The Synthetic Biology Future with Michael Specter

Abdul El-Sayed.

Today, we're talking about synthetic biology. The idea that humanity has developed molecular tools that can, with more precision than ever before, start to tackle health problems that have plagued us for eons. These approaches certainly offer tremendous promise, but they also come with real perils. First, the promise synthetic biology can fundamentally reshape the landscape for our health.

In fact, it already has. Let's go back to Covid-19, sorry, but it's endlessly relevant. The COVID-19 vaccines, as politicized as they've become, were an absolute scientific miracle. Make no mistake about it.

You have this awful, extremely transmissible, deadly virus spreading like gangbusters across an increasingly globalized world. First China, then Italy, then every major city in Europe, then Seattle, then New York. People are filling up hospitals, dying in their homes, filling up morgues. And then, within less than a year, less than a year. Scientists literally download the virus's genetic code off the internet and design a safe, effective vaccine, take it through clinical trials, and then deploy it at scale in the population. That miracle.

MRNA, short for messenger RNA, is basically the body's notes app. It translates DNA, the body's holy Book, containing the instructions for every single thing the body makes into proteins in the body's cells, every time the body makes a new cell. There's a whole lot of energy invested in checking and rechecking that DNA, that all-important holy book, that it's copied correctly. If it's not, it means disaster, but making mRNA, it's different.

The body literally opens up the Holy book, untwists the bit of DNA it needs, and then it takes a quick note through the mRNA. Since mRNA is being generated all the time in the cell, it doesn't need to be checked and rechecked, it's just a note. After all, the mRNA leaves the cell nucleus where the DNA is and is quickly translated into proteins that go off and do the business of the cell. Whether it's allowing you to see, think, hear or lift something heavy. Our ability to harness that tool to create mRNA in a lab that can then float into cells, get translated and make protein that ability has saved millions of lives.

But that that's just one possibility. For synthetic biology. The ability to understand and even manipulate DNA means that we can literally edit embryos so that the genetic diseases they'd be born with can be erased like they never existed. You can see where I'm going here. I said, Promise, but I also said, Peril. The ability to edit DNA comes with all sorts of interesting quirks.

Because biology isn't linear, it's extremely complex. That quote book of our DNA doesn't read linearly, left to right, top to bottom, page after page. To construct those complex molecules that make our cells as varied as the ones that make up our retina. Encoding light to neurons that then send them to our brains, to the glial cells that support those neurons, to the muscles that turn our eyes. All of them borrow from bits and pieces in different parts of the book. So when you erase one piece here, you literally don't know all the other pieces. That it can affect, all the ways that it can reshape self-function.

If there is a dark underbelly to humanity's long history of trying to muck with the biology that contains us, it's the unintended consequences of those attempts. Think about it. Whenever we talk about a new medication, which is just a really simple version of biological engineering, we talk about quote safety and quote efficacy. Safety comes first. We have to prove that we've documented the unintended consequences of manipulating our biology before we even begin to talk about the intended consequences.

And even then we get it wrong. Consider thalidomide. It was first marketed as an over-the-counter morning sickness medication for early pregnancy, except that it caused severe birth defects in infants. The thing about synthetic biology is that it's many orders of magnitude more powerful than simple medication. But with great power, as Uncle Ben reminds us, comes great responsibility.

I wanted to understand the power of synthetic biology, its promise and its perils with someone who's been thinking a lot about them. Michael Spector is a staff writer at The New Yorker. He recently wrote, or, should I say, spoke, a really cool audio book called Higher Animals about exactly that topic. So I invited him on the show to talk us through all of this and more, Here's my conversation with Michael Spector.

All.

I really appreciate the opportunity to.

Well, I got into, I've.

And that is wonderful because it means you can download the sequence to the Covid virus. Make a vaccine Moderna had a vaccine made in literally in days. But it also opens us up to lots of problems and risks. And I think we need to be aware of what biology that can move at the speed of light really means.

And I think this is the beginning of many more advances that will be exciting, both in medicine and in other areas.

And the idea that we can make vaccines, and also, it must be said, make viruses quite easily and relatively cheaply.

But that's sort of akin to lighting a fire with a flint. What we're talking about here, what are the kinds of things that we have the capacity to do? When you move past? In vivo engineering, that moves at the pace of selective mating to in vitro engineering, which allows us to sort of synthesize things de novo.

