ResearchPod
ResearchPod
Future horizons and trans-disciplinary thinking in synthetic biology
Synthetic biology, as showcased by Stephen Freeland's work at UMBC, redefines biological systems for groundbreaking applications in biotechnology and medicine, promising to solve global challenges and unlock new frontiers in science.
Or, at least, that’s what ChatGPT has to say about it.
Our interview also covers how Artificial Intelligence is changing the wet-lab experience of doing research. Plus, the importance of the public domain in owning, understanding, and advancing all the many ways the future is taking shape.
Read his original research : https://doi.org/10.3390/life13122281
00:00:04 Will Mountford
Hello. I'm Will. Welcome to research pod.
00:00:07 Will Mountford
Synthetic biology, as showcased by Stephen Freeland's work at UMBC, is revolutionizing future research to redefines biological systems for groundbreaking applications in biotechnology and medicine, promising to solve global challenges and unlock new frontiers in science.
00:00:23 Will Mountford
Or at least that's what ChatGPT has to say about it. We do indeed cover many of these aspects of his work in our discussion today, but also how generative tools like digital AI are changing the wet lab experience of doing research, plus the importance of public domain in owning understanding and advancing.
00:00:41 Will Mountford
All the many ways, the future is taking shape.
00:00:46 Will Mountford
Professor Stephen Friedland. Hello. Thanks so much for your time today. Could you tell me and everyone listening to this a bit about yourself, your background?
00:00:54 Prof Stephen Freeland
Sure. I mean the other one gets the more one has too much to pick from. So guide me here, but I'm a biologist. I think that's probably the most important thing to say. I'm a biologist in my heart and in my soul. And I'm not saying I chose it. I'm saying that somewhere during school it just seemed to be both something I was better at than average, but something I just.
00:01:15 Prof Stephen Freeland
And I won't kid you. There are years that go by. If you choose the academic route where you hate what you're doing. But I've never.
00:01:20 Prof Stephen Freeland
Stopped loving biology.
00:01:21 Prof Stephen Freeland
Right. So that might be the most important thing to tell you. What else would you like to know?
00:01:25 Will Mountford
Out of anything why biology and not plumbing or?
00:01:29 Prof Stephen Freeland
Why biology, you know, isn't it fun? You do something like this? Some people ask you the questions you never get asked. That make you think. Let me try as you're talking. Even my reflection is probably that firstly, it was pragmatic.
00:01:40 Prof Stephen Freeland
I was doing well in it at school and I wasn't doing well at other things. I suck at languages, thank goodness I was born English. Given that that's the the world, the the scientific world's language, because I probably could do this otherwise. I know be a lot harder. Anyway, I was good at it, so there's positive reinforcement. That's the practical answer. But to give you a a a soulful answer, yeah, I guess that if I think about it, I was raised in the country so.
00:02:03 Prof Stephen Freeland
And raised to believe very much in the OR to see the beauty of nature right. Sounds hokey, but it's never let me down. And by the way, nature is ugly and cruel and hard. But there is a savage beauty there, and there's just something that draws me. And then perhaps at this stage, final trip, third of the answer, it's true.
00:02:21 Prof Stephen Freeland
So much that's unknown. I mean, a lot of that has changed in my lifetime. But I would say go into a science where there's so much that it's unknown because you stand a real chance.
00:02:29 Prof Stephen Freeland
Of finding out new.
00:02:30 Prof Stephen Freeland
Stuff, right? And that's a big draw with biology.
00:02:33 Prof Stephen Freeland
I want to give them a shout out here, the University of York in the UK, very analogous to the university on our work out. But it was sandwiched to me between Oxford and Cambridge, and both were wonderful. Both have extremely fine minds, but University of York changed everything by taking on way ahead of its time. A small crew of biologists each year until Masters programme to teach them fundamental.
00:02:53 Prof Stephen Freeland
Mathematics and computer science. Now I'm a bioinformatician, have been ever since.
00:02:58 Prof Stephen Freeland
Fancy way of saying I use computers to ask biological questions. They were so ahead of their time and it still inspires me that a smaller, humbly university can wisely find something that is forward facing and beat Cambridge and Oxford and everyone frankly. So there you go. That was a big milestone. Learning that you can use computers and mathematics.
00:03:18 Prof Stephen Freeland
The study, at least part of the beauty and biology enrollment in biology degrees, is declining. Computer science exploding, and we could speculate all you want, but the answers are probably pretty obvious. I think that matters. I think I want more biologists, right? There's so much there and so much we don't know. And so much potential.
00:03:37 Prof Stephen Freeland
And often we think about that biomedically and heavens sake, I'm glad that we have biomedical, but there's so much more origins, understandings, products, manufacturing. I want more biologists.
00:03:49 Will Mountford
And on a personal note, are you prone to kind of poetry philosophy looking out the window and getting all wistful about it? Or a more kind of a boots on the ground? Get in the lab and.
00:03:59 Will Mountford
Get things done. Kind of guy.
00:04:01 Prof Stephen Freeland
I'm probably more like the the the philosophical poet than I'd like to think, but yeah, yeah.
00:04:08 Prof Stephen Freeland
I guess that is a driver, isn't it? All the way through? I mean, that's what it does for you. If in childhood you love nature and you choose to develop that academically, that's gonna be with your lifetime, isn't it?
00:04:22 Will Mountford
What we talked about in some of our setup course of this is framing things as lies to children, and that's possibly unkind because it's never really a lie to tell people what it is they are capable of processing and dealing with with the rest of the context that it sits in. So to start off from a point of.
00:04:39 Will Mountford
DNA.
00:04:40 Will Mountford
Can you tell me and people listening, what is DNA and how is that relevant to, I don't know, let's say a 10 year old, a 15 year old, a 20 year old. And what are the layers of understanding that we add on with every stage key stage of learning or like whatever the American grading system comparator is?
