Speaker 1: Brought to you by Toyota. Let's go places. Welcome to
Speaker 1: Forward Thinking. Hey there, and welcome to Forward Thinking, the
Speaker 1: podcast that looks at the future and says, in just
Speaker 1: seven days, I can make you a man. I'm Jonathan
Speaker 1: Strickland and I'm Joe McCormick. Was that a reference to
Speaker 1: the Ring? No, No, No, that was a lyric straight
Speaker 1: from Rocky Horror Picture show the Charles Atlas song in
Speaker 1: just seven days, I Can make you a man? All right, Well,
Speaker 1: it's because today we're gonna talk about making life forms synthetically, artificially,
Speaker 1: not through the old biological way, like taking all the
Speaker 1: building blocks of pieces of life and cramming them together
Speaker 1: until you get some sort of glorious Frankenstein's monster of
Speaker 1: a creation that can rampage throughout the countryside and make
Speaker 1: the peasants all scared, or a single celled organism, or okay,
Speaker 1: well we gotta we gotta crawl before we walk. Yeah, well,
Speaker 1: we've got a flagellum before we crawl, that's right. That's
Speaker 1: also a little bit of paddling through some fluid. Yeah. Yeah,
Speaker 1: So today we're gonna be talking about synthetic biology, which
Speaker 1: is a very interesting area of future research, present research,
Speaker 1: and especially future research because synthetic biology comes up all
Speaker 1: over the place when you start talking about future solutions
Speaker 1: to problems. Like one great example is we've talked about
Speaker 1: I know, we've referenced it before in the idea of
Speaker 1: colonizing other planets, like how can we make all the
Speaker 1: materials we need and you know, the food and the
Speaker 1: fuels and the medicines and stuff like that on the
Speaker 1: surface of Mars without having to carry just tons and
Speaker 1: tons of supplies and cargo along with us. And one
Speaker 1: of the solutions people are proposed is, well, what if
Speaker 1: we created organisms that we could take in tiny colony
Speaker 1: cultures with us that would multiply once we got to
Speaker 1: the planet, and then make all of these things we need,
Speaker 1: right taking the raw material that is available on Mars
Speaker 1: and converting it into the stuff that we would find useful.
Speaker 1: But of course we'd have to take a step back
Speaker 1: first and say, wait a minute, can we create organisms
Speaker 1: like that? And if we can, should we We've got
Speaker 1: a lot of questions, But first the first question we
Speaker 1: have to ask is what is synthetic biology? Because it's
Speaker 1: such a relatively new discipline, they're actually multiple definitions for it,
Speaker 1: and it depends largely upon what perspective you're taking. It's
Speaker 1: clearly related to genetic engineering. Uh, you're talking about manipulating
Speaker 1: the genes of an organism to create some sort of
Speaker 1: biological change, but it kind of goes a step beyond
Speaker 1: just that, and Uh, creating a firm definition for it
Speaker 1: is tricky, but one way to look at is take
Speaker 1: the principles behind engineering and apply them to biology. Uh. Now,
Speaker 1: there is a website synthetic biology dot org and they
Speaker 1: aid define it as the design and construction of new
Speaker 1: biological parts, devices, and systems, and the redesign of existing
Speaker 1: natural biological systems for useful purposes. And they also state
Speaker 1: that there are two different types of synthetic biologists. The
Speaker 1: first group uses quote unnatural molecules quote unnatural molecules meaning
Speaker 1: man made uh, to mimic natural molecules with the goal
Speaker 1: of creating artificial life. This would be that Frankenstein's bacterium
Speaker 1: I was just talking about. The second group uses natural
Speaker 1: molecules and assembles them into a system that acts unnaturally.
Speaker 1: This would be closer to what you were talking about, Joe,
Speaker 1: finding some sort of or creating some sort of organism
Speaker 1: that can take something that we don't find useful and
Speaker 1: turn it into something we do find useful. So, uh,
Speaker 1: you know, you can think of synthetic biology as a spectrum.
Speaker 1: On one end, you have the modification of existing biology,
Speaker 1: and on the other end of it, you have the
Speaker 1: quest to create an entirely new life form from scratch,
Speaker 1: whether it's a new maybe not a totally new life form,
Speaker 1: but maybe a specific individual within a pre existing species,
Speaker 1: but with a synthetically created genome. Yeah, and so you
Speaker 1: might be wondering, well, what does this look like in reality, Well,
Speaker 1: we don't have to speculate, because in fact, synthetic organisms
Speaker 1: already exist. Yes, they've already been created around six years old.
Speaker 1: Uh back in two thousand ten, so a little more.
Speaker 1: And in fact, just about six years ago from this
Speaker 1: week was when the scientists at the J. Craig Venter Institute,
Speaker 1: why do you why does the why does he leave
Speaker 1: the J in there? Nobody says the J the Craig
Speaker 1: Venor Institute when they announced the creation the first synthetic cell,
Speaker 1: and that this was not the first time that synthetic
Speaker 1: DNA had been put together, but this was the first
Speaker 1: time that there was an organism that began as pure information.
