Remarks
Office of the Science and Technology Adviser
Washington, DC
February 28, 2012


E. William Colglazier:

Well, let me welcome all of you here. We're very glad you're coming to our Jefferson Science Fellows lecture today. Very pleased to have Alan McHughen to give his lecture. He's not only a distinguished Jefferson Science Fellow, he's also working part of his time at OSTP as a senior policy analyst on a special project, and at the State Department he's working in the INR Bureau. Alan earned his doctorate at Oxford. He worked at Yale and then at the University of Saskatchewan before he joined the University of California at Riverside. He is a molecular geneticist with an interest in crop improvement and environmental sustainability.

Before I came to the State Department, I worked at the U.S. National Academies and the National Research Council, and Alan served on a number of panels and studies at the academies dealing with issues associated with genetically modified crops. He served on one looking at the environmental effects of transgenic plants, a second one investigating the health effects of GMO foods, and the third was looking at sustainability and economic impacts of biotechnology on U.S. agriculture, so he's got a depth of experience on issues associated with genetically modified agriculture.

He's developed commercial crop varieties using both conventional breeding as well as genetic engineering techniques, and he has considerable experience bio-safety and policy issues arising with this technology. Plus, also, he has an award-winning book communicating to the public on these issues entitled "Pandora's Picnic Basket: The Potential and Hazards of Genetically Modified Foods," which, as you know, in various places around the world, it can be somewhat of a controversial issue.

So he has a great title, I think, for his talk today: "What Everyone Needs to Know About Modern Genetics, or Who's Getting in Your Genes." So we're very happy to have Alan. Thank you.

[applause]

Alan McHughen:

Thanks, Bill, and thank you all for coming. It's certainly a great honor to be part of the Jefferson Science Fellow family, and I know we've already had several superb talks in the series this year, so my colleagues in the Jeffersons have set a high bar.

Why did I come to State Department? How did I get interested in the Jefferson Program? Well, I've been an academic scientist my whole career, and I noticed over the past number of years that more and more public issues have some kind of a scientific basis, yet many of our leaders and our followers don't have the scientific training to really comprehend the intricacies of science and technology. And when we consider things like not only genetics or genetic engineering but climate change and the internet, cyber-security, all of these things have a scientific basis, and if we develop policy with a poor foundation, well, like any building that's erected on top of a poor foundation, it's eventually going to crumble. So I thought that part of my job as a scientist, and as a public scientist, is to get more involved with teaching people who don't have that scientific background--very capable in other areas, perhaps--but to try to help them build a solid foundation so that, whether it's simply public understanding of what the issues are or developing public policy, the foundation is solid and we can move on from there.

Now, today we're going to investigate some aspects of modern genetics, what I think people should be aware of. You don't have to become a scientist, let alone a geneticist. All you have to do is apply some critical thinking skills, which I know you all have already, with some basic information that I'm going to provide today. But I hasten to add, I'm not going to give you all the answers. I'm going to give you something far more important; I'm going to give you the questions.

So if we take--what we have here is a representation of a rice plant. It need not be a rice plant. It could have been a wheat plant, or, for that matter, it could have been a mouse or a human, a fungus. If we take a closer look at any part of this organism, we'll see under the microscope it's composed of cells. Now, these particular cells are kind of generic. We've taken it from the leaf here, but we could have taken it from the root or the flower, anything else. They look pretty much the same. If we take a closer look at the nucleus inside any one of these living cells, we'll see chromosomes. You've heard of chromosomes, these dark, wormlike things that are inside the nucleus, again, of any living cell from any higher organism. You'll see these chromosomes. And then, as we take a magnified view of the chromosomes, this is where we find the DNA, all right? I mean, DNA is famous. It's a pop culture celebrity. You see DNA mentioned frequently in ad campaigns. You know, "It's in my DNA," or, "We built it into our vehicles' DNA." Fewer people know that it actually stands for deoxyribonucleic acid. But, nevertheless, this is the material of heredity. Inside the chromosomes, it's packed inside proteins, so it's more easily visible at certain stages of the life cycle of the cell.

We move along. We see the DNA is actually composed of long chains of--there's a backbone material and then the DNA bases, or the A, G, T, and C, chemicals abbreviated from their chemical names, but it makes it easier for us to comprehend, to visualize them. If we took the DNA out of our rice plant, take a single cell of the rice plant, took the DNA and stretched it, it would be maybe four inches long. If we did the same exercise from a human cell, and, again, taking it from any cell in the human body, extracted the DNA and stretched out, it would be a couple of meters, six feet long, approximately. Now, just to prove to you that size doesn't matter, if we did the same thing with the wheat plant, it would be much longer still, all right? So just because we have six feet of DNA doesn't make us, in any way, genetically superior to a rice plant, unless you want to, using the same logic, admit that we are inferior to a wheat plant.

I'm going to take you back to high school for a few minutes, just to refresh your minds on what you learned in high school. All living things are made up of cells. Bacteria are made up of one cell, typically. But things that you can see visually are made up of multiples of cells and cell products. The DNA is the hereditary material. It's the storehouse. And I call it a recipe book. All living things use DNA to transmit hereditary information from one generation to the next. Every cell carries the entire DNA recipe book for the entire organism.

So, as I mentioned initially, we took a cell from a leaf of rice, and we looked at that DNA. It was maybe four inches long. Exactly the same DNA would come out of a root. We could do the same with a human. If we took a human liver cell, extracted the DNA, the DNA would be exactly the same as if we took the DNA from a skin cell or a brain cell. So one cell could, in theory, grow into an entire plant, animal, including humans, if it's stimulated in the right way. Now, you've heard of stem cells, human stem cells that can grow into any tissue type. Well, just elaborate that a little bit more. You can create an entire organism, right? And this is the theoretical basis of cloning. We can do cloning in a lot of plants. We can do it in some animals, and, theoretically, there's no reason why we can't do it in any. We just have to find out the right environmental conditions that will stimulate a given cell to grow into an entire organism based on the species that that cell came from in the first place.

