Making Vaccine

405
by johnswentworth 5 min read 3rd Feb 2021 125 comments

Coronavirus DIY Market Inefficiency Prac cal Frontpage

Back in December, I asked° how hard it would be to make a vaccine for oneself. Several
people pointed to radvac. It was a best-case scenario: an open-source vaccine design,
made for self-experimenters, dead simple to make with readily-available materials, well-
explained reasoning about the design, and with the name of one of the world’s more
competent biologists (who I already knew of beforehand) stamped on the whitepaper. My
girlfriend and I made a batch a week ago and took our rst booster yesterday.

is post talks a bit about the process, a bit about our plan, and a bit about motivations.
Bear in mind that we may have made mistakes - if something seems o , leave a comment.

e Process
All of the materials and equipment to make the vaccine cost us about $1000. We did not
need any special licenses or anything like that. I do have a little wetlab experience from
my undergrad days, but the skills required were pretty minimal.
 One vial of custom peptide - that little pile of
white powder at the bottom.

e large majority of the cost (about $850) was the peptides. ese are the main active
ingredients of the vaccine: short segments of proteins from the COVID virus. ey’re all
<25 amino acids, so far too small to have any likely function as proteins (for comparison,
COVID’s spike protein has 1273 amino acids). ey’re just meant to be recognized by the
immune system: the immune system learns to recognize these sequences, and that’s what
provides immunity.
 Each of six peptides came in two vials of 4.5 mg each. ese are the half we haven't dissolved; we
keep them in the freezer as backups.

e peptides were custom synthesized. ere are companies which synthesize any (short)
peptide sequence you want - you can nd dozens of them online. e cheapest options
su ce for the vaccine - the peptides don’t need to be “puri ed” (this just means removing
partial sequences), they don’t need any special modi cations, and very small amounts
su ce. e minimum order size from the company we used would have been su cient
for around 250 doses. We bought twice that much (9 mg of each peptide), because it only
cost ~$50 extra to get 2x the peptides and extras are nice in case of mistakes.

e only unusual hiccup was an email about customs restrictions on COVID-related

peptides. Apparently the company was not allowed to send us 9 mg in one vial, but could
send us two vials of 4.5 mg each for each peptide. is didn’t require any e ort on my
part, other than saying “yes, two vials is ne, thankyou”. Kudos to their customer service
for handling it.
 Equipment - stir plate, beakers, microcentrifuge tubes, 10 and 50 mL vials, pipette (0.1-1 mL
range), and pipette tips. It's all available on Amazon.

Other materials - these are sold as supplements. We also need such rare and costly ingredients as
vinegar and deionized water. Also all available on Amazon.
Besides the peptides, all the other materials and equipment were on amazon, food grade,
in quantities far larger than we are ever likely to use. Peptide synthesis and delivery was
the slowest; everything else showed up within ~3 days of ordering (it’s amazon, after all).

e actual preparation process involves three main high-level steps:

Prepare solutions of each component - basically dissolve everything separately, then

stick it in the freezer until it’s needed.
Circularize two of the peptides. Concretely, this means adding a few grains of
activated charcoal to the tube and gently shaking it for three hours. en, back in the
freezer.
When it’s time for a batch, take everything out of the freezer and mix it together.

Prepping a batch mostly just involves pipetting things into a beaker on a stir plate,
sometimes drop-by-drop.
Finally, a dose goes into a microcentrifuge tube. We stick the intake tube of a sprayer into
the tube, and inhale.
 at’s the process, at a high level. Multiple boosters are strongly recommended, so there’s
a few iterations of this, though only the “take stu out of the freezer and mix it together”
step needs to be repeated. See the whitepaper for the full protocol details, as well more
information about each of the peptides and what the other ingredients do (summary:
chitosan nanoparticles).
 e Plan
e key problem is how to check that the vaccine worked. If it were injected, that would
be easy: just get a standard COVID antibody test. Inhaling makes it a lot harder to hurt
yourself, but also complicates testing.

e whitepaper goes into more detail and half-a-dozen di erent types of immune
response, but the basic issue is that immunity response in the mucus lining (i.e. nose,
lung, airway surfaces) can occur independently of response in the bloodstream.
Commercial COVID antibody tests generally check a blood draw. In principle one can run
a similar antibody test on a mucus sample, but <reasons>, so the commercial tests check
blood.

(Side note: in many ways immunity in the mucus lining is better than in the blood, since it
blocks infection at the point where it’s introduced. is is an advantage of inhaled
vaccines over injected. So why do most commercial vaccines inject? Turns out logistics
are a major constraint on commercial vaccine design, and injections are surprisingly
easier logistically. One of the major relative advantages of radvac is that it’s intended to be
prepared on-site shortly before administration, so it can use techniques which work better
but don’t scale as well. at largely balances out the constraints of readily-available
materials and simple preparation. As usual, the whitepaper goes into much more detail on
this, including several other logistics-related relative advantages - multiple boosters,
custom peptides, frequent design updates, etc.)

e whitepaper claims that “over a hundred” researchers have self-administered the

vaccine so far, but I have not been able to nd any data on test results from any of them.
e paper says that inhaled vaccine can induce immunity in the blood, but I don’t have a
quantitative feel for how likely that is, other than the usual assumption that more dakka°
makes it more likely. Meanwhile, I don’t have a convenient way to test for immune
response other than the commercial tests.

