So my big question is, do you think that sometimes ethics can get in the way of science?

I'm Insoo Hyun, Director of the Center for Life Sciences at the Museum of Science.

Today, my guest is famed geneticist Craig Venter.

Today we talk about synthetic biology, ethics and what it means to be a maverick in science.

the way I like to think about biotechnology is this basically leveraging nature's processes for industrial or commercial purpose is very, very broadly construed, don't you think?

You know, breweries were our first biotechs.

Well, they were.

And part of the early uses of genomics was once Saccharomyces cerevisiae was getting sequenced, a lot of different breweries wanted their yeast strains to be sequenced, you know, to understand consistency and even to establish intellectual property control over them.

And so it's been become a big part of fermentation, both for industrial purposes as well as for producing wine and beer.

And people hold some of those strains very sacred.

Oh, very much so.

I didn't know this until kind of recently that the reason why beers like Heineken always tastes like Heineken every single time is because of the yeast strain that they have.

And now that's kind of I think, why you wanted to kind of control that.

Strange, because that's your distinctive flavor, right?

I didn't know there was that specific.

But some claim it's the water and the various places.

But you know, it's the flavors definitely come primarily from whatever yeast strains being used and how long it's been used for.

And Yeah, yeah, we owe it all to the microbe.

And so you've been doing some pretty amazing work with microbes.

what got you really interested in microbes, right?

A lot of times people enter biology because they think, I want to work with large animals, I want to work with things.

You can see.

But for microbes that are just invisible to the naked eye and but they're extremely important.

What drew you to the microbe?

I came at it from two different points of view.

So when I got drafted off my surfboard in the 1960s and ended up running the infectious disease ward and Bible Hospital and then spent a year in Vietnam dealing with every imaginable infectious disease amongst every other kind of insult that war instills on people.

And then I was actually working primarily on on human genes when my good friend and colleague, Ham Smith, who got the Nobel Prize in 1974 for discovering restriction enzymes, suggested we sequence his favorite bacteria, Haemophilus influenzae, which he isolated the first restriction enzymes from the time a whole shotgun sequencing idea.

Yeah, so am one of the most cited and rewarded microbiologist, but I've never had any training as a microbiologist, so I learned it one genome at a time.

And so getting the that the genome of the first bacteria in history.

And then it was just trying to understand life from there, you know, can we understand it from the genetic components.

And that's led to so many different directions that we've gone on from there.

But it's been one bacteria at a time, one microbe at a time up until the expedition.

Well, you know, I'm a pretty reasonably well known bioethicist, but I've never taken a bioethics course.

So maybe that's the secret.

I think one of the really good in the field just you don't study it in school.

Well, in fact, you know, because I've dealt with so many things on the front line, I've always argued that every scientist has to be their own bioethicist.

You can't it's not like a priesthood where you rely on bioethicists to make the decisions.

But it's important, you know, having the broader discussion and documenting points of view and stuff.

But I've never had any formal training either.

We all go on our own moral compass.

Yeah, I've done lots of consultations in bioethics, both in the clinical setting in a hospital and also, you know, for research bench scientists.

And sometimes I feel like a priest in secular clothes, like they kind of expect that I'm going to have the answers and I try to tell them you need to sort of find a way to work it out yourself because there'll be a time like tomorrow when I'm not going to be here with you and I'm not going to be here to bounce ideas off.

I had this one student who tell me when she was a medical student, she had she had to miss class one day.

is more your area than my area.

And I thought, Are you kidding me?

I'm never going to write a prescription for somebody.

I'm not going to make a decision that could end their life.

This is more your area than my area.

You know, it could ever be.

So I really hope the more people kind of take that ownership, that that ethics is something that they have to embrace and think very seriously about.

Well, we commission on Bioethical Review when we were contemplating making the first synthetic cell, and we know that would be very disruptive to society potentially.

And so we commission with Art Caplan and his colleagues Mildred Cho There are many, yes.

