Science Friday - Synthetic Genomes, Climate Panel, Local Recycling. March 1, 2019, Part 1

Episode Date: March 1, 2019

DNA is the universal programming language for life, and the specific code to that program are the combination of the base pairs adenine, guanine, cytosine and thymine. But are those the only base pairs that could be used to create DNA? Scientists looking into this question were able to create 4 different base pairs that don’t exist in nature. Chemist Floyd Romesberg, biologist Jef Boeke, and bioethicist Debra Mathews tell Ira how altered genomes could be used for creating novel medicines and fuels—and whether this is considered a new form of life. Plus: The climate is changing. Globally, of course. But also in Washington, where growing numbers of Republicans are jumping behind policies that would result in meaningful action on climate change. And yet, even as Congress appears ready to at least discuss the issue, and the government’s own scientists and military leaders sound louder alarms about the impending dangers of global climate change, the White House is assembling a group of climate change adversaries to counter those mainstream views. David Titley, a retired rear admiral who founded the Navy's task force on climate change, explains. Last year, China tightened standards for recycled materials it would accept, and now local recyclers nationwide find themselves struggling to find new homes for plastics, cardboard, and other materials that fell below par. Dana Bate, health and science reporter for WHYY, tells Ira how Philadelphia and its suburbs are handling the issue in the State of Science. And Sophie Bushwick, technology editor for Scientific American, explains how extreme climate change might cause stratocumulus clouds to disappear for good, and other top science news headlines, in this week's News Roundup. Subscribe to this podcast. Plus, to stay updated on all things science, sign up for Science Friday's newsletters.

This is Science Friday. I'm Ira Flato a bit later in the hour. The White House is assembling a coalition of climate skeptics to advise the president on climate science. We'll talk about how that's shaping up and how the climate is changing in Washington. But first, you know the old song, Blue skies smiling at me. Nothing but blue skies, do I see? Lyrics by Irving Berlin about Happy Times. I'm sure he sank it much better than I did. But a new study says that under certain extreme conditions of climate change, a certain type of cloud might be gone forever.

Blue skies smiling at me. It's not as cheerful as it sounds. Here to tell us more about the sad story. Someone is never sad. Sophie Bushwick. Technology editor at Scientific American Eye, Sophie, nice to have you back. Nice to be here. So researchers say extreme climate change could create conditions where there are no clouds?

So, yes, specifically this kind of cloud called stratocumulus. They're the ones that they're kind of low lying and they look sort of flat, almost like spread out like a blanket. And they reflect a lot of sunlight. But the problem is for them to maintain their integrity that they, at certain high temperatures, the air within them becomes so turbulent that they would just break up. And researchers have estimated that when or if we get carbon dioxide in the atmosphere at about 1,200 parts per million, that will be, the Earth will get hot enough that we won't have any stratocumulus clouds. And if that happens, the climate could go up by another 8 degrees Celsius on top of the existing 4, which would be devastating to life on Earth. Well, I guess hopeful news is that we're at 400, it has to go to over 1,000 parts.

Right. The problem is that if we don't do anything, that we could be getting close to that area by the end of the century. Wow. I don't even want to think. Eight degrees, that is some rise, isn't it? That's a lot, yes. That would melt a lot of icebergs. Yeah, the equator would be pretty much uninhabitable, but the Arctic would be, you know, balmy.

Not good for the Arctic. No, not good for any place. All right, let's move on this update a little more interesting or hopeful researchers genetically modified breweries yeast to make it produce CBD. That's right. So they modified this yeast. to make it produce CBD and THC, which are two of the two compounds called cannabinoids found in marijuana. They actually also said that this is a platform for them to make rarer cannabinoids. So marijuana contains more than 100 different of these compounds that fall into this family,

but it's just hard to extract anything except CBD and THC because those are the ones you find in the highest concentration. So they say this is also an opportunity to make all these other compounds, which could have really interesting applications. So CBD gets a lot of attention for potential medical applications. It's non-psychoactive, so taking it won't get you high, but researchers have investigated it. It's shown promise for treating epilepsy, but there's also a lot of hype about it, and it's hard to pick through just what it can do until more research is available. They say it makes you sleep better, you know, it can actually calm you down or it might be helpful in some sort of pain medication, too. Right. The issue is just getting, being able to research it.

So it's still anything derived for marijuana is still. classified as a Schedule 1 drug, that's the same category as heroin. So CBD researchers are really, they need to get licenses from the federal government, and they need to get funding in order to do these investigations. Because at the moment, CBD is being touted as a treatment for so many things. And whenever any single substance, people say it can cure anything, that's sort of like a red, flag warning. Yeah.