Speaker 1: So it's just a sequence of code inside a com pewter,
Speaker 1: which was then translated into a real live organism built
Speaker 1: out of organic chemicals and became a new living species
Speaker 1: that could survive on its own and reproduce. And we're
Speaker 1: still here. So it didn't create like the zombie apocalypse
Speaker 1: or anything. Yeah, it has it's a very slow burn. Yeah,
Speaker 1: well in reality it probably would be I think, I
Speaker 1: mean Dead season two was pretty slow. We don't have
Speaker 1: to get into that right now. The cool thing. Craig
Speaker 1: Venter himself gave a quote about this. Craig Venter, uh known,
Speaker 1: you know, big guy in genomics, you know him from
Speaker 1: the biotech field. Craig Venter said, quote, this is the
Speaker 1: first self replicating species we've had on this planet whose
Speaker 1: parent is a computer. It's a fun, quicky way of
Speaker 1: putting it. He's full of yeah. So yeah, So it
Speaker 1: was a self replicating synthetic bacterium and the team that
Speaker 1: built it, they built it out of one point eight
Speaker 1: million base pairs that went into a chromosome from the
Speaker 1: genome of a modified bacterium called Mycoplasma mi coites or
Speaker 1: miquities m y c o I d e yes mi couities.
Speaker 1: It's a strange word. It is. I've heard people say it.
Speaker 1: They all say miquities. My ability to pronounce such words
Speaker 1: is so limited that I'm I'm just going to accept
Speaker 1: whatever pronunciation you give us as the proper one. Okay, Well,
Speaker 1: there it is. Uh. And so Dr ham Smith, who
Speaker 1: is one of the leaders on the project said, quote,
Speaker 1: with the first synthetic bacterial cell and the new tools
Speaker 1: and technologies we developed to successfully complete this project, we
Speaker 1: now have the means to dissect the genetic instruction set
Speaker 1: of a bacterial cell to see and understand how it
Speaker 1: really works. So one of the things he's pointing out
Speaker 1: here is that it's not just about creating Frankenstein bacteria.
Speaker 1: It's about understanding the the understanding the building blocks of
Speaker 1: life better. By building something, you understand what it is
Speaker 1: that makes that thing work, right. Sure. Yeah, And you
Speaker 1: can see this like in in engineering again, showing the
Speaker 1: parallels to the engineering disciplines that you know, if you
Speaker 1: give someone a kit to build something, through the construction
Speaker 1: of that something, they get a better understanding of how
Speaker 1: it works. Once it's all put together. Like a radio, right,
Speaker 1: And there's a really interesting thing I'm going to talk
Speaker 1: about in a moment where the that idea comes into
Speaker 1: the very d N a of this new organism itself,
Speaker 1: the literal DNA, not the figured of DNA exactly. So,
Speaker 1: so the creation of this viable synthetic cell was a
Speaker 1: project that took a long time, tons of tons of research.
Speaker 1: It took almost fifteen years, and uh to hear Venter
Speaker 1: explained it himself and in his press release, he you know,
Speaker 1: he talked to the press about it, and he summed
Speaker 1: it up by saying, there were two major challenges they
Speaker 1: were dealing with. They'd already dealed with the sequencing the genome,
Speaker 1: so that that was a hurdle they'd already overcome going
Speaker 1: into this project. But the two maining remaining challenges. The
Speaker 1: first one was chemistry. How do you build this gigantic
Speaker 1: DNA molecule from its constituent parts. So it is a
Speaker 1: huge molecule, it's made out of lots of tiny little
Speaker 1: base pairs and it's just gigantic, and all of the
Speaker 1: base pairs have to be correct, you know, or not.
Speaker 1: A single error in some cases can cause the organism
Speaker 1: not to be viable, So you have to start with
Speaker 1: the genome of the bacterium in question. At first, what
Speaker 1: they were working with was microplasma genitalium. They changed that
Speaker 1: later for a reason I'll let you know. But uh so,
Speaker 1: they sequenced this genetic information and then they had this
Speaker 1: digital information that's spelled the recipe for the organism's DNA.
Speaker 1: But how do you turn that into a physical chromosome
Speaker 1: that goes into a cell. The second major challenge was
Speaker 1: essentially surgery. Once you've got a synthetic chromosome, how do
Speaker 1: you transplant it into a living cell and have that
Speaker 1: cell be viable and self reproducing. Uh So, for example,
Speaker 1: they discovered that one host cell they were trying to
Speaker 1: transplant this foreign chromosome into was it was full of
Speaker 1: nuclease that was defensively destroying the foreign d NA when
Speaker 1: it was introduced. In inventor's words, it would just eat
Speaker 1: up are synthetic chromosome. So I mean, good good on
Speaker 1: that cell. Right, Yeah, I was doing what it was
Speaker 1: supposed to do. Yeah, it doesn't want to be a
Speaker 1: synthetic organism. Right, It's like when you're being attacked by
Speaker 1: a virus um. So this is interesting. So the first
Speaker 1: challenge being, well, you're just creating the synthetic chromosome in
Speaker 1: the first place, and then once you have that, you
Speaker 1: still have the challenge of how do you introduce this
Speaker 1: into a living because otherwise you just got data but
Speaker 1: no computer to run it on. Essentially, if you want
Speaker 1: to have a comparison to to our our technology, so
Speaker 1: you have to insert that that software into a computer.
Speaker 1: In this case, it's a computer that already has its
Speaker 1: own software and that software wants to kill the new software. Yeah.
Speaker 1: Uh So once they got all that figured out that,
Speaker 1: the way eventually they went about the US was they
Speaker 1: built the synthetic DNA chromosome inside a yeast cell and
Speaker 1: then removed it from the yeast and they had to
Speaker 1: methylate it in order because they discovered that methylation protects
Speaker 1: the DNA from being digested by the host bacterium and
Speaker 1: then transplant it into a shell bacterium or a host
Speaker 1: bacterial cell. In these cases it was microplasma capriculum. So
Speaker 1: another problem they encountered along the way they talked about
Speaker 1: was that the cell wouldn't grow fast enough they were
Speaker 1: trying to do this, and so they ended up uh
Speaker 1: starting with the genome of a different organism. After microplasma
Speaker 1: genitalium didn't work well enough, they went with microplasma micodes
Speaker 1: and this organism had a much larger chromosome. It's bigger,
Speaker 1: harder to work with at over one million base pairs.
