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Unravelling the secrets of our genes · Luke's English Podcast

• 0:06
  Speaker 1: Simon, I hope you've had a good week.
• 0:07
  Speaker 2: Yeah, it's been great. Thank you. Busy, but good.
• 0:10
  Speaker 1: Yeah, I know that feeling. Beginning of the week, I
• 0:11
  Speaker 1: was going to do all sorts of things, write papers,
• 0:13
  Speaker 1: write grants. No idea what I've actually done. But anyway,
• 0:17
  Speaker 1: here we're here today and we're going to talk about
• 0:19
  Speaker 1: DNA sequencing. We are.
• 0:21
  Speaker 2: Yeah, absolutely.
• 0:22
  Speaker 3: And so I think perhaps before we dive into the
• 0:25
  Speaker 3: details of DNA sequencing itself, perhaps for those listeners who
• 0:29
  Speaker 3: are not experts, maybe we should perhaps discuss what DNA
• 0:33
  Speaker 3: is and why we might want to sequence it.
• 0:35
  Speaker 1: Well, we've got a couple of real experts coming in later,
• 0:38
  Speaker 1: which is going to be exciting. We'll introduce them when
• 0:40
  Speaker 1: they turn up, where we're going to talk to them.
• 0:43
  Speaker 1: But actually, you know more about DNA than me, so
• 0:46
  Speaker 1: I can play the idiot here.
• 0:49
  Speaker 4: Play?
• 0:52
  Speaker 1: So DNA, obviously, is the kind of molecule that codes
• 0:56
  Speaker 1: for life. It's a self-assembly instruction booklet for an organism,
• 1:00
  Speaker 1: isn't that right?
• 1:00
  Speaker 2: Yeah, absolutely.
• 1:02
  Speaker 1: And what I know is.
• 1:04
  Speaker 1: It's like a ladder that's been twisted. So it's a
• 1:08
  Speaker 1: famous double helix spiral.
• 1:10
  Speaker 2: Yeah, sure.
• 1:11
  Speaker 1: And so what are the up bits of the ladder
• 1:13
  Speaker 1: and what are the cross bits?
• 1:15
  Speaker 3: Okay, so the up bits of the ladder is what
• 1:18
  Speaker 3: we call the backbone. And that's made up of two
• 1:21
  Speaker 3: different types of molecules, a phosphate and a sugar.
• 1:24
  Speaker 2: And they don't change, right?
• 1:25
  Speaker 3: So the up bits are always the same. However, the
• 1:29
  Speaker 3: rungs of the ladder are what we call bases, right?
• 1:32
  Speaker 3: And those bases do vary. There's four different types. And
• 1:37
  Speaker 3: it's that sequence in which they appear that where we
• 1:41
  Speaker 3: get this idea of the code.
• 1:44
  Speaker 1: And so amino acids are the building blocks of proteins. Yeah.
• 1:47
  Speaker 1: And these are all molecules.
• 1:49
  Speaker 2: Yeah. So you're right. Absolutely right.
• 1:50
  Speaker 3: So we have these four bases and the sequence in
• 1:54
  Speaker 3: which they appear carries a code. The code is the
• 1:57
  Speaker 3: blueprint for making these 20 different amino acids. And you
• 2:02
  Speaker 3: can think of the 20 amino acids as 20 Lego
• 2:04
  Speaker 3: bricks with which we build proteins. And these are molecules
• 2:09
  Speaker 3: that we sometimes refer to them as the workhorse of
• 2:12
  Speaker 3: the cell or the body. So they carry out very
• 2:15
  Speaker 3: many of the functions and make us look like we
• 2:18
  Speaker 3: do and all the things the body does. A lot
• 2:21
  Speaker 3: of it is done by proteins.
• 2:23
  Speaker 1: And so how does the code work? So how do
• 2:26
  Speaker 1: you go from... some bases, a string of bases. So
• 2:31
  Speaker 1: they're called, I'm going to get this wrong, adenine, cytosine, guanine, thymine?
• 2:38
  Speaker 2: Yes, excellent.
• 2:39
  Speaker 1: Okay. And I struggle to remember those. And those four
• 2:45
  Speaker 1: somehow code for 20 amino acids. So how do we
• 2:49
  Speaker 1: go from the four types of base pairs, adenine, cytosine, guanine, thymine,
• 2:58
  Speaker 1: So that's ACGT to an amino acid. Not the whole
• 3:06
  Speaker 1: kind of complicated molecular mechanism, but what the code is. Sure.
• 3:10
  Speaker 3: So the three of those bases will give us one
• 3:14
  Speaker 3: amino acid. So it's the blueprint for one amino acid.
• 3:17
  Speaker 3: So the different order in which they appear.
• 3:21
  Speaker 1: Yeah, okay.
• 3:21
  Speaker 3: And so there's machinery in the body which will, you know, again,
• 3:24
  Speaker 3: without going into the details, which will read that order.
• 3:28
  Speaker 3: and know, oh, I've got these three, so that means
• 3:30
  Speaker 3: I must make this amino acid. And so it makes it,
• 3:33
  Speaker 3: and then there's something else which adds them all, connects
• 3:36
  Speaker 3: them all up, and then makes the protein.
• 3:37
  Speaker 1: Okay. So you have a chain of DNA, a double
• 3:41
  Speaker 1: helix of DNA, made of these bases, and then that's
• 3:46
  Speaker 1: translated into a chain of amino acids.
• 3:50
  Speaker 3: Yeah, there's a bunch of doses, but basically that's what happens.
• 3:54
  Speaker 3: And these amino acids make proteins and the differences in
• 3:58
  Speaker 3: the proteins you have, for example, compared to the ones
• 4:01
  Speaker 3: I have and the different numbers of them make us
• 4:04
  Speaker 3: different in.
• 4:05
  Speaker 2: The ways we differ.
• 4:06
  Speaker 3: We look differently, we have different characteristics and that's a
• 4:10
  Speaker 3: function of this code and these proteins.
• 4:13
  Speaker 1: But we only use kind of one Because it's a
• 4:17
  Speaker 1: double helix, but we only use one bit of that
• 4:20
  Speaker 1: for reading the code. Is that right?
• 4:22
  Speaker 2: Yeah, at a time.
• 4:23
  Speaker 3: So you split them off and then it gets read.
• 4:26
  Speaker 3: And actually, the really interesting thing is that the strands
• 4:29
  Speaker 3: come from our parents. And so this is why siblings
• 4:33
  Speaker 3: will look alike. But actually, we don't look alike. we're
• 4:37
  Speaker 3: not all identical because there's differences within that, but it's the, the,
• 4:42
  Speaker 3: we get once, you know, the strands come from our
• 4:45
  Speaker 3: mother and our father and they get combined.
• 4:47
  Speaker 1: And they get mixed up, don't they? So even though
• 4:49
  Speaker 1: we've got half our DNA from our mom and half
• 4:52
  Speaker 1: our DNA from her dad, it's not like we've got
• 4:54
  Speaker 1: one half of the helix and one half isn't. I mean,
• 4:58
  Speaker 1: cause I, I used to think that.
• 5:00
  Speaker 2: Yeah, me too.
• 5:00
  Speaker 1: Yeah. I think that's a common misconception, but so, and,
• 5:04
  Speaker 1: and it, When an egg or a sperm is made,
• 5:08
  Speaker 1: they're a mix of... So we've got two chromosomes eat.
• 5:12
  Speaker 1: We've got chromosome pairs, don't we?
• 5:13
  Speaker 2: That's right.
• 5:13
  Speaker 1: So I suppose we need to take a step back
• 5:16
  Speaker 1: and mention that. So that means we've got... So DNA
• 5:20
  Speaker 1: is snipped up in the body into, like, chromosomes.
• 5:23
  Speaker 2: Yes.
• 5:24
  Speaker 1: And we've got 23 chromosome pairs.
• 5:26
  Speaker 3: Is that right?