And Brewers yeast, right? They're always talking about using brewers yeast to make all kinds of stuff. stuff. Yes. So not only is brewer's yeast, it's traditional uses, you can make beer, you can make bread, which, you know, it's man's best friend, as a microbe, I guess, but it also has been modified to make a lot of other things.

It's already been modified to make hormones like insulin, and previous studies have actually used it to make opioids as well. Speaking of yeast, there's a controversy brewing. See what it did. In the world of evolutionary microbiology, tell us about that one. So

French scientists have analyzed these sort of microfishers in rocks that they say suggest that they were left by some sort of moving microorganisms, some kind of ancient organisms, sort of like slime mold that moved and left mucus trails that left these marks in the rock. But if they're correct, that these are not just random cracks, then that would push back the first earliest moving life on Earth to 2.1 billion years ago, which is 1.5 billion years before we thought. And that's not trivial, is it? I mean, that's a long time.

That's a long time. That's like a rewriting of evolutionary history. Yeah, and so what the scientists on the other side of the debate say about that? So they say that, as Carl Sagan said, extraordinary claims require extraordinary evidence, and that the evidence in this case, they say, is not sufficient. That he's made a good case, but that they want to investigate further and find other sources that would back up this claim. Yeah, you always have to look for you.

Yeah. Yeah. I mean, if this is science working the way it should, you know, if someone makes a claim, you should be, you should interrogated and test it and see if you can reproduce these results. Finally, we're going to leave our listeners with some food for thought, which is, researchers know why our brains crave sweets when we're anxious. I know that is so true of me. You know, when I'm watching a ball game, or the score is wrong, or there's politics, as a she-behers.

I'm going to that refrigerator because I want to relieve that anxiety. Now we know that. Yeah. It's your brain is because your brain is really greedy. So your brain is hungry. Of all the carbs you eat in a day, your brain consumes half of them. Is that right? That's right.

Yeah. So your brain is already using up all this energy. And when you're stressed out, it increases its energy intake by about 12%. So it basically can bypass the rest of your body, which is signaling, I'm not hungry. You know, I'm at a comfortable energy level. and your brain says, no, I need energy right now. And so your body's reaction to that is like, what's the quickest form of energy I can have? It's carbohydrates.

And what's the sugary carbohydrates are even better than starch and ones for getting you that quick energy boost. So it goes right to junk food. Yeah, yeah. Like if you always crave chocolate when you've got, you know, a paper dew or something. Wait a minute. Let's not put chocolate in the junk food. No, no. To me, allow me to be clear.

Chocolate is a magical. wonderful thing, but it's maybe not the most healthy choice. Okay, well, I'll agree with that. Thank you, Sovey, Bushwick, technology editor for Scientific American. Now, it's time to check in on the state of science. This is KERNO, St. Louis Public Radio News. Iowa Public Radio News. Local science stories of national significance that will affect all of us.

Now, why don't you put your soda can or your peanut butter jar in the recycling bin? And you do that, don't you? Where does it go? Well, up until last year, the answer was often China, which once took 40% of U.S. paper plastic and other recyclables. But after China dramatically clamped down on the quality of the materials, it would accept from other countries, local recycling plants in the U.S. have been struggling to find a home for their output.

In Philadelphia, half of recyclables currently end up in an incinerator every day. That's not what supposed to happen. was supposed to happen. And in the suburbs, it's a patchwork of different responses, depending on where you live. Here with more on that story, my guest, Dana Bate, a health and science reporter at W-H-Y-Y-Y in Philadelphia. Welcome to Science Friday. Thanks so much for having me. So 40% of our recyclables used to go to China. What changed there? Well, China changed its policy at the beginning of 2018. It was called the Chinese National Sword, and they basically cracked down and said they wouldn't take certain types of materials,

and the ones that they did take had to be 99.5% pure, which, put another way, could not be more than 0.5% contaminated. And that means anything from pizza grease on a pizza box to yogurt in a yogurt container, you know, sodas and waters in your plastic bottles, nothing could be, which for a lot of communities effectively was a ban, because their, you know, recyclables were about, you know, 50, 20, 30% contaminated in some cases. People were not cleaning out the peanut butter from the jar before they put it in the bin.

And so that leaves a problem for our local recycling plants that were relying on that Chinese market, right? Exactly. And they've had to look elsewhere. They've looked to Vietnam. They've looked to other countries in Southeast Asia, Malaysia, Indonesia, some have looked to Mexico. But none of them were really prepared to take the amount of recycling that China had been taking. So the Guardian reported on this story about Philadelphia's response, basically the city sending half of its recyclables to the incinerator right now. But you took a look at suburbs to see what's happening there, and some of them are adapting.

