-19. I see this a lot in CS too. It's easy for people in these more abstract fields to look at another problem space and see patterns that remind them of their own work. They seem to discount experience and familiarity.
  - ttfkam 6y ago
    People always want to believe the Dunning-Kruger Effect applies only to other people.
    - djaque 6y ago
      Hahahaha... I guess that's one way to put it.
- cameldrv 6y ago
  Sometimes you need an outsider. I don't think that the issue with this is scientific -- basically we know that it might work, but we'd have to test it to know. The problem is that medical ethics deviates from everyday ethics, and also ethics in other government regulated fields. This is mostly the legacy of Josef Mengele and to some extent the Tuskegee experiment, but collectively we essentially said "we never want to do that again, so let's make rules that keep us well away from that line." The reason the idea isn't getting much attention is that anyone in the field that is serious knows that the study would never get past an Institutional Review Board, so it's pointless to even try. It seems to me that we need to revisit our tenets of medical ethics in borderline cases like this one, where the stakes are so high. To me, you should be able to do riskier experiments in these cases if the subjects are truly informed volunteers, and you keep the risk to them to an absolute minimum consistent with doing the experiment. There's a very similar issue with vaccine challenge trials.
Cactus2018 6y ago
The part that stood out to me is: > Doctors sought to monopolize the simple treatment by convincing the public that the procedure could only be done by a trained professional. The procedure was now preceded by a severe bloodletting, in which the patient was bled, often to faintness, in order to 'purify' the blood and prevent fever. Doctors also began to favour deep incisions [versus superficial scratches], which also discouraged amateurs.
vikramkr 6y ago
Variolation refers specifically to smallpox. The terminology for a similar approach against COVID is "inoculation" not "variolation." I understand the proponent of it for COVID is an economist and not a medical professional, but keeping the terminology clear is important to avoid confusion. Inoculation is not guaranteed to be effective against covid. Just because there was a version of it called variolation that worked against smallpox before being eliminated because it was not as good as other approaches does not mean inoculation is automatically safe and effective against a completely unrelated virus. Other coronavirus are known to display antibody dependent enhancement, where a weak immune response makes following infections worse, and we already don't see consistent, strong responses from people who were sick. What the economist Hanson is essentially suggesting is that we take a worse method of immunization (just the normal live virus) and waive the regulatory burden to show safety and efficacy because a similar approach worked with smallpox. If we are getting into the business of ignoring the requirement for an immunization approach to be clinically validated, then there are a few dozen vaccines with far better theoretical safety and efficacy profiles that we should be using instead. The reason a vaccine isn't coming immediately is because we have to show they wont kill people and that they'll work, and then we have to scale up production. You dont get to rebrand your worse vaccine approach as "variolation" and then say it should be held to a different standard so you can get the economy humming again.
- pmayrgundter 6y ago
  Thanks for making the point about the name. I got in touch with Hanson after his blog post[1] and co-authored a proposal with Hanson and three doctors on low-dose inoculation of respiratory system, gut or skin[2]. We ended up not using the name Variolation since it has too many connotations and it's necessary to distinguish modes of inoculation for vaccination. I think Hanson's blog post[1] about the general idea of variolation was useful to get discussion going but agree that as stated it was not a good approach. In contrast, the proposal we developed subsequently focused on making use of human challenge trials[3] (where the control arm of the clinical trial is actively exposed to the pathogen) to search for safer forms of inoculation, hopefully benign. I disagree with your point that live virus is necessarily a worse form of immunization; I think it actually depends on the route of inoculation and on finding a reasonable dose. I am working on the skin route separately[4] and from this I've learned live-viruses are used in some (many?) of the most successful vaccines (adeno, polio, measles, smallpox)[See appendix in 4.1]. In polio and measles the virus was attenuated, but in the case of adenovirus, it's used in its original wild-type form and inoculated into the gut via oral dose to avoid the primary respiratory infection. Adenovirus is also notable for comparison as it causes an ARDS-like condition and the gut infection (benign diarrhea and fever) was considered secondary and acceptable enough that the US Military doses all recruits this way since the 80s. And although smallpox variolation had relatively high mortality rates, it's unclear how specific the methods in use were. It's possible that the primary (respiratory!) infection wasn't avoided e.g. by the methods of scab snuff (ew!). Lastly, non-live virus vaccines may not provoke a sufficient immune response, e.g. in the killed polio vaccine that was eventually retired. I think this is generally a concern for potential synthetic CoV vaccines as well. So it seems like the idea from smallpox and adenovirus is to inoculate where the body has a good chance of dealing with the infection (skin and gut, respectively) when the primary infection (respiratory in both cases) is dangerous and there aren't better alternatives. I'm working on the skin route since it seems plausible (it appears skin can be infected by CoV2) and the least risky (almost all reports of associated infections are benign; though there are some reports of skin tissue necrosis). The gut route is also interesting but in my opinion we're too early in the clinical understanding to prioritize it since it is often associated with the primary infection. I'm just starting to treat this as an open-source project[5]. Please feel free to join! [1] "Variolation (+ Isolation) May Cut Covid19 Deaths 3-30X" http://www.overcomingbias.com/2020/03/variolation-may-cut-covid19-deaths-3-30x.html http://www.overcomingbias.com/2020/03/variolation-may-cut-co... [2] "Targeted Immunization of Low-Risk Individuals Using a Low-Dose Inoculation (LDI)" - https://docs.google.com/document/d/1gSj-mrjFwswU35RzBnkjTt9Ep_OQNGIwcD9HyNlDSdg/edit https://docs.google.com/document/d/1gSj-mrjFwswU35RzBnkjTt9E... [3] https://academic.oup.com/jid/article/221/11/1752/5814216 https://academic.oup.com/jid/article/221/11/1752/5814216 [4] "SARS-CoV2 Live Virus Skin Vaccine" - https://tinyurl.com/y8ujrcze https://tinyurl.com/y8ujrcze [4.1] "Appendix: Live Virus Vaccines" - https://tinyurl.com/y8ujrcze#heading=h.wpx27u7fe2kp https://tinyurl.com/y8ujrcze#heading=h.wpx27u7fe2kp [5] https://sites.google.com/view/open-vax https://sites.google.com/view/open-vax

