Mon July 23, 2012
Unraveling The Genetic Code That Makes Us Human
Originally published on Mon July 23, 2012 12:18 pm
There's enough DNA in the human body to stretch from the sun to Pluto and back. But don't confuse DNA with your genes, says writer Sam Kean.
"They are sort of conflated in most people's minds today but they really are distinct things," he tells Fresh Air's Terry Gross. "Genes are like the story and DNA is the language that the story is written in."
In The Violinist's Thumb, Kean goes inside our genetic code, looking at the stories written by the fundamental building blocks within us. The book explains things like why some people can't handle drinking coffee and why some human babies are born with tails. It also delves into the history and science of the story of DNA, a nucleic acid which contains the genetic instructions that form the basis for all living organisms.
Among the stories Kean shares is that of Tsutomu Yamaguchi, who survived the bombing of Hiroshima, took a train home that evening to Nagasaki and then survived a second atomic bomb blast.
"He ended up surviving for an amazingly long time, despite being close to both nuclear bombs," says Kean. "He actually lived until 2010. So he must have had inside his cells a very efficient way to repair DNA and to make sure any mutations he might have had got patched up."
All living things accumulate mutations as they age. Segments of DNA can get cut out or swap with one another or never stop forming.
"Cancer is really a DNA disease," he says. " ... We have these certain genes that prevent our cells from growing out of control at the expense of the body. And it's a pretty good, robust system. But if a couple of these genes fail, then that's when cancer starts and cells start growing out of control."
On genetic tests
"Genes work with probabilities; they don't work with certainties. So most things that you're looking at with these genetic tests, it's not like you're condemned to automatically get the disease or the syndrome. There's a lot of factors in play there."
On babies born with tails
"At some point in our past, we did have a tail. It was interesting to me that in some cases, we have the genetic blueprints to make these atavistic traits inside us like tails. Another famous example is human embryos. You can see our gill slits. So it's interesting to me that we have these remnants that never quite got pruned out. We don't use the DNA for much anymore but every once in a while it can pop up and you get things like a little baby with a tail."
On nature and nurture
"The more that I looked at DNA, the more I realized it was nature and nurture. It's how genes and your environment work together to produce the person you are. So I don't feel like I'm really hemmed in because of my DNA. Obviously there's some things that were never going to happen for me — I was never going to play in the NBA — because I'm not tall enough or bulky enough. But even now we're finding a lot of behavioral traits that have some sort of genetic influence or roots in DNA somehow. We're also finding that those things don't rigidly dictate who we are. Genetic determinism is an idea that really scares people and understandably so. But thankfully the more we find out about our DNA, the more we realize we're not determined by our DNA."
TERRY GROSS, HOST:
This is FRESH AIR. I'm Terry Gross. My guest, Sam Kean, has written a new book about what DNA has to tell us about the mysteries of human history and about what our individual genetic makeup reveals about ourselves. The book is called "The Violinist's Thumb: And Other Lost Tales of Love, War and Genius, as Written by Our Genetic Code." 1
The violinist's thumb refers to Paganini's genetic disorder that gave him what Kean describes as freakishly flexible fingers. Kean's previous book, "The Disappearing Spoon," was about the periodic table of the elements. That might sound dry or arcane, but it was a best-seller. His work has been published in the New York Times Magazine, Mental Floss and Slate, and he's been featured on the NPR program "Radio Lab."
Sam Kean, welcome to FRESH AIR. Well, the book starts with you sending in a saliva sample so you can get your genome mapped. Why did you decide to do that? Was that just, like, research for the book?
SAM KEAN: It was research for the book, and I admit I did it on a bit of a lark. I just thought I would find I had an interesting gene or maybe something about my background that I didn't know, and so I sent it off and forgot about it for a couple weeks.
But then I went online and had to register the test, and that's when things got a little hairy for me because they go into and they look for susceptibilities to certain genetic diseases. Most of them I was comfortable looking at and knowing whether I had a susceptibility, but when I saw the one for Parkinson's disease, that is the one that got me.