They are. None of them are sending things straight to the incinerator, though after talking to them, some of it does end up there or in a landfill anyway. because all this contamination we're talking about if, you know, sodas or water spills on the paper recycling, or there's too much peanut butter in that peanut butter jar, or things that just aren't appropriate, you know, a vacuum cleaner or some sort of old toy, that stuff can't be recycled. It contaminates the entire load, and so all of that does end up in a landfill of the incinerator. They were estimating anywhere to 30 to 40 percent of the entire load in most suburban regions. But, you know, a lot of places are adapting.

they're taking different approaches. In Atlantic County, New Jersey, I spoke to someone there. They're only taking plastics number one and two. They've stopped taking three through seven because they just can't find a market for it. And they said we don't want to contaminating the load. We want to be able to recycle the things we know we can recycle. So that's the approach they've taken. Other places are very much going back to basics.

They're educating their residents, sending out flyers, trying to get people to go on the website, keeping that up to date. and really reminding people, you know, here's what you can recycle, here's what you can't, here's how you can make sure that you're been as clean and uncontaminated as possible. Well, how about putting some pressure on the producers to make the materials easier to recycle? Exactly. Well, that is something, one person I talked to who runs a recycling program in Montgomery County here outside Philadelphia, she mentioned this.

It's called an extended producer responsibility model, and the idea is that, you know, producers would have more skin in the game. You'd have them at the table. Maybe they would make products that were easier to recycle because they would have the responsibility of taking that packaging back. And if they were a part of the process and there was a requirement that they had to take back some of this packaging and be part of the recycling process, it would be maybe therefore easier to recycle. Canada has done this. A number of their provinces have programs that are this sort of model. Europe's looking at it. Apparently California is looking at it.

hasn't really trickled down to a lot of the other states. But it could be something in the future that really makes a lot of sense. We'll have to watch it, Dana. Thank you. Great story. Thank you. Dana Bait, the Health and Science Reporter for W.H.Y.Y. in Philadelphia. We're going to take a break, and later, coming back soon, President Trump is assembling a panel of advisors on climate change whose qualifications for the job may be that their skeptical climate change is even happening.

The last stand of the climate change deniers coming. up after the break. Stay with us. This is Science Friday. I'm Ira Flato. The climate is changing globally, of course, but also maybe in Washington, where growing numbers of Republicans are jumping behind policies that would result in meaningful action on climate change. Take Representative Frank Lewis, a Republican from Oil Rich, Oklahoma, and a ranking member on the House Science Committee. Here's what he had to say as he introduced a hearing last month called the state of climate science and why it matters. By investing in research to develop carbon capture, carbon use, advanced nuclear, and renewable energy technologies, we can incentivize innovation

and growth in these industries and reduce carbon emissions in the process. Innovation is good for the global environment and the American economy. I take environmental policy very seriously. Congressman Frank Lewis of Oklahoma, and yet even as Congress appears ready to at least discuss the issue, and the government's own scientists and military leaders sound louder alarms about the impending dangers of global climate change. Pentagon calls it a matter of national security. The Trump White House is assembling a group of climate change adversaries to counter those mainstream views. And here to explain is David Titley, a retired rear admiral who founded the Navy's Task Force on climate change. He's also director of the Center for Solutions to Weather and

Climate Risk at Penn State University. Welcome back to Science Friday, Dr. Tilly. Thanks so much, Ira. Dave, what's going on here? Why is this panel being assembled? I wish I really knew that. It's an interesting story. You had John Bolton, the head of the National Security Council, hire Dr. William Happer for Director of Emerging Technologies last fall, and that's a great thing to do. We need somebody to look at emerging technologies. But Dr. Happer also has some views that I think could only be described as fringe, even within the climate denial community. He thinks the earth is too cold and we don't have enough carbon dioxide

and we need more. And in fact, he feels that carbon dioxide is demonized. So rather than working on emerging technologies, he's, Dr. Happer is focusing on science that we have all known for about 150 years. And we found out two weeks ago, he was trying to form a committee to basically roll back the intelligence community and the Department of Defense findings that climate change is a risk to our national security. That was exposed to the light of day by the Washington Post, and now what we understand is happening is the National Security Council is not focusing so much on the Pentagon, but really on the basic science, as if we're going to find, I don't know, two or three guys after a couple of beers who were somehow going to overturn 150 years and thousands. and thousands of peer-reviewed papers on very well-known aspects of why our climate is warming right now. And just to note, we reached out to Dr. Happer. We have yet to receive a comment back by airtime. You know, I've heard about this. I've heard this panel being assembled referred to as a red team.