104 points by Cactus2018 6y ago

Amusingly, this is one of the few cases where - extremely broadly - one general idea of homeopathy works: you're basically just microdosing virus. This is amusing because a lot of anti-vaxxers (at least in Germany) will also be into homeopathy. There's possibly a good pro-vax-comms strategy in here: reframe vaccines as homeopathic viral microdoses (instead of complicated pharmaceutical compounds) and you might save a few kids.

kevin_b_er 6y ago
That might increase belief in homeopathy, which is bad too. Homeopathy beliefs are that the stronger the dilution, the more powerful the medication. Homeopathy would be diluting the virus to the point where there's a strong probability of zero virus particles remaining in the "medicine" because of the belief the water has the memory of the virus. This is false, because homeopathy has no effect other than placebo and placebo does not stop covid 19 deaths.
- DataWorker 6y ago
  Any cite for your claim placebo can’t prevent a covid death? That seems unlikely given how powerful and common the placebo effect seems to be.
yetihehe 6y ago
But this has a side effect of supporting homeopathy. I'd prefer we found some better way to educate people.
PeterStuer 6y ago
Not really. Homeopathy assumes that which causes likewise symptoms to be a candidate for cure, while here it is the idea of microdosing the disease, which hopefully would not case symptoms like the full blown disease, and the second tenant of homeopathy, the dilutions increase potency, would also hopefully be absent as that would be like the viral load factor, but in reverse.
- yetihehe 6y ago
  You are using facts. This is not very effective (against antivaxers and homeopathy enthusiasts).
  - cmendel 6y ago
    Facts are very effective against homeopaths, you just have to dilute them 100x first.
  - mistermann 6y ago
    Upon what evidence is this generalized statement based? Did you fact check it? Note: I pose this question not as snark, or as some sort of a "disproof" of the "general truthiness" of your statement (with which I do not disagree, fwiw), but 100% literally.
- inimino 6y ago
  A tenant is someone who resides in a building, tenet is the word you want.
  - PeterStuer 6y ago
    Thx. Many errors in that post, but beyond an edit now.
jhbadger 6y ago
Although vaccines aren't the same thing as variolation, and were developed because of the inherent risks of microdosing a dangerous pathogen. They are called "vaccines" because of the use of cowpox (a virus related to but much less dangerous than smallpox) in Jenner's vaccine and cow is "vacca" in Latin (similar to modern Spanish vaca).
np_tedious 6y ago
You're definitely on to something. I couldn't find the original source, but this FB comment has become something of a meme https://twitter.com/Golfergirl2018/status/1216905848179609600?s=19 https://twitter.com/Golfergirl2018/status/121690584817960960... > I am not anti-vax, but I understand why some parents do not want chemicals in their childrens bodies. I think instead of chemical shots, doctors should give a very small amount of the virus so the body can build up immunity.

