Niko McCarty on Building Asimov Press and Writing for Ambitious Readers

Samuel Arbesman:

Welcome to The Orthogonal Bet, where we explore the weird and wonderful ideas that shape our world. It's a cabinet of curiosities for the ears and the mind. I'm your host, Samuel Arbesman, Complexity Scientist, Author, and Scientist in Residence at Lux Capital.

In this episode I speak with Niko McCarty, the Founding Editor of Asimov Press. Niko has a long background in biology and science journalism, and currently runs Asimov Press which publishes deep and thoughtful articles at the frontiers of biology, as well as about its history.

I've long been a fan of Niko's writing and wanted to talk to him for so many reasons. He's building a new press and publishing fascinating articles, which means he thinks a lot about science journalism, but Niko also has his finger on the pulse of the future of biology. We had a chance to speak about Niko's start in science journalism and how his newsletter changed his life. We discussed what Niko's vision and approach to Asimov Press is. Why he publishes science fiction short stories, and even how Asimov Press is moving into publishing and print, and how he thinks about this.

When it comes to biology, Niko provides so much wisdom into how to think about the cutting edge in biology and biotech. We explore the levers that create biological progress and Niko's vision of the future in biology. There is so much in this conversation, and I had a wonderful time speaking with Niko. Let's jump in.

So Niko, great to be speaking with you and welcome to The Orthogonal Bet.

Nicholas McCarty:

Thanks for having me.

Samuel Arbesman:

So I want to talk to you about a whole bunch of different things, about biology and Asimov press, but I think maybe a great place to start might be just to hear a little bit about your own background and how you got started in the world of biology.

Nicholas McCarty:

Well, when I was a little kid, I told my dad I wanted to be a journalist, and I guess you could say he convinced me that I should study science or engineering instead. So I went to school with kind of a desire to be a writer. I went to a school that is very much known for its writing. I studied at the University of Iowa, which is in this beautiful place called Iowa City, which is a UNESCO City of Literature along with Edinburgh, Scotland. And so great writers pass through there all the time, you know?

Roxane Gay would come all the time, and Stephen King, and Kurt Vonnegut used to live there and teach at the Iowa Writers' Workshop. So it's a very legendary sort of writing place. But anyway, I was there studying science and basically writing for a magazine on the side.

Samuel Arbesman:

Was the magazine a university magazine?

Nicholas McCarty:

No, it was a local magazine called Little Village, Little Village Magazine, and I picked it up in probably one of the bars. You know, I went out to a bar at some point and it was kind of one of those free magazines that they leave around the city, and I wrote science for them.

Samuel Arbesman:

That's pretty cool.

Nicholas McCarty:

I did my first reporting trips. I would drive out and interview people about bees and stuff. So yeah, very interesting gig, but I really did not take that seriously, and I was pretty all-in on biology and I took that much, much further after my undergrad and went and did advanced degrees in that as well.

Samuel Arbesman:

Okay. And so you were doing the biology stuff, and then what led you back to the writing world? Was there some specific thing? Was it kind of just you realized there was this constant desire to do more writing and more engaging with the public? Was it a specific moment where you're like, "Okay, I have this story that I really just want to be telling?" Was it something else entirely?

Nicholas McCarty:

You know, there was no story, and I wish there was some narrative in my life that makes sense and tell some kind of cohesive picture, but everything is just kind of an accident. You know, I loved science. I was doing synthetic biology stuff, engineering cells, engineering yeast and microbes.

And the honest truth was, I was doing my PhD at Caltech and I was in a very heavy physics lab, a pretty intense biophysics lab with lots of mathematicians walking around, and I was one of the few experimentalists, actually in the lab, nose to the grindstone, so to speak, coming in on the weekends. The theorists don't come in on the weekends.

And covid hit, and I was just at home and I was like, "Wow, I kind of want to be doing something different." And I decided to just go for it. I liked writing, so I decided to drop out and I moved across the country and started a master's degree at NYU.

Samuel Arbesman:

Oh, wow.

Nicholas McCarty:

And it was very fortuitous because I emailed this guy, his name is Dan Fagin. He runs the science journalism program at NYU, and I found him because I read a book. He wrote this book called Toms River, which is about a cancer cluster in New Jersey.

Basically, all these Little League baseball players in Toms River, which is like this legendary Little League baseball town. They win the Little League World Series, and these kids started getting cancer, there was a cluster. And he wrote a book about the investigation and why that happened, and it won the Pulitzer for nonfiction.

And I emailed him and was like, "Hey, I love your book," and he's like, "Hey, come to NYU." So everything was ... You know, it's kind of just life is a series of accidents.

