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Vincent Racaniello
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- 2021-09-01
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- 2021-09-01
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“Can look at it because now that we have the three dimensional structures solved by structural biologists, we take the coordinates and we put it in a 3D printer and you can make amazing models, right? Any virus”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“It will not Reproduce outside of the cell. So this mug of viruses can in no way be living, in my opinion. However, once it gets inside of a cell, now the cell is a virus-infected cell. It's alive. So a virus, in my view, has two phases, right? It's this non-living particulate phase that everyone is used to. I'll send you, you need a virus for your table. I'll send you a nice model. I think it would look good here. To go with all this other stuff.”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“So right now our definition includes parasite because a virus cannot do anything without a cell. If this mug were full of viruses, it would not do anything for years. It would eventually probably lose its infectivity, but it's not going to reproduce here. It needs cells. And to the first people who discovered viruses, that was astounding that they didn't just reproduce, divide on their own like bacteria. So a virus needs to get inside of a cell, inside the cell. It can't just hang around on the surface. It needs to get in in order to make more of itself. And so we call it an obligate intracellular parasite because it needs to get in a cell and then it takes things from the cell in the form of all kinds of molecules and processes and energy and so forth to make new viruses.”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“There can be. So that's the dichotomy, I think, is that we define them as parasites. Yet I just told you 20 minutes ago that many viruses are probably beneficial. So I think what it means is at some point we're going to have to change our definition. After all definitions we make are just constructs that make it easier for us to study that necessarily represent what's right.”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“It's great. I mean, I talk in my first lecture for 20 minutes before I get to that. And I wonder if I should put it up front. But it's kind of a boring definition. So if you do that first, people will turn off. So first you tell them about all the millions and billions of viruses around. So a virus, we have a very specific definition because it's different from everything else on the planet. Because first of all, it's a parasite. Paris, that means you take something from someone else. We have human parasites who take money from others, right? But in biological terms, a parasite takes something from the host that the host would otherwise use energy or some building block or something.”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“Yeah, it's unfortunate. And he would agree with you because many vegetables are delicious. Salads even are delicious not cooked, but they can have parasites in them, meats, fish people like to have uncooked fish. So if you want to be really safe and boring, just make sure everything is cooked. Now, we have a case this week on Twip of a young man who went, I forgot where he went, but he stayed in a hotel. I think he, oh, Oaxaca, Mexico. Stayed in a hotel And he said he came back with diarrhea and fever. And he said, I don't know where I stayed in the hotel. I just ate hotel food, lots of vegetables and fruits, and probably they weren't washed with clean water. He got something from that. The bottom line is most of these. Infections with parasites can be diagnosed and you can be treated and you'll be fine. So if you really want to”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“Can get worms from sushi. And the solution is to freeze it. And many sushi restaurants now have liquid nitrogen. They snap freeze their sushi, and that kills all the parasites. And a study was actually done in Japan showing that freezing does not alter the taste of sushi because it's... Or you see a big industry”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“So, Daniel is interesting because he's very adventurous and he doesn't, he's not afraid of any of this. So there's a famous lake in Africa, Lake Malawi, which harbors a lot of these parasites. And he said, oh, yeah, yeah, I just make sure I towel off vigorously when I get out.”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“Water as well. And in parts of Africa, there are parasites in the lakes that if you go swimming, they can invade you and infect, can go into your hair follicles and burrow in and get into your bloodstream.”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“Very easy if you have the right diagnostics. Now, Daniel often goes to parts of the world where they don't have diagnostics and he has to use other mechanisms. He may have to take a bit and look at it under a microscope. And then you may not be able to get the drug depending on where he is. But often he sees patients who come back to the US and they get diarrhea or they have a fever. And he says, where have you been? And he can put two and two together. And so we let our listeners do that. And they all send in guesses. And it's wonderful to hear them. Through this. So, there are a lot of parasites”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“She ate raw fish. She was somewhere Southeast Asia or something. And she ended up with red bumps all over her skin. And it turned out was a parasite from the fish that moved around in her. And very easy to cure. You have the right doctors and the right drugs. You can cure all these things.”