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LINDA RAYOR: Hi. Can you hear me? Yeah, you can hear me. Hi. I'm Dr. Linda Rayor, and I'm very, very pleased to introduce David Hillis. David Hillis is a renowned researcher in the fields of phylogenetic systematics-- I suspect many of you in here have seen his Molecular Systematics book-- molecular evolution, computational biology, and diversity research, both from lower levels of individual [INAUDIBLE] all the way up to population levels. And one of the reasons we want to bring him in is because he likes talking about the science and communicating it to other people.
David Hillis is a professor at the University of Texas in Austin, where he studies molecular evolution and biodiversity in the Department of Integrative Biology. He was awarded the MacArthur Fellowship and has been elected to the American Academy of Arts and Sciences and the National Academy of Sciences.
He's published over 200 publications-- scientific research papers over his career. But really, one of the real reasons why I was excited about bringing David here is because he's so good at communicating science and values that it's not just doing the science, but it's actually conveying the science to the public and to students, and I hope that he'll be doing this tonight.
Along this line, he's the director of Dean's Scholars Program of the Natural Sciences Curriculum at the University of Texas. He served on the National Research Council's Committee on Biology Education and was one of the co-authors of Biology 2010-- Transforming Undergraduate Education for Future Research.
So I mentioned his book Molecular Systematics, which was really one of the first books that talked about how do you do it and got people excited. He coauthored a broad, general introductory biology text, Life-- The Science of Biology, which is now in its 10th edition.
But for a long time, he was interacting with the publisher and saying, wait a minute. Undergrads don't really need to know enormous amounts of details. What's really, really important are the broad concepts. What you guys-- what all of you guys need to get out of it are, why does it matter? And I think one of the things that David has done best is conveying why it matters.
So just as a query, how many of you in here have taken the Evolution and Biological Diversity class and used David's text? Some of you. How many of you are CIBT teachers or have associations? How many of you are high school teachers or non-college teachers? How many of you are high school or younger students? OK, great. I really want to welcome you here.
After the talk, we have a reception at the AD White House that is specifically for school teachers-- not the academics in here as well, but school teachers and their students to talk to David about the information that he's talked about today. Thank you very much.
[APPLAUSE]
DAVID HILLIS: Well, thank you very much, Linda, and thanks for inviting me. I've had a week this week meeting with all the various student groups and other groups, giving various talks, and it's been a lot of fun.
So what I want to do tonight is talk about two of the great ideas that integrate biology today, and one of those is obviously DNA, the main subject that's up on my title slide. And then the other one is going to be evolution, and that's really where my research intersects, those two things. I study DNA, but I look at it in a particular way to look at the evolutionary biology of life and the evolutionary history of life in particular.
And so what we'll do is examine a few of the ways that DNA is portrayed in popular movies and television and think about how it affects-- some of the ways that it affects our life. And of course, we're just going to barely touch on those things and then think a little bit about how it can-- may be affecting our life into the future.
So just to get some of the fiction out of the way right off the bat-- does anybody see one of the big fictions on my title slide? Yeah? You do? What is it?
AUDIENCE: Just the [INAUDIBLE] just doesn't [INAUDIBLE].
[CHUCKLING]
DAVID HILLIS: OK, so there's a model of the double helix of DNA, and actually, of course, it is a double helix. So it spirals around, and there's two ways you could twist the double helix, right? And for some reason, in depictions of the double helix, if people did it just at random, then you would think that they would twist it one way or the other way pretty much at random.
But in fact, when you see depictions of it, it's usually the wrong way. And I don't know why that is. Anybody have an explanation for that, you can tell me. But you can always tell if it's spiraling correct or not by-- if the strand toward you is going from left to right, as it is here, that's actually backwards. It really should be going from right to left across the double helix. So just a minor point, but it's an interesting one that I've never had an explanation for.
So here's the correct way for it to spiral. And of course, this molecule is so important because it's universal across all of life. So all the genetic codes for whether you're a human or a pine tree or a bacterium, they're basically using the same molecule, very, very simple language of just four nucleotides. And so we have Ts, Cs, As, and Gs. And T always pairs with A, and G always pairs with C.
And in spite of the simplicity of this molecule, it's able to encode all the proteins that make us and have us function and determine whether or not we're people or pine trees. And so that's one of the real strong bits of evidence that all of life has a common ancestry and shares this common ancestry in these common features.
And of course, evolution is all about changes in the DNA. So when mistakes are made as the DNA is replicated, it changes through time, and the changes through time have gone from-- it's fascinating to me to think about the changes. There were some DNA molecules back about a billion and a half years ago that were replicating, and there were changes made and there were lineages that divided about a billion and a half years ago. And one of those lineages ended up being pine trees, and one ended up including me. And so that's something that's fascinated me from very early in my biological training.
So this idea of commonality of life actually precedes, though, our discovery of DNA and understanding of DNA. So this is a figure from-- this one of the left has become very popular recently. So Charles Darwin was scribbling one day in his notebooks in 1837, and he started realizing that you can have a lineage of organisms and descendants from that, and that lineage could split into two, and that would split into two, and it formed this tree of life.
And so the idea of the tree of life was so fundamental and important to Darwin in writing the Origin of Species, that little sketch became the basis for his only figure in the first edition of Origin of Species, and that's what's shown on the right there. He hedged a little bit. He said, well, maybe they were-- whether there was one origin or a few origins, then you could have these giant trees of life that diversified and spread and continued diversifying up to the present day.
So the word that describes that relationships among lineages "phylogeny." And so "phylogeny" is a word that is less familiar to most people in the general public than, say, DNA is, but it's become extremely important throughout biology.
