Speaker 1: Brought to you by Toyota. Let's go places. Welcome to
Speaker 1: Forward Thinking. Hey there, and welcome to Forward Thinking, the
Speaker 1: podcast that looks at the future and says, carry on
Speaker 1: my wayward son. I'm Jovin Strickland, I'm Lauren Bocubon, and
Speaker 1: I'm Joe McCormick. And we wanted to kind of talk
Speaker 1: about genes and genetics and d n A and chromosomes.
Speaker 1: And it's because we have this whole podcast where we're
Speaker 1: going to be talking about gene therapy coming up. But
Speaker 1: really to understand gene therapy, we kind of need to
Speaker 1: lay that foundation first, so a little bit. And yeah,
Speaker 1: so for those of you, those of you who who
Speaker 1: have been out of middle school science for quite some time,
Speaker 1: like me, might need a refresher course, or maybe you
Speaker 1: never really studied this. For those of you who have
Speaker 1: a significant grounding in this, either educationally or perhaps professionally,
Speaker 1: just humor us because we wanted to make sure that
Speaker 1: we define in some terms and understood things before we
Speaker 1: launched into a full gene therapy discussion. Come on, that
Speaker 1: makes it sound a little dry and sterile. We're we're
Speaker 1: about to talk about some really huge molecules. I mean,
Speaker 1: I mean big, big molecules, Yes, big enough where if
Speaker 1: they weren't so darn thin, you would be able to
Speaker 1: see them with the naked eye once they are unfurled,
Speaker 1: because DNA molecules could be a couple of centimeters long,
Speaker 1: depending upon what you harvested them from. Ye, but they're
Speaker 1: very very thin, so they wouldn't see them anyway. But
Speaker 1: they're quite long. Um. So, early days of modern biology,
Speaker 1: you had scientists looking at cells through microscopes, and uh,
Speaker 1: normally you wouldn't be able to see things like chromosomes
Speaker 1: within the nucleus of a cell except during cellular division,
Speaker 1: because at that point the chromosomes kind of get all
Speaker 1: compact and they get dark enough where you can see them.
Speaker 1: So that led people to think. Specifically, scientists think, huh,
Speaker 1: I wonder what that stuff is around around What part
Speaker 1: of the timeline was this did you, oh, gosh, this
Speaker 1: would be in the nineteen well, nineteen thirties and forties really,
Speaker 1: But if you want to talk about the actual evolution
Speaker 1: of of of genes and heredity and this sort of
Speaker 1: these sort of concepts, you actually have to go back
Speaker 1: quite some ways to the mid nineteenth century. Actually this
Speaker 1: is interesting and a lot of people don't even know this.
Speaker 1: Charles Darwin didn't know anything about jenes no, well maybe
Speaker 1: sort of as a concept like the idea of inherited traits,
Speaker 1: but didn't know anything about d n A. Right, he
Speaker 1: had this practical evidence that that he was being presented
Speaker 1: with and that he was thinking about really hard. But
Speaker 1: but they had no way of knowing what the discreet
Speaker 1: element of transferral of traits actually was. And in fact,
Speaker 1: there there were other people working on learning about, you know,
Speaker 1: how traits are passed down at the same time, at
Speaker 1: the same time, and they didn't. They didn't they didn't
Speaker 1: match up. In fact, the first one really Gregor Mendel,
Speaker 1: who was an Austrian monk, and uh he decided that
Speaker 1: he was going to investigate how traits were passed down
Speaker 1: by using hybridized p plants, and he wanted to just see,
Speaker 1: you know what determines how certain traits get passed down.
Speaker 1: And a lot of experiments in these early days would
Speaker 1: only last a few months, maybe a year, and so
Speaker 1: you would only have a certain number of generations of
Speaker 1: plants to work with. And the general thinking at that
Speaker 1: time was that you would get these unusual traits that
Speaker 1: would pop up in plants, but that the hybrids would
Speaker 1: eventually revert back to the original form of the plant
Speaker 1: several generations down the line, like like it would just
Speaker 1: be a little side step, but then it would re
Speaker 1: orient itself. That well, Gregor Mendel decided to kind of
Speaker 1: really look at this, and over the course of about
Speaker 1: eight years and thousands and thousands of plants, he discovered
Speaker 1: that there were some interesting things going on, that that
Speaker 1: there were different types of traits that were being passed on,
Speaker 1: and actually started to lay the groundwork for things like
Speaker 1: dominant traits versus recessive traits, things that you know, if
Speaker 1: if a p plant had once certain type of trait
Speaker 1: that was more likely to be passed down than other ones.
Speaker 1: And he really started to put all this together, but
Speaker 1: no one really gave it much thought, including including himself.
Speaker 1: He thought that this was an interesting thing, but didn't
Speaker 1: apply it to a wider range of life forms beyond
Speaker 1: pe plants. Well, he didn't know about DNA either. No, No,
Speaker 1: this is men daily in genetics. So again it's just
Speaker 1: based on um sort of phenotypical markers that show up
Speaker 1: things you can see with the naked eye parent physical traits.
Speaker 1: So he he did, he did figure out the or
Speaker 1: he did lay the groundwork for pre dominant traits versus
Speaker 1: recessive traits. And he also figured out that the traits
Speaker 1: were not necessarily dependent upon one another, right, they were independent.
Speaker 1: A lot of traits just had one set of traits
Speaker 1: and another set of traits didn't necessarily have to be
Speaker 1: present for the next generation to start to exhibit them.