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“Yeah, so toxoplasmosis, it's mainly. A big issue is if you're pregnant and you get toxo, then your fetus is going to be very badly malformed. It's going to have brain defects and so forth. And animals can get it as well. So there are a lot of parasites of that nature, which you often acquire by food, eating food of different sorts. And it usually happens elsewhere. On this week in parasitism, we do a case. So Daniel Griffin is our resident physician. He's a doctor, a real doctor, right? And every month he comes up with a case. Okay, this is a person I saw. And last month this young lady had traveled somewhere.”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“What you learn is that You travel somewhere and you can get infected and bring it back home. Here in the US, we do have certain kinds of parasites, but because of our lifestyle, we more or less have avoided them. For example, there is a parasite called toxoplasma, which is infected most of the world, actually, because a lot of people like to eat raw meat and you would get it from raw meat. We're not as fond of that here in the US. We like to cook our meat, but that could be a consequence of eating raw meat.”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“In its devastation, and in between, there have been smaller pandemics of other viruses, but it doesn't happen all that often. So we have a lot of viruses. We have a lot of bacteria of various sorts that can cause infections in us. And it's a limited number, right? Your streptococci and staphylococci and Clostridia, we could go on and on, but we know how to handle those as long as we have antimicrobials. It's just that we abuse them and we get resistance. So that can be a problem. Then we have fungi. not mushrooms, but much smaller fungi that multiply sub-microscopic or just at the microscopic level. They can, in dry climates of the US, you can inhale their spores and they can grow in your lung if you're immunosuppressed and so forth. So those are the tiny guys. And then we have parasites, which we do this week in parasitism, where single cells, even worms.”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“Yeah, I think the big picture is that the things that can kill you are a minority of everything that's out there. And we're talking about. Molecules, so we have in us proteins that can kill us Prions that are just it's a protein in us, and if it misfolds, it makes all of its other copies misfold, and then you die of a neurological disease. That's pretty rare. But there are proteins, there are viruses. As I said, only certain ones can kill us. But even if we get those from animals, it's not straightforward. If you look at SARS-CoV-2, right? This is probably a once in a hundred year pandemic, I would say. equivalent to 1918.”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“Machine learning people, and you would say, Look, this is the biological problem. Is there a way we can use your tools to attack it?”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“We do that. We do that. But with people from a field that we're not used to, I suppose people who would it be AI, I suppose?”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“All the drug resistance. But the problem is people like me, the experimental virologists don't know how to do any of that, so we need to collaborate with people, I guess.”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“You could say what is the antibody looking at? Where antibodies bind on proteins are called epitopes, right? You could map them all and change them in a simulation one by one and go back and forth between the antibody and the virus. So all these evolution is what we call an arms race, right? The virus changes and then it evades the host and then the host can change. The host takes longer to change though, unfortunately. It takes geological time, but it can, and then the virus can change and it can go back and forth. And we can see evidence of this in genome sequences of both viruses and their hosts. And so you can take a protein in a host that is a receptor for multiple viruses. And you can see all the impacts of virus pressure on it. And you could simulate that for sure. And that's just one thing that you could do. You could simulate changes in, say, an enzyme that makes it resistant to a drug and predate.”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“It's all in simulation. So, an example would be we have all these variants of SARS-CoV-2 arising, right? Which look to be selected by immune responses. But we know what amino acids are changing in the spike and how they block antibody bonding. You could simulate that.”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“Well, so that's what the ultimate goal of getting a structure is that then you can do experiments and figure out what the structure means, right? So many in the old days, structural biology was a career in itself. You worked with people who had a system and just solved proteins for them and then you moved on to another one. You didn't really do any experiments. The other people got to do all the interesting experiments. Now young structural biologists are multifaceted. They solve the structure and then they say, what happens if we change this amino acid? Oh, look, it blocks binding to the receptor. This must be the receptor binding interface. So that's the exciting stuff, absolutely, is doing the experiment.”