My grandfather had it, and when I saw that they tested for susceptibility to Parkinson's, I had a very strong visceral reaction to that, and I sort of blacked it out, in that you can go in and prevent yourself from seeing any information about that.
GROSS: So you decided to basically redact the part about your genetic susceptibility to Parkinson's disease, but then later you got a note in the mail saying that you may be more at risk for Parkinson's than was originally stated in the first report that you got back. So explain what that note said and how you responded to it.
KEAN: Sure. Actually, I went in after I'd written the book and I felt like I had really gotten an education about what genetics means. And I felt like I was more prepared to handle the information. So after I finished writing most of the book, I went in, I broke the electronic seal, and I found out that I did not have, according to the information they had, a higher susceptibility.
And this was a big, big relief for me, obviously, that I wasn't facing this. But then later, as you said, I got an email saying they had updated test results for me, and one of those updated ones was for Parkinson's. And I clicked on it, and there was a bit of a switcheroo in that now, suddenly, it seemed like I did have a slightly higher risk for Parkinson's.
And beforehand, I think that really would have gotten me because it's one thing to suspect you might have it and to find out that you do. It's another thing to suspect you might think that you don't have it, kind of feel the relief, and then find out that you do anyway.
But at that point, again, I'd learned enough about genetics and how genes work where I felt comfortable with it, and I really feel like going through the book gave me an education on how genes work and the fact that genes really work with probabilities. They don't work with certainties.
And with most of the things that you're looking at with these genetic tests, it's not like you're condemned to automatically get the disease or to get the syndrome. There's a lot of factors in play there. And so I just felt more comfortable with the information.
GROSS: Well, exactly how predisposed are you? Like what changed from the first report to the second report?
KEAN: It was something like a 20 percent greater risk, and this is for a disease that only affects, you know, a couple percent of people anyway. So it was pretty modest risk. But I think that beforehand, it was just even the idea of Parkinson's, it was just a strong, visceral, emotional reaction to it. And once I educated myself a little bit, I realized that the risk wasn't that great anyway.
GROSS: So you're wondering if by getting your genetic profile, that if you would learn interesting things about your genes or about your background, did you find any, you know, surprises besides the unfortunate Parkinson's slight predisposition surprise?
KEAN: No, a lot of it confirmed things that I already kind of knew about myself, like the fact that I don't deal with caffeine all that well. I get a little jittery, or I have to end up staying up too late.
GROSS: Wait, wait, now what in your genetic profile would confirm that?
KEAN: There are some people who just don't break down caffeine all that well, and so it ends up staying in their system for longer than other people do, and they just know that there are certain genes out there that make proteins that can break it down pretty easily, and other people, they just can't break it down as well.
GROSS: OK, so you have empirical proof that coffee is difficult for you.
KEAN: Yeah, it was kind of - it was kind of nice to have it spelled out that it wasn't just me kind of making it up or kind of cherry-picking evidence. I could look at it and say OK, no, I probably do have something like that.
GROSS: So let's talk a little bit about what is a gene versus what is DNA.
KEAN: DNA is really a chemical, fundamentally. It's a substance, you know, it sticks to your fingers. It's a thing. A gene is made of DNA, but in some ways, it's better to think about a gene a little more abstractly. The way I mention it in the book is that genes are like the story, and DNA is the language that the story is written in.
Genes are something that scientists have known about for a long time. Gregor Mendel discovered them in the 1860s, and then in the very early 1900s his work was rediscovered and scientists really started digging in to genes. But we didn't know that genes were DNA for a long time after that.
So they are sort of conflated in most people's minds today, but they really are distinct things, and as hard as it is for us to understand it looking back, most scientists thought they were completely separate at the beginning of the 20th century.
GROSS: One of your chapters is framed around a Japanese man who managed to survive the Hiroshima nuclear bomb blast and then fled to Nagasaki, arriving just in time for the second atom bomb, which he also survived. How does his story relate to your book about genes?
KEAN: This man was Tsutomu Yamaguchi. He was in Hiroshima temporarily and as you said had to end up fleeing to Nagasaki, where he was from. And I explain it in terms of DNA because radioactivity, when it attacks your body, what it's really attacking most of the time is your DNA. It creates these things called free radicals inside you, and they go after DNA and end up kind of cutting it into pieces.