So, the current plan is to search under the streetlamp°. We’ll just use the commercial
tests. Both of us got an antibody test before starting the project, and both came back
negative.

My current model is:

If the vaccine induces an immune response in the blood, then it almost certainly
induces one in the mucus lining, but the reverse does not hold. So a positive blood
antibody test means it de nitely works, a negative antibody test is a weak update
against.
 ere’s some chance that a few doses are more than enough to induce a blood
response.
ere’s some chance that more dakka will induce a blood response, even if the rst
few doses aren’t enough.

So, we’ll do (up to) two more blood tests. e rst will be two weeks after our third
(weekly) dose; that one is the “optimistic” test, in case three doses is more-than-enough
already. at one is optimistic for another reason as well: synthesis/delivery of three of the
nine peptides was delayed, so our rst three doses will only use six of them. If the
optimistic test comes back positive, great, we’re done.

If that test comes back negative, then the next test will be the “more dakka” test. We’ll add
the other three peptides, take another few weeks of boosters, maybe adjust frequency
and/or dosage - we’ll consider exactly what changes to make if and when the optimistic
test comes back negative. Risks are very minimal (again, see the paper), so throwing more
dakka at it makes sense.

Consider this a pre-registration. I intend to share my test results here.

Motivations
Why am I doing this?

I imagine, a year or two from now, looking back and grading my COVID response. When
I imagine an A+ response, it’s something like “make my own fast tests, and my own
vaccine, test that they actually work, and do all that in spring 2020”. We’ve all been
complaining about how “we” (i.e. society) should do these things, yet to a large extent
they’re things which we can do for ourselves unilaterally. Doing it for ourselves doesn’t
capture all the bene ts - lots of fun stu is still closed/cancelled - but it’s enough to go
out, socialize, and generally enjoy life without worrying about COVID.

I’ve written a blog post about Benjamin Jesty°, the dairy farmer who successfully
immunized his wife and kids against smallpox the same year that King Louis XV of France
died of the disease. I explicitly use this as an example of what Rationalism should strive to
consistently achieve. Yet when a near-perfect real world equivalent came along, on super-
easy mode with most of the work already done by somebody else, it still took me until
December to notice. e radvac vaccine showed up in my newsfeed back in July, and I
apparently failed to double-click. at level of performance is embarrassing, and I doubt
that I will grade my COVID response any higher than a D.
 So I’m doing this, in part, to condition the mental motions. To build the habit of Doing
is Sort Of ing, so next time I hopefully do better than a D.

Of course, the concrete bene ts are nice too. But at this point it’s only ~4 months until I’d
get a vaccine anyway, so the price tag is only arguably worthwhile. It’s still a fun project in
its own right, and it gets dramatically cheaper with more people (remember, $1000
bought enough supplies for ~500 doses). Concretely, the largest bene ts are in risk
reduction. If there’s big hiccups in commercial vaccine deployment, this becomes much
more worthwhile. If the South Africa strain turns out to evade commercial vaccines, this
becomes much more worthwhile - the radvac design is frequently updated based on the
latest COVID research, so we hopefully wouldn’t need to wait around for approval of a
new commercial vaccine.

Finally, I'm curious whether it will work - or whether we'll be able to tell that it works. It's
a data point as to just how often large bills are left sitting on sidewalks just a little ways o
the beaten path.

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[-] gwillen 2d 48
Do you have any thoughts on the risks/hazards involved here? To me that's a much more significant
considera on than the price. Some thoughts / priors:

Snor ng chemicals I got from the Internet / mixed up myself without really knowing what I was doing:
Superficially, seems poten ally pre y risky.
Snor ng pep des (assuming that the stuff ordered online was what it claimed to be, was pure and not
contaminated with anything hazardous, and that I didn't accidentally create anything hazardous in the
process): Definitely not as risky as snor ng arbitrary unknown substances. Seems unlikely to be directly
poisonous (although that's without reading about the other contents of the vaccine.)
Snor ng COVID-19 pep des, in par cular: Should I be worried about things like an body-dependent
enhancement? Are there other possible hazards specific to experimental vaccine administra on that I
should worry about? I'm sure the paper talks about this stuff, but I'm not a biologist so I can't promise I'd
understand it if I read it.
Is there a possibility that this vaccine is both ineffec ve, and interferes in some way with the
effec veness of subsequent administra on of a different vaccine?

... (read more)

Reply

[-] johnswentworth 2d 70
The main answer here is "see the paper"; there's a lot of discussion about this stuff. I'll summarize a few
points, as I understand them, relevant to your par cular thoughts.

The "snor ng chemicals" aspect is generally not much of an issue, since every ingredient other than the
pep des is food-grade, and the quan ty in a dose is ny (one dose is <1 mL, and most of that volume is
vinegar and water). If you were ea ng this stuff in your food and coughed on it, you'd probably get a
higher dose than what's in the vaccine.
Pep de synthesis services generally provide various quality control checks on the product (some free,
some upcharge). So at least you'll know what you're ge ng.
An body-dependent enhancement is one of the main things the paper discusses. It's pre y rare to
begin with, and the cases where it's happened have some pa erns to them which can be avoided; the
pep des are chosen to avoid those pi alls. Reading between the lines, it sounds to me like historical
cases were largely a by-product of historical vaccine techniques (e.g. a aching pieces of one virus to
the backbone of another in the case of Dengvaxia) which aren't used here.
As I understand it, interfer

... (read more)

Reply

[-] Den n 2d 23
Regarding the final paragraph, "you need some level of exper se yourself before you can dis nguish real
experts from fake": that has been the number one reason I didn't beat johnswentworth to the punch and
post first with my experience.