kh_hk 6y ago

https://en.wikipedia.org/wiki/Balmis_Expedition https://en.wikipedia.org/wiki/Balmis_Expedition

barrald 6y ago

For anyone else watching The Great, Catherine's interest in variolation is apparently a true story: https://smarthistoryblog.com/2016/10/05/catherine-the-great-risked-her-life-for-science/ https://smarthistoryblog.com/2016/10/05/catherine-the-great-...

40four 6y ago
Fascinating. Since I never paid attention in history class, I'll admit The Great did remind me of this practice. It's interesting people were experimenting with techniques likes this so long ago, when their understanding of medical science was so rudimentary compared to today.
jcroll 6y ago
It was also done in the HBO John Adams miniseries

OJFord 6y ago

These aren't to me the clearest Wikipedia pages, but I think I now understand that - in modern usage, ignoring origins - vaccination and inoculation are both types of immunisation; the latter using a sample of the thing to immunise against, while a vaccine is actually strictly speaking immunisation through other means, some other substance to the thing that should be immunised against? I suppose I thought they were synonyms, but I certainly thought a vaccine was 'a bit of' the thing to immunised against, despite remembering Jenner and his cow.

war1025 6y ago
> certainly thought a vaccine was 'a bit of' the thing to immunised against A lot of the original vaccines were made from deactivated viruses. I don't know how that process works exactly, but your understanding isn't far off at least for how they were originally produced.
- twic 6y ago
  A lot still are. Sinopharm (the two "Institutes of Biological Products") and Sinovac are both developing inactivated virus vaccines for COVID-19: https://www.who.int/blueprint/priority-diseases/key-action/novel-coronavirus-landscape-ncov.pdf https://www.who.int/blueprint/priority-diseases/key-action/n...
- Cactus2018 6y ago
  >> were made from deactivated viruses. I don't know how that process works exactly Check out the history of the Rabies vaccine, where the virus was weakened through aging: > derived from the spinal cord of an inoculated rabbit which had died of rabies 15 days earlier. https://en.wikipedia.org/wiki/Rabies_vaccine#History https://en.wikipedia.org/wiki/Rabies_vaccine#History > A vaccine typically contains an agent that resembles a disease-causing microorganism and is often made from weakened or killed forms of the microbe, its toxins, or one of its surface proteins. https://en.wikipedia.org/wiki/Inactivated_vaccine https://en.wikipedia.org/wiki/Inactivated_vaccine > The virus is killed using a method such as heat or formaldehyde. > Whole virus vaccines use the entire virus particle, fully destroyed using heat, chemicals, or radiation. > Split virus vaccines are produced by using a detergent to disrupt the virus. > Subunit vaccines are produced by purifying out the antigens that best stimulate the immune system to mount a response to the virus, while removing other components necessary for the virus to replicate or survive or that can cause adverse reactions

gerland 6y ago

Additional trivia - Benjamin Franklin was a big proponent of inoculation. He tried to spread the awarness and convince people that it's safe and effective. Unfortunately his first son died of smallpox before he could be inoculated. He was 4 and developed some other infection, so BJ decided to wait with inoculation. Before he could perform it, he contracted the disease. It was huge blow to the credibility of BJ claims about inoculation, but he continued his mission nevertheless.

peterwwillis 6y ago
Claims about variolation/inoculation, not vaccination. Vaccines were discovered 6 years after Franklin's death.
ptaipale 6y ago
I think it is somewhat incorrect to call this vaccination, because the proper term for what was available in Benjamin Franklin's time was variolation, or inoculation.
- elliekelly 6y ago
  An interesting tidbit about the origin of two terms from Wikipedia: > Until the very early 1800s, inoculation referred only to the practice of variolation, the predecessor to the smallpox vaccine. Edward Jenner introduced the latter in 1798, when it was called cowpox inoculation, or vaccine inoculation (from Latin vacca = cow). Smallpox inoculation continued to be referred to as variolation (from variola = smallpox), whereas cowpox inoculation was referred to as vaccination (from Jenner's use of variolae vaccinae = smallpox of the cow). The article goes on to explain how the meanings of the terms have since expanded: https://en.m.wikipedia.org/wiki/Inoculation https://en.m.wikipedia.org/wiki/Inoculation
  - twic 6y ago
    I suppose the analogue of Jenner's cowpox innoculations would be infecting people with coronaviruses other than SARS-CoV-2 and hoping that the cross-immunity is helpful. There is evidence for such cross-immunity, but not strong enough for this to be a strategy you'd bet on.