And just to give you some indication of this, here's a graph of the number of papers that are published each year for the past whatever that is, 35, 40 years, 30-- yeah, 40 years. And during that time-- so this has-- it's a search of all the papers and the scientific literature that include the word "phylogeny" or some form of the word "phylogeny" in the title or abstract of the paper.
And so when I first got interested in this concept of phylogeny-- I don't think I have a pointer up here. You can see there were just hundreds of papers that were published each year, so I could read every single paper that was published in the field. And in fact, if a paper came out with a phylogenic three in it, then I was sure to read it because it was going to be important to me. And then you can see the [INAUDIBLE] went along like that through much of the '80s, started increasing a little bit.
And along about 1990, something dramatic happens, and the dramatic thing that happens there is that biologists began realizing the importance and power of using phylogeny, looking at phylogeny and understanding everything we do in biology, making comparisons throughout biology, looking at including evolutionary history.
And so today, if you go-- last year, the last dot on there, had something like over 14,000 papers. That doesn't include all the papers that have this-- that include phylogenetic analyses. That's just the ones that have this word "phylogeny" in the title or abstract. And to give you some sense of that, that's about one out of every 100 papers in all fields of science combined.
So if you take all the papers that are published in physics and chemistry and mathematics and biology, about one out of every 100 has this word. So you can see it's beginning to become extremely important. And it's impossible to pick up any journal in any field of biological sciences and not see phylogenetic analyses and phylogenetic trees in them.
All right. So what exactly is it? What is phylogeny? I said it's the relationships among lineages. And so I'll be talking a little bit about an example from HIV, from human immunodeficiency virus. So let's just think about. So if we think about this through time, in a lineage through time-- so if we think of, let's say, a single virus particle and the descendents it's leaving, then that would form a lineage through time.
And if this first virus infected a single person and then it was going along-- it'll be descendants in that individual. And then if that person infects somebody else, then you have a split in the lineage, and now you have one lineage of the virus in one person and one in the other person, and that causes the splits in the tree.
Well, that's an example of one of many [? things, ?] [? biological ?] processes that can cause splits in lineages. Other things would include things like, well, DNA replication. We already mentioned that. When you have DNA replication, you have a split in the lineage. When you have gene duplication, you have a split in the lineage. There's all kinds of processes that produce these kinds of lineage splits. Speciation events obviously is another one. That was one that interested Darwin the most.
And so of course it continues, and through time, each of these lineages continues to split, and some lineages can become extinct. And over time, you have this structure that looks vaguely like a tree, so we call this a phylogenetic tree. And if we were to take samples of viruses from these lineages at some point in time, well, we would miss this one because it went extinct.
And so we can sequence those viruses and reconstruct this evolutionary history, in which case-- this case, we'd miss that extinct one, so it'd look like that. And this is what we mean when we talk about a phylogenetic tree.
So how does that work, exactly? Well, it's actually fairly simple. If you think about these lineages, of course, mutations are occurring. HIV is evolving very, very quickly, which is one of the reasons it's such a difficult disease. And so each one of these tick marks represents a mutation that's occurring in the particular lineage.
So all of these are different mutations somewhere in that genome of HIV. And so we can then use that by looking at the mutations that are shared. So if we sequence this one and this one, there will obviously be some mutations that are unique to one and some that are unique to two, but then there will be all these that will be just found in one in two and not in these other ones. And then likewise, there'll be other mutations that are found in lineages one, two, three, and four because they were found in the common ancestor.
And so that's basically the kind of information we're using. It's a little more complicated than that because we have to take into account a little bit more of the biological information. We have to have a model of evolution of how these different sites are evolving. And of course, with many genomes it can be very, very large.
So one of the things that held biologists up-- that curve only went up in recent decades-- was the molecular biology revolution, having DNA that we could sequence, being able to sequence it rapidly, and then the computational power to be able to look at all these sequences and process them. So all those things coming together allowed this application of evolutionary biology throughout all fields of biology.
So normally, as I said, we use actually a little bit more detail there. But essentially, what I described to you is accurate. All right, so this is depicted in-- how does this relate to depiction in art and movies and television? So what I'll do is-- I'm going to play now a clip from an episode of CSI. Anyone not know what CSI is, crime scene investigation? There's a whole lot of different versions of it. Real popular TV show-- and on the TV show, they investigate crimes, and they use all kinds of technology to figure out basically whodunit.
And in this particular one, they're investigating a snuff film. So they discovered a film in which someone is taken in for processing, and a murder is actually committed on the film. And so they're trying to find the person, and they use all sorts of ways to track down the suspect. And then in the course of the investigation, they're going to use phylogenetic analysis in order to connect him to the crime.
So let me get out of this and go to our clip. All right. So this will be the final scene, basically, when they confront the victim with the evidence. That's what you're about to look at.
[VIDEO PLAYBACK]
-OK, one more time for the record. You have never had sexual intercourse with Susan Hodup?
-I told you, I've never even met her.
-I know, but I got to ask. You've never had sex with her?
-Not ever.
-OK.
DAVID HILLIS: They're smiling because they know they got him now.
-You still have those chills, Mr. Sampson? Feeling hot, achy? Back of your throat scratchy?
-Yeah, it is.
-Original flu. Happens at the onset of HIV, sero-conversion. Usually presents two to six weeks after the exchange of fluids.
-Exchange of fluids?
-That temperature is your body working up a resistance to the virus.
-HIV? Me? Come on. You just took my blood a few days ago.
-A private lab can run a virus test within a day. CDC doesn't broadcast that. Tests are very expensive.
-We dipped into the budget just for you.
-You're playing me. I don't have HIV.
-Susan Hodup had it, the exact same strain that you have.
-We had that lab do what's called a phylogenetic analysis of your HIV's DNA, and Susan's.
-As you can see, the genes are identical, which means Susan gave it directly to you.
-But we never had sex.
