THE WHITE HOUSE Office of the Press Secretary________________________________________________________________________For Immediate Release October 12, 1999 MILLENNIUM EVENING AT THE WHITE HOUSE INFORMATICS MEETS GENOMICS East Room 7:35 P.M. EDT MRS. CLINTON: Good evening, and welcome to the White House.Imagine for a moment that it is the year 2030. You could instantlyteleconference with your children any time, anywhere, if they willaccept the teleconference. (Laughter.) You could speak into a computerand have your words instantly translated into any language. If you'reparalyzed in an accident, you can regain your mobility. And if you loseyour sight, you will regain it. Well, welcome to the future, and to the 8th Millennium Eveningat the White House. Tonight we will explore the explosion ofinformation technology and genetic research, and how they are combiningto shape how we live, learn, and think in the next century. I'd like to thank our sponsor, the National Endowment for theHumanities, which every day helps create informed citizens and publicdebates like this one. And I'd like to recognize its chairman, BillFerris, for his work. I also want to recognize the many members of the President'sadministration who are here, including Secretary Donna Shalala;Secretary Dick Riley; NIH Director Harold Varmus; NASA Administrator DanGoldin; National Science Foundation Director Rita Colwell; Director ofthe NIH Human Genome Project Francis Collins; and the President'sScience Advisor Neal Lane. I also want to thank the Library of Congress and theSmithsonian for the exhibits in the foyer. We're actually using some of the science that we arecelebrating tonight. People from all over the world can participate inthis event via satellite and over the Internet, thanks to John Shoemakerand the entire team at Sun Microsystems. And you will watch video allevening on these plasma screens, thanks to Pioneer New Technologies. For the past two years, we have used these Millennium Eveningsto showcase the art, culture, history and science that define us as apeople and as a nation. When Professor Bernard Bailyn lectured, thisroom was filled with historians. When Wynton Marsalis played here, itwas filled with musicians. And it's safe to say tonight that we havethe largest gathering of geneticists and IT experts ever assembledtogether in the East Room of the White House. (Laughter.) These lectures are part of the work of the White HouseMillennium Council that the President and I started to encourage allAmericans to use this unique moment in time to honor the past andimagine the future. And that is exactly what we will do this evening. If we pick up any magazine or newspaper these days, these arethe kinds of headlines we're likely to find: "Twins Unlocking theSecret of Identity;" "How the Wireless World Will Change Your Life;""DNA Mapping: Light at the End of the Tunnel." We are on the brink of discoveries that are astonishing intheir complexity and implications for human life in the decades ahead.But they didn't happen overnight. These revolutions have been driven byour American quest for knowledge and discovery -- and the willingness ofboth the public and private sectors to invest in the necessary research. More than 200 years ago, before we had even drafted aConstitution, our second President, John Adams, created the AmericanAcademy of Arts and Sciences to, in their words, "cultivate every artand science which may tend to advance the interests, honor, dignity andhappiness of a free, independent and virtuous people." That same spirit is what drives us to go to the nextgeneration Internet and to find the 3 billion letters of geneticinstructions to the human body. And it must continue to drive us as weeducate and inspire Americans to understand these breakthroughs, andcontinue investing in science and technology research well before weknow whether it has any commercial applications. After all, when Vint Cerf and Robert Kahn found a way forcomputers to talk to one another, they certainly didn't imagine E-Bay orAmazon.com. (Laughter.) But, now, even in the face of these great breakthroughs thereare many who rightly worry that our science is developing faster thanour ability to understand its implications. Because behind each of theheadlines we read we find not only great possibilities, but alsoprofound ethical questions that we must answer together. As we gather more information -- whether it is commercialtransactions posted on the Internet or genetic information collected bydoctors -- who owns that information? How will we protect our privacy?How will we make sure that knowledge about our genes is used to heal us,not deny us health insurance or jobs? What do justice and equality meanin a digital age? In one of his short stories, Ray Bradbury's vision of the year2030 has some similarities to the one I started with tonight: thewindows wash themselves, breakfast cooks itself, and a voice machinereminds you of birthdays, anniversaries and bills to be paid, which isespecially handy as one gets older. (Laughter.) There's only one bigdifference: There are no people. The population has been completelywiped out and all that's left are machines. Standing here with only 80 days left until the year 2000, wehave a chance to imagine and create a very different future. One inwhich the revolutions in information and biology benefit, rather thaneclipse, our humanity; where our ethics keep pace with our science;where our investments in science dramatically improve not only how longwe live, but how well we live. Because unlike science fiction, how thisstory ends is in