Illustration by Nick Vokey; Source photography by Marla Aufmuth


It’s Time to Believe in Synthetic Biology

Juan Enriquez bets on the end of undruggable targets, the power of programmable cells, and a machine that cooks up biological material.

When Juan Enriquez takes the stage at TED or some other venue, he makes his entrance with a slow, leonine deliberation. At turns gruff, foreboding, waggish, and witty, Enriquez proceeds to do what he does better than most: explain clearly and forcefully such weighty topics as genetically redesigning people and the future of life on earth — and perhaps beyond. He is unafraid to predict what could go right, or wrong, with synthetic biology, gene editing, stem cells, bionics, hybrid organisms, 3-D-printed cells, environmental manipulation, and more.

Two years ago, Enriquez co-authored with Steve Gullans Evolving Ourselves: How Unnatural Selection and Nonrandom Mutation are Changing Life on Earth. It’s a grand and gracious tour through the possibilities emerging across a raft of new technologies, and what to expect. (My review is here.) Enriquez and Gullans, who are both managing directors at Boston-based Excel Venture Management, believe that a radical reshaping has already begun. “We are the primary drivers of change,” Enriquez and Gullans wrote in Evolving Ourselves. “We will directly and indirectly determine what lives, what dies, where, and when. We are in a different phase of evolution; the future of life is now in our hands.”

The vision they describe is fraught with perils, and Enriquez is realistic about the risks. Yet he is ultimately optimistic that humanity will thrive, a philosophy that he applies to a wide range of investments, including stakes in companies like Synthetic Genomics, co-founded by Craig Venter. Synthetic Genomics is built on the idea that biological systems can be custom-built to produce useful products, from foods to drugs to fuels. Just this week, the company published details of a prototype of what it calls a digital-to-biological converter: a machine that converts digital files of DNA sequences into real biological material, such as strands of RNA that can be used in vaccines.

I sat down with Enriquez at a busy Chinese restaurant in San Francisco last week to discuss what’s on his mind right now as an investor and a scholar. Here are some highlights.

You see the future of health and biomedicine from a number of angles — technological, philosophical, and practical. Let’s first talk about the practical part. What are you looking at as an investor now?

The way I think about investing is: find a great big problem, find it as it’s being developed. I research the hell out of it. Get to know the academics in it. And then I invest in it two or three years later. Sometimes, I wait longer.

So you don’t just leap right in.

Look at genomics. Did the research in ’97, ’98, ’99, when everyone was investing. But most of these investments didn’t really pay off until 2010, 2012, 2017.

So you had no irrational exuberance around genomics in the late ’90s like everyone else?

It was a really exciting time, and I made some money, but I also lost money. I learned from that.

Who did you invest in back then, and what’s happening in this space now?

The usual suspects: Celera, Geron, Millennium. I was smart enough to sell some but not most. Today there are a whole bunch of genetics companies, genomics-based companies, that are real. Also, there isn’t really a division between biotech and pharma companies anymore. They are all doing genomics. Most of the agriculture companies have become genomics companies. So we just take it for granted and we just assume life code is part of the system that operates as a whole there and it’s normal and natural.

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Do you invest in some of the more traditional biotech companies?

No. We like to find big problems to try and solve with new ideas. For instance, I wrote case studies on antibiotic resistance for Harvard because it was apparent 20 years ago that antibiotic resistance was going to be a big deal, and then the question was “when do new technologies allow you to scale this stuff to the point where it really becomes interesting?” Twenty years later we think that we can now use synthetic chemistry to create the next 10 generations of antibiotics. I’m not as scared of antibiotic resistance as I was.

Why not?

It’s now not that difficult. You just need to repurpose some of the antibiotics we have now. What resistant bugs do is they change their camouflage slightly and then they don’t get zapped [by antibiotics]. We use exactly that trick in reverse. Change the camouflage of existing chemicals like tetracycline, and you can generate the next 2,000 antibiotics that can hit anything that’s nasty in India and China. We’re are doing that with Tetraphase [Pharmaceuticals].

What else are you looking at?

The second field I think is going to be very important is the ability to design thousands of specific molecules and hit what have been undruggable targets. We have seen several companies that open up entirely new fields of pharmacology. This will also have an impact on broad industries including chemicals, agriculture, energy.

What else?

I think a third area that’s interesting and important, if you truly want to go after reducing healthcare costs, is prevention. But that’s just not part of the current healthcare debate. The Japanese spend three times as much we do per person on healthy food. And a third as much on medicine. And their outcomes are far better. We know that certain diets can really hurt you. We also know how to fix that.