-You did stab her, though. And at that moment, her arterial blood hit your eyes, entering your body through the conjuctival membrane.
-Non-sexual transmission is extremely difficult, but obviously, it's possible. Susan's blood was absorbed into your bloodstream.
-Where the new HIV cells immediately started attaching to your healthy white blood cells. Get inside one, replicates about 2,000 times, disables the host cell, pinches back out, infecting more good cells. Lowering your immune system until your body loses its ability to fight off even the simplest invader.
-Of course, the strains will have changed by then, and you and Susan Hodup will have a different strain of HIV. The sooner you see a doctor, better your chances for longevity.
-But for now, we got you. You killed her.
-I guess she killed you back.
[END PLAYBACK]
DAVID HILLIS: So fact or fiction? Well, there's some of each in there, obviously. So clearly the story is fictional, but they try to do in CSI-- there's a lot of things that are really unrealistic about the show, right? So there's no way that you have the same person that's going out and investigating crimes and collecting the data and going to the laboratory and confronting the victim, right? Those are all done by different people. So they take some liberties with that.
But what about the science in there? Well, most of that science is actually pretty good. There's a few places, little minor things you can pick on that they slip up. They talk about HIV cells. Of course, HIV is a virus. It doesn't have cells. But except for that and little minor little tweaks, the science they're talking about is actually very good, and I think this is actually a really good educational example of applications of this technology.
So they talked about the transmission. You actually can follow transmissions of HIV from person to person, and it is true that initially, you have a virus that's exactly the same, and it begins to change. And so they encapsulate a lot of truth in that. Well, they did that because actually, basing this on a real crime story-- it's very different in its details, but it's one in which I was involved. I'll tell you a little bit about the truth about this. behind what, basically, they were using as a basis for this CSI episode. So this is a physician who is in Lafayette, Louisiana. And he had a long-term affair with a woman. And she kept threatening to break it off if he didn't leave his wife.
He wouldn't leave his wife, so she finally called off the relationship. And that night, he had a key to her apartment. So he came over to her apartment, and came in, and he forcefully gave her what he said was a vitamin B-12 injection.
And she tried to kind of fight it off. But she kicked him out of the house after that. And she had a bad reaction from this injection. But she didn't really think much more about it. She broke up with the physician, didn't see them anymore.
Then the next year, she met somebody else and got married, and got pregnant, went in for prenatal testing, and found out she was HIV positive. So her partner wasn't HIV positive. The physician wasn't HIV positive. She wasn't an intravenous drug user.
She didn't have any known risk factors for HIV. So she really couldn't imagine how she could have been infected, except that she remembered this strange injection this physician had given her, and the threats that he had made her about breaking up with her. And so she went to the police, and the police decided to investigate it.
So they went to the physician's office, and they asked to see the blood draw records. And the blood draw records, the page for the week in which this injection occurred were missing. And so he claimed that he had just lost it somewhere.
And so they got a search warrant, and searched his practice, and eventually found the missing page in a box of old records from about 10 years previously, mixed in with those. And on that page, there had been two blood draws taken from patients that had not been sent on to any other lab for testing. So they said, why wasn't this sent on to any other lab? He said, I don't remember the circumstances.
So they took the names, and contacted the patients. And they found out that one of the patients was HIV positive. The other one was hepatitis C positive. And it turned out the victim was infected with both HIV and hepatitis C.
So they had means, and motive, and opportunity. But at that point, the district attorney decided, well, we can't really prosecute this case unless we have some means of showing that the HIV present in the victim was really derived from this physician's patient, not from somewhere else. And that's where the DNA phylogenetic analysis came in.
And so when I talked to the district attorney about this, this is sort of the theory that I presented and talked about. So when someone's infected with HIV, they're actually usually infected with a single virus. And then that virus actually begins to change and divide.
So before, I was talking about all this being a lineage. But in fact, you have lots of lineages within even a person who's infected with HIV. So there's lots of different copies.
And so after a while, a person has lots of different copies of HIV with many different sequences. And that's why it's actually such a difficult disease to treat, cure, or make a vaccine for. It's constantly evolving.
Now, when this person infects someone, what happens? Well, the next person gets usually just a single copy of these viruses. But they're only going to get one of them.
And so one of these will go into the recipient. And at the instant of transmission, there's actually an identical virus or virtually identical virus in the recipient from the source. But there's a lot of divergence among the ones in the source. So it's like it's a subset of the viruses that are present in the source.
And of course, evolution doesn't stop there. The virus continues to evolve. And you have lots of lineages going extinct, because your immune system is actually clearing them out. And you have more lineages evolving within both recipient and the patient. But you still have this embedded relationship of a subset of viruses.
So that's a phylogenetic tree based on the genomic sequences of these viruses. These are the actual data from that court case. And the tree is now just turned on its side. So it's exactly what we're looking at. We've just taken it and flipped it on its side.
And these all represent a single sample from all the other HIV-positive individuals in the Lafayette, Louisiana area. And the ones at the top in this box-- the ones in red-- are viruses that we sampled from the patient. And the ones in blue are from the victim-- so exactly consistent with what you'd expect if there was a transmission directly from the patient to the victim.
Now, the usual defense, we knew when we presented this, when we had the several-day hearing about the admissibility of the evidence, the defense argued that yes, it looks like there's a match there. But there could have been a contamination in the lab. And of course, it's possible that could happen, if there was contamination. You wouldn't expect it under normal laboratory conditions.
But we could actually address that in this case. Because we could take new blood from the patient and send it to one lab, and new blood from the victim and send it to a completely different lab, so they were never anywhere in the same vicinity. There was no chance for contamination.
And so by the time the trial came up, we had done that. So you can see the new sequences here. You can see additional evolution.