all of our hands. So I want to thank you for coming this evening. And we haveinvited two distinguished scientists to help us understand that promisesand perils of information tm prestigious universities; and both arevisionaries. First, Dr. Vinton Cerf will give us a quick overview of thegrowth and future of the Internet. Then Dr. Eric Lander will tell usabout the revolution in genetics and where it is leading us. Dr. Lander actually started his career as a mathematician. Asa high school student, he even won a place on the U.S. team to theInternational Mathematical Olympiad held in East Germany. This was atthe height of the Cold War. But when his team and the Russian math teammet at the competitions, they hit it off. They spent evenings together,tossing water balloons down on to the streets of East Germany indefiance. And he has been bringing people and disciplines together eversince. (Laughter.) He's built bridges to public policy, and by contributing histime, has really added to the public debate as an NIH advisor. He'salso the founder of Millennium Pharmaceuticals, and now he's buildingbridges between genetic discoveries and their potential to improve ourlives as the Director of the Whitehead Institute/MIT Center for GenomeResearch. Now, I'm told that Dr. Cerf, one of the fathers of theInternet, also got his start in high school. Back then, he and his bestfriend got permission to use a computer at UCLA. When the building waslocked on weekends, they would simply climb up to an open third-storywindow. The machine was a size of a refrigerator and had the computingpower of today's hand-held calculators. But he was consumed by thepossibility computers held, and has been scaling wall after wall eversince then to fulfill it. (Laughter.) As the Advanced Research Projects Agency of the Department ofDefense, he helped to develop the procedures or protocols that computersuse to communicate with each other. And he's chairing the new InternetSocietal Task Force that is helping to make the Internet accessible toeveryone. He's a senior Vice President at MCI WorldCom for InternetArchitecture and Technology. And I think that every parent should takeheart that people who throw water balloons and scale to third-floorwindows do have a future -- (laughter) -- that will in one way oranother be redemptive. Therefore, I am especially honored to introduce our firstspeaker, Vint Cerf. (Applause.) DR. CERF: I didn't know you were going to dig up that storyabout our high school escapades. Let me thank you, Mrs. Clinton, forintroducing me not as an "extinguished" scientist. I appreciate that.One wonders, as time goes on. Well, Mr. President, Mrs. Clinton, ladies and gentlemen,Internet is the consequence of the work of many people. In 1997,President Clinton recognized the contribution that my partner, Bob Kahn,and I made when he awarded us both the National Medal of Technology forthe design of the architecture and communication protocols of theInternet. Bob is here tonight, and I'd like to acknowledge his creativeleadership. Bob, would you stand up for a minute? (Applause.) I also want to acknowledge the contributions of PresidentClinton and Vice President Gore in shaping the administration policy,and in legislation supporting research and development that's needed tomake Internet a global reality, and to continue its astonishingevolution. The 19th century invention of telegraph and telephone systemsdramatically changed the way in which people could interact with eachother. Dial-tone has become the symbol of voice communication aroundthe world. During the 20th century, we learned that computers couldusefully talk to each other, too, using packet switching as their datatone. You can think of packet switching as a kind of electronic postalservice in which everything that moves through the system is like anelectronic postcard that's forwarded from one computer to another untilit reaches its destination. The special computers that perform thisfunction are called routers, and you can think of them as forming manydifferent bucket brigades spanning continents and oceans, moving bucketsfull of electronic postcards from one router to another, until thepostcards reach their destination. Each bucket brigade is a network and there are hundreds ofthousands of them in the world, connected together to make up thenetwork of networks that we call the Internet. Everything we know aboutpostcards applies to these packets of the Internet -- they can get lost,they can be delivered out of order, and they can be delayed by varyingamounts in the net. They can even be duplicated by the net, which isnot something that the U.S. Postal Service offers as a service.(Laughter.) Of course, packet switching is about a billion times fasterthan the Postal Service or bucket brigade would be. Now, the procedures by which computers communicate with eachother and the formats of the electronic postcards that they send arecalled protocols. And the most basic protocol on the Internet is calledthe Internet protocol, or IP for short. Now, to make the Internetservice reliable -- which it is not using just those postcards that Idescribed -- you have to add other layers of protocol on top. One ofthe most important of these is called TCP; it stands for transmissioncontrol protocol -- and you're getting your dose of geek vocabularytonight. This takes care of resending to recover from a lost postcardor a lost package, or putting the package back in order if they havebeen received out of order. One sometimes hears the term, "TCPIP" withreference to the Internet. Those are the two fundamental protocols