Additionally, we can take a piece of DNA and transplant it from one living thing to any other and have it function in the new host, the recipient host, as it did in the original. This is the basis genetic engineering. This is what allows us to take a gene from, for example, a human and put it into anything else, a bacterium even, and have the bacteria read the gene, read the genetic information on that piece of DNA, and make a given protein. And it is the presence or absence of a protein, usually multiple proteins, that give us traits. Okay? So a gene is a unit of information. It's carried on the DNA. The information is read by the machinery inside the cell to make a protein, and the presence or absence of that protein is what gives us our traits. It also gives rice plants the rice plant traits.

What is a gene? This is interesting, because although I'm a geneticist and we've had geneticists coming along ever since Gregor Mendel, and even before--they weren't called geneticists then, but people who studied these hereditary units--we don't have a standard definition of a gene. We talk about genes. We talk about genetics. But there's no agreed, standard, simple definition of a gene. It's different to different people. We all know kind of theoretically what it refers to, though, and that's usually all we need to do. Probably the simplest way is to think of a gene as a unit of information that tells the cell machinery how to follow a recipe to make a particular kind of protein. Proteins are often enzymes. All enzymes are proteins; not all proteins are enzymes. Could be structural proteins as well. But most of the work of the cell is done by enzymes.

Now, getting back to that A, C, T, and G, those base letters we talked about in the composition of DNA, it's the particular order of these bases, just like in English, particular orders of our 26 letters that we use to make words gives us different meanings, all right? So it's the specific order of the letters. The recipe book--in DNA, the words, unlike in English, are all three letters long. For example, if we have the basic A-T-G, that tells the cell machinery to bring in the amino acid methionine. There are 20 of these amino acids floating around in the cell, and when the machinery starts reading a recipe on the DNA, it'll see base letters A-T-G in that sequence, and it knows, "Okay, I'm going to bring in a methionine." And then it reads the next three letters, understands the word. It brings in another amino acid. And it slowly builds up. It attaches the new amino acid to the methionine, and it slowly builds up what's called a polypeptide chain, ultimately becoming a functional protein. Now, of course, sometimes there's some processing done to this chain. It's not always simple. Sometimes it is very simple. But, essentially, a protein is a long chain of amino acids, the order of which is specified by the particular sequence of the letters in the DNA.

We have an example here, and I've converted some of these letters into English so we can understand it better. We have "the cat ate the rat." Okay, not a particularly exciting recipe, very simple. But even in the DNA language, this is extremely small. You'll notice that we have other letters here. They don't make words. We don't really understand what those mean. The same is true in the DNA recipe. There are a lot of bases. In fact, most of the bases of human DNA don't really code for a particular amino acid. They're not part of a functional gene or a coding region. You'll notice, also, that we have start and stop symbols. We have the beginning of the recipe: "Start here." And there's an ending, a terminal sequence, to tell the cell machinery, "Stop. You've made the protein. Stop making further. Stop reading at this point."

So, getting back to this material, at either end of the gene, you have a lot of these bases. Most of the bases in our DNA are not actually part of the recipe itself, but they are regulatory. They are important. They used to be called "junk DNA," because we didn't understand what it was there for, and, you know, maybe it was just junk. It isn't, but that's a different story. Get into that on a different day. This is the crucial lesson: DNA uses the same language in every species. So we can take the recipe from the human genome for, say, insulin. We're all familiar with insulin? We know what insulin is, right? We can take that recipe, make a copy of it from humans, and put it into a bacterium, and the bacteria, which has no use for insulin--bacteria don't have blood; they don't have blood sugar; they don't have any need for insulin; they've never seen an insulin recipe before--but they can read the human recipe for insulin and make insulin, exactly the same as it's made in humans. And diabetics who are dependent on insulin now are using, almost all of them, genetically engineered insulin that came from bacteria based on the recipe that originated in humans. This only works because the DNA language is the same in bacteria as in humans.

An average gene--maybe 1,000 of these base letters. I don't expect you to read these, but the machinery of the cell can do that. So here's approximately 1,000 in a single recipe. You know, "the cat ate the rat" is pretty small. This is much more typical. We can't read this. But what we can do, we can take a closer look at one portion, and you can see, again, the same four letters of the biological genetic alphabet, A, T, C, and G, is there, and it's in a particular sequence. We can't read this, but if we change things, we can convert this to English. And I just made this very simple again. You know, add one cup ice and one up tea, you're making, you know, iced tea, obviously. At least you can understand this, right? Bacteria don't make iced tea. But you can understand what this recipe--it's pretty simple. It's pretty simple. But you could follow this recipe to make iced tea if you so wished. Now, again, this is a very small segment. It's only a few bases long. If we had a recipe composed of three-letter words and we had, you know, 1,000 letters, so that's, what, 330 words, that's a pretty standard recipe. You could get away with a much more complex recipe using that number of words, and that's typically what biological systems use.

How does this fit in with the chromosomes? Well, again, if I use the analogy that our genome is like a recipe book and we go back to our example of rice, the entire complement of DNA in that rice cell, i.e. in the rice plant, consists of 37,544 recipes. Now, I show it as a huge book here. In reality, they're strung together, so a better visualization would be like in a long scroll where the recipes are associated one after the other on this long scroll, but for illustration, consider this as a huge book with 37,544 pages in it. And somewhere in this book is the recipe for iced tea, or for whatever the rice plant needs to make, slipped in there.