peterwwillis 6y ago

Some things to note about variolation wrt Coronavirus: - About a 2% death rate when used with Smallpox (compared to 20-30% without variolation), so we could expect mortalities from variolation with Coronavirus. - You actually get infected with the virus, and are contagious, though the effects are lowered and you gain an immunity to the stronger/regular virus. So you'd still need to self-quarantine and people would need to still wear masks/do social distancing and close places with lots of people.

zbjornson 6y ago
There's no reason to expect any parallels between variolation with these two unrelated viruses.
- ggreer 6y ago
  If you read Robin Hanson's blog post on the topic[1], he found data on other diseases: > The most directly relevant data is on SARS[2] and measles[3], where natural differences in doses were associated with factors of 3 and 14 in death rates, and[4] in[5] smallpox, where in the 1700s low “variolation” doses given on purpose cut death rates by a factor of 10 to 30. It looks like the initial dose size has a huge impact on mortality for a wide range of diseases. 1. http://www.overcomingbias.com/2020/03/variolation-may-cut-covid19-deaths-3-30x.html http://www.overcomingbias.com/2020/03/variolation-may-cut-co... 2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367618/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367618/ 3. https://pubmed.ncbi.nlm.nih.gov/3723239/ https://pubmed.ncbi.nlm.nih.gov/3723239/ 4. https://www.nlm.nih.gov/exhibition/smallpox/sp_variolation.html https://www.nlm.nih.gov/exhibition/smallpox/sp_variolation.h... 5. https://www.npr.org/sections/goatsandsoda/2018/02/01/582370199/whats-the-real-story-about-the-milkmaid-and-the-smallpox-vaccine https://www.npr.org/sections/goatsandsoda/2018/02/01/5823701...

kauffj 6y ago

Robin Hanson has a been a strong proponent of this idea. If you're curious about this subject, this post is a must read: http://www.overcomingbias.com/2020/03/variolation-may-cut-covid19-deaths-3-30x.html http://www.overcomingbias.com/2020/03/variolation-may-cut-co...

beepboopbeep 6y ago
This man is claiming that staying at home increases deaths... He's also claiming a vaccine could be years away. I also see zero evidence as to why he should be considered a credible source for effective covid treatments. The man is an economist at a university. Am I looking at the wrong Robin Hanson?
- skosch 6y ago
  You've got the right Robin Hanson. The key argument is that there is lots of uncertainty, but variolation is probably worth trying. And if volunteers can be found, why not? One shouldn't need to be a virologist to credibly make that argument.
  - zbjornson 6y ago
    Well, for one, orthopoxviruses cause skin lesions, replicate in keratinocytes, dermal fibroblasts and other skin cells and evoke strong immune responses there. Coronaviruses don't.
    - pmayrgundter 6y ago
      I've been looking into this.. you might be interested in my work on a Live Virus Skin Vaccine for CoV2. Comments welcome! https://docs.google.com/document/d/1x91Ef7G6xbm77DcRDvjAXbFmkn6jklTf_4-U_aepDbQ/edit https://docs.google.com/document/d/1x91Ef7G6xbm77DcRDvjAXbFm...
  - powersnail 6y ago
    I'm not a medicine professional, so I'm just curious here. Since variolation has basically the same principle as vaccination, it's hardly an alternative to vaccination. Is it really worth trying? To me (with my very crude understanding), proposing variolation as an alternative to vaccination is akin to proposing knife without a handle as an alternative to a regular knife. Is there any case where vaccination fails to work, while variolation succeed?

marcosdumay 6y ago

Isn't discovering a good dosage and application frequency for this just as hard as testing a vaccine?

