Into the Impossible With Brian Keating - The Origins of Life and the Work of Primo Levi (#026)

Episode Date: July 16, 2019

   Links: Dr. Luca Legnani, Ph.D., The Blackmond Lab, Scripps Research Institute Primo Levi The Arthur C. Clarke Center for Human Imagination on Facebook and Twitter Email us at [e-mail]. Learn more about your ad choices. Visit megaphone.fm/adchoices

The only thing we can be sure of about the future is that it will be absolutely fantastic. Five, four, two, one. Hello, everybody. Welcome to this special episode of Into the Impossible. Recently, the University of California and San Diego Institute for the Arts and Humanities commemorated the 100th birthday of Primo Levi with a symposium, remembering his life, and the example he said of uniting scientific and literary cultures. Primo Levy was a chemist, a writer, and a survivor of Auschwitz.

He said that stitching together molecules taught him to stitch together words and ideas. This episode of Into the Impossible is dedicated to the memory of Primo Levy. Today we're going to have a conversation with Dr. Luca Lignani. He's a research fellow at the Scripps Institute, and he studies, among other things, things, the origins of life, and how that is affected by the chirality of molecules. So why don't you introduce yourself? Tell us a little bit about you and how you get into this work. Yeah, hi, everybody.

Yes, my name is Luca Leni, and this is the field I'm studying. So I'm a postdoctoral fellow in the group of professor. Blackmond and what we are trying to understand or to collect more evidences about is the general picture is the origin of life so our life started on our planet and more specifically our I was the origin of homo charyality so why the molecules that are part of our body and part of the body of many living organisms why they have a specific clarity and how these started So Luca, you're obviously Italian.

Primo Levi was Italian, so you know you know about him. What was it about his work that inspired you? Yeah, well, Primo Levi is very famous in Italy and worldwide, mainly because of his work about the Holocaust during the Second World War. But Primo Levi was also a chemist. And he was inspired by chemistry, so he wrote many short stories about about chemistry. And I'm pretty sure, I would say that also with these short stories, with this writing, yours inspired different generations of chemists, for sure in Italy, but I'm also

pretty sure worldwide. Tell us about how your work intersects with this interest you had in Primo Levy. Well, Primo Levy wrote probably regarding chemistry's most famous book is the periodic table in which he has different short stories and every story is dedicated to a specific element of the periodic table. But we don't have to forget that also Primo Levy was one of the main other big topic he was interested about was also a region of life. That's a little bit the branch of research I'm involved too. So he wrote, for example, the short story is his own maker that was published in 1971, in which Primo Levy imagines to have such a long memory by which you can go back in the past and look at the different stages and pests that brought simple

bacteria evolving to more complex animals, so also bringing it to the form of a human. Another interesting short stories, for example, carbon, that was also published in the 70s. And in the short-stores carbon, he takes an atom of carbon and he follows it into different stages. So in the atmosphere as a molecule of carbon dioxide, then ending up in a plant, for example, or in different animals. The literature, the writing and the metaphors and the state, the state, style of his writing inspired a lot of science, a lot of scientific investigation. I think it's both ways. So it's for sure, as you're saying, his writing interested many chemists, many scientists, and for sure many have been inspired by his work and also the other

way around. So Primo Levy was, as I said, it was a good chemist, and he well knew what was going on in the scientific community, and more specifically in the chemistry community. community. So he was also, he took inspiration for many of these short stories by the scientific discoveries and by reaction, elements and molecules. And we can find them in many of the short stories he wrote. So here's one of your slides that talks about the carbon cycle. Yeah, exactly. The short stories carbon that was published in the 70s, in 1975, the journey of an atom of carbon, as I said, into different living organisms, such as like plants,

animals, but also as a non-living matter. So, for example, in the atmosphere as carbon dioxide or in the ground. And, yeah, in the 70s, also other authors were interested in the origin of life. So, for example, Karl Sagan, as in the first slide, he tried to imagine the... origin of life and he condensed the story of the of the of the universe in a one-year calendar and he condensed the original life only in one in one month so right here at UCSD we have a legacy which was the famous Miller Yuri experiment which is trying to prove a biogenesis right that life could have came from physical processes organic matters.