Explain that concept. Sure. In the military, we use red teams all the time, and the private sector does too. And red teams are really good for examining policy options. So I'll give an example. Let's say NASA, as we all know, they want to go to Mars. But should we build a base on the moon first? Should we go directly to Mars? Those would be some policies.

And NASA, I'm sure, is going to convene, or already has, convened a red team of really smart people to go and really kind of what we would call scrub those ideas. Find the risks, find the opportunities, find the things nobody's thought about. NASA is not convening a red team to dispute the fact that gravity makes it really hard and really expensive for us to go to Mars. And what the National Security Council and Dr. Happer are doing is they're not looking at policies, which is what we all should be doing. What they're trying to do is really overturn basic physics, which is not going to happen. With scientists who are not climate scientists, not experts in their fields. Well, exactly. I mean, I'm a retired naval officer, but trust me, Ira, you would not want me in the cockpit

finding a Navy fighter jet at night on an aircraft carrier. You don't want to be anywhere near that. So just because I was in the Navy doesn't mean I'm qualified to do everything there. And that's the same with science, too. And to amplify on that, we spoke this week with Jeffrey Supran, a postdoctoral fellow at Harvard and MIT, about how not all scientists are qualified to give their opinions on climate change. You know, taking William Hapah and these other physicists on class, change would be like getting a car mechanic to fix your airplane. You're never going to get on that

flight. You know, I sort of similar to William Happer, was trained as a physicist at Cambridge University in undergrad, and I have a PhD doing laser optics at MIT, you know, and that may all sound very impressive. And yet I'm here to say, believe me, you know, that does not make me qualified to make, you know, controversial pronouncements on atmospheric physics and chemistry. You know, I, like most people, look to the experts who in this case are the climate scientist, and William Happer is not one of those. Your reaction, of course, you must agree with Dave on that. Well, yes, I mean, that's exactly where this is.

Just because you have a degree in science doesn't mean that you can overturn 150 years of what we've known. But the military, and you're an old Navy man, the military, and the Navy in particular, and over the years we've been on Science Friday, the Navy has been in the forefront of going green and all its areas, and it knows because it's two biggest naval bases, what San Diego and Norfolk are on the water, and these are national treasures, and the oceans are rising. Well, exactly, Ira. I mean, the reason the military pays attention to this is, frankly, this is about making sure we are ready.

We are ready as a military. So when operating environments change, like the Arctic is changing, the ice is melting out, we need to be ready. We need to be ready to defend our bases and our training ranges from rising seas, from droughts, from floods, from wildfires. We need to be ready to understand where there may be conflicts in the world that are going to arise, in part, due to climate change. We have to be ready for these. That's why the military cares. Yeah, I played a little cut at the beginning about Congress possibly, Republicans in Congress, possibly breaking with the White House and coming around to the idea that we need some action to be made on climate change,

whether for economic or environmental reasons. Do you see that change happening yourself? I do, Ira. I actually wrote a piece for the Washington Post to paraphrase or steal from Churchill, and I called it the end of the beginning on climate wars there. And to me, it is quite remarkable seeing some of the ranking members of the House committees saying very reasonable things, just as you played. We have Senator Barrasso co-sponsoring a bill with Senator White House, one of the most outspoken climate advocates for research into negative emissions. We have Governor Kasich saying very reasonable things about climate.

That doesn't mean all the Republicans are there, but things are changing, and it just makes the White House and the National Security Council effort with Dr. Happer really look like the deadenders. Dead enders. What about the Senate? Senator Brian Shats of Hawaii tweeted the other day that he and a few other senators want Senate Majority Leader Mitch McConnell to debate Democrats about climate change on the Senate floor. Is that ever going to happen? I'm not sure, Ira. Of course, you know, we see the politics playing out. But as long as the politics is playing out over what to do, not if we have a problem, but what to do about the problem, that's okay. That's what we have a political process for. And, you know, we've got everyone from AOC and the Green New Deal to different solutions. Let's have that debate about what we're going to do because we need to do something and we need to do it now. It will be a focus of what we cover for the rest of the year and focusing on climate change, the Congress and the new Green Deal, the Green New Deal, whichever way you'd like to say it. Thank you very much for coming on and talk with us, Dr. Titley.

Thank you so much, Ira. David Titley, a retired rear admiral in the Navy and director of the Center for Solutions to Weather and Climate Risk at Penn State. And just a note again, we reached out to Dr. Harper to join us, but did not receive a comment back in time. Well, you've heard this your whole life. It is the programming language of our cells and that the four base pairs known as AGCT make up the code of DNA. But could our DNA be built on a different code? Maybe more letters in the code.