Speaker 1: So that was also interesting. Uh. In eighteen sixty nine,
Speaker 1: that's when Friedrich Mischer, who was a German chemist, was
Speaker 1: the first person to isolate DNA from cell nuclei that's
Speaker 1: where you would find DNA generally speaking, And uh, he
Speaker 1: wasn't sure what the heck it was, this this sort
Speaker 1: of white, acidic substance, and no one was really sure
Speaker 1: if it even had a purpose. In fact, for for
Speaker 1: years they just sort of discounted it as just like
Speaker 1: this is just something that's in cells, but it doesn't
Speaker 1: do anything important, and uh, but it's understanding. There was
Speaker 1: no way from him to know really. Inties and forties,
Speaker 1: that's when you had scientists really looking at it and
Speaker 1: trying to figure out exactly what this stuff was. What
Speaker 1: was important about it. They began to learn that DNA
Speaker 1: was made up of a five sided sugar uh, and
Speaker 1: that it also had these base pairings of well, they
Speaker 1: didn't even know what it was pairings at the time.
Speaker 1: They knew that there were these other polynucleotides inside DNA,
Speaker 1: they didn't know the significance of it. And they also
Speaker 1: knew that DNA had a protein involved with it. The
Speaker 1: protein is the scaffolding that DNA wraps itself around, but
Speaker 1: they didn't they weren't sure what significance any of that was.
Speaker 1: To take get to about nineteen fifty, that's when a
Speaker 1: check scientist named Irvin Cargoff discovered the base composition of
Speaker 1: DNA and measured the amount of the four nucleotides you
Speaker 1: can find in DNA. And I'll cover that in a minute.
Speaker 1: And he also noticed that something interesting that you know,
Speaker 1: the four nucleotides, we generally call them A, T, C,
Speaker 1: and G for their names. And again I'll go through
Speaker 1: the names when I can get my tongue around them.
Speaker 1: Can I try? Can I try go for it? Okay,
Speaker 1: it's uh oh manin, thiamine, adeni ad and id ad
Speaker 1: anine and oh guanne Okay, so how close was I
Speaker 1: think I was messing up some idine thymine citazine gun
Speaker 1: And then if you're going with RNA, which of course
Speaker 1: is the other component we have to talk about eventually, Uh,
Speaker 1: arny doesn't have thymine, but it does have ur a
Speaker 1: cell and your cell ends up acting pairing, pairing with
Speaker 1: at an in the same way thyman does. So it's
Speaker 1: you don't have you're really uh, consult your physician. No,
Speaker 1: your cell it fulfills that same purpose because what happens
Speaker 1: is these these based nucleotides pair with one another. Now,
Speaker 1: at this point in nineteen fifty, they didn't know anything
Speaker 1: about pairing. What Chargov saw was that if you looked
Speaker 1: at the ending and the thyming nucleotides, they were roughly
Speaker 1: equivalent to each other. And the same was true for
Speaker 1: the site of zine and guani nucleotides. Those were equivalent
Speaker 1: to one another. And so this, uh, this gave rise
Speaker 1: to what is now known as Chargovs rules, which was
Speaker 1: just that if you find a certain amount of one,
Speaker 1: then you know that that's the same amount for the
Speaker 1: other one. And it also laid the groundwork for later
Speaker 1: scientists to kind of figure out about this nucleotide pairing
Speaker 1: that the reason why there are equal amounts is because
Speaker 1: they pair up in a strand of DNA. So that
Speaker 1: takes us up to that. Nineteen fifty two, that's when
Speaker 1: Alfred Hershey and Martha Chase really uh they got behind
Speaker 1: the idea that it was DNA that carried genetic information,
Speaker 1: that it carried this hereditary information, rather than the protein
Speaker 1: scaffolding that the DNA was wrapped around, because at the
Speaker 1: time no one was really sure and there were some
Speaker 1: people who were saying, it's the protein that carries the
Speaker 1: hereditary information, not the DNA molecule. And uh so they decided,
Speaker 1: should we sort that out? Now? Are we getting to that.
Speaker 1: We'll get to it. We'll get to never you fear
Speaker 1: trust in Jonathan, Yes, but but trust in specific instant.
Speaker 1: There's a lot of molecules in here, all right, all right,
Speaker 1: to be fair, all right, So the protein is the
Speaker 1: scaffolding that the DNA wraps itself around. Okay, so, and
Speaker 1: DNA itself at least is in the business of making proteins. Yes, yes,
Speaker 1: so it makes proteins. What technically, what does is really
Speaker 1: gives the instructions for amino acids. Which amino acids are
Speaker 1: the building blocks for proteins. But I'll get there, trust
Speaker 1: me anyway. So, uh, they weren't sure whether or not
Speaker 1: it was the protein element or the DNA element that
Speaker 1: actually passed down U hereditary information. And so they Hershey
Speaker 1: and Chase, who thought it was DNA, decided they would
Speaker 1: do an experiment, and so I think there was. They
Speaker 1: got some They got some DNA and they from a
Speaker 1: bacterial virus called T two. Actually, uh, it would raise
Speaker 1: its thumb as it was lowered into lava. Uh. The
Speaker 1: T two virus, Actually it has a shred of it's
Speaker 1: it's a virus that has a shred of DNA inside
Speaker 1: and a little tiny piece of protein inside it as well.