Yeah, Miller and Yuri were, they later on became professor here at UCSD and they were the first that could confirm the hypotheses of operin. So operating was this Russian biochemist and he was the first one who suggested that molecules could grow into more complex structure and more complex molecules. And Miller and Yuri, that's what they could prove. So basically they took some sort of these apparatus and they started refluxing and applying electrical charges to a mixture of inorganic and simple metals,

inorganic molecules, such as, for example, methane, ammonia, hydrogen. And by refluxing under warm temperature for many days, after analyzing the content of these apparatus, they could find more complex molecules, such as, for example, amino acids. So this was the first time that somebody could prove a little bit the hypothesis that was formulated like 30 years before by operating by this Russian biochemist.

So do you buy it? I mean, is abiogenesis something that has been proven, Is there more evidence for it or less? There are definitely more evidence. So since the experiment in the 50s by Miller and Yuri, also more, even more complex molecules have been built into conditions that are called prebiotically plausible. So like into, for example, warming them up

and by applying them electrical charges. So, yeah, even more evidences have been. collected since the 50s. For sure, the experiment of Miller-Iurie is the most famous one, but there are even more than those. So your work gets more into this, showing in this slide, which is the concept of chirality or the handedness of molecules. So first, tell us what chirality is. Yes, chiroreity is what interests me, but again, it's also a big topic about which Primo Levi also was very interested, and he was so interested that he also wrote his master thesis as an undergraduate student at the University of Turin. So chirality is actually,

well, we can describe an object as being chiral when it's not possible to superimpose it on its mirror image. So the classical example that chemists use to describe a chiral object is the example of one hand, because if we take, for example, the right hand, the mirror image of it is going to be a left hand, but we cannot superimpose the two images one onto the other. So also for this reason, we usually speak about right hand and left hand molecule. Another easy example can be also the one of a chair. So if we take a normal chair, this is a non-chiral object because we can take the mirror image of a chair and superimpose onto it. But on the other hand, if we take a chair like a conference chair with a side table on the side,

in this case we cannot superimpose the image of this kind of a chair onto its mirror image. So in this case we are in the presence of a chiral object. And chirality is an extremely important property in chemistry. Because if we have an atom of carbon, that's the fundamental atom in the molecules of life, and this atom of carbon is connected to four different groups of atoms to four different molecules, then we are in the presence of a chiral molecule. And it's very, very important because usually it interacts with living organisms in two different ways, according if we are using a right-hand chiral molecule or a left one.

So very famous, for example, example of chiral molecules are the one of thalidomide. So, right, thalidomide was commercialized many years ago, like in the 50s, if I'm not wrong, and it was commercialized as a drug to fight the nausea in pregnant women. The only problem is that the molecule that was active that was having the benefit of combating this nausea effect was the right-hand molecule. And the problem, the main problem was that this kind of molecule was not commercialized as a pure, so it was not just commercialized the right-hand molecule, but because it's just easier to prepare, it also costs less, it was commercialized as a racemic mixture.

So, 50% of the right-form molecule and 50% of the left-form molecule. And the left molecule was then, was, as being seen, that was causing the heterotogenic effect onto the babies that those pregnant women were waiting for. So just to be clear about it,

there's no difference in the physical properties of the molecule. Exactly, exactly. Same melting point, boiling point, same solute properties, same, you know, chemical formulas,

chemical formulaic table, same, exactly. number. Exactly, you're right. They have the same physical chemical properties. So this part of the, this part, this combines why they are so interesting and also so difficult to work with. So the main difference is that they interact in a different way with other chiral molecules. So that's why living organisms that are full of chiral molecules, they, if we take other chiral molecules we are going to see them interacting in a different way with, for example,

with our body, with the body of the living organisms. So here's another example. Yeah, exactly. This is the other example. So methamphetamine, the left form of the molecule is sold as an over-the-counter drug as a nasal decongestant. So this kind of molecule can be easily both in many pharmacies. is not so easy to get your hands on is actually the right form of this molecule because the right