acqq 6y ago
It's actually even harder, as the starting point is much, much worse. That's the reason the modern vaccines were developed: they are much safer from the very start. We simply know much more today than at these times, so we can know (almost) exactly what is going on in the building blocks, and actually use the building blocks and track the effects of the building block without ever having the risk of having to handle and manage the more dangerous thing -- the complete, fully functioning and easy to spread virus -- applying it to every human that we want to "protect". In analogy world for the modern vaccines, imagine a science fiction scenario: the evil aliens look like humans, can and want to easily kill them, but look exactly like humans and we don't know how to recognize them. Variolation is like catching them but them setting them free to go around and kill more in order to train us, expecting that it is possible to set free small enough number of them over and over so that in the fight we will "manage somehow" to win and also learn something while fighting, wheres, producing modern vaccines is like just finding out that the evil aliens look differently in infrared light and just teaching us to use infrared cameras to locate them, completely avoiding the real additional fights among the population "just for training." Variolation, as defined in the article, was the best method that we knew a few centuries ago, but now we simply know much more now. And solving the problem is still complicated enough even with the "better start." We want to minimize false alarms, friendly fire etc. practically, we know what we want and how to measure it and we do all we can to minimize the number of bad outcomes.
zozbot234 6y ago
Right, and scaling it up to a large population is just as hard as making vaccines. Not much reason for variolation nowadays.
- davidw 6y ago
  The 'reason' for variolation is for people like the aforementioned Robin Hanson to get attention by suggesting something controversial.

alkonaut 6y ago

Variolation is a form of vaccination like any other (a treatment given to healthy individuals) so is subject to all the safety requirements of any other vaccine. So its an idea for a vaccine but it's not a magical shortcut compared to all the other vaccines under development (some of which are based on attenuated virus).

ttfkam 6y ago

Epidemiologists and virologists have literally dedicated their lives to effectively containing and dealing with infectious agents. Other medical doctors have focused at least a decade of intense study on the human body and the processes by which human life perpetuates and ends. But by all means, let's all presume that an economist like Robin Hanson—whose primary interest it would seem to be opening up commerce during a pandemic—has somehow come up with an idea that has escaped the notice of that entire segment of the population dedicated to human health. Let's ask Mike Pence about his thoughts on the use of bloom filters as relational database indexes while we're at it. I'm sure he'll point out that mauve seems to have the most RAM. Sure, experts can have blind spots, but c'mon!

djaque 6y ago
I'm a physicist and I cringed hard when the HEP people in my department started pushing out arXiv papers about covid-19. I see this a lot in CS too. It's easy for people in these more abstract fields to look at another problem space and see patterns that remind them of their own work. They seem to discount experience and familiarity.
- ttfkam 6y ago
  People always want to believe the Dunning-Kruger Effect applies only to other people.
  - djaque 6y ago
    Hahahaha... I guess that's one way to put it.
cameldrv 6y ago
Sometimes you need an outsider. I don't think that the issue with this is scientific -- basically we know that it might work, but we'd have to test it to know. The problem is that medical ethics deviates from everyday ethics, and also ethics in other government regulated fields. This is mostly the legacy of Josef Mengele and to some extent the Tuskegee experiment, but collectively we essentially said "we never want to do that again, so let's make rules that keep us well away from that line." The reason the idea isn't getting much attention is that anyone in the field that is serious knows that the study would never get past an Institutional Review Board, so it's pointless to even try. It seems to me that we need to revisit our tenets of medical ethics in borderline cases like this one, where the stakes are so high. To me, you should be able to do riskier experiments in these cases if the subjects are truly informed volunteers, and you keep the risk to them to an absolute minimum consistent with doing the experiment. There's a very similar issue with vaccine challenge trials.

Cactus2018 6y ago

The part that stood out to me is: > Doctors sought to monopolize the simple treatment by convincing the public that the procedure could only be done by a trained professional. The procedure was now preceded by a severe bloodletting, in which the patient was bled, often to faintness, in order to 'purify' the blood and prevent fever. Doctors also began to favour deep incisions [versus superficial scratches], which also discouraged amateurs.