So now there are people trying to make energy that way, they're trying to replace all sorts of chemicals that way. And very importantly, there are enormous groups of people who are trying to synthetically make drugs. That will focus very narrowly on the types of things that cause specific cancers, because the way we treat cancer, by and large, is the way we always have. Which is to poison cells and hope we kill enough bad cells before we kill too many good ones or we cut them out. And increasingly, we're going to have the opportunity to say we want to focus on those cells. And we're going to make something synthetically that will deliver itself and attach itself to those cells, and only those receptors.

It also was scary because we didn't necessarily know what the implications of mixing species was, and there were implications. So those hearings are kind of remarkable because they're the first really public acknowledgment that we're embarking on a new and very difficult world. And the mayor of Cambridge, who had one of those classic Boston accents, was infuriated. I mean, there's a long history of Cambridge and Harvard fighting with each other.

But this was particularly hostile in many ways, and some of the questions he asked. If you listen to the tapes, I have the original archives in the book. They seem crazy, and they were crazy at the time, but honestly, none of them are crazy now. Like he started talking about, are you going to be able to create a new species?

Can you be sure you're never going to make an accident? Can you be sure you'll never leak something from a lab? Those things weren't that important at the time, they're critically important now, and those are questions we need to start supplying answers to.

And now we have far more impressive tools. Can you talk about the CRISPR revolution and the role of thinking about RNA? As if we were talking about cut here and scissors, now we're talking about almost biological 3D printing. Can you walk us through that?

And when CRISPR came along, CRISPR is a molecule that is basically like a genome. And it will target exactly the place you send it. And it will do what you want. You can encode a gene or a molecule to put it inside CRISPR, have it delivered, it will cut the genome where you want it.

And then it could cut out what you don't want and replace it with something else. So there are lots of experiments now, and some of them have been quite successful. Where, when you have these sort of single gene diseases, scientists are just replacing those genes. And you can start to think about some of those diseases being fixed in embryos. By just taking out the bad wiring and replacing it with wiring, we know works. That's something that I don't think anyone ever thought was possible before, and so that was the first remarkable tool along these lines.

Now they have something called base editing and prime editing, where CRISPR is kind of like a pen, where you rewrite the DNA permanently. You can now kind of erase one nucleotide and have it come back later. Because RNA is the stuff that delivers molecular messages throughout your body, and the mRNA revolution is one. Because it doesn't do what? For instance, what vaccines have always done, which is, on some level, basically infuse a version of the illness you are trying to defeat into your body. Either a little bit of a live version or a dead version, and it gets your antibodies revved up, but mRNA doesn't do that.

You shoot that. In its blueprints, it just says, build a protein that will go to this spike thing and rope it around like a lasso and block it. So viruses can't get in there. And one of the great things about that is that RNA disappears after a little while. So once RNA makes that protein, you won't find it in your body after that, but you'll find the antibodies. Because they have memories, so that's why when we get a vaccine, we're protected for a while.

And as we all know, we're not protected perfectly or forever. But that's not really what vaccines usually do. One of the analogies that I find very helpful.

And then the protein is like the meal you make from the end outcome. And the nice thing about using mRNA is that it's kind of cheap. You can take as many pictures as you want, it still encodes the information, and if you lose that picture, you're kind of okay with it.

Versus if you use DNA and you borrowed your grandmother's cookbook from your mother's and you lost it. That'd be a very different ball game than, Oh, I deleted the picture. And so it's at the perfect level of information carrying, in a way where it's biologically cheap, but it is good enough to carry information. That allows it to be really a fantastic tool for manipulating a biological outcome. So in the past, in the battle days, when we wanted to vaccinate somebody against a virus, we would literally beat down a version of the virus and then send it in the ring with our body and hope that our body would learn enough from it so that it was ready to fight it, but that that virus wouldn't do anything, we literally called that live attenuated virus, and then we figured out how to kill the virus and send it in there.

And then our bodies would react to it. And now what we can do is we can say, actually, I'm going to give you one hair from the virus, but it's not even going to be a hair. It's going to be a blueprint to make the hair. And then your body's going to make the hair. Your body's going to recognize the hair, and the next time it sees the hair, it knows how to fight it.