Speaker 1: Another thing that's really cool that they did is they
Speaker 1: put water marks in the d NA to leave no
Speaker 1: room for doubt as to whether the DNA was synthetic
Speaker 1: or natural. And what these were were stretches of non
Speaker 1: coding DNA, which DNA that doesn't actually make any proteins.
Speaker 1: You could just think of it as kind of metadata
Speaker 1: or the you know, slash slash notes sections in a
Speaker 1: piece of computer code. Uh. And these were used to
Speaker 1: code in written messages in the organism's DNA, including names
Speaker 1: of the authors on the research a web address associated
Speaker 1: with the project project so Ventor said, you know, if
Speaker 1: you can decode this, you can email us. Yeah. Three
Speaker 1: three quotes. They put some quotes in there. So one
Speaker 1: was a James Joyce quote, this is great to live,
Speaker 1: to air, to fall, to triumph, and to recreate life
Speaker 1: out of life. Good quote. A second one was from
Speaker 1: the book American Prometheus, which was about Robert Oppenheimer, and
Speaker 1: the quote was see things not as they are, but
Speaker 1: as they might be. That's a good one too, not
Speaker 1: not a bad open higher quote. I could think of
Speaker 1: one that would have been worse. Yeah, I have become death.
Speaker 1: The third was, of course from Richard Feynman, when Speineman
Speaker 1: said what I cannot build, I cannot understand. And that's
Speaker 1: the quote that I was referring to earlier. Right, I'm
Speaker 1: very sad that they didn't include the Frankenstein quote fire bad.
Speaker 1: But maybe maybe if we decode the that email address
Speaker 1: right when I can write when I make my synthetic bacterium,
Speaker 1: that's definitely going in there, you know. Listening to Ventor
Speaker 1: explain all of the different problems they encountered and fixes
Speaker 1: that they had to go through to to finally arrive
Speaker 1: at this research success, it is amazing that they were
Speaker 1: able to do this. I want to read one particular
Speaker 1: paragraph from Ventor's presentation from May two thousand ten about this,
Speaker 1: because I found this part really fascinating. It was about
Speaker 1: how the team had to develop debugging software to debug
Speaker 1: the organism because you know, they were they were creating
Speaker 1: a synthetic chromosome, so here's how it goes. So the
Speaker 1: team developed a new debugging software where we could test
Speaker 1: each synthetic fragment to see if it would grow in
Speaker 1: a background of wild type DNA, and we found that
Speaker 1: ten out of the eleven one hundred thousand base pair
Speaker 1: pieces we synthesized were completely accurate and compatible with a
Speaker 1: life forming sequence. We narrowed it down to one fragment,
Speaker 1: we sequenced it and found just one base pair had
Speaker 1: been deleted in an essential gene So accuracy is essential.
Speaker 1: There are parts of the genome where it cannot tolerate
Speaker 1: even a single error, and then there's parts of the
Speaker 1: genome where we can put in large blocks of DNA
Speaker 1: as we did with the water marks, and it can
Speaker 1: tolerate all kinds of errors. So it took about three
Speaker 1: months to find that error and repair it. And then
Speaker 1: one early morning at six am, we got a text
Speaker 1: from Dan saying, now the first blue colonies existed, and
Speaker 1: that's referring to you know that these things were reproducing
Speaker 1: within within a couple of days. I think they were.
Speaker 1: There were enough of them that you could physically see
Speaker 1: them in the Petrie dish. Wow, that's pretty impressive. I
Speaker 1: love this that they had to create a debugging program
Speaker 1: for the organism. Yeah, you imagine like that. That's a
Speaker 1: whole new discipline of quality assurance having to go through
Speaker 1: and because I you know, we know people who do
Speaker 1: q A for a living. They have to go through
Speaker 1: and test every single element of code. This is in
Speaker 1: fact biological code. It is exactly the the it's in line.