How do we do something about this?

We know that people make about 220 decisions a day as to whether to eat or drink something. Do I have sip of coffee? Do I not have a sip of coffee? Do I have that candy? Do I order this? Do I order that? Marketing people understand this very well. As you walk down the street, as you walk into the supermarket, as you walk past a newsstand, as you walk into a restaurant, everybody is trying to nudge you to make a decision to consume something else. And it has a huge effect on you. So the ability to just think through that, in a somewhat rational way, is something we’re trying to do with a San Francisco company called Zipongo. We can have a measurable impact on healthcare by just making people aware of these decisions and nudging better choices.

How does that actually work?

The first thing is: “What do you like to eat? You want a hamburger and pizza diet? Fine, we’ll give it to you. You’d like to eat more greens or this, that, and the other? Okay.” Depending on your preferences you will receive a daily email that says, as you walk into the company cafeteria, “Today there are 17 dishes for breakfast; consider the following three.” It does the same thing at lunchtime, and at snack time. You don’t have to pick the choices. It’s not going to track you. It’s not a nanny. It’s just nudging you so that out of the 220 decisions you’re making a day you make 10 to 15 percent of them better. It’s an app that is localized for you to include every supermarket, every restaurant, every business work cafeteria.

“Over the next year or two you’ll be seeing six or seven deals in a row that will be significant deals that scale and start to change everything.”

What’s happening with Synthetic Genomics, the company you co-founded with Craig Venter?

I think Synthetic Genomics is really going to surprise people because synthetic biology has been a long time coming. You’re now beginning to see scalable products and that’s going to be a big deal. Over the next year or two you’ll be seeing six or seven deals in a row that will be significant deals that scale and start to change everything.

Besides drugs, what are other possibilities with synthetic biology?

Everything. This is where we can begin to re-engineer people and animals. The field is really exploding right now. People are working on using synthetic biology to build hybrid machines and biological materials, where you begin to mix living cells with an artificial leg, say, to build hybrid things that we traditionally consider nonliving.

Putting back on your business hat, what practical uses in the near term can come out of this?

What’s fascinating about life sciences is that it has so many possibilities. Just this week Synthetic Genomics published a digital-to-biologic converter in Nature Biotech. That means eventually we will be able to print and grow drugs and chemicals at scale anywhere.

We’ve created desktop printers that make programmable cells for specific functions. [That] can change where you make oil and the quantities of oil you make. You can make cells that do all sorts of things — [turn into] food, feed, fiber for instance. This could alter global agricultural, chemical, and energy outputs.

You’re talking about being able to make a steak at the cell level, and not needing an actual cow.

You just clone the cells to create the meat and you get what some people would call “ethical beef” without the need to grow and kill an animal. But it is still a steak.

Why is the cell so important?

Because it’s the perfect little factory. It’s very good at absorbing energy. It’s very good at executing code. It’s very good at making things. So as long as it’s written in life code you get almost any organic output out of a cell. You can do so with an efficiency in a space that is much, much smaller.

“We have to work hard to be sure these technologies are used the right way. But in the end I think we will manage.”

It’s been two years since your book Evolving Ourselves came out. You encountered some skepticism for your idea of unnatural selection.

Two years ago there was quite a bit of debate and pushback about conceiving of evolution with a different, parallel mechanism. There’s no debate and push back today. It’s become so clear that we humans are increasingly in charge of evolution as our ability to code life forms in non-DNA-based stuff has moved forward. For instance, you can now build six-letter lifeforms. Nothing like that has existed in the history of this planet that we know of.

Explain what that is, adding nucleotides.

Every living form we can observe or look at is based on the same four-letter code of DNA [A, C, T, G]. What if we created more of these letters, these nucleotides, making six of them instead of four? Then all of a sudden you can code in 172 amino acids. That’s a big bloody deal because all of a sudden, using the power of synthetic chemistry, you can make something that is living and reproducing and evolving in a code unknown to any other life form on Earth. That’s change in a radical way. And by the way, [Scripps Research Institute’s] Floyd Romesberg has already built this; life that may or may not interact with current life forms on Earth.

Let’s talk ethics. Is it all going to be good or are you worried about things?

Nothing’s ever all good. I worry about things. Politics, for instance, right now. We have to work hard to be sure these technologies are used the right way. But in the end I think we will manage.

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