Life from scratch

Scientists stripped a cell down to its most essential genes in order to find out what makes life...alive. What they found was more bizarre than they could have imagined. This is the first episode of our new three-part series, Life from Scratch. Guests: Kate Adamala, associate professor at the University of Minnesota; John Glass, leader of the JCVI Synthetic Biology Group. For show transcripts, go to ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠vox.com/unxtranscripts⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ For more, go to ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠vox.com/unexplainable⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ And please email us! ⁠⁠⁠⁠⁠[email protected]⁠⁠⁠⁠⁠ We read every email. Support Unexplainable (and get ad-free episodes) by becoming a Vox Member today: ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠vox.com/members⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ Learn more about your ad choices. Visit podcastchoices.com/adchoices

• 0:00Speaker 00

  Support for the show comes from Google Gemini. You know that moment when curiosity strikes? You're exploring a new city with the family and a sculpture catches your daughter's eye. What is that? Who made it? With Gemini, you can snap a picture and get a fully interactive breakdown of its history, architecture, and even hidden secrets. Gemini is built for moments like that. Whether you're learning something new, solving a problem, or looking for your next favorite thing, Google Gemini is here to help. Download Gemini, Google's AI app, or visit gemini.google.com to learn more.

• 0:39Speaker 01

  This episode is brought to you by Michelob Ultra. Good times mean competitions between you and your friends, like seeing who can throw some pigskin the farthest or rush the field the fastest. Winner gets an ultra. Because it's not just a superior-like beer, it's also giving fans superior access to their favorite sporting events. Superior is worth playing for. Visit michelobultra.com/superioraccess to enter. Enjoy responsibly. Copyright 2026 Anheuser-Busch InBev Michelob Ultra Beer, St. Louis, Missouri.

• 1:15Speaker 00

  There's this saying about the difference between biology and chemistry. Yogurt can make more yogurt, but shampoo can't make more shampoo. That is to say, yogurt has a community of living microbes or tiny organisms. Some yogurt cultures can live for decades, and it takes just a little bit of yogurt to turn milk into more yogurt.

• 1:43Speaker 00

  Shampoo, on the other hand, is just shampoo. It's inert, it's dead, it doesn't make more of itself. For now.

• 1:53Speaker 02

  That's what we need to do. You know, yogurt can make more yogurt. Why cannot shampoo make more shampoo?

• 1:59Speaker 00

  Kate Adamala wants to make chemistry look a lot more like biology.

• 2:04Speaker 02

  And enable anyone in all parts of the world to refill their own shampoo bottle. They shouldn't have to order their shampoo from the five places in the world that make shampoo. Again, using shampoo is just an analogy.

• 2:18Speaker 00

  Shampoo as an analogy for all sorts of chemicals that we rely on every day. Medicines, food, fuel, materials. Today, making these things in a chemistry lab is messy, wasteful, and sometimes toxic. Instead, the idea here is to harness life to help us grow what we need.

• 2:40Speaker 02

  During COVID, for some reason, we rediscovered the bread making. Everyone was having their own Sardo starter. My Sardo starter, his name was Hank, and I was making my own bread for a while. And that should be possible. Everyone should have their own Hank, their starter of shampoo, bread, all the other essential chemicals that we need.

• 3:00Speaker 00

  Kate wants to radically tinker with cells so they can make all those helpful chemicals in a renewable way.

• 3:08Speaker 02

  You can draw a direct line from the work I'm doing towards something that will actually change someone's life, create a new drug, and create new technologies that will help our economy, that will help the climate. That's the driving goal.

• 3:24Speaker 00

  But before scientists like Kate can harness this power of biology, first they have to understand it. Because how life works on a cellular level is still a mystery. We don't really know what makes cells alive, what animates them, what drives them. And we have to understand this to reach Kate's vision for the future.

• 3:50Speaker 00

  Cells are staggeringly intricate, and the more we dig in for answers, the more questions we find.

• 3:57Speaker 03

  One of the things that distinguishes biology from chemistry and physics and other science is its incredible complexity.