Right, and this is way better biologically, because, well, and folks with immune disorders, sending in a live virus can be a real problem. And you know, folks remember back to the polio outbreaks that we had late last year, these were actually polio that had emerged from live, attenuated viruses. And the funny thing about it is that anti-vax people used the fact that the polio had come from a vaccine to argue against the mRNA vaccines. Which are intended specifically not to create this problem.

Right, and so you can't have it both ways.

The last note on this that I think is worth offering here is that this kind of technology, I think is. We're just scratching the surface around the overall value in medicine and health care. You talked a little bit about the role that CRISPR and other mRNA might be able to use be used in taking on genetic disorders. Can you talk a little bit more about some of the exciting uses of what this technology could be used for? First of all, I agree with everything.

As to some of what this stuff is already doing, there are some really promising tests with diabetes with sickle cell. Sickle cell is something that I don't want to ever say anyone's cured. But there have been some really excellent treatments using CRISPR-delivered molecules that replace the sickle cells that cause the problem and end up killing many people. There are lots of sort of one gene diseases, there are actually thousands of them, and a couple of them are eye diseases, where if you have one broken gene, you end up going blind.

Several companies have gone pretty far in developing treatments for those kind of illnesses. Because if you're gonna get rid of one broken part of your genome, it's not that hard to do right now. Some of the more complex illnesses, cancer, all sorts of autoimmune people are working on that and there's a lot of progress that has been made. But it's not as easy as. Sort of, you know, the low-hanging fruit are these simple single gene mutations. And there's been great success.

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Because every year we get these vaccines and they kind of suck, they're better than not getting them. But you know, you can't say, hey, you're going to get this, and there's no chance you'll get terribly sick. And that's because you know this. But maybe some listeners don't, you know? Influenza looks sort of like a stalk of broccoli, and the broccoli head keeps changing. Every year and every year we get new vaccines. We haven't been very good until now at trying to address the stalk, which stays the same.

And the mRNA technology is so far in tests, being able to do that. So there's a lot of hope that we would be able to develop an influenza vaccine that you would use maybe not once in a lifetime, but every 10 years. Like Tetanus, for instance. And that would be wonderful, because flu is a very serious illness, it kills a lot of people and it threatens all the time to kill more. Because we never know when we're going to have a deadly pandemic.

But some of the time, those mistakes make the virus that much more efficient, whether it's more transmissible or deadlier. From our standpoint, both of those things are worse. And so, as it's evolving, we're sort of taking a shot in the dark about where we think it's going to go. Based on sampling that we get from what the flu season looked like in Australia, where they have sort of a flipped flu season because of flipped summer and winter. And so we're always kind of guessing. And now with mRNA, we can be way more efficient at meeting it where it's going, and we can micro-target in a far better way.

I liked how you used that analogy of broccoli. We can target the stock instead of targeting the floret part. The same goes with Covid, and there's been some work on a universal target there. The interesting question I have for you. And we touch on this. It's kind of part of our beat here at America. Dissected is the implications around the incentives to produce these.

Pharmaceutical corporations have a real incentive to innovate treatments for diseases that are somewhat chronic, and for which treatments will have to be taken regularly. And, ideally, they're not deadly diseases because people have the means of attaining this medication. So I always say that the perfect drug is Cialis or Viagra, right? Something someone's going to take regularly. They're usually in a position to be able to obtain it and it's going to work very, very well to do the thing it does.

The worst possible drug you can make is the next generation of antibiotics, where physicians literally have an incentive not to use it. And when you use it, you get it for two weeks, and that's that right. And so I'm wondering where we have these situations where mRNA technology could offer a once-and-done kind of response. Is there an incentive on behalf of the industry to actually pick that up? Right? Because you could see Covid, for example, is a perfect example of this.

There is no incentive, from a pharmaceutical corporation standpoint, to produce an Omnicovid vaccine, because then it would be once and done. Rather than here. Take one every year and we can sell that to you.

And I think once you get a good universal influenza vaccine, it's going to be really hard to keep it down. I mean, the government of the United States is going to have a very difficult time saying no, we don't want to adopt this thing that every single test says would save. You know, 40,000 people die every year of influenza, it's no joke. So I actually think mRNA technology is going to win. But I think these things have been delayed because of the very problem you point out.