00:05:00 Prof Stephen Freeland
Good, that actually helps me. That last little twist helps me with a very big.
00:05:04 Prof Stephen Freeland
Imagine where would you begin? Let's begin with something that maybe everybody already knows, just to agree where we're starting from DNA is genes. It's genetic material and genes program life. They are the instructions that you decode to make life. And it's interesting already out of you. There. That's the beauty of it. There's no you there. That's if they decode themselves.
00:05:23 Prof Stephen Freeland
To make life right.
00:05:24 Prof Stephen Freeland
OK.
00:05:25 Prof Stephen Freeland
Yeah. So that's the that's the 10 year old thing and it's important to know because you will at every grade. I think these days you would be taught something of that to understand the power, good and bad that that exercise is over your life. You know, you are genetically predisposed to certain medical conditions. You also have genetic predisposition.
00:05:46 Prof Stephen Freeland
To certain things, you're good at, much harder to measure, by the way.
00:05:50 Prof Stephen Freeland
It's not everything, and that's where a lot of the debate lies. Nature, nurture. But that's what we need to remember.
00:05:54 Prof Stephen Freeland
Is genes program life?
00:05:56 Prof Stephen Freeland
We don't know how or what it even means to be alive without genetic programming. That's part of our fundamental understanding of life. Right. So you ready to go up a level from there? Do you want to ask anything about that?
00:06:07 Prof Stephen Freeland
OK, I think the next thing I would want to teach you is that they DNA is a polymer which is just a fancy way of saying it's a lot of building blocks linked together.
00:06:18 Prof Stephen Freeland
And right here, let's introduce an analogy that I think will take us surprisingly far on our conversation. It's like it's like words are built of letters. DNA is built of things called nucleotides. They're the building blocks. They're only four of them. They are the famous AC GT, and it's all a question of what you spell out with them. They think there's only four, but then you think there's only 26 English letters and that's.
00:06:39 Prof Stephen Freeland
Suffice to bring us all of modern life.
00:06:40
Yeah.
00:06:41 Prof Stephen Freeland
Fiction and nonfiction, right. And. And it's like, oh, there's power in those four. Yeah. So that's the next thing of what's a polymer built of those four and the polymer means that you link them together. So it becomes one big molecule, chemically speaking, but it's the sequence that we've just said, like, it's the sequence of letters that.
00:06:57 Prof Stephen Freeland
Make a word.
00:06:58 Prof Stephen Freeland
So DNA is a sequence, and we've heard that DNA sequencing, right?
00:07:02 Prof Stephen Freeland
So that's probably layer two I want to think hard, but my temptation is to leapfrog you now very close to what I do with layer three. I think you do a biology degree. You're gonna find out 15 layers. I've just skipped over. But the next thing I want to tell you is that most biologists and I would have the guest chapter GTP would.
00:07:18 Prof Stephen Freeland
Tell you wrongly that there are only four letters.
00:07:20 Will Mountford
So we've set the bounds 4 letters. That sounds pretty comprehensive. That sounds like a good structure to work within. So why is it not true?
00:07:30 Prof Stephen Freeland
Because it all depends how you meant the question and if you want a philosophical theme to resonate throughout the rest of our conversation, that would be it. It all depends on what you meant by the question boy. If you ever go into computer science, remember that for me is everything in computer science, we call it guy, go garbage in, garbage out.
00:07:46 Prof Stephen Freeland
Less formally, Hitchhiker's Guide to the Galaxy, they built a supercomputer called Planet Earth to figure out the meaning of life, the universe and everything. And after 4 billion years, it concluded the answer was 42 that asked the wrong question. So let's go there. If you mean it as a geneticist, it's trueish in the sense that life builds with those four all of life.
00:08:06 Prof Stephen Freeland
Right that we know of. And to be fair, there was a very big splash. You know, flash in the pan. I want to say three years ago for finding that it was viruses, wasn't it that have a 5th letter. But to be fair, they sort of changed one of the four.
00:08:21 Prof Stephen Freeland
But I wrote a little opinion piece on the back end of that to say, you know what that is the final nail in the coffin of this whole idea of.
00:08:27 Prof Stephen Freeland
Not only four.
00:08:27 Prof Stephen Freeland
But of.
00:08:28 Prof Stephen Freeland
Other building blocks we'll talk about, that's just the empirical proof, because biologically there are four. But we know that there are hundreds, if not thousands of derivatives. We tend to call them like, you know, they're not those chemicals that are used.
00:08:40 Prof Stephen Freeland
Cells, they're just not used to spell out genetic messages the way we preach it, and I'm thinking everything I say I'm like.
00:08:47 Prof Stephen Freeland
No, that's wrong.
00:08:47 Prof Stephen Freeland
Right. You actually some forms of derivative are used to control which genes are expressed, which ones are decoded. So you know in a sense we are using those in genes. But traditionally we say no. There are 4 letters that are decoded.
00:09:01 Prof Stephen Freeland
To build proteins which then make metabolism OK, but there are hundreds in a cell, there are. Where should we go next? Chemically they are infinite. It's a class of chemical.
00:09:12 Prof Stephen Freeland
You have to adhere to certain rules, but at least functionally, unless you introduce some sort of maximum size, you could have infinite nucleotides, so certainly before we have sit in a theoretical space that is much larger and biology demonstrates that space space is useful and used, and then perhaps the the final strand, because so much of this will echo.
00:09:32 Prof Stephen Freeland
You know, assets when we get there is that we've actually known for quite a while now that there are more than four that are formed abiotically by the universe for free outside of our.
00:09:42 Prof Stephen Freeland
Traditionally, the way we've understood what is what is formed chemically is to look for a meteorite which is just a word for space debris that lands on earth, but you can take it into a lab and you can analyze it. And UM, that plays a very big role for both amino acids and nucleotides. But for nucleotides, we've known that there are more than 4. You know, there are 10s. So I would suggest that all indications.