Yes.

She was the one who actually led the review.

They published their findings in science.

And but I think it really helped.

And then once we announced the first synthetic cell, President Obama started the new bioethics commission.

And the first charge was just to review making synthetic life.

Yeah, that really was quite something at that time.

I got my start in bioethics because when I was a graduate student in philosophy, my advisor was on President Clinton's bioethics council, and this is when Dolly the Sheep was cloned and President Clinton, as his counsel to police, come up with the report on the ethics of human cloning.

And I was the graduate assistant on that paper.

And I realized this is such a cool area because I was in philosophy and I thought bioethics is so interesting because you've got science, you have some a little bit of religion, you have a little bit of, you know, sociology, a lot of politics.

Everybody's interested in some of these technologies, some of these groundbreaking, very, you know, steps forward.

And that's really sparked my interest.

So I could really appreciate at that time when you were announcing the results of your work on a synthetic genome, synthetic cell, it was like another one of those moments where everybody was just so interested in what's going on.

Well, I think I'm one of the first scientists in modern history, maybe since Galileo, where we got comments from the President Obama and the Vatican says the pope said Dr.

Venter did not create life.

He just changed one of life's motors.

Who knew life had motors.

It's because you use the bacterium and you just.

Yeah, But I was so difficult, right?

Putting DNA that's not in a nucleus.

Right?

Prokaryotic cell into wasn't that difficult to do that transplant?

No, the transplantation was one of the big breakthroughs that our team did working out how to do that.

And it's but it's like putting a new operating system in a computer.

Yeah.

Cells can't live without DNA, and DNA is the basis of every life form we know.

So everything in the cell totally changed every molecule in the cell change based on the new genetic code being there.

But the machinery in the cell has to be compatible with the genetic code that's going in.

So the ribosomes have to recognize and stop.

So you can't do this across very divergent species.

You know, it has to be a recognizable system.

But we thinking that we can create a universal recipient that has both E coli type recognition systems, mycoplasma recognition systems that would work with a variety of different DNA is.

But that hasn't been done yet.

So it it's it thinks that the donor and the recipient as in transplantation have to be more closely related.

Yes.

So you synthesize the DNA and then you put the DNA into into an existing bacterium.

So it was a existing bacterial cell and it was done in two different ways.

One was getting rid of the genome in the cell first.

So it was just basically an empty dead cell.

The other way we use the restriction enzymes, the molecular scissors that cut DNA, and we designed the genome.

So that the new genome going in would be totally resistant to any enzymes in the cell.

But we programed in restriction enzymes that would recognize the native chromosome as foreign DNA and chew it up.

So as soon as the new synthetic chromosome started being expressed, it expressed enzymes that chewed up the other DNA and the third mechanisms as the cells segregate, the original chromosome would go off with one cell body and the new one off with another.

And then we used antibiotics to kill off the old system.

So there's multiple ways that it happens.

But the key thing is if people still want to build a cell from scratch, whatever that means, you know, we know what it means with making a cake if you start with flour instead of a cake mix.

But you know, with life, you're not starting with carbon and oxygen and putting things together.

So, you know, but starting with the operating system, everything in our bodies, everything and every cell derives from its genetic code.

So you change the genetic code, you change the species.

this seems to be this really cool analogy between biology and cells and DNA and computing, right?

So I think you've mentioned once several times about like digitized biology or digitizing.

Could you say a little bit more about that idea is really quite intriguing because of course, computer science has exploded.

Yeah.

And do you think this is a next wave for biology?

Well, it has been for some time.

So we describe when we sequenced the genetic code, we're converting it from a biological molecule of the four bases of DNA into digital code in the computer.

And now we've shown we can go the other way, we can start with the digital code, recapitulate making the molecules and recapitulate life.

So it goes through this digital phase.

And so when we sequence DNA, we describe it as digitizing biology, because that's in essence what we're doing.

the synthetic DNA that you created was that quote unquote like minimal DNA.

