Online NewsHour: Progress in Gene Studies During 1996 -- January 1, 1997

PAUL SOLMAN: What makes us tick and what makes us sick? Gene research is literally about the stuff of life, and this year saw major new advances on the scientific and commercial front. We begin with this background from Fred De Sam Lazaro of KCETA-St. Paul-Minneapolis.

FRED DE SAM LAZARO: Seven years ago cystic fibrosis, a degenerative lung disease of children, was traced to its genetic foundation. Scientists were able to identify a gene that, when defective, causes cystic fibrosis. The discovery by a team of scientists led by Dr. Francis Collins was widely acclaimed. Isolating a single gene from the 80,000 or so found in every human cell was the equivalent of locating a house somewhere between California and New York, with no clue as to the street address or even the city.

DR. SCOTT McIVOR, Geneticist: Cloning the cystic fibrosis gene was really a great leap forward and in cloning technology, and it was a huge and laudable effort. And a lot of those techniques are still certainly, you know, applicable to today.

FRED DE SAM LAZARO: University of Minnesota geneticist Dr. Scott McIvor says since the cystic fibrosis breakthrough shortcuts have been honed and developed to sift through the complex maze of DNA. Individual genes, the basic building blocks that determine every aspect of life, are not only numerous, each consists of tens of thousands of precisely sequenced bits of protein called bases or nucleotides.

DR. ALEXANDER KAMB, Geneticist: The DNA samples are loaded here where you see these teeth sticking in.

FRED DE SAM LAZARO: Today, new techniques have allowed scientists like Dr. Alexander Kamb to screen DNA samples in search of genes.

DR. ALEXANDER KAMB: There's a laser here which excites the fluorescent dyes, and that's internalized in the computer, displayed here as an image in color, and so you can see now the result of that, all these little ladders here, little bands corresponding to different bases in the nucleotide sequence. And if a person has, for example, a mutation at a particular position and a particular gene, this kind of analysis will tell you that.

FRED DE SAM LAZARO: Meanwhile, under the auspices of the federal government's Human Genome Project now headed by Dr. Francis Collins, the entire genome is being mapped. Scientists across the world add to this database when they locate a gene. Those who want to study the genetic basis of the disease now have access in journals or on the Internet to a growing road map that can lead them to candidate genes, providing either a general location, like which of the 23 chromosomes the gene is on, or a more precise address.

DR. SCOTT McIVOR: The analogy in this case would be that the chromosomal assignment would tell you which state it's in, and the much more fine structure map that's provided by the Human Genome project, and eventually the sequence would give you an actual street map, or an even house-to-house map.

FRED DE SAM LAZARO: Pursuing that analogy further, once McIvor has located a house, he can then start to look for burned out light bulbs, defects or mutations in genes, like missing or wrongly sequenced bases, the kind of things that lead to disease.

DR. SCOTT McIVOR: Doh is working with a retro viral vector that she's been engineering for treatment of a disease called Hurler Syndrome and the idea is to use this retro viral vector to introduce a functional gene and hopefully, if we can use this retro virus to introduce a functional iduronadase gene, then we may be able to correct the disease conditions in Hurler Syndrome.

FRED DE SAM LAZARO: McIvor's is one of several labs that have taken the next step to gene therapy, trying to find a way to re-introduce functioning genes to take the place of faulty ones.

DR. SCOTT McIVOR: We don't really have the capability yet to go back and turn on specific light bulbs again, but we may be able to plug in an extra light bulb somewhere else that would illuminate the area that needs to be illuminated.

FRED DE SAM LAZARO: Although gene therapy has shown promise in limited trials, most scientists agree it's in early infancy, years away from clinical application. For now, the big news has been in the discovery of genes. So far nearly 1/4 of the genome, 20,000 genes, have been located, most of them just identified, others linked to traits or conditions ranging from obesity to anxiety. More importantly, mapping has been used to locate 78 crucial proteins that are directly linked to diseases. In 1996 alone, 21 such disease genes were identified responsible for certain forms of Alzheimer's, diabetes, and skin cancer, among others. Last month scientists located markers, the approximate location of a gene linked to Parkinson's Disease, and in another significant find one responsible for certain forms of prostate cancer, one of the most common causes of death in American men.