When we do genetic engineering, we can take a recipe, make a page with the recipe on it, and slip it into the rice plant somewhere, right? We don't know exactly where it will go. It could be near the front, could be near the end, could be somewhere in the middle. Nevertheless, once the recipe is in there, the rice cell machinery can find it, read it, understand it, and make the new protein, giving a new trait to the rice plant.

Now, in higher organisms, as you realize, you know, we have two sets of these genomes, one from each parent. In this situation, I'm just illustrating, you know, we have a male side and a female side. We slipped--in our genetic engineering, we slipped that recipe into the male one, just, again, more or less randomly, to give this side an additional recipe, 37,545 as opposed to 37,544. Most of these are exact copies of each other coming from the mother and the father. Some of them are a bit different. Some of them are unique.

Now, let's take this a step further and a more practical use. We can consider we have, out in the desert, a plant that is happy to grow with lack of moisture, okay? It's sitting in the sun. It's hot. It's dry. Yet, it's still healthy. It produces its leaves. It flowers. It's just fine. Alternatively, we can consider a corn plant, right? A huge crop in our country and around the world. A corn plant needs water. It cannot survive in the desert. Water is a diminishing resource virtually everywhere in the world, so wouldn't it be nice if we could figure out what this desert plant does to enable it to thrive in the absence, the large absence, of water. Can't go without water at all, but it does much better with smaller amounts of water.

If we find--if scientists find there is a genetic basis for the drought tolerance or water-use efficiency in that desert plant, it's possible to identify it from the genome or the genetic complement from that desert plant, make a copy of it, and transfer it into the corn plant. You'll see that when this transfer occurs, it's inserted--the copy of the drought resistance gene is inserted into the corn genome, but there's no destruction of the corn genes; it's an addition. In that situation, the corn plant is now growing in drought conditions or lower water conditions, and the gene, obviously, in this case, has affected drought tolerance or increased water-use efficiency for this thing.

The desert plant is not deprived of its gene. We simply make a copy of it. I've had this question once when I was talking about genetic engineering, of taking a gene from a mouse and putting it into a plant, and the reporter was shocked that I would deprive the mouse of its gene. But we geneticists--it illustrates how sloppy sometimes we geneticists--and other scientists--can be when we say we take a gene from one organism and put it in something else. We don't actually take it in such a way that it deprives the source. We simply make a copy, so... Similarly, when we take that gene and insert it into the corn plant, we're not losing any genes from the corn plant. The corn plant still has its full complement, but it has one additional gene. This is relevant to issues of biodiversity. We're not losing any genetic biodiversity by engineering a gene into a given plant. All of the original genes are still there.

Now, here's a situation, going back to staining wheat chromosomes in this particular slide, looking under the microscope. This is not what they look like normally. The stain is artificial. But it illustrates in bread wheat certain varieties of bread wheat that have the red wheat chromosomes and fragments from secale, or rye. Right? This is not genetic engineering, but it is the transfer of genes from one species--in fact, one different genus--into another, wheat. Breeders do this--cytogeneticists do this because rye has certain features that are important, such as cold tolerance, and if we want to grow wheat varieties in places where the climate is cooler, then by adding some of these genes from rye, we can get the wheat plant to grow and survive where ordinary wheat plants would suffer.

Now, these fragments of chromosomes contain hundreds of genes. Don't even know what they are. We don't know what they do. We do know that the fragments will contain the cold tolerance genes and they function in the wheat plant. But this is not genetic engineering in terms of recombinant DNA technology. It is a transfer of genes across what you may have heard as the species barrier. Right? Why is it that people are fully accepting of this technology but not of the previous technology of inserting drought-resistance genes into corn? So much anxiety around the world caused by genetic engineering, particularly in agricultural products, by using a more precise technology called "recombinant DNA," or "genetic modification," to produce something that could be beneficial. No one questions this. Is that because they accept it? And if so, if they accept this form of genetic modification, why don't they accept the other form of genetic modification? Alternatively, maybe they're simply not aware that plant breeders have been doing this for years and crossing this so-called mythical species barrier. That's a question I have, right?

We have mutants in DNA. Mutations occur naturally. There are a number--you know, we call them polymorphisms and variance because most people get upset at the term "mutant." They don't like to think of ourselves--we don't like to think of ourselves as mutants, but we all are. We have single-nucleotide polymorphisms, which is simply where we have a DNA base changes. It can be spontaneous, and very often it is spontaneous. Mother Nature does this to us. She does it intentionally. It's good for us in the long-term. We can also induce it, which is usually not a good idea. So we can have a situation, you know, going back to "the cat ate the rat," where we have a single base change. Now, you know, the message, the information, the recipe says, "The bat ate the rat." Well, it still makes sense, but it's not the same as the original message, "the cat ate the rat," right? This is a single base change, a snip, what we call a snip mutation. It could also occur--the change could also occur outside of the recipe itself, right? So over here is where the change is, out of the coding region. This won't make any difference to the recipe. It's still, you know, "the cat ate the rat," which was the original message, so that's maintained. But there is a difference now between this organism that has this mutation and this organism that has this mutation and the ancestral type that didn't have any mutations, at least at this point. And we can use these changes, these mutations, to identify different lines that arose from these mutations. These organisms that then had progeny, they will have the same mutation, because it's carried on generation to generation.

We also have short tandem repeats, three to seven bases with many, many copies. In the example here, we have the gene is now "the cat at the rat rat rat rat." If you're a cook and you read this recipe, you'll figure, "Okay, there's a typo in here." If you're a bacterial cell or a rice plant or a human cell, rice cell, they're very good at reading and following instructions but they're not very smart at saying, "Oh, there was a mistake here." They can't figure out what went wrong, but something went wrong.