Samuel Arbesman:

No, that's amazing though to hear. Well, first of all, the fact that you reached out, that requires a certain amount of proactive effort. So I wouldn't just chalk it up to random accidents.

But okay, so then you did this writers' program, this writing program. And then after that, was the goal to get a science journalism job? What were you thinking after that, because you mentioned you'd also been doing some synthetic biology stuff as well. Were you kind of thinking about trying to blend these things together?

Nicholas McCarty:

You know, that's good. You're really opening up some past thoughts. I think at the time, when you're in an environment, like a science journalism school, there are just certain sort of mantras or dogmas or expectations. As an example, you're probably not going to be an editor in the first several years of your career, right?

You're lucky. In the journalism industry, you're lucky if you get a staff writer job. Those things are hard to come by. Certainly, it's going to be years before you become an editor and potentially decades before you start a publishing company or you start an ... So I was not thinking at all of things like that.

My priority was, "I'm completely broke. I'm in debt. I'm living in an apartment that is roughly the size of a closet and paying 3,000 a month for the privilege, and I just need to get a job."

Samuel Arbesman:

Sure.

Nicholas McCarty:

So my first internship, which was fortunately paid was actually at Retraction Watch. Retraction Watch is this great blog that covers kind of scientific fraud, scientists doing bad things, retracted articles, and the backstory behind why papers were retracted.

So I got some investigation chops. I became better at interviewing people and sort of extracting information for a story and convincing people to talk to me. Very valuable skills.

And then from there, I worked as a staff writer. I was actually a data reporter, was my title at the Simons Foundation. So the Simons Foundation in New York Funds two newsrooms, Quanta, which is very famous and well-known, and then Quanta's little brother, The Transmitter, which is a neuroscience magazine. And I worked for The Transmitter before it was called The Transmitter. At the time it was called Spectrum, and I kind of did data stuff for them. So lots of Python, and making tools for the newsroom, and also writing some articles about the brain.

Samuel Arbesman:

This is fascinating. So I think I first came across your work just through your own newsletter. It was just your own writing. Did you start doing that alongside these other roles or was that the next thing after these more traditional science journals and roles?

Nicholas McCarty:

So I was doing that all at the same time. I started the newsletter on a whim one day. I was sitting in my apartment, kind of bored or not feeling super motivated about the things I was forced to write for school. And so really, the way that the newsletter started, and the newsletter really just changed my entire life.

I tell people who ask, lots of people want to go out and write masterpiece essays on their first attempt. "I'm the next Paul Graham. I'm going to write these essays that hundreds of thousands of people read." But you know, usually I think one of the ways to grow that early audience, in my case, it was just to have a very useful newsletter, not to try to be provocative or a great writer. I was literally just collecting links from the internet and throwing them into a newsletter and sending them out to people, and people thought that, that was valuable.

I was just rounding up new research papers and reviews about synthetic biology, and then I quickly sort of gained this core audience of two or 3,000 synthetic biologists who really loved it.

Samuel Arbesman:

Yeah, I was going to say, I think yeah, I remember looking at it when it was more of the aggregator mode, just finding interesting articles and kind of quickly go through them all. But then you started switching more towards longer-form essays, not necessarily very long essays, but essays about a specific topic, still somewhat in the maybe explainer mode. Is that the right way to describe how you began writing some of the essays for the newsletter?

Nicholas McCarty:

Yeah, totally. I kind of had a fear of going too far out on a limb, if that makes sense. I was so used to the institutional education of, everything is serious. Being trained as a scientist for a decade and then trained as a very serious reporter, like, "You shall not be friends with your sources," and these sort of things.

And so I think my first essays on my own, where I was just kind of writing what I want to write were very conservative of, "Well, I'm just going to explain the facts. I'm not going to be too interesting. I don't want to ..." And it really took me time to come out of that shell. And actually the impetus, if I'm just being completely honest, I think a lot of writers and artists in general are competitive. We see other people write things or create things and we think, "Wow, they got a huge response. I could do that too, or I could do that better."

And if I'm being honest, that's the reason I started writing essays. It was, I was seeing different bloggers on the internet covering stuff or getting traction and I was like, "You know, I should just write essays. People seem to like opinions. They seem to like ..." Also, my audience just wasn't growing. I really feel like I kind of reached the synthetic biology audience and it was kind of flatlining. So, that was the impetus there.

Samuel Arbesman:

Was it only when you started writing the essay? You mentioned that the newsletter changed your life in many different ways. Was it only once you started writing the essays? What were the moments that caused that inflection point in terms of the changes?

Nicholas McCarty:

Yeah. Well, I think the reason I said it changed my life was because every job that I've had since my staff writer job has been a direct result of the newsletter.