FRED DE SAM LAZARO: Also in 1996 building on the discovery earlier of genes linked to some breast cancers tests became commercially available to screen women for the genes and, therefore, their predisposition to these breast cancers.

PAUL SOLMAN: Now to our discussion. Dr. Francis Collins, as we've just seen, directs the Human Genome Project, officially known as the National Center for Human Genome Research. Mary Jo Ellis Kahn is a patient advocate with the National Breast Cancer Coalition. Steven Holtzman is chief business officer of Millennium Pharmaceuticals, a biotech firm in Boston, and Patricia King is a professor on law and medical ethics at Georgetown University Law School here in Washington. And, welcome to you all. Dr. Collins, let's start with you. How significant a year was it in terms of genetics and why?

DR. FRANCIS COLLINS, Human Genome Project: I think it's been a remarkable year. At the basic science level, the Human Genome Project which started in 1990, past its sixth birthday, able to claim victory with the genetic maps that were the first milestone for the project well ahead of schedule. The physical maps that we needed are also probably about 96 percent done. We finished--

DR. FRANCIS COLLINS: The physical maps you can think of as sort of chunks of DNA, the road maps of the cities and counties that you need to achieve that house-to-house search that you eventually need to get to if you're going to have all the games in front of you. The sequence, i.e, the series of the letters, the A, C, G, and T, i.e., that four-letter alphabet of DNA, of all of the human DNA is now the part that we are rolling up our sleeves and wading into. And there are 3 billion letters in that particular instruction book.

PAUL SOLMAN: That's what Fred was looking at with the guy in the computer, looking at--

DR. FRANCIS COLLINS: Right. Coming out of that colored ladder on the screen. If you printed out the entire human instruction book in books with average font size and page size and piled them one on top of the other, it would be about the height of the Washington Monument. And so far we've only done about 1 percent of that. But seven or eight years from now we'll have done it all.

PAUL SOLMAN: Mr. Holtzman, in terms of what we've done in terms of commercial breakthroughs, we've seen genes for I think there's novelty-seeking even, somebody said, anxiety, things like that. How big a breakthrough in a commercial sense has this year been?

STEVEN HOLTZMAN, Millennium Pharmaceuticals: (Boston) Well, as little as two to three years ago, there was a common belief that genetics would be important only for relatively rare disorders which are called single gene disorders, such as cystic fibrosis. What's happened in the last year to year and a half is a recognition that genetics is essentially a tool, genetics and genomics, as it's called, for elucidating the underlying biological causes of disease, including the most major forms of common diseases, our susceptibility to them, and elucidating the causes of the progression and initiation of those diseases. That kind of understanding provides the basis for starting to develop drugs which can address those diseases at their underlying cause, and not just gene therapies but early available drugs of the type that major pharmaceutical companies are interested in.

PAUL SOLMAN: Are we close to getting those kinds of drugs? Have we begun to get them?

STEVEN HOLTZMAN: No, we haven't even begun to get them. What we've begun to get is the kind of understanding that allows us to begin to think about developing medicines which can actually prevent and cure disease for the first time, as opposed to only palliating symptoms. And as a result, the pharmaceutical companies have made significant investments in young biotechnology companies, such as Millennium, who've made early investments in this technology.

PAUL SOLMAN: Okay. Ms. Kahn, how big a year from the consumer or patient point of view?

MARY JO ELLIS KAHN, Patient Advocate: Well, it's been a wonderful year for great potential. There's a potential that we will find out the secrets of breast cancer enough that we can prevent or cure it, but we're not there yet. And from the viewpoint that we are in--breast cancer patients are in grave danger at the moment because we have not put in place the policies that we need to protect us from discrimination.