• 4:07Speaker 00

  John Glass, Kate's mentor, has been studying the inner workings of biology for decades.

• 4:14Speaker 03

  Our goal has been to understand life. What is life, right?

• 4:19Speaker 02

  Right now, any living cell that we know of, it's too complex. We don't understand where every molecule of that cell goes.

• 4:26Speaker 03

  You go to the doctor and they think they know what's going on in your body and they tell you, take this drug, that drug. But in reality, of the kernel of life, there are potentially things that cells do, essential tasks necessary for life, that we're completely oblivious to.

• 4:45Speaker 00

  John and Kate are some of the leading voices in synthetic cell biology, a field where scientists focus on engineering life at its most fundamental levels. So as one of the founders of the field and its new rising star, together, John and Kate are pushing to figure out what makes cells tick with, as they see it, the future of our health and the health of our planet at stake.

• 5:15Speaker 00

  This is the beginning of our three-part series, Life from Scratch. I'm Meredith Hodnot, and this is Unexplainable.

• 5:38Speaker 00

  All life on this planet is related. Every living cell in every living thing, from a deep-sea bacteria colony to your next-door neighbor. All of those cells came from another cell. A long, unbroken lineage going back billions of years to the very origins of life on Earth. This is our tree of life. This is what it means to be alive here.

• 6:09Speaker 00

  For scientists trying to understand cells today, that means unwinding billions of years of these evolutionary tangles, all to figure out what's absolutely necessary for life.

• 6:23Speaker 03

  Science has always advanced using simple systems. Scientists as far back as the 1930s had aspired to have this simplest of all organism, to use this to understand biology.

• 6:43Speaker 00

  And by the simplest of all organisms, John means an organism with the smallest possible genome. A genome is like the instruction manual, teaching a cell step by step what it needs to do to live. Each gene or combination of genes gives the cell an instruction, and those genetic instructions are written in DNA. In general, the smaller the genome, the fewer instructions it needs to live, and so the simpler the organism. For context, complicated human beings, we have about 20,000 to 30,000 genes in our DNA.

• 7:23Speaker 00

  Something smaller, something simpler, like an E. coli, has only about 4,000 genes. John spent his early career studying the DNA of some of the simplest organisms known to science, a type of single-cell bacterium, a kind of micro, called mycoplasmas, which can have around 1,000 genes or even fewer.

• 7:47Speaker 03

  They don't make anything except more mycoplasmas, so this lets them have exceedingly simple genomes.

• 7:57Speaker 00

  You can find them in lots of places, like the eyes and lungs of animals like goats, or in the case of John's personal favorite mycoplasma.

• 8:07Speaker 03

  I joke that this was a marine bacterium because it was originally discovered in the Urogenital tract of a British marine in about 1980.

• 8:18Speaker 00

  Uncomfortable for the marine, but a boon to science, helping researchers find the very limits of genetic simplicity. But how simple could a cell get while still keeping that mysterious spark of life? That's what John wanted to make.

• 8:35Speaker 03

  A simplest of all organisms, a minimal cell.

• 8:42Speaker 00

  So in 2003, John teamed up with some of the most famous biologists of the day.

• 8:49Speaker 03

  J. Craig Venter led the world in a number of amazing discoveries about biology, changing the way science is done globally.

• 9:00Speaker 04

  An iconoclast with a brilliant mind and an outsized ego who has flaunted the staid scientific establishment at every turn.

• 9:08Speaker 00

  Craig had just made headlines all over the world for helping to decode the human genome.

• 9:15Speaker 05

  Dr. Craig Venter, I thank you, Craig, for what you have done to make this day possible.

• 9:22Speaker 00

  And now he was assembling an all-star team of researchers, including a Nobel laureate, to start making this dream of a minimal cell into reality. Is this like joining the Avengers or something? Were these some of the biggest names in biology at the time?

• 9:39Speaker 03

  Oh, yeah, these were heroes of mine. And what they really needed was a mycoplasma expert. And I, I fit that bill.