There's nothing in it for pharmaceutical companies beyond market incentives. What do you?

However, I can tell you, if we had an HIV vaccine, which would be miraculous and wonderful. There would be a lot of people in this country running around saying, I'm not giving my child a vaccine. That will encourage them to have premarital sex. And, believe me, I've interviewed a lot of people and I wish that this was a ridiculous thing to say, but it's not so. I think we've seen a lot of people wondering about what they think is new technology. MRNA seems brand new.

It's been worked on for 20 years, but it is true that we didn't have hundreds of millions of people using it until this pandemic. So I could understand the hesitation. I don't understand it now because it's been used so much and it's really, very safe.

So I kind of always feel that the biggest problem is making sure people understand that there are risks and benefits to technologies. Because people on one side usually only talk about the benefits, and on the other side, they only talk about the risks.

I also, I think I have to add that this technology is becoming so easy to use that it's stupid to pretend that bad people won't use.

That's just not, that's not usually how that works. And instead, what you're doing is you're creating a circumstance. Where the consequences of that, when they're twenties, thirties or forties, become so much higher. So you're right, like, that point about this sort of misappropriated sense of how people actually engage with the world and their sense of risk is a big challenge. The other is, you know, when it comes to RNA tech, you know, I started this conversation just talking about, you know? When I was in college, I remember reading about how mRNA was going to be the future of vaccines. When I was in med school, I remember reading about how we were almost there on that ability.

And then, you know, in in my adult life, I, unfortunately, as along with all of you, had to live through the pandemic. In which the answer was going to be mRNA based technology. So, you know, the hard part about what is what is new technology is that that scales according to how close you are to that technology, right? You know, you talk to folks about AI, for example, and a lot of the engineers. When you bring up ChatGPt. They're like, Oh, we've had this, like, that's, that's not new, and I'm like, Okay, so what do we actually have?

Because Chatgpt sounds downright scary to me, it's funny because I'm working on a.

Why is this shocking you? because ChatGpt version 10.0, that's when you need to get scared. And that might not be 50 years from now.

But Covid has already killed more people than a nuclear weapon dropped on Moscow, New York or London would kill. But at least with nuclear weapons, there is a framework for arms control and for understanding where the components are. We actually tell people, Oh, you got a virus? well, don't spread the virus around. But please publish it as soon as possible so we can have the blueprints. The blueprints of every virus pretty much known to man are just living on the internet.

You don't have to be smart or sophisticated to find them. And for a long time, that was fine because there were very few people who could do anything with those blueprints. But that's changing in the same way that once computers filled giant rooms and buildings and they weren't as powerful as the watch you're probably wearing right now. Well, we're in the early days of that transition in biology and it's going to be great. But pretty soon your fourth grader is going to come home and say, Dad, look at the virus I just made.

And you're not going to be that happy when he says that. So we need to think about these things a little more seriously than we ever have before. Yeah, and you were getting there in the conversation.

There was this gain-of-function research, and what you're painting is a future. Where? Instead of having to do gain-of-function research at the Wuhan Institute of Virology, behind a protected lab space, like you said, your fourth grader can be doing gain-of-function research with a synthetic biology kit. Is there an effort to try and restrict some of this access and certify who gets access to it? So you understand where these things come from, because, of course, the nature of viruses is they're microscopic and they don't have a fingerprint. And so the notion that one can pick up this information and then leverage it to create something extremely dangerous.

I mean, synthetic DNA. You can order it online, the way you order shoes from Zappos, or a book from Amazon, or anything, a plane from Amazon for that matter. And there are certain stretches of genetic sequencing that one can say, why are you ordering that? We need to have some central group that isn't the police. But sort of says, Hmm. There are about 157 sequences out there that we know you really aren't using for research, so what are you using it for? You can do that.

You can barcode DNA now that there are DNA printers that are relatively inexpensive, where you put sugars in and DNA comes out, you can barcode that DNA. You can watermark it the way dollar bills are watermarked, so at least you'd have a way to trace it. A lot of this is sort of a gun control argument.

Are you going to get rid of every threat? Probably not, but you can do a way better job than we're doing. There are people trying to investigate whether certain wavelengths of UV light would kill viruses without harming other things. We actually care more about. And if so, it's possible that there would be places where we could put light bulbs in and that would work.

