SciencePodcast_210903

SciencePodcast_210903

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09/03/21 Page 1 of 11 SciencePodcast_210903

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0:00:05.6 Sarah Crespi: Welcome to the Science Podcast for September 3rd, 2021. I'm Sarah Crespi. Each week, we feature the most interesting news and research published in Science and the Sister Journals. First up this week, staff writer Jon Cohen joins me to discuss the search for the origins of SARS­CoV­2 with or without help from China. Next, researcher Ed Narevicius, is here to talk about creating vortex beams of atoms, a quantum state in which individual atoms have orbital angular momentum.

Like the pandemic itself, the debate over COVID­19's origin seems to come in waves, heating up and cooling down multiple times over the course of the past 18 months. This week in science, staff writer Jon Cohen summarizes where we're at now and what we might be able to learn in the future with or without help from China's government. Hi, Jon.

0:01:02.5 Jon Cohen: Hi, Sarah.

0:01:03.5 SC: Why are you writing this now, as I mentioned, we're kind of up and down with the heat of this debate, would there ever be a good time to write this story?

0:01:10.7 JC: The reason to do the story now is because there's a lot of information being debated, whether it's evidence or speculation is debatable. [chuckle] The pendulum took a major swing this spring toward the lab leak theory, and it had initially been ridiculed by some scientists as a conspiracy theory, it also had been touted by President Donald Trump without any evidence that in turn made many scientists doubt it. Then after the WHO sent an international team of scientists to China to work with colleagues there on origin questions, issued a report saying it was extremely unlikely. All of that combined created a backlash from scientists and from journalists saying, Hey, wait a second, this is too blasely dismissing something that deserves serious scrutiny.

0:02:09.7 SC: So the main crux of these debates is whether the virus that's causing this current pandemic came from a lab in China, or perhaps it crossed over from an animal or maybe it arrived from caves. Why do so many people think that this is a lab leak, this came out of a lab in China.

0:02:29.5 JC: That's a really simple question to answer, it's one of the only simple questions to answer.

0:02:34.3 SC: Yeah, let's start there then. Yes.

0:02:36.1 JC: Because the Wuhan Institute of Virology is in Wuhan and it specializes in bat coronaviruses, and we know that there's a link to bat coronaviruses and the disease called SARS, that pre­dates SARS­CoV­2, the virus that causes COVID­19. We know also that the closest virus to SARS­CoV­2 is a bat coronavirus that came from China, that was found by the group at the Wuhan Institute of Virology. So that's pretty clear cut, it's proximity.

0:03:08.5 SC: Right. But as they say, Jon, co­localization is not causation. [chuckle]

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0:03:13.3 JC: No and in fact, if we look at other emerging infectious diseases over the past 50 years, Los Angeles was the place where AIDS surfaced in 1981, HIV isn't from Los Angeles. The H1N1 virus that caused the flu pandemic in 2009 was first sequenced here in San Diego where I live, and we know for certain that it came from Mexican pig farms in Central Mexico. So the coincidence of location often is looking for keys under the light, it often is misleading, but that's the reason why so many people turn to the lab because a major lab is in that city that studies this very question.

0:03:55.0 SC: What about animals being sold in markets in Wuhan, this is another contender for the origin of the jump to humans or the start of this pandemic.

0:04:04.5 JC: So a big problem here all along has been the international scientific communities distrust of the Chinese government, because the Chinese government has obscured... And this is a fact, has obscured many aspects to the early days of the outbreak and then the pandemic. And in the WHO Joint Mission report, they flatly state that there was no evidence of animals being sold at Wuhan markets that have been linked to the early cases. Well, in June, we find a report in the scientific literature of nearly 50,000 live animals being sold at the Wuhan market. Something went wrong in the Joint Mission where they didn't know about all these live animals, and all those live animals provide a map of sorts to investigate potential origin, because you can go back through those animals, through the people who farmed them, for the people who traded them, and you can check to see whether there are relatives of SARS­CoV­2 either in animals still in remote villages, let's say, or antibodies in animal handlers that don't look exactly like the SARS­CoV­2 antibodies, but look like it could be a precursor, we have enough technology now to see with clarity, answers to those questions.

0:05:23.5 SC: We don't just have animals that happen to be potential carriers for this, but we have these cases that are related to that site.