ofthe network. Now, there's another way of thinking about the power ofinterconnecting computers through networks, and that's to think aboutthe way we use electrical power generation and distribution andfractional horsepower motors in our daily lives. Think about how manylittle modems are working for you every day to keep your ice cream frommelting, to start the car and to keep the clock turning. That's thekind of thing that we relied on in our mechanical world. Well, computers are like fractional horsepower motors, andinformation is like electricity. Information flows through networks andfeeds computers in a fashion that's very similar to the way electricityflows through the electrical power network and runs motors. During theindustrial revolution, we learned to put motors to work to magnify humanand animal muscle power. In our information age, we're learning tomagnify brainpower by putting computing power to work wherever we needit to work with information for us whenever we need help. Filled with software, computers allow us to use them asinfinitely flexible tools. Networked together, they allow us togenerate, exchange, share and manipulate information in uncountableways. There are about 60 million computers on the Internet todayserving about 180 million users. Internet service is found in varyingdegrees in over 200 countries and territories. Now, for comparison,today's telephone system has 950 million telephone lines and about 3billion users. So Internet, despite all the hype, has a long way to go.But, by the end of the year 2000, I estimate there will be at least 300million users on the network. And a straightforward projection of thegrowth of the Internet brings it to nearly the size of today's telephonesystem by 2006. Indeed, the Internet may have become the telephonenetwork by that time, if our ability to do Internet telephony works outas well as some of us hope it will. Some people are confused about the relationship between theWorld Wide Web and the Internet. Internet provides the plumbing totransport data for a variety of applications, and the World Wide Web isone of them. But there are others, including electronic mail, Internettelephony, Internet radio and television -- which is how we'remulticasting this event tonight over the net -- group interactive games,collaboration tools, and a host of other applications. Today, almost 8,000 radio stations put their audio on theInternet. And on the net today there's also a little bit of video, anda certain amount of telephony -- speaking of which, my colleagues and Iback in the 1970s did experiments with voice on the Internet. But wehad so little capacity in the system that we had to compress the voice-- to shrink it down into a smaller number of bits per second. When youtalk on the telephone net today, you're using 64,000 bits per second ofcapacity to deliver the sound. But on this very small little Internetin the '70s, we had to squeeze it down to 1,800 bits per second. Itworked very well, except one little side effect -- it made everyonesound like they were Norwegian. (Laughter.) But, apart from that, itworked very nicely. (Laughter.) Mobile access is also emerging, with wireless local areanetworks, digital cellular telephones and mobile data radios which allowyour computer to connect to the Internet over the radio now. Now, in addition to conventional desktop and laptop computers,there are many other devices that are becoming Internet-enabled --things like Internet televisions, two-way radio pagers like this onethat can do e-mail on the Internet, over the air. You can see, it has akeyboard that is suitable for people who are three inches tall --(laughter) -- but, apart from that, it's a minor detail, everything elseworks. Cellular phones today can surf the World Wide Web. You'll beable to program your VCR by pulling up a pay on the web, clicking on theprograms that you want to record. And the instructions to do that willgo through the net to your VCR. This beats trying to find an11-year-old to help you do it. (Laughter.) And, by the way, once theVCR is on the net, it can find out what time it is and get rid of theflashing 12:00 that's on -- (laughter.) Indeed, many kitchen appliances, such as the refrigerator andthe washing machine may be on line in the future. And there are somepretty funny scenarios that result from that. For example, the bathroomscale that sends your weight to the doctor and that becomes part of themedical record. Unfortunately, the same information may get to yourrefrigerator -- (laughter) -- which will refuse to open because it knowsyou're on a diet. (Laughter.) The refrigerator could scan the barcodes on items that were put into it, so it could keep track of what wasin the refrigerator and how old it is. So you might get an e-mail fromyour refrigerator warning you the milk is three weeks old -- (laughter)-- and it's going to crawl out on its own if you don't do somethingabout it. It might even compose a potential shopping list for you basedon what it knows you've bought in the past. Well, the Internet's also playing a major role in facilitatingelectronic commerce. By 2003, electronic commerce of all kinds mayreach somewhere between $1.8 and $3.2 trillion in value. That's betweenfive and ten percent of the world's economy. So it's no surprise thatthere's a lot of interest in what the Internet is doing to us in termsof legal issues and personal issues. Internet is going to get into everything. Here's an exampleof a web-server that fits on a single chip. In fact, the chip issmaller than the plug that connects the server into the