Speaker 1: So what Chase and her She did or hers Chase
Speaker 1: because it's usually called Hershey Chase experiment. They ended up
Speaker 1: inserting a radioactive tag in the DNA of this virus
Speaker 1: and then allowed the virus to go ahead and do
Speaker 1: its a little viral thing where it would go and
Speaker 1: replicate replicate itself. And then they noticed that all the
Speaker 1: viruses that were replicated also were radioactive. They had this
Speaker 1: radioactive tag. They repeated the experiment by tagging the protein
Speaker 1: with this radioactive tag and did the same thing and
Speaker 1: saw that the the next generation of viruses did not
Speaker 1: have the radioactive tag. Uh huh. They say, this shows
Speaker 1: that the DNA is what's passing down this hereditary information,
Speaker 1: not the protein. So bite me, although they said in
Speaker 1: a much nicer way scientific yes, that was probably whatever
Speaker 1: the latin is for biting me, right, it's it's pure viewed.
Speaker 1: So that brings us to nineteen fifty three, and this
Speaker 1: is when the probably the most famous of the discoveries,
Speaker 1: um you could argue for for the whole history of
Speaker 1: DNA and jeans it comes about. And that's when the
Speaker 1: actual molecular structure of DNA was discovered. The soul Watson, Crick, Franklin,
Speaker 1: and Wilkins. Yes, James Watson and Francis Crick are the
Speaker 1: one to who are normally credited. It's Watson and Crick.
Speaker 1: You always hear Watson and Crick, but they their work
Speaker 1: was made possible by the work of two other scientists,
Speaker 1: Rosalind Franklin and Maurice Wilkins, who all had been working
Speaker 1: on this And without the work of Wilkins and Uh
Speaker 1: and Franklin, you wouldn't have had the information Watson Krick
Speaker 1: wouldn't have had the information they needed to learn the
Speaker 1: actual structure of DNA. UH. Franklin had been using X
Speaker 1: ray diffraction to observe living cells and it was that
Speaker 1: that gave them the ability to take a look at, uh,
Speaker 1: this double helix structure that DNA has, and they could
Speaker 1: tell that it was this double helix structure that would
Speaker 1: pull apart to make copies of itself during cellular division. UH.
Speaker 1: And then if you wanna, you know, the next big, big,
Speaker 1: big moment in genes, which will talk about more in
Speaker 1: another episode, it was the ninety seven which was the
Speaker 1: first sequencing of a complete genome, which was the bacteria
Speaker 1: fage f x one seven four. So, um, now we're
Speaker 1: going to talk a little bit about what these structures
Speaker 1: actually are and what you know, the define some more
Speaker 1: terms because there's a lot of confusion when it comes
Speaker 1: to DNA, genes, genome, chromosomes, and just kind of use
Speaker 1: them interchangeably, right, and and you know it helps to
Speaker 1: get get a little more precise. Okay, Well, one clear
Speaker 1: distinct shinn' make I think is that gene is sort
Speaker 1: of a classification where that we have whereas d N
Speaker 1: A as a molecule UM and what so the structure
Speaker 1: of DNA, we could talk about that for a little. Sure,
Speaker 1: it's like it's like you said, it's a double helix,
Speaker 1: so you'd have to imagine kind of a twisted ladder.
Speaker 1: Take a ladder and twist in a right handed or
Speaker 1: clockwise direction, and so correct me if I'm wrong. But
Speaker 1: I think I just I just realized for the first
Speaker 1: time that what the ladder is actually built of is
Speaker 1: that the sides of the ladder are basically just sugar molecules,
Speaker 1: and it's the wrongs of the ladder that contain the
Speaker 1: crucial genetic information. Those are the that's the nucleotide pairings. Yeah, so, yeah,
Speaker 1: you've got the and. And the reason why the nucleotide
Speaker 1: pairings have to be A and T and C and
Speaker 1: G is that if you tried to put up any
Speaker 1: other type of pairing, the wrongs would be the wrong
Speaker 1: width and you wouldn't have of a a stable structure anymore.
Speaker 1: The only way the wrungs are of the correct width
Speaker 1: so that this double helix structure can remain stable and
Speaker 1: remain intact is to have it paired up the way
Speaker 1: I said a t n C. And it's the only way. Uh.
Speaker 1: DNA of course stands for de oxyde de oxy ribonucleic acid.
Speaker 1: I knew I was going to mess that up before
Speaker 1: I could get through it once. But deoxy acid. Yeah,
Speaker 1: you know, you just had the benefit of hearing me
Speaker 1: say it twice. Mr Adenine thyming that one. So they
Speaker 1: the acid here has this, Uh, the base pairings they
Speaker 1: bond with hydrogen bonds the four nucleotides, right, And it's
Speaker 1: the sequence of bonds, the sequence of pairings that create
Speaker 1: genetic information. Uh. Not all of DNA is encoded genetic information.
Speaker 1: Some of it is behaving in a way that we
Speaker 1: don't fully understand yet. It's sometimes it's called junk DNA.
Speaker 1: Sometimes it's called non coded DNA. At any rate, it
Speaker 1: almost seems like it's, you know, gibberish. That's just there
Speaker 1: to break up the genetic coding. Now, when I say
Speaker 1: just there to break up, that's what I'm saying from
Speaker 1: a from an uninformed perspective, that's what it looks like.
Speaker 1: But we may learn in the future that it has
Speaker 1: a very specific purpose that we just don't know about yet. Right, Okay, Well,
Speaker 1: I think we don't hear the term junk DNA is
Speaker 1: often these we just don't know what, so we often
Speaker 1: call it noncoding because we we don't recognize it as
Speaker 1: coding for specific type of protein. So one, what what
Speaker 1: makes DNA so special is a molecule. What makes it
Speaker 1: not like any other molecule. There's a lot of things
Speaker 1: that make it not like any other molecule. For the fact,
Speaker 1: one thing is that this the sequence of bonds, can
Speaker 1: actually pass on actual information. These instructions for creating amino acids,
Speaker 1: which in turn create proteins, and the proteins are pretty
Speaker 1: much what tell your cells what to do and when
Speaker 1: they're what makes your body go. It's it's right, it's
Speaker 1: it's it's what makes you grow. What makes your your
Speaker 1: you know, body parts develop into the body parts that
Speaker 1: they are, rather than makes you be you is when
Speaker 1: it really comes down, it's the size of your brain pan.