You probably heard of CODIS, the combined DNA index system that we use in forensic work. This is--the short tandem repeats and the Y chromosome tandem repeats are the basis of the CODIS system, using 13 different loci scattered around the human genome. They're not part of a functional gene, so you can't associate a particular CODIS locus with a phenotype, which is an appearance situation.

Human karyotype--you've probably seen pictures like this, which shows that the human chromosomes--there are 23 pairs, and it includes an X and Y if you're a male. This is obviously came from a male because it has the Y chromosome down here. If we take a closer look at one of these, chromosome 11--now, there are hundreds of genes on this particular chromosome. We have, in this slide, both the male and the female, or the source from the male and female, but we can't tell which is male and female by simply looking at it like this, but we know one of them came from the dad, one of them came from the mom. They both carry hundreds of genes, and one of them is the insulin gene. So we mentioned insulin a little while ago. Let's take a closer look.

The base sequence of the insulin gene from humans is over 4,000 of these bases long, but most of them are not part of the actual recipe itself. Remember, there's information, or genetic bases, on either side, front and back. It starts here at this A-T-G, all right? Remember what A-T-G means? Methionine, great. [laughs] What a gift. So our proteins start with methionine as an amino acid. That's just standard, right? It's the way biology does it. Sometimes it gets clipped off later on before it actually becomes a functional protein, but when you're reading DNA bases, you look for this A-T-G as a starting point, and then we know. The Human Genome Project sequenced all 3 billion bases in the human. There's over 3 billion of these, so we're looking at a very small fragment here. It happens to be human insulin, but, you know, we can also look at other organisms, you know, other relatives. And if we look at the homology, which is the similarity of genes in different species, you'll see that with insulin we're actually very similar to the rat, okay? So the rat, it's 102 amino acids long. It starts with methionine, just like in humans. It's followed by alanine, and then lysine, and then so on, until we have, you know, all of the amino acids that make up insulin. There are 19 differences, though, between the rat insulin and the human insulin. These 19 differences may or may not make a big difference, right? I mean, remember when diabetics used to have to inject insulin that was extracted from pigs or cows or other farm animals? They could probably get away with using rat insulin as well, because it's still functionally much the same, right? I mean, rats, unlike bacteria, do have blood systems, do have blood sugar, and they have to be able to control it somehow. So this is the concept of homology. If we look at other mammals, we'll find that there's a great degree of similarity between the insulin genes for all those different animals.

And then another concept is called synteny. If we look at human chromosome 21, right, remember, we--down syndrome is caused by trisomy. It's where people have three copies of chromosome 21. We're ordinarily supposed to have only two copies, right? But let's look at this a little bit closer and compare it to the mouse, chromosome 16. We take chromosome 16. We line them up like this. We say, "They look pretty similar, don't they?" Well, karyotypes are not particularly useful for this kind of genetic analysis. But in recent years--we've been looking at chromosomes through microscopes for, you know, 100 years. We look at it using modern molecular tools. We can see a schematic here of a human chromosome 21 and a mouse chromosome 16 lined up, and if we take a fragment from the long arm of the human chromosome and compare the gene sequence--I know you're not able to read this, but this is a listing of all of the gene recipes in order on the human chromosome 21--we find that it lines up almost exactly with the same gene sequences in the mouse chromosome 16. Fascinating.

If we buy a recipe book, our typical arrangement is that you have all the appetizers in one chapter, entrees in another chapter, desserts in another chapter. Biology doesn't do that. Mother Nature doesn't care. She just dumps them all in there. They're not arranged in any particular order. But, interestingly, the order is maintained across different species. So we have situations where we likely have a common ancestor, okay? We have the universal language of DNA. Every organism from bacteria up to humans--or perhaps I should say up to wheat plants--use the same DNA language. The bacteria with human insulin gene make human insulin, as we already mentioned. We've seen that. The homology of genes across species--so many different of our mammals produce insulin, and it's very similar--you know, very subtle changes from one to another. There are at least 23 genes that are common across all living things. Humans and bacteria, rice plants, wheat plants, corn plants, flying foxes--they all contain these 23 genes, absolutely identical.

And then synteny, the order of the genes in chromosomes, is maintained across higher organisms at least, the ones that have chromosomes. It's not just mice and men. We also have it in cereals. Wheat, rice, corn, sorghum, oats, millet, et al. All cereals, all recognizable, all important crops. You can line up their chromosomes and see the order of the genes within them match up, right? Now, there's some distribution. We do have mutations occurring. We do have translocations and different chromosomal changes, so it's not perfect. But for a chunk of chromosome, you can--a given chunk of chromosome, whether it comes from a human or a mouse or a corn plant, you can look at relatives to that species and see similar chunks, similar arrangements in other species.

Some popular misconceptions--the concept of proprietary genes, right? You've heard of fish genes or tomato genes or human genes. Geneticists don't use these, except when they're being sloppy, which is fairly common. But there are very few genes that are actually unique to a given species. Traits, on the other hand, traits are a function of our genetic makeup and our environment, and especially the environment acting on those genes. And genes do mutate. Mutations are, as I say, normal occurrences. They accumulate the changes over many generations, so that's how we contract them.