0:05:31.0 JC: Yeah. So let's turn back the clock. December 31st, 2019, the Wuhan Municipal Health Commission issues a press release saying that there are 27 cases of an unexplained pneumonia that are linked to the Huanan Seafood Market in Wuhan, that's how we learn of this pandemic, that's the origin of our knowledge of the pandemic. A lot of studies took place at the Huanan Seafood Market, but it also became clear early on, and I wrote about this in January of 2020, that there were early cases that predated the Huanan market that weren't linked to the market, but then we learned later that there are other markets involved. And environmental samples from the Huanan market that look at floors and walls, things like that, found abundant virus so much so that they were able to actually culture two islets of the virus, and it's incredibly difficult to culture bat coronaviruses from the wild. Shi Zhengli who heads the Wuhan Institute of Virology's program on bat coronaviruses in 15 years has only been able to grow three of them in culture. That's a remarkable finding.

0:06:41.7 SC: And going back to the lab theory for a second here, have there been any confirmed cases from people who worked in those labs?

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0:06:49.4 JC: No, and Shi Zhengli had an extensive email correspondence with me that we published in 2020 in July, in which she said that everyone in her group and in the institute had been tested for SARS­CoV­2 and related antibodies, and no one had the virus. You can question whether she's telling the truth or whether the government is allowing the truth to be told, but those are the facts that we know, and there's been rampant speculation about laboratory workers who became ill prior to the outbreak surfacing at the Huanan marketplace, but nobody has ever provided compelling or convincing evidence that those sick workers existed or had SARS­CoV­2 infections.

0:07:33.2 SC: Another option for the origins of this virus puts us back even further in time, and this is it came from a cave, this was in the Yunnan Province?

0:07:43.1 JC: The cave story dates back to 2012, and there were miners in Mojiang in Yunnan Province who were cleaning bat feces out of a copper mine, and six of them became seriously ill with an unexplained pneumonia. Shi Zhengli was brought in with her team to sample bats in that cave to look to see if they could find a link. They also were given samples from the ailing miners to see if they could find the coronavirus or antibodies to it in their bodies. They did find a bat coronavirus that is 96.2% similar to what we now know as SARS­CoV­2. In evolutionary time, that's decades of difference. It's not as though that virus infected the miners and is SARS­CoV­2, that cannot be. But it raised suspicions, and there were many suspicions raised about how Shi Zhengli reported and didn't report details about the miners and details about the related bat virus she found, and so a lot of speculation has centered on the miners, and a master's thesis that was published in 2013 that alleged that they had SARS related antibodies. Now, I spoke with Linfa Wang who collaborated with the Wuhan Institute of Virology in analyzing those samples, and he said they were eager to find coronaviruses and very disappointed that they could not. He said, "Of course we would have published that if we had found it, there'd be no motivation whatsoever to not have reported that." That's what the whole lab was trying to find, they wanted to find it. He says It's preposterous to make this claim.

0:09:23.1 SC: One last option before we kind of get to the bigger picture here, and this is the idea that this isn't a lab leak accident, that this is somehow a modified virus that is intentionally made more dangerous or changed in some way by a lab and then leaked or released on purpose.

0:09:43.0 JC: There's a concern about what's called gain­of­function research that dates back to 2012 and influenza studies that were being done in ferrets that created an international furore. Those studies took a deadly bird flu virus that killed humans at a high rate but could not transmit between humans, and asked the question, "Can we genetically manipulate the virus so that it does transmit between ferrets so that we can better understand how that dangerous virus might even become more dangerous for humans?" Those experiments led to a grinding halt to all gain­of­function research because they so obviously raised profound dangers, and the question was do the risks merit the benefits? Gain­of­function research in the United States was stopped for a time while the NIH and others said, "We have to come up with a framework to evaluate all studies that potentially are gain­ of­function. Now comes Shi Zhengli who in 2017 publishes a paper where she does research that some people contend is gain­of­function research with bat coronaviruses. If you look closely at them, it's almost a semantics debate. I go into some detail in the story about this because there's a tremendous amount of confusion about what she actually did. Remember I told you she could only grow three bat coronaviruses after having found more than 2,000 of them.

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0:11:17.3 SC: Mm­hmm.

0:11:17.9 JC: Well, she had one bat virus growing in culture that she could then test in human cells, and she had a bunch of viruses she couldn't grow, so she wanted to take the surface protein from those viruses and put them into the one that did grow in culture to see whether they had similar properties.