• 5:27
  Speaker 1: That's right, yeah. Yeah, OK. And one chromosome in each
• 5:31
  Speaker 1: pair came from our mum and one from our dad.
• 5:35
  Speaker 2: Yeah.
• 5:36
  Speaker 1: But my mum's chromosome, the one that came from my mum,
• 5:38
  Speaker 1: would have been a mix of her mum and her dad.
• 5:41
  Speaker 1: So it would have been my grandparent.
• 5:43
  Speaker 4: Is that right?
• 5:44
  Speaker 2: Yeah, absolutely.
• 5:45
  Speaker 3: And so it gives us actually quite a repertoire of
• 5:48
  Speaker 3: different characteristics that can come from all those mixtures. But
• 5:52
  Speaker 3: of course, because they come from our parents, siblings will
• 5:56
  Speaker 3: look alike.
• 5:57
  Speaker 1: Yeah. My sister got all the looks and all the brains.
• 6:01
  Speaker 2: Mine got the normal coloured hair.
• 6:03
  Speaker 3: That's not quite how genetics works.
• 6:07
  Speaker 1: So it's an amazing molecule. It is. It's also, it's
• 6:11
  Speaker 1: very stable, isn't it? It doesn't react with. I mean,
• 6:14
  Speaker 1: it's kind of very good at keeping the code, but
• 6:16
  Speaker 1: it's rubbish and getting involved in chemical reactions.
• 6:18
  Speaker 3: Yeah, I mean, the code is protected, right? You know,
• 6:21
  Speaker 3: it has a certain.
• 6:24
  Speaker 3: Certain shape and morphology, we call this, and it's all
• 6:28
  Speaker 3: coiled up and tangled up. So it's not really able
• 6:30
  Speaker 3: to get, as you said, involved in other things that
• 6:33
  Speaker 3: happen in the cell. The bases are very well protected.
• 6:36
  Speaker 3: And one interesting fact about DNA is that the DNA
• 6:41
  Speaker 3: we have in a single cell, if we were to
• 6:44
  Speaker 3: uncoil it all up and unwind it, actually is six
• 6:46
  Speaker 3: feet long in just a single cell.
• 6:49
  Speaker 1: Yeah, that's amazing. And it's billions of base pairs, right?
• 6:53
  Speaker 1: It is, yeah. Billions of bases in each of our DNA.
• 6:56
  Speaker 1: It is, yeah.
• 6:57
  Speaker 2: And that varies with organisms.
• 6:59
  Speaker 3: So because we're complicated, you know, highly evolved organisms, we
• 7:03
  Speaker 3: have many of them. Simpler organisms like bacteria, for example,
• 7:08
  Speaker 3: will have shorter DNAs and fewer bases.
• 7:11
  Speaker 1: Yeah, okay. And then you've already said this, we share,
• 7:15
  Speaker 1: if we had an identical twin.
• 7:17
  Speaker 2: Yes.
• 7:17
  Speaker 1: I don't, do you? No. No, but they would have
• 7:21
  Speaker 1: the same genetic sequence as us, an identical twin. Our
• 7:25
  Speaker 1: siblings have about half, or have half the amount of DNA,
• 7:30
  Speaker 1: we share 50% half of our DNA with them.
• 7:33
  Speaker 2: Yes.
• 7:33
  Speaker 1: Ditto with our parents.
• 7:35
  Speaker 4: Yes.
• 7:36
  Speaker 1: And then 25% on average with our grandparents, but it
• 7:39
  Speaker 1: can actually vary. It varies, yeah. But we can use
• 7:41
  Speaker 1: that because we can build family trees by looking at the, well,
• 7:46
  Speaker 1: so some bits of all of our DNA are, is identical, right?
• 7:50
  Speaker 1: There's conserved genes, which if they break, then we don't
• 7:54
  Speaker 1: function properly.
• 7:55
  Speaker 3: That's right.
• 7:56
  Speaker 2: Yes.
• 7:56
  Speaker 1: Okay. But for the variable bits, when we're talking about
• 8:00
  Speaker 1: sharing 50%, or when we look to see how much
• 8:04
  Speaker 1: we share with other organisms... They're the bits that vary
• 8:07
  Speaker 1: between organisms, right? Yeah, okay.
• 8:09
  Speaker 3: And we can use those variations to detect, for example,
• 8:12
  Speaker 3: you know, origins. So where we deviated from each other,
• 8:16
  Speaker 3: for example, where there are similarities. One can build up historic,
• 8:20
  Speaker 3: almost if you like, family trees and this sort of thing,
• 8:22
  Speaker 3: just looking at DNA.
• 8:23
  Speaker 2: It's actually odd how.
• 8:26
  Speaker 3: how much the DNA is shared between organisms and entities
• 8:31
  Speaker 3: that are completely different in appearance. And, you know, so
• 8:34
  Speaker 3: it's quite, yeah, it's fascinating, I think. And actually that
• 8:37
  Speaker 3: also makes life difficult because if we want to use
• 8:40
  Speaker 3: the DNA to understand differences, so much.
• 8:42
  Speaker 2: Of it is the same.
• 8:43
  Speaker 1: Yeah. Okay. No, I see. Yeah. But what we can,
• 8:47
  Speaker 1: what scientists have done, and this is kind of closer
• 8:49
  Speaker 1: to things that I've been involved with the DNA is
• 8:52
  Speaker 1: you can, you can work out, not just family trees
• 8:55
  Speaker 1: between individuals, but family trees between species. And in fact,
• 8:59
  Speaker 1: when they've done that, they've estimated that the genetic code
• 9:02
  Speaker 1: that we use today, that all life uses today, evolved 3.9
• 9:06
  Speaker 1: billion years ago. And I think one of the things
• 9:10
  Speaker 1: that's really interesting about that is Earth kind of only
• 9:13
  Speaker 1: evolved about, appeared about, or formed about 4.1 4.6 million
• 9:21
  Speaker 1: years ago. So it didn't take that long on the
• 9:23
  Speaker 1: grand scheme of things for life to get going.
• 9:26
  Speaker 2: That's amazing.
• 9:27
  Speaker 3: If we think about the grand scheme of, yeah, as
• 9:29
  Speaker 3: you said, the life history of the earth.
• 9:31
  Speaker 1: Yeah. But one of the big challenges is we'll talk
• 9:36
  Speaker 1: more about sequencing with our guests just now. But I
• 9:40
  Speaker 1: think after that, one of the things is trying to
• 9:43
  Speaker 1: understand how the genetic code got started and how life
• 9:45
  Speaker 1: got started. Because as you've just explained it, The chemistry
• 9:49
  Speaker 1: is incredibly complicated. DNA replication and what have you. And
• 9:55
  Speaker 1: it certainly didn't spring into existence from nowhere. So we'll
• 9:58
  Speaker 1: talk to people who have been thinking about how life
• 10:01
  Speaker 1: got started and how genetic code but let's just talk
• 10:04
  Speaker 1: about sequencing because we're going to talk to some experts
• 10:06
  Speaker 1: about that that the sequence is the string of the
• 10:10
  Speaker 1: bait of the of the basis isn't it it's the acg.
• 10:14
  Speaker 3: It's the order it's the order in which they appear
• 10:16
  Speaker 3: and that's You know, it's just like, it's a little
• 10:19
  Speaker 3: bit like a computer, really, because it carries a code
• 10:22
  Speaker 3: that can be interpreted for a way of holding any
• 10:25
  Speaker 3: kind of information.
• 10:26
  Speaker 1: Or even kind of letters in a book. There's only
• 10:29
  Speaker 1: four of them and there's no spaces.
• 10:30
  Speaker 5: That's right.
• 10:32
  Speaker 2: A very limited language in a way.
• 10:33
  Speaker 3: But actually, because they encode for amino acids, then that
• 10:37
  Speaker 3: language becomes vast.
• 10:40
  Speaker 1: But not all of our DNA makes... amino acids does
• 10:46
  Speaker 1: it there are other bits and bobs in there that
• 10:48
  Speaker 1: do other.