Genetic purity is another misconception. We geneticists don’t like to talk about purity. We talk about homozygosity or homogeneity, but we don't talk about purity, genetic purity, in the way that you sometimes see in the popular press. Racial or genetic purity is not a biologically meaningful construct. So get suspicious whenever anyone talks to you or you read an article about genetic purity. And particularly, think of this. Recent research shows that most humans, homo sapiens, carry genes from Neanderthals. Anywhere from 1 percent to 4 percent of our genome actually originated with this other species, Neanderthals. Now, how many people are happy to be related to Neanderthals genetically, right? [laughs] We have at least some in the room. But, you know, there's some people who are not related to Neanderthals. The only people who are genetically pure are from sub-Saharan Africa. They did not take part in the--what do you call it? The impure Neanderthal genes. So, again, the next time you hear somebody talking about genetic purity and maintaining purity in the human genome, you know, think of the Neanderthals and the contributions they made to our human civilization.

Another popular misconception--a given gene is rarely "for" a disease or trait. Sometimes it's associated, and that's often the best we can say it. There's an association, a statistical association at that, or a linkage. Correlation is not causality, all right? We see this all too often in the popular press, where simply because you see an association or a correlation between something, it has to be there because it caused it. And predisposition--you may have, if you get your DNA analyzed, you'll get a report with lots of possible predispositions to particular conditions. That doesn't make it a certainty. And, you know, we have the proof of this. Predisposition is not inevitable. Even something like a predisposition to, you know, anorexia, you can work around that. It isn't necessarily so.

The Human Genome Project--touch on that for a few minutes. It cost $3.8 billion, an international effort. It took 13 years to compile the rough draft. It's still being refined. It's not fully complete, but, you know, pretty close. Nowadays, we can do a genetic analysis of a human for a few hundred dollars, and it takes a couple of weeks. Several companies offer this service, so you can pick and choose which one you like best. As I say, you pay your money and they will do an analysis. It's not a complete DNA sequence. You can do that too, but that costs more money. You'll get a report on several dozen genetic traits such as predisposition to obesity or breast cancer, certain types of cancer, other types of cancer, and so on. So, you know, most people who do this are particularly interested in the health and medically related issues. Some are more concerned about their ethnic ancestry, right? If you're a genealogist, you want to know, you know, your ancestry. The DNA analysis is really useful for sorting that stuff out. And then there's some other assorted things, eye color, male pattern baldness, and so on. More curiosity. Your blood type. Why you would have to get your DNA analyzed for several hundred dollars when you can get your blood type much more easily, well...

Okay. I had my DNA tested. I sent my DNA off, and--disclosure--this is my result. So I'm giving up privacy on certain aspects here. What we get back from this particular company, deCODEme Com, is a schematic diagram of the different chromosomes lined up, and within that, I can, online--and unfortunately we can't do this live online, because we don't have access here, so these are screen caps. We can focus in on certain parts of any given chromosome that we choose, and, you know, if we wanted to go back and look at my DNA sequence for insulin, we could go back to, you know, chromosome 11 here, focus in on the top end, near the top end of chromosome 11, and take a look at the DNA sequence and see how my sequence compares to the standard human. Now, I focused in here on the insulin gene, and what this shows--first of all, this here shows that the insulin gene is located near the end of this chromosome. Down here is the actual DNA base sequence for a standard human, and it's in different colors just to highlight the four different bases, A, T, Cs and Gs. The red bar is the coding region for insulin, and then down below we have areas where there are snips, right? Remember snips? Single nucleotide polymorphisms? The cheaper studies will focus on the differences in these snips rather than reading the entire genome, which is a full-sequence analysis. Snips occur--there's probably, what, 3 million or so in the human genome--3 billion bases, 3 million snips--so 1 out of 1,000 bases is a variant; it's a mutation; it's a snip. And those are shown here on the website, and they give you the alternate. Some people have a C. Some people have a T at this location. All right? It doesn't make any difference. It doesn't make you superior or inferior. It just is a difference. We can tell the difference. Most snips are simply nonfunctional. There's changes. They don't cost us anything. They don’t reward us with anything. They just make us different from other people--similar to our parents, who gave it to us, but different from others who don't have it.

So, uses of personal DNA. DNA in forensic and legal issues, we touched on already. The CODIS, with the 13 STRs. The "C.S.I." factor--we all watch "C.S.I." or spinoff programs and we wonder, "Why can't we get DNA analysis overnight and put in jail all of these crooks?" Right? "C.S.I." is great in some respects in that it tells people that, yeah, there's a lot of excitement in genetics and forensics these days, but it's very poor in giving false expectations, and I know--I run a program on law and science where I teach judges and lawyers--my colleagues and I teach judges and lawyers about, you know, recent developments in science, and they're saying that, more and more, they get juries coming in saying, "Where's the DNA evidence?" And whether it's a criminal trial or a civil case, they want to know where the DNA evidence is, and it simply isn't always appropriate or available. In civil cases--again, in legal disputes, we use it for ancestry, paternity, right? Disputed paternity is pretty well a thing of the past now because of the DNA stuff.

Health issues--again, predispositions--and they are predispositions.

Personalized care--this is going to become more important. When I get my DNA analysis done, one of factors they looked at was warfarin, which is a common blood thinner. I don't take warfarin, but when I do, I'm going to tell my doctor, if I ever need to, my doctor that I need a higher dose than normal. All right? Drug dosages are established by what the average person is and how a drug works on the average person, but with my particular genetic makeup and the way I metabolize warfarin, I will need a higher dose than most people, right? That's useful information. Some people will require a lower dose to get the same pharmaceutical effect--therapeutic effect.

Ancestry, very interesting stuff with genealogy. I was able to find out that my ancestors came from Ireland. [laughs] Was that worth $1,000? [laughs] But it's fun. It can be fun. On the other hand, you can look at things like human patern--down to $79 to get a paternity test. This is not the full sequence. It's not even the snip analysis. It's just, you know, a single bit of information. You send in, you know, the DNA samples, like, swab samples from your cheek, a spit sample, and the company will tell you, for $79, whether, you know, the supposed son is actually, you know, a product of the supposed father. But you can get your cat and dog done also for 150 bucks, get their DNA done. And a lot of people do this, for curiosity or for security, whatever. So, you know, there's a new business building up on this based on science.