• 9:48Speaker 00

  So John joined what would later be called the J. Craig Venter Institute, or JCVI. Their plan was to get down to a genome even simpler than a mycoplasma, something way simpler than anything found in nature. But at this point, they couldn't manipulate the natural genome inside the cell. So they decided to make their own synthetic version in the lab. That way, they could edit it however they wanted. But a lab-made synthetic genome wouldn't be able to tell them anything unless they could get it inside of a living cell and see if its instructions kept that cell alive.

• 10:30Speaker 00

  It was the 2000s, so they talked about these experiments in computer terms. Like, the DNA was the software, the code programming the cell and telling it what to do. And the cell itself was the hardware, the physical computer executing that code. Except there's no downloading a new operating system update for a real-life cell in a Petri dish.

• 10:56Speaker 00

  So it was John's job to see if it was even possible to transplant a whole DNA genome into a living cell. John and his team tried different techniques and different combinations of natural mycoplasmas, but the cells kept dying.

• 11:14Speaker 03

  We're trying everything.

• 11:16Speaker 00

  One postdoc in particular, Carol Latig, spent two years on this.

• 11:21Speaker 03

  Nothing was working and nothing was working. And she came into my office one day and said, I want to quit. I want to go home. I'm tired of this. This is not working. And I talked her into going back into the lab. And the next day, she comes into my office bringing plates that showed two colonies of a successful transplant.

• 11:47Speaker 00

  This was a eureka moment. For the first time, the cells with the transplanted DNA didn't die. They grew. They flourished into a colony that was big enough to see without a microscope. And John and Carol knew that the transfer had worked because they had added in a gene to the new DNA that turned the cells blue.

• 12:09Speaker 03

  The colonies, they're blue, they're gorgeous, they look like fried eggs. She had gotten it to work.

• 12:19Speaker 00

  They were on the right track. The transplanted DNA worked, even though it wasn't original to the cell. It coded for proteins and it kept the cell alive. With this crucial DNA transplantation technique, the JCVI team were able to take their lab-made version of a mycoplasma genome and transplant it into a living cell.

• 12:43Speaker 06

  Today, we found one blue colony. And we believe that this is our first synthetic cell. It's alive.

• 12:53Speaker 00

  This was the first time in history that a natural living cell, a cell from that long, unbroken lineage of cells going back to the very origins of life on Earth, was kept alive by a synthetic genome. All the genetic instructions that let these cells grow, thrive, and divide were made by human technology.

• 13:17Speaker 07

  For the first time, they have produced a living cell in which the active DNA was put together by computers.

• 13:24Speaker 08

  We have a biological self-replicating organism whose parent was a computer file, an email attachment, if you will.

• 13:31Speaker 09

  It's a world first, a living cell driven by synthetic DNA code put together by a computer. This new cell, nicknamed Cynthia, is a milestone for science. And if you believe the razzmatazz, the dawn of a new era.

• 13:48Speaker 02

  That, that sounds mind-boggling.

• 13:50Speaker 00

  This is Kate again, John's future mentee. She was getting her PhD at the time.

• 13:55Speaker 02

  And I was not in synthetic biology back then. But I was following it really closely because they have proven that you can chemically synthesize a whole genome, a genome of an organism. And then, not only admire it because it's pretty, you can actually use it.

• 14:13Speaker 02

  It showed us that there is nothing magical about biology. There is no magic, secret life force that makes cells tick. And that kind of sounds sad, but it's actually good from, for, from our point of view because it gives us hope that we can truly understand biology.

• 14:29Speaker 00

  They named the cell JCVI Sin 1.0, their starting point. The synthetic mycoplasma genome had about 900 genes, a lab-made copy of the mycoplasma's natural DNA. And now the JCVI team could push farther than nature had ever gone. What was the absolute simplest a DNA genome could be and still keep a cell alive? When they broke into that uncharted territory, what they found was more bizarre than they could have ever imagined.

• 15:07Speaker 00

  That's after the break.