Speaker 1: I won't say it's exactly the same thing, but it's
Speaker 1: in line with that same sort of discipline. It's also
Speaker 1: absolutely what they had in Jurassic Park. Yes, using virtual
Speaker 1: reality and mr DNA. Uh So. Another thing that I
Speaker 1: just wanted to emphasize. I know I've already said it,
Speaker 1: but I just find so fascinating about this and what
Speaker 1: it illuminates about the nature of life is how zilient
Speaker 1: the DNA code is in some ways and how fragile
Speaker 1: it is in other ways. A missing a missing or
Speaker 1: deleted base pair in one section of the code can
Speaker 1: completely make you a non viable organism, but other parts
Speaker 1: you can just do all kinds of crazy stuff with. Well, again,
Speaker 1: I think if you if you compare that to the
Speaker 1: idea of software like there are there are errors you
Speaker 1: can make when you're coding something in software, and it
Speaker 1: might make something unusual happen when you're trying to execute
Speaker 1: the software. But there are other errors you can make
Speaker 1: that can make that software completely unstable, and it will
Speaker 1: won't even run problem, not only crash, but crash your
Speaker 1: entire system. Right, I'm thinking about every video game that's
Speaker 1: been released over the last twelve months. But maybe that's
Speaker 1: just because of a little bitter about bug game destroying
Speaker 1: bugs released on day one. I don't really know which
Speaker 1: one is you're referring to the pretty much yeah anyway,
Speaker 1: well but but but but I'm saying that the similarity
Speaker 1: really is there, and as much as I'm making fun
Speaker 1: of of of something that's running rampant through the video
Speaker 1: game industry, the idea being that, uh, when you start
Speaker 1: to think about d n A is being similar to software,
Speaker 1: at least in a in a general sense, then you're like, oh, yeah,
Speaker 1: I get it. Because some errors in encoding are not
Speaker 1: that huge a deal. You might be able to pick
Speaker 1: up on it, uh if something unusual happens while you're
Speaker 1: executing the code, and others are absolutely deal breakers. Yeah,
Speaker 1: but anyway, I I think this is so cool that
Speaker 1: you can chart how they went from information to chemistry
Speaker 1: to biology, like there was the entire pathway from just
Speaker 1: from idea to life. And so this first synthetic cel
Speaker 1: was called micro plasma MI codes j C v I
Speaker 1: for j Craig vinor institute sin one point, oh, not
Speaker 1: sin like like doing evil and synthetic. Yeah, so in
Speaker 1: one point. Oh what does it mean? Well, it helps
Speaker 1: us understand better the chemical basis of life. That's one
Speaker 1: big thing where we you know, learn a lot about
Speaker 1: about chromosomes and DNA and the role different genes play
Speaker 1: than we can do continuing research. Now that we have
Speaker 1: the basis for creating synthetic organisms. Uh, it might be
Speaker 1: useful in synthesizing germs that cause diseases so those diseases
Speaker 1: can be treated and overcome. Uh, it might be useful
Speaker 1: for creating synthetic biological organisms like we were talking about earlier.
Speaker 1: So you know, if you want to make some algae
Speaker 1: that could remediate waste products or capture CEO two, or
Speaker 1: create biofuels or food or or whatever. Yes, so these
Speaker 1: are uh, you know, basic ideas well where you visit
Speaker 1: that towards the end of the episode two, when we
Speaker 1: start talking about the the various things you can do
Speaker 1: with the discipline of synthetic biology. This is a pretty
Speaker 1: important part of that. Yeah, an amazing first step. Yeah.
Speaker 1: So the interesting thing is that's not where the story ends.
Speaker 1: That was, but we have continued the advancement of synthetic
Speaker 1: biology since then. Yeah, an inventor and his team specifically have.
Speaker 1: After they created SIN one point. Oh, they set out
Speaker 1: with a new goal to design a bacterium with the
Speaker 1: absolute minimum GENO. And why would you want to do that? Well,
Speaker 1: they wanted to figure out what bits of code are
Speaker 1: essential and what are not essential. Yeah, and this is
Speaker 1: this is really smart to do, I think, because we
Speaker 1: had this problem last time, right where some parts of
Speaker 1: code it seems like it don't matter. You can change
Speaker 1: them with no no big impact. Other parts can our
Speaker 1: our game breakers. Well, and we've also found that there
Speaker 1: are segments of DNA within different organisms that ultimately originated
Speaker 1: from other species and don't have any useful uh you know,
Speaker 1: useful performance, or they don't do anything, or it's a
Speaker 1: duplicate of something else that already works perfectly. Right, So
Speaker 1: maybe we can make life better more efficient, cut out
Speaker 1: the fat and and Furthermore, Yeah, just just what you
Speaker 1: were talking about, Joe, just figure out exactly what the
Speaker 1: different pieces do, because because even though we've we've sequenced
Speaker 1: plenty of genomes, we really don't understand very well what
Speaker 1: all of the individual genes do and and specifically how
Speaker 1: they work together in the genome. That's that's way beyond
Speaker 1: us right now. Um but this can help us learn hypothetically.
Speaker 1: I mean, their first attempts totally failed, so uh and
Speaker 1: and and no one was more surprised than Ventor. He
Speaker 1: there's a great quote where he was like, I was shocked, Like, well,
Speaker 1: you know, I love you, I love the idea. We
Speaker 1: gotta remember you learn more through failure than you do
Speaker 1: through success. Completely that that is literally how science works.
Speaker 1: Um So, ideally you can learn from other people's failures
Speaker 1: in your own successes. That way you look like you
Speaker 1: are awesome, right, much preferable. But yeah, okay, So the
Speaker 1: first attempt that they made, two different teams each independently
Speaker 1: tried to build a bacterium from the ground up, and
Speaker 1: it was just it was too ambitious given our current
Speaker 1: aforementioned lack of knowledge about genetics and genomics. Um So,
Speaker 1: to give you like a metaphor here additive manufacturing a
Speaker 1: genome didn't work. But but what about whittling something down?
Speaker 1: What about removing all the parts of the genome that
Speaker 1: are not the statue of David gotcha? All right? So
Speaker 1: so the traditional subtractive approach where you you are taking
Speaker 1: away everything that is not necessary for whatever the finished
Speaker 1: product needs to be. So so they took SIN one
Speaker 1: point oh and they started labeling all of its pieces.