• 10:48
  Speaker 3: Things absolutely it's a tiny tiny proportion the vast majority
• 10:52
  Speaker 3: is non-coding oh.
• 10:53
  Speaker 1: I didn't know okay i didn't know it's yeah but
• 10:56
  Speaker 1: some of that instructs um it some it's not useless
• 11:02
  Speaker 1: that dna.
• 11:02
  Speaker 3: Yeah it does other things like um starts off other
• 11:06
  Speaker 3: processes help create creates a template for RNA, for example,
• 11:13
  Speaker 3: and RNA, which is a molecule that carries out other
• 11:15
  Speaker 3: functions that help with, it could help with DNA replication.
• 11:20
  Speaker 3: It could help with, you know, protein synthesis, lots of
• 11:24
  Speaker 3: other functions that happen, but it doesn't encode, as you said.
• 11:27
  Speaker 2: For amino acids.
• 11:29
  Speaker 1: But the, so if I'm, Because in our bodies, we've
• 11:32
  Speaker 1: got like lots of different cell types. They're all come
• 11:35
  Speaker 1: from the same, each cell has the same genome essentially.
• 11:39
  Speaker 3: That's right.
• 11:39
  Speaker 1: But we've got like 220 different cell types. So in
• 11:43
  Speaker 1: each one of our cells, and we've got like 37
• 11:46
  Speaker 1: trillion cells in our bodies. That's right. In each one
• 11:49
  Speaker 1: of those, there's a six foot of DNA. Yeah. And
• 11:54
  Speaker 1: a fraction of that DNA creates proteins, amino acids that
• 11:58
  Speaker 1: form proteins.
• 11:59
  Speaker 6: Right.
• 12:01
  Speaker 1: Not all of those cells have the same proteins or
• 12:04
  Speaker 1: use the same proteins.
• 12:05
  Speaker 2: No, not at all.
• 12:06
  Speaker 1: So how in some cells do we make some proteins
• 12:10
  Speaker 1: and other cells our DNA makes others?
• 12:13
  Speaker 2: Yeah, OK, you're absolutely right.
• 12:14
  Speaker 3: We've got vast quantities of DNA in every cell, right?
• 12:18
  Speaker 3: But then this non-coding part of the DNA has these
• 12:22
  Speaker 3: other functions. So, for example, has regions that proteins come
• 12:25
  Speaker 3: along and bind to and they can... enhance or accelerate
• 12:29
  Speaker 3: or initiate or block the production of amino acids.
• 12:35
  Speaker 2: So you can think of it a little bit like
• 12:36
  Speaker 2: a factory.
• 12:37
  Speaker 3: All this stuff inside our cells is going on all
• 12:39
  Speaker 3: the time. And not all of it is to make stuff.
• 12:42
  Speaker 3: Sometimes it's to stop things being made. And this is
• 12:45
  Speaker 3: how things are regulated with these other parts of the
• 12:48
  Speaker 3: DNA that don't make or code for amino acids.
• 12:53
  Speaker 2: They have these other functions.
• 12:55
  Speaker 1: So what's going on in our cells? is way more
• 12:58
  Speaker 1: complicated than what goes on in, say, my iPad.
• 13:02
  Speaker 2: Vastly so.
• 13:02
  Speaker 3: And I think, for me, one of the mind-blowing things
• 13:06
  Speaker 3: about biology when I first started to sort of delve
• 13:09
  Speaker 3: into it and understand this, if I'm sitting here now
• 13:12
  Speaker 3: talking to you, it looks like I'm static. But the
• 13:16
  Speaker 3: sheer amount of movement that's going on at a very
• 13:18
  Speaker 3: small level inside all of my cells is vast. There's
• 13:22
  Speaker 3: things moving around all the time.
• 13:24
  Speaker 2: You know, the DNA is being.
• 13:27
  Speaker 3: The DNA is being read and proteins are being, amino
• 13:31
  Speaker 3: acids are being made, they're all being connected up, proteins
• 13:33
  Speaker 3: are being made, and the whole thing is somehow regulated
• 13:37
  Speaker 3: and choreographed.
• 13:38
  Speaker 1: It really is amazing. And I think what's incredible was
• 13:44
  Speaker 1: when I was at school and when Rich, our wonderful producer,
• 13:46
  Speaker 1: was at school, we got taught Mendel. They knew what
• 13:50
  Speaker 1: DNA was.
• 13:50
  Speaker 2: Are you sure they knew what it was in those days?
• 13:53
  Speaker 1: LAUGHTER Thank you. Yeah, Darwin adjusts that often as well.
• 13:58
  Speaker 1: So anyway, Mendel had, we were taught Mendel and we
• 14:02
  Speaker 1: knew the structure of DNA, but everyone thought there was
• 14:05
  Speaker 1: probably just a gene for everything, right? So there would
• 14:08
  Speaker 1: be a gene for how tall you were going to be,
• 14:10
  Speaker 1: a gene for how intelligent you are. But what we've
• 14:12
  Speaker 1: learned now is actually it's incredibly complicated. And we've learned
• 14:17
  Speaker 1: that through a mix of DNA sequencing and a mix
• 14:20
  Speaker 1: of looking at the products that DNA makes. And so
• 14:24
  Speaker 1: one of the exciting things is we're now going to
• 14:26
  Speaker 1: talk to some.
• 14:28
  Speaker 5: Experts, right?
• 14:30
  Speaker 1: Okay.
• 14:34
  Speaker 3: So Tim, now we have two, uh, real DNA scientists
• 14:37
  Speaker 3: here with us experts. In fact, we're leading experts and
• 14:40
  Speaker 3: should we let them introduce themselves?
• 14:42
  Speaker 2: So over to you, Gordon.
• 14:44
  Speaker 1: Thank you very much.
• 14:45
  Speaker 4: Uh, my name's Gordon Sangira. I am a, one of
• 14:49
  Speaker 4: the founders of oxygen nanopore technologies. which was a spin-out
• 14:53
  Speaker 4: from the University of Oxford 20 years ago this year.
• 14:56
  Speaker 1: 20 years, wow.
• 14:58
  Speaker 6: Hi, thank you for having us. My name is Lakmal Jaisingh.
• 15:02
  Speaker 6: I'm the CSO of Oxford Nanopore. I was one of
• 15:08
  Speaker 6: the very first scientists to join Oxford Nanopore, a first-rate
• 15:13
  Speaker 6: lab scientist, and I've been there for 18 years as well.
• 15:17
  Speaker 4: I've just come from a government meeting, a lot of acronyms. CHIEF.
• 15:21
  Speaker 4: scientific officer, CSI. Thank you, Gordon. I shall be bringing
• 15:27
  Speaker 4: him back down out of acronyms.
• 15:30
  Speaker 2: Well, this is wonderful.
• 15:31
  Speaker 3: I mean, I'm quite, you know, sort of taking them back,
• 15:33
  Speaker 3: you saying 20 years, because I think we first met
• 15:36
  Speaker 3: each other maybe about 18 years ago when things had
• 15:40
  Speaker 3: started moving. And on that vein, you know, DNA sequencing
• 15:45
  Speaker 3: is something that's been around for a long time. So
• 15:48
  Speaker 3: can you tell us a little bit about why next
• 15:51
  Speaker 3: generation sequencing is needed? This is what you do and
• 15:55
  Speaker 3: what your company does.
• 15:56
  Speaker 4: Absolutely. And I'm going to trivialise the science. And it
• 16:01
  Speaker 4: took 10 years and it cost several billion pounds to
• 16:05
  Speaker 4: make this happen. But the way that you read DNA,
• 16:09
  Speaker 4: you read it 20 years ago, and a lot of
• 16:12
  Speaker 4: it's still done the same today, is you take something
• 16:15
  Speaker 4: like a human being, We have two billion letters, G-T-A-C,
• 16:20
  Speaker 4: that's your source code. And you shrink it down, chop
• 16:25
  Speaker 4: it up into 200 letters on a string. In reality,
• 16:29
  Speaker 4: there's three billion in that one string. And then you
• 16:33
  Speaker 4: use colour chemistry, optical systems, large complex laboratories, lots of scientists,
• 16:40
  Speaker 4: multi-million dollar infrastructure and million dollar equipment to decode. and
• 16:45
  Speaker 4: piece those 200 letter-sized pieces back into your three billion
• 16:50
  Speaker 4: letter puzzle. What we do is actually read the DNA
• 16:58
  Speaker 4: in its native form. What do I mean by that?