Samuel Arbesman:

Okay.

Nicholas McCarty:

So in other words, I was hired explicitly because the boss liked the newsletter.

Samuel Arbesman:

That's amazing.

Nicholas McCarty:

So my first job like that was at a place called New Science. It was one of these metascience organizations that I know you have it in your index, Sam. We were basically searching for young scientists, who we felt were geniuses, and giving them money to start their independent research programs because the average age of an initial RL1 grant from the NIH is, I don't even know, 41 or something crazy.

So we were like, "Hey, let's identify young geniuses and give them money." The founder of that organization actually hated my newsletter, interestingly. He thought it completely lacked personality, but someone else told him to hire me, who really liked my newsletter.

Samuel Arbesman:

That's funny.

Nicholas McCarty:

And then basically that is the guy who first told me, "Hey, your writing is extremely boring. You're not being adventurous enough. You should just write what you want to write," and that piece of advice is really what helped, I would say, the newsletter go in its new evolutionary direction.

Samuel Arbesman:

Maybe that's like jump forward to Asimov Press, which you're working on now. I'd love to hear, what's the story and goals and reasons behind Asimov Press and why it does what it does?

Nicholas McCarty:

Well, you know when I was initially starting Asimov Press, I want to say October 2023, I was busily writing Google Docs, outlining everything. Outlining, "What do we publish? If somebody sends me an idea for an article, how do I know if I should say yes or no? What is it that we're known for? What is it that we want to be known for? Everything." It's like, "What is our style? How do we grow? Who is our audience and what is our North Star?" In other words, "How will we know when we've succeeded? Is there something better than just likes on Twitter or number of subscribers? Can we actually make an impact in the world and try to measure it?"

And honestly, we've gone back and forth on North Star, big picture, why we exist. But if I'm just being completely honest, we just want to publish really good stuff, that is the deepest stuff written in this area that has ever been written. That's really the goal.

The initial motivation was that I am convinced ... You know, I'm biased because I studied this for so long, but I am convinced or brainwashed or whatever that biology is this really important technology. Sure, there's a lot of hype and there's a lot of stuff that just is not scaling and it doesn't work in the real world, even though it sounds great in principle, but obviously I'm convinced that there are amazing things on the frontier, like gene therapies. Those are coming to patients, and reprogramming immune cells to fight cancer and all these things.

And I just was not seeing truly deep, incredibly substantive writing on these really complicated subjects, and that was the initial motivation. And at the time, I think I was writing a piece for Works in Progress, which is a great magazine on progress, and that was also a huge inspiration.

And in my original docs, I was like, "We want to be the Works in Progress for biology." That was really the initial motivation. And over time we've become great friends with Works in Progress and now we're launching stuff together that will come out soon. So it all worked out. But yeah, it's hard to know, "Am I actually achieving these things, or what do people think?" but we're kind of unapologetically technical about a lot of our publishing.

Samuel Arbesman:

That's great. And I feel like there definitely is ... That is a lane, whether it's a Works in Progress, what you're doing with Asimov Press, and you mentioned Quanta before. I think Quanta is also, it is not really dumbed down. I mean, it's geared towards a general audience, but a very smart, engaged general audience that wants to know the nitty-gritty details of certain things in mathematics and physics or whatever it is.

Yeah, so there definitely are these audiences. So when you think about an audience for Asimov Press, what is the core audience, maybe larger rings around it? Who are the kinds of people, because there clearly are. There is an audience for this, but who do you have in mind as potential readers?

Nicholas McCarty:

You know, when we started, we really didn't know, and you kind of learn as you publish, what resonates, what works, what doesn't. And what we've arrived at is, I mean really this is taken from Tammy Winter who is a great publisher with Stripe Press. And we were at an event, a publishing event in New York, and Tammy Winter was on stage talking about how Stripe Press ... I think this is public, right? But this year, they were selling 1,000 books a day, and it's like a miracle if a book published today even sells 1,000 copies. Most books do not even sell 1,000 copies.

And she was talking about how they're unapologetically writing for the ambitious reader. They're not ashamed if their book has math equations. It's unapologetically for the ambitious reader.

And I think we're the same thing. We started very much targeting bioengineers and scientists working at biotech companies, but increasingly I was just kind of bored of publishing some of that stuff and I wanted to do other stuff on global health or vaccine development or things that my audience didn't necessarily care about, and we went for it.

And I think over time, the picture I've gotten of our audience is, it is a very ambitious reader, but increasingly it's like computer scientists and it's Tyler Cowen's audience. We've gotten thousands of subscribers just from Tyler Cowen sharing our stuff. Increasingly, it's very much broader than I had initially envisioned, and that has been great.