• 15:16Speaker 01

  This episode is brought to you by Michelob Ultra. Good times mean competitions between you and your friends, like seeing who can throw some pigskin the farthest or rush the field the fastest. Winner gets an ultra. Because it's not just a superior-like beer, it's also giving fans superior access to their favorite sporting events. Superior is worth playing for. Visit michelobultra.com/superioraccess to enter. Enjoy responsibly. Copyright 2026 Anheuser-Busch InBev Michelob Ultra Beer, St. Louis, Missouri.

• 15:45Speaker 10

  Are your ad campaigns lighting up the dashboard? But not the pipeline? That's bullspend. And marketers are calling it out in Dashboard Confessions.

• 15:54Speaker 01

  My boss asked for results, so I opened my dashboard for the only positive-sounding metric I had: impressions.

• 16:02Speaker 10

  Cut the bullspend. See revenue, not just reach. LinkedIn delivers the highest return on ad spend of major ad networks. Advertise on LinkedIn. Spend $250 on your first campaign and get a $250 credit. Go to LinkedIn.com/campaign. Terms and conditions apply.

• 16:15Speaker 11

  College football is back. So Hilton called to me, the superstition concierge, to make your fan rituals a reality. Need a room to match your lucky number? We got you. Want to make sure our team doesn't wash your lucky jersey? Oh, that smells lucky. Hilton's unmatched hospitality can keep up with any superstition, even a marching band wake-up call at 5:55 in 55 seconds. Hit it! When you need a team that will do whatever it takes on game day, it matters where you stay. Hilton, for the stay.

• 16:49Speaker 03

  A DNA strand like me is a blueprint for building a living thing.

• 16:54Speaker 00

  Deep inside the JCVI synthetic cell genome, there is a watermark, a kind of copyright or patent written into the lab-made DNA itself. They did this so that they could tell the difference between their synthetic cell and natural ones. But in this case, they also decided to have a little fun with it. So they inserted a secret message. It says, "Prove you've decoded this watermark by emailing us," and has a link to their email address in the DNA of a living cell. But this watermark also included a lot more.

• 17:34Speaker 03

  It had the names of all the people working on the project. It had quotes from Robert Oppenheimer, from James Joyce, um, Oppenheimer, James Joyce, Oppenheimer and James Joyce. And I, I'm sorry, I forget the other one. I'm embarrassed.

• 17:53Speaker 00

  The last quote is from Richard Feynman.

• 17:56Speaker 03

  Feynman wrote, "What I cannot build, I cannot understand." And we made it, "I cannot understand what I cannot build." So we got that wrong, but we went back and fixed it.

• 18:08Speaker 00

  It's no accident that the JCVI team saw themselves in the quotes of not famous biologists, but famous physicists. Oppenheimer and Feynman both worked on the Manhattan Project and both famously wrestled with how they ushered in the nuclear age by studying matter at its most fundamental levels.

• 18:29Speaker 03

  Scientists used the hydrogen atom to understand the nature of matter, the hydrogen atom, the simplest of all atoms. What is true for hydrogen is true for all matter. And so using the hydrogen atom is what has led to our fundamental understanding of matter in chemistry.

• 18:52Speaker 00

  This was the same motivation driving John and the JCVI team, essentially applying the same logic to a different field.

• 19:01Speaker 03

  The hydrogen atom of biology.

• 19:05Speaker 00

  But like the physicists they quoted, they didn't know what they'd discover when they probed the foundations of existence.

• 19:17Speaker 00

  Imagine you wanted to figure out how a car works. Even a very simple car has a lot of extra stuff. GPS and entertainment systems and seat warmers. None of those extras will tell you how the car actually works, though, how it drives down the street. But if you can strip away all the non-essentials, throw out the air conditioning and the seat belts and the windshield wipers, until you get to the point where if you throw out just one more thing, the car won't drive anymore. Then you could study what is essential to making a car run without any of the bells and whistles. You'd have a minimal car. Mycoplasmas were a good start.