MARY JO ELLIS KAHN: I am a breast cancer patient with a family history, and I have two young daughters, and although finding out our genetic status may be very useful to the family to learn who needs to be followed more carefully and what medical care we should receive, it's too dangerous at this point because my daughters could lose their health insurance based on just testing.

PAUL SOLMAN: And that's the kind of issue that these breakthroughs raise, right, Professor King?

PATRICIA KING, Georgetown Law School: That's correct. This has been a banner year but it's not unusual at all. The resolution of some of the legal and ethical problems really lag far behind the scientific breakthroughs. So we're still trying to work out the policies not only for clinical screening but for an introduction of new tests for general use. But we have bigger problems like health insurance, keeping information private and confidential. We have problems with discrimination. We have potential problems with discrimination in the work place based on one's genetic traits. So we have a lot to do, I think, but I'm hopeful because major breakthroughs have a way of crystallizing the public mind to tackle these kinds of issues, and that may be what we needed.

PAUL SOLMAN: Let's go back to the issues in a minute, if we could. There are a couple of questions I just have personally. For example, Dr. Collins, how close are we, do you suppose, in years to a major breakthrough on the aging process? I say this out of some personal concern here. I mean, are we at the point where we could begin to think about reversing or making headway on the aging process?

DR. FRANCIS COLLINS: It's always hard to answer these questions about how far are we away. We have certainly made strives in understanding aging, actually from a genetic point of view. A relatively rare condition called Werner's Syndrome, which is one of these premature aging disorders, had its gene found this year. And that is probably a window into a process that's been pretty obscure until now. Certainly when it comes to some of the diseases of aging, such as Alzheimer's and prostate cancer, there have been breakthroughs this year. But in terms of understanding the process by which everything sort of wears out and runs down, that is going to be a very difficult process. And I don't think we're anywhere near to that fountain of youth model that some people hope for.

PAUL SOLMAN: Mr. Holtzman, average longevity for a kid born in the year 2000, for example. I mean, I don't--we'll never get back to you on this, but do you think we're going to have substantially increased longevity say for kids being born in the next few years?

STEVEN HOLTZMAN: Not in the next few years. I think, as Dr. Collins indicated, if we look at what gets in the way of longevity, namely certain diseases of aging, we will have insight into those and better drugs for treating those.

PAUL SOLMAN: What about cancer? We're talking here about breast cancer specifically. I think the cancer rate has for the first year gone down in terms of survival. That's a five-year survival rate still, or no?

STEVEN HOLTZMAN: No. That's mortality statistics across the population for a number of cancers for the first time this century have begun to decline, not entirely clear all the reasons for that, but obviously not declining nearly fast enough to suit most of us. Cancer is an area where I think the potential for advances in the next ten to fifteen years are really quite substantial because cancer comes about because of mutations in DNA. We are learning a lot about mutations in DNA, and we should be able to harness that into the development of more effective therapy in the not-too-distant future, but we're not quite there yet for most of the common cancers.

PAUL SOLMAN: So that's why you're happy. What exactly are you worried about? I mean, explain to us what you mean when you're worried about knowing things for you and for your children.

MARY JO ELLIS KAHN: Well, until we have in place a treatment that goes with genetic testing where we can say that there is obvious benefit, and everyone agree you should be tested, you should get this treatment, then what we're left with is a lot of information, powerful information, that may or may not improve our quality of life.

PAUL SOLMAN: Currently there is a cancer, a breast cancer test available of some sort?

MARY JO ELLIS KAHN: Well, there are two genes that are--if you have a mutation in them--are associated with an increased risk of breast cancer. But it's not clear in everyone who carries a mutation what your risk is. It's not clear at what year you'll get breast cancer if you do get it. There's a lot of things unknown still, but there is a test, and in some high risk families where there are lots of members affected by breast and ovarian cancer it might be useful to know if you carry one of these mutations. But since you can't prevent it, and you can't cure breast cancer in every incidence, then what you really need to do is provide a way to do the research. And if we have discrimination as a major risk, one will not be able to participate in these studies. We can't get to a decreased mortality.