form of methamphetamine has actually effect as a recreational drug. So if you want to get this then you will have to ask for example, yeah, Walter White in the very famous TV series Breaking Bad to prepare this for you. So Primo Levy was a good chemist and he knew that in a chemical reaction So if we want to prepare like a product formed by the left and the molecule and the right hand molecule, if we are in the absence of a chiral template, so if we don't have any chiral molecules into our reaction mixture, what we are going to prepare is a so-called arcemic mixer. So 50% of the left form molecule and 50% of the right four molecule. But in the other hand, if we are in the presence of a chiral template, so of a chiral molecule,

we are going to be in the presence so it's possible. It's not always occurring. But it can be that we are forming 60% of one molecule and 40% of the other, or to the point where we are with 99% of a left molecule and 1% of the right one. And this part are very interesting, where they're linked together with originating. of life is because as I was mentioning before, our body and the body of mostly all the living organisms are formed by chiral molecules. So for example, all the sugars that we are using are in the right-hand form and the

amino acid that we are using are in the left-end form. So for example, amino acid forming protein or sugars that are part of DNA and RNA. But now the big question that again, Primo Levy was asking himself in the short story, asymmetry in life, is how it's possible that starting from simple molecules, we could form only one hand form of the molecule. So the question is not if we can take water, hydrogen and methane, for example, and forming amino acid, because that was, as we discussed before,

was proven already by Miller and Yuri. But the point is that how at the origin of the universe, if we didn't have any chiral template in it, why life is formed by 100% one form of the hand molecule? So why we are in the presence only of right sugar and the left amino acid and not the other way around? So why we don't have like racemic mixture in the living organism, or why we don't have the other way around, why we don't have left sugar and right amino acid, for example. That's also the very big and general question.

Chemists nowadays, in order to address this question, they divided this process that would have potentially brought to the formation of, again, left amino acid and right sugar and all the other molecules, into different steps. So from a condition where we had a racemic mixture, so 50% each of the two molecules, we need some events that would bring to an unenched form of the two molecules. So a symmetry breaking, so going from 50-50 to 51-49. Then following this step, we would have to increase this kind of imbalance that were formed,

so going from 51-49 to maybe, let's call it, 90% 10, and then how these molecules here, once they are enriched to this level, how they are finally enriched to the 100% form of, again, for example, in this case, right sugar and left amino acid, and how this caroline formation is even transferred into more complex molecule, such as DNA or proteins. One of the idea for what concerns, for example, the first step, the symmetry breaking, was already published discoveries in the 70s. So it has been seen that if we take, for example, an accemic mixture of this amino acid, valine, so 50% of each, and if we are irradiating this mixture with left circularly polarized light,

we are going to degrade this mixture, but we are not going to degrade the two molecules at the same way. molecules are the same way. So at the end of the process, we are going to be in the presence of a little bit more of the left form of the amino acid versus the right form. So it's not a big difference. It's going to be just 1%, but is important to start the whole process. What's interesting is that left circular circularly polarized light was not probably present in the prebiotic herd. But what has been discovered is that from the space dust that is falling on our planet, some amino acid are a little bit an antinriched so there is a little bit more of

the left form of this amino acid. Again, it's not a big amount, it's just like a few points percentage of this EE, that's a parameter that chemists use to describe the chirality. But this is also pretty fascinating because

it might suggest that the origin of life actually as an origin out of our planet. Part of the, for what concerned, the second steps, there are different processes that have been described, that have been discussed. Many of them, for example, taking account different crystallization processes.

So, crystallization is a purification method that all the chemists use in their lab to purify molecules, but they also might be involved in this process of growing this imparity in the mixture of right and left molecules. So for example, if we take a suspension in which there are amino acid derivative in the dissolved, in the solvent, so in solution, but also in equilibrium with their solid form, if we start from a little bit of an imbalance,

so from 51, for example, of the left form versus 49 of the other one, and if we start steering in a very vigorous way, this kind of suspension, after a few days, we are going to be in the presence of 60% and 40% of the other form. So we are growing into this imbalance. And if we keep steering our suspension for even more days,