But again, the victim sequences are embedded within this cluster of patient sequences, and outside of all the other individuals from in the area, so exactly what you'd expect from a transmission directly from the patient to the victim. That doesn't tell you how the transmission occurred. And so they also had to present lots of other evidence-- the fact that this patient and the victim didn't know each other.
They'd never met. And the only contact between them that anybody knew about was that the physician had taken blood from this patient under very mysterious circumstances, and that same week had injected the victim under mysterious circumstances. And so by that, they were able to convince the jury that this was a purposeful attempt by the physician to kill his ex-mistress.
And so he was, in fact, found guilty of attempted murder. And this established the principles of using phylogenetic analyses in criminal cases in the United States. And since then, there have been a number of other cases in which it's been used. And so this is becoming increasingly common as a means of forensics of using DNA in these criminal investigations.
And here's one. I'll let you all be the jury on this one. This is from a few years ago. This one happened in Texas.
An individual was accused of aggravated assault of a number of different women, and in the course that infected him with HIV. He was himself HIV positive. So these are sexual assaults.
And these numbers just represent the different individuals in the case. It's blinded so we don't have any bias about what we find as the results. So here are our results.
I've color coded all the individuals by color. And your job is to figure out, are any one of this cluster, is it consistent with being the source of the other individuals? Anybody have a suggestion for someone who's a potential source, based on what I've said so far? Anybody? You can shout it out. CC01.
We have a vote for 1. And if you look at 1, you can see it scattered across this phylogenetic tree. It's all over the tree. All the other individuals form these single groups that descend from a single virus.
So this is the only individual that's consistent with being the source of all these other infections in other people. And so at the trial, that was decoded. And CC01 was revealed to be the defendant, and he was found guilty of six counts of motivated assault by the jury.
Now, it's not always used to convict people. It's also used to free the innocent. And maybe one of the most dramatic cases was one that was very much in the news a few years ago. How many of you heard about the case of a series of Bulgarian health care workers-- several doctors and a lot of nurses?
They went to Libya on a humanitarian help mission to work in a children's hospital. And shortly after they arrived, there were all kinds of terrible epidemics of HIV and hepatitis C that broke out in the hospital. And so the Libyans accused the Bulgarians of purposely infecting the kids.
And so it was, if true, obviously a horrible crime. They were tried in Libyan courts with kind of a minimal amount of evidence and found guilty, because they basically had been there at the right time, at the time at which these things had occurred. And they were sentenced to death.
And about that time, news of this began reaching other places. And so people began trying to do phylogenetic analyses to see what had happened. And in this case, what they did-- what this graph shows-- is a molecular clock analysis, which means you look at the time at which these events occurred, and look at the origin of those different epidemics in the children's hospital.
So each one of these points represents an origin. And then this is the confidence limits for that origin. And so this one, for instance, suggests that the origin of this epidemic was probably about 1992 or '93 with a range of possibility of extending back into the '80s and up to about 1996.
And you can see all of these estimates of origins of these epidemics in this hospital were before this red line. Well, March 1998 is when the Bulgarians arrived. So they arrived in the hospital just as these epidemics were taking off, and becoming really prevalent in the hospital. And so they arrived there at the wrong time.
They clearly had nothing to do with it. They couldn't possibly have had anything to do with it, because they all started well before that. And so then eventually, with pressure from Western governments, the Bulgarians were eventually-- actually, by Libyan law, Libyan courts can't ever say that they're wrong, apparently.
But eventually, what they did was negotiate with the Libyans, and get them to release them back to Bulgaria to serve out their life sentence in Bulgaria. And then as soon as they went back to Bulgaria, the Bulgarian courts, of course, found them innocent and freed them. And so eventually, it all turned out OK. But it was very touch and go for a little while, where those health care workers were about to be put to death for something they clearly had nothing to do with.
So this part about estimating time-- how does that work? So let's just look back a little bit about where HIV comes from. Again, it's a phylogenetic question. We can look at evolutionary relationships to figure that out.
And you're probably aware that these human immunodeficiency viruses are related to other viruses. We call them simian immunodeficiency viruses found in various African primates. So there's a lot of different African primates with these viruses-- apparently been evolving in them for a long time.
And they've transmitted into humans from other primates twice-- once from chimps. Up here, we call that HIV 1, and once down here from sooty mangabeys. We call it HIV 2. So this happened in central Africa. This happened in Western Africa. And so we know it's coming from at least two different sources.
Now let's look at a little more detail at this part right up here. We're just going to look at this portion of the tree with the chimps and the humans. And if you do that-- if you sample lots of these viruses-- you get a tree that looks like this.
All the black ones are ones sampled from chimps, the red ones from gorillas, and then the blue ones from humans. So you can see that we have black ones going all the way back. All these are black ones.
So this is a virus that we think was originally in chimps. And then it's been transmitted once into gorillas, and then at least three different times in humans. So what's going on here? Why is this virus, not just from several species, but even within chimps, being transmitted multiple times into humans?
And so this is kind of a little bit of a puzzle as to what was going on. Because we thought all these viruses were suddenly appearing. We didn't know about HIV until the late 1970s or early 1980s.
Early 1980s, we really began learning about it, but the first evidence of it was in the '70s that we had. And so people thought this was a real recent thing. But why would this suddenly be jumping from chimps to humans?
And so the answer to that, we could ask, well, when did these viruses actually get into humans? So now what we're going to do is do the same thing, and expand this part of it right up here-- just this one group of one lineage in humans-- and ask, when did that one get into humans? So we can do that, again, with this kind of phylogenetic analysis.
So we've sampled these things. We started sampling them, as I said, in the early '80s. We have samples dating back to the early '80s. We know when they were collected.
We can build a phylogenetic tree relates that back to their common ancestor. And then if you notice, this is the amount of change in the DNA sequence. And we've plotted that out on this axis, and then put the dates on.