And that also, surprisingly makes me feel more comfortable publishing very different experimental types of stuff because I just don't know anymore what our audience actually wants in terms of topic. I just know they want detail, depth, nerd out, go crazy, but I feel more comfortable doing that in very different areas now.

Samuel Arbesman:

That's great. And I feel like you've done even broader things. I think you've published a number of works of fiction, like short stories as well. What have been the internal discussions around choosing to do something like that, far different? And I imagine it was well-received, but before the fact, it might've been a little bit harder to know how people would respond.

Nicholas McCarty:

On average, our fiction is our most popular at least. I shouldn't ascribe best or not-

Samuel Arbesman:

Sure. Yeah, yeah, yeah.

Nicholas McCarty:

Just in terms of numbers, on average, our most popular pieces ever are our nonfiction actually, short nonfiction. People love arguments and stuff. On average, people love the fiction. And that's usually what spreads around the internet a little bit more, like on Hacker News and whatnot.

And actually, fiction was in the plan from day one. It was in the original docs because I was thinking, I was kind of trying to build a roadmap of, "How do we make an impact?" And I imagined a funnel as a publisher, where the top of the funnel is, bring more people into biology. Get more people excited about what is happening in this space. And then I kind of saw the bottom of the funnel as our extremely long-form nonfiction, which has become our bread and butter, I think. That was really like, "Okay, now that they're in the funnel, let's get them excited about very specific nitty-gritty things." All right?

I always saw the fiction as the top of the funnel and I still kind of see it that way. Fiction is just a way for us to get people excited about biology, and we only publish fiction about biology, and we try to publish pieces that are positive, and that sometimes has interesting results because our most recent science fiction piece was written by Richard Ngo who used to work at OpenAI, and he writes a lot about the intersection between AI and biology. And his piece ends on this very optimistic note, like a utopia in the future, and a lot of people really did not like that.

Samuel Arbesman:

Oh, interesting.

Nicholas McCarty:

A lot of people were like ... You know, it was about the AI singularity and brains start entering the cloud, and you can love more deeply than you've ever loved because your brain is literally shared with other people, and the ending is a utopia. A lot of people liked it, very popular piece, but some readers were like, "Oh, I loved this until it was clear that this was a positive story."

Samuel Arbesman:

I guess there's been a push in some areas of science fiction to kind of portray these more positive visions, but apparently at least some parts of humanity are unwilling to accept something that's a little bit more optimistic.

And so the people who end up writing these fiction pieces, or at least the ones you end up publishing, are they more coming from the science fiction world, the fiction world, or are they scientists and engineers trying to articulate a vision of the world that they're trying to actually bring about in their own work?

Nicholas McCarty:

So the first thing I should say is that all of our fiction stuff is really made possible by my colleague, Xander Balwit. So she leads all of our fiction stuff, commissions all of it. She has written sci-fi in the past for Asterisk Magazine. She's a really great fiction author who increasingly is doing a lot of nonfiction writing for us, besides editing all pieces and stuff.

You know, interestingly when we started doing the fiction thing, I think we expected that we would work with a lot of traditional sci-fi writers. I have always really, my favorite sci-fi writers in terms of short stories are Ted Chiang and qntm probably, Q-N-T-M.

Samuel Arbesman:

Sure.

Nicholas McCarty:

I love their short stories. Those are basically my favorite sci-fi short stories besides Isaac Asimov and stuff like that. But I think the reason I really like them, those two people in particular is because their pieces are so mechanistically detailed, like qntm especially. It's not just like a technology exists in the world. He really tries to explain how the technology came to be and how it works mechanistically, which is what we have always been after in our fiction.

I think we've only published four or five pieces of fiction ever, and all of them are really technically detailed and specific about the thing that is happening. But we get hundreds of pitches from science fiction authors all the time.

Samuel Arbesman:

Oh, really? Wow.

Nicholas McCarty:

Because I think we ended up on some sci-fi forums.

Samuel Arbesman:

Oh, interesting.

Nicholas McCarty:

And we pay well in the sci-fi world. We pay 1,000 bucks for a short story. And most sci-fi magazines pay nothing, basically. So very, very little. And so we get a lot of pitches, but so many of the pitches are just kind of like, they're very plot-based or situational-based, like astronauts stranded on a place.

And that's just not ... You know, I love that kind of sci-fi, very narrative stories, but it's really just not what we publish. We publish actually, arguably kind of dry, not plot-focused, very conceptual sci-fi in all of our science fiction pieces. Interestingly, I've never actually thought about this until you just asked. All of them have been written by scientists, practicing researchers.