• 17:01
  Speaker 4: We'd still chop it up, but we'd chop it up
• 17:03
  Speaker 4: into very long pieces, like tens of thousands or hundreds
• 17:07
  Speaker 4: of thousands of bases, and we don't do anything else
• 17:10
  Speaker 4: to it. And we use... a method called nanopore sequencing,
• 17:15
  Speaker 4: which I'm sure Lachmar will articulate later, which allows us
• 17:18
  Speaker 4: to read native DNA in its natural form, the way
• 17:23
  Speaker 4: it exists inside an individual, rather than chopping it up
• 17:28
  Speaker 4: and maybe getting a crude black and white approximation. You're
• 17:32
  Speaker 4: seeing your DNA biology in high definition and full colour.
• 17:36
  Speaker 1: So the traditional way would be like trying to, if
• 17:39
  Speaker 1: you had all the separate words for a book, trying
• 17:41
  Speaker 1: to put the book together. Is that all?
• 17:43
  Speaker 5: Indeed.
• 17:44
  Speaker 4: And I think you could take it one step further.
• 17:46
  Speaker 4: You've almost got seascape and skyscape.
• 17:50
  Speaker 1: Oh, yeah.
• 17:51
  Speaker 4: And it's all almost the same blue.
• 17:52
  Speaker 1: Yeah.
• 17:54
  Speaker 4: So you're putting the sky where the sea should be
• 17:57
  Speaker 4: and the sea where the sky should be. And that
• 17:59
  Speaker 4: exists today in existing recoding of the biology when you
• 18:04
  Speaker 4: smash it up and then reassemble it.
• 18:06
  Speaker 1: So what's the longest read you can do at the
• 18:09
  Speaker 1: longest string? Say hundreds of thousands now, is it?
• 18:11
  Speaker 4: That's right. So the world record is four and a
• 18:14
  Speaker 4: half million CNA bases. Remember, it's three billion on one channel.
• 18:19
  Speaker 4: And the technology would and could eat all of that.
• 18:24
  Speaker 4: Think about somebody sucking spaghetti. This machine can suck a
• 18:28
  Speaker 4: three and a half billion lettered spaghetti piece. But the
• 18:32
  Speaker 4: problem is it's very fragile. So just the action of
• 18:37
  Speaker 4: taking it from your body, extracting the human DNA, cleaning
• 18:41
  Speaker 4: it up, even pipetting it onto the device, breaks it up.
• 18:46
  Speaker 4: So that's why tens of thousands or 100,000 bases is straightforward.
• 18:51
  Speaker 4: But there is an ambition to read ever-increasing lengths. There's
• 18:56
  Speaker 4: lots of interesting biology you get from reading intact genomes.
• 19:02
  Speaker 3: So Gordon, if we take things one step further, so
• 19:04
  Speaker 3: Tim and I have discussed DNA and the genetic information
• 19:08
  Speaker 3: that it holds and you're saying that you've developed these
• 19:11
  Speaker 3: techniques to read the DNA and sequencing it can you
• 19:15
  Speaker 3: tell us a little bit about why do we want
• 19:17
  Speaker 3: to sequence it why do we want to know what
• 19:19
  Speaker 3: the code.
• 19:19
  Speaker 4: Is so if you think about DNA and RNA and
• 19:25
  Speaker 4: just to give you a distinction DNA is a source
• 19:28
  Speaker 4: code so that's your complete music catalog your code RNA
• 19:35
  Speaker 4: is your current music playlist. So you want to know both.
• 19:40
  Speaker 4: And all diseases, our predisposition to diseases, our efficacy of treatments,
• 19:49
  Speaker 4: even developing new drugs, and whether we're going to get
• 19:52
  Speaker 4: these aging diseases like neurodegeneration, they're all hidden and wrapped
• 19:58
  Speaker 4: up in our genomes. And today, with this short read
• 20:02
  Speaker 4: black and white sequencing in legacy systems, about 25% of
• 20:07
  Speaker 4: all human genomes, some of the toughest ones, pernicious cancers, neurodegeneration,
• 20:13
  Speaker 4: and many, many others are wrapped in what is referred
• 20:16
  Speaker 4: to as the dark genome.
• 20:18
  Speaker 1: Okay. I've not heard that expression.
• 20:20
  Speaker 6: That's right.
• 20:21
  Speaker 4: It's a real thing because with short reads, you miss
• 20:24
  Speaker 4: all these things. And so shedding light on those will
• 20:30
  Speaker 4: have a huge impact. And we really are, even 20
• 20:33
  Speaker 4: years after the first human genome was mapped, still scratching
• 20:37
  Speaker 4: the surface of our understanding of our source codes.
• 20:42
  Speaker 3: So you're saying that inside our DNA, in the code
• 20:45
  Speaker 3: and in this dark genome, there's information that can perhaps
• 20:49
  Speaker 3: tell us about which diseases we're predisposed to as part
• 20:54
  Speaker 3: of our makeup and even which treatments would be more
• 20:57
  Speaker 3: effective for us compared to other people. And that's a
• 21:01
  Speaker 3: big motivation for understanding what's inside us, what's inside this code.
• 21:05
  Speaker 2: Is that right?
• 21:05
  Speaker 4: That's right, 100%. But don't forget, Our DNA is dynamic.
• 21:12
  Speaker 4: So over our lifetimes, we have GTA C. There's something
• 21:17
  Speaker 4: called the fifth base, which is methylated. So it's chemically
• 21:22
  Speaker 4: corrupted C. And that is a smoking gun in all cancers.
• 21:28
  Speaker 1: Oh, wow. And so you can detect that in your...
• 21:31
  Speaker 1: That's right.
• 21:31
  Speaker 4: You cannot do it with the existing systems. And you
• 21:34
  Speaker 4: can pick that out. And that's a really exciting... piece
• 21:39
  Speaker 4: of biology that everybody's starting to think about and look
• 21:42
  Speaker 4: at and and that that modification is important so dna
• 21:47
  Speaker 4: is not dynamic and that's you know if you smoke
• 21:49
  Speaker 4: one cigarette four of your c bases are corrupted now
• 21:54
  Speaker 4: don't worry you've got three and a half billion so
• 21:58
  Speaker 4: there's quite a lot there but it you know it's
• 22:01
  Speaker 4: the external factors your lifestyle your diet all of these
• 22:05
  Speaker 4: things can can be part of that and so it's
• 22:09
  Speaker 4: Not just what we are, how we were built from
• 22:13
  Speaker 4: our parental hereditary genes, but what we do and how
• 22:18
  Speaker 4: that becomes corrupted or not, depending on your lifestyle during
• 22:23
  Speaker 4: the course of your lifetime.
• 22:25
  Speaker 6: To add to that, when we talk about why DNA
• 22:27
  Speaker 6: sequencing is required, so the human genetics is a big part,
• 22:31
  Speaker 6: but beyond human genetics, what you can do in agriculture
• 22:36
  Speaker 6: and sequencing plants to see which soil condition is suitable
• 22:41
  Speaker 6: for different crops and different varieties, and to monitor environmental
• 22:47
  Speaker 6: samples to see what's in there and to monitor water
• 22:53
  Speaker 6: samples and sewage waste samples. So applications are huge, but
• 22:58
  Speaker 6: obviously human genetics and diseases is a big part of it.
• 23:02
  Speaker 3: So it's not just our sort of human genetics, DNA
• 23:06
  Speaker 3: that we want to sequence, but that of plants and
• 23:08
  Speaker 3: animals and other organisms too.