Speaker 1: They took its nine one genes and played with deleting
Speaker 1: or disrupting different sections in turn. And when they plugged
Speaker 1: the resulting experiments into a m capric column, it did,
Speaker 1: you know, either be viable or totally not viable? And
Speaker 1: if if it died, if it was not viable, they
Speaker 1: knew that they had removed something important science. This this
Speaker 1: makes me think of what early medicine must have been, like, yeah,
Speaker 1: it turns out you needed that one. It reminds me
Speaker 1: of that moment where Bones is, you know, in the
Speaker 1: twentieth century, and he's like these savages. But but eventually
Speaker 1: it produced what they call SIN two point oh, which
Speaker 1: was the first micro but with a genome smaller than
Speaker 1: the world's smallest known natural genome, which is microplasma genitalium,
Speaker 1: which has only five UM. And then along came SIN
Speaker 1: three point oh, which is a living, reproducing organism with
Speaker 1: just four hundred and seventy three genes. They trimmed out
Speaker 1: all of those non essential or a lot of those
Speaker 1: not essential and duplicate genes. Um. But but even at
Speaker 1: this point the critter still might contain some some coding.
Speaker 1: Blow to the researchers are not sure what a hundred
Speaker 1: and forty nine of those genes do. I do like
Speaker 1: the idea that they can cut out a whole bunch
Speaker 1: of genes and pass the savings onto you. I think
Speaker 1: that's that's very forward thinking. Other than other than those
Speaker 1: amazing savings, Um, why would you want to do this? Uh? Well,
Speaker 1: this resulting organism SIN three point oh can be used
Speaker 1: to study what specific genes do, both the ones that
Speaker 1: it currently possesses and also all of the bits that
Speaker 1: they removed from versions one and two in order to
Speaker 1: make three. By by adding them back in one at
Speaker 1: a time, they can watch the results play out. And furthermore, uh,
Speaker 1: the SIN three point oh grows like and reproduces really fast.
Speaker 1: So uh SIN three point o cell populations double in
Speaker 1: about three hours. So that's a great laboratory tool. And
Speaker 1: and eventually they're hoping to create a living organism for
Speaker 1: which the entire genome is understood. And I cannot stress
Speaker 1: how rad that would be. I mean, I mean, even
Speaker 1: if you're only talking about the world's very biddiest genomic code, uh,
Speaker 1: because you know, like I said, like just because we can,
Speaker 1: we can sequence the whole genome, even very much more
Speaker 1: complex genomes. Humans for example, have some thousand genes. Uh
Speaker 1: that that absolutely doesn't mean that we know what what
Speaker 1: all of that coding does. It would be a really huge,
Speaker 1: really huge mile marker. And I think what's really cool
Speaker 1: here also is by adding in those genes one at
Speaker 1: a time and seeing what they do. It's not even
Speaker 1: as simple as that, because genes can interact with one another.
Speaker 1: So sometimes it may be that you let's say that
Speaker 1: you've got one version of this artificial life form and
Speaker 1: you add in one gene and you see how that
Speaker 1: that works. You've got a different version of that same
Speaker 1: artificial life form that has a slightly different series of
Speaker 1: genes in it. It may not have exactly the same
Speaker 1: as the first one. You add that same gene into
Speaker 1: that one, and you see that it expresses itself in
Speaker 1: a different way. That tells you there's going to be
Speaker 1: sort of interaction going on. It also displays, yeah, we
Speaker 1: there's so much we don't know. And it's once you
Speaker 1: start looking at these numbers, like even just with a
Speaker 1: few hundred, it's complicated. When you get to several, you know,
Speaker 1: tens of thousands, it gets really really tough. So let's
Speaker 1: take a look at maybe something that might be a
Speaker 1: touch more ambitious, creating the first artificial human cell. Yeah,
Speaker 1: so in May, we are recording this. At the end
Speaker 1: of May, about one fifty genetics experts met at Harvard
Speaker 1: to talk about the possibility of building an entire human genome,
Speaker 1: not altering one, not sequencing one, but building one. And
Speaker 1: the project is called h g P right w R
Speaker 1: I T E. Testing Large synthetic genomes and cells and
Speaker 1: h g P stands for the Human Genome Project. So
Speaker 1: this approach would require you to have access to a
Speaker 1: DNA synthesizer computer and the raw materials, cop cars, some sunglasses.
Speaker 1: I'm sorry, I think about the Blues Brothers, DNA synthesizer,
Speaker 1: computer and raw materials. Where what you would need. Basically,
Speaker 1: they would build the entire genome from the ground up,
Speaker 1: and the next step would be to insert that synthetic
Speaker 1: genome into a human cell, kind of like what you
Speaker 1: were talking about, Joe, just to see if it could
Speaker 1: replace the already existing DNA within the human cell. Boot
Speaker 1: that all the way and kind of reboot the cell
Speaker 1: so that it now is the synthetic one. Uh So
Speaker 1: it's talking about really programming a new type of human cell.
Speaker 1: You you program a human in the sense that you're
Speaker 1: the one who determines the DNA sequence from beginning to end.
Speaker 1: And Dr J. Keisling of the University of California, Berkeley
Speaker 1: is part of a group putting together a standardized or
Speaker 1: putting together a database of standardized DNA chunks, and they're
Speaker 1: calling these chunks bio bricks. This is actually an idea
Speaker 1: that I think dates back to about two thousand six.
Speaker 1: But uh these these bio bricks represent specific stretches of
Speaker 1: genetic material, and assembling the full genome involves putting these
Speaker 1: chunks together kind of like a big puzzle, like a
Speaker 1: like a Lego but yeah, squishy human person at the end.
Speaker 1: I think Lego is even better. Than than puzzle. Definitely. Yeah.