Researchers have built unnatural base pairs now, and they've added them to the genetic alphabet, doubling the number of base pairs to eight in some cases in some of the research. The results were recently published in the journal Science. This is one way to retool DNA. Other scientists have been trying different types of base pairs, trying to build genomes from scratch. All kinds of new products are possible, right?

Medicines, fuels. What could go wrong, right? Haven't we heard this before? That's what we'll be talking about next. The brave new world, literally, of synthetic genes, the good, the bad, and the who knows. Let's open the discussion about technology with my next guests, both deeply involved.

Dr. Floyd Romsberg is Professor of Chemistry at the Scripps Research Institute in La Jolla, California. Hi, Dr. Romsberg. Hi, Ira. Dr. Jeff Foboko is Director of the Institute of System Genetics. I'll get it right, Jeff. System Genetics and a professor in the Department of Biochemistry and Molecular Pharmacology

at New York University Langone Health here. Welcome back, Jeff. Good to see you again. Good to see you. Just to define terms, how would you define synthetic genome to someone who has never heard of it before? Well, a synthetic genome, the way we look at it, is a genome that's built starting from non-living matter and can be designed on a computer and introduced into a living cell to essentially reprogram that, sort of like upgrading your operating system from the old to the new. You can add new features to the genome by changing the DNA sequences in specific ways.

But the recent research that you highlighted goes way beyond that in actually adding new letters to the alphabet that we have to play with. Is that something a lot of people are aiming to do? Well, I think it's a small group, a small and very select group of people that are carrying out that type of research, and it has all kinds of interesting challenges, but it is very exciting to see that expansion of the alphabet, at least in a test tube. Floyd, you weren't part of this latest study, but you have created your own unnatural base pairs in your lab, right?

Yeah, that's right. Tell us why you do that and why this latest study is such a big deal. Okay, sure. So why someone would want to do that? So the natural letters, as you already mentioned, G, C, A, and T, they're what cells used to make proteins. Proteins are what cells use to do what they do. So everything that you do is largely carried out by the proteins that you're able to make. But it turns out that those natural four letters encode for generally only 20 amino acids,

sort of canonical natural amino acids. And those amino acids don't actually do some things that we might want them to do. They're actually, if you went to a medicinal chemist and said, you know, is there anything interesting here? They'd be less than inspired compared to the sorts of molecules they build where they include different functionalities that help make drugs, for example, be the drugs they are. So what we're trying to do is what we tried to do, what we set out to do 20 years ago was to create a new base pair. Instead of four letters and two base pairs, we wanted to make six letters and three base pairs. that would increase the information that you could store, give you new information in a cell that the cell could retrieve and make new proteins with, and maybe proteins designed to have properties, like, for example, being drugs to treat diseases that were formally untreatable. So this latest work by Steve Benner, it's a little bit different. Steve's a good friend of mine. I have a lot of respect for him.

In fact, he's been doing this longer than I have, and his work was a real inspiration to me when I was starting my own lab. But what Steve has done is he's doubled these letters, but it's only in a test tube. been, what we try to do is something a little bit different. What our goals are are to have these extra letters where they can be replicated by DNA prelim races and not only in a test tube, but in a living cell where they can be used to produce proteins. What Steve has recently done in this paper that you mentioned was create these four additional letters that he's been optimizing for quite a long time and simply looked

at their stability in terms of forming duplex DNA. So their recognition, single-stranded DNA forms a duplex, apparently. together and he's shown that you can make those same pairings with these four extra letters. I'm Ira Flater. This is Science Friday from WNYC Studios. Talking with Dr. Floyd Romsberg and Dr. Jeff Buka. Have they been functional? Do these extra DNA, you know, if you're using these six pairs, can they reproduce and make themselves over again? So it's six letters and three pairs. And so in our case, yeah, in my lab, we've now have what we call semi-synthetic organisms. They're just bacteria right now, E. coli.

They live and they grow and they divide and they maintain those extra letters in their DNA. They can transcribe them into what we call M RNA and T RNA. Those are sort of the intermediate functional versions of DNA that go out into the cell and make proteins. And we've, in fact, made proteins with unnatural amino acids. And I started a biotech company called Synthorics, and they're using the technology to develop some anti-cancer. drugs that is really exciting to watch. Jeff, do you think an entire organism could be built this way with unnatural base pair? I think that we're really a long ways off from that for more than one reason.

