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DNA: The Machinery Behind Human Beings - Part 1


From NPR News, this is ALL THINGS CONSIDERED. I'm Robert Siegel.

On this day when we celebrate an explorer, we're now going to hear for the next half-hour about a different kind, a more recent kind, of discovery and exploration. Five years ago scientists completed the working draft of the most ambitious map in history, the map of us.

President BILL CLINTON: We are here to celebrate the completion of the first survey of the entire human genome. Without a doubt, this is the most important, most wondrous map ever produced by humankind.

SIEGEL: The human genome contains the instructions for making a human being. When President Clinton made that announcement in June of 2000, 90 percent of those genetic instructions had been read and recorded by machines. The project purported to answer questions about who we are. It also raised questions about what we would do with all that self-knowledge.

Well, five years later the map is still not quite complete, but scientists have been filling in the last small gaps and they've been learning more about the genetic landscape. How many genes do humans actually have and what do they do and how should genes be defined?

Well, in this half-hour, some of the advances in genetic research and some of the commercial applications of these discoveries. First, NPR's Joe Palca.

Joe, you've been covering the Genome Project since it was conceived 20 years ago.

JOE PALCA reporting:

That's right and I remember at the very start people thought, `God, this is going to be an expensive boondoggle and I don't know what we're going to do with it.' But now I don't think you could find a geneticist alive that doesn't think it's one of the most important things ever done.

SIEGEL: Well, you've been working on a story about how lately huge regions of the genome that scientists used to think was just junk actually turns out to be very important.

PALCA: Yeah, that's right. I was talking with Phillip Zamore recently about this. He's a biochemist and geneticist at the University of Massachusetts Medical School in Worcester, and he was saying that scientists used to think differently about what was a gene.

Mr. PHILLIP ZAMORE (University of Massachusetts Medical School): There was a time when people thought it was all about the protein-coding genes.

PALCA: Zamore says in the traditional view genes contained instructions for making molecules called proteins and proteins did the work inside cells. They transport nutrients, they allow cells to talk to other cells and they recognize foreign invaders like viruses and bacteria. But, Zamore says, at some point scientists began to think about genes differently.

Mr. ZAMORE: And that began in 1993, but in 2001 everything changed.

PALCA: Zamore says in 2001 scientists stumbled across something called microRNAs. Here was a case where genes weren't making proteins but another molecule, RNA, and it was the RNA that was doing the work inside cells. In many cases the job the microRNAs did was regulating how other genes worked, making more nutrient transports or helping a cell speak louder to its neighbors. Zamore says the discovery of microRNAs was a shock.

Mr. ZAMORE: And there were whole classes of genes we had missed for the 40 years of intense molecular investigation. And people go around at meetings saying to each other, `Remind me again how we managed to miss this?'

PALCA: So how did they manage to miss it?

Mr. ZAMORE: I--you know, science is like every other endeavor: You see what you're trained to see.

PALCA: Now scientists are busy scouring DNA for more surprises in regions of the genome they once thought were filled with junk. In particular, they're looking for more regulatory elements, genes that control other genes. The problem is where to look. Barbara Wold says the search has been made easier by the vast amount of data scientists have amassed. Wold is a geneticist at Caltech. She says knowing the DNA sequence of a variety of different organisms has been incredibly valuable. It tells you what regions of DNA nature has kept around for millions of years of evolution, presumably because they were valuable.

Ms. BARBARA WOLD (Geneticist, Caltech): If you look at lots and lots of genomes and sift out those things that have not been permitted to change, in general, that means that they're very important things even if we have no clue as to what their importance is.

PALCA: But you still can't look at a sequence of letters and say, `Aha, this is a regulatory sequence, even though it's not near any genes I recognize.'

Ms. WOLD: Well, on a good day, with just the right algorithm and a bunch of computers, you can actually begin to sneak up on them.

PALCA: Scientists are just getting a clear picture of how much of what they once thought was junk is actually important. Richard Myers is a geneticist at Stanford University.