I have learned more about biochemistry in the last three months than in my en re prior life combined. It
has taken me three months of research, asking ques ons, and conferring with experts to get sufficient
confidence in my understanding to commit to the project.

I'm incredibly thankful to you (johnswentworth) for pos ng this ar cle; it tracks almost perfectly with my
understanding, and I have no significant model conflicts with any of your observa ons. It raises my
 confidence in both my understanding, and the project, substan ally.
Reply

6 johnswentworth 1d I'd be very interested in a post on what you learned! I relied mostly on gene…

[-] gwillen 2d 15
Thanks, I really appreciate you taking the me to respond.

I should probably have clarified my current views / epistemic status in my comment, since I think it sounded
more skep cal than I actually am. I would say it's something like: "I expect this is quite possibly a good idea,
and most probably at worst a neutral idea. I am interested in trying to elicit anything in the long tail of risks
that could change that."

(I guess I did also want to encourage other people to at least briefly consider risks before trying this
themselves -- although given the complexity and expense, perhaps I shouldn't worry that anybody might
rush to try it.)
Reply

[-] johnswentworth 2d 12
No worries, these are the right ques ons to ask and I'm glad someone brought them up.
Reply

[-] lincolnquirk 2d 25
I think a lot of these ques ons are answered in the radvac paper. I sent a copy of it to a biologist I know, and
asked if he thought it was crazy to do this, and he read it and said “geez this looks safer than doing drugs”. I
don’t have enough exper se to add anything beyond that.
Reply

5 gwillen 2d Thanks, that's helpful (and hilarious.) I am looking through the paper now, and it defini…

[-] AllAmericanBreakfast 2d 32
I double-cruxed this ar cle because my "voice of cau on" objected to it.

I eventually realized the issue was that part of my decision-making process when I do something weird,
poten ally risky, or expensive, is to consult with friends and family. Yet I feel that the feedback I would get from
them would be so thoughtless, nega ve, frustra ng, and poten ally damaging, that it's not worthwhile. And I
don't want to ignore this "consult someone first" rule, because it seems like a generally good rule that loses its
force if ignored.

However, I do know some specific people who might be good to talk it over with. They're warm, open-minded,
very smart, scien fically literate, unconven onal, have my best interests in mind, trustworthy, and willing to
discuss this kind of stuff at length. My next move is probably not to read the paper, but rather to discuss it with
them.
Reply

[-] JenniferRM 1d 21
I think what you have done here is re-invented the actual helpful version of a prac ce whose authoritarian
bureaucra c cargo-culted version is called "anonymous peer review".

It is easy (and maybe dangerously wrong) to come to the straigh orward conclusion that peer review in
general is simply evil bullshit... un l one finds the place from which a benevolent truth-oriented human (like
oneself) finds a reason to consult with an actual "epistemic peer" as a prudent and socially-embedded
response to one's own uncertainty about things one cares about.
 Reply

[-] Den n 2d 32
Speak of the devil. I literally just placed my pep de order a couple of hours ago. My experience (finding
supplies, test runs of mixing the solu on, safety profile, analysis, etc.) basically matches up with this post.

Thanks a lot for pos ng it.

Reply

[-] JenniferRM 2d 30
You have my admira on, and my hope that you are calcula ng the risks accurately!

I have not read the RaDVaC paper so I don't have a good object level model of safety and risks. From a distance
it looks like heroism, because from a distance it looks like taking a risk in a way that could provide a role model
for many if it works safely! It reminds me a bit of Seth Roberts who was a part of the extended tribe who did
awesome stuff over and over again (seemingly safely) but who also may have eventually guessed wrong about
safety.

I guess I just want to say: "This is so freaking awesome, and PLEASE be very careful, and also please keep going
if the risks seem worth the benefits."

If you get a posi ve an body result, have you thought about a personal challenge trial?

The big benefits to be gained from vaccina on seem to be to be behavioral: going out, doing life similarly to the
Before Times... which is similar to a par al/random/natural sort of "challenge trial".

I wonder if 1daysooner can or would be interested in keeping track of people who have tried the RaDVaC
op on, to build up knowledge (based on accidental exposures or inten onal challenges) of some sort.
Reply

[-] jsteinhardt 1d 28
Have you run this by a trusted bio expert? When I did this test (picking a bio person who I know personally, who
I think of as open-minded and fairly smart), they thought that this vaccine is pre y unlikely to be effec ve and
that the risks in this ar cle may be understated (e.g. food grade is lower-quality than lab grade, and it's not
obvious that inhaling food is completely safe). I don't know enough biology to evaluate their argument, beyond
my respect for them.

I'd be curious if the author, or others who are considering trying this, have applied this test.