The current three base pair system that Floyd talked about, it's amazing what his group has been able to do. but it's as far as I understand it's only possible to put one of those special base pairs in a row, whereas the natural genetic code allows you to put any number of them in a row. So there are limitations to the systems that exist right now that might make it hard to really program an entire organism. Even more daunting is the fact that we barely know how to prove. program an organism from scratch with the four natural bases. So I really think that that's still very far on the horizon,

not to mention the fact that the eight-based system that was recently described is only working at a test tube level right now and not, as Floyd said, inside living cells. So, you know, call me the conservative in the group. The four base pairs of DNA are plenty wild and crazy for us to work with right now. now, but we're not even creating, we're not creating truly new organisms for this. We're sort of endowing existing organisms with new functions. Our number 8447248255 if you want to call us. You can also tweet us at the Cy Fry.

But even using and can you rearrange things, the base pairs? Your eyebrows went up when I said that, Jim. Well, yes. We've sort of taken that to an extreme recently. So we had a paper last year where we had a lot of fun with the yeast genome. Now, the yeast, which is our favorite organism of choice, has its genome packaged into 16 units called chromosomes. And I'd like to just mention an analogy of them thinking of what we did. So if you think of, I don't know how many people remember what encyclopedias are,

but an encyclopedia is a series of volumes that has a whole bunch of information. information in it. And it's a good analogy for a genome. The volumes would be the chromosomes. I'm going to stop you there because we have to take a break. And we'll stop at the Encyclopedia. Think of your books. Think of them how they're lined up. We'll be back to talk with Jeff Buka and Floyd Romsberg. And Deborah Matthews is going to join us to talk about a little bit about the ethics of all of this work. So stay with us. Our phone number 844-724-825. We'll be right back after this break. Don't go away. This is Science Friday.

I'm Ira Plato. We're talking about synthetic genomics with Floyd Romsberg and Jeff Buka. And Jeff was talking about building a synthetic, completely synthetic genome in yeast. You got us up to an encyclopedia with a lot of books in it. Right. So the genome can be thought of as an encyclopedia consisting of 16 volumes. And essentially what we realized was we could rip off the back cover. of the first volume of the encyclopedia

and the front cover of the second volume and then glue those two volumes together. And by doing that over and over again, we created essentially a genome on one giant chromosome. And it has all the same information in it, so it's still useful. It's a little bit more tedious to handle.

But remarkably, the cells took this very much in stride and didn't complain very much. And that was a very surprising result to a lot of people that you can really rearrange the DNA sequences in such a dramatic way and still have everything work more or less normally. Let me bring on someone else who can talk about and react to the research that's going on here.

I want to bring on Dr. Debra Matthews, assistant director for science programs of the Berman Institute of Bioethics. and Associate Professor of Pediatrics at Johns Hopkins University. Welcome to Science Friday. Happy to be here. You've been listening, right? Yep.

What's your take on all of this? Which piece? I mean, first I want to emphasize something that Jeff said earlier, which is that this is all at a very early stage, right? Either whether you're talking about the Hachimoji DNA, these four new bases, with the best name ever, by the way, or whether you're talking about Jeff's synthetic genomes, they're fairly basic.

But we need to think about, I think, sort of what we do going forward, both what these technologies mean for us now, for science, what they can do for us, right? Lots of great potential applications like new drugs, new vaccines. Lots of really interesting basic science, but potentially risks as well. Floyd mentioned that he's working in E. coli. And E. coli was the organism that sort of kicked off our worries about recombinant DNA. So when we first in the 1970s, we were able to cut and paste DNA.

The experiment that was done that was sort of freaked people out, scientists and the public alike, was introducing an antibiotic resistance gene into e-coli. E-coli lives in all of our guts. And that worried people, we didn't know then what the risks would be. And so the scientific community sort of asked for regulation, both because they were concerned about safety, both of themselves and the general public, and also because they sort of understood that this was controversial.

Well, let me ask my scientists here. Jeff or Floyd, how do you control the synthetic genomes to make sure that the organisms, when you put these genes all together, and they've never been together before, make what you think they're going to make? Right. Well, so we take a number of precautions. We tend to work on the yeast front. Of course, it is naturally a very safe organism, but we work with strains that carry mutations that essentially render them unable to compete well in the wild. And we can introduce much more extreme forms of control.

It's actually an area we've worked on because we take this matter of safety of engineered organisms very seriously. So, and I know, I mean, in Floyd's case, I think he'll have a lot more to say about that, that with an extra base pair, you can exert a special kind of control. So maybe I'll hand it over to him. Yeah, if I could just inject. So our X and Y, our fifth and sixth letter that form that third unnatural base pair, like Debrage just said, we have it working in E. coli. We're working on getting it working in other organisms and other cell types. but we have to provide X and Y, the precursors of X and Y to the cell. And this isn't a Jurassic Park like situation because life's not going to find a way.