So if you take those dates on which they're sampled, and then measure the distance from the tip of the tree back to there along this axis, then you can see this positive relationship. You can see how quickly this virus is changing through time. So you can see, it's a very clear, linear relationship, and it's increasing rapidly, evolving through time just since the '80s to the present. There's been lots of change.
Well, you can also extend that back in time. So we don't have to stop with a branch length of 0.11 or 0.12. We can extend it.
So we're going to take this part of the graph up here, and extend this line backwards in time until we get down to zero. We can estimate a time for this point. And you can see the white portion there shows the confidence limits for this particular estimate.
But we end up getting a date of about 1930, plus or minus a dozen years. And so when people saw that, they couldn't believe it. Because nobody had heard of HIV back in the '30s. We didn't even know about it until the '70s.
So people thought, well, if that's true-- if it's been around in human populations that long-- maybe we can go back and look at old medical samples, and see some cases where we have HIV isolated from a long time ago. And so there were some samples back in Africa in the 1950s. And people began looking at them. They're still frozen away in freezers.
And when they did that, they started finding, yes, actually, there were people who were sick, and died, and had HIV back that long ago. So here's a 1950 sample. And you can see it on the tree, 1959, and see where it is on the tree-- a much shorter branch than all these others, right where you'd expect it to be.
If we plot out that distance on this graph, this would predict 1957 plus or minus 10 years, so pretty clearly within our range of estimates. And so this gives us a fairly high degree of confidence that we're really talking about this range back here for the origin of this particular lineage. So now, it helped us understand where HIV came from, how it got into populations, when it was getting in, how it's being transmitted.
And the general thought now is that these viruses have been getting into human populations probably for millennia, as people hunted and ate different primates in Africa for food. So in central Africa, they hunt and kill chimps and eat them. In the process of doing that, they get a cut on their skin, and transmit the virus. And so the difference was really that these viruses would probably just be in very localized populations.
In the middle of the last century, there were lots of wars of independence, civil wars, people moving around, the urbanization of Africa, people coming together in big cities, a lot more contact from person to person. Of course, there was also the sexual revolution, increased use of drugs that could transmit HIV, vaccination programs where sometimes people ran out of hypodermic needles and so they might reuse them and transmit the virus. All those things allowed these little, localized infections to turn into global epidemics. And that's how we had all these different cases of different lineages of HIV getting into humans.
Let's jump from that to think about how DNA technology and phylogeny can be used at a very, very different scale. And we'll jump and think also a little bit about the future. So one of my favorite television shows, and also movies, for kind of illustrating this was Star Trek. I loved Star Trek when I was a kid.
One of things I liked best about it were these tricorders. And unfortunately, my clip that I have for this isn't working today. But I think I'll remember what happened. So basically, they would land on some planet they'd never been on, pull out the tricorder, instantly know everything about all of the organisms on the planet.
Well, clearly pretty fictional for lots of different reasons. But the idea is really an interesting one. And the truth is that today on planet Earth, we don't begin to know about most of the organisms that live on the planet with us and affect our daily lives.
So when you get sick and you go in to see a physician, when I get sick-- almost every time I get sick and go in and see my doctor, he says, well, you probably have a virus. And I don't know what it is. And there's nothing I can do about it. So go home and drink lots of fluids and call me if you don't get better. And that'll be $200.
And so it's not very satisfying. It's really frustrating. And that's just an example of one of the many things that affect their daily lives because we don't understand the biodiversity of our own planet. We don't even know the organisms that infect us and make us sick.
So one way of dealing with this-- we can think about these phylogenies across all of life now. There are genes in which we all share, that we can sequence and relate all the way back to the origins of life-- kind of Darwin's dream of the Tree of Life. So this is a sample.
You can't read the names here, because they're too tiny, but there's 3,000 species around here sampled across the Tree of Life. And this shows their relationships. So we take it now and put it into a big circle. So you can just think of this great, big phylogenetic tree being twisted up in a circle that starts here, and then radiates outwards and shows these different relationships.
Now, I originally actually made this as sort of a joke as a poster for our biology building, because we're in a very large campus. And at the beginning of every semester, we have tons of students there wandering in, lost, wondering where they are. And so I put this poster up in our foyer to kind of help them out.
And so they look at it, and they can see. You zoom in here. You can see here-- there you are, right there.
And people sometimes look at it, and they're trying to figure out their way around campus. But doesn't help very much for that. But it will help you around the diversity of life.
Now, I said it was just a sample of things. So the other thing I produced it for was to think about displaying the Tree of Life and the size of the Tree of Life. I said there are 3,000 species in there.
That's about the square root of the number of species we think exist on the planet Earth-- so somewhere around 9 or 10 million. People have estimates that go quite a bit higher than that. And so if we took every tip of this tree I just showed you, and expanded it into another tree of that size-- so every tip of the 3,000 expanded into another tree of 3,000-- that's approximately how diverse the life on Earth is.
So what could we do with that? Well, here's our tricorder over here. We have to wait a long time to get that device-- that particular one.
But I took a trip as an undergraduate with this guy right here, Henry Fitch, while I was an undergraduate. He was a Professor at the University of Kansas. And I went on a trip. I took a semester off from college and went through Central America with him.
And one of the things I really admired about him was that wherever we went, I would go out and find all sorts of organisms, and have no idea what it was. I'd bring it back. And he could almost always tell me something about it.
He didn't always know exactly what species it was, but he knew what group it belonged to. And it was the most educational experience I've ever had, because he was this resource. He could tell me what it was. And then we had a of books. I could look up, and read about it, and find out about it.
And that's actually one of the big problems with going out-- for anyone, any biologist going anywhere in the world. Most of the organisms they encounter, no matter how good of a biologist they are, there are very few people like Henry Fitch that have a broad enough knowledge to recognize most of what they see. And so not knowing what it is means we can't connect it to the literature of what's known about it, or even know if it's known.