• 20:01Speaker 00

  Training wheels to make sure that they could make a synthetic genome or instruction manual for life and successfully transplant it into a living cell. Now they could use the synthetic DNA that they already made, that they knew worked and whittle it down by process of elimination. For years in the lab, they tried new designs, throwing out non-essential genes and testing whether their genomes could keep cells alive. And finally, they had it. A minimal cell, just under 500 genes. So it was seven years to get to the point where you could make a man-made version of a naturally occurring cell.

• 20:46Speaker 00

  And then another six years to strip that down into as simple a man-made genome as humanly possible.

• 20:57Speaker 03

  Now, so the genome is about 85% essential.

• 21:02Speaker 00

  They could have gone further. They could have thrown out even more genes.

• 21:06Speaker 03

  And if we were trying to get into Guinness Book of World Records, we might have done that. But we had something that was really tractable and it worked. Within days, scientists all over the world were contacting us, saying they want to work with us. They would like our cell to use it to investigate the first principles of biology.

• 21:30Speaker 00

  If you had started with a different microbe, would you have ended up with a different minimal cell?

• 21:37Speaker 03

  Absolutely.

• 21:39Speaker 00

  So how does that interact with this idea of like first principles of life and trying to get down to the essentials?

• 21:46Speaker 03

  Sure. That's an excellent question, Meredith. So the way we were thinking about this is not so much, what are the essential genes for life? What we were trying to answer is what are the tasks that a cell has to do to be alive?

• 22:08Speaker 00

  So going back to the car metaphor, I can strip down my Subaru and you can strip down your Tesla and we'd end up with different minimal cars. There are different parts that are essential to making both of those cars run. But whether your minimal car has a gas tank or a big battery, the problem those parts are solving is that a car needs to store energy to make the wheels turn.

• 22:33Speaker 03

  Either way, you accomplish the task.

• 22:37Speaker 00

  Right. So it's less about the like universal tools and more about universal problems that life solves in different ways.

• 22:48Speaker 03

  Certainly.

• 22:49Speaker 00

  With the minimal cell, the JCVI team had their hydrogen atom of biology. They were ready to uncover which genes were absolutely essential for life.

• 23:01Speaker 03

  Now, to our astonishment, one-third of those genes, we didn't know what they did.

• 23:09Speaker 00

  A third of the minimal cell genome, so about 150 genes that were essential to life, were a mystery. John knew they were essential because without these genes, the cell would die. But the JCVI team just couldn't figure out what instructions these genes were giving to the cell. Today, about 10 years later, we know a little bit more. Only about 80 of these genes are unknown. But still, the minimal cell was supposed to clarify. Instead, it showed us how much more we had to learn.

• 23:46Speaker 03

  And these genes, there are similar genes in everything, in you and me, in the plants outside, in almost all bacteria, in yeast, in my dog here, everything. And so what that says is that after all we have learned about biology over the last 100 years, all that we've accomplished in medicine, a third of the essential genes for life, we don't know what they do. This really, really surprised us. We thought that we had a better understanding of this.

• 24:28Speaker 00

  Here you are with the minimal cell and there's still like a horizon to our understanding of biology that you couldn't see over.

• 24:36Speaker 03

  Yes. It really surprised me.

• 24:42Speaker 02

  It was one of the coolest discoveries of the century, in my opinion. Now we realize that a cell is even more complex than we initially thought when we started figuring it out. It just keeps getting more complex as we dig deeper into it.

• 24:58Speaker 00

  In 2017, Kate was gearing up to start her own synthetic biology lab. But she was thinking about a different scientific approach.

• 25:08Speaker 02

  I'm scared of cells. I don't believe that we'll ever be able to understand a complex living cell. So my approach is I think we can build ourselves a cell.

• 25:19Speaker 03

  Let's just build with that. If we can build a cell, we may be able to understand a cell.

• 25:25Speaker 00

  John and the JCVI team had always started with an already living cell and just kept it alive as they transplanted their lab-made DNA to give it instructions. But it would be something entirely different to spark life from its inanimate parts. In essence, not growing life, but building it, making a membrane, taking all the goo and isolated parts of a cell, putting them together.