These are incredibly complex biological molecules that nature doesn't make. They don't make anything like them. They each would take something like 15 new steps based on enzymes that nature doesn't have anything like right now. And the notion that nature cut out of nowhere assemble such complex pathways, it's just a dauntingly, it's a very unlikely thing. I'm myself, I'm going to catch all sorts of flack for this. I'm comfortable calling it zero. So we have, in our case, a built-in safety system

because if we don't provide the precursors of X and Y to the cells, they can't maintain them in their DNA. And so if they escape into the wild, they'll die. And we've shown that many times. DeBri, you satisfied? No, I think, I mean, as I said, this is very basic right now. we're actually in a, you know, even sort of safer place because there's control over who has

very strict control over who has access to the new bases, right? It's not like you can just buy them. Or can you? You actually can. You can. Some of them you can. Some of them you can. So there's more control over the technology now, I would imagine, than there will be in the future. And I think we're in a really sort of strong position to think about what this does look like going forward. What do you mean you can buy them? Well, so actually, this wasn't even my lab. A few years ago, I was sitting at my desk and I got a phone call from a company that makes nucleotides. That's our name for these letters.

That's what scientists call them. And they said, well, we have a question about a paper you published in the synthesis of one of these analogs. Could we ask you a question? So I obviously knew nothing about it because I sit at a desk and I'm fortunate enough to work with some really talented people who actually do do things. So I had to go get my coworker and then we explained to them. And in this process, we found out that they had, based on our papers, decided to make them and sell them. So there's actually a couple of different companies now that sell some of the analogs. And they could make a functional semi-synthetic organism.

But in their hands, it also will not be able to escape. But they can do their own work on it. Yeah. Yeah. And several labs are. Jeff, can we buy your yeast? You can't buy it, but if you work at an academic institution, you can certainly obtain it. We don't really charge money for it.

I don't know. I feel a little queasy about that. Deborah, do you share my queziness? Yeah, I certainly would want there, ideally, to be a process in place to sort of a vet who has access to think about what the possible uses of these new nucleotides might be in the organisms that take them up. We don't, you know, the fact is we don't know how, you know, our system would react to novel nucleotides necessarily. And an issue that frequently comes up, almost always comes up when you're talking about synthetic biology generally, is that

of dual use, right? We, these scientists are doing fantastic, creative work with the best goals in mind, but not everyone in the world has the best goals in mind, right? So we might design something for very good purposes, but someone else might use it for bad purposes. And if, for example, these new nucleotides were able to make drugs more potent or more persistent,

which would be great in terms of treating disease, but more potent and more persistent would be bad in the context of a really harmful disease. Let me go to the phones. 8447248255. Let's go to Patrick in Yardley, Pennsylvania. Hi, Patrick. Hi, how are you?

Yeah, thank you. Great subject. My question is, how does this research intertwine with CRISPR technologies and how will it enrich CRISPR? Okay. going in the future. Jeff, what's the difference between this and CRISPR? It's a good question.

So CRISPR is an extremely useful tool that most of us use. I know Floyd has used it in interesting ways as well. So a lot of the work we do in yeast actually can be done without CRISPR, and I would say 95% of the work we do with our synthetic yeast genome is done without use. using CRISPR, but CRISPR is an amazing tool. It can be deployed in yeast as it can in many other organisms. If and when you fully synthesize the yeast, is it another form of life? Well, we call it SC2.0, so it has a different name, but it can interbreed with Saccharomycese

cerevisii, the natural counterpart, so it is formally part of the same species. So I would say no, by the biological species definition, it's not a new species. But would it be a new living thing? Well, remember, it's just a form of this brewer's yeast, and there are many forms of it out in nature. This one has engineered components in it, and it has a lot of engineered components in it. So it is able to do things like rearrange its genome on command that the natural yeast cannot do. But again, by the sort of traditional species definition, is part of the same species. So I think that is a yes, then?

That depends what the question was. So is it alive, a living, is it a form of life? It's a new form of life, absolutely. But it is part of the species we know and love as brewer's yeast. Floyd? Can you take out everything from a cell and put all your synthetic genome in there? And now we have a cell with something totally different for the nucleus. So as Jeff just alluded to a few minutes ago, no, you can't do that.