My (fairly uninformed) es mates would be:

- 10% chance that the vaccine works in the abstract
- 4% chance that it works for a given LW user
- 3% chance that a given LW user has an adverse reac on
-12% chance at least 1 LW user has an adverse reac on

Of course, from a selfish perspec ve, I am happy for others to try this. In the 10% of cases where it works I will
be glad to have that informa on. I'm more worried that some might substan ally overes mate the benefit and
underes mate the risks, however.
Reply

[-] Den n 12h 14

 In my case, yes. My bio expert indicated that it was likely to be effec ve (more than 50%, but less than 90%)
and that the risks were effec vely zero in terms of serious complica ons.

Regarding the food grade versus lab grade ques on, as well as inaccuracies or mistakes in construc on of the
vaccine, this was a ques on I spent a reasonable amount of me on. The TL/DR is that the engineering
tolerances are incredibly wide; the molecular weight of the chitosan isn't that important, the mixing rate isn't
that important other than it be fast enough, the quan es aren't that important, exact pep de quan es
aren't that important etc. A lot of these can be off by not just percentage points, but integer factors, and the
result will s ll be acceptable.

It's also worth poin ng out that unless you make serious, significant mistakes that drama cally impair
effec veness, you can always just use "more dakka" to overpower the varia ons. My plan is to mix each
batch independently, such that at least some of the construc on varia ons are expected to cancel. (Also,
freezing the final vaccine is likely to impair effec veness, from what li le I've found on the topic.)
Reply

[-] benjaminikuta 2d 28
I was banned from r/neoliberal for sharing this.

"Spreading dangerous medical informa on"

Reply

[-] Yoav Ravid 2d 25

I think dele ng it was a fair response (though perhaps banning is a li le over the top). assuming the
moderator has no way of checking for himself whether this makes sense and he knows he doesn't, he's le
with a bet about whether this is the real thing or just bullshit. he expects more bullshit than real things, and
he expects the bullshit to be dangerous. so he removes everything that fits this class of things, knowing he
might end up also removing something real.
Reply

5 jimmy 1d I think this is inaccurately charitable. It's never the case that a moderator has "no way" …
4 Yoav Ravid 19h I agree i was being charitable. and yes, i was talking specifically about my expect…
4 Den n 2d I agree as well. It takes a non-trivial amount of knowledge and research to evaluate the…
4 benjaminikuta 2d Even with a Harvard professor as an author?

[-] Yoav Ravid 2d 13

It depends more on the ignorance of the moderator and on how much me he's willing to spend than on
the quality of the evidence. there definitely are cases of of PHDs and maybe even professors advancing
pseudoscience. so this doesn't guarantee trustworthiness.

the moderator has to make a decision in a state where he can't trust himself to dis nguish real stuff from
bullshit. he goes for minimizing harm at the cost of dele ng novel good ideas. seems like a sensible
decision to me.
Reply

2 benjaminikuta 1d How o en do scholars of such prominence promote dangerous pseudoscien…

[-] jsteinhardt 1d 10
O en, e.g. Stanford profs claiming that COVID is less deadly than the flu for a recent and related
example.
Reply
 1 Yoav Ravid 19h Interes ng ques on, i don't know. but it also doesn't ma er here. if the mod…
5 Den n 12h Again, I have to disagree - misinforma on is much more likely than informa on …
1 Yoav Ravid 12h I agree with that. not sure what you think i meant that you disagree with i…
2 Den n 20m Sorry about that; I believe I misread your comment as implying that if the m…

2 Chris anKl 1d I think there's a difference here between sharing a link to RadVac and sharing a li…

5 AI_WAIFU 18h I wouldn't look too deeply into that. The selec on process for moderators on reddit …

[-] Raemon 2d Moderator Comment 27

Note: this post was frontpaged (despite a general policy of not frontpaging covid content) both because a) it
seems pre y important, and b) the ra onality life lessons seemed pre y meless.
Reply

[-] jsteinhardt 1d 23
Hmm, important as in "important to discuss", or "important to hear about"?

My best guess based on talking to a smart open-minded biologist is that this vaccine probably doesn't work,
and that the author understates the risks involved. I'm interpre ng the decision to frontpage as saying that
you think I'm wrong with reasonably high confidence, but I'm not sure if I should interpret it that way.
Reply

[-] johnswentworth 1d 13
You should make a top-level comment about this. Chance that the vaccine works and the associated risks are
object-level ques ons well-worth discussing.

In general, frontpage decisions are not endorsements (though I don't know Raemon's thoughts in this
par cular case), and this comment sec on is not the place for a debate about frontpaging norms. This is
definitely the place to talk about chance the vaccine works and associated risks, though.
Reply

6 jsteinhardt 1d I don't think I was deba ng the norms, but clarifying how they apply in this case. …
4 johnswentworth 1d Yeah, I don't mean to say your comment was bad as-wri en, just preemp…
4 jsteinhardt 1d Ah got it, thanks!

[-] AllAmericanBreakfast 2d 21
Vaccines that are brought to clinical trials have a 33.4% approval rate, which seems like a reasonable es mate
of the chances that this vaccine works if executed correctly. Note that this is from trials conducted from 2000-
2015.

I probably have a roughly 5% chance of catching COVID before I'm vaccinated. Given my age, COVID would put
me at a 0.2% risk of death. Let's double that to account for suffering and the risk of long-term disability.