• 23:10
  Speaker 1: Can you give us an example? I mean, as well
• 23:12
  Speaker 1: as producing the technology, you're also involved in some of
• 23:15
  Speaker 1: the research that's doing this. Is that right? You're doing
• 23:19
  Speaker 1: some work, I think, in Sri Lanka at the moment.
• 23:21
  Speaker 3: Yeah.
• 23:21
  Speaker 5: So I think COVID is a good example.
• 23:23
  Speaker 6: Like I think when it started in Wuhan, first thing
• 23:29
  Speaker 6: they did in China was using uh min iron to
• 23:33
  Speaker 6: characterize the uh covid sequence.
• 23:36
  Speaker 2: And min iron is one of your your.
• 23:37
  Speaker 6: Devices yes so min iron is basically this one so
• 23:41
  Speaker 6: this is our latest version so this is just handheld device.
• 23:45
  Speaker 1: Sorry wait a sec that that does all this that
• 23:48
  Speaker 1: that will read your billions of base pads exactly i
• 23:53
  Speaker 1: thought you were going to like be dragging in a
• 23:54
  Speaker 1: wardrobe size.
• 23:56
  Speaker 6: That's that's why we need this technology because the other
• 23:59
  Speaker 6: technologies have this huge fridge size devices.
• 24:02
  Speaker 1: Can you hold that up to the camera there? Just
• 24:04
  Speaker 1: so that you can see quite well.
• 24:07
  Speaker 2: Yeah.
• 24:08
  Speaker 5: So that's our device.
• 24:10
  Speaker 1: It's smaller than a mobile phone.
• 24:12
  Speaker 5: It is, yeah.
• 24:13
  Speaker 6: This is our smallest version, portable version, and we have
• 24:16
  Speaker 6: different scale devices as well.
• 24:19
  Speaker 1: Sorry, I interrupted you. You were telling us about, yeah.
• 24:21
  Speaker 6: So during the COVID time, it's mainly like this that
• 24:24
  Speaker 6: went around the world. So when it started in Wuhan,
• 24:29
  Speaker 6: like obviously they went into using this. And at one point,
• 24:33
  Speaker 6: like most of the Chinese CDC labs using this machine
• 24:38
  Speaker 6: to characterize COVID and then across the world, like more
• 24:42
  Speaker 6: than 120 countries used this device to characterize DNA. So
• 24:49
  Speaker 6: if you like, I mean, the familiar.
• 24:52
  Speaker 5: Words like alpha, beta, gamma, like Omicron, all.
• 24:54
  Speaker 6: The variants and which variant is spreading in different countries
• 24:58
  Speaker 6: to understand that you need to sequence COVID virus to
• 25:02
  Speaker 6: understand the mutations. And so we had like these end
• 25:07
  Speaker 6: to end workflows. So we develop all these things so
• 25:11
  Speaker 6: the customers can very easily sequence COVID sequence and understand
• 25:15
  Speaker 6: the mutations and understand which variation is spreading in certain communities.
• 25:20
  Speaker 5: So that was huge.
• 25:21
  Speaker 6: So in Sri Lanka, actually, like when I got to
• 25:25
  Speaker 6: know that South Asia entirely like really struggling with sequencing capacity.
• 25:33
  Speaker 6: So I contacted my friend who was leading this only
• 25:38
  Speaker 6: lab in Sri Lanka capable of doing DNA sequencing. And
• 25:43
  Speaker 6: she was by then using a different technology, one of
• 25:45
  Speaker 6: our competitors. And they were spending $ 400 a sample. And
• 25:52
  Speaker 6: as a result, they could only do 100 samples a month.
• 25:57
  Speaker 6: with the available funds. Uh, so they were really struggling.
• 26:00
  Speaker 6: And then, uh, I talked to Gordon and we donated, uh,
• 26:04
  Speaker 6: one of our, uh, MINA and Mark 1C packages. Uh,
• 26:08
  Speaker 6: and then immediately they could do like 96 samples a day.
• 26:11
  Speaker 1: Wow.
• 26:12
  Speaker 6: Cost came down from 400 samples to, uh, $ 400 per
• 26:14
  Speaker 6: samples to $ 5 a sample. And more importantly, because it's
• 26:24
  Speaker 6: very easy to use this machine, our sample preparation is
• 26:27
  Speaker 6: quite short.
• 26:29
  Speaker 5: They could go home.
• 26:31
  Speaker 6: They said with the previous technology, when they come early morning,
• 26:35
  Speaker 6: they can't go home till midnight. So it was quite cumbersome.
• 26:39
  Speaker 1: So it was a complete game changer.
• 26:41
  Speaker 5: Complete game changer.
• 26:42
  Speaker 6: And then the government got to know that there is
• 26:45
  Speaker 6: this very easy method and they using WHO funding they
• 26:50
  Speaker 6: set up six labs. In Sri Lanka some of those
• 26:55
  Speaker 6: labs were in very rural hospitals and kind of makeshift
• 27:00
  Speaker 6: labs in a truck and they didn't have any, well
• 27:04
  Speaker 6: I went to see some of these labs and you
• 27:06
  Speaker 6: couldn't do anything else other than putting one of those
• 27:09
  Speaker 6: on this little space they had. So it was a
• 27:11
  Speaker 6: complete game changer and so within a couple of months
• 27:15
  Speaker 6: entire sri lanka was on um uh was on midline
• 27:19
  Speaker 6: and that was other like especially third world or low
• 27:23
  Speaker 6: and middle income countries um and 50 percent of uh
• 27:28
  Speaker 6: all covid sequencing was done in africa was done with
• 27:32
  Speaker 6: sequencing wow so that was quite uh quite something.
• 27:36
  Speaker 3: And so now that they have this capability and they
• 27:39
  Speaker 3: can do this high throughput sequencing, this is going to
• 27:43
  Speaker 3: help clearly with pandemic preparedness for the future.
• 27:46
  Speaker 5: Yeah, so that's a big thing now, right?
• 27:47
  Speaker 6: Like pandemic preparedness for the future is in every country
• 27:51
  Speaker 6: they are trying to do something. So people who have
• 27:53
  Speaker 6: this capacity, who have these devices already set up in
• 27:56
  Speaker 6: their countries, in their labs, and currently they are using
• 28:01
  Speaker 6: it for different things. But when the next pandemic hits,
• 28:06
  Speaker 6: so the system is there for them to.
• 28:08
  Speaker 2: Yes.
• 28:08
  Speaker 1: But presumably, Presumably not just pandemics. Presumably you can take
• 28:11
  Speaker 1: this into any hospital and you can work out what
• 28:15
  Speaker 1: illnesses individuals that people are suffering from.
• 28:17
  Speaker 4: Yeah. Well, I was at Guy's and St Thomas' this morning.
• 28:22
  Speaker 4: So before we touch on that, we sent 200 of
• 28:25
  Speaker 4: these sequences to Wuhan at the start of the pandemic.
• 28:29
  Speaker 4: There's a very important point to make. The equivalent incumbent
• 28:33
  Speaker 4: machine will cost you a quarter of a million dollars.
• 28:37
  Speaker 4: These we sell for $ 5, 000. So the important thing there
• 28:42
  Speaker 4: is when you think about disruption and tech revolutions, this
• 28:47
  Speaker 4: is the equivalent of moving from a mainframe computer, which
• 28:51
  Speaker 4: is the preserve of rich nations and large multimillion-dollar international businesses,
• 28:59
  Speaker 4: to a PC, affordable for everybody. And if we are
• 29:03
  Speaker 4: going to prevent the next pandemic and the fight in
• 29:06
  Speaker 4: the last pandemic, Everybody needs to have access. So part
• 29:11
  Speaker 4: of this revolution, because it is a tech revolution, is
• 29:16
  Speaker 4: the social impact of affordable, accessible democratization and access to DNA,
• 29:21
  Speaker 4: RNA information. Back to London. So at Guy's in St.