Now, here's where something went wrong. There was a woman, dearly loved her pet, and, the way of all flesh, this poor pet eventually died. She was so distraught, that she had the thing cloned. And a company in Korea cloned her pet, and she thought that this was reincarnation. Right? So it's heart-rending. A very simple scientific misunderstanding. Somebody made money out of this. Now, you could also argue that, well, this woman is happy again. She got her pet back. She's thrilled. What's the big deal? Nobody tell her that this is not really her pet.

[laughter]

Not my job. Sorry.

Okay, final exam. Remember, I told you I wasn't going to give you the answers; I'm going to give you the questions. Here come the questions.

What about people, they have a child, the child has, say, polycystic kidney disease, a genetic trait, and by the time that child hits, you know, early adulthood, middle age, they're going to need a new kidney. So this family decides, you know, we were going to have only one child, but now we're going to have another one, because our child is going to need a donor. Right? How would you like to be conceived primarily for the purpose of being, you know, a spare organ bank for your sibling? We in society haven't really addressed this question, but people are doing this. People are doing this now. And you can, you know--people say, "It's none of your business why we have an additional child." Who's looking after the rights of the child who's supposed to be the organ donor here? Gets a little bit more insidious when you look at orphan selection, people shopping around orphanages to acquire a new baby, and they're demanding DNA tests, because they don’t want to take a chance on, you know, going through all this hassle, spending all this money, loving this child, and then turn out that it has some predispositions to some nasty disease. So I'm going to insist before I sign the papers of getting a spit sample from this child, and I'm going to send it away. And, you know, you could make a short list of, like, four or five babies that you like the look of, send away their DNA, get the results back, and then make a choice based on the results.

Lots of issues here. First is, you know, we find, perhaps it is reprehensible, or perhaps it isn't, depending on your point of view. We haven't really done this in the past as a society. Who's looking after the rights of these orphan children? And particularly when you consider four of them, say, got rejected and one of them got chosen, there's very personal, intimate information--our most intimate knowledge, our DNA, is known by strangers. What are they going to do with that information? You know, if I'm one of these orphans, I don't even know that these people that I've--well, maybe I've met but I certainly don't remember--they have my genetic database. They know more about me than I know. Is that right?

Dating services, right? Online dating has been wonderful for those of us who are looking for a mate, right? Sometimes it works. Sometimes it doesn't. It's becoming more and more accepted, right? And, you know, we all go into these situations knowing that, you know, there are pitfalls, but there's also opportunities, right? I don't have to go to a bar to try to pick up somebody if I don't like bars. And, you know, I know a number of very successful relationships using online dating services. When are we going to start supplying DNA to these services, just to make sure that this person on the other end of the internet is actually who they say they are? Huh? And mate selection, right? Just in ordinary dating, before you get married, "I want a sample of your DNA, just to make sure, you know, I know that, you know, you're telling me the truth about your ancestry or that, you know, you don’t have heart disease running in your family, because, you know, I had a parent died of heart disease and I really don't want to put up with that grief again." You know, little understanding that you are the one that's more likely at risk, but nevertheless.

Identical twins and the Huntington's dilemma. Huntington's is a very, very nasty neurological disease. It's one of the few for which we can actually identify, with a high degree of certainty, that if you carry the genetic marker for Huntington's, you're going to come down with Huntington's, and it's very unpleasant. There is a test available, right? You can get it. It's on the market now. And if it runs in your family, you can get this to see, you know, whether you should start preparing now for your demise. You know, you don't want to spend a lot of money on your retirement plan and that kind of thing.

[laughter]

Interestingly, most people who are at risk don't want to get the test. They want to let nature take its course. "If I'm destined to get it, fine, I'll deal with it when it comes, but I don't want to know for sure, you know, at my age of 20 or 22."

But what if we have a pair of identical twins who have identical genomes, right? They're essentially clones of each other. One of them wants to get the test and the other one doesn't. Hmm. How do you deal with that? I hope you're writing down your answers.

Hit the wrong one. Okay.

Who's your neighbor's daddy? You know, they say in Britain every village has an idiot. In America, every neighborhood has a busybody who just has to know what's going on in the street. They have to know, and, you know, they have identified all of these kids that look more like the milkman than their dad. Who knows? Well, now they can find out, because the cost of DNA testing has come down into the range of recreational hobbyists who think nothing of spending a few dollars to answer, you know, their questions, fulfilling their hobby interest, and that includes things like, you know, "My neighbor's a little bit odd. I think I'll, you know, get a sample of their DNA, have it tested."

And you're thinking, "Oh, how are they going to get my sample?" Right? Well, in the U.S., anything that you discard is open season for salvage. Anybody else can pick up, can go through your trash--you've thrown it out--pick up your hair brush, your band-aid with a bit of blood on it. You know, that's theirs, and there's nothing you can do about it. And they can send that off. And even without sending it off, we're getting do-it-yourself-ers, garage scientists who can get the DNA chips--it comes it what's called a chip--and you can do your own analysis. So you don't even have to be, you know, underhanded about sending their sample off, saying, "Oh, this is actually my sample; it's not the neighbor kid down the street." You can do it yourself in the garage.

Genetic Information Nondiscrimination Act of 2008. Right? Does that protect you? Well, it protects you against potential employers and health insurance companies using your genetic information, but it doesn't protect you against life insurance or nosey neighbors. So we don't even have a statutory protection against, you know, somebody finding out who you really are. And this is more intimate information. I mean, we go to great lengths to protect our financial information, and we do nothing to protect our genetic information, which is far more intimate.