Speaker 1: It's like like you've got the lego blocks and your
Speaker 1: your bio bricks, like, oh, here's here's one that is
Speaker 1: this particular gene, and then we need to have this
Speaker 1: other one, this other connective piece here before we put
Speaker 1: this other gene in. Otherwise it's not all going to
Speaker 1: fall apart. It definitely don't spill them on the floor
Speaker 1: because those hurt like a mother. Yeah, you step on
Speaker 1: a bio brick and it's gonna be squishy and it's
Speaker 1: gonna go right into the heel. So they're they're meant
Speaker 1: to be interchangeable parts. Uh. And you could build biological
Speaker 1: systems living within a cell and you can arrange them
Speaker 1: to make quote unquote useful devices, which is I thought
Speaker 1: a really interesting way of putting it, Like you can
Speaker 1: use bio bricks to create useful to vices. You're really
Speaker 1: talking about biological elements, and it's weird to think of
Speaker 1: a biological element as a device, but it does show
Speaker 1: again how engineering and biology are very commingled in this approach.
Speaker 1: And I mean technically, like our hands are devices. I guess,
Speaker 1: I guess I you know, I mean, I I very
Speaker 1: rarely think of anything that is part of me as
Speaker 1: a device. And I mean, I realize I'm almost physically
Speaker 1: attached to my phone all the time, but I don't.
Speaker 1: I still don't think of it as part of me.
Speaker 1: I don't pick it up and say, at last, my
Speaker 1: arm is complete again. But then you have a group
Speaker 1: called bio Bricks Foundation, and that builds itself as quote
Speaker 1: a bio biotechnology in the public interest and the purpose
Speaker 1: of this organization has developed the tools and processes of
Speaker 1: synthetic biology in a responsible manner. So it's supposed to
Speaker 1: be uh concerned with ethics, with the cost of this,
Speaker 1: with the access of it, so that people can learn
Speaker 1: from the research that they do and us apply it
Speaker 1: to their own research. And they also want to make
Speaker 1: sure that they limit the spread of mad scientists, you know,
Speaker 1: keep that to a bare minimum, uh or at the
Speaker 1: very least of shortsighted projects that might have bigger ethical
Speaker 1: problems down the line that you might not have anticipated
Speaker 1: just because you were focused on the first stage and
Speaker 1: not thinking, oh, what are the implications of this. One
Speaker 1: of the founders of the bio Bricks Foundation is Dr
Speaker 1: Drew Inde E. N d Y, who played a role
Speaker 1: in developing the bio brick standard part technology, so the legos.
Speaker 1: In other words, he played a role in developing those
Speaker 1: And interestingly, he actually declined to participate in that project
Speaker 1: I was talking about with the hundred fifty researchers at Harvard.
Speaker 1: He said he wasn't going to go because he was
Speaker 1: concerned that perhaps they were rushing ahead toward a goal
Speaker 1: without really contemplating the ethical consequence system. Yeah, like, maybe
Speaker 1: maybe start with a goldfish first, you guys, like, do
Speaker 1: we really need to move straight to human And you know,
Speaker 1: we've talked about this on previous episodes, where if you
Speaker 1: set yourself a specific goal, it hones you in, It
Speaker 1: focuses you so that you can really take the steps
Speaker 1: necessary to solve some big problems that ultimately can end
Speaker 1: up benefiting you in other ways and other applications. But
Speaker 1: it helps to have that goal there, to have something
Speaker 1: to work toward. But he still felt that perhaps this
Speaker 1: was a little too grandiose and idea with too few
Speaker 1: actual um uh thought given or too little thought given
Speaker 1: to the ethical implications. Now, when can we expect this
Speaker 1: to happen? Assuming it it goes forward, We don't know
Speaker 1: they're talking about a ten year time frame, but that
Speaker 1: seems incredibly ambitious. For one thing, this project is not
Speaker 1: funded yet, and for another, it's really difficult to say
Speaker 1: how hard it would be to actually synthesize a full
Speaker 1: human genome um, and because that genomes five thousand times
Speaker 1: larger than that bacterium we talked about earlier, the sin
Speaker 1: one point. Oh, it's gonna be expensive, though less so
Speaker 1: than it would have been a decade ago. In two
Speaker 1: thousand three, it cost four dollars to sequence an individual
Speaker 1: letter in the genome. Now it's closer to three cents.
Speaker 1: So the money, the cost side of it is falling dramatically,
Speaker 1: but still, if you want to sequence the human genome,
Speaker 1: that's a three billion letters total, so that the cost
Speaker 1: about ninety million dollars. It's a lot of money. Um.
Speaker 1: If we continue to drive down the cost, then obviously
Speaker 1: genome synthesis could get closer to a more affordable amount.
Speaker 1: One estimation is that in twenty years you could get
Speaker 1: down to about a hundred thousand dollars, which could be
Speaker 1: something that a major scientific research project could actually do.
Speaker 1: But that's twenty years, and that's that's ten years beyond
Speaker 1: what the ten year uh span of the project was
Speaker 1: proposed to be um so, I don't know if this
Speaker 1: is actually gonna go anywhere. It may end up being
Speaker 1: that that people like Dr Indy are able to say, hey,
Speaker 1: let's before we jump into this project, let's have a
Speaker 1: deeper conversation about the implications of this and make sure
Speaker 1: we truly understand what we are doing, and that if
Speaker 1: we choose to go forward, we do so in a
Speaker 1: responsible manner right, because the potential upsides of this are
Speaker 1: really incredible. Yes, I mean, I I think the sky
Speaker 1: level hope for any kind of genetic study is is
Speaker 1: that we will be able to design bits of code
Speaker 1: to replace genetic code that's causing deadly, terrible and curable
Speaker 1: diseases and suffering in people. Um Or to to to
Speaker 1: make our food sources grow better, faster, stronger, and more
Speaker 1: nutritious and maybe vegan and in difficult conditions and all
Speaker 1: that kind of thing. Um Or I don't know, to
Speaker 1: make house cats that do care about us at all,
Speaker 1: or tall order giraffes with built in rollerblade. I don't
Speaker 1: know what people get up to, but yeah, I mean,
Speaker 1: you know, everyone's got a hobby, so I agree. I
Speaker 1: think that that is definitely the the ideal goal of this.