If I value my life at $10,000,000, then an interven on that gives me a 33.4% chance of avoiding a 5% chance of
a 0.4% chance of death is worth $668. So it seems like I'd want to be vaccina ng at least one other person in
order for this to be worthwhile.

I welcome any further thoughts on this expected value calcula on. In par cular, I think it's possible that I'm
drama cally underes ma ng the risk and poten al severity of long-term symptoms. It doesn't take much
addi onal risk to make this project worthwhile for a single person.
Reply

[-] Den n 1d 16
Regarding the 33.4% approval rate: based on what I've learned about tradi onal vaccine development and
produc on in the last few months, I am not at all surprised. Both pep de and RNA vaccines are effec vely
"state of the art" technologies compared to tradi onal vaccine techniques. It's like comparing modern non-
invasive out-pa ent surgery to the 1970's equivalent.

You need look no further than the russian and chinese vaccines - those use the rather crude technology of
"throw big chunks of inac vated virus par cles at the immune system and hope that the immune system
guesses the right an bodies to deal with the live version."

Both pep de and RNA vaccines are instead, "we have iden fied very specific an bodies which we know are
effec ve both from the serum of recovered pa ents and from computa onal modeling, then use exactly the
minimal protein sequences needed to generate those an bodies."

Both the russian and chinese vaccines use chunks of proteins that are thousands (and likely tens of
thousands) of amino acids long, in a mostly inac vated form. The immune system has no idea what to latch
onto, what will be effec ve at stopping replica on, ... (read more)
Reply

4 Chris anKl 1d That seems to me like a strange statement. In what way are amino acids sequences…
3 TheSimplestExplana on 1d It's my impression that the pep des in ques on are the an gens to …
4 Den n 1d Yes; sorry I was unclear. Those pep des generate the an bodies we care about, that…
2 Chris anKl 1d It's unclear to me to what extend we know this and your descrip on looks to …

[-] Den n 13h 12

A lot of people have been working really hard for the last year to discover, understand, and know
these things. It's the founda on for how the mRNA vaccines work.

Perhaps take a look through this:

h ps://www.sciencedirect.com/science/ar cle/pii/S2319417020301530
Reply

2 Chris anKl 1h I seems my intui on is well-founded here. According to Sarah Constan n [h…
4 Den n 15m Sarah Constan n is confused, and likely has not spent significant me review…

1 TheSimplestExplana on 14h Do you have doubts? It seems plausible to me?

8 Chan Bae 2d Do you value your life at ten million? As in, would you take a 50% chance of death for …
4 AllAmericanBreakfast 1d Well, a couple of researchers es mated [h p:// p.iza.org/dp8224.pdf] …
3 Bucky 1d Say my life expectancy from now is 50 years and I work at an hourly salary of $30 (~$60…
5 Czynski 5h This is an inappropriate reference class. This has no in vitro tes ng conducted; it's en re…
4 AllAmericanBreakfast 4h I agree with the point of your comment, that vaccines brought to clinica…
4 johnswentworth 4h I'm not sure what your level of background knowledge is, but I heard that th…
5 waveBidder 2d You're missing the very real possibility of long-term nega ve side-effects from the v…
4 Den n 12h Yes. The differen al tradeoff is how one should evaluate this. The only reason my eval…
3 cursed 2d I don't follow. Don't vaccines have trials on cells, mice, primates, before clinical? So unles…
[-] Czynski 5h 19
Via Sarah Constan n's Twi er:

I looked into this, because yay ci zen science. I could not find one research study using any of the
pep des in the RADVAC white paper that found they inhibited SARS-CoV-2 infec on in cells, let alone
animals or humans.

and

“Take a random pep de that has never been tested on any living thing” is not at all the same thing as
“take a well-known, well-studied recrea onal drug”, as far as risk goes.

She doesn't explicitly state that this has never been tested on any living thing. Possibly because she wasn't
confident enough in her research survey to claim that, possibly because she was drawing a starker contrast
than applies to this instance. But all the COVID tes ng for RADVAC is purely in silico, so while the chemicals
involved may be studied for safety in vivo, efficacy is completely untested even at the (much simpler than
organism) cell level.

So the EV of the benefits are low, and the risks are unclear.
Reply

3 kjz 29m This ar cle [h ps://www.technologyreview.com/2020/07/29/1005720/george-church-diy-…

[-] Sniffnoy 2d 15
Wow!

I guess a thing that s ll bugs me a er reading the rest of the comments is, if it turns out that this vaccine only
offers protec on against inhaling the virus though the nose, how much does that help when one considers that
one could also inhale it through the mouth? Like, I worry that a er taking this I'd s ll need to avoiding indoor
spaces with other people, etc, which would defeat a lot of the benefit of it.

But, if it turns out that it does yield an bodies in the blood, then... this sounds very much worth trying!
Reply

8 Den n 2d My understanding is that it helps a lot. The biggest benefit seems to be that the immune…

[-] u8k 2d 14
My jaw dropped at "~500 doses". At $2 per dose... that's significantly cheaper than it's cos ng the companies
to produce the official vaccine. What am I missing here? I know you're making a different thing than Moderna,
but if the thing your making exists and is this cheap then why is Pharma leaving the money on the floor and not
mass producing this?