So the first one that we announced in 2010 was largely similar to the native chromosome.

Nobody had ever synthesized a piece of DNA that large and that was just a huge challenge on its own.

Nobody's ever booted up a piece of DNA, a new chromosome.

So just showing that it was possible to chemically make the genetic code and boot it up to get a living cell was a major breakthrough that then allowed us to spend the next four years designing and making what's now a minimal cell.

That's a fantastic tool being used by hundreds of labs around the world.

Now by adding genes back, we argued if we had a minimal cell to start with, we could recapitulate much of evolution by adding genes back and adding functions back to the cell.

And that's what's begun to happen.

Recently.

A team added back genes that cause cell motility and the cells started walking around the plate.

So when you have a minimal life form that if you take any genes out, it doesn't function.

It's a tremendous research tool starting point to understand the fundamentals of biology and by adding back specific genes, trying to get specific functions, you know, either works or doesn't because, you know, we're still in an early stage of discovery.

And I think that's one of the most important things, is we tried designing just on paper what a minimal cell gene components would be, but when we made it, we couldn't living cell out of it.

So we had to add genes back until we could get life.

So you get that just that minimum bare minimum level needed.

But about a third of the genes in the minimal cell were genes of unknown function.

All we know is they're essential for life.

Mm hmm.

So it kind of proves how ignorant we still are about most of biology.

You know, we always reach these plateaus where the scientific community thinks it knows a lot.

Yeah, well, we know a lot more than we used to know.

But compared to what there's left to learn, we still have a very long way to go.

I was just so fascinated with this idea of the minimal cell that once I had a conversation with George Church at Harvard Medical School and I and I said to him, because he does a lot of work where it sort of raise questions about whether or not he's creating embryos or creating, you know, from stem cells.

His models look like they're sort of recapitulating early human life and really creating persons in the lab from, you know, skin biopsies, basically.

And then I said to him, what if we came up with some concept of a minimal person?

Once we have that in mind, then back it off, like they'll never get to that point.

So what will we need for a minimal person?

You know, not it's not just cells.

It can maybe not even be cell based, but maybe it's more about intentionality, consciousness, autonomy, self-determination, those kind of like bare characteristics to call something a person, a moral agent.

And, you know, I might want to work on that idea a little further, but I think that might be kind of a cool bioethics kind of guidepost where you say this is what minimally we might possibly mean by the word person, and then just don't bioengineer something that can do that.

Well, you might remember back from the late Bernadine Healy was NIH director, and she suggested growing humans without heads for organ transplantation.

And I commented on that.

But humans without heads are dead Just like we need the DNA in our cells.

Human needs a brain, including a brain stem, to to have life and organ development and function.

So we don't have to think and look at minimal humans.

We can just look back and evolution because we share so much of our genetic code certain with every other mammal, but most other species, even back to all the bacteria and organisms we discovered in the oceans.

So minimal life with consciousness.

I have two dogs that I think are more human, uh, than a lot of humans that I've met in my life.

They have great sensory perception.

They're great observers of behavior.

They get hurt feelings, their affection that.

So we just have to look even at other non-human primates to see that most of our traits evolved from these other species.

We understand less than 1% of the human genome.

So trying to be manipulating that and creating variance of that I think is to me it's unethical to do because we're doing it without knowledge.

Yeah, at some point it would be really good to get rid of diseases like Tay-Sachs and other horrible, debilitating diseases for young children.

But we don't know enough about the human genome, that knocking out genes.

We don't know what other functions they have, things like CRISPR are not the precise tool that they're made out in the press to be.

They have what's called off target effects.

They make changes in other genes.

We're just so not ready for doing this.

And my team created the first genetic changes for what's being used for the humanized pig organs of the second heart transplant was just on last week.