Internet. We'llbe able to Internet-enable almost anything. And Internet is goingeverywhere. Here, you see two young men putting up an Internet sight inKihihi, Uganda, in a village far, far away. Well, a vast array of public issues arise with the use of theInternet. As the Internet begins to carry all of its predecessor media-- television, radio, print media and telephony -- questions about theprotection of intellectual property and regulation become increasinglyimportant. Taxation of transactions on the Internet is yet anothermajor topic, because Internet is global and any effort to tax itstransactions will require global agreement on suitable practices andprocedures. The question of control of content on the net is anotherfrequent topic of debate highlighting the tension between freedom ofspeech between adults, on the one hand, and the protection of youngpeople who might not need to be exposed to some of that informationwhile they're on the net, on the other. And similarly, citizens areinterested in protecting their privacy as they use the Internet. Well now, let's look to a more distant future. My colleaguesat the Jet Propulsion Laboratory and I have been working on an extensionof the Internet to outer space. As we all recall, JPL has beencommissioned by NASA to launch a series of missions to Mars every 26months. Last year, we all shared in the excitement of seeing dramaticphotographs relayed from Mars by the rover of the Pathfinder mission. A year or so ago, several of us interested in the use ofInternet in space began to work on the use of Internet to support futurecommunication needs of robotic and manned missions in the exploration ofspace. This is really a different environment. It takes 80 minutes fora signal to go from Earth to Mars and back again, for example, in theworst case. We're designing an interplanetary backbone which we hope to befunctioning between the Earth and Mars as early as 2008. NASA'sAdministrator, Dan Goldin, often speaks of Internet-enabled Mars, as away of capturing this notion. And by 2040, we hope a stableinterplanetary backbone can be established between the planets. Meanwhile, back on Earth, the link between the information ofthe Internet and the human genome is most vividly illustrated by geneticresearch which uses information technology to determine and analyze the3 billion pieces of information that make up the complete DNA sequenceof a human being. And speaking of biotechnology, I believe it will beroutine in the 21st century to interconnect our nervous system withelectronic equipment. The best example of this, using today's technology, is thecochlear implant. The implant bypasses the mechanics of the inner earto directly interface to the auditory nerve. A speech processor, acomputer about the size of a pager, is connected to a sound source, suchas a microphone, and delivers stimuli to the implant which directlysignals the auditory nerve. This is a direct computer nervous systeminterconnection. My wife, Sigrid, who is here with us in the audience , losther hearing at the age of 3, and she was profoundly deaf for 50 years.Three years ago, she learned enough about cochlear implants through theInternet to determine she might be a candidate for an implant. After apositive evaluation, she had the implant done as an out-patientoperation at Johns Hopkins University, and after the surgery had healed,she returned to be activated. (Laughter.) About 20 minutes after this was done, she called me on thetelephone -- and for the first time we had a telephone conversation --for the first time in our 30 years of marriage. Now, we have a bigproblem -- we have a 56-year-old teenager in the house. (Laughter.) She uses the telephone regularly, she listens to radio andtelevision. She carries a variety of patch cables that allow her toconnect her computer speech processor to any source of sound. And onairplane trips she just plugs into the arm rest, she doesn't have towait for the headphones. (Laughter.) Sigrid's surgeon, John Neparco (phonetic), is here tonight,too. John, would you stand up for a moment to be recognized.(Applause.) Sigrid, can you stand up and show us what that speechprocessor actually looks like? We can get the camera on this so that weshould be able to see it on the screen in a minute here. There we go.Hold it still. And, Sigrid, could you tell us what it was like tosuddenly regain your hearing after 50 years of silence? MRS. CERF: It's been a party every day. It's been such fun-- I'm going out and hearing the birds, rushing to the phone to gettelemarketing calls -- (laughter) -- DR. CERF: I like the one where she listened to the AT&T spielall the way to the end with a big smile and then said, "No, Vint theCerf works for MCI WorldCom, we don't think we'll switch." (Laughter.) MRS. CERF: A peak experience is being able to hear andrecognize the voices of President and Mrs. Clinton on the radio. DR. CERF: That's neat. Thank you, Sigrid. (Applause.) Well, to sum up, Internet is becoming and will be central tohuman communication in the decades ahead. It enables interaction amongcultures and societies on an unprecedented scale and among individualsand groups with a facility unknown in the past. In simple terms, thereis an Internet in your future; resistance is futile. Thank you verymuch. (Laughter and applause.) MRS. CLINTON: Thank you very much, Vint, and thank you,Sigrid, for being part of this evening and for that demonstration. Vint told us about how one information system is changing ourlives and foreshadowed what will happen when it becomes even morepossible to be combined with biotechnology. Now, to