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“Actually, you can do viruses, but you can't do small proteins. So that speeded it up, but it's still too fast to solve. You get a new protein you want to solve its structure. So if we could predict it, and I know from talking to structural biologists, this has been their holy grail from day one. They want to be able to take a sequence of a protein, put it in a computer, and have the structure put out without having to do all the experiment. So that's why this is very exciting. Can predict it. I mean, it's not finished, obviously, and there's more to do. But I think there will be a day where you could take any amino acid sequence and predict what it's going to look like.”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“Then as computational power increased, then they could start to do viruses. But it took a long time. X-ray crystallography depended on getting crystals of the virus, right? And now we can do cryoelectron microscopy, which is much faster. You could solve the spike of SARS-CoV-2 was solved in two months by JSON McClellan here in Austin, actually, at the beginning of the pandemic. But you're limited. You can't do huge proteins. You can only do moderately sized ones.”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“Machine learning absolutely because in all this dark sequence you can translate it and make a protein. You can see what a protein looks like. It has what we call an open reading frame, right? Starting to stop. And right now it's just a bunch of amino acids. But if we could fold it, maybe the fold would be like something we already know, some protein fold which gives you Lot of clues, right? Because there are only so many protein folds in biology and that dark matter is probably one of them. So I think that's very exciting because for years I've followed structural biologists for years. And in the beginning we couldn't even solve structures of viruses. They're too big. We could do small molecules like myoglobin. That was the first one done. Took years to do that”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“That's a very good question. So, whenever you do sequence, right, you get some environmental sample and you extract nucleic acid and you sequence it. What you do is you run it past the database. The gold standard is the GenBank database, which is maintained here in the US. And you see if you get any hits, and then you can say, ah, look, this sequence is similar to this virus, and you can classify all the viruses you see. The problem is 90% of your sequence is dark matter. It doesn't hit with anything. It's probably a lot of it is unknown viruses, and that's going to be hard to figure out because someone's going to have to go after it and sort it through. So yes, you can find a lot of viruses. And the numbers you get are astounding. You can find thousands of new viruses just by looking in various life forms, but there are many more that we don't pick up because they're not in the database.”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“Ask them, yeah. No, I would have to sacrifice them and take tissue and then. Bring it in the lab and do genome sequencing.”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“And birds too. Birds can give us their viruses that's happened. Influenza viruses come from birds mainly. So I think those are the three species, not species, it's higher than species, obviously, but those are the three I would worry about in terms of getting their viruses. And we don't really know what's out there, right? We have very little clue about what viruses. And I've for years wanted to capture wild mice in my backyard and see what viruses they have because no one knows.”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“And the most common virus in human feces is a plant virus that infects peppers. It's called pepper model mosaic virus. And that's because people eat a lot of peppers. And it just passes right through you. Cabbage is full of viruses from the insects that walk on the cabbage in the fields. We eat them. They just pass us. So I think most of the viruses we don't need to worry about, except when we're talking about species that are closest to us, mammals, of course, and I think the most numerous ones are the most concerning. They're viruses like bats. Bats are 20% of mammals and rodents are 40% of mammals. And we humans live nearby, right We know throughout history many viruses have come from bats and from rodents to people. No question about it.”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“To a certain extent, I mean, they have it's twofold they're good and bad, right? Viruses, no question they can be bad. We know that because they've infected and caused disease throughout history, but we're also, you and I are full of viruses that don't hurt us at all and probably help us. And every organism is the same. So they are clearly beneficial as a consequence. So I think So every living thing on the planet has multiple viruses infecting everything you can see. And most of them I think we don't worry about because they can't infect us. They're unable. In fact, Now you could actually take your feces and send them to a company and they will sequence your viruses in your feces for you, your fecal virome, right?”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“Well, you don't have to figure out. It just happens, right? Because molecules are so diverse that a molecule gets into a cell. And if there's a protein that sticks to it, it's going to stick. And that gives an advantage. There's no planning. There's no thinking about it, right? It just happens.”