So who's getting into your genes?

Thank you. I think I'll stop there.

[applause]

I think we have a few minutes for questions. Please use the microphones.

Male Speaker:

Alan, thank you very much.

Alan McHughen:

You're welcome.

Male Speaker:

You made a comment in there comparing your DNA to the standard human. What is the standard human that you were comparing to?

Alan McHughen:

Well, I hope one of the messages I got across is, we're all different. We all have lots of mutations in our genome. But when you look and consider that, you know, we have over 3 billion of these bases. We all have changes. There is no standard human. We're all standard humans. So I know that's almost paradoxical, but enjoy who you are. Enjoy your genetic makeup.

It was one of the questions in doing the genomic analysis, the Human Genome Project, of, "Well, who's DNA are we going to take?" In a way, it doesn't matter. We did this for mitochondrial--I didn't talk about mitochondria, but we also have a small segment of DNA in all of our cells called mitochondria. It's not part of the chromosomes. And when that was first analyzed, it was taken from a single person in Cambridge, England, and that became the Cambridge reference standard, and now everybody who gets their mitochondrial DNA compared is compared against that one person, who was just chosen because she worked in the lab. So, in a way, it really doesn't matter. It doesn't make, you know, an ancestral type to be, you know, the epitome of humans. We're all different. We're all of equal value genetically.

Female Speaker:

Good morning.

Alan McHughen:

Good morning.

Female Speaker:

And thank you very much, Alan. Great lecture, indeed. As the only pure human in the--

[laughter]

--in the auditorium, I wanted to share something that I found--I discovered last week. Last weekend I was visiting my daughter at Yale, and we watched, on National Geographic, there is a documentary that's going on on the migration of humans. And actually, they showed that the inhabitants of sub-Saharan West Africa, actually more recent, have all of the European genes that is well known, the sequence, 350,000 human beings, and they were actually very shocked to see people from Maui having identical genes, Y chromosome markers, with Europeans. It's actually going on now. It's quite fascinating. West Africa was only occupied 12,000 years ago, whereas the Europeans migrated out of Africa about 30,000, 35,000 years ago, so some of them didn't like the cold, and they went back to Africa and went down to sub-Saharan, so apparently we're not as pure as people think.

[laughter]

Alan McHughen:

The research in this area is absolutely fascinating and ongoing. I mean, almost every day there's an article either in the scientific literature or the popular press, and, you know, it's a wonderful time to be a geneticist. I just love it.

Male Speaker:

I enjoyed it very much. Just by chance, I was working in the Senate on Gene when we enacted that back in 2008. One of the really scary things was, health and employment we could get consensus on, but there was a battle that went on for years about, "Do we let employers, for example, into this data to do some theoretically beneficial things with it?" Sort of leaving an open door. And even talking to privacy experts at the time, people didn't get it, that you had to not only prohibit bad conduct. And it took us 12 years to get the bill passed, so that tells you right there the functionality, or the dysfunction, of congress sometimes. But I think we finally convinced people you have to have control of the data. That has to be secured. Now, I don't know how many people saw the--and maybe you can comment--the article that just came out in the New York Times, and I'm forgetting the exact story, but it dealt with the Target Corporation collecting data in a retail environment, which was a surrogacy issue. And I think this was the greatest concern. I never intended--I was a health advisor in the Senate--I never intended, at the time, to get involved in civil rights. But when you get into an issue where we've had all these great advances in discrimination on sex, gender, race, et cetera, if I can get into your genome and pick out particular gene alleles that are a surrogate but not exactly the same thing, you kind of unravel all of civil rights. I don't know if you have a comment, but I thought I'd just propose that idea.

Alan McHughen:

One of the great things about the Jefferson program, as a scientist, is that I can come to Washington, work in State Department--you know, I'm also over at OSTP and the White House--and provide some scientific underpinnings so that the people who are actively involved in policy and negotiations and discussions can go in with some confidence that they understand, not the technicalities necessarily, but the scientific basis of these issues. So I feel great that I can make a contribution to that, and I think that's one of the wonderful things about the Jefferson and similar programs, AAAS Fellows, for example.

But you're right. There's a lot of questions. We are running ahead of society's ability to deal with some of these issues, you know, genetic privacy. The argument about, for example, life insurance companies. Well, to some--some people would say, "Well, that's actually beneficial, to get the genetic information, because then the actuarial analysis will be more accurate, right?" And if people--I think--personal opinion, I think people absolutely have a right to know, you know, what their genome is, what it says, and also who else has it. But I might say, you know, I happen to know longevity runs in my family, and if I can get a better confidence in that from my genetic makeup, from my DNA test, then, you know, I should be able to perhaps get a better deal from health insurance companies--and a worse deal from life insurance companies. But, you know, that's on a personal basis.

We also have legal situations. There's a case ongoing. I was going to give this one as one of your questions in the final exam. A case where litigation between an individual and a company where the company had been shown negligence, and the victim--the plaintiff here had already been awarded lifetime medical support because of the company's negligence, okay? Now, in the subsequent phase of the trial, how much should they get? Well, the negligent company wanted to get the DNA from the victim so to contest it to see whether they had any life-threatening conditions that would then enter the calculations of how long the company should pay. "If you only have a life expectancy of a further ten years, well, we should only have to pay your living expenses for ten years." Okay? Where do we go with that? This is uncharted waters.

Of course, on the other end, you know, the victim might say, "Well, what if my DNA shows that I actually have an enhanced life expectancy? So does the company then have to pay me, you know, for an extended period? And I want the payout now, by the way." So it depends on who actually has the information. If the company has the information and the victim doesn't, they could be suckered into a contract that isn't' appropriate.