• 29:26
  Speaker 4: Thomas is what started out as a brilliant clinician, infectious
• 29:31
  Speaker 4: disease clinician, Professor Jonathan Edgeworth, looking at long COVID patients.
• 29:36
  Speaker 4: trying to understand what other co-infections they had. That trial
• 29:41
  Speaker 4: continued post-pandemic. And in the last three years, they have
• 29:45
  Speaker 4: been using this device in ICU to look at respiratory infections.
• 29:51
  Speaker 4: So they get a patient coming in with a respiratory
• 29:55
  Speaker 4: infection and they send a sputum down to the lab
• 30:00
  Speaker 4: In four to six hours versus 48 hours, two days,
• 30:05
  Speaker 4: they return a result. It takes three days in the
• 30:08
  Speaker 4: conventional method to say there are drug resistant strains, antimicrobial
• 30:13
  Speaker 4: resistant strains of pathogen. So a broad spectrum antibiotic will
• 30:17
  Speaker 4: not work. They do all of that in that four
• 30:20
  Speaker 4: to six hours. And then now we have precision infectious
• 30:24
  Speaker 4: disease management targeting the patient individually. and they demonstrated 45%
• 30:31
  Speaker 4: of patients were on the wrong antibiotic.
• 30:36
  Speaker 6: 45%?
• 30:36
  Speaker 5: 45%.
• 30:36
  Speaker 1: Wow.
• 30:37
  Speaker 4: Now, but there's an additional bonus. If and when you
• 30:42
  Speaker 4: see the next pandemic, you will see it emerging in
• 30:46
  Speaker 4: intensive care, the most vulnerable, and it's almost certainly going
• 30:51
  Speaker 4: to be a respiratory infection. And what you will see
• 30:55
  Speaker 4: is this new variant that we haven't seen before but
• 31:00
  Speaker 4: it will be there and it'll appear in Brighton and
• 31:02
  Speaker 4: it'll appear in Manchester and it'll start popping up everywhere.
• 31:06
  Speaker 4: And it's the same. And the difference here is instead
• 31:10
  Speaker 4: of doing what you do in conventional diagnostics, let's test
• 31:14
  Speaker 4: for pneumonia or let's test for E. coli or this
• 31:19
  Speaker 4: thing does a scan. It's called a metagenomic scan and
• 31:24
  Speaker 4: it pulls, the net pulls in everything and then you
• 31:28
  Speaker 4: can see everything in there. And then you can say, OK,
• 31:32
  Speaker 4: here's some drug resistance rates, here's co-infections, multiple infections. Here's
• 31:37
  Speaker 4: something new and novel. So you start to get this
• 31:40
  Speaker 4: additional benefit of clinical and biosecurity.
• 31:44
  Speaker 1: So when you set 20 years ago, when you set
• 31:47
  Speaker 1: up Oxford Nanopore, were these things you could see down
• 31:51
  Speaker 1: the pipeline or is this kind of. You know, you
• 31:55
  Speaker 1: could reinvent a bit of history now if you want.
• 31:57
  Speaker 1: You know, you said, yes, that's exactly what I wanted
• 31:59
  Speaker 1: to do. Or is it just have some of these
• 32:01
  Speaker 1: things come out?
• 32:01
  Speaker 4: I think the.
• 32:04
  Speaker 4: So this is my second spin-out. So I'd been involved
• 32:07
  Speaker 4: with the company that helped transform type 1 diabetics testing
• 32:12
  Speaker 4: at home, which is really important for blood glucose control
• 32:16
  Speaker 4: and insulin injection. But the electronic methods and the scalability
• 32:21
  Speaker 4: of that technology... The first thing I realised was we
• 32:24
  Speaker 4: could apply that here. So we didn't think too much
• 32:28
  Speaker 4: about applications. We thought about how can we take a
• 32:33
  Speaker 4: brilliant academic experiment that is limited, complicated, in a laboratory
• 32:40
  Speaker 4: with four PhD students running it into a ubiquitous device
• 32:44
  Speaker 4: that anybody could use. And that was the first five years.
• 32:47
  Speaker 4: But we always, always knew, and we always had an
• 32:50
  Speaker 4: eye on the fact that Rapid Insight's in infectious disease,
• 32:55
  Speaker 4: in critical care, near the patient would be something that
• 32:58
  Speaker 4: would be huge. And so we always kind of knew
• 33:01
  Speaker 4: that would come first and it pretty much is our
• 33:04
  Speaker 4: most advanced commercial application.
• 33:08
  Speaker 1: Everyone wants to talk at once.
• 33:10
  Speaker 2: I know.
• 33:11
  Speaker 6: Taking it to a different level, like I think NASA
• 33:14
  Speaker 6: took this to International Space Station to sequence in space.
• 33:16
  Speaker 6: So that was the first sequencing done in space to
• 33:20
  Speaker 6: see what's out there, or even to monitor the health
• 33:24
  Speaker 6: of astronauts.
• 33:25
  Speaker 2: So that's wonderful.
• 33:27
  Speaker 3: And I think sort of from what Gordon was saying
• 33:31
  Speaker 3: and what you're saying, this idea of this being an
• 33:32
  Speaker 3: academic experiment with four PhD students brings me sort of
• 33:37
  Speaker 3: into the idea that I realized that we haven't actually
• 33:39
  Speaker 3: touched upon what the technology is. So maybe you can
• 33:42
  Speaker 3: tell us how, you know, how does it work? So
• 33:45
  Speaker 3: we know it's a nanopore, but what does that mean?
• 33:47
  Speaker 6: So in the technology, so we have what we call
• 33:52
  Speaker 6: flow cell, which is a chip. So in this chip,
• 33:55
  Speaker 6: we have a membrane. So the membrane is quite stable.
• 33:58
  Speaker 6: We kind of, rather than using, in body you have
• 34:03
  Speaker 6: like natural, every cell has a natural lipid membrane, which
• 34:06
  Speaker 6: is quite unstable. And that's what we use in all
• 34:09
  Speaker 6: the academic experiments. If you go like closer to this
• 34:13
  Speaker 6: uh the complicated setups and bilayer breaks is that unstable
• 34:18
  Speaker 6: so we had to make it very stable enough so
• 34:21
  Speaker 6: that we can send around the world ship these things
• 34:24
  Speaker 6: to all the countries so we build the uh the
• 34:27
  Speaker 6: membrane uh synthetically uh which is very stable.
• 34:30
  Speaker 2: So the job of the membrane is to separate separate.
• 34:34
  Speaker 6: Things yeah to separate things so like uh And then
• 34:37
  Speaker 6: we put a biological nanopore on this membrane, which it
• 34:42
  Speaker 6: basically punch a hole in the membrane, a single hole,
• 34:45
  Speaker 6: very tiny nanometer level holes. And then we pass the
• 34:51
  Speaker 6: DNA and RNA through this nanopore. So DNA and RNA
• 34:56
  Speaker 6: are both negatively charged. So electrochemistry 111, if you have
• 35:00
  Speaker 6: like a positive charge underneath, then you can pull the
• 35:03
  Speaker 6: negative charge molecule. So that's what we do. So underneath
• 35:06
  Speaker 6: this membrane, we applied positive voltage. So the DNA and
• 35:10
  Speaker 6: RNA goes through this tiny little hole.
• 35:13
  Speaker 3: So the negative is attracted to the positive and can
• 35:16
  Speaker 3: come through the hole. And if the hole wasn't there,
• 35:19
  Speaker 3: the membrane is impermeable.
• 35:21
  Speaker 2: So we have the hole.
• 35:22
  Speaker 5: That's the force.
• 35:23
  Speaker 6: And then if you don't have the DNA and RNA,
• 35:27
  Speaker 6: so the current is going through this pore. The level
• 35:32
  Speaker 6: of the current is what we call open pore current.
• 35:35
  Speaker 6: And then it's equivalent to like, for example, if you
• 35:38
  Speaker 6: imagine a water flowing through a hose pipe. So water
• 35:43
  Speaker 6: goes through a steady state level. And then when something
• 35:47
  Speaker 6: blocks the hose pipe and then it blocks the water flow. Similarly,
• 35:51
  Speaker 6: the current passing through this tiny hole or the nanopore
• 35:56
  Speaker 6: blocks when the DNA and RNA is passing through the nanopore.