So of those 9 or 10 million species that inhabit the planet, we've only discovered so far 1.8 million of them. So most of the species of those 9 or 10 million-- or maybe more than that-- are still undiscovered and unknown. And so this vast area of ignorance of our planet is a real impediment to a lot of studies in biology.
So could we do something like that? Could we create a device like that tricorder? And it turned out, I found it really quickly I couldn't call it a tricorder, because that's a registered trademark of Paramount Pictures. We'll call this thing a biocorder.
And you can actually do this. Biologists do these following three steps all the time. But they do them in the big labs with large, expensive equipment.
So you can isolate DNA, and amplify a series of target genes, sequence those genes. And then once you have that information, that sequence information, we've already got a big database. I just showed you one-- a Tree of Life of relationships.
And you can plug it into that tree, and figure out if it's something we know about. Or if it's not something you know about, it's already showing you how it's related to everything else on the planet. So it's essentially giving you the classification. It's putting you in the context of what we know.
That's really all you need to build this biocorder. And it turns out that, as I said, these three steps were done with large labs and equipment. But now each one of these steps has separately been miniaturized.
So we have little microfluidic devices that allow us to take a tiny bit of tissue, and isolate DNA from it. We can do little, tiny devices that amplify those genes, that sequence them. And we have the computational power now to take those sequences, and put them into the context of the Tree of Life.
So the only thing we haven't done is taken all that together yet, and put it together in a single handheld device. But there are a lot of efforts to do that. And there's actually a race and a prize to the first person who makes a really effective, handheld biocorder.
So just to impress upon you how this would work, and also to show you that it's not just little, tiny microorganisms that no one has ever seen. It actually includes very large, charismatic organisms that we still have not discovered. I'll give you this example that literally from my own backyard.
So I live here in Austin, Texas. And right down the road is San Antonio. And this part in green are the Edwards and Trinity aquifers in Texas. That's where most of the freshwater in Texas comes from-- large, underground aquifers.
And it either comes there directly-- like San Antonio is the largest city in the world that relies on an underwater aquifer for its primary drinking source-- or it's from the springs that pop up and feed the lakes that are used for places like Austin. In any case, there's a huge amount of political interest in these aquifers, because so many people depend on them. And there are also a lot of agricultural interests that depend on them.
And many, many, many species-- there are huge ecosystems-- lots of endemic species that live in the springs and caves throughout this region, and so huge political fights. But nobody really understands the aquifer very well, because it's deep underground. And it's got all these strange, little, tenuous connections. It's very difficult to study.
But the organisms that live there actually give us our best clue to mapping out and understanding the relationships of different parts of the aquifer. So just like we can look at how the organisms are related, by doing that, we can see how different portions of this aquifer are related. And so that's why I began studying some of the underground fauna that lives in Edwards aquifer.
And in doing that, one of the major first groups we looked at was a group of salamanders that live underground and in springs of this aquifer. And this is a picture of a park in downtown Austin called Barton Springs. And it's a very popular place. It's actually hard to get a photograph like this with this few people in it, because there's usually a lot more people swimming around.
So obviously, we're not talking about some little, distant, unknown, remote place in the tropics. And we were very surprised when we started doing these surveys that there was an undescribed species of salamander that lives in this spring system-- in that swimming pool, basically. It's endemic to that swimming pool in downtown Austin.
And so I used to make a lot of fun of my colleagues, because many, many dozens of herpetologists-- people who study reptiles and amphibians have gotten their PhD at the University of Texas. And they've gone swimming in Barton Springs. And yet here, right there under their noses, was this undescribed salamander, endemic to this swimming pool.
So it was listed as an endangered species. And the city got very interested in it. It became kind of a rallying cry for protection of the aquifer.
And they began doing weekly scuba dive surveys. And this Barton Springs became probably the most intensively studied site for salamanders in the world. You wouldn't have any place on the planet that had been more intensively studied with all these weekly scuba dive surveys done.
After about a decade of that, one of the women who studied this-- Dee Ann Chamberlain-- came to me and said, well, have you noticed how some of the little salamanders are kind of white and others are dark? And I said, well, yeah, that's interesting. I wonder if maybe their eggs are laid in different places or something. Why don't you raise some of them up and look at them, see what they turn into?
So she did. And then a few months later, she came into my office with this animal. And I looked at that, and I said, what in the world is that? And she said, that's one of those little, light-colored salamanders I raised up.
And I looked at it. And I said, I just can't believe it. First of all, it's a blind salamander. It has no functional eyes. The other one I showed you had big, functional eyes.
This has no functional lenses. It can detect light and dark, but not images. It's completely different in its morphology, its color, its shape, everything about it. I couldn't believe that there could be another salamander at this site, right in the middle of Austin, intensively studied.
And so, of course, the way you can do this is exactly what I told you. So we can now just take a little tiny bit of this. And in fact, we could have-- all along-- just been sampling the water from the spring. And there's enough salamander cells sloughed off in the water that, even without ever seeing the salamander, we could detect that it was there, and done the following experiment.
So here's our big Tree of Life I showed you-- 3,000 species. If we were really dumb and so klutzy that we didn't know that this was even a salamander, then we could do an analysis with this whole thing, and put it up here, and tell us it was an amphibian. And then we could go off to the next level of this to an amphibian tree.
Now obviously, this is going to depend somewhat on our ability to sample the species. So this gives you an idea of our knowledge of salamanders. This is the number of known species through time.
And then this lower graph is the number of species of salamanders that have DNA sequences in GenBank, a big data repository for data. And so you can see, we first started doing DNA sequencing of salamanders in the late 1980s. And then it went up, very slowly at first, but then quite rapidly more recently.