Speaker 1: It's also the DNA is in most of our cellular nuclei,
Speaker 1: and so essentially the entire record of what makes you
Speaker 1: you is in every single nuclei of these cells. Did
Speaker 1: you know, though, that the nuclear nuclei aren't the only
Speaker 1: part of your cells that have DNA shut your mouth, Yeah, yeah,
Speaker 1: that's right, which you get from your mom and not
Speaker 1: from your dad at all. Really. Yeah, So you get
Speaker 1: your nucleic DNA that that comes from your mom and
Speaker 1: your dad, and that's in the nucleus of your cells
Speaker 1: and tells tells the rest of your body how to
Speaker 1: make itself and what to do. That comes from both parents,
Speaker 1: but just from your mom. You get mitochondrial DNA, and
Speaker 1: that's a separate little bit of DNA that lives in
Speaker 1: the mitochondria and the cells, and the mitochondria of a
Speaker 1: all is sort of like the power plant. Sure, yeah, yeah, exactly,
Speaker 1: And when you talk about genes, you're really talking about
Speaker 1: a specific strip of DNA. It's sort of a think
Speaker 1: of it like magnetic tape. For for if you're a
Speaker 1: computer storage kind of person. So this would be a
Speaker 1: length of magnetic tape upon which there are instructions, and
Speaker 1: then there would be noise between the instructions and the
Speaker 1: next set of instructions, which are for something totally different, right,
Speaker 1: some other some other process. Now, in this case, the
Speaker 1: process we're talking about, it's usually to create proteins through
Speaker 1: the production of amino acids UM. Now the other thing
Speaker 1: you can the other thing that's really important to remember
Speaker 1: that genes are like the fundamental unit of heredity. Okay,
Speaker 1: so that's sort of like you can think of a
Speaker 1: gene as the equivalent of an atom, but only when
Speaker 1: we're talking in terms of of heredity. So this is
Speaker 1: as small as it gets. Uh. The relationship between genes
Speaker 1: and traits is very complex. Uh. There our genes that
Speaker 1: can manifest in several different traits. Uh, and then there
Speaker 1: are some traits that require multiple genes to manifest, so
Speaker 1: it's not a one to one relationship at all. Right.
Speaker 1: One thing you can think of making a gene discrete
Speaker 1: is that a gene is sort of a section of
Speaker 1: information that can have different what are called alleles, and
Speaker 1: so that's a different variation on that set of information.
Speaker 1: And in a gene pool, there will be multiple alleles.
Speaker 1: So you can have one gene and then a different
Speaker 1: version of that gene, different version of that gene found
Speaker 1: in different individuals. All right. So a human gene is
Speaker 1: typically between twenty seven thousand and two million base pairs. Okay,
Speaker 1: so those nucleo tide pairings, that's how many are in
Speaker 1: a typical gene. Between twenty seven thousand, two million, which
Speaker 1: is a huge range. And it's also interesting to know
Speaker 1: that a thousand base pairs would technically be enough to
Speaker 1: encode most proteins. And that's what these genes are doing
Speaker 1: there for the most part, they're meant to encode proteins. Uh.
Speaker 1: And so it's interesting to think that the typical genes
Speaker 1: and the human seem to be really inefficient. And that's
Speaker 1: because there are large parts of genes that are not
Speaker 1: meant to encode, and they're they're also really complicated. Most
Speaker 1: of them make more than one protein the average is
Speaker 1: three actually, right and um and and they are not
Speaker 1: they're not really discrete units. They interact with each other
Speaker 1: in interesting ways, right and so so here's how they
Speaker 1: actually work. So cells make a copy of the gene
Speaker 1: through you know, they take the length of DNA where
Speaker 1: the genetic information is relevant. This whole process is called transcription.
Speaker 1: That copy ends up moving to another part of the
Speaker 1: cell where it's used to create a chain of protein
Speaker 1: subunits amino acids. That parts called translations. So transcription uses RNA,
Speaker 1: that's the copy that is created out of this RNA
Speaker 1: is made up of ribonucleotides, and so those bases U
Speaker 1: compliment the ones in DNA. But like we said earlier,
Speaker 1: there's no thymine, so they uses eurusil instead, which you
Speaker 1: and A buying together. So there's no real problem there. Uh. Now,
Speaker 1: the genes have protein coding sections called xns and non
Speaker 1: coding segments called in tron's. So the RNA section RNA
Speaker 1: sections that correspond to in trons, the non coding parts.
Speaker 1: Those parts get generally they get removed from the RNA.
Speaker 1: It's called splicing. It splices out. It's kind of just
Speaker 1: like you know you're splicing film. You take out the
Speaker 1: part you don't want, and then you merge the other
Speaker 1: two pieces together. So that way you just have the
Speaker 1: coding parts left, the xns in other words, and that
Speaker 1: becomes what is known as messenger RNA. Well, then you've
Speaker 1: got these other bits of RNA, uh, the the the
Speaker 1: transfer ribonucleic acid or t RNA. So you've got your
Speaker 1: messenger RNA, you got your transfer ribonucleic acid. Uh. You
Speaker 1: get the two of them together, and it's like a
Speaker 1: spaceship docking with a space station. So you look at
Speaker 1: these three base pair will not even base pair uh
Speaker 1: three exxons. So you code this by the three letters
Speaker 1: that they might be like g G G or it
Speaker 1: could be g U A or so anyway, you you
Speaker 1: get those those three codes, the appropriate t RNA will
Speaker 1: doc with that, and that gives the t RNA the
Speaker 1: instruction to make the amino acid whatever it's supposed to
Speaker 1: be according to the messenger RNA. So the messenger RNA
Speaker 1: is essentially the recipe. The t RNA all will only
Speaker 1: produce one specific amino acid, and it only will work
Speaker 1: if they can doc with that part of the m RNA.
