synthetic biology

SynBioBeta is the largest gathering of the synthetic biology community worldwide.  It’s taking place May 23-25 in Oakland, California.  John Cumbers is the founder and CEO of the conference, and he joins us to talk about trends in the space and preview this year’s confab.

First, we discuss the impact Washington D.C. is having on the field.  What doe’s Biden’s love for bio mean for synbio? 

At the foundation of the industry, DNA synthesis continues to see dynamic innovation.  Cheaper, and faster, and longer DNA unlocks new potential for synthetic biology companies.

But wait a minute.  John says it is still science that is challenging the field:  “biological dark energy.”  The solution, he says, is DeSci, or decentralized science, biology on the blockchain. 

From climate tech, to generative AI, to DeSci, you can catch it all at SynBioBeta this month in Oakland.

Long DNA has arrived.   Elegen, a new company based in San Carlos, California,  is out this year offering just long DNA.  According to their founder and CEO, Matt Hill and today's guest, the company’s product is twenty times more accurate than anything else presently available.

What does this mean for the world of biology and the world in general that we're seeing the emergence of a new subindustry devoted specifically to long DNA?

“Our vision is to unlock the programming of biology.  Long DNA—something that constitutes a full program—is slow, expensive, and cumbersome to build today,” says Matt.

Formerly at the DNA testing company, Natera, Matt dramatically improved the scale for some of the company’s assays.  In working on these projects, Matt saw the need for a company that would provide longer DNA directly.  The idea behind Elegen is that companies--and there are many in today's world from therapeutics to synthetic biology to agriculture-- should not be spending their time building DNA.  Elegen can provide it at any length.  Matt says it is long DNA at scale, at high accuracy, and at quick turnaround times that will unlock the coming revolution in synthetic biology as well as so many other applications which involve the programming of cells.

When will that happen?  Matt gives his best guest at the end of today's show.

Remember all those firsts for synthetic biology that we heard about coming from Craig Venter’s company, Synthetic Genomics in San Diego? The first genome of a whole organism transplanted. First genome synthesized. First synthetic life created.

A company was born to commercialize the technology from all that science, Codex DNA, which renamed itself Telesis Bio last year. Their product, called the BioXP, is a benchtop gene printer that uses enzymatic synthesis. Their competitive edge is the quality they offer—their genes have a higher accuracy rate. John Gill, Senior Director of Research and Innovation at Telesis Bio, joins us to talk about the company's vision and how they fit in what has become a dynamic marketplace for DNA.

Why does the improvement in quality mean so much in this field? How does this benchtop synthesizer differ from the other options in DNA and gene synthesis? And what applications can we look forward to as synthetic biology begins to change our world?

To begin the year, we head across the pond for an outlook on the thriving community of synthetic biology in the United Kingdom.

Paul Freemont was a co-author of the UK's synthetic biology roadmap and co-directs SynbiCITE, the national center for the commercialization of synthetic biology. A few years ago the government put an initial investment of $300 million pounds into the field, and "everything was going swimmingly well," says Paul. "Then COVID happened."

Paul himself was running what is called the London Biofoundry which is similar to what we call an accelerator here in the States--except that it's funded publicly.

"And the pandemic was such a moment because in the UK in March of 2020, we had a total capacity--nationwide-- to do about 10,000 SARS Cov-2 tests. All the hospitals and others didn't have any capacity for testing. So we pivoted our whole Biofoundry to do an open testing platform. Within eight weeks, we had a working platform that was doing 2,500 tests per day."

We know the rest of the story--the UK became a success model for testing during the pandemic. With things stabilizing around COVID and researchers free to go back to business as usual, what excites Paul about synbio today?

He says that scaling for all synbio companies holds some exciting challenges and opportunities right now. As for the 800-pound gorilla we often discuss here in the U.S.--that is PR--Paul says that the UK is a bit of a different animal. Society there is "tech literate" and with the cost of energy skyrocketing this winter, the average person has become much more open, by necessity, to arguments that synbio holds big promise to bring sustainability to a plundered planet.

Our goal with today’s show was twofold: bring you a practical holiday gift idea and to take you into the world of a synthetic biology entrepreneur. Our guest: Zack Abbott, CEO of ZBiotics.

Zack is a scientist turned businessman who is on a mission to change the conversation around GMOs. His first product is a genetically engineered probiotic that alleviates the morning-after hangover by breaking down acetaldehyde. Zack says he chose this product because it’s something consumers can choose to take—unlike a medicine that’s necessary like insulin.

“In general, people never got a choice with GMOs. But with ZBiotics, it’s an option. We clearly label every box and every bottle: “This product is proudly GMO.” And then we talk about what genetic engineering is and how it benefits the end user."

We chat with Zack about a day in the life of a synbio CEO. It’s not all about PR. There have been logistical challenges working with probiotics.

But even there, it does come back to the stigma around GMOs, for some suppliers who want to use the organic butterfly sticker are hesitant to work with them. Zack says the new synbio industry needs the “Responsibly Engineered” Bumblebee sticker. Let's own this, he says.

Hear, hear!

Has the pandemic unleashed the molecule of RNA to be the new future of drug development?