vikramkr 6y ago

Variolation refers specifically to smallpox. The terminology for a similar approach against COVID is "inoculation" not "variolation." I understand the proponent of it for COVID is an economist and not a medical professional, but keeping the terminology clear is important to avoid confusion. Inoculation is not guaranteed to be effective against covid. Just because there was a version of it called variolation that worked against smallpox before being eliminated because it was not as good as other approaches does not mean inoculation is automatically safe and effective against a completely unrelated virus. Other coronavirus are known to display antibody dependent enhancement, where a weak immune response makes following infections worse, and we already don't see consistent, strong responses from people who were sick. What the economist Hanson is essentially suggesting is that we take a worse method of immunization (just the normal live virus) and waive the regulatory burden to show safety and efficacy because a similar approach worked with smallpox. If we are getting into the business of ignoring the requirement for an immunization approach to be clinically validated, then there are a few dozen vaccines with far better theoretical safety and efficacy profiles that we should be using instead. The reason a vaccine isn't coming immediately is because we have to show they wont kill people and that they'll work, and then we have to scale up production. You dont get to rebrand your worse vaccine approach as "variolation" and then say it should be held to a different standard so you can get the economy humming again.

pmayrgundter 6y ago
Thanks for making the point about the name. I got in touch with Hanson after his blog post[1] and co-authored a proposal with Hanson and three doctors on low-dose inoculation of respiratory system, gut or skin[2]. We ended up not using the name Variolation since it has too many connotations and it's necessary to distinguish modes of inoculation for vaccination. I think Hanson's blog post[1] about the general idea of variolation was useful to get discussion going but agree that as stated it was not a good approach. In contrast, the proposal we developed subsequently focused on making use of human challenge trials[3] (where the control arm of the clinical trial is actively exposed to the pathogen) to search for safer forms of inoculation, hopefully benign. I disagree with your point that live virus is necessarily a worse form of immunization; I think it actually depends on the route of inoculation and on finding a reasonable dose. I am working on the skin route separately[4] and from this I've learned live-viruses are used in some (many?) of the most successful vaccines (adeno, polio, measles, smallpox)[See appendix in 4.1]. In polio and measles the virus was attenuated, but in the case of adenovirus, it's used in its original wild-type form and inoculated into the gut via oral dose to avoid the primary respiratory infection. Adenovirus is also notable for comparison as it causes an ARDS-like condition and the gut infection (benign diarrhea and fever) was considered secondary and acceptable enough that the US Military doses all recruits this way since the 80s. And although smallpox variolation had relatively high mortality rates, it's unclear how specific the methods in use were. It's possible that the primary (respiratory!) infection wasn't avoided e.g. by the methods of scab snuff (ew!). Lastly, non-live virus vaccines may not provoke a sufficient immune response, e.g. in the killed polio vaccine that was eventually retired. I think this is generally a concern for potential synthetic CoV vaccines as well. So it seems like the idea from smallpox and adenovirus is to inoculate where the body has a good chance of dealing with the infection (skin and gut, respectively) when the primary infection (respiratory in both cases) is dangerous and there aren't better alternatives. I'm working on the skin route since it seems plausible (it appears skin can be infected by CoV2) and the least risky (almost all reports of associated infections are benign; though there are some reports of skin tissue necrosis). The gut route is also interesting but in my opinion we're too early in the clinical understanding to prioritize it since it is often associated with the primary infection. I'm just starting to treat this as an open-source project[5]. Please feel free to join! [1] "Variolation (+ Isolation) May Cut Covid19 Deaths 3-30X" http://www.overcomingbias.com/2020/03/variolation-may-cut-covid19-deaths-3-30x.html http://www.overcomingbias.com/2020/03/variolation-may-cut-co... [2] "Targeted Immunization of Low-Risk Individuals Using a Low-Dose Inoculation (LDI)" - https://docs.google.com/document/d/1gSj-mrjFwswU35RzBnkjTt9Ep_OQNGIwcD9HyNlDSdg/edit https://docs.google.com/document/d/1gSj-mrjFwswU35RzBnkjTt9E... [3] https://academic.oup.com/jid/article/221/11/1752/5814216 https://academic.oup.com/jid/article/221/11/1752/5814216 [4] "SARS-CoV2 Live Virus Skin Vaccine" - https://tinyurl.com/y8ujrcze https://tinyurl.com/y8ujrcze [4.1] "Appendix: Live Virus Vaccines" - https://tinyurl.com/y8ujrcze#heading=h.wpx27u7fe2kp https://tinyurl.com/y8ujrcze#heading=h.wpx27u7fe2kp [5] https://sites.google.com/view/open-vax https://sites.google.com/view/open-vax