Richard Ngo is an AI researcher. We had a great piece from Avi Mahajan called Models of Life that was exploring a future in which scientists can fully simulate cells and what that means for drug development and curing diseases. And again, there was no plot there. It was vignettes of future years without characters. There were no characters. So the pieces are kind of, I think, not everybody's cup of science fiction tea.

Samuel Arbesman:

No, that's good that you're providing a venue for a very different kind of thing. And speaking of that, you also recently switched, or not switched, but branched out into publishing and print. Historically, all of your stuff has been online, but you now actually, and I'm showing it to you. Our listeners cannot see it, but I'm lifting up an actual print thing from Asimov Press.

What prompted the switch into print publishing and how did you think about that approach? What were you trying to do with that? Has it been as successful as you expected, or rewarding? Are you going to continue in that? How are you thinking about all of the print aspects?

Nicholas McCarty:

You know, that's a great question. If I'm being honest, from the get-go, again, I mentioned Works in Progress, but I've always been a fan of Stripe Press. I think the big difference between us and Stripe Press is that they actually publish original books.

We have only published to this point, anthologies. So we put existing essays into print and we work with these great book designers in New York called Everything Studio, and they design our books from top to bottom, cover, texture, feel, typography, everything is very meticulous.

And to be honest, I think the reason we did print, as best I can recall, I want to say it was just like, I'm almost sad to say the word, but almost like a superficial thing. It's like, "Well, people will take us more seriously if we put stuff in print. That's cool. If we just publish blogs on Substack, people will not think that we're super serious, so we should print things and sell books."

I really think that's almost how it started. It was like a credibility thing.

Samuel Arbesman:

Oh, interesting.

Nicholas McCarty:

That's a way for us to go and be taken seriously. Over time, a lot of our writers that, I think maybe would not initially have been attracted to contributing to our magazine, decide to contribute because we are in print and they like to see their work in beautiful books. A lot of authors actually really care about that. So I think that's an upside.

The downside is that it's by far the most time-intensive part of our lives. So, Xander and I work on books for months. It takes months and it costs many, many tens of thousands of dollars to do a full design and print run and then you have to actually sell them. There's no guarantee you're going to make that money back. We sold out of our first book-

Samuel Arbesman:

Oh, that's great.

Nicholas McCarty:

I think we sold ... In total, we printed 1,800 copies and we sold out and we broke even once you factor in everything involved with getting that set up. And we're now in the midst of publishing our second book, which is very cool and maybe we can talk about the DNA thing. It's the first commercially available book sold as both a book and as DNA. So when people buy the book, they also get it in DNA form.

Samuel Arbesman:

You mean, the book itself is encoded in a string of DNA that you receive?

Nicholas McCarty:

Yes. But that has been done before. People have encoded books in DNA, but they've never sold the DNA with the book.

Samuel Arbesman:

Got it. Okay. So you can get it in-

Nicholas McCarty:

So this is the first-

Samuel Arbesman:

So it's multiple formats, but instead of print book and e-book, it's print book and DNA book?

Nicholas McCarty:

Exactly.

Samuel Arbesman:

Okay.

Nicholas McCarty:

The DNAs, you can open it and sequence the DNA, but-

Samuel Arbesman:

Yeah, yeah, I'm sure.

Nicholas McCarty:

... really, it's like a display thing. And actually, I got the proof from the printer today.

Samuel Arbesman:

The DNA proof or the book?

Nicholas McCarty:

I got the proof of the book.

Samuel Arbesman:

Oh, there it is.

Nicholas McCarty:

I'm just holding it up on screen and I can ... But this is just a proof. So the capsule goes in here.

Samuel Arbesman:

Oh, that's fantastic. Oh, there's a little space for it. That's fantastic.

Nicholas McCarty:

And then this gets wrapped around with the book. So there's also, I get a lot of emails, "How do I read the DNA?" I'm like, "You know, it also comes as a book?"

Samuel Arbesman:

Correct. Right.

Nicholas McCarty:

But no, I mean increasingly, I guess what I would say is our books are well-received. There's clearly a market for books. So far on this DNA book, in pre-orders, we've sold about $50,000 worth of pre-orders-

Samuel Arbesman:

That's fantastic.

Nicholas McCarty:

... which is good, but I don't want to break down all our expenses, but we're still not profitable on print. If we sell out of our books completely, we'll make a small profit, which we then actually donate to charity. So we don't collect any money from anything.

But increasingly, I'm actually trying to commission original books. I think that's the new thing for us, is that even though this is so time-intensive and so expensive, I just really love it. I love shipping books out.