And we're pretty much about to catch up. It will be in very short order, all the species of salamanders in the world will have been sequenced, and they'll all be in the database. They're not all quite there yet, but it's getting to be very close to being complete.
And so we can look at all the species of salamanders in the world. We have a tree for them. And so on the screen of this little device now-- now, we don't actually have a little device. We do these analyses, but the little, handheld devices doesn't exist yet.
But imagine this is the screen, the output. And it lights up over here and tells you, OK, here's the family you're in. And now we can click on that and zoom in on that family. They're all the Plethodontid, lungless salamanders.
And you can see our screen is showing us a hit over here. So we zoom in on that portion of it, and do a little click there. And now here's the tree that you have of these lungless salamanders.
And the ones up here, this picture is the one I showed you of the Barton Springs salamander. There's that little cluster of Barton Springs salamanders. You can see each of these represents other salamanders, other places in the Edwards aquifer.
Here's one that occurs down near the town of San Marcus, the Texas blind salamander. And you can see there are similarities between these two that made us wonder if they could be related to each other. And in fact, the DNA plugs right in for this one-- this one from Barton Springs here. And in fact, it turned out that there were actually two endemic salamanders in this one swimming pool in a park in the middle of downtown Austin-- one that lives deep in the aquifer and rarely comes up, and one that stays up in the springs.
So I use that as an example, because if that's true for salamanders in downtown Austin, then you can imagine how it is for almost any other organism in other biodiverse places that are less well studied. And it shows you how poorly we understand our own planet, and how this technology can be used so we can really build this technology to be able to do it. So not only will you very soon be going in to the doctor and have them be able to identify the virus, and then once we identify viruses, then once we know what they are, then we have an ability to think about whether we know whether we can or can't do anything about it.
Also, just imagine the other applications you could have. So if you're wandering around the woods collecting mushrooms to eat, it's very difficult to know if it's a toxic mushroom or a tasty mushroom, one that will be great on your salad or one that will kill you. If you had a device like this, you could be able to do that. And I think very soon, people will be going out, and these devices will first be like the little digital cameras, where initially, they're very expensive, and only a few people have them.
And then soon, they'll be in everyone's hands. And then you'll be exploring your backyard, and discovering new species, and then connecting that to all of the information we have about the species of life. So I think it will really change the way that we approach and deal with the biodiversity of our own planet.
So lots of different advantages to this. People worry about the cost, but I think actually, once you develop the technology, it actually greatly lowers the cost from what we do now. And the most important part of it's probably this last one-- is that connects you, gives you a quick connection, to universal databases that connect it to the entire diversity of all the information about the biodiversity of life on Earth. And that's an enormously powerful kind of thing to do.
So I'll just end with this thought, which is I'll return back to 1837, thinking of Darwin scribbling in his notebook and making this little design. And a few years ago, somebody was asking me, well, what do you think would surprise Darwin the most if he were to come back to Earth today, about the modern world? And I thought, well, there's all kinds of ways you can answer that-- all kind of things.
But one thing that would certainly shock him would be this little scribble that he made in that notebook back in 1837 is now something that is becoming so popular, so important for biology, and so popular that people are actually drawing it on their bodies in permanent ink and in tattoos. This is a beautiful tattoo that was based on the design of a figure I had on the front cover of my book, Molecular Systematics. And this graduate student wrote me and asked me if she could replicate it on her back.
And so I said, well, I think it's a great idea. Send me a picture. But if I were you, I would not label all of the tips in too much detail, in case there's any changes, if you're going to tattoo it on your back.
So thank you very much. I appreciate the opportunity to be here. And I'm happy to answer any questions you might have.
[APPLAUSE]
I think we have a little microphone that we can walk around if you have a question, if you can ask it to the microphone, so that other people can hear it. Does anybody have a question? Nothing like the universe, and everything, and nobody has a question? There's one up here, Penny.
AUDIENCE: Hi. I'll go out on a limb. This is very fascinating. Over the next 100 years, what's the future of genetic tinkering with the human genome to produce a better human being?
DAVID HILLIS: Yeah, so it's pretty hard to predict what will happen. I think there's going to be probably more limits on that, based on our discussions as a society than from the science. So what we can do is probably going to far outstrip what we will do, is my guess.
So I think there's a lot of things that could happen. You think about, like the movie Gattaca, would have been another great example to think about-- so the future of kind of the dystopia of all this information, of being able to instantly sequence a genome of a human, and know everything about them. And so all of the selection that was done in the movie for selecting for idealized humans, and the problems of that.
I think that we're probably, as a society, going to realize that there are all sorts of ethical issues with that and not do it. Technically, I think it's completely doable. But my guess is, the constraints will actually be our decision to not do it, more than the technology. Any other questions? There's one up here, Penny.
If you can shout out [INAUDIBLE].
AUDIENCE: Yeah. So a generation ago, we had Jurassic Park make us think about what could be possible in the future that we could-- and the future is apparently here. So my question for you, and for the rest of the audience is, what have we learned about fossil DNA since that book and that movie? What is the limits and what are the possibilities now that we know more about DNA?
DAVID HILLIS: Yes, there was a period when we were thinking that we could pull out a lot more of DNA from ancient remains. And it turns out that most of the really ancient ones turned out to be various types of contaminants. So we can recover DNA from back a few thousand years. So we can get kind of 1,000-year-old, 2,000, maybe up to 10,000 years.
The samples beyond that are all pretty questionable. And so if you really wanted to reconstruct dinosaur sequences, for instance, we're nowhere close to being able to do that. There was one report a long time ago of someone who thought they had dinosaur DNA, and it was very clearly human contaminant-- contaminants from human DNA.
And so there's not really any credible evidence that we could do anything like that. So I think there's another thing that's probably a little more hopeful, which is you can estimate what the sequences were like of ancient sequences, without actually examining them through that phylogenetic technique. And that's actually much, much more profitable.