Also, PPE, you know, the personal protective equipment that we have is pretty primitive. It could be a lot better, a lot more sophisticated, possibly less upsetting to some people who are upset by it. I mean, we can do all these things. And there's even, I think, serious attempts to sequence DNA in wastewater, because if you look at the wastewater, you can see viruses.

If you sequence a virus and you see that it's multiplying exponentially, then you can say, Hmm, what is going on there? Is this man-made? Is it real? And there'd be a way, you know, because mRNA is very flexible. There is a way to make vaccines really, very rapidly, but we have to know what we're making our vaccines for.

Well, there's a vaccine for the plague, but you can't run around Wyoming, South Dakota, North Dakota and Utah vaccinating every single ferret running around. But you could splice the vaccine into the genes of a ferret so that, when that ferret made it all, the subsequent progeny would have heritable vaccines, they would be born protected. And that's something that the United States government and private researchers are working on now. That kind of stuff can really help protect a lot of things.

There are people working on this to protect coral, which is being bleached to death by sun. That shouldn't be as bright as it is, but we know why it is. So I see lots of solutions to lots of really significant problems. We're talking about growing things instead of making them in chemical plants and making huge amounts of pollution, and I think that can really solve enormous problems that we have.

Really moved by Elizabeth Colbert's book Under a White Sky. And she talks about the ways in which we innovate solutions to problems that were themselves the consequence of innovations that we've had. And there's this Russian doll issue of continuing to have to fix problems that we've created. How often do you feel like? With this kind of new power, we are going to find the easy way out of problems? That our public policy really should have stopped in the first place. And what kind of worries do you have about the unintended consequences of this kind of thing? You could imagine that situation with the ferret species you talked about, and we didn't realize that programming it this way ended up giving them a genetic disorder that wipes out the whole species.

So these are the kinds of things that hopefully you have smart, careful scientists who are thinking through them. But when you're talking about biology, there's so much complexity there that when you pull one piece, you don't really appreciate, either inside the body or even in an ecosystem, all the implications of that pulling. How do you think about the way that we should be adjusting for, or engaging with that level of complexity as we try to pull on pieces?

I think we have to start thinking about technology as not just this broad sword that we're going to use all the time. But once in a while, it will make sense. The thing with the black-footed ferrets, they've done endless amounts of tests. You're right, there could be some sort of unusual circumstance. But what we're looking at right now is the extinction of a species that could be saved, and researchers can't find any reason not to do it. Mosquitoes We can change mosquitoes so that they don't kill hundreds of thousands and millions of people with malaria. But there are lots of implications to doing that. Because when you start releasing edited mosquitoes by the tens of millions, you better be sure that you understand the consequences.

And that's a really hard thing to do. I don't think it's impossible. I think we have the ability to do it. But if we just jump in blindly, we will make terrible mistakes and it will end up being worse than it was in the first.

And I think there are a bunch of people who might be willing to listen for a few hours, who might not sit down and read a long book about synthetic biology. And it's just an attempt to reach a different audience, a broader audience, maybe entertain them a little, but to gather a message across.

It's a really compelling listen. Our guest today was Michael Spector. He is a journalist with The New Yorker, and he is the author of the new audiobook Higher Animals. Michael, thank you so much for taking the time today. Oh, thank you for having me.

It was great.

And eyes, well, they're really helpful if you want to see where you're going. For three years, the New York Times has kept what I would argue was one of the most important data feeds on Covid. Even when the CDC's data was spotty or less reliable during the Trump administration, the New York Times database was right there, showing us where we were headed. This week, the New York Times announced a pause on their data collection efforts. They're officially switching over to CDC data.

I raise this because of what it tells us about the pandemic. On the one hand, three years in, with cases, hospitalizations and deaths near an all-time low. It's sensible that the resources we once needed to keep real-time information on the pandemic should sunset. On the other, unilaterally disarming our infrastructure, when the virus could always mutate and evade our immune responses, could ultimately have a scrambling to build this infrastructure back up anew. It also raises a bigger question, one that we've asked several times here on this podcast How does a pandemic end?

We've been circling around this question for a while now Is it when literally no one gets sick or dies of Covid? If so, then the pandemic will never end. As we've discussed on this podcast, Covid is with us permanently. The endgame here isn't a complete defeat.