Yeah, but we started by completely sequencing the pig genome from the strain of pigs that was being used compared it carefully found reasons sites that through known recombination were safe sites that we could put a so-called landing pad to add new genes and that wouldn't be subject to genetic changes wouldn't just be randomly adding a new gene, have an insert in the middle of a key functional area.

But our knowledge is at an absolute minimum now, and we've learned more from altering ten genes in the pig than we have from most of the sequencing of the human genome.

So far you've been pushing the boundaries in biology for so long, people have called you a maverick.

Do you think do you think you're a maverick?

Well, they've called me all kinds of things.

I think maverick and maverick is one of the more pleasant ones.

scientists should be mavericks where, you know, our whole career is based on discovering the unknown.

My biggest complaint about U.S.

science is 90 plus percent of it is just me too science, including most of the the government funding.

So we need a whole lot more mavericks to push the boundaries.

I've argued that the American public should feel outraged that we're spending billions of dollars and not getting far more breakthroughs than we're getting.

But I was actually asked by a recent administration what I want to be NIH director.

Hmm.

And I said, well, if you get Congress to set aside 10% of the budget for funding totally new science ideas, I would consider doing it.

I think I know what the answer was.

You know, that's not going to happen.

Right?

Said, well, you know, this isn't going to happen.

Well, I mean, think about the scientists people most admire in history.

I mean, Charles Darwin getting on the Beagle, that was pretty mavericky right at that time.

Well, at that time, he was going on a survey ship just as a naturalist, you know, what I describe in my book as exploratory science, something that's sort of gone out of fashion and you can't get grants to do exploratory science, but or observational science.

But that's exactly what we did.

And we showed it's just as viable today as it was in Darwin's age.

Just the tools of science have improved, so he couldn't see any of the organisms that we discovered didn't even know they existed.

And so now the tools we could go out like he did and just make observations.

What's there, What does it mean?

What's it doing, How is it changing?

Uh, but, you know, he was the first to do that on a meaningful scale by going to places like the Galapagos where he saw that by having genetic isolation or physical isolation that would lead to unique genetic traits and even rapidly changing characteristics of a species like the beak of the the the finch beak changes just based on the hardness of the food that's available.

So we are genetic leap plastic species.

Everything on this planet is and we change based on the environment, you know, but when you get isolated environments or populations that just in breed, you lock in unique characteristics.

And he was the first to make that observation before he knew what the genetic basis of things was.

well, speaking of scientific mavericks, we had Jane Goodall here last week.

And when you think about her career, I mean, to go out into Gorilla Country, Chimpanzee Country with just a notebook and binoculars when she was a young woman, she was laughed at that time.

Yeah.

And I think she'd be the first to say that she thinks that the great apes are persons.

And and she just made so many wonderful observations that we all lean on today to sort of even reset, recalibrate, kind of how we think morally about our closest cousins.

I can imagine somebody being able to do that today, getting a grant to do something like that today, for example, maybe there are people or there are foundations that do fund, but it's not always and unfortunately Jane's been funded well, to keep doing that has been phenomenal work for a long time.

But I think there have been in the news other mavericks that are not so admired.

Right.

Right.

So we have Jiankui He, who created the CRISPR babies in China and went to jail for that, Woo Suk Hwang in South Korea, who said that he cloned human embryos and got stem cells and that was fabricated.

He also went to jail.

So there have been mavericks kind of on the back in the bad sense.

Yeah, I don't consider those mavericks so much.

As you know, in the case of fabricating science, that's becoming a bigger and bigger problem in science.

And now with these new AI tools, we're probably going to even see more of that.

Some people estimate as many of a quarter of the scientific publications contain fabricated data or altered data.

So that's a giant moral dilemma for the entire scientific community.

But some people do things, you know, either their own moral compass is askew or they're doing it just for grandstanding.

So, you know, mavericks, in my view, you know, push things to good limits versus doing stunts or trying just to get publicity for things.

So, you know, those are cases that win against, you know, the plurality of thinking in the scientific and nonscientific communities that, you know, we're we're not ready for human cloning.