00:10:02 Prof Stephen Freeland
Are that the four are an evolutionary outcome, not a.
00:10:06 Prof Stephen Freeland
Requirement for life and not even a truth about what life is currently.
00:10:10 Will Mountford
When we say that meteorites contain amino acids as we understand it, the building blocks of life, there will be some people out there who will leap to the conclusion that, well, that means alien life, because if they have the right building blocks, then life is surely inevitable.
00:10:26 Will Mountford
And mark?
00:10:27 Prof Stephen Freeland
There's several things going on. What you just said, for what it's worth, lets me just confess, I do believe that there should, in our current state of scientific understanding, be life everywhere. I'm not sure about multicellular intelligent life at all, but there should so that bit. But yeah, the the fundamental point here is we find the building blocks in meteorites. Well, isn't that a residue of alien life? No, I think there is good reason until further.
00:10:48 Prof Stephen Freeland
Shocking evidence emerges if it ever does that to. To think these are formed abiotically I could give you some technical details and maybe that's going a bit far fast, but I just say that there are various features.
00:11:00 Prof Stephen Freeland
Of amino acids produced outside of biology that you don't get by amino acids and nerve. That sounds too opaque that there are mirror images of amino acids in particular that can be made. It's you're equally likely to make the left-handed form as the right-handed form, but life only uses the left-handed form. Whole other rabbit hole. We could go down point is that in meteorites you find both in an equal mixture.
00:11:23 Prof Stephen Freeland
That's one example of the sort of technicality, but these days I could chase it through and say we even understand the reaction pathways. We understand how the chemistry is.
00:11:31 Prof Stephen Freeland
Thing. So it's sort of like we've got the whole story on how these things are being produced by the universe without life, right? Maybe that's what I should have said.
00:11:40 Will Mountford
I may put this question to you then, if we know that they can be formed abiotically have we successfully made them on Earth? And if we are capable of synthesizing DNA on Earth, what does that tell us about the origins? Possibly.
00:11:56 Will Mountford
Of these molecules elsewhere.
00:11:58 Prof Stephen Freeland
Good. And I'm going to have to untangle a bit here, because, like a bad sort of St. performer, I accidentally allowed you to let us slip into talking about two different.
00:12:07 Prof Stephen Freeland
Things.
00:12:08 Prof Stephen Freeland
We were talking about nucleotides and DNA and amino acids are what are the other half of it. So I want to go there first because you the point is that with the exact question you've asked you get.
00:12:17 Prof Stephen Freeland
Very different answers for those two.
00:12:19 Will Mountford
Let's try and work on the building blocks at their smallest resolution. So a nucleotide that is an AACAT or AG or otherwise.
00:12:31 Will Mountford
And it can be created using non organ. It can be assembled using non organic means assembled created.
00:12:40 Prof Stephen Freeland
Because a nucleotide is a chemical structure that contains a sugar molecule called ribose, linked to a nuclear base, which is actually the genetic letter, and to a phosphate laser chemistry. But those things are deeply challenging to make. We absolutely can and have for a long time have known how to make nuclear bases. And those are the things we find on meta.
00:13:00
Right.
00:13:01 Prof Stephen Freeland
It is highly controversial a couple of groups in England believe that they have basically shown an ingenious mechanism to make a nucleotide, but without wanting to start a whole fight here, it's not consensus science. If I paraphrase crudely, a lot of colleagues say it says more about their ingenuity and brilliance as chemists than it does about the abiotic.
00:13:24 Prof Stephen Freeland
And we go to that if you want, but that's so right there, it's nucleotides, no nuclear bases yet and amino acids, yes. And we haven't talked about amino acids yet, but I do think it's significant that at that level you get those two for free almost everywhere and its nuclear bases where there are 10s of them in the meteorite, it's not just the four, it's very challenging to get them stuck onto a ribose and phosphate which makes a nucleotide.
00:13:46 Prof Stephen Freeland
Which is the building block of DNA, and it is exceedingly challenging to get those building blocks to link together, let alone to do so in a useful sequence.
00:13:57 Prof Stephen Freeland
And somewhere in that I've actually transversed from huge challenges of chemistry to huge challenges of mathematics, and we can talk about.
00:14:04 Prof Stephen Freeland
That if you want.
00:14:06 Will Mountford
We're straying further and further from, you know, Capital B biology then.
00:14:10 Prof Stephen Freeland
Yeah, yeah, you. But what does it tell you about life? I mean, just to sort of conclude the original question and then we can dive into this bit more. That's one of the big three lines of evidence that I think suggests to me that I'd be surprised if life wasn't common in the universe. The exact stuff at the core of what makes life on Earth is we now would say, is given to us by free a lot of places.
00:14:31 Prof Stephen Freeland
In our own solar system, let alone.
00:14:32 Prof Stephen Freeland
The rest of the Galaxy.
00:14:38 Will Mountford
Well, if we have nuclear bases to make nucleotides, what can you do? If you can make the building blocks of life?
00:14:47 Prof Stephen Freeland
So that is a different intellectually overlapping field. It's a much bigger field and the first thing to sort of hint that your question is an important one is it's a much bigger field because there's a lot more money flowing through it, primarily biomedical.
00:15:03 Prof Stephen Freeland
But into sort of biochemical engineering, you know, the the borders get boundary because there are so many useful things you can do. If you start playing with nucleotides beyond the four. Now there are whole classes that only begin to sort of like, well, a lot of them do this and a lot of them do that. But one thing is you can jam up life in very, very specific.
00:15:22 Prof Stephen Freeland
Ways. So these things are very powerful for fighting viruses and cancer, right? And so synthetic biology that's. But. But honestly, they're good to jam up anything you want to study, you can almost sort of jam the machine and freeze it and then study it, which is often the enemy is like, it's happening too fast or whatever. That's one of their common uses.
00:15:42 Prof Stephen Freeland
For other we would, what would I say? Non canonical nucleotides would be one phrase that you could use for them. Another big class of using them is you can attach weird chemical groups to them that make it easy to find them later.