Speaker 1: You know, it's not too it's not too welcome. This
Speaker 1: is human version two point. Oh, we've built a right,
Speaker 1: It's that's that's not what people are going for necessarily.
Speaker 1: Crab claws and clamps with you, Joe, Yeah, they're the best. Yeah. Well, well,
Speaker 1: I mean we learned I didn't really learn anything about Joe.
Speaker 1: We just had something kind of reinforced a belief that
Speaker 1: we had already discovered earlier. I mean, hold on, do
Speaker 1: you guys go out of your way to mess with
Speaker 1: a crab? No? You don't. No. I mean, if there's
Speaker 1: a crab in my way, I'll go ahead and mess
Speaker 1: with it. But I don't go out of my way
Speaker 1: to mess with a crab. I really only mess with
Speaker 1: them when I'm trying to consume their delicious flesh and
Speaker 1: mostly toss them aside now just out of fear, all right,
Speaker 1: at any rate. That so that's that's the big big picture.
Speaker 1: Like if we can figure it out, maybe we can
Speaker 1: defeat lots of genetically uh or lots of diseases that
Speaker 1: are genetically based, more conditions or things like that, perhaps
Speaker 1: extending lifespans, things of that nature. That's that's like the
Speaker 1: gold standard a goal that we have, but there are
Speaker 1: other ones as well, right, Yeah, And most of it
Speaker 1: is kind of along the lines of what Joe you
Speaker 1: were talking about earlier and what we have talked about
Speaker 1: previously on this show about genetically engineering bacteria to produce
Speaker 1: useful stuff like biofuel or or bacteria that eat explosives
Speaker 1: and can thus be used to dismantle landmines. By building
Speaker 1: an entire genome, we can hypothetically make very very efficient
Speaker 1: bacteria that do those sorts of things. And for example,
Speaker 1: Dr Kisling of the bio Brick Project worked on this
Speaker 1: one proof of concept project in the early aughts in
Speaker 1: which a team created Equali bacteria that produce an anti
Speaker 1: malaria drug. And the yield from these bacteria is so
Speaker 1: much more efficient than from the traditional method of growing
Speaker 1: and harvesting sweet wormwood, which is how you usually get
Speaker 1: the drug component. Um, it's like a million times more
Speaker 1: efficient than doing that, so the price of the drug dropped.
Speaker 1: Everybody wins. That's super awesome. Yeah, And I was reading
Speaker 1: that synthetic biology has already led to the development of
Speaker 1: diagnostic tools for lots of different diseases, including things like
Speaker 1: hepatitis and HIV. So there are a lot of different
Speaker 1: potential applications for synthetic biology in the medical field. Not
Speaker 1: a big surprise. I mean, it makes sense that that
Speaker 1: would be a place where we would really focus that.
Speaker 1: But there's the possibility that synthetic biology will play a
Speaker 1: role in lots of other different things, like, for example,
Speaker 1: biologically based computational systems. I mean, there's there's the possibility
Speaker 1: for that too. I mean, we could we could engineer
Speaker 1: biologically engineer an organic computer, and that is so science
Speaker 1: fiction that it makes my head spin a little bit. Yeah,
Speaker 1: and there's research teams out there that are working on
Speaker 1: coding data in d n A s Yeah exactly. Yeah.
Speaker 1: Uh and and and along those lines, you've also, of
Speaker 1: course got the thing that we always like talking about
Speaker 1: on this show, which is the pure research angle. You sure,
Speaker 1: these lines of inquiry will help us figure out what
Speaker 1: genes do and how they interact with each other, and
Speaker 1: that is so worthwhile, right, And I think I think
Speaker 1: to the general public, it's news that we don't understand
Speaker 1: all of this yet, because exactly right, once we got
Speaker 1: to the point of the sequencing of the human genome.
Speaker 1: Everyone said, oh, so we we now know what everything
Speaker 1: does and you have to explain. No, what we found
Speaker 1: was the complete text of what we are, but we
Speaker 1: don't understand the language it's written in yet, not fully.
Speaker 1: And we don't know how this passage fourteen chapters down
Speaker 1: actually depends heavily on something that's written in chapter two
Speaker 1: and something else has written in chapter thirty seven. Like
Speaker 1: that makes it super hard for you to be able
Speaker 1: to interpret that. Yeah, so figuring that out it would
Speaker 1: would be nifty Yes, I agree, I agree. Okay, so,
Speaker 1: so we've covered the wonder and and the potentials of
Speaker 1: the future. Guys, let's get into some dubin gloom. Okay,
Speaker 1: what could go wrong? Well, you know, this is what
Speaker 1: Dr Indy was concerned about, right, the idea of let's
Speaker 1: think about the consequences of research to make sure that
Speaker 1: we're doing doing any sort of research in the most
Speaker 1: responsible way possible. So, one possibility, although it's definitely in
Speaker 1: the realm of like more of the Stephen King horror
Speaker 1: story approach, is that someone develops a synthetic life form
Speaker 1: that ends up not being contained within the lab and
Speaker 1: that ends up encountering the rold at large and perhaps
Speaker 1: starts to replicate itself. This could be on the you know,
Speaker 1: single cell level. It doesn't necessarily have to be Frankenstein's
Speaker 1: Monster like I keep joking about, or a zombie apocalypse.