• 25:53Speaker 03

  And hope that it comes to life.

• 25:56Speaker 02

  John and others at JCVI, they gave us the goal. It told us, okay, this is the minimal set of functions that a cell needs to have. Now go recreate it.

• 26:07Speaker 00

  For Kate, the minimal cell gave her the instruction manual, incomplete with some of those mystery genes, but still a list of the tasks that a cell needed to do in order to live. A list that she could use to build her own cell from scratch that could do those tasks.

• 26:26Speaker 02

  You know, if you talk to a normal biologist and say, I want to make life from scratch, they look at me like I grew a second head.

• 26:32Speaker 00

  But John was different.

• 26:33Speaker 02

  He's going to be angry that I said it, but he's the father. He's, he seriously, his vision pretty much started the field. He believed that it's possible to make a cell from scratch before anyone else thought it was cool or indeed possible. And he's been at it ever since.

• 26:53Speaker 00

  Building a cell from scratch, assembling it from pieces rather than growing it from another living cell would mean starting a whole new tree of life without this history of billions of years of evolution.

• 27:07Speaker 02

  I'm thinking of it more like making a molecular machine rather than making a living cell.

• 27:13Speaker 00

  A cell without mystery genes or unknown functions. A cell that's more understandable, more controllable, more capable of taking us into that sustainable future.

• 27:25Speaker 03

  I, I believe that synthetic biology is going to save the world. Maybe not me, but you know, maybe Kate.

• 27:39Speaker 00

  Coming up next week in our Life From Scratch series.

• 27:42Speaker 02

  If you have a cell that can be engineered to do whatever you want, you could imagine engineering it in a way that it makes something harmful.

• 27:50Speaker 12

  Suddenly, we're talking about something which, if we're right, could be a catastrophic threat to life on this planet as we know it.

• 28:00Speaker 03

  So do you fear us more than the people who made nuclear weapons?

• 28:07Speaker 00

  This episode was produced by me, Meredith Hotnoff. It was edited by Lissa Soep, Joanna Salatarov and Jorge Just. Christian Ayala did the mixing and we collaborated on scoring with music from Noam Hassenfeld. Melissa Hirsch checked the facts. Valerie Schenkman, Shelby Smith, Alex Coles, Jacob Reynolds and Kareem Karrea all made this series possible. Special thanks to Drew Endy, Marlene Dogtrum, Orion Verano, Tyler Gosha, Julia Longoria, Brian Walsh and Rebecca Revard. And thanks as always to Brian Resnick

• 28:47Speaker 00

  for co-creating the show with Bird Pinkerton and Noam Hassanfeld. If you have thoughts about the show, we'd love to hear from you. Please email us at [email protected]. And if you'd like to support this show and the journalism that Vox does, you should become a member. It's very easy to do. Just go to vox.com/members. And for those of you who have emailed us to let us know that you signed up because of Unexplainable, just thank you. It really means a lot. Thanks also to those of you who gave us a nice review on your podcast platform or just told somebody in your life about the show.

• 29:31Speaker 00

  Unexplainable is part of the Vox Media Podcast Network and we will be back very soon next week with more from our series, Life From Scratch.

• 29:47Speaker 13

  This episode is brought to you by Born in Roma Fragrances by Valentino Beauty, the iconic fragrance duo. Donna Born in Roma Eau de Parfum is a feminine fragrance featuring juicy black currant, central jasmine, woody cashmerin and warm vanilla. Its masculine counterpart, Womo Born in Roma Eau de Toilette, has notes of fresh violet leaf, aromatic sage, green vetiver, spicy ginger and mineral salt. Shop at macy's.com.

• 30:16Speaker 14

  At Edward Jones, we believe rich is more than caring about the latest and greatest. It's also taking care of what gives your life meaning. That's why your dedicated financial advisor meets you where you are with personalized financial strategies that help protect what matters so you can preserve your progress while creating a path forward. The key to being rich is knowing what counts. Let's find your rich together. Edward Jones. Member SIPC.