• 36:00
  Speaker 2: So that current is carried by ions.
• 36:02
  Speaker 4: Yes, correct.
• 36:04
  Speaker 1: Yeah.
• 36:04
  Speaker 6: So based on the composition of the basis ATCG of
• 36:08
  Speaker 6: the DNA or RNA, this current level changes based on
• 36:12
  Speaker 6: the blockage of the current.
• 36:14
  Speaker 1: So ions are charged atoms.
• 36:17
  Speaker 3: Yes, if we take normal table salts, as you know,
• 36:19
  Speaker 3: it's made of sodium and chloride. The sodium is positive,
• 36:22
  Speaker 3: the chloride is negative. So under this setup, the sodium
• 36:27
  Speaker 3: ions would move in one direction, the chloride ions would
• 36:30
  Speaker 3: move in one direction, you detect the current.
• 36:32
  Speaker 2: But because the.
• 36:33
  Speaker 3: DNA is also negative, it will move in the same
• 36:35
  Speaker 3: direction as the chloride ions.
• 36:37
  Speaker 1: But so you've got, okay, I'm a bit confused. You're
• 36:40
  Speaker 1: pulling through, you're basically using electric charge to pull through
• 36:45
  Speaker 1: a strand, strands of DNA or RNA that can be,
• 36:51
  Speaker 1: you know, 3.5 billion base pairs long. It must take forever.
• 36:57
  Speaker 6: Yeah, so we run this actually quite fast. So we
• 37:01
  Speaker 6: also control the speed using a biological motor on top
• 37:06
  Speaker 6: of this hole. So if we don't have this motor,
• 37:10
  Speaker 6: it will pass through like hundreds of thousands of bases
• 37:13
  Speaker 6: a second. So currently, then you don't get the high
• 37:18
  Speaker 6: enough resolution. So the accuracy will go down. So we
• 37:22
  Speaker 6: control the movement of the DNA and RNA through this motor.
• 37:25
  Speaker 6: So currently we use about like 400 bases a second speed.
• 37:33
  Speaker 6: So we can run any time that you want to.
• 37:36
  Speaker 6: I mean, until the experiment is done, you can run
• 37:39
  Speaker 6: this device. So we typically, to do the human genome,
• 37:46
  Speaker 6: we kind of advise a 72-hour run. And within that,
• 37:53
  Speaker 6: you can get enough information.
• 37:54
  Speaker 5: And it's heavily... information reach.
• 37:57
  Speaker 6: So we get this current blockage signal and then using
• 38:00
  Speaker 6: our AI machine learning tools, we convert this current blockage
• 38:05
  Speaker 6: signal to decode the DNA.
• 38:08
  Speaker 3: So have I understood this correctly? So basically you're saying
• 38:12
  Speaker 3: that you have a nanopore, which is made of a protein.
• 38:16
  Speaker 3: And then on top of that protein is another protein,
• 38:18
  Speaker 3: which is the motor.
• 38:20
  Speaker 1: Yes.
• 38:20
  Speaker 3: And then the DNA comes through, the motor helps to
• 38:23
  Speaker 3: slow it down somewhat as it goes through the pore.
• 38:26
  Speaker 3: Because if it goes through at normal speed, it's so
• 38:29
  Speaker 3: fast that by the time it goes through where the
• 38:31
  Speaker 3: sequence is read, because the differences in the current are
• 38:35
  Speaker 3: quite small between A, T, C, and G, we could
• 38:37
  Speaker 3: get mixed up and we can make mistakes in the readout.
• 38:41
  Speaker 1: Absolutely.
• 38:41
  Speaker 3: Is that right?
• 38:42
  Speaker 4: Yes.
• 38:43
  Speaker 1: And you said earlier for the COVID virus, you don't
• 38:48
  Speaker 1: have $ 5 a sample, I think, or £ 5 a sample.
• 38:52
  Speaker 1: A human genome, how much would that cost these days?
• 38:55
  Speaker 4: So let's go back 20 years when the first human
• 39:00
  Speaker 4: genome was mapped. It cost $ 3 billion. And it took
• 39:04
  Speaker 4: 10 years. And it was a worldwide consortium. In the
• 39:08
  Speaker 4: last 20 years, even with the decentralized machines, and a
• 39:14
  Speaker 4: lot of the academic research that we leveraged, came from
• 39:17
  Speaker 4: something called the $ 1, 000 genome. And that barrier was breached
• 39:22
  Speaker 4: in about 2012 to 2014. So we went from 3 billion.
• 39:27
  Speaker 1: 3 billion to 1,000.
• 39:29
  Speaker 4: And at that point, the technology was outstripping Moore's law.
• 39:32
  Speaker 1: Yeah, wow.
• 39:33
  Speaker 4: It was moving faster. So you have this real technology explosion.
• 39:37
  Speaker 4: And today, we can do a fully comprehensive genome for $ 600,
• 39:44
  Speaker 4: $ 400 to $ 600. And that has everything in it.
• 39:46
  Speaker 1: And so.
• 39:50
  Speaker 4: That kind of is, you know, people now are looking
• 39:54
  Speaker 4: at rare disease. So these children growing into adults can
• 40:00
  Speaker 4: be on a five or ten year diagnostic odyssey where
• 40:04
  Speaker 4: they're trying battery after battery of tests. You can do
• 40:08
  Speaker 4: a whole human genome and you can find these multiple
• 40:13
  Speaker 4: modes of genetic aberrations that cause the disease in these
• 40:18
  Speaker 4: rare disease people. It doesn't necessarily mean you can solve them.
• 40:21
  Speaker 4: Sometimes there can be some quick fixes. Just a diet
• 40:25
  Speaker 4: change can change quite dramatically. But what we're doing now
• 40:29
  Speaker 4: is building the atlas of rare disease. And as we
• 40:32
  Speaker 4: understand that better, that's something that pharmaceutical companies and drug
• 40:36
  Speaker 4: researchers can really get at. So yeah, it's affordable, it's accessible,
• 40:43
  Speaker 4: and it's becoming global.
• 40:45
  Speaker 1: So what, I mean, it's a fantastic story. And clearly it's...
• 40:50
  Speaker 1: You know, it's already revolutionising diagnoses, you know, and as
• 40:54
  Speaker 1: you say, you're beginning this journey. It's a bit of
• 40:57
  Speaker 1: technology that, you know, we hear about as scientists, but,
• 41:01
  Speaker 1: you know, more and more people are going to be
• 41:02
  Speaker 1: discovering this in their everyday lives going forward by the
• 41:04
  Speaker 1: sound of it. So many congratulations on that for the company.
• 41:09
  Speaker 1: What next? Where do you go next? I mean, you've
• 41:10
  Speaker 1: solved it all, haven't you?
• 41:11
  Speaker 2: You've been out to space. You've been out to hospitals
• 41:14
  Speaker 2: all around the world.
• 41:15
  Speaker 1: I think, well.
• 41:19
  Speaker 4: So we, another thing, it's more about this, you know,
• 41:24
  Speaker 4: this country creates phenomenal academic excellence. It creates phenomenal innovation.
• 41:32
  Speaker 4: And I was involved with a company called Medisense that
• 41:34
  Speaker 4: was sold to the Americans in the foothills of commercialization.
• 41:38
  Speaker 4: And we vowed to try and become a British tech,
• 41:41
  Speaker 4: global tech player out of London. So we floated three
• 41:45
  Speaker 4: years ago. At that point, I was asked if I
• 41:47
  Speaker 4: was going to retire and head for the hills. I said,
• 41:50
  Speaker 4: no way. This is just the beginning of what we
• 41:52
  Speaker 4: can do. And the use cases, not just as we've
• 41:57
  Speaker 4: talked a lot about clinical applications, but in environmental, in
• 42:01
  Speaker 4: food safety, in pandemic preparedness, in biosecurity, we're just at
• 42:07
  Speaker 4: the tip of the iceberg. And the opportunities are phenomenal.