00:15:58 Prof Stephen Freeland
Run so you can sort of like paint the target on them so that you can then figure out where they went to to study processes that you're interested in, right? So those are just two examples of fast subfields that are very commercially and engineering oriented, right, that use these other bases.
00:16:18 Prof Stephen Freeland
And I think one of the things we are rapidly learning to do in our smaller community that is interested in origins and astrobiology is to try to get much more serious about keeping pace.
00:16:28 Prof Stephen Freeland
With that, it's moving so fast it's almost impossible to keep tabs on it, and it's not our field. But is that enough of an answer to get you going right?
00:16:36 Will Mountford
I mean to think about things in kind of to pass it in terms that I can hopefully keep up with. It's like an adhesive that you can stick things to it, but also it can fix things in place. If I think of videos. So I see people doing carpentry and they flood the wood with resin, a synthetic, you know, boat lacquer basically to fix the wood in place and then they can.
00:16:48 Prof Stephen Freeland
Yeah, yeah.
00:16:56 Will Mountford
Tape it to their whim or put called collars on.
00:16:58 Will Mountford
Twit.
00:16:59 Prof Stephen Freeland
I think as a keyword worker myself, if that's what you take away from it, that's good enough. But let's go back to layers and layers. I would say that the only thing the first thing I would change about that metaphor, if you wanted a better understanding is it's not like you saturate natural DNA with these things. It's more like you place them carefully inside the DNA sequence because you can find them.
00:17:18 Prof Stephen Freeland
Well, because you know how that DNA sequence folds up and catalyzes a reaction, and you can place them at a specific position where the one reaction they jam the one reaction they do, gets jammed midway. And now I can study how that reaction takes place. Does that make sense?
00:17:34 Will Mountford
To go.
00:17:34 Will Mountford
In there with a very specific wrench for the big deal, rather than just.
00:17:37 Prof Stephen Freeland
Yes, that was the metaphor I was searching around for and think about that it really is like a toolkit for studying biology at the molecular level.
00:17:46 Will Mountford
What boundaries would you say have been set on the research that you are doing and how do you see ways in which future research, 5-10 years down the line, if there's anything that's, you know, a twinkling in some distant researchers, I might explode in?
00:18:01 Will Mountford
New directions like we can be as rosy. Glasses or cyberpunk glasses as appropriate about this.
00:18:08 Prof Stephen Freeland
Gotcha. So I'm gonna be slightly cautious in what I say because for the first time in my scientific career, the truth about what is actually happening right now in Europe as a result of the work we're doing is scoopable and very poachable. And so I'll just be a little guarded, but we'll be fine with that.
00:18:22 Prof Stephen Freeland
In fact, at this point I think I must respectfully drag us back to this thing. I keep hopping on about amino acids and DNA very different. So at a very simple level that we might teach high schoolers these days, you can think of the molecular basis of biology being two halves, two different chemicals wrapped up in 1/3.
00:18:44 Prof Stephen Freeland
And the three concerned are DNA proteins and membranes. Membranes are made of lipids and they probably won't feature again in this story, but it's those other two DNA and proteins. When I talk about genes decoding themselves, they decode themselves into one very specific other chemical language. That is the chemical language of amino acid.
00:19:04 Prof Stephen Freeland
Which themselves link together to form a polymer, but that polymer is known as a protein. All of metabolism, which just means the network of chemical reactions that R cell is, to a first approximation of proteins. Proteins are the catalysts. There are also many of the structures that make up a cell. So when we talk about genetic programming, we mean programming to make proteins.
00:19:25 Prof Stephen Freeland
Because proteins make the cell, but then the cell for at least from an evolutionary perspective, its primary purpose is to replicate the DNA and round and round we.
00:19:32 Prof Stephen Freeland
Go.
00:19:32 Prof Stephen Freeland
That's life.
00:19:34 Will Mountford
Cell viruses and bacteria workers keeping that cell going as.
00:19:38 Prof Stephen Freeland
Absolutely. And of course, that's what makes viruses so sort of interesting and debates about whether they are life is they only contain the genetics they need to hijack a cell in order to make proteins to complete their life cycle. So yeah, two halves very, very important conceptually, but also very important to understand chemically unrelated languages. If anybody is familiar with fundamental computing, there's a really good analogy.
00:19:59 Prof Stephen Freeland
There are words and letters here. If you're typing English in computing in its simplest character based form notepad in Microsoft, there are characters that are available to you.
00:20:11 Prof Stephen Freeland
And there is a binary encoding of those characters, right? So you're typing G, but the computer only speaks in ones and zeros. We all know, so it has a strings of ones and zeros that, if it sees that it produces a G on the screen.
00:20:23 Prof Stephen Freeland
Or you type AG. It stores it as that binary encoding that is incredibly close to what life is doing with.
00:20:28 Prof Stephen Freeland
Genes.
00:20:28 Prof Stephen Freeland
And proteins, the biggest difference is that life has four letters instead of two binary, and that there are 20 amino acids rather than 26 English letters. And if even that was too much computing Morse code, same thing, 2 languages, but they're very different. A dot is not a letter.
00:20:44 Prof Stephen Freeland
And it kind of matters that they're not right and I wanna. That's why I keep saying, well, DNA, amino acids, different story amino acids are a different chemical language. They're the ones that I study. And that's where I can talk about both now and the future with far more authority, because it's what I what my career has studied. I made a very deliberate decision not to study DNA except as a fascinated observer.
00:21:04 Prof Stephen Freeland
Because there was amazing work going on by people far better than me already. And so I chose amino acids because they felt under studied in comparison. So I've told you that in DNA we have hundreds and thousands of.