I think you're underselling the poten al benefit here! Doing a batch of this and distribu ng it to 500 people
may be unfeasible. I assume the FDA or something comes for you if you're trying to commercially
distribute home-brewed vaccines.

But say, to 20 friends? Why not. Which brings the price down to $50 per/person, which seems like it'd be
totally worth it to have immunity even a month earlier than the official vaccine is available to me. And it
poten ally gives immunity to your whole social scene.

I'll wait for your results, and then will strongly consider doing a batch of this myself.
Reply
[-] Den n 2d 24
Oh, it's far, far worse (be er?) than $2 per dose. As a thought experiment, I price es mated buying enough
pep de for a hundred thousand doses, and it only costs about ten thousand dollars. Ten cents a dose is closer
to realis c if you buy in bulk.

Which also brings to mind a ques on of civiliza onal inadequacy: if we really cared and it really ma ered,
why not have every university with a lab in the country crank out a hundred thousand doses per week to their
local populace?
Reply

[-] ryan_b 1d 11
I don't think this has ever been possible in previous epidemics, at least for at-home manufacture.

That being said, I would strongly support compiling a list of low-risk interven ons like this, so next me we
can publicize them at the outset and try mi ga ng the problem while wai ng for the low-risk&high-success
solu on to be developed.
Reply

[-] Silver_Swi 2d 17

If the thing your making exists and is this cheap then why is Pharma leaving the money on the floor
and not mass producing this?

There are a number of costs that Moderna/Pfizer/Astrazenica incur that a homebrew vaccine does not. Of the
top of my head:

1. Salaries for the (presumably highly educated) lab techs that put this stuff together. I don't know
johnswentwort background, but presumably he wouldn't exactly be asking minimum wage if he was doing
this commercially.

2. Costs of running large scale trials and going through all the paperwork to get FDA approval. I think I'm
generally more in favour of organisa ons like the FDA than a lot of people
here, but even I expect this to be a very non-insignificant number.

3. Various taxes and costs of shipping/storing the vaccine un l it can get to customers.

4. Costs of liability and a desire for the company to make a profit on this (as well as to pay the salaries for the
all of the people needed to keep a large company running).

Given all that I don't think the gap between this and the commercial vaccines is that insane.
Reply

4 Bucky 1h Trying to quan fy these effects: 1. Salaries can't add much, especially if you're looking a…

[-] johnswentworth 1d 16

why is Pharma leaving the money on the floor and not mass producing this?

Both the other comments here are on-point. The materials for large amounts of radvac would cost pennies
per dose, because the cost-per-unit of the pep des drops very rapidly as you scale up (remember, we doubled
our order for <10% extra cost).

However, in general, people and logis cs are a bigger expense than materials for most products these days,
and I certainly expect that to apply to vaccines.
Reply
 [-] Czynski 5h 11
As someone else said, the logis cal difficul es for this are much larger than the standard jab method, the
produc on process doesn't scale well, and once prepared it doesn't last long even if you freeze it. Making this
for 20 friends and distribu ng it to them is very plausibly net-harmful, because you need to gather in close
quarters to hand off the prepared vaccine, do it within a fairly short window (1-3 days) for all 20, and then
repeat all that, including the produc on of new doses, at least once per week and ideally 2-3x per week.
Given that the only evidence for efficacy is in silico, none in vitro let alone in vivo or in actual humans, it's not
at all clear that the benefits outweigh the increased risk of spread from all that close contact.
Reply

1 kjz 25m Why would they have to gather in close quarters? One person could make it in their kitch…

3 Andrew_Clough 4h That's only for raw materials. Actual produc on seems to have involved a fair a…

[-] AnnaSalamon 2d 12
Neat! Will you also use try commercial an body tests on your mucus, or is that known to not-work?
Reply

7 johnswentworth 2d The way the tests we've used work is a nurse takes a blood draw, then ships it …
3 jmh 1d Would an alterna ve (and possibly easier) approach be to simply take some addi onal do…
8 TheSimplestExplana on 1d Wasn't there something about to much an gen possibly reducing i…
7 johnswentworth 1d Yes, good job catching that. I'm currently using rela vely low dose of each…
2 johnswentworth 1d Yeah, more dakka is s ll the default plan right now if the next test comes ba…

[-] TheSimplestExplana on 1d 10
From the white paper:

An body can be measured in nasal wash, however this is less quan ta ve and reliable than
measurement in serum.
Reply

[-] Daniel Kokotajlo 1d 9

Related: This was discussed on LW in August 2020, someone claims to have done it in December:
h ps://www.lesswrong.com/posts/62WuBbQpSwAbctGDP/what-price-would-you-pay-for-the-radvac-vaccine-
and-why°
Reply

[-] johnswentworth 1d 16
I'm afraid I'm not flexible enough to kick myself that hard.
Reply

4 Den n 13m I believe that ini al post is what got me going down the rabbit hole of pep des and p…

[-] cursed 2d 9
Props to you for taking ac on here, this is some impressive stuff.

That being said, I'm extremely skep cal that this will work, my belief is that there's a 1-2% chance here that
you've effec vely immunized yourself from COVID.
What do you believe is the probability of success?