We've taken very much sort of, in some respects to the opposite approach, where we're sort of starting in a top-down approach, where we're going into an organism that has a full genome. Our base pairs, our fifth and six letters that pair to form a third base pair, they pair in a completely different way than nature's base pairs do. actually do exert a small distortion on the duplex, and they do rely on being flanked by natural letters. Now, we're actually just publishing some work that shows that we can actually put several in a row,

and we can actually put a pretty high density such that you wind up getting amino acids in a protein that are right in a row. But, for example, they'd be separated. We can put two in a row in DNA and still have cells replicate it and hold onto it. And we can put many as long as they're separated by one or two. But the way this works is these letters form codons. These codons are what determines proteins. These codons are combinatorial.

So in order to encode a new protein, you don't need them to be replicated in a row. Nature has existed, life has existed to this point by synthesizing every one of the proteins it's ever made with 61 codons. That's these words that can. And we now have 64. We've now added three. We're about to publish a paper where we've now, have our E. coli cells decoding three new codons. And, you know, to do that kind of thing,

and there are just so many fascinating applications that one could think about applying this to, you know, it is certainly correct that we can't put long strings in a row, but we also don't have any applications that would need that. There are just so many neat things that we can do the way that we're doing it. I'm Ira Flater. This is Science Friday

from WNIC Studios. running out of time unfortunately because you you were the last one to mention the neatest thing what would be what would be Floyd the neatest thing that you can do you said you can do so many neat things quickly I'll tell you right now the two things are working on in collaboration with this company synthetics that I mentioned we're actually making an IL2 drug that is really pretty impressive and I the chance to watch them possibly go cure and curable diseases will be just so gratifying. And secondly, we're going to make organisms that instead of providing proteins to us to do things, we're going to make new organisms that they themselves do new things. For example,

like eating oil spills and digesting them down to carbon dioxide, hydrogen, and water. So these would all be patentable new organisms, that? That is correct. That's Floyd where the rubber meets the road, so to speak. Well, so some of the work done in my lab is funded by this company that I mentioned, and they are, of course, interested in funding it if they can own it. Jeff? Yeah, I think my last word would be it's really important for us to think about the things that might go wrong, but we should also really think about the things that could go right, and there's a lot of them. Deborah?

Yeah, there's certainly potential opportunity costs, but there are also, you know, there are very very very very very very very very. values beyond scientific values that are important. And the public should have an opportunity to think about and talk about and voice their own values about how this technology ought best be put to use. That's what we're doing here today. One last thought before I want to leave you. If you can come up with new kinds of synthetic DNA, does that mean if we go to other planets,

we should be ready to find things we did not expect to find if we find living thing. Jeff. Yes. Floyd? That was me. Jeff? I think it's possible. But, you know, Francis Crick actually was a proponent of the idea of panspermia, which is that our DNA bases actually came from outer space.

They're floating around throughout the cosmos, and they're a universal. So I think that's a formal possibility we should also consider. Deborah, are you ready to find new life? Absolutely. Do you think it would radically change the way we look at life here on Earth? Well, I think it's incredibly interesting that there are these other bases that can be made and can function in systems, but we ended up with the four we ended up with. And I'm very happy for that.

We all are. I want to thank my guest, Dr. Debron Matthews, Assistant Director for Science Programs. of the Berman Institute of Bioethics, Associate Professor of Pediatrics at Johns Hopkins, Dr. Jeff Buka, director of the Institute of System Genetics, and Professor in Department of Biochemistry and Molecular Pharmacology at New York University,

Langone Health, right down the block here. Dr. Floyd Rumsberg, Professor of Chemistry at the Scripps Research Institute in La Jolla, California. Thank you all. Good taking time to do this. My pleasure. One last thing before we go.

Science Friday is hopping on a subway over to Brooklyn for an evening of science at Bam, Brooklyn Academy of Music. It's on Saturday, April 27th. We're putting on a special live edition of Science Friday with music and demos. And we're going to look at the secretly sciency lives of city pigeons. Those don't worry, wonder about, oh, how did city pigeons live and function? We're going to tell you everything you ever wanted to know. And you're not going to want to miss us so you can join us.

Saturday, April 27th at Bam. Saturday, mark it on your calendar. It's at night. Saturday night, April 27th, at BAM. Tickets and info, ScienceFrauddy.com slash Brooklyn. See you there, as we say in Brooklyn. Charles Berkowitz is our director, a senior producer, Christopher Taliatta. Our producers are Alexa Lim, Christy Taylor, Katie Feather. Technical and Engineering helped today from Rich Kim, Sarah Fishman, and Kevin Wolf.

We're active all week on Facebook, Twitter, Instagram, all social media. If you have a smart speaker, you can ask it to play Science Friday. If you can't hear it on the radio, whenever you want. So every day now is Science Friday. We'll see you in Brooklyn, Saturday, April 27th at Bam. I'm Ira Flato in New York.