00:21:16 Prof Stephen Freeland
Are alternatives and two alphabets in amino acids synthetic biology has hundreds if not thousands of alternatives and doing much the same classes of phenomenon we talked about for DNA. Same sort of reasons, same sort of motivation. There are no alphabets and I guess that's where I can finally conclude what we're doing is working our way towards producing the 1st.
00:21:36 Prof Stephen Freeland
Alternative amino acid alphabet as a direct sort of comparison, almost an homage to what they've already achieved with genetic material, but for some reason nobody's gone there. So that's where we're going with collaborators in Japan and Europe and you know.
00:21:50 Prof Stephen Freeland
But we are doing that because nobody else is doing it.
00:21:53 Prof Stephen Freeland
That we're aware of.
00:21:54 Will Mountford
As far as I understand it, the measures for success are to be the best or to be the first.
00:21:58 Prof Stephen Freeland
You know, and let's say that for for it doesn't matter if you wanna be a businessman, but also if you wanna be an academic, find an area where nobody's doing it. Because what you said be the first.
00:22:08 Prof Stephen Freeland
You're the best.
00:22:09 Will Mountford
That or possibly is in the case for.
00:22:12 Will Mountford
Amino acids for life be the one that survives.
00:22:16 Prof Stephen Freeland
Yeah. I mean, I think that we won't. You want some pure conjecture, I'd say informed conjecture. I think we won't find it hard to make an alternative amino acid alphabet, but I think we have a ways to go studying why those ones are inferior to the one that life is used with just where I expect we're going with origin story, which brings us back to economics.
00:22:34 Prof Stephen Freeland
All of that is conjectural at the moment, it's informed, but personally, that's what interests me. I would love it if 10 years from now we might have enough information to conclude whether or not lifers amino acid alphabet was a sort of almost inevitable outcome of natural selection, because again, that says very interesting and important things about our expectations for life elsewhere in.
00:22:53 Prof Stephen Freeland
The universe.
00:22:54 Will Mountford
Amino acids, DNA, RNA, nucleotides. These are all things that to my A level understanding of biology, one leads to the other. They are in sequence. They are.
00:23:04 Will Mountford
Family it sounds like to your eyes, they are in competition. Almost.
00:23:10 Prof Stephen Freeland
Yes, but I think in a happy competition mostly.
00:23:13 Prof Stephen Freeland
RNA is the sister language to DNA and the popular paradigm may be changing right now about where life started as it started with RNA, because RNA can do the work of both DNA and proteins, it works like DNA, but it really folds up and catalyses reactions as if it thought it were a protein. So that's the RNA world hypothesis. Biggest single problem with the RNA.
00:23:33 Prof Stephen Freeland
Of hypothesis is showing how you would make RNA in the absence of life and This is why I was so strong and that point you don't find even the building blocks in meteorites you find the subunits of the build.
00:23:44 Prof Stephen Freeland
Box and the interesting thing here is that you do find amino acids, no qualifications, no ifs, no buts, no small print. You find amino acids. In fact, you find half of the 20 that are used in you today to make you and you find a ton of others that there's half of. What makes you that you don't find? And that's part of an interesting story. And there's a ton of other ones that.
00:24:05 Prof Stephen Freeland
One in you one have never been in life as far as we know it and that's.
00:24:08 Prof Stephen Freeland
An interesting part of the story.
00:24:09 Prof Stephen Freeland
It is true that if you're a biochemist, one of the decisions traditionally you've had to make is are you an RNA person or a proteins person? And I think 50 years on, that is part of where they're not talking to each other as much as.
00:24:20 Prof Stephen Freeland
Would be helpful, right?
00:24:22 Prof Stephen Freeland
But a lot of the competition is like, I think the way I'm trying to tell it and it got the excitement out of me. They inspire me and I wonder if we can't cross, inspire them and actually see it as not competition, but complementarity, because that's the way life sees it. Proteins are complementary necessary other art to DNA, and DNA is the necessary complementary other half to proteins is the only way we know how to build life.
00:24:43 Will Mountford
Well, apart from that, it sounds like you found a third half to put in there.
00:24:47 Prof Stephen Freeland
Yeah, we're just growing both halves and saying it doesn't have to be this way. And we're increasingly chemically competent to state that as fact, so.
00:24:56 Prof Stephen Freeland
All those big questions, then necessarily tumble to might well, why this one then? Accident inevitability. What would be the consequences of doing it? Other ways? At least one of the consequences is making a lot of money and owning it. But.
00:25:07 Prof Stephen Freeland
There are others, yeah.
00:25:09 Will Mountford
Scene of Fritz Lang's metropolis.
00:25:11 Prof Stephen Freeland
No, but I'm so aware of it as the seminal sci-fi work, right?
00:25:16 Will Mountford
There is the separation of the intellectual higher echelons, the head and then the labouring hands, and that the.
00:25:26 Will Mountford
The Synthroid the gynoid in the middle becomes a heart uniting them. And what do you say about growing both halves? It sounds like there is something to be said for the complementarity, but also an elevation. A unification, lots of words of a very similar.
00:25:40 Prof Stephen Freeland
I couldn't agree more and I love the way you've put that.
00:25:48 Will Mountford
To look at the structure of the classical structure of DNA being a double Helix, how much does that topology? That engineering that shape hold true for synthetic DNA?
00:26:01 Prof Stephen Freeland
I think I would answer in the following order of priority. The number one where this is a field in its infancy.
00:26:08 Prof Stephen Freeland
So we don't know and that's Harkins back to this idea of there's so much we don't know in biology. The next thing I tell you is I've really understated a bit because at the DNA side of things, they've gone further. Two fully synthetic alphabets have been produced, which sort of replace DNA altogether, right.
00:26:29 Prof Stephen Freeland
Alphabets yes. Instead of the four that all of life is used for most of its history on Earth, it's a different alphabet. One is known as the Hachi Mochi alphabet, and that's Steve Bennett's group. And you can look it up on Wikipedia and and the other one doesn't really have a catchy name, but it's the. I think it's the Feldman alphabet again, you can.