We're not ready for massive, unethical, fake science.

some people may think that ethics gets in the way.

I mean, my plea question for you is, do you think that ethics can sometimes get in the way of science?

Depends on whose ethics you know, it's you know, ethics is not an agreed upon, you know, set of values that everybody shares.

The rules in China are very different than they are in the U.S.. Mm hmm.

You know, so, you know, a lot of people do things outside of the boundaries of what I would consider ethical.

Like, I think we chatted about this a little bit funding gain of function research and a lethal virus in China where we have no control over what's done, how it's done, or how that's used.

That's just wrong for the U.S.

government, the NIH, to be doing that.

You know, it's something I would never do, ever allow, you know, but we have people doing that.

But we've seen so much, sadly, over the last decade in this country where, as you know, 40% of people now have been convinced to not believe in science, not to be believe, in fact, based decision making, you know, to degrade university education.

So we have a much bigger problem.

And we've seen, you know, the term fake news become an everyday thing with a former president who can say whatever he wants.

You know, he's finally getting called down on some of that stuff.

But, you know, it's created a fairly large block of our population and that does not value what you do, what I do or what much of the scientific community does or the education system.

You know, I think that looking at a lot of your work, you seem to be taking ethics very seriously.

I'm so, so good.

Case in point was the the work around the synthetic cell and synthetic genome.

You said that you collaborated with some bioethicists who ended up writing a commentary that I think was published in the same issue that that your paper came out on the it was really the same or earlier, very, very close by.

Right.

So so there was like collaboration early on with some of these folks.

I mean, do you think that science and bioethics ethics, they should they should kind of go together from the beginning?

Should they kind of?

Well, as I said, every scientist should have their own moral compass, just as every physician needs to, because we're in a position to make decisions and do things.

You know, there's.

Yeah, you know, there's not an ethics committee everywhere.

You know, there is clinical review, you know, approving human experimentation.

But when you're working on the forefront, the first to sequenced the human genome, nobody's been there before, making the first synthetic cell.

Nobody's been there before.

And we know that if we don't do that responsibly, it could set science back.

And so what we're trying to do is move it forward.

So we had an extensive review just about, you know, whose DNA should be sequenced.

People were totally afraid of it.

If you look back at that literature before the genome were sequenced, people thought it was going to be used just as a tool of discrimination.

Nobody wanted to have their genome sequenced.

That's in fact why my genome and Ham Smiths were two of the first donors.

I figured if we didn't have understand informed consent about what we were doing, nobody this we couldn't explain it to somebody else.

And there's a history of that about the scientist using themselves is the first experimentations versus forcing that on others.

And you know, but at the forefront you do that versus just pushing the boundaries and letting the chips fall wherever they may.

You know, we one of the reasons that we agreed to the so called tie in the White House announcement, which actually got me a lot of grief from a lot of scientists around the world because the law was so far ahead was sequencing the human genome.

You know, a lot of people were angry at the government and angry at NIH and wanted us to see them very embarrassed and ridiculed.

But I made the personal decision that would be one of the worst things for science if we hurt the main institution, even though I disagree with a lot of their approaches and policies.

Yeah, that was funding science.

So I personally set up the process to have the president declare a tie versus trying to humiliate the government and the NIH.

So mean when you're at the leading and bleeding edge, you have to make personal decisions.

You can't rely on somebody else to make that decision for you.

As I say, a lot of people got very angry with me for doing that, but I think it was best for science and the scientific community overall.

Wow, that's quite the experience.

I didn't know that.

So what's next for you?

I read in the Nature article that you're not going to retire anytime soon, Right?

So.

So what's next for Craig?

I think I said retirement is death.

So it's a well, in fact, that's that's fairly true.

Most men die within a few years of retiring.

And I understand that, you know, I've I've been fired from two companies that I started.