MARY JO ELLIS KAHN: Well, our biggest risk right now is health insurance discrimination. And if the health insurance industry were able to say for those people who can be tested for breast cancer, colon cancer, Alzheimer's, any number of diseases that we'll soon have tests for, that from birth you are no longer eligible to buy insurance, then you will have a genetically-disadvantaged population who eventually could die of these diseases simply because they can't get care.

PAUL SOLMAN: So you wouldn't take the test, you haven't had your kids take the test?

MARY JO ELLIS KAHN: My family's decided that it's not in our best interest because my daughters and my niece, the next generation, need their health insurance more than they need this information.

PAUL SOLMAN: So it's not out of fear of finding out the results; it's out of the health insurance, the worry about health insurance?

PAUL SOLMAN: And Patricia King, how do we deal with that? I mean, is that the major issue that's raised by genetic testing or screening?

PATRICIA KING: Well, it's one of the major issues. It's not the only one. But not only does it present problems for individuals because the information is powerful, not only do you have a problem in getting health insurance, you may have a problem getting employment because remember, most health insurance in this country is provided for by employers. Health insurance is expensive. So you not only have to worry about your coverage; you have to worry about your employment; and you have to worry about what to tell your children or, indeed, whether to have children. So the information is quite powerful. And this information feeds on existing inequities in our system. We can't currently protect persons who know they are at risk for certain diseases or, in fact, have certain diseases with respect to health insurance or even employment. We're just beginning to come to grips with this problem. We can't yet assure you that the information, should we get it, would be protected and kept confidential. So it's not only an individual problem; it's a huge social problem that feeds into a system that already has problems, not to mention that if we actually can do something for people who are screened one day for breast cancer, we can't assure some people that they will have access to the health care system at all, not with just with respect to insurance, but because they may not be able to afford it. So this is the tip of the iceberg in terms of our social problems.

DR. FRANCIS COLLINS: I think many researchers are deeply concerned about this as well. I certainly am. I think it will be a terrible tragedy if this set of scientific advances with so much promise to benefit humankind gets, instead, converted into a new way to discriminate against people in an ever more powerful and unfair fashion, and the whole field ends up, therefore, stillborn as the advance in medicine that we would have wanted it to be, that would be the greatest tragedy. I think there is some movement, though, in addressing these issues. Only a few months ago, the Kassebaum-Kennedy Health Insurance Bill was passed and signed by the President. It does say that at least in some circumstances health insurance companies may not use genetic information to deny coverage. It has areas that it doesn't cover which seriously need to be addressed quickly, but in this past year, there were no less than a dozen bills in Congress that dealt with genetic discrimination and privacy. And I suspect in the 105th Congress there will be at least that much interest. But it's--the time is now. We have to wait this time for a crisis, for a catastrophe for everybody running around, wringing their hands, saying, how did we get to this point, that will be so unnecessary and so tragic.

PAUL SOLMAN: I want to ask Mr. Holtzman, how do you respond to this from a business point of view? For example, there's this breast cancer test that's being sold in Utah. Do you think that a company should be marketing a breast cancer test, given the little amount we know, and the potential for discrimination that currently exists until such legislation would come in?

STEVEN HOLTZMAN: Well, I think the first point to make is the industry has taken a stand completely consistent with the scientific community stand, as represented by Dr. Collins. The Biotechnology Industry Organization was highly supportive of taking position papers in support of the Kennedy-Kassebaum legislation as an active Bioethics Committee supporting these sorts of anti-discriminatory--discriminatory and anti-privacy kinds of issues.