For example, after two weeks, we are going to be in the presence of only the left form of the amino acid. So this is, for example, an experiment that would suggest how it's possible to go from a 51-49 imbalance into a much bigger one. The last step of all of this process is also how to connect all of those reactions. So all of these reactions communicated together to bring at the end the molecules that are forming life. So again, for example, sugar into DNA and amino acid into protein. So what we are doing for example right now is to take molecules such as amino nitriles that are likely to be present in our prebiotic hurt. And if we have an aracemic mixture of them and if we are inducing them to basic condition,

we are going to form amino acid derivative in a 50-50% mixture, so in an aracymic mixture. But if we, again, in this kind of reaction, we are in the presence of a chiral molecule and not a random one, but right sugars, what we are going to form is more of the left form of the amino acid. why do you think this happens is it it seems like there's a there's physical processes that tend towards this handedness with with no enzymatic or no bioactive uh process that needs to happen um yeah exactly one of the in these in these hypotheses in these reactions that we are working on we think that enzymatic reactions were not quite there, because at that point was much forward in the origin of life pathways.

So all of these reactions and processes, they actually are occurring because of the interaction of chiron molecules that were already there. So starting again, as I showed in the presentation, so starting from this little imbalance, it's then enough to have a little bit more of one form of the chiral molecule to give the, to bring this carol information and to propagate it into different molecules. So in your lab, how do you study this?

How are you breaking this down? We have different reactions, different processes that we are studying. One, for example, I show it right now. it's understanding how sugars and amino acids are communicating together. Because again, also how this chiral information is transferred to different molecules. So again, in this case, the two most important ones. So sugars and amino acids. There are also different studies in which they involve the polymerization, for example, of amino acid

into more complex structures that are called peptides. And now, for example, the current information of peptides is also transferred to other reactions. And this last slide you have, it's kind of asking, it's kind of begging the question that we started with. Yes, because the origin of life is, of course, it's part of a big picture. And the origin of homo-chiority, that's what we discussed to do. can also maybe help us to address our original life occurred. So if it occurred via a sequence of pre-ordained events, so in a deterministic view,

or as a series of random events, so in a stochastic point of view. Of course, we can also not exclude that intelligent design played the role in the original of life, but yeah, as scientists, we feel that this would be pretty boring, pretty boring answer to give. And in your career, what's got you excited? Where do you want this to lead?

I think, for example, there is much more to do for what concerns, sticking to a region of life, for what concerns, for example, the different metals. So metal catalysis is actually a big field in organic chemistry. But I have the feeling that many, the role of different, metals into the reactions at the origin of life and not has not been studied enough. So this would be, for example, also a big picture to try to get more of an idea about. Simple metals, so iron, copper, all these metals at the role at the origin of our planet, at the origin of life on the Earth.

So we just had a tour of our cosmology lab and you saw the polar bear telescope and you saw the small aperture telescope that's headed for the Simon's Observatory where we're looking at polarity of the universe's oldest light, the CMB or cosmic microwave background. How do you feel about that? Did you see some comparisons, some parallels to your work? Yeah, I would say definitely like the polarized light might of course as an influence

in the in the in the chirality that then is part of our life of our life and of life of the living organisms. So there are many, many

possible connections. I think it's a matter of understanding if also the the energy of life is like enough to be transferred into a process, to a reactions where it would imbalance, again, I will repeat a little bit myself, but if it's able to imbalance into one direction or the other, our systemic mixer.

So again, if we are in the presence of a 50%, 50% a mixer of the two molecules, if this light is possibly, inducing either the degradation of one or the other one or the formation of one process versus the other to go in either one or the other direction. Well, Luca, I want to thank you for being an into the impossible. Thank for the opportunity. Giving us some insight into your work and into the work and life of Primo Levy in celebration of his 100th birthday. Imagination.ucsd.edu.edu.

For the Arthur C. Clarke Center for Human Imagination, I'm Stuart Balto. Thank you for listening. The only thing we can be sure of about the future is that it will be absolutely fantastic. USAA knows dynamic duos can save the day, like superheroes and sidekicks or auto and home insurance. With USAA, you can bundle your auto and home and save up to 10%. Tap the banner to learn more and get a quote at USAA.com. slash bundle. Restrictions apply.