Tim Mercer is the Director of the BASE Lab at the University of Queensland which has recently become one of Australia’s leading national facilities for the manufacture and research of RNA technologies. Tim is the next guest in our series on enzymatic DNA synthesis which he says is "a quantum shift” in our ability to synthesize DNA.

Tim then goes on to explore the future of mRNA vaccines and other RNA therapeutics.

"There is a change in how the drugs are developed. It allows us to target diseases in ways that current drug development has been unable to address.”

For example, Tim discusses mRNA cancer vaccines and vaccines for rare diseases that are truly customized treatments.

"We can deliver a corrected version of a gene to the patient which is then expressed and translated in their cells and produces the corrected protein to clear the toxic metabolic products and essentially treat the disease. We're designing a particular drug to treat the disease."

If this isn’t trippy enough, we finish with a discussion of applications in synthetic biology. For Tim, it’s all the same thing whether it’s clinical applications or agriculture or industry.

“It’s all a spectrum,” he says.

The DNA synthesis space is seeing some real creativity and disruption this past year. One newcomer, in particular, is shaking things up.

Sylvain Gariel is the co-founder and chief operating officer of DNA Script, who has recently launched the world’s first benchtop enzymatic DNA synthesizer. In today's show, Sylvain, co-inventor of the new system, tells how he met his co-inventors at a French gas company and came to invent a whole new way of writing DNA.

“We spent a ton of time at the bench doing genetic engineering. And we started thinking, we are incredibly good at reading DNA, but we are still very inefficient at writing DNA. And the dream became very logical and very simple. What if you had a benchtop system that would be just like an Illumina MiSeq that would do all of that DNA work for you. That’s the dream, right?”

And that’s what they did. Voila! DNA Script's SYNTAX. It’s a remarkable story of scientists having a dream and executing on it to improve a technology that had been stagnant for years.

Today we get into the details. What is the bench top workflow, the turnaround time, the throughput? What are the hurdles for the market which has become used to ordering their oligos from providers the past twenty years? What is the company hearing from their customers a few months into the launch?

Join us as we dive deeper into this new technology for writing DNA.

“DNA is changing everything for the better,” says today’s guest, Emily Leproust, CEO of Twist Bioscience. Twist has emerged at the heart of what a New York Times Magazine write-up recently headlined The Gene Synthesis Revolution. 

For years, DNA synthesis plodded along as the straightforward “boring" industry underlying much more exciting work. It was the foundation of biotech and drug development and synthetic biology, yes, but what was there new to achieve with synthesizing plain old oligos?

Emily and her company have turned this paradigm upside down with a dynamic new model for what a DNA synthesis company might look like, being at the center of and affecting many new ventures and partnerships this past year. Early in 2022, they have announced a new method of DNA synthesis to enable better DNA storage—we dive into this early on in the program—and a new partnership with Pacific Biosciences. And late last year Twist spun out a drug development company based on their own research.

These are great times to be “Twisters!"

According to scientists, 30,000 species per year are going extinct. That’s 6 an hour, 150 per day. Up to one half of all species could be extinct by 2050.

These are facts gleaned from the website of the company Colossal, the new commercial venture launched this last September by Harvard geneticist George Church and Texas entrepreneur Ben Lamm. While the goal of the company is ostensibly to de extinct the wooly mammoth—a project which has long gone underfunded in George’s lab—the company has a much larger vision of developing new scientific tools, advancing de extinction for many species, and catapulting forward the science of conservation.

"We’re not limited to wooly mammoth genes. We can harvest all kinds of elephants, living and extinct, from all over the world and all the way back to a million years ago. And we’re not even limited to that: we can use synthetic biology to make them virus-resistant, to control their tusk length, to make them larger or taller.”

That’s George talking with Ben on today’s show about how the name of the company represents their larger project.

"We wanted to do so much more than mammoths. We felt like this problem of climate change and the loss of biodiversity was a colossal problem. So the word kept coming up over and over again. And we thought it also gave use enough breadth from a brand perspective that we could do a lot of innovation both in software and hardware tools out of the lab that Colossal encompassed our vision, the engineering, and the problem," says Ben.

How did the two meet? What will success look like for the startup? Who will their customers be? And what are the critics saying? Join us as we go behind the scenes with one of the year’s most visionary commercial ventures.

Chris Mason is back on the program for our end-of-year special. He’s Professor of Genomics, Physiology, and Biophysics at Weill Cornell School of Medicine and the author of such an outstanding book that we had to have him on the program a second time this year. Called The Next 500 Years: Engineering Life to Reach New Worlds, the book delivers on its title.

Chris was deeply influenced by a book of Isaac Asimov he received at the age of 15 from his parents, writing that this book “never left his head.” Join us as he shares the haunting idea he received from Asimov, his ethical and philosophical positions, as well as the outline of his plan for the next 500 years—and a lot of other scientific tidbits. Any takers for chloroskin? The book serves as a summary of Chris’s years in the field of genomics—a basic biology textbook—as well as a passionate plea to take our common future—what for some of us seems a very distant future but for Chris can seem to be moments away—more seriously.

Happy Winter Solstice, fellow Earthlings!