00:26:49 Prof Stephen Freeland
Look it up. I wish it had a name. I think he he. Yeah anyway.
00:26:53 Prof Stephen Freeland
That one is actually more interesting to me, because if you really want to get into the biochemistry, it's closer to breaking fundamental rules that we've all grown up on. But there are two alphabets at work for DNA in addition to all of this careful placing of hundreds and thousands of individual modified nucleotides at specific places to do a specific job.
00:27:13 Prof Stephen Freeland
Right. So that's the state of the.
00:27:15 Prof Stephen Freeland
Field there.
00:27:16 Will Mountford
Now when we say alphabets, is that just a pure like case substitution, a cipher if you will for DNA. So A is replaced with one or green like a one in one out substitution or?
00:27:22
Gotcha.
00:27:28 Will Mountford
Or like how many rulers can you break?
00:27:31 Prof Stephen Freeland
That's the open question, and I mean this is does injustice to Benny's group because it was an amazing thing he achieved. But I would say his one is more like the one for one.
00:27:39 Prof Stephen Freeland
Substitution the Haji moji.
00:27:40 Prof Stephen Freeland
Is you look at the chemical structures and if you're trained as a biologist with a bit of biochemistry at first you think you're looking at life and then you look, wait. The groups in the wrong place, right. So it's more like a one to one sub.
00:27:51 Prof Stephen Freeland
Institution subgroups within the chemical structure. The Feldman one interests me precisely because it's much nearer to rule breaking. You can totally tune out the next 15 seconds if this doesn't make sense, but for anyone who's listening, who does think chemically, the standard DNA and the Hashimoto alphabet use hydrogen bonding to make Watson Crick.
00:28:11 Prof Stephen Freeland
These pairs. That's one type of chemical bond.
00:28:14 Prof Stephen Freeland
Almost to sort of show off, but in the best possible wow way the Feldman 1 uses something called Van der Waals forces, which is what holds graphite sheets together.
00:28:23 Will Mountford
What holds echoes on the walls?
00:28:24 Prof Stephen Freeland
Right, right. It's the the fundamental rule of biochemistry that has been broken and I didn't see that coming. So that's why I'm slightly more impressed by that one. No disrespect to.
00:28:34 Prof Stephen Freeland
Lee Benner, right.
00:28:36 Will Mountford
What you've said there is essentially on a field like it uses magnetism or gravity to hold together. It's that same fundamental universal force.
00:28:43 Prof Stephen Freeland
Yeah, yes. And if we do deeper down, both of them deliberately adhered to the double Helix.
00:28:50 Prof Stephen Freeland
Partly because they're already going to quantum light year ahead of anything we knew was possible, but partly, I think, because I don't want to mislead you, that the current state of play to the best of my knowledge, meaning there might be things happening in companies I'm not aware of, is that these things are inserted as long stretches within an otherwise normal genome. So you can sort of switch over the genome to the alien language to do your thing.
00:29:10 Prof Stephen Freeland
So it's kind of important that they adhere to the basic geometry of DNA, but I think this is where I would see a logical progression like the dot dot dot ellipsis Benner to Feldman to Holy cow. We could make something that was not even a double Helix in my lifetime, right?
00:29:26 Will Mountford
That's that's a lot to throw out there in 15 seconds.
00:29:29 Prof Stephen Freeland
OK. Oh, you know, and I need to just say once more and we aren't talking about amino acids and there is key differences. So when we get to amino acids which.
00:29:38 Prof Stephen Freeland
Is what I.
00:29:38 Prof Stephen Freeland
Do and love, but the analogy is so powerful I'm more than happy to have this conversation with.
00:29:43 Prof Stephen Freeland
You about DNA? Yep.
00:29:46
Well.
00:29:47 Will Mountford
To stand with the Feldman alphabet and the Hashimoto alphabet and look back at traditional DNA, you know your homegrown.
00:29:54 Prof Stephen Freeland
It's so fun to use that word with.
00:29:55 Prof Stephen Freeland
The traditional DNA right? Please take it away.
00:29:57 Will Mountford
Your organic grass fed DNA is the state that we find so much of chemistry in life.
00:30:00
Right.
00:30:05 Will Mountford
Just a matter then, of availability of energy of economics.
00:30:12 Will Mountford
If we can establish that these rules can be broken, that the fundamental bonds that hold DNA together don't necessarily have to be hydrogen bonds, then what can we reflect on and say this must be why life on Earth is the way it is if.
00:30:28 Will Mountford
There.
00:30:28 Will Mountford
Is reason to be found.
00:30:29 Prof Stephen Freeland
Good. I mean, you've nailed it. That's why people like me are interested in all this, even when it's synthetic biology. Because we're interested in why is life? Why is life on Earth just full stop? Why is life on Earth? But why is it what it is? Why? And this is a powerful way to get at that, isn't it? Even as a graduate student in the mid 90s.
00:30:47 Prof Stephen Freeland
Many of my colleagues were respectfully tolerant of the work that my Pi was guiding me to do, but felt like these were unanswerable questions. There's one example of life. One way of doing it.
00:30:58 Prof Stephen Freeland
It seemed a little bit out there to talk about, you know, why and what were the alternatives. And now it is clearly a very good question that most of the early career scientists in one way or another are thinking about. I think your question is the.
00:31:10 Prof Stephen Freeland
Right. One, I absolutely believe you've nailed the cause. Personally economics, but be aware that that is not yet fully established. I'm just excited by the way that for me the clues are pointing at it. In fact, give me one moment of being. That philosophical poet I've come to change the way that I understand what we do in science, and I want to encourage others if this makes.
00:31:30 Prof Stephen Freeland
Them more interested to do it.
00:31:31 Prof Stephen Freeland
I think I was raised to believe it was about proving things like bricks on a wall. I think I see it much more now, like a form of statistics we call Bayesian statistics, which is more.