Mr. RICHARD MYERS (Geneticist, Stanford University): Our best measure right now is about 1 percent of our DNA makes up the genes, the parts that code for proteins, and another 4 percent, meaning four times that amount, make up some other important elements that are probably these regulatory elements that control genes and do other things.

PALCA: Myers says scientists are also just coming to grips with what these other important elements might be important for.

Mr. MYERS: Because of the focus in the last 10, 15, 20 years on the genes themselves, people haven't looked in the regulatory elements as much for mutations. But when they do look, they do find them frequently, and I wouldn't be surprised if a lot of disease is due to changes in these other extragenic, the non-gene segments, the regulatory segments.

PALCA: Several laboratories are collaborating on a project designed to better understand these non-gene elements in the 4 percent of the genome once called junk. It's called ENCODE, for ENCyclopedia Of DNA Elements. University of Massachusetts biochemist Phillip Zamore is an adviser to ENCODE.

Mr. ZAMORE: The biggest hope is: Can we find new kinds of genes that we missed, things like microRNAs? What is the next microRNA, the thing we can't imagine now but it's there?

PALCA: In other words, finding more gems in the junk.

SIEGEL: That's NPR's Joe Palca, and, Joe, I want you to stick around for a few minutes...

PALCA: Sure.

SIEGEL: ...after we hear about some of the implications of a growing industry that's sprung up thanks to the Genome Project, genetic testing marketed over the Internet. Here's a sampling of what's out there. Ryan Phelan's company is called DNA Direct. For anywhere from $200 to more than 3,000, DNA Direct will test for genes predicting six diseases, including breast cancer, ovarian cancer and cystic fibrosis.

Ms. RYAN PHELAN (DNA Direct): The reason we started DNA Direct is because these tests are often not easily accessible. And so the very first thing that we're doing is providing Web access to determine whether or not testing is right for them. They can purchase a test that allows them to test with privacy and anonymity. And then most importantly, when that test result comes back to our company, we really do the important work, which is to put that test result in context. And, interestingly enough, we are often asked, `Is this something that just the worried well is interested in?' And the truth is, we don't see that at all. We see people who have a real good reason. They have had a personal experience or they have a family member who has died of a medical condition and they want to know. What can they learn from a genetic test that might provide that kind of valuable insight and help them make better health care decisions? It's really about personalizing your health care.

SIEGEL: Are people coming directly to you or are they coming through a physician to you?

Ms. PHELAN: It's an interesting question. When we started the company, our assumption was that we were going to be getting direct-to-consumer response. They wanted to keep this off their medical record. But the truth is we do get customers who test for privacy purposes but we also get customers who have been referred by their physician. And you may ask why would a physician send a patient to DNA Direct? It's a very simple answer. Physicians, in many cases, do not have the time or the inclination to provide the level of genetic interpretation that we do. And the beauty of the Web, of course, is that people can go as deep or as shallow as they want. They can use this information to share it with their family members. They can share this information back into the health care system with their health professionals.

SIEGEL: I've spoken to some people who can see that given where we were 20 years ago with genetics and identifying people's DNA thought, frankly, all of this would have taken off a lot more by now and I wonder whether you're upbeat about the--simply as an entrepreneur--about the prospects for this industry or whether there seems to somehow be a drag on it that keeps it from taking off.

Ms. PHELAN: I'm extremely optimistic that genetics is going to be increasingly integrated in everybody's lives. There's a significant amount of interest in this whole field.

SIEGEL: Like Ryan Phelan's DNA Direct, Howard Coleman's company Genelex is offering a medical application of genetic testing. Genelex has long done paternity and forensic tests. Now Coleman has branched out into pharmacogenetics.

Mr. HOWARD COLEMAN (Genelex): If you're taking medicines, you can find out whether these medicines will be safe or effective. I think it has a potential to make a huge impact on the drug safety problem. Adverse drug reactions--and that's taking the drug at the recommended dosage, especially with combinations of drugs--causes about a hundred thousand deaths per year in the US and two million plus serious adverse reactions.