Speaker 1: It'll build a protein based on all these amino acid chains.
Speaker 1: And uh, and that's the basis there. So you've got
Speaker 1: your amino acids and proteins. That gives the instructions for
Speaker 1: everything else that's going on. Really and uh, there's your
Speaker 1: there's your basic genes and how those genes work and
Speaker 1: how they replicate proteins. Now, let's talk about chromosomes. So
Speaker 1: we've we've got DNA. That's the molecule. We've got the genes.
Speaker 1: That's lengths on the molecule that give instructions for things
Speaker 1: like protein generation. Chromosomes are essentially packages of genes, all right,
Speaker 1: so life forms have chromosomes, they don't all have the
Speaker 1: same types of chromosomes or the same number of chromosomes. Uh.
Speaker 1: Humans have twenty three pairs of chromosomes, one pair of
Speaker 1: that sex chromosomes. So uh, that's different if you're female
Speaker 1: or male. Obviously for females too, X chromosomes. If you're male,
Speaker 1: it's an X and Y chromosome. Why because we like you.
Speaker 1: And then the rest of the chromosomes are all other types, right,
Speaker 1: And you've got these are the ones that uh, you
Speaker 1: have one pair you have inherited from your father, and
Speaker 1: one pair you've inherited from your one half of the
Speaker 1: pair I should say you've inherited from your mother. And
Speaker 1: so you've got these packages of genes. They are of
Speaker 1: different sizes. Uh, they have different types of genes in them.
Speaker 1: Things that would be important for very related elements in
Speaker 1: our lives, like things that might be uh important instructions
Speaker 1: for the production of one type of cell that's very
Speaker 1: similar to another type of cell could be found in
Speaker 1: totally different chromosomes. So it's not like, you know, it's
Speaker 1: not like you would go to a library and pick
Speaker 1: out a book and like everything. There's no decimal system
Speaker 1: new it's kind of all jumbled up, but it makes
Speaker 1: sense to biology it were, or sense in the sense
Speaker 1: that it works. And we're here. Yes, So that those
Speaker 1: are your basic definitions, right, You've got your DNA, your genes,
Speaker 1: your amino acids and proteins, you've got your chromosomes. Essentially
Speaker 1: the collection of all this information we call the genome
Speaker 1: for a specific life form, right, every every human genome,
Speaker 1: there's a mouse genome, there's an E. Coli genome exactly.
Speaker 1: So there we go. That's that's my I'm done, I've defined.
Speaker 1: I'm back in a way. Take over. Would you guys
Speaker 1: like to talk about the sequencing of the human genome please?
Speaker 1: That sounds wonderful, excellent. Let us do that pretty recent,
Speaker 1: wasn't it? That was extremely recent? That was that thing
Speaker 1: in two thousand three that I was talking about. Um
Speaker 1: the Human Genome Project was kicked off October one of
Speaker 1: ninet so basically after the Department of Energy helped create
Speaker 1: the atomic bomb. Um Us Congress said, hey, guys, this
Speaker 1: is some some wacky stuff that you have created, and
Speaker 1: we would really like you to apply some of this
Speaker 1: amazing scientific technology and know how that you have to
Speaker 1: figuring out how this horrific creation is screwing up our genetics. Um.
Speaker 1: And they technically said this to the Atomic Energy Commission
Speaker 1: and the Energy Research and Development Administration, which were the
Speaker 1: predecessors to the Department of Energy. But at any rate,
Speaker 1: the the what what became the Department of Energy got
Speaker 1: together with the National Institutes of Health and started the
Speaker 1: Human Genome Project, which was to sequence the entire human genome,
Speaker 1: which enormous, enormous tasks, which is a which is a
Speaker 1: big deal. I mean, at the time, they thought that
Speaker 1: there were a hundred and fifty thousand genes making up
Speaker 1: the genomes. As it turns out, like Jonathan said that
Speaker 1: it's more like so, human chromosomes range in size from
Speaker 1: fifty million to three hundred million base pairs, and in
Speaker 1: order to to sequence out the genome, you have to
Speaker 1: split that down um by a process that's called bacterial
Speaker 1: artificial chromosome UH sequencing into into smaller, smaller little bits
Speaker 1: of base pair information only hundred and fifty thousand base
Speaker 1: pairs a GOO. This was super complicated because, like I said,
Speaker 1: you know, we have identified genes and figured out what
Speaker 1: some genes do and what you know, what they're encoded
Speaker 1: to do, what kind of proteins there they make. But
Speaker 1: there's a lot of replicated information within human genes. There
Speaker 1: there are a whole segments that you look at, Like
Speaker 1: when I made that talk about the magnetic tape, it's
Speaker 1: as if like let's say that we're talking about magnet
Speaker 1: tape and it's an old cassette tape that has music
Speaker 1: on it. It would be like you're listening to an
Speaker 1: album and three songs after the first song, like, you
Speaker 1: listen the first song like that's pretty good. Three more
Speaker 1: songs go by, and then the first song comes on again,
Speaker 1: like why did they do it twice? The human gene
Speaker 1: genome is kind of filled with stuff like that, including
Speaker 1: stuff that we still call non coding DNA because we
Speaker 1: don't know if it actually is doing anything all right,
Speaker 1: So they had to they had to split up the
Speaker 1: total genome into these kind of workable fragments. They split
Speaker 1: it further than I just mentioned, know what's called subclones,
Speaker 1: and then let these bacteria replicate these little pieces of
Speaker 1: DNA and in a way that they can really get
Speaker 1: in and figure out what the pairs are doing and
Speaker 1: and and how everything fits together. So they wind up
Speaker 1: with a with A, B, A C library and and
Speaker 1: from that, you know, have have determined the sequences of
Speaker 1: the chemical base pairs that make up DNA and have
Speaker 1: put all of this information into databases for researchers to
Speaker 1: play around with. Yeah, it's also interesting to me that
Speaker 1: early on, when they were first identifying genes, it was
Speaker 1: at such a slow pace relatively speaking, that there were
Speaker 1: people who thought that it was going to take a
Speaker 1: century to map out the human genome. The projected timeline
Speaker 1: for the project was from two thousand and five. They
Speaker 1: completed it two years early in two thousand three, and
Speaker 1: um about point three billion under budget. So and that
Speaker 1: was so part of it is because they could not
Speaker 1: anticipate improvements in the processes. I mean, we we never can, right.