Speaker 1: I'm but but it could certainly disrupt an ecosystem, right, right, Yeah,
Speaker 1: So if for example, it doesn't even have to be
Speaker 1: like a pathogen that attacks humans, right, It could merely
Speaker 1: be invasive. It could just be a very very successful
Speaker 1: organism that outcompetes everything that naturally lives around it. Right,
Speaker 1: And then we end up seeing uh, decrease in biodiversity,
Speaker 1: We see various species uh end up fighting so that
Speaker 1: they don't go extinct. Uh, it ends up creating big issues.
Speaker 1: So there's that one um and you know, if it
Speaker 1: were to turn into a pathogen, that would obviously be
Speaker 1: even worse. But it doesn't have to for it to
Speaker 1: have negative consequences in our world. There's also the question
Speaker 1: going beyond like that that approach, who owns the life form?
Speaker 1: This is a whole new area of science. And does
Speaker 1: it mean that you would be able to protect a
Speaker 1: an engineered life form like using intellectual property approach like
Speaker 1: you would software would you copyright a life form. You're
Speaker 1: not supposed to be able to do that right now,
Speaker 1: but maybe the rules need to change if we're talking
Speaker 1: about a purely synthetic creature designed from the ground up.
Speaker 1: So somebody if they find this organism dwelling on your
Speaker 1: skin or in your hair or something like that, they
Speaker 1: can file a d m c A claim against you,
Speaker 1: right or or you could end up suing the company
Speaker 1: that made the thing and say you have not been
Speaker 1: very careful with your containment procedures, because I've got it
Speaker 1: on me now. So, I mean, it's a weird thing
Speaker 1: that fortunately you put all these uh these copyright clauses
Speaker 1: into its d n A, so I know where it
Speaker 1: came from, right, Look, you signed the service agreement as
Speaker 1: soon as that bacteria made contact with your skin. Uh yeah,
Speaker 1: this is I mean, it's we're joking about it, but
Speaker 1: it really is the question of who owns that, Like,
Speaker 1: does the person who made the technology own it? Does
Speaker 1: the person who actually sequenced there are created synthesized rather
Speaker 1: the genes in that sequence? Did they own it? Is
Speaker 1: ownership not even a thing. We don't have the answers
Speaker 1: to that. And then of course they're just the big
Speaker 1: ethical concerns. Is it all right? Is it? Is it?
Speaker 1: Is it ethical to design a life form, just any
Speaker 1: life form, let alone a human? And if it is,
Speaker 1: then is there a is there a line like? Is
Speaker 1: there a point where we say before this it's it's
Speaker 1: totally cool. But after this we have to start asking
Speaker 1: ourselves some questions. Yeah, how many cells does an organism
Speaker 1: have to have before we start to be worried about it? Right? Ken?
Speaker 1: Is it? Is it all right to engineer bacteria so
Speaker 1: that we can do lots of medical research and potentially
Speaker 1: cure diseases? I think most people would say, yeah, that
Speaker 1: sounds like that would be all right or all right?
Speaker 1: Is it okay to genetically design assuming we ever got
Speaker 1: this capability, which is a big assumption, But it was
Speaker 1: okay to genetically design an animal so that it most
Speaker 1: most closely resembles a pet that you used to have?
Speaker 1: Is that okay? Is it okay to design a human
Speaker 1: being so that the human being has as many positive
Speaker 1: attributes and as few negative attributes according to some given persons? Yeah,
Speaker 1: according to to the designer, is gatica, okay? Is what
Speaker 1: I'm getting at is gantica? Okay? Not Galagha, which is awesome,
Speaker 1: but Gantica. Uh. I mean, these are these are big questions.
Speaker 1: And again that's the source of stuff that dr Indy
Speaker 1: was asking. He was saying, you know, we need to
Speaker 1: consider this. Maybe we need to ask the should we
Speaker 1: question before we ask the could we question. That's you know,
Speaker 1: Patton Oswald's like always asking the kudah, never asking the shouda.
Speaker 1: He's saying, we should ask the shuldah. Let's do that, guys,
Speaker 1: And um, I can't disagree with that. I think that's
Speaker 1: I think that's the responsible thing to do. But then
Speaker 1: I'm I'm a liberal arts major, not a not a
Speaker 1: super scientist like the folks over at at that Harvard
Speaker 1: meeting where so really interesting. Do you guys have any
Speaker 1: other thoughts about synthetic biology before we sign off? It's
Speaker 1: okay to say no, I think you've spoken all my
Speaker 1: thoughts for me. That's fair. It's also really hot in
Speaker 1: here at this at this juncture. I have thoughts about snacks. Yeah,
Speaker 1: I have thoughts about air conditioning. Let's wrap this up. So, guys,
Speaker 1: if you have suggestions for future episodes of forward thinking,
Speaker 1: you want to know how something's gonna you know what
Speaker 1: it's gonna be like in the future, or you've got
Speaker 1: comments or thoughts about any of the episodes we've done
Speaker 1: in the past. Maybe you want us to do an
Speaker 1: update to an old episode where we've got more information
Speaker 1: now that we're further into the future than we were
Speaker 1: when we started. Let us know. Send us a message
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