So there's lots of questions here, and I hope I've showed you that we've just scratched the surface. But don't go making policy without understanding the science. I think that's the main message. It doesn't have to be all that difficult or erudite or technical. At least talk to a scientist who knows how to explain it to you in a language that you understand.

Male Speaker:

Hello. In your talk today, you discussed mainly about humane genomes and the fact that we can detect what genes people have and the sort of information that we can derive from that. But in other areas of genetics, people are working steadfastly to produce new types of crops, to cure diseases, and in recent events, to create whole new plants out of cloth, out of--

Alan McHughen:

Synthetic biology.

Male Speaker:

Right, synthetic biology. And I was just wondering if you could comment on that, especially from your perch at the OST.

Alan McHughen:

OSTP.

Male Speaker:

OSTP--I'm sorry. And also, as to how--whether technology is moving faster than policy can keep up. What are policy developments in that area? What are regulatory developments, that sort of thing?

Alan McHughen:

First, the disclaimer: nothing I talked about today relates to work I'm doing either at State or in the White House, so I am not speaking for the Secretary of State nor for the President. Everything I've talked about today, I developed as a professor at the University of California, and that continues through the question period here now. So I'm not at liberty to discuss the work that's ongoing at OSTP.

However, as you can tell, we are aware of at least some of the issues. We know what the status--we have a pretty good idea of the status of the technology, not only in the government but also in the university system. You know, we have a pretty good handle on what the technology is. And I think you've seen that we have a pretty good idea of what some of the social and policy questions ought to be. What the answers are to those questions is not up to the scientific community, or it shouldn't be up to the scientific community. I would like to think that the scientists contribute and provide a foundation for then further elaboration on policy, to have that solid foundation, but with policy being built on top of that solid foundation, which is not always the case. I think you gave a good example in terms of crops that can be grown that are disease-resistant or more nutritious. There are plenty of countries in the world that have a faulty scientific foundation, which means that no matter how stringent the regulator structure and policy structure is on top of that, it simply doesn't work, and those chickens are coming home to roost in those countries, and it's kind of sad to see, you know, people starving and malnourished unnecessarily because of them.

Female Speaker:

Hi. I was wondering if you could speak a little bit about the current state of GMO regulation in this country.

Alan McHughen:

I haven't talked about GMO regulation, and I'm not sure, you know, whether I have time to get into it, because that's a lecture in itself. But, you know, GMOs are regulated in every country. Every country does have quite stringent regulations on genetically modified organisms. As I've showed you in one of the earlier slides, you know, we're particularly concerned about recombinant DNA and putting a water-use efficiency gene into a corn plant, but we have no concerns whatsoever about taking entire blocks of genes out of rye and putting them into wheat. So those are the kinds of social issues or policy issues I like to raise so that people can think about them. But as far as regulation's concerned, I think what I will leave it at is that, you know, we have been eating GM food since--what was it? 1994. They're all over the world now. 30-some countries are growing GM crops. There's still not a single documented case of harm, either to humans or animals from consumptions or to environments from growing them. So one could argue that the regulations seem to be working if they are designed to protect us.

Female Speaker:

So now I have a curiosity to go to deCODEme.com and do my genome analyses. Should I be concerned that that information will get out to an insurance company or somewhere else in the future, or is your information, you know, protected?

Alan McHughen:

Yeah, you can't get onto my site. I had to log in, and I have control over who gets in. Now, obviously, I don't have any control over hackers. But quite honestly, you know, if you want to hack into my deCODEme Com and look at, you know, the sequence of my insulin gene, have at it.

[laughter]

I got better things to do. [laughs]

I mean, it is my personal information, and I hold it dear, but if you're interested in it, or if anybody else is interested in it, you know... [laughs]

Female Speaker:

But, I mean, could an insurance company have access to that information in the future because the policies around, you know, privacy are not clear at this current time?

Alan McHughen:

You know, crooks are going to get around whatever regulations we have, right? I mean, privacy is important. It is important to me, right? I'm not going to give you my bank account number either, but if you acquire it illegally, well, that's--you might do that, or other crooks might do that. I still try to protect it. And even though I don't particularly care whether you know what my insulin base sequence is, or actually the snips near the base sequence is, it's still my private information, and I would like to keep that to myself. I will share it with you, as I have done this morning, but that's my choice.

Female Speaker:

Okay. Thanks.

Male Speaker:

Alan, there are reports that there's a huge Chinese lab analyzing many sequences, but the difficulty they're running into is not doing the chemical analysis but in handling the mathematics and statistics needed to interpret this, and this is running way behind. Would you like to comment further on analysis of what these fast machines are producing?

Alan McHughen:

Well, this has given rise to an entirely new field of scientific endeavor, you know, genomic analysis. And you're absolutely right. You have 3 billion bases. In my talk today I showed you tiny, tiny fragments of a handful of them. But when you get huge amounts of data, the question is, how do you mine that to get useful information out of it? So, yeah, I'm not at all surprised, and I think we've encountered this, you know, long before the Chinese labs got involved. We can focus in on certain loci on the genome, for example the insulin gene or any other particular gene that we're aware of, but there are huge tracts of the human genome alone that we really don't--we haven't explored it very well. We have the information, but we don’t really know what it all means. And it's a career work for any number of bright young scientists, so, again, it's attractive, and I encourage people who are interested in this subject to learn more about it. But it's probably not going to be fully decoded, if I can use that word, in my lifetime. I don't expect it to. Maybe it will.

That's it?

Male Speaker:

Let's thank Alan for his great talk.

[applause]

Alan McHughen:

Thank you again.