They do a lot of damage to DNA, and that's what gives rise to a lot of the problems with radiation exposure, especially things like cancer that come in down the line. And I looked at the story of Yamaguchi because he ended up surviving for an amazingly long time after being close to both nuclear bombs.
He actually lived until the year 2010, 65 years later. He must have had inside his cells a very efficient way to repair DNA and to make sure that any mutations he might have had got patched up. And so I - again, I used him as kind of a frame to explain how mutations come about, and then again how our body fixes mutation, sometimes in really incredible ways.
GROSS: And you write all living organisms have - like they accumulate mutations as they age. Like what?
KEAN: Well, there's a couple ways that this can happen. DNA uses four letters to store information. There's A, there's C, there's G, and there's T. Those are chemicals. But again, they're what DNA uses to store information. Sometimes a mutation will swap one of these letters in for another one, and it will change the protein that ultimately gets produced.
Other times, genes have a definite starting point, and a definite stopping point. It's just like a sentence that has a capital letter at the beginning and punctuation, a period, at the end. Sometimes the period gets erased, and so it turns into basically a run-on sentence and just keeps going and going.
Other times, especially with radioactivity, segments of DNA can actually get cut out completely. I like to think about this as those old gnarled telephone cords that you sometimes see, when they get completely twisted into a ball. If a bit of radioactivity comes streaking through and cuts the DNA at a certain point, some of those coils actually end up getting pulled aside, and your cells will solder the DNA together and leave that coil out completely. So there's a lot of different ways that DNA can get damaged.
GROSS: And is cancer basically the kind of mutation that you're talking about?
KEAN: Yeah, cancer, despite all its various forms and presentations, is really a DNA disease. It comes down to the fact that we have these certain genes that prevent our cells from growing out of control, from proliferating at the expense of the body, and it's a pretty good, pretty robust system.
But if a couple of these genes fail, then that's when cancer starts, and cells start growing out of control. So yes, cancer is very intimately tied to DNA mutations.
GROSS: My guest is Sam Kean, author of the new book "The Violinist's Thumb: And Other Lost Tales of Love, War and Genius, as Written by Our Genetic Code." We'll talk more after a break. This is FRESH AIR.
(SOUNDBITE OF MUSIC)
GROSS: If you're just joining us, my guest is Sam Kean. He's the author of the new book "The Violinist's Thumb: And Other Lost Tales of Love, War and Genius, as Written by Our Genetic Code." You have several pictures in the book. My favorite is a picture of a newborn baby with a tail. The tail is what is known as an atavism, an evolutionary throwback to, you know, an earlier time in our evolutionary past, like a tail.
Why does this interest you in terms of, you know, your book about the genetic code?
KEAN: Well, the book really tries to take us through human history, from our very earliest hours, and even in our microbial past, all the way to the glories of modern civilization. So yeah, all of us had a tail at one point in our development, and then it kind of gets reabsorbed into the body unless you have a mutation or something that prevents it from getting reabsorbed. And at that point, you can be born with a tail.
They're usually perfectly harmless, these tails, and this was of course one step along the way. We used to be, you know, monkeys, basically. Human beings share a common ancestor with apes and monkeys, and at some point in our past, we did have a tail.
And it was just interesting to me that in some cases, we have the genetic blueprints to make these atavistic traits inside us like tails. Another famous example is human embryos. You can start to see our gill slits. And that, of course, is even way farther back in our past than tails.
So it's just interesting to me that we have these remnants of traits inside us that never quite got pruned out. We don't really use the DNA for much anymore, but every once in a while it can pop up.
GROSS: When the fetus is being developed, does it ever have a tail?
KEAN: Oh, yes. The fetus actually does have a tail up until about 16 weeks or so.
GROSS: What are some of the other atavisms that you found in your research?
KEAN: Gill slits was another one. We also have - this is more of a controversial one. We also have the remnants of what's called the vomeronasal organ. It's basically a second kind of nose inside us. A lot of mammals have this. Mice, for instance, depend very heavily on their sense of smell, and so they have this organ inside us.