STEVEN HOLTZMAN: Well, I think it's--the organization which represents the biotech industry. Personally, I have the great fortune of serving on the National Bioethics Advisory Commission, and this is a major issue on our plate, as well, and we are addressing. Clearly, we have a stake as an industry and as people who have gotten into this industry because we believe in the power of the technology to ensure better technological sophistication is not dis-served by our social--lack of social maturity and the misuse of it.

PAUL SOLMAN: Please. I wanted to ask one last question. I didn't mean to cut you off, but parental screening is an issue that I'd read about and heard about, the idea that you could prevent a kid who--as I say--who had some propensity to be, I don't know, anxious, too anxious, and you didn't want that kind of kid, or homosexual, or some of the things that we felt about with respect to possible involvement of genes. That's an issue we haven't talked about here. Patricia King.

PATRICIA KING: Well, first of all, let me say, we already have some capacity to screen fetuses prenatally for pretty severe diseases.

PATRICIA KING: Down's Syndrome, sickle cell anemia, for example, so this won't be new; it will be magnified. And one of the--

PATRICIA KING: That's exactly right. You have a lot more screening tests for fetuses. You have magnified your issues, and you've magnified them in the following way. We think of Down's Syndrome as being a very serious disease, sickle cell as being serious. Some of the characteristics that we could potentially screen for in the future some of us might not think of as being so serious that we should think about not having that fetus. So one of the things that I think about with respect to genetics is not will it--not only will it change our immediate lives in a way that we have to think about but it has the potential for changing where we see ourselves, our parent-child relationships, what we want from our children, what we tell our children. Now, I agree with Dr. Collins. I don't think I should go around crying tears about what is to come. I think the real challenge is to try to figure out ways to take on effectively some of these issues, and I think that we have sort of laid a groundwork in the last six, seven years, but we really need to have more concentrated, I think, national attention to deal with some of the big social issues. We're dealing with in a piecemeal fashion--health care in the Congress, states are passing their own laws to deal with discrimination. They are doing it piecemeal. We need a more concerted look at the immediate issues and how they affect individuals, but some of the broader social issues. In the past the President's Commission on Ethics in the early 80's did wonderful work with respect to big issues then and helping to educate the public and prepare us for the technology. We need something like that again. We need a broader group to take a look at some of these issues.

PAUL SOLMAN: And I take it--because you're nodding, Ms. Kahn--that you fully agree with this?

MARY JO ELLIS KAHN: Oh, absolutely. I think it's very hard for policy to keep up with the rapid pace of science. And we need a better method of doing that. But in part, it's educating the public about how to think about this, rather than thinking in terms of designer children and how you make a perfect child with genetics, you really need to be thinking--in my family it's not that the person's not valuable; it's that the disease is very bad. We need to treat the disease. And if we try to generalize too much--and I think that's where the discrimination comes from--that just because you have one mutation in all of these billions of genes that that does not change the person. And so we really need to keep focused on what kind of treatments we're looking for.

PAUL SOLMAN: And that's that genetic determinism that you're dead set against, isn't it, Dr. Collins?

DR. FRANCIS COLLINS: Which I'm very concerned about. We hear about the gene for this and the gene for that. And if you're talking about something like anxiety or novelty seeking, good grief, this is ridiculous. Those are personality characteristics which have genetic contributions that are enormously complex. No single gene would account for more than a tiny fraction of such characteristics, and much of that is learned behavior that comes about as we're growing up as kids and interacting with our environment. And I'm deeply concerned that in our enthusiasm--and I'm certainly enthusiastic--to promote what genetics can do for us in the medical sense that we are also geneticizing other aspects of human behavior to the point where people begin to conclude that every aspect of what they did today was controlled by these invisible marionette strings made of the double helical DNA. That ain't so. We're not going to eliminate free will. We're not going to eliminate the environment, even when we understand the whole genome.

PAUL SOLMAN: Excellent. Well, then with free will I say it's the end of the discussion. Thank you all very much.

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Genetic Advances

January 1, 1997

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