That's when we get our biggest response. That's when we hear from readers. Right? So it's just a great way to bring us closer to our audience and provide beautiful things that we think will stand the test of time. And so yeah, increasingly I think that's a big area that we'll push deeper into.

Samuel Arbesman:

Maybe now is a good point to switch into the content of biology, some of the stuff that you've been commissioning and exploring. You were talking about one of the reasons, with Asimov Press behind it, you wanted to get people excited about all these cutting-edge things that are happening. You mentioned gene therapy and doing deep dives in that.

Are there any particular exciting stories in biology that are happening right now, particularly ones that people outside of the world of biology are either just unaware of, or think are not as exciting, or it could even be ones inside the world of biology that biologists themselves don't quite have the context to realize how earth-changing these things could be?

Nicholas McCarty:

Yeah. Well, you know I think the most exciting part about working with writers is exactly that, that we get to hear about all sorts of interesting ideas and spend a lot of time with people who are thinking a lot about those ideas, which is a very exciting thing.

When I think of biotech and when I think most people picture biotech, they probably picture drugs and vaccines, and that's very common, human health. And I think that's common because that's the realm of this area that enters the human life, the human experience.

One of the reasons I think AI stuff is so popular right now is because there are consumer tools, so people can log in and actually use it. And so it's interesting when there's a podcast with the CEO of Anthropic because you can actually play with those tools and use those, but so much of biology is just inaccessible. It's just not the same sort of consumer business.

You know, what I would say is there is a lot of stuff happening in the biotech industry that, I think a lot of people don't know if they're not in biology. I think some of the cancer treatments, CAR-T therapies are still really, not as well-known as maybe they should be. Tons of interesting things on vaccine development, but a lot of it is early stage or it's not quite there, but I still find it very interesting.

In terms of things that not even biotech people seem to know, I often look outside of human health and medicine, and a lot of what we publish at Asimov Press is outside of medicine just because we feel like so many other people are writing about that. There's STAT and Endpoints and lots of websites devoted to biopharma, but it's rarer to find articles about people engineering ants, to study how ants communicate, and which neural circuits in the brain fire when ants smell a pheromone.

So we had an article about that. It was with a researcher engineering the neurons in ants to light up so you can actually watch their brain fire in real time as they go about their life.

Samuel Arbesman:

Oh, wow.

Nicholas McCarty:

That's very cool, but that's a kind of a basic science sort of thing. In terms of things that are actually scaling in the real world, that's kind of what I look for, is why is the drug industry so popular in biotech? Well, because you can sell a very small amount of a drug for a very large amount of money. So, the margins are good.

Why have the bioplastic industries not scaled? Well, it's because plastic is a commodity, and if you're making plastic using fermenters and engineered microbes and then selling it as plastic, it's really hard to make a profit. So that's why the drug industry is so big. It's like gold. You're making small amounts of things that sell for a lot of money. But there are places outside of medicine that are actually scaling and reaching sort of commercial adoption, one of which is animal welfare.

I think lots of biotech people, I've been very surprised that they don't know more about it. Just this year, the first in-ovo sexing technologies have come to the U.S. So the U.S., just this year is implementing technology that allows the egg industry to sex an egg before it hatches so they can say, "This egg will be born male or female," and they can get rid of the male eggs before they hatch.

Samuel Arbesman:

Yeah, I was going to say, what is the reason behind getting rid of the male eggs, or what are the costs and benefits here?

Nicholas McCarty:

Yeah. So there are basically two types of things in the chicken industry. There are broiler chickens which are raised for their meat, and those chickens are engineered to grow quickly, or specially bred to grow as quickly as possible, and then there's the layer industry.

And these female hens, I guess are specially bred to lay lots of eggs. When these hens lay male eggs, those male eggs cannot profitably be raised for meat. So what happens is they hatch and all the males are thrown into a blender.

Samuel Arbesman:

Oh, boy.

Nicholas McCarty:

And this happens to six billion baby chicks every year, six billion.

Samuel Arbesman:

Wow.

Nicholas McCarty:

And so it's a huge thing. It's like they cannot be raised profitably. It's not the right strain of chicken. The layer hens are not giving birth to male broiler chickens that will grow big. There's no use for the males, so they just kill them and they keep the hens and they use those hens to lay more eggs.

And now just for the first time, we actually have a technology. So it's not just that it's a humane thing either. It's not just about the animal welfare. It's like, it will literally make it faster and more efficient for farmers to find the eggs that they want. Right?

Samuel Arbesman:

Wow.

Nicholas McCarty:

It's not like they want to throw chicks in the blender. If they could get rid of that whole apparatus and figure this out before they hatch, that would actually be profitable and more efficient. And that just came to the U.S. market and that uses biotech.