It doesn't work with 100% precision, but I think it's good enough. It has been good enough that people have been able to reconstruct what we think individual ancient proteins were like, build them in the laboratory, and then test them to see what their function was like. So that's sort of the truth of Jurassic Park. Actually recreating a dinosaur, I think, is pretty much pure fantasy, other than the living ones like that flying around today. Yeah.
AUDIENCE: What about the passenger pigeons? Or the [INAUDIBLE]
DAVID HILLIS: Yeah, so that's much more possible, since we have really good samples of those DNA for, say, passenger pigeons. So they just went extinct 100 years ago. And there are close relatives.
And so potentially, you could take the DNA from, say, a passenger pigeon, and take a close relative and replace the DNA, and actually have it. And there are efforts to do that. I think that there's been a lot more hype in those experiments than I think is justified.
I don't think that our progress is actually nearly as far along as a lot of the press reports make it out to seem. But there are some possibilities to do that. There are certainly efforts to do that, were people alive today think that they can bring back recently extinct species. And so I think it is at least a possibility. Whether it's a good idea or not is a whole other discussion. Yeah.
AUDIENCE: Hi. I hear about personalized medicines a lot. Is that likely to become a real thing when DNA and genetics become more available?
[INTERPOSING VOICES]
AUDIENCE: And how do you think it's going to become in the future, like for how long and [INAUDIBLE]?
DAVID HILLIS: Yeah, so the question is about personalized medicine, and will it become a reality? And I'd say it is already reality. I mean, you can, right today you go out. If you want your entire genome sequenced, you're only talking about a few thousand dollars now.
And so I think very shortly, it will become fairly routine that, when you get your medical profile, that you'll have your entire genome. And the real question we'll have to struggle with is how much of the information we want to use. So there's a lot of things that we could identify problems that we don't have a cure for. We don't have any way to deal with it.
So you can find out, for instance, that you're likely to have a disease that's likely to kill you when you're 40, but we can't do anything about it. Do you want to know that or not? Well, some people do want to know it. Some people, it would affect the way they live. Some people would just as soon not know it, because it'll affect the way they live.
I think that, again, it's going to be more about society decisions and personal choices. The technology is certainly there. And obviously, we're going to get more and more information about that genome, about what it means. And the amount of information is going up exponentially every year about the different portions of how different diseases are connected to, or genetic diseases are connected to our genome.
AUDIENCE: But I think also it promises [INAUDIBLE] right now. It's kind of exercised more on the risk part because of the human genome [INAUDIBLE].
DAVID HILLIS: The risk of the--
AUDIENCE: [INAUDIBLE] risk. So instead of treating the illness, they're treating the risk instead of--
DAVID HILLIS: Right, so yeah, there's certainly things you'd probably want to know about. So if you realized that you had a disease that made you much more sensitive to cholesterol in your diet, much more likely to have a heart attack if you eat high cholesterol, then you're probably going to be much more concerned about your diet. And if you don't have that gene, maybe you're not going to be as concerned.
And so that will probably change people's behavior with that information, and changing your risk for developing certain problems and diseases Is certainly something we can modify our lifestyles in response to that information. That's here today. We can do that now. Yeah, Brian?
AUDIENCE: David, can you talk a little bit about the competition to develop the biocorder? Who's funding that? How much money is involved? And is anyone getting close?
DAVID HILLIS: I don't know all the details about it, because it's largely a lot technology competition. So the science is basically there. I've tried to get a bunch of companies interested in doing this, so I'm really happy that there's a prize there, because that will give an impetus to do it.
I think it's $1 million dollar prize. I'm not sure the about the exact number. But it's a grand challenge that's being offered for anyone that can develop it. And I'm not sure exactly even what the rules are, the details are.
But my guess is that that'll help somewhat get a little ways down the road. But I really think the technology's going to come more from other applications. So all the money in the medical applications, and then the military.
Military has tremendous interest in this, because they want to instantly be able to identify pathogens in biowarfare. So if their troop's under attack, they want to know what the organisms are. So the military is very interested in it.
And there's lots of money in biomedicine. And so the technology is going to happen. And then once it happens, it will, obviously, be adapted and used for other purposes.
And then all of the interests I have in biodiversity will obviously-- if it takes $1 billion to develop it, no one's going to fund $1 billion dollar effort to develop a device just for biodiversity. But they'll do that for the health applications and the military applications. And then it will be a spinoff that can be used for everybody else, and affect the rest of our lives. I think we're probably out of time. Why don't we maybe take one more over here.
DAVID HILLIS: Is phylogenetic testing perfect or fallible? And if errors are possible, what is the mechanism for checking for them and correcting them?
DAVID HILLIS: Yeah, like any kind of method, I showed confidence limits associated with a lot of the analyses I did. And like any type of analysis where we're making an estimate from data, we make our best estimate, and then we have a confidence limit on that estimate. So in that sense, yes, there's clearly errors associated with it.
But we can measure that error and say what that error is. Any measurement in science is like that, really. And so the phylogenetic analysis is no different than that. All right, well, thank you very much. Appreciate it.
[APPLAUSE]
Forensic analysis of DNA has revolutionized crime scene investigations. DNA evidence from trace human tissues is used routinely both to exonerate and convict individuals accused of crimes. DNA has also been used in a number of high-profile criminal investigations to study pathogens that have been transmitted through criminal intent or activity.
These investigations have captured the imagination of Hollywood, but are depictions of DNA forensics in movies and on TV accurate? Evolutionary biologist and A.D. White Professor-at-Large David Hillis looks at the science behind crime scene investigations, and the possibilities and limitations of DNA forensics, as well as some of the new applications being developed for understanding human health and the biodiversity of the world we live in.
