Wow, this is really impressive! Keep up the great work.
How well would this approach translate to other viruses (I'm thinking of herpesviruses like EBV and CMV)? I'm guessing these would be harder to express as VLPs in yeast, right?
Thanks for commenting - I love this question. The funny thing is that I still don't know exactly *why* the BK polyomavirus VP1 protein I drank worked to elicit neutralizing antibodies. It could be because VP1 is a repetitive geometric structure that sets off innate alarm bells in the immune system. Or it could be because VP1 binds a certain type of sugar on an intestinal structure called an M cell. We're doing the ablation experiments in mice to try to sort it out - but no matter how it comes out we ought to be able to extend the needed features to all sorts of other viruses, including herpes envelope proteins. This type of thing should be straightforward to put in yeast:
The fact that independent scientists out there in TV land could theoretically test the hypothesis in their own kitchen right this minute is bananas. If you'll pardon the pun. I mean it when I say it's understandable that my colleagues find the idea unsettling - but I don't view the existence of vaguely unsettled colleagues as a strong argument for refusing to do experiments. See:
The earth-shaking thing about the realization that vaccines can be food is that we can now try to democratize the whole thing. You don't need to sign up for my study - you can start your own study. We included extremely detailed methods in the manuscript covering the independent kitchen experiments.
A next step will be for us to convince the big yeast manufacturers to sell products to local microbreweries and homebrewers. But while we wait for that to happen it's 100% plausible to imagine independent scientists (meaning you) to order the DNA from Addgene, put it into yeast, and lawfully rock out in the kitchen.
I'm sort of just saying beer for shock value - and because beer is one of my lifelong passions. The truth is that the whole thing is just about the live yeast - not the fluid they're suspended in. Our work with mice has even shown that dried yeast (think supermarket Fleischmann's) work pretty well too. So welcome aboard, children, Muslims, alcoholics, and beer-haters! Everybody's welcome here.
At a technical level, I intentionally made it so the yeast turn on the production of the vaccine protein in response to maltose (the primary sugar in barley malt). Mead wouldn't work with the particular system I designed because honey has very little maltose. Doesn't mean it's not possible - just means it's an interesting challenge for mead-lovers.
We chose them because we figured they'd be sturdier as a dried-down product than the fragile lab strain yeast. There are a lot of variables to consider - boulardii are more resistant to stomach acid than other yeast strains but they're more sensitive to bile salts. This could be a good thing - it might be that having the yeast break open high up in the proximal small intestine is good for immune priming. Or it could be a bad thing, if it turns out immune priming is better farther down in the distal intestine. Another variable to consider is temperature preference. Boulardii - and the Lithuanian farmhouse yeast I drank at first - are perfectly happy at body temperature. The wheat ale yeast I drank for the booster dose is happier at room temperature.
Yeast can deliver DNA for expression in human cells, but RNA is fragile - and the mRNA vaccines depend on fancy chemicals to get the RNA into human cells. Just working directly with protein expression in the yeast is technically simpler and seems a lot more likely to work - that's where this initial wave of experiments should invest.
Wow, this is really impressive! Keep up the great work.
How well would this approach translate to other viruses (I'm thinking of herpesviruses like EBV and CMV)? I'm guessing these would be harder to express as VLPs in yeast, right?
Thanks for commenting - I love this question. The funny thing is that I still don't know exactly *why* the BK polyomavirus VP1 protein I drank worked to elicit neutralizing antibodies. It could be because VP1 is a repetitive geometric structure that sets off innate alarm bells in the immune system. Or it could be because VP1 binds a certain type of sugar on an intestinal structure called an M cell. We're doing the ablation experiments in mice to try to sort it out - but no matter how it comes out we ought to be able to extend the needed features to all sorts of other viruses, including herpes envelope proteins. This type of thing should be straightforward to put in yeast:
https://www.science.org/doi/10.1126/scitranslmed.abf3685
The fact that independent scientists out there in TV land could theoretically test the hypothesis in their own kitchen right this minute is bananas. If you'll pardon the pun. I mean it when I say it's understandable that my colleagues find the idea unsettling - but I don't view the existence of vaguely unsettled colleagues as a strong argument for refusing to do experiments. See:
https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.0020069
I've brewed cider before and I would love to try brewing vaccine beer. Can I sign up for your un-study?
I just found you due to 1440 linking a Science News article about this. Your work is important and amazing and ethical!
The earth-shaking thing about the realization that vaccines can be food is that we can now try to democratize the whole thing. You don't need to sign up for my study - you can start your own study. We included extremely detailed methods in the manuscript covering the independent kitchen experiments.
https://zenodo.org/records/17968622
A next step will be for us to convince the big yeast manufacturers to sell products to local microbreweries and homebrewers. But while we wait for that to happen it's 100% plausible to imagine independent scientists (meaning you) to order the DNA from Addgene, put it into yeast, and lawfully rock out in the kitchen.
I'm sort of just saying beer for shock value - and because beer is one of my lifelong passions. The truth is that the whole thing is just about the live yeast - not the fluid they're suspended in. Our work with mice has even shown that dried yeast (think supermarket Fleischmann's) work pretty well too. So welcome aboard, children, Muslims, alcoholics, and beer-haters! Everybody's welcome here.
At a technical level, I intentionally made it so the yeast turn on the production of the vaccine protein in response to maltose (the primary sugar in barley malt). Mead wouldn't work with the particular system I designed because honey has very little maltose. Doesn't mean it's not possible - just means it's an interesting challenge for mead-lovers.
Yes! Boulardii are actually in the main manuscript:
https://zenodo.org/records/17969224
We chose them because we figured they'd be sturdier as a dried-down product than the fragile lab strain yeast. There are a lot of variables to consider - boulardii are more resistant to stomach acid than other yeast strains but they're more sensitive to bile salts. This could be a good thing - it might be that having the yeast break open high up in the proximal small intestine is good for immune priming. Or it could be a bad thing, if it turns out immune priming is better farther down in the distal intestine. Another variable to consider is temperature preference. Boulardii - and the Lithuanian farmhouse yeast I drank at first - are perfectly happy at body temperature. The wheat ale yeast I drank for the booster dose is happier at room temperature.
Yeast can deliver DNA for expression in human cells, but RNA is fragile - and the mRNA vaccines depend on fancy chemicals to get the RNA into human cells. Just working directly with protein expression in the yeast is technically simpler and seems a lot more likely to work - that's where this initial wave of experiments should invest.