0:11:34.8 SC: Right, 'cause the surface proteins are important for interacting with cells.

0:11:38.0 JC: Yeah, that's how the virus gets into cells. So here's the deep question, the bat virus she had growing in culture, we know how dangerous it was. It was dangerous. When put into mice, it didn't look as dangerous as SARS, let's say, but it looked dangerous. If you replace the surface protein with a different one, are you making a more dangerous virus? Well, you could argue, "No, not really, it's already dangerous. All you're doing is asking, 'Does this one have similar properties?' You are not doing what the flu vaccine researchers did, which was took a virus that could not move between humans and created one that could potentially."

0:12:16.4 SC: You're adding a function, or are you just...

0:12:18.9 JC: You're adding a function.

0:12:20.2 SC: Manipulating a function.

0:12:21.9 JC: Exactly, and what Shi Zhengli says, in this case she checked in mice and the viruses she made were less deadly than the one she already had in culture, so you could argue it's a loss of function study. But all of this circles around the question of could a laboratory have made SARS­ CoV­2? And researchers who have looked closely at the genetics of the virus say no, because there's no known backbone that you could build on that's close enough to SARS­CoV­2 to have created it. It would require too many changes, and nobody had that knowledge ahead of time how to do this. So in all of the different theories that you've mentioned that one has from the beginning been given the lowest level of likelihood, and I think over time, as people have investigated the specific arguments of how you would have done this, it has become less and less compelling of an explanation.

0:13:21.5 SC: Here we are today with some likely scenario, some less likely scenarios. What's gonna move this forward? Will we see more research more sleuthing around in this area of China, trying to see where the virus came from, where it might have existed in the end of 2019?

0:13:40.3 JC: Well, there was great hope that the WHO joint mission could launch what they called phase two studies to look at many questions of natural origin, those are now on hold indefinitely because China has taken great umbrage at the many attacks that have occurred recently that involve the lab origin theory. The head of the WHO, President Joe Biden have called on China to allow an audit of the labs in Wuhan. There were three in all that worked with coronaviruses from bats. The Chinese government has ridiculed this idea that they will allow outsiders to come in and investigate

09/03/21 Page 5 of 11 SciencePodcast_210903 their laboratories, to the point where the Chinese government has suggested that maybe this comes out of a military lab in the United States and maybe there should be an international investigation of that laboratory. So it's become a political morass.

0:14:29.9 SC: Right. And so one thing you bring up in your story, is, well, there are places that are very close to China that have similar bats, maybe that's where the research needs to continue.

0:14:40.7 JC: And researchers are doing that. So we have found now that bats in Thailand, Cambodia, Japan, harbor related coronaviruses to SARS­CoV­2. It's not as though those bats infected a human, that's not the point. The point is trying to figure out what's the pathway from the bats into the humans? Because in all likelihood it went from bats to another species, to another species, to another species, and then jumped into humans and maybe jumped between humans and that species, back and forth and ping­ponged becoming more adapted to humans before the outbreak took off. We just don't know, but we're trying to piece together this puzzle with every clue we can find. I know that there's research going on in China, not much of it's being published or publicly discussed, some of it is, and it could be that China becomes more collaborative and allows more researchers to come to the country and help researchers there do studies that can further information. There's an impatience right now that people have. I've covered so many outbreaks, infectious disease, emerging diseases, and the origin stories, they take time, they take time.

0:16:02.5 SC: Right and I guess that gets to the very... The heart of this, why is the origin important, especially if it wasn't a lab accident? So we're not gonna change safety protocols, if it was something that moved from animals to people maybe even more than once, what do we do with that information?

0:16:20.9 JC: Well, the stock answer to that is that if we understand how this happened, we can prevent it from happening in the future. That answers a little bit pat to me. We know that biosecurity is incredibly important at laboratories, and we know that humans who are interacting with wild animals have a chance of becoming infected with viruses that can harm us. And surveillance of wild animals has gone on for dangerous pathogens for quite a while. Should we ramp it up? Maybe so, but we know that regardless of whether this was the origin, I think some of the arguments about what we're going to learn are built on something of a House of Cards. I think there's a blame factor that is motivating some people for political reasons, but I do think also that if we learn that the virus traces back to, let's say the fur industry in China, well, that would put intense scrutiny on the fur industry and would ask what sort of precautionary practices are taking place with people farming animals for fur or butchering the animals. If we know that the marketplace is involved, what sort of live animal marketplaces do we want to exist? So I do think it could further strengthen concerns that already exist about how to protect us from emerging pathogens. I think there's a high likelihood that over time, the picture will become clearer than it is today.