And humans have some sort of remnant of it, but no one quite knows if it works yet. There's a lot of scientists who don't think it does, but then there are other scientists who say, no, they think it does do a little bit of something. And its basic job in most mammals is to detect pheromones. You know, we hear about pheromones sometimes in the news, or there are products that claim that they have pheromones added to them to make you more attractive to the opposite sex, things like that.
But this pheromone detector, we have a trace of it inside us. So that's another good example of a genetic atavism.
GROSS: In your book "The Violinist's Thumb," you write about cannibalism, which I didn't expect to see a chapter about, and why cannibalism is not only, you know, a kind of, you know, abhorrent action, but it's also unhealthy.
KEAN: Yeah. There are certain diseases, prion diseases, they are called, that you can get from eating other human beings, specifically if you eat their brains. These prions can get inside you and they can attack your own brain. And if people remember the mad cow scare from the mid-1990s; that was another example of a prion disease.
But there is some indication in our DNA that perhaps cannibalism was a lot more common in our past than we might like to think about. There are certain genetic signatures that protect us against prion diseases, and these signatures are pretty widespread among human beings worldwide, and for them to get that widespread, you know, it's possible that we would have had to indulge in a lot of cannibalism.
This is another controversial theory, but there's a lot of scientists who think that it's good evidence for widespread cannibalism.
GROSS: One of the pictures in your book is about Dolly, the sheep that was cloned. It's like the first cloned animal. What do you think the odds are, as someone who's not really an expert on calling the odds on this, but what do you think the odds are of a human being being cloned one day?
KEAN: Human beings are actually tougher to clone than other animals are for a few reasons. And actually it's not just human beings, it's primates, generally. We have this apparatus inside our cells that holds part of the nucleus in place. And when they try to take the nucleus out - which is a step during the cloning process - when they try to remove the nucleus, it ends up kind of tearing some things.
So human beings actually are tougher to clone than most other animals are. So that's one of the big technical limitations, and I'm not sure we know how to overcome that yet. If we could overcome that, then I think it would be feasible to clone a human being. But as I explained in the book, I'm not sure that there would be a lot of demand for cloning a human being simply because, again, your genes don't determine who you are.
So if you cloned someone, you might get someone who looks sort of like the person, or a lot like the person, but it would be a different person. The world we live in now is much different than the world was 30 years ago. People will have different memories. They will just be a different person. They would probably be less alike than most identical twins were. So even if we could clone human beings, I'm not sure there would be a lot of demand for it.
GROSS: So now that you have a map of your human genome, to what extent do you feel like your script has already been written, you're predisposed to certain characteristics or, you know, possibly an illness, and, you know, part of your script was written when you were born?
KEAN: The more I got into studying genes and human DNA, the more I realized that genes really deal in probabilities. They don't deal in certainties. And that wasn't something that I really understood before. The usual dichotomy is between nature or nurture, and the more we look into DNA, the more we're realizing it's really nature and nurture. It's how genes and your environment work together to produce the person you are.
And so I don't feel like I'm really hemmed in because of my DNA. Obviously, there's some things that were probably never going to happen for me; I was never going to play in the NBA or something like that because of, you know, I'm not tall enough, I'm not bulky enough. Things like that.
But even though we're finding a lot of even behavioral traits that have some sort of genetic influence or roots in DNA somehow. We're also finding that those things don't rigidly dictate who we are. Genetic determinism is an idea that really scares people, and understandably so. But thankfully, the more we find out about our DNA, the more we realize that we're not determined by our DNA; that who we interact with, our environments, things like that, it works with us to make us who we are.
GROSS: Well, I want to thank you so much for talking with us.
KEAN: Well, thank you for having me.
GROSS: Sam Kean is the author of the new book "The Violinist's Thumb: And Other Lost Tales of Love, War and Genius, as Written by Our Genetic Code." You can read an excerpt on our website, freshair.npr.org. I'm Terry Gross, and this is FRESH AIR. Transcript provided by NPR, Copyright National Public Radio.