Perhaps it could have been if we made a whole set of different decisions, both before and during the worst parts of this, but it isn't now. So we're not getting to zero. The challenge is that some folks will never be comfortable with any Covid, but here's what I struggle to understand. Most of these folks seemed a lot more comfortable before Covid, with diseases that routinely kill a lot of folks, like the flu.

Will folks feel okay with back to normal when Covid death rates are more similar to the flu? Mind you, that's still 50 to 70,000 deaths a year. And look, it's really hard to be comfortable at all with a number like that. At the same time, an average of 300 people died every day last week, that's almost as low as it's been in the Covid era.

But 300 a day, that's still, well, more than the flu. The truth is that there is no answer to the question of when a pandemic ends. It's a Rorschach test for competing values. Even then, we're learning a lot more about the long run consequences of the pandemic. In one study out of Vanderbilt, researchers found that the pandemic led to 719 fewer steps on average. Which, of course, for all of us who lived through this thing makes a whole lot of sense.

It's like the world stopped all of a sudden, because, well, we stopped. Here's what I'd like to understand, though. How many folks took up new exercise hobbies during the pandemic? I certainly did. Is it possible that, even though during the acute phase of the pandemic we were moving less, it may have reminded us just how much we need and love movement?

That perhaps out of all of this, we ended up moving more because of it. Dear researchers at Vanderbilt, please ask that question I'd like to understand and then come on the show and tell us the answer. But the pandemic, well, it didn't always leave us doing less of things. There are some things we did more of.

About nine months after the initial lockdowns, there was a mini baby boom. In 2021, there were 51,000 more babies born than in 2020. Those kids owe their existence to countless hours mommy and daddy spent in lockdown. This week, the Biden administration dropped what should have been a routine economic report, but they did something different. Here, they included a specific chapter in the quote economic report of the president, which is usually as boring as it sounds. Detailing all of the ways that the climate crisis could drive federal government spending and how federal policy may be contributing to the climate crisis.

Now I know this is a health podcast. Abdul I know, but hear me out. The linchpin between government policy and climate change almost always runs through the people, what we do and how it affects us, and that that's a health issue. For example, think about the vulnerability to climate catastrophes.

Think about people who live in floodplains, vulnerable coasts or fire prone climates. Obviously, floods, hurricanes and fires are harmful to people. But the only reason people can live in these communities is because the federal government underwrites the insurance they need to live there. Maybe that's not a great idea, considering that these events are happening faster and more powerfully every single year. Look for those of you who live in floodplains, vulnerable coasts or fire prone climates. It ain't me, don't at me.

I'm just saying, the federal government is making this argument, and that's exactly. The problem is that we're not willing to hear the truth about the consequences of the choices we're making. And I think in this report, the Biden administration is trying to make us pay attention. The report also talks about Medicare.

We don't think about Medicare as a climate issue, but hear them out. Increasing temperatures and climate events are already driving higher rates of illness, particularly among seniors, whose healthcare, by the way, is paid for by Medicare. The more the climate crisis presses on, the more Medicare costs. You'd think Republicans would want to do something about that, hmm.

Folks, it's just another reminder that the climate crisis is a health crisis. That's it for today. On your way out, please rate and review. Please rate and review. I'm going to ask you one more time, please.

Would you do me the kindness of rating and reviewing? Thank you. Also, if you love the show and want to rep us, I hope you'll drop by the crooked store. For some America dissected merch, we've got our logo, mugs and t-shirts.

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America dissected is a product of crooked media. Our producer is Austin Fisher, our associate producers are Tara Terpstra and Emma Elk. Frank Vasilis Fotopoulos mixes and masters the show.

Production support from Ari Schwartz. Our theme song is by Takashi Ozawa and Alex Uguiera. Our executive producers are Leo Duran, Sarah Geismar, Sandy Gerard, Michael Martinez and me. Dr. Abdul El-sayed, your host. thanks for listening.

This show is for general information and entertainment purposes only. It's not intended to provide specific healthcare or medical advice and should not be construed as providing healthcare or medical advice. Please consult your physician with any questions related to your own health. The views expressed in this podcast reflect those of the host and his guests, and do not necessarily represent the views or opinions of Wayne County, Michigan, or its Department of Health, Human and Veteran Services.