• 42:14
  Speaker 4: And I do want to share one. with you and
• 42:17
  Speaker 4: that is today there are something like 18,000 children with
• 42:22
  Speaker 4: brain tumours. It takes four to six weeks to diagnose them.
• 42:27
  Speaker 4: All the samples go off to a lab in the
• 42:30
  Speaker 4: southeast of England. Somebody at the University of Nottingham pioneered
• 42:35
  Speaker 4: a workflow where they want to go in and interrogate
• 42:41
  Speaker 4: the tumour. It's a routine practice. before they decide on
• 42:45
  Speaker 4: treatment so you do the biopsy so they take a
• 42:48
  Speaker 4: biopsy and in two hours it gives them a guide
• 42:54
  Speaker 4: on which way to direct their treatment do they want
• 42:56
  Speaker 4: to cut it out do they want to do chemo
• 43:00
  Speaker 4: do they want to do something different that interoperative tumor
• 43:04
  Speaker 4: profiling using what i talked about earlier methylation to c
• 43:11
  Speaker 4: base so this is characterization of cancer with this chemically
• 43:17
  Speaker 4: corrupted sea base to tell you what type of cancer
• 43:20
  Speaker 4: it is. And that's just the start. We see a
• 43:24
  Speaker 4: breakthrough like that every single week. And, you know, people
• 43:26
  Speaker 4: always say, what gets you out of bed? Why are
• 43:28
  Speaker 4: you still doing this after 20 years? Because you go
• 43:31
  Speaker 4: to work every day. The clinicians I met at Guy's
• 43:33
  Speaker 4: and St Thomas' this morning, they are just so energising.
• 43:39
  Speaker 4: They're so excited about the disruption and the change it
• 43:44
  Speaker 4: will bring in treatment for them and seeing that right
• 43:47
  Speaker 4: up front and close and personal is so invigorating.
• 43:53
  Speaker 6: Sorry, also going forward, the platform that we have developed
• 43:56
  Speaker 6: is very modular, so we can easily take this biological
• 44:00
  Speaker 6: nanopore for DNA out and put a new pore in
• 44:04
  Speaker 6: for RNA or put a new pore in for proteins
• 44:08
  Speaker 6: or put a new pore in for like metabolomics without
• 44:11
  Speaker 6: having to redesign the entire system. So as a result,
• 44:14
  Speaker 6: we are now like, I think the genomics field is, um, uh,
• 44:19
  Speaker 6: advancing to include more, uh, multi-omics approaches, which means like, uh,
• 44:25
  Speaker 6: you get information from DNA, RNA, and the next thing
• 44:28
  Speaker 6: is what actually the DNA, RNA changes do in the body.
• 44:33
  Speaker 6: So then you need to analyze proteins. Uh, so we
• 44:36
  Speaker 6: can now, we are now working on proteomics to, uh,
• 44:39
  Speaker 6: so you can hopefully very soon you can, uh, read
• 44:44
  Speaker 6: protein molecules through this tiny force in our system. And
• 44:48
  Speaker 6: that will give another layer of information to add into
• 44:51
  Speaker 6: DNA and RNA.
• 44:52
  Speaker 1: So do you need to unwind? Do you need to...
• 44:55
  Speaker 1: break down the structure of the protein to create the
• 44:58
  Speaker 1: string of amino acids or can you read the whole
• 45:00
  Speaker 1: protein going through?
• 45:01
  Speaker 6: We can do I mean there are a few methods
• 45:03
  Speaker 6: that we are developing at the moment in one method
• 45:06
  Speaker 6: we do pass the entire polypeptide through the nanopore but
• 45:11
  Speaker 6: in one method we chop the peptide into small pieces
• 45:14
  Speaker 6: and then try to detect these pieces so that we
• 45:19
  Speaker 6: can correctly call the protein identity.
• 45:24
  Speaker 1: It's a really inspiring story. I mean, and congratulations. And
• 45:27
  Speaker 1: it's also fantastic that, you know, this is, as you say,
• 45:30
  Speaker 1: this is a British tech company and it's going to
• 45:32
  Speaker 1: remain British. There are a lot of scientists out there,
• 45:35
  Speaker 1: young scientists who are starting their careers. What advice, you know,
• 45:39
  Speaker 1: who will come up with some great ideas that, you know,
• 45:43
  Speaker 1: potentially have the opportunity to have major impacts on the world,
• 45:47
  Speaker 1: much as you have done. What advice would you give
• 45:49
  Speaker 1: them having set up two successful companies?
• 45:53
  Speaker 4: I think I get asked this a lot.
• 45:58
  Speaker 1: Sorry.
• 45:58
  Speaker 4: I think you have to be so, you know, I
• 46:02
  Speaker 4: still sometimes look back and think, how did I have
• 46:07
  Speaker 4: that much self-belief? But somehow you just, in the moment,
• 46:13
  Speaker 4: failure is not an option. It's just not an option.
• 46:17
  Speaker 4: And all we ever said about ourselves was we're a
• 46:19
  Speaker 4: big company. We're just temporarily small.
• 46:24
  Speaker 1: So you're the chief scientific officer, aren't you? So why
• 46:31
  Speaker 1: did you get up in the morning?
• 46:33
  Speaker 5: Well, for me, I think.
• 46:36
  Speaker 6: I'm hugely passionate about what we can do, especially in
• 46:39
  Speaker 6: like low and middle income countries. And also the potential
• 46:43
  Speaker 6: of this technology is enormous. And as Gordon said, like
• 46:47
  Speaker 6: at the beginning of the company, like for five years,
• 46:49
  Speaker 6: nothing was really working, but we never, never gave up.
• 46:53
  Speaker 6: we kept going. And then also like at the right moment,
• 46:56
  Speaker 6: we changed the technology. So we were very agile and
• 47:00
  Speaker 6: that got us where we are. And even now, like
• 47:03
  Speaker 6: we are a very agile company. So we are at
• 47:06
  Speaker 6: the right time. We do things differently. And there is like,
• 47:10
  Speaker 6: especially to get into proteomics and metabolomics, there is so
• 47:14
  Speaker 6: much to do. There's a mountain to climb. And that's what,
• 47:17
  Speaker 6: I mean, keep me up all night. Because the opportunities,
• 47:26
  Speaker 6: and I can see how it changed the RNA world,
• 47:30
  Speaker 6: and I could see that how can it change the
• 47:33
  Speaker 6: proteomics world as well. And then together, it's kind of
• 47:38
  Speaker 6: like very, very powerful. Imagine you go to a GP's office,
• 47:41
  Speaker 6: and when you talk to the doctor, by that time,
• 47:45
  Speaker 6: you have your diagnosis, like whether you are infected with
• 47:49
  Speaker 6: the viral or bacteria and what antibiotics you should take
• 47:51
  Speaker 6: and if you can take it to the next level
• 47:54
  Speaker 6: to analyze proteins that's huge and we can do that
• 47:57
  Speaker 6: we are the only company can do all that in
• 48:00
  Speaker 6: one platform.
• 48:01
  Speaker 1: That seems like a good enough reason to get out
• 48:03
  Speaker 1: of bed to me.
• 48:04
  Speaker 3: And you certainly were small as a group of people
• 48:07
  Speaker 3: when i first met you and honestly it's uh just
• 48:10
  Speaker 3: hearing the the stories you're telling and also i think
• 48:14
  Speaker 3: just seeing in your eyes the personal clearly satisfaction you
• 48:17
  Speaker 3: get from talking to clinicians for me is uh well
• 48:19
  Speaker 3: it's made my week really it's been really really nice
• 48:23
  Speaker 3: we're we're
• 48:23
  Speaker 1: Very privileged to have you come on and chat to
• 48:26
  Speaker 1: us so thanks for taking the time to do that
• 48:27
  Speaker 1: really appreciate it