00:31:40 Prof Stephen Freeland
The odds that you use a betting course.
00:31:42 Prof Stephen Freeland
You use the information you have to guide you to what is most likely to be the current best understanding of the truth, and that's why things change and paradigm shift that that paradigm has shifted over this issue since I was a grad student, and I would say that right now there is reaching the tipping point of saying life on Earth. DNA is what it is because economics.
00:32:03 Prof Stephen Freeland
Now a lot of fine detail. Which economics what exactly you're talking about. In fact, I should stop and say that I think that case is much clearer for the amino acids. But then again, that's what I study and can talk.
00:32:11 Prof Stephen Freeland
About with authority economics. So we'll get there. Yeah. OK.
00:32:14 Will Mountford
Ohh, let's go there now and to say.
00:32:16 Will Mountford
Be that the case for amino acids applications, research and the kind of the synthetic possibilities therein, it's been a focus of of recent paper, a review that you put out. So if you could talk us through some of the the core concept behind that paper, how it relates to your research, the research that your group is?
00:32:36
Good.
00:32:36 Prof Stephen Freeland
Good. So actually we've done 2 reviews and it's been a January project, 2 years running except that last year's January project took 12 months to write up. So yeah, but the first one was exactly what you said. It was a review of synthetic biology.
00:32:49 Prof Stephen Freeland
In this field, for the amino acids and really making the case that we've made in this conversation that one community really wants to know more about why life is what it is, because that carries very interesting implications for looking for life beyond Earth as apart from anything else, another field is excitedly doing this for biomedical and commercial purpose.
00:33:08
That.
00:33:09 Prof Stephen Freeland
And that there's relatively low communication between the two groups at the moment. They think differently. They're asking different versions of the question, but it was a paper about trying to sort of cross educate. If that doesn't sound too condescending, 2 fields, oh, by the way, for any young listeners who might go into biology, please, please start to believe.
00:33:29 Prof Stephen Freeland
How little we understand about each other these days, right? I think this is assumption that I could never do that because they understand everything. Then we fake it, right? And my origins people don't really.
00:33:37 Will Mountford
I mean, biologically or just in terms of what?
00:33:40 Will Mountford
The department does to.
00:33:42 Prof Stephen Freeland
I think all academics team, I think.
00:33:44 Prof Stephen Freeland
I think we have specialized to an extent in an atmosphere where.
00:33:49 Prof Stephen Freeland
Yeah, we don't often find it easy and vulnerable to admit how much we're struggling to understand. A colleague in our own discipline these days. Just a personal opinion, but the only point there was meant to be a +1 to say. Don't let that. Don't let a lack of understanding stop you from.
00:34:03 Prof Stephen Freeland
Going into.
00:34:03 Prof Stephen Freeland
This that's exactly.
00:34:04 Prof Stephen Freeland
What gets me into Twitter right? Anyway, sorry. Back to the script. Where were we?
00:34:09 Prof Stephen Freeland
Commercial people. Sorry, you did the two reviews. So we wrote the one that was explicitly cross educating the.
00:34:15 Prof Stephen Freeland
Last year, we wrote one that was much more focused on the origins question, but they do add up to your point, it's saying that we have abundant evidence that life could be other we have growing pools of data about what would be the consequences of being other, and the time is here to start putting those two together and coming up with answers to questions that seemed unanswerable.
00:34:34 Prof Stephen Freeland
25 years ago.
00:34:36 Will Mountford
That feels, if anything, like not just the light of children, but a a simplification to me in the call with you of.
00:34:43 Will Mountford
Like there's a lot of asterisks and parentheses in that sentence of ways that it could go or not.
00:34:51 Will Mountford
Or different.
00:34:51 Prof Stephen Freeland
Absolutely.
00:34:52 Will Mountford
Or sideways or spiral elsewhere.
00:34:53 Prof Stephen Freeland
Yeah, yeah. I mean, it could go anywhere, couldn't it? And I think that part of what we do is believe that the safest place to put as much information as we can is in the public domain. That could be so naive because science can be used for all kinds of purposes. But I know that I trust the public domain more than I trust proprietary.
00:35:13 Prof Stephen Freeland
Companies, I do believe that science, when it's particularly when it's about truth rather than making money, is a uniting force global.
00:35:21 Prof Stephen Freeland
I do regularly converse with people from nations that we aren't terribly friendly with right now, but our conversation never goes there because we're talking about what we're learning about the universe, and that is yet another reason why I'd love to see more people go there. And I do believe given the amount of money flowing through this.
00:35:41 Prof Stephen Freeland
For all kinds of purposes that the companies are doing this, but part of the way the world works is they're not telling us because that's.
00:35:47 Prof Stephen Freeland
How they're gonna make?
00:35:47 Prof Stephen Freeland
Money, right? So I mean, a lot of what we're doing is trying to put the data and the information.
00:35:52 Prof Stephen Freeland
Out there and encourage a global community of people interested, hopefully in truth, rather than money per se, to sort of grow this body of knowledge so that we can be informed both scientifically and as a, you know, as global citizenry about what's going on and what we want to do with it.
00:36:15 Will Mountford
Well, in terms of other things that are moving fast and hopefully happening as much for the public benefit as possible.
00:36:22 Will Mountford
Synthetic biology X DNA all the components that you're working on.
00:36:28 Will Mountford
You've said already how they lead into mathematics, into chemistry, into computational biology, all of which are undergoing something of a radical change with advents of generative AI, machine learning database warehouses of DNA.
00:36:43 Will Mountford
How do you see these two fitting together in terms of stuff that could be happening today could be happening next, or that anyone listening to this who thinks that maybe they have the same verve for biology as inspired you could lead in their lifetime.
00:36:57 Prof Stephen Freeland
The thing that drives me now for a career, I can say that in the interface of computers and biology is the untapped potential, not least because computing itself is improving. So.