Why are established pharmaceu cal companies spending billions on research and using complex mRNA
vaccines when simply crea ng some pep des and adding it to a solu on works just as well?
Reply

[-] Den n 2d 28
My rough guess is that there's a 75% probability of effec vely full immunity, and a 90% probability of severity
reduc on. This is a pre y well tested and understood vaccine mechanism, and the goal isn't "perfect
immunity" as "prime the immune system so it doesn't spend a week guessing about what an bodies it needs
to combat the virus effec vely".

As to why established companies don't do it, I believe it's par ally logis cs, and largely red tape. Logisi cs first
(though it should be noted that at least some of these could likely be tackled with a bit of effort):

Shots are well understood and easy; people are used to them, people know how to give them, etc.
Nasal spray is irrita ng and makes you want to blow your nose, which washes out a lot of it and
reduces effec veness.
You need mul ple of these annoying doses in the nose, staggered a few days apart, to generate a
'good' response.
This par cular nanopar cle vaccine doesn't have a long shelf life due to pep de degrada on. Pep des
don't last forever, and while they're more stable than the RNA vaccines, you'd have to ship them frozen
as well.
Nanopar cle vaccines in general suffer from par cle aggrega

... (read more)

Reply

9 cursed 1d You can buy nasal sprays over-the-counter [h ps://www.walgreens.com/store/c/nasal-…

[-] johnswentworth 1d 11
I wouldn't take 50/50. I do think it's much more likely than that to induce mucus an bodies, but not blood
an bodies. I would take 3:1 odds.
Reply

[-] Den n 13h 10

My es mate for whether or not I would test posi ve on a blood test was only about 50%, since blood isn't
the primary place that the response is generated. I'm already be ng a substan al amount of money
(pep de purchases and equipment) that this will be helpful, and I see no reason to throw an addi onal $50
on a break-even bet here.

I would, however, be happy to commit to sharing results, whether they be posi ve or nega ve.

... and now it occurs to me that if Lesswrong had a 'public precommitments' feature, I would totally use it.
Reply

7 dxu 1d This is a very in-depth explana on of some of the constraints affec ng pharmaceu cal co…
7 Den n 1d While I generally agree with the concept, I'm going to push back a li le here. I read th…
1 cursed 1d I don't understand the argument about SAD. A simple Google search shows thousand…

[-] dxu 8h 10

A simple Google search shows thousands of ar cles addressing this very solu on.
 The solu on in the paper you link is literally the solu on Eliezer described trying, and not working:

As of 2014, she’d tried si ng in front of a li le lightbox for an hour per day, and it hadn’t
worked.

(Note that the "li le lightbox" in ques on was very likely one of these, which you may no ce have mostly
ra ngs of 10,000 lux rather than the 2,500 cited in the paper. So, significantly brighter, and despite that,
didn't work.)

It does sound like you misunderstood, in other words. Knowing that light exposure is an effec ve
treatment for SAD is indeed a known solu on; this is why Eliezer tried light boxes to begin with. The point
of that excerpt is that this "known solu on" did not work for his wife, and the obvious next step of scaling
up the amount of light used was not inves gated in any of the clinical literature.

But taking a step back, the "Chesterton’s Absence of a Fence" argument doesn't apply here
because the circumstances are very different. The en re world is desperately looking for a way
to stop COVID. If SAD suddenly occurred out of nowhere and affected the en re economy
... (read more)
Reply

[-] Chris anKl 7h 7

If nasal applica on doesn't provide a blood immune response it might be worth tes ng whether anal
applica on will lead to a blood immune response.
Reply

[-] korin43 21h 7

FYI, there's a map of people working on this that you can add yourself to for coordina on:

h ps://radvac.org/researchers-map/
Reply

2 Jayson_Virissimo 8h Does this add you to an email list where discussion is happening, or merely pu…
1 korin43 7h I think it just puts you on the map.

[-] benjaminikuta 2d 7
How do you know this is safe?
Reply

[-] Den n 2d 36
The whitepaper is a good source, but like johnswentworth, I also contacted a medical professional to evaluate
it. The response came back quickly and confidently, and was along these lines:

"Oh, yeah, this is safe. Nasal vaccines are safe. The biggest worry is that it might not work, so make sure you
get the commercial vaccine too. I'd be interested in doing this with you as a joint project and giving it to my
family, and I also have a colleague who might be interested in doing it."

The biggest point of disbelief on their part was that it's possible to order all the equipment and pep des
online and have them shipped to your door.
Reply

3 johnswentworth 2d See the answers to gwillen above, and also the whitepaper.
[-] Adele Lopez 1d 6

The cheapest op ons suffice for the vaccine - the pep des don’t need to be “purified” (this just means
removing par al sequences), they don’t need any special modifica ons, and very small amounts
suffice.

Seems like par al sequences could contribute to the autoimmune disease risk since they would be much more
likely to match to normal cellular proteins. Has this been considered?
Reply

7 johnswentworth 1d Just based on general background knowledge, if autoimmune problems were i…

6 Adele Lopez 1d So at what point does a pep de go from triggering an immune reac on, to being …

[-] Adele Lopez 1d 12

Alright, so the thing that an bodies are "trained" to detect is called an epitope. On page 23 of the white
paper, it says:

6. VED might arise through vaccine design-induced distor on of viral epitopes, as has been
proposed to occur by formalin treatment of RSV. a. Our preferred epitope type is synthe c
pep des. Such pep des are chemically well defined and have a high degree of structural
integrity.