What happens is a little laser drills a hole in the eggshell and then siphons out some liquid, and then there's an automated machine that runs polymerase chain reaction or PCR to see what the chromosomes are, and then you can automatically with robots dispose the male eggs.

And then there's another similar technology that uses hyperspectral imaging. I guess, male or female, I can't remember which, they start to form feathers inside the egg, and you can actually see that development using hyperspectral cameras, so you don't need to drill a hole. But this has been available in Europe for three years because Germany passed a law banning chick culling. So the technology was kind of forced to be adopted in some EU countries.

It's like, that's something I just ... I talk to a lot of biotech people and they just don't even know about that. And it is kind of a niche. I guess we don't often think about our food, but food is a big deal. What does biotech touch? It really is medicine and food.

Samuel Arbesman:

One of the other pieces you wrote recently in terms of, we were talking about a lot of these ideas are fairly at the basic research stage. And the question becomes, how do we scale these things up or make advances so they can actually reach lots of people? This piece that you wrote recently was around the levers for biological progress.

I'd love it if you can talk a little bit more about how you think about bottlenecks, and roadmapping, and these levers, and making changes in how biology is able to move forward.

Nicholas McCarty:

You know, that's the thing that we all want, is in the industry, at least in the biotech space, we want biotech to scale and offer better, more sustainable solutions to problems, right? It would be great if biotech could scale and make awesome spider silk materials that are better and less damaging for the environment and break down in the soil and stuff.

If we do master biology, I think interesting things can happen. It's just clear that there's economic things and regulatory things, and the tech doesn't always work the way we hope it will. And so I think a lot about, like you said, these levers. And I would say there's a whole industry of people who think about the regulatory components.

The Institute for Progress released a great report on how to reform clinical trials and speed up clinical trials, or how to do more Operation Warp Speeds and get more vaccines developed for influenza or adenovirus or the common cold? Wouldn't that be great? I don't often think of those things just personally because I always came from sort of the bench side. I've never worked in the policy space.

And so when I think of levers, I think of things that individual scientists could work on to make a really big difference, often in unexpected ways. And so a lot of these things, and I can give some examples, but-

Samuel Arbesman:

Yeah, that'd be great.

Nicholas McCarty:

... they're really things that I just feel like have a flywheel effect. If we develop X, it will have serendipitous sort of flywheel outcomes on a wide range of things. So a classic example is a DNA sequencing technology. When the Human Genome Project was starting and they're launching this big initiative and all this money floods sort of that goal, well, what happens?

A bunch of people come in and they invent technology to make sequencing much cheaper. The human genome doesn't really pan out the way people thought it would. Right? It's great to have that, but it's not like curing cancer in the way that some people predicted. But one of the great outcomes is all the sort of serendipitous benefits of what happened as a result of that, which are things like metagenomics.

Because DNA sequencing became cheap, thanks in parts to the Human Genome Project, this whole new branch of biology popped up called metagenomics, which is basically people who collect dirt and water and the air, and they sequence things in those samples to discover hidden microbes or hidden biology, and that has been a complete revolution.

It is because of metagenomics that our genetic databases are completely swelling with information. And now we can use AI tools and computational tools to go through that information and pull out gene clusters that might produce valuable antibiotics, or pull out genes that might encode useful proteins.

CRISPR was initially discovered that the CRISPR loci were discovered in a Haloferax bacteria in Spain or in the Mediterranean by Francisco Mojica. It was because he was sequencing this weird microbe that he saw these repetitive sequences in the genome, and that was the ... Obviously, he didn't create what Doudna did and show it's a programmable sort of DNA editing tool, but that's kind of where it began.

So when I think of things like that today, I guess there's a couple of things. One is that I really feel like measurement technologies, people who focus on measuring things and building tools to measure more things, those can often have huge, sort of unexpected outcomes on biology as a whole. Right?

Samuel Arbesman:

So what do you mean by measurement tech, like in terms of certain things around microscopy or what else? What are you thinking there?

Nicholas McCarty:

Yeah. So one of the problems with biology is that even in a simple cell like E. coli, there is so much happening at any given time, and our tools to study what is happening often require that we either destroy the cell or we freeze the cell in time so that we can finally get a picture of things. Right?

So how do we solve the structure of proteins? Well, we kill the cell from which the proteins came, and then we freeze the proteins, and we shoot things at them to figure out what they look like. That's a lot of biology, right? When we sequence an organism, well, we kill the organism and we strip out its DNA and we read it. You're getting these extremely myopic views of one component, right?