0:17:48.6 SC: Alright, thank you so much, Jon.

0:17:50.1 JC: Thanks, Sarah, I'm glad you're doing this.

0:17:51.6 SC: Jon Cohen is a staff writer for Science. You can find a link to this story we discussed

09/03/21 Page 6 of 11 SciencePodcast_210903 and all of our COVID­19 coverage at science.org/podcast. Yes, that's our new website, science.org. Stay tuned for a chat with researcher Ed Narevicius about vortex beams of atoms and molecules.

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0:18:20.2 SC: We're surrounded by vortices, that's the word vortex, the plural form. We're surrounded by vortices on all scales, in the movement of water or the disturbance of air behind the wing of an insect. This kind of vortex is the classical physics sense. But we're gonna talk about the quantum version today. This week, Ed Narevicius and colleagues write about creating vortex beams of atoms and molecules. You write one of the ideas that motivated this work was not to do this for atoms, but to do it for protons in the hopes that this might give access or more information about their internal structure, the internal structure of protons.

0:19:01.4 Ed Narevicius: So that's exactly the point. Actually, this experiment started with a discussion that we had between two of our students, how to explore the inner workings of a proton. And his idea was that imparting this vortex state on a proton might give you a glimpse of how protons are built. We realized that actually, yes, we do have an interesting way to produce these beams of protons, so what you see, this paper is actually the first step towards that goal.

0:19:27.8 SC: And that will help you perhaps get insight into the internal structure of a proton.

0:19:33.3 EN: It's an open question, and this is one of the reasons that we made this experiment. It's very difficult to understand what will happen. It's a new quantum number. It's a new angular momentum that you are able now to give to particles that have internal structure atoms and even more interesting, molecules, which is a completely different game actually. And how this new quantum number interacts, where internally there is a freedom, is really still an open question.

0:19:57.3 SC: These aren't classical physics definitions of a vortex, right Ed?

0:20:01.5 EN: What we are doing is really imparting this angular momentum, this vortex state on a single atom and a single molecule.

0:20:09.0 SC: So it's a particle, not a group of particles. It helps remember that in quantum physics, everything can be described as a wave and a particle. You can describe electrons as waves, you can describe atoms as waves. So in this version of the vortex, the quantum version, we're talking about the wavelike properties of atoms and the phase of this wave, the undulations of the wave twist around as the particles move forward when you have a vortex. Vortex beams were first created using photons. So Ed, can you describe for us what some of the features are of vortex beams of photons?

0:20:44.8 EN: So a typical picture that you see is, instead of a spot that usually you'll get when you use a laser, you will have a bagel. You will have a spot which has a missing center and that happens because you have a discontinuity right in the center.

0:21:00.0 SC: I've seen the illustrations of this and from the side, a single particle vortex looks like

09/03/21 Page 7 of 11 SciencePodcast_210903 a spiral staircase. So if you're looking at it and it's coming straight at you, in the center would be a hole like a donut or a bagel.

0:21:12.8 JC: Right, exactly. So the staircase is a phase. The phase of the field which rotates or circulates around the propagation direction.

0:21:23.0 SC: Why do you say this is a quantum state of an atom or a photon?

0:21:29.5 EN: Vortex... It's not a continuous variable. So you see in our graphs, that you get a discrete set of these donuts and each donut, if you look, is different. It becomes bigger and bigger and the hole becomes also larger. So each one of these donuts has a variable­defined quantum number. This is the vorticity. So how many times this phase turns around, this is the quantum number, so how fast it rotates.

0:21:56.0 SC: So how many times it goes around in a wavelength, right?

0:21:58.5 EN: Exactly.

0:22:00.3 SC: This has been done before in photons. There's been vortex beams of electrons. In this paper, the focus is on atoms. All of these vortex beams are useful because one, you can assign another quantum value to a particle, like a spin as well as a vorticity. The second thing that it gets you is there might be an interaction between this quantum number, the vorticity and other properties of the particle. This is what we were talking about when we were saying, "Oh, we can maybe use this to look inside of a proton." Okay Ed, so in this paper, you show how to make vortex beams of atoms and even molecules. What did you do differently than previous attempts?