00:37:12 Prof Stephen Freeland
Quickly, but biological knowledge is improving so quickly. I told you earlier in the conversation I'm a bioinformaticist. That's how I'm classified professionally by the university where I work. It's not untrue, but I believe that bioinformatics has come to come to represent a subset of a bigger interesting frontier called computing and biology.
00:37:32 Prof Stephen Freeland
And what I do lies right on the edge of the two, but I want to encourage anyone listening that that is an interface with untapped potential. It is a bit like, you know, the border between the US and Canada or the England and Scotland, how we want to pick it depends where you're at on the border as to what you're seeing. Could be anything great, could be mountains could be.
00:37:49 Prof Stephen Freeland
It could be whatever, so it's that frontier, it's breadth, its diversity that is so exciting to me. I think that the best sort of grandma advice I could give to anybody considering this for a college and maybe a career is train a little in both fields. Maybe pick one of them to be your major and the other one to be the minor as the Americans would say.
00:38:12 Prof Stephen Freeland
Or just train them both, but you don't need to become an expert in both because there's so much untapped potential.
00:38:18 Prof Stephen Freeland
The reason to train them both is obvious, but it's what I was just saying. I mean, I say within a discipline, we barely understand each other. Computer scientists don't understand DNA, and biologists don't understand GEICO, right? And there's just so much there, so much to explore and find and discover and be the first person ever to have discovered it.
00:38:34 Will Mountford
From a student retention and recruitment point, we should say biology major with computer science.
00:38:39 Prof Stephen Freeland
No, we should. There we go. There we.
00:38:41 Prof Stephen Freeland
Go although I.
00:38:42 Prof Stephen Freeland
Sometimes think that I dream. I dream of futures where we stop bothering with that. Sort of. You've got to be one of the.
00:38:48 Prof Stephen Freeland
Just, you know, maybe. Yeah. Somebody who does both.
00:38:51 Prof Stephen Freeland
If we have to teach computer scientists more biology, it's a retooling of our profession, but a very noble one. In an age of chat, GTP and that same architecture being applied to no end of sort of biomedical frontiers, right, I'd like more, more biologically savvy computer scientists. I think that'd be a good thing for the world. Yeah.
00:39:10 Will Mountford
Interesting and important things about the inevitability and possibly predestination of life on Earth.
00:39:16 Prof Stephen Freeland
Absolutely.
00:39:17 Will Mountford
For anyone listening to this to find out more, where can they find you on the Internet, academically speaking.
00:39:25 Prof Stephen Freeland
We have a humble little lab website which you're welcome to go to the Freeland lab. My university is called UMBC, and it is a great place. So by all means come and visit UMBC, visit the biology department and visit our lab website, and you'll certainly have links to our papers there. I did all of that. Even that was last year and I'm like, OK, let's do this. And I did all the.
00:39:44 Prof Stephen Freeland
Basic stuff.
00:39:45 Prof Stephen Freeland
We're working with a group in Prague who are building our alphabets and that is the Kochevar lab. I think Europe is ahead of America right now on the sorts of things that I care about. So kochevar is HLOUCHOVA. That's another great place to visit where they're building stuff in the laboratory to explore the unknown world of proteins.
00:40:06 Prof Stephen Freeland
Right.
00:40:07 Will Mountford
And to round things out, if there's anyone listening to this who is considering a academic switch to Bioscience, possibly from computer maths.
00:40:16 Will Mountford
Geology or anything else, or they want to get started.
00:40:20 Will Mountford
Is now a good time to get into Bioscience.
00:40:23 Prof Stephen Freeland
Yeah, yeah. Let's say a market reality is the best time to get into something is when it's enrollments are going down because they're starting it's supply and demand. They're starting to compete for you. You can get into a better school now for biology because everyone's hurting a bit. So there's there's a simple reason. Yes. Good time. Intellectually, yes. Good time. Exciting things are happening. You asked me earlier.
00:40:43 Prof Stephen Freeland
What? What is my dream for 5-10 years? I do believe that we should find life independent life outside of Earth within a generation.
00:40:50 Prof Stephen Freeland
Most of my community would say we'd be surprised if we didn't find it within 10 years. The the only rider is to say, equally excitingly, if we don't, that's telling us there's something fundamentally missing from our understanding of the chemistry and history of our planet. So it's an exciting time. Synthetic alphabets, biomedical engineering, genetic engineering, taken to the next level on one front.
00:41:11 Prof Stephen Freeland
And on the other front of very real search for signs of life outside of Earth, which biggest reason when people say, well, why haven't we found it yet? We haven't actually looked. There were three experiments in the mid 1970s, the Viking. And one of those came back by its own terms as having demonstrated the existence of life on Mars. But it was explained away as we hadn't understood soil chemistry at that point.
00:41:31 Prof Stephen Freeland
So the point is, we haven't looked. So I think two different reasons why this is intellectually a great time and the market says, yeah, get into biology right now because they'll fight.
00:41:40 Prof Stephen Freeland
To get you.
00:41:41
Right.
00:41:44 Prof Stephen Freeland
One of the ways to start sewing them together is by saying we we reach a point of common interest when we say it could be other. Those people are inspiring me more than the people who study detailed genetics these days, I mean.
00:41:54 Prof Stephen Freeland
I struggle to.
00:41:55 Prof Stephen Freeland
Keep up, but I know a lot about the synthetic DNA because it inspires me. And so thank you for that. And you know, maybe we inspire a generation.
00:42:03 Prof Stephen Freeland
There are at least a few individuals to be the next steps in sewing those two back together again.
00:42:07 Will Mountford
That would be nice. Nice to meet you.
00:42:08 Prof Stephen Freeland
That would be nice.
00:42:10 Will Mountford
And if anyone is listening to this, we're recording it in the early days of 2024. But you know, should we all still be here in 20-30, then drop us a line and let us know. For now, we'll say Professor Freeland, thank you so much for your time.
00:42:22 Prof Stephen Freeland
Thank you.