This is like the reductionism view. Can you piece together a million reductionist observations and arrive at a holistic understanding of how biology works? I think increasingly, the consensus amongst biologists is, probably not. We need tools to study cells as they are without disrupting them across space and time.

And so when I think of measurement technologies, it's things like, can we read out RNA transcripts in real time without killing cells? Just in the last year, there have been two serious new technologies to do that. So one way is, there's actually a group that invented a tiny pipette that goes into the cell membrane and sucks out a little bit of cytoplasm and sequences the RNA without killing the cell. Right?

So there are ways now to strip out some of these molecules and read them or measure them in quasi real time. So I'm really excited about stuff like that. I think that we'll have weird, unexpected discoveries that it enables.

You know, there was a whole revolution in spatial biology in the last decade. There's technologies like seqFISH which is, you freeze a cell in time. So it's very hard to measure both dimensions at once. It's very hard to measure both time and space in biology, but the spatial technologies, like you freeze the cell and then you can see the positions of genes, physically where they're located, and you can see the positions of mRNAs and you kind of get a spatial view. I think that's very cool and that's leading to all kinds of unexpected discoveries.

So that's what I mean by measurement. So I'm not really thinking at the commercial scale at all. I'm really thinking of, "Well, if we figure out this stuff way down here at the level of a cell and we understand cells much more than we understand them, that will help us scale because we'll be able to engineer cells much more reliably, more predictably. How do we make biology and engineering biology, not a discipline of trial and error, but an actual engineering discipline?

That has been the goal of synthetic biology for 25 years, and obviously it's not there at all. When we edit cells, it is not really a predictive thing. Sometimes it is. We know how to do some things, but a lot of stuff just doesn't work in the way that we expect. So I've always been very focused on the cell.

Samuel Arbesman:

Yeah, and I feel like there are these enabling technologies that make it possible to understand things well enough that you can do things more reliably or deterministically or whatever it is. Maybe a good final question would be, looping back to some of the science fiction stuff, you were talking about all these technologies that are still fairly fundamental in terms of understanding biology.

Do you have a vision for what the biology or biotech world might look like in several years? And I'm kind of leaving that vague, so you can take it in whatever direction you want, but do you have a sense that once we figure out these enabling technologies, we'll be able to do certain impressive things, or we're still in that enabling stage and we need to lay the groundwork over the next few years?

Nicholas McCarty:

Well, I think we're still very much in the enabling stage, and there's a lot of hope for AI and models of biology and lots of people working towards virtual cells, but they all seem to have very different definitions of what a virtual cell really is.

My personal dream, and I'm not saying this is a 10-year vision or maybe even a 20-year vision. My personal dream is I would like a complete mechanistic understanding of how a single cell works, and some people have told me that that's just simply impossible.

You know, I was meeting with someone in San Francisco and they said, "Could we ever build a mechanistic view of the entire city of San Francisco? Could we ever know everything that is happening in San Francisco at any given time? That's just impossible. You know, the cell is kind of like that." That was their argument.

You know, I don't necessarily buy that. I don't think we need to measure everything at once. I think we can, with AI and with some mechanistic models or a compilation of models, I think we could get to really good in silico models of biology where we could actually do computational perturbations of an in silico cell and get out the actual result that you would see if you did it in the lab.

That's been a dream of my life for many years. More realistically, or on sort of a shorter horizon, I feel like the protein stuff has gotten so good. We're so good at designing proteins. Once we figure out the bottleneck of how to make proteins extremely cheaply. Right now, it just costs too much money to make different types of proteins because you have to synthesize DNA. DNA is expensive. Then you have to put the DNA into cells, coax the cells to make your protein, and then you isolate the protein.

That's just too time-intensive. It takes too long, and at the same time we can't yet just build proteins chemically because the efficiency drops off after a certain number of amino acids. So we're kind of in this hole right now where a dream would be very cheap protein synthesis so that someone could just design a protein on the computer, synthesize it on their desk in a few minutes and have a functional thing. Right?

The beauty of proteins is that they can execute all kinds of interesting functions, like they can be materials or medicines or antibodies or whatever. I think it's not crazy to think in the next 10 years we'll have AI-designed protein printers, and I think that would be really cool. I thought about writing a sci-fi piece where people basically have superpowers, but it's just like they're making proteins-

Samuel Arbesman:

Oh, interesting.

Nicholas McCarty:

... and using proteins to fight other people and do different things, but I haven't started writing that yet.

Samuel Arbesman:

Well, this is awesome. This is great. I love kind of this vision of explaining biology to a broader audience and thinking about what are the technologies to build a even better biological future. So, thank you so much for taking the time to chat. This is amazing.

Nicholas McCarty:

Oh, thanks for having me.

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