Speaker 1: We never think in ten years we'll be able to
Speaker 1: do this much more quickly because of X. We usually
Speaker 1: think in terms of what we're capable of doing right now,
Speaker 1: and that's how we project out how long it's going
Speaker 1: to take us. If we're lucky, then technology and science
Speaker 1: progresses at such a rate that the task becomes less overwhelming. Also,
Speaker 1: we learned that it wasn't as big a job as
Speaker 1: we as we original thought. Yeah, well it's um, you know,
Speaker 1: intracellular biology progressed and really dovetailed with the computer industry,
Speaker 1: and if we had not had the kind of developments
Speaker 1: and computers, then shortly we've taken Yeah, that's what I
Speaker 1: was just thinking of starting in the early nineties. I mean,
Speaker 1: think of how crappy computers were back then. But another
Speaker 1: interesting thing, mine still ran on a O L that's
Speaker 1: not how that so another wow, it was like a
Speaker 1: thousand people cried out in anguish. I'm imagining that they're
Speaker 1: doing the Human Genome project with like the desktop calculator
Speaker 1: application and Windows three point one. Well, you know what's
Speaker 1: also interesting is that this is not directly related to
Speaker 1: the Human Genome project, but it's it's a similar field. Uh.
Speaker 1: You know, I was talking about proteins earlier, these long
Speaker 1: chains of amino acids. One of the other interesting things
Speaker 1: about proteins is that they fold, and when they fold,
Speaker 1: that's what gives them certain features of property properties exactly,
Speaker 1: thank you. And we don't fully understand the folding process. Well,
Speaker 1: the folding is determined we think by the amino acid sequence, right,
Speaker 1: So it's it's a long chain and you can imagine
Speaker 1: that it's like a chain of letters in a particular sequence, right, um,
Speaker 1: and what order the letters come in determines the three
Speaker 1: dimensional shape that the protein twists up into. Right. And
Speaker 1: there's actually a really cool project called Folding at Home.
Speaker 1: Have you guys heard of this. Folding at Home is
Speaker 1: one of those distributed computing networks where, uh, you can
Speaker 1: participate in helping scientists determine what proteins will take, what shapes,
Speaker 1: why they do it, what kind of properties they have.
Speaker 1: It's really be useful for things like potential medical uses.
Speaker 1: So what happens is it's one of those that you
Speaker 1: sign up for this project, you install some software, and
Speaker 1: then your computer, when it's idle, is actually working on
Speaker 1: these various computer models of proteins, and as it solves
Speaker 1: these different models, it then sends that information back off
Speaker 1: to the centralized server which collects it and you know,
Speaker 1: vets everything that comes back in. Keep in mind, this
Speaker 1: is all automatic. You're not putting in any even put here,
Speaker 1: but it vets it all and then essentially puts it
Speaker 1: in a database. So that the body of knowledge about
Speaker 1: proteins and how they fold grows dramatically over time as
Speaker 1: more and more people joined this project. I love that
Speaker 1: kind of distributed simulation. Just that that's steady, right, But anyway,
Speaker 1: that's that's getting even further afield. So back to the
Speaker 1: human genome. So along with sequencing the human genome, the
Speaker 1: project led to UM a lot of other creatures genomes
Speaker 1: being sequenced UM like I said earlier, ecal um, mice,
Speaker 1: the fruit fly, stuff like that, UM to to help
Speaker 1: us start working in the larger gene field. And basically
Speaker 1: all of the research that's happening today and in gene
Speaker 1: therapy and in genetics is because of the research that
Speaker 1: was pioneered in the Human Genome project. I think that's
Speaker 1: really useful having the full genomic information about like fruit
Speaker 1: flies or icola. I mean, you can run so many
Speaker 1: generations of those organisms in the lab, which you can't
Speaker 1: do with humans and and probably can't even realistically do.
Speaker 1: And and usually the genomes are a lot shorter on
Speaker 1: on more simple organisms, which is interesting. It's not always
Speaker 1: the case because there are like like the number of
Speaker 1: genes you can find in certain creatures can be dramatically
Speaker 1: larger than that of UM, or dramatically more than what
Speaker 1: you would find in humans. It's the plexity doesn't necessarily translate.
Speaker 1: It does not and uh and it depends on I mean, like,
Speaker 1: for example, the platypus has ten sex chromosomes. Yeah, it does.