So distor ons of the epitope can cause an autoimmune reac on, and synthe c pep des are good because
they're stable and you know exactly what you are ge ng. But if you have a bunch of par al pep des mixed
in, then it substan ally weakens this point.

Re: 3. It does seem to be true that "damage" is required. Substances which provoke an immune response
are called adjuvants, and the adjuvants in this vaccine are the Chitosan and the Tripolyphosphate.

Reading the paper more closely, it says that the truncated pep des are fine because the pep des get
chopped up by proteases anyway. This does make me feel a bit less worried about this, but it also implies
that this would be a poten al issue for purified pep des as well.

ETA: I also did a spot-check to see at which point this woul... (read more)
Reply

[-] PatrickDFarley 1d 5
Very impressed by this, I really hope it works. These are the kind of audacious efforts that I love to see in this
community
Reply

[-] sarelbic 2d 5
If anyone knows of anybody planning to do this in the Maryland/DC/Virginia area, please let me know
Reply

[-] Chris anKl 1d 4

Are there other nasal vaccines that are based on nanopep des currently on the market and FDA-approved?
Reply
 2 johnswentworth 1d I don't know this, but the whitepaper does men on that this approach is quite…

[-] gojomo 2h 3
Curious, are the pep des-as-ordered shipped in freezer packs?
Reply

2 johnswentworth 2h No, they ship dry.

[-] andrewseanryan 4h 3
Have you tried making at home rapid covid tests? I have o en wondered if it is possible to make an at home
version of the spit paper rapid tests. No clue what this would take but would be great since the government
hasn’t allowed them yet.
Reply

[-] Borasko 1d 3
Thanks for pos ng this, I didn't know about radvac before and now I am excited. I will read the white paper and
probably make some myself. If your results are good which I really hope they are, I will try to help my family
members get some as well. I don't mind paying $1000+ for family safety, and with the delayed vaccine rollout I
would feel be er even ge ng the vaccine to them one month earlier. So thanks again! I hope all goes well.
Reply

[-] jmh 1d 3
Thanks for the write up! I started to do this myself but quickly found I was a bit confused on how to even order
the pep des. I was expec ng to be able to search product lines but.... Not really possible. So...is the process to
simply iden fy some suppliers (not hard to find with Google) give them the amino acid sequences in the
instruc ons and ask for a quote? (Hit that ini al speed bump and have not go en back to looking for phone
numbers or customer support chat windows.)

Just a thought. So this doesn't scale well for storage and shipping it sounds... (read more)
Reply

4 johnswentworth 1d The one I used had an online "custom pep de synthesis" order form. I just pas…
6 Den n 12h Yeah, the pfizer vaccine looks like it just uses mRNA to construct the RBD (receptor bi…
3 johnswentworth 7h Holy crap, the en re RBD!? These mRNA vaccines are a technical marvel, I'…
4 Chris anKl 1d How about sharing the link? Besides different epitopes, if the RadVac vaccine gives …
8 johnswentworth 1d I don't want people giving the company crap if this post ends up very widel…
3 Chris anKl 1d Are we really living in mes where "company helped people with doing somethi…

[-] mingyuan 1d 17
obviously yes?
Reply

[-] Den n 13h 14

Absolutely obviously yes. I have some level of concern that this post will go viral (ha ha), get a lot of
a en on outside of lesswrong, and the company I'm working with will cancel my order because it's
"covid misinforma on" related.

The FDA might be slow and take months to approve safe things while thousands of people die per day,
but they're perfectly capable of announcing an immediate and indefinite pep de ban in under a day
 because a news ar cle crossed the wrong person's desk.
Reply

8 habryka 4h About the "viral" part. This post is currently at the top of HN: h ps://news.yco…
2 Den n 2m Ugh. Thanks for the link.

[-] kjz 2d 2
Crazy thought, and I doubt this is likely on large scale or it would have been in the news, but any chance this
could explain the higher than expected percentage of nurses who have rejected ge ng the vaccine? Perhaps
some have already vaccinated themselves under the radar! And therefore have no need to take the "real" one.
Reply

[-] Den n 2d 10
My personal es mate is that the the percentage of nurses who have done this is effec vely zero (less than
one in a thousand with high probability, less than one in ten thousand with moderate probability.)

Further, those who did do it are likely to have read through the whitepaper, and therefore are also likely to get
the commercial vaccine, as it covers different epitopes than the radvac vaccine.
Reply

1 kjz 1d Agree it is extremely unlikely that many nurses have done so, and your probabili es seem q…
5 Den n 1d Yes, I s ll plan to get the commercial vaccine once it's available to me (likely some m…

9 jayterwahl 2d I predict that is an overly-op mis c reason for why they're rejec ng the vaccine.
2 Chris anKl 1d Given that this vaccine targets a different part of the immune system there's no goo…
1 kjz 1d For the average Less Wrong reader, I tend to agree. But a nurse in an area with a strong, vo…
3 Chris anKl 1d The average nurse in a an -vaccine community is not going to make their own va…
2 Eigil Rischel 2d This seems prima facie unlikely. If you're not worried about the risk of side effects fr…