Fortunately, I haven't been fired from my own research institute now in its 34th year, but it happens to everybody in professions for sure that your identity gets tied in with your job.

And that persona and somebody who spends 30 or 40 years of a career doing something and then all sudden that's cut off, you know, without having plans, they have to establish a new identity for themselves, a new self-image.

And quite often, you know, depression sets in and, you know, people die from the stress, from losing that.

So unfortunately, retirement can be death.

In my own case, you know, I have my own research institute.

I have one of the best jobs in the world.

I'm able to ask questions about life and try and do things to further the knowledge and understanding.

So I can't imagine just mowing lawns again.

It is one possible next step.

Looking further into research on longevity, are you interested?

So we're building off of what we started human longevity of.

There's been this misinformed idea that just sequencing more human genomes will lead to understanding of the human genome.

We're a, as you know, a very complex species, and without having extensive phenotype information, we'll never be able to interpret the human genome.

Doing lots of human genomes is great for population studies and, and, you know, tracking lineages.

But if we want to know why you have this particular trait or this particular personality, your physical being, it's only going to be by having extensive phenotype data to compare back to the genome.

So that's what we started at human longevity with the most comprehensive, noninvasive physical you can do other than drawing blood.

And now we're trying to extend that at the Venter Institute in the not for profit world to indigenous populations and underserved communities, people who can't afford the $5,000 a year for the comprehensive physical where their employer won't pay for it.

If you look at reservations, they have almost a 20 year shorter expected lifespan than the rest of the country.

We've done a miserable, miserable job as a nation with our indigenous populations, and these are sort of goes back to Darwin.

A lot of populations due to their unique isolation, have unique diseases, a lot of unique liver diseases and things.

When you look at the existing genome databases, they're mostly Western European derived individuals and now more and more Chinese derived individuals, but they don't represent the population of the U.S., let alone the world.

And so that's the other way with comparative genomics just at everybody that's similar.

For example, if you look at the polymorphism rates in different populations.

So Africans have the highest rate of polymorphisms, the most diversity of any population.

Caucasians are sort of in the middle the least genetic diversity is in Chinese populations.

It's not totally clear why that happens other than, you know, from physical isolation.

But it means that due to that limited genetic diversity, if you just look at Chinese populations, you're not going to understand the human physiology, you're not going to extend human behavior.

And the same with Western European populations.

So we we all need the complete diversity to get to understanding and.

We think that we can help with the same way we've done early diagnosis, doing presymptomatic testing, help these populations that are definitely underserved medically.

At the same time, maybe solving some of the diseases and providing new therapies for them.

So we're trying to take it to a different direction because the medical community is not going to change on its own.

We're become strong advocates of presymptomatic testing.

You can feel healthy.

You can tell me you're healthy only if you go through a program like ours.

I can tell you whether you're healthy or not.

Yeah, and in my own case, I felt perfectly healthy six years ago and testing the machines, setting up the clinic, I was told that I had high grade prostate cancer.

This was actually being told by the medical establishment that I did not have cancer.

Oh, we discover cancer in 5% of asymptomatic people over 51% of the entire population has a brain aneurysm they don't know about.

So you can feel fine with all these things.

But by doing presymptomatic testing with the new tools, we can find things at a stage where they're totally treatable.

I'm now six years post having my prostate removed.

My cancer was so advanced had I not accidentally discovered it by testing the MRI machine, we wouldn't be having this conversation now.

So just think 5% of people over 50 with no symptoms have a major tumor that they're unaware of.

That means at least two or three people.

In our audience tonight will have a major tumor that they don't know about.

Well, there's so much to do, so little time.

Your career is just remarkable.

And it seems endless.

I mean, this seems like a whole new other avenue.

I'm hoping that's the case, at least not endless.

But.

Well, you know, the prostate, if I take you out.

So you got more years here.

That's right.

Keep chugging along.

Well, Craig, thank you so much for joining me.

This was really a conversation I enjoyed.

Thanks for having me.