Speaker 1: I don't even know what that's for. Only platypus is no.
Speaker 1: They have a they have a don't ask, don't quack policy.
Speaker 1: Do they know? What do they do? They pretty much
Speaker 1: don't do anything. Have you not watched They don't do
Speaker 1: very much have some kind of crazy sex. Al Right, guys, guy,
Speaker 1: if you know what a platypus, if you know the
Speaker 1: platypus sounds like I want to hear it, let me
Speaker 1: let me know. Okay, all right, that's fair. So so
Speaker 1: the first person who can send us a sound of
Speaker 1: a platypus, when's Laurence applause? Yeah, okay. So we've mentioned
Speaker 1: some basic research in the abstract, but what can you
Speaker 1: actually do with genetic genetic information? Like, how do you
Speaker 1: apply it practically? Gosh, Joe, I don't know that was
Speaker 1: your segment. I was hoping you'd tell us. So one
Speaker 1: of the things we want to talk about was this
Speaker 1: idea of DNA matching, right, the idea of being able
Speaker 1: to to I mean, think about if you are able
Speaker 1: to understand your genetic information, if you're able to know
Speaker 1: that this sequence is something that was inherited, then that
Speaker 1: means that you can find links between you and other people.
Speaker 1: It means that it could be useful for things like
Speaker 1: a genealogy. It can be useful for things like paternity testing.
Speaker 1: It can be useful for things like someone left some
Speaker 1: blood behind at this crime scene. I wonder whose blood
Speaker 1: this is. There are a lot of different potentials. Yeah.
Speaker 1: So one of the interesting things I was thinking about
Speaker 1: was was paternity testing, and I wondered, how did they
Speaker 1: do this before they had genetic testing, and then furthermore,
Speaker 1: just how does it actually work? But it so, one
Speaker 1: of the things I found that I thought was interesting
Speaker 1: was before they had genetic paternity tests, they would often
Speaker 1: use blood type testing. Okay, that makes you know enough sense,
Speaker 1: I suppose. I mean, it's it's pretty inaccurate considering the
Speaker 1: number of humans that are out there with similar blood types. Yeah,
Speaker 1: they didn't have a lot to work with. But so
Speaker 1: with blood testing, so you have a scheme of blood typing,
Speaker 1: and they're actually different types of blood typing. There's not
Speaker 1: just one type of Uh. One thing you can look
Speaker 1: at is like the A B O antigens, right um,
Speaker 1: And so that's your system where you can be like
Speaker 1: A A B oh um and O positive negative. And
Speaker 1: so these things are inherited. But some of these are
Speaker 1: dominant and some are recessive. And once we had a
Speaker 1: Mendalian genetic model for how blood types A B O
Speaker 1: blood types are inherited. You could use that to say, well,
Speaker 1: you couldn't identify for sure that somebody was somebody's kid,
Speaker 1: but you could rule out that they could be their kid. Right,
Speaker 1: so someone narrowed down the field. Well, one thing I
Speaker 1: read about it apparently this happened to Charlie Chaplin. Like
Speaker 1: somebody said that Charlie Chaplin had had fathered her child
Speaker 1: and he denied it. And uh, and the genetic not genetic.
Speaker 1: It was before genetic testing that the blood type testing
Speaker 1: said that he was not the father um in a
Speaker 1: very more Povich kind of way. But but apparently they
Speaker 1: couldn't use this in the courts at that time, and
Speaker 1: so he ended up paying child support anyway. So, so
Speaker 1: tell me about the the progression from this fairly primitive
Speaker 1: in the grand scheme of things approach to matching to
Speaker 1: DNA matching. Well, now that we've got d N A,
Speaker 1: we've got a much higher uh, we've got more things
Speaker 1: to match, basically to give you a stronger piece of confidence.
Speaker 1: So let's say that your blood type test only shows agreement. Well,
Speaker 1: that doesn't narrow it down much at all, like we
Speaker 1: talked about. But let's say you can identify a certain
Speaker 1: number of genetic markers between the suspected father and the
Speaker 1: child and look for matches. Now, if you only have
Speaker 1: a suspected father and the child, it's a little bit
Speaker 1: harder to get a positive match, um, because you can
Speaker 1: look at a child and say, like they say, they
Speaker 1: have a gene like A and B, and um, the
Speaker 1: father has genes B and C. You don't know if
Speaker 1: that be in the child necessarily came from the father. Yeah. Um,
Speaker 1: But you can get a much better idea if you
Speaker 1: also have the mother's DNA and find that in that
Speaker 1: same genetic marker the mother does not have B. So
Speaker 1: there you have a much higher level of confidence. You
Speaker 1: do this over multiple genetic markers, and if you keep
Speaker 1: finding matches between the father and the child that do
Speaker 1: not match with the mother's DNA, then you have a
Speaker 1: near certainty. Um, the more markers you measure, the higher
Speaker 1: certainty you can get. What they don't do, though, is
Speaker 1: they don't compare the entire genome, because, as we've talked about,
Speaker 1: lots of it just wouldn't make any difference, and and
Speaker 1: lots of it would be identical anyway, because it's identical
Speaker 1: in everybody. Also, processing all of that would be way
Speaker 1: more work than is in any way necessary. Yeah. Well,
Speaker 1: in fact, all human beings have it's like ninety nine
Speaker 1: point nine percent the same DNA, and right, it'd be
Speaker 1: like taking a book that's a thousand pages long, and
Speaker 1: nine hundred and ninety nine of those pages are going
Speaker 1: to be identical. They kind of the identical words on them.