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“Remember, we have these precellular, they're called precellular replicons, right? And so we have a precellular stage where we have these self-replicating molecules, then cells arise, and then Self replicating molecules invade the cells. Why? Because it's a hospitable environment. They didn't know that. They just went in and it turned out it was beneficial for them. So it stuck. And they replicate inside the cell now where they have pools of everything they need. They get more and more complicated. And then they steal proteins from the cell to build a protective shell. And then they can be released as virus particles. They're now protected. They can move from host to host. because they're at the earliest stages of cellular evolution, they can diversify to infect anything that arises. And that is why I think there's so many of them. And everything on the planet is infected because the answer of everything was infected many years ago.”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“Think so. Actually, not my idea. It's Nick Jones. Have you heard of Nick Jones? He's an evolutionary biologist in the UK. And he's done experimental work on this. And it's his idea that the defining point was the ability to make a lot of energy, which a mitochondria can do. It's basically a whole bacteria inside of a bigger cell. And that becomes what we now call eukaryotes. that they can get more and more complicated. So let me bring you back to the viruses. I want to finish that story.”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“So Are mostly single cells. They do make colonies. They get together in biofilms, which are really important, but they're all single bacteria in that. And the key is making an organism where cells do different things. We have skin cells and eye cells and brain cells. Bacteria never do that. And the reason is probably energy. Bacteria can't make enough energy to do that. And so there was another cell existing at the time the Achaea. The idea is that a bacteria went into an archaea and became the modern day mitochondria, the energy factory. And that now led that cell develop into more and more complicated organisms like we have today. It was all about energy”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“Very long DNA genomes, and you need a lot of DNA to make a complicated cell. And so we think at some point the RNA became DNA. And probably one of the earliest enzymes that arose is the enzyme that could copy that RNA into DNA, which we now know today as reverse transcriptase, which my former boss, David Baltimore and Howard Temmond co-discovered. That enzyme arose and copied RNA to DNA, and then you could build big cells because DNA can be millions and millions of bases in length and RNA. The longest RNA we know of is 40,000 bases, not much bigger than the SARS-CoV-2.”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“Is pretty fragile in the world, and it probably didn't get very big as a consequence. But then proteins evolved, and I'm skipping like hundreds of millions of years of evolution. Proteins evolved, maybe without a cell, maybe with a cell. But then to make a cell, there probably were some RNA-based cells early on, but they were pretty simple. But the cells that we know of today, even bacteria and single-celled eukaryotes”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“So, the It does not all fast, not all viruses are fast. Some are 20 minutes per cycle. Some take weeks per cycle. But that's just per second. There's so many viruses in the ocean that that's what you get per second, no matter how fast the cycle is. But I look at it this way. Viruses were probably the first organic entities to evolve on the planet. Long ago, billion years ago, just as the Earth cooled and organic molecules began to form. I think these self, we call them self-replicators. They're just short things that today would look like RNA, which is the basis of many viruses, right? They evolve and they're able to replicate. Of course, they were just naked molecules. They had no protection. And it was just RNA-based. And that's tough because RNA...”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“And if you lined up those viruses and to end, they would go 200 million light years into space. It's so big a number. It's amazing. And then, yes, 10 to the 20-some infections per second of these viruses killing bacteria and releasing all this organic matter. And that's part of this, what we call the biogeochemical pump cycling of material in the ocean. The bacteria die. Start to sink, and then they get metabolized and converted to compounds that are needed. A lot of it gets released as carbon dioxide and so forth. So these are actually really important cycles that are catalyzed by the virus.”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“That's my goal. And that's what my students tell me one student once said every day, after every lecture, I could go home and tell my roommate something she didn't know. And blew her away. So the number of viruses is really an amazing number. So that number, 10 to the 31, is actually just the bacterial viruses in the ocean. So there are viruses that infect everything on the planet, including bacteria. There are a lot of bacteria in the ocean. And so 10 to the 31 is from basically particle counts of seawater all over the world. So there are more viruses than 10 to the 31. But just in the ocean, and that number is so big, First of all, the mass exceeds that of elephants on the planet by a thousandfold”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source
“So the numbers you're quoting, they're in my first virology lecture, right? People don't know these numbers and they get whoa, they get wild by them. So I love to give them. By the way,”
2021-09-01 · Lex Fridman Podcast · #216 – Vincent Racaniello: Viruses and Vaccines · IDENTIFIED FROM THE TRANSCRIPT · source