SIEGEL: Could I get the answer `Will my child have a allergic reaction to penicillin?'

Mr. COLEMAN: No, it's not so much allergic reactions as it is toxic reactions. When you take any kind of medicine, most of it gets processed through your liver. And the enzymes in your liver that break these down or, in some cases, activate them, a lot of us are not genetically equipped to make those enzymes.

SIEGEL: And so this might warn me off a particular drug?

Mr. COLEMAN: Yes, with the help of your physician or your pharmacist, your clinical pharmacologist, for example, you could choose an alternative drug. They might adjust the dosage based on this, alter the combination of drugs you're taking.

SIEGEL: Then there are the DNA testing companies that don't tell you how you are, but rather who you are. Bennett Greenspan's company Family Tree DNA does genetic genealogy.

Mr. BENNETT GREENSPAN (Family Tree DNA): We can give you the tightest prediction of the time to the most recent common ancestor and, after all, that's what genealogy is all about.

SIEGEL: Your information online tells me about how many haplotypes there are. What is my haplotype?

Mr. GREENSPAN: A haplotype is a DNA signature. So if we were to do a DNA test on you we would end up with values at a series of different markers and we would then compare those markers between you and all the other men in our database. And only the matches that were extremely close or identical to you would be shown to you because those are the only ones that have any relevance to you genealogically.

We have another database that makes comparisons a little bit further out. That's a haplogroup database and that looks at migration patterns. So there are 18 branches of the tree of mankind. For example, if your ancestry happens to be Semitic, which would track back to the Middle East, that would be very easily discernable by comparing your DNA signature against other people in our database with an identical or similar signature.

SIEGEL: That's Bennett Greenspan of Family Tree DNA.

Joe Palca, we found on the Web also a DNA diet Web site where you can send in a swab and you'll get recommendations for nutrition. There was one that was doing customized skin cream based on your DNA, which has since closed its doors...

PALCA: Yeah.

SIEGEL: ...since we interviewed them. What do you make of this over-the-counter DNA testing industry?

PALCA: Well, it's a bit of a wild frontier out there. I mean, I think there's no question that the genetics has opened some doors, and I think some clever entrepreneurs have seen a way to walk right on through and, perhaps, make a buck. It strikes me that some of these things--there may be room for direct-to-consumer under certain circumstances but in, for example, the pharmacogenomics, you're not going to be taking any drug over the counter that's going to cause these kinds of strange reactions probably. It's going to be a physician...

SIEGEL: There's going to be a physician involved here.

PALCA: So it's a little unclear to me why you need to go directly to a company. You might want to know about susceptibility to diseases but, at some point, it's going to be the doctor or the medical community that's going to help you out in figuring out what to do about these things.

SIEGEL: So it's not clear yet whether these are things that customers will find on their own or whether there'll be intermediaries like pharmacists or doctors who will do this?

PALCA: Right. Well, there are bound to be intermediaries. And there could be times when, because of issues of privacy or health insurance denial of claims and things, there may be times when consumers want information that only goes between them and a private company and isn't shared with other people. There may be issues like that, but this is all so new and we're figuring it out or the people that are doing it are figuring it out as they go.

SIEGEL: Well, if there's really something of value that we can learn from our DNA, then people are probably going to be willing to pay for it one way or another.

PALCA: That's usually the way it works, yeah.

SIEGEL: Is there a great deal that I could learn that would be useful information to me from my DNA?

PALCA: Probably at the moment less than you might think. But that's the idea is that there will be, and I think people are getting ready for that day.

SIEGEL: Well, in a moment we're going to hear about the effort to make an affordable, personalized genome--that is each of us according to our genes--on a chip. That's coming up on ALL THINGS CONSIDERED from NPR News. Transcript provided by NPR, Copyright NPR.

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