0:22:40.3 EN: So the biggest problem is that they have to behave as waves and usual classical particles are really just like billiard balls. Wave properties are extremely tiny. So what we call the de Broglie wavelength, is very small compared to the size of that object. So first thing that you have to do, you have to generate a beam of atoms or molecules where the de Broglie wavelength of these particles is large, it's microscopic. And in our case, it's reach is almost a micron, which is several orders of magnitude larger as compared to the size of any atom. Atom is an angstrom­sized object and we reached 10,000 angstroms.

0:23:19.0 SC: You were able to increase the de Broglie wavelength. That helps you to increase the wavelike properties of these atoms. What about adding orbital angular momentum, getting the phase to rotate as the atom moves forward?

0:23:33.0 EN: So if I look at the beam that comes out of the hole, it will look like a pancake. It will have no structure. So we have to imprint phase. We used a trick that is usually used for photons. So we use a mask, which is a grating mask, so it's made of slits. But these are not simple slits. So usual slits, this is a well­known diffraction experiment, deflects your beam imparting linear momentum. Our slits look really strange. If you look at the picture, they look like fork. So this fork type of grating imparts angular momentum and after it gets out of our mask, you will see this strange pattern of the helix. So this is where magic happens.

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0:24:16.0 SC: So once it passes the grating, you have the angular momentum.

0:24:18.3 EN: Exactly, imparted on the phase of that particle.

0:24:20.8 SC: And then you can look at it and see that it's happened.

0:24:23.5 EN: Exactly, by looking at the far field, by simply looking to the image that has accumulated after many, many particles hit a screen. So every particle produces a dot. We make actually a few millions of experiments and wait until a final picture is formed. And what you see, you see this nice shape. So at the center, this is just a pancake. So you see just a beam without any structure. On the sides you see two rings. So each ring is the vortex state.

0:24:53.5 SC: Okay, so that's been seen before with photons, that's been seen with electrons, and now it's been seen with the atoms and molecules that you used in this experiment, which were helium?

0:25:02.8 EN: These were special helium. So it's not the helium atom, it's excited state of helium. So these are metastable helium atoms, they have extremely long lifetime, almost 8,000 seconds, but they have a lot of internal energy about 20 electronvolts. So it's easy to detect.

0:25:17.0 SC: Now is there anything you learned about helium atoms by applying vorticity to them?

0:25:22.5 EN: Probably not because we really understand very well the structure of helium, but I think there is still a very interesting question to ask because if we are able to show that we can probe internal structure of helium using vorticity, that of course will reflect also on these really challenging proton experiments.

0:25:39.8 SC: Protons are smaller than helium. We've done helium. Can you go bigger than the atoms used in this experiment?

0:25:46.0 EN: Absolutely, you can really go to big molecules. So there are similar experiments, molecule diffraction experiments, pushing to higher and higher masses, so definitely we can do it with even heavier particles.

0:25:57.5 SC: So this is, as you said, assigning a new state. Does that mean that some of these things can be information carriers and be used in communication or other kinds of technologies like that.

0:26:08.8 EN: So for quantum technology, that might be an interesting question because you have now additional quantum numbers. You could think even of generating entanglement using this additional quantum number. For example, if you start with a vortex beam of molecules and you dissociate these two molecules, you will get two atoms that will be entangled with this vorticity, with this vortex state. So yes, I think really, there are many, many ideas, and I'm sure the

09/03/21 Page 9 of 11 SciencePodcast_210903 community now they'll... Seeing our paper will definitely jump on this and think even more.

0:26:39.8 SC: Thank you so much, Ed.

0:26:41.5 EN: Sarah, thank you very much, it was a pleasure speaking with you.

0:26:43.5 SC: Ed Narevicius is a professor in the chemical and biological Physics Department at the Weizmann Institute of Science in Israel.

And that concludes this edition of The Science Podcast. If you have any comments or suggestions for the show, write to us at [email protected]. You can listen to the show on the science website at sciencemag.org/podcast. On the site, you'll find links to the research and news discussed in the episode. And of course, you can subscribe anywhere you get your podcasts. This show was edited and produced by Sarah Crespi with production help from Podigy, Megan Cantwell, and Joel Goldberg. Transcripts are by Scribie and Jeffrey Cook composed the music. On behalf of Science Magazine and its publisher, AAAS, thanks for joining us.

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