Speaker 1: But if you but there's one page worth of words
Speaker 1: that will be different, and you have to go through
Speaker 1: the whole thing. They're spread out throughout the entire For
Speaker 1: those words are spread out, Yeah, it's it's our Our
Speaker 1: code differs it around um ten million points out of
Speaker 1: you know, three point two billion. Yeah, that's right. So
Speaker 1: it would be like the genetic expertise. What you do
Speaker 1: there is you open the book to a certain page
Speaker 1: that you already know is going to have a variant
Speaker 1: on word number three on this page, and then you
Speaker 1: can compare it from there, and then you just do
Speaker 1: that as many times as possible on down the line. Now,
Speaker 1: of course, once you get a certain number of matches,
Speaker 1: it's it's so certain that you really just don't need
Speaker 1: to mess with it anymore. Sure that that the odds
Speaker 1: of any other person it's a are are just incredibly tiny.
Speaker 1: This is from a BBC right up. So forensic DNA
Speaker 1: test and this is it's talking about forensic d so
Speaker 1: that this isn't a paternity business. Yeah, it would be
Speaker 1: a crime. But so to identify a blood sample to
Speaker 1: the same person, you'd examine like six to ten genetic
Speaker 1: markers and they say the chances of two unrelated people
Speaker 1: having the same matches in those cases is one and
Speaker 1: one billion. Those are those are some pretty high odds there, um.
Speaker 1: And of course, so that brings up the other thing.
Speaker 1: Genetic matching is often often also used in forensic analysis,
Speaker 1: so you can use it in the court system to
Speaker 1: try to prove somebody guilt. And I know that this
Speaker 1: is difficult in a lot of cases because there's frustration
Speaker 1: that I think both sides in court cases have the
Speaker 1: juries don't really understand DNA evidence in a lot of cases,
Speaker 1: and they value they can value eyewitness testimony above DNA evidence.
Speaker 1: I mean, there are plenty of cases where either someone
Speaker 1: was pronounced guilty or not guilty, and there have been
Speaker 1: a lot of there's been a lot of criticism in
Speaker 1: in cases all across the board where it seemed like
Speaker 1: a jury was ignoring any sort of DNA evidence in
Speaker 1: favor of eyewitness testimony. And one of the things we
Speaker 1: can tell you a lot about is that human memory
Speaker 1: is not infallible. You can't. You can't just think that
Speaker 1: human memory is perfect. And even if someone is being
Speaker 1: completely honest when they're on the stand, they could be
Speaker 1: telling that doesn't mean that they're not wrong. Yeah, they
Speaker 1: could be telling something that's totally wrong. It's essentially a falsehood,
Speaker 1: but it's not one that they intended to be false.
Speaker 1: It's just that they remember it differently than how it
Speaker 1: actually happened. Whereas DNA testing, assuming everything is on the
Speaker 1: up and up right, assuming there's no tampering, assuming that
Speaker 1: everyone was following proper procedure and proper controls, is far
Speaker 1: more reliable. But that's not generally understood. Yeah, I mean,
Speaker 1: if you have a reputable lab doing this, and especially
Speaker 1: if you get redundant results from multiple labs and they're
Speaker 1: testing a large number of markers, it's going to be right,
Speaker 1: you know. Yeah, again, unless you're identical twin committed the crime,
Speaker 1: or or unless unless you've been framed. Yeah, right right,
Speaker 1: that's that's the other that's the only other real option.
Speaker 1: So identical twins are not always genetically identical. That's yeah,
Speaker 1: that's true. Interesting point. Yeah, it's it's those you know
Speaker 1: that that you know, ten million different differentiation points are
Speaker 1: can be can be different. I think monos I gottic
Speaker 1: twins are. They're sort of generally con sidered genetically identical.
Speaker 1: But is it a case where what there is variation
Speaker 1: but there's so little variation it's negligible, or or what's
Speaker 1: the deal. Well, there's um those differences that I was
Speaker 1: talking about are called single nucleotide polymorphisms, and and so
Speaker 1: few of them can be different. But you know that
Speaker 1: that for for all phenotype, all visual intents and purposes
Speaker 1: to people would be identical. But but for example, some
Speaker 1: some identical twins are more likely to get certain mental
Speaker 1: health issues or physical issues like one over the other. Yeah,
Speaker 1: so one might could that could that also be influenced
Speaker 1: by environmental factors like causing genetic changes? Oh yeah, you know,
Speaker 1: our genes definitely can undergo changes that aren't you know.
Speaker 1: It's not like when you inherit your genes that that's
Speaker 1: the way they are for the rest of your life.
Speaker 1: They can change and do change due to lots of
Speaker 1: different factors, including environmental factors. Uh. That's that's whole the
Speaker 1: process of mutation, which we will cover in depth in
Speaker 1: another episode. Join us next time when we talk about
Speaker 1: gene therapy and x men. Yeah, that's right, that's coming
Speaker 1: up in the next episode. We're really excited to talk
Speaker 1: about it. So you guys have to wait a couple
Speaker 1: of days, but we get to wait all of you know,
Speaker 1: a couple of minutes. So we're gonna wrap this up. Guys.
Speaker 1: If you have any suggestions for future episodes of Forward Thinking,
Speaker 1: go to f W thinking dot com. That's where we've
Speaker 1: got all the podcast blog posts, we've got links to
Speaker 1: other articles. You can get in touch with us through there,
Speaker 1: and we are excited to hear from you and for
Speaker 1: you to be come fart of this conversation about the
Speaker 1: future and what's gonna be awesome about it, and we
Speaker 1: will talk to you again really soon. For more on
Speaker 1: this topic in the future of technology, visit forward thinking
Speaker 1: dot Com, brought to you by Toyota to go places