explain theinformation system known as the genome is Dr. Eric Lander. (Applause.) DR. LANDER: Thank you, Mrs. Clinton. I want to thank boththe President and the First Lady for the invitation to speak heretonight. We are in the midst of one of the most remarkable revolutionsin the history of mankind. The revolution was sparked by scientificcuriosity about life, but its consequences would be so far-reaching asto touch every aspect of society. It is an information revolution,unlocking databases of human heredity and evolutionary history. It is amedical revolution, holding the prospect that our children's childrenwill never die of cancer. And it is an intellectual revolution that mayreshape, for better of for worse, our notions of human potential. I refer, of course, to the revolution in genetics andgenomics. Now, genetics is the study of biological diversity within aspecies. This is my favorite slide to illustrate the spectacular degreeof diversity in our own species. It's a famous old picture of WiltChamberlain and Willie Shoemaker, and it shows the wonderful range ofdifferences in such traits as height, weight, skin color. But it's also emblematic for me of the many differences youdon't see -- in susceptibility to heart disease, cancer, asthma anddiabetes. All these differences are underlain by the action of multiplegenes working together with environment. Now, to geneticists, suchdifferences provide clues to the common biological mechanisms at work inall of us. Genetics is quintessentially a child of the 20th century, bornin the opening moments of this century. Of course, genetics does goback to Gregor Mendel's experiments with peas in 1865, but the work waslargely ignored for 35 years. The real explosion began with threepapers that rediscovered Mendel's work, the first of which appeared, asif keeping an appointment with history, in January 1900. Now, at the start of the century, heredity was known to obeycertain laws of transmission, but the hereditary information itself wasa complete mystery. By quarter-century, heredity had a physical basisand a cellular structure -- the chromosomes. Chromosomes carried genes,whatever they were. By mid-century, heredity had a molecular basis, in the form ofdeoxyribonucleic acid, DNA. It was clear that DNA somehow encoded theinstructions to make every protein in our body: the hemoglobin in ourblood, the keratin in our hair and the olfactory receptors with which wesmell the fragrance of a spring day. But, at the same time, it wasn't possible to read even asingle gene. Now, three-quarters of the way through the century therecombinant DNA revolution burst on the scene, making it possible notonly to read DNA sequences, but to isolate, modify and propagate genes,giving rise to the entire biotechnology industry. And, now, as the century draws to a close, we're turning fromthe study of individual genes, genetics, to global views of all genessimultaneously -- genomics. We stand on the verge of having thecomplete sequence of the human genome, the complete 3 billion letters ofgenetic instructions for the human being, comprising roughly 100,000genes. Biologists will barely pause to mark this milestone, eager torace on to understand the information in the genome. But we shouldreflect a moment on the extraordinary journey, covering nearly 10 ordersof magnitude, 10 powers of 10, in 10 decades. Genetics has been largely the story of undirected,curiosity-driven research; arcane experiments about fruit fly familiesand bacterial defense mechanisms that paid huge dividends. The humangenome project itself is the handiwork of thousands of scientists aroundthe world in academia and in industry. But the American people andtheir government deserve special credit for having had the vision tolaunch this project more than 10 years ago, to invest in basic sciencewhen its benefits were still unclear. And I particularly want toacknowledge the leadership of Dr. Francis Collins, the Director of theHuman Genome Project who is, of course, here tonight. (Applause.) Now, what will it mean to know the complete sequence of agenome? The right analogy, I believe, is with the discovery ofchemistry's period table of the elements in the late 1800s. Therecognition that all of matter could be described in terms of about 100building blocks set the stage for chemistry in the 20th century. Itrendered chemistry finite and predictable. It gave rise, on the onehand, to the chemical industry, among the other -- the theory of quantummechanics. Oh, genomics is now providing biology's periodic table. Not100 elements, but 100,000 genes. Not rows and columns, but a morecomplex tree, showing the similarities amongst genes. The effect willbe much the same -- to render biology finite. Scientists will know thatevery phenomenon must be explainable in terms of this measly list of100,000 components. And just as the chemistry textbooks have theperiodic table in the front cover of the textbook, so, too, will biologytextbooks of the sequence of a human genome. Conveniently, one humangenome fits snugly on a single CD rom. How is genomics being used in medicine? First of all, to findgenes for disease susceptibility. This can be done by correlating theinheritance patterns of a disease in families with the inheritancepattern of chromosomal regions, to home in on the location of a diseasegene and discern its nature. For cystic fibrosis, for example, the DNA sequence looked likethis -- lots and lots of letters. And I call your attention to thistiny spot boxed in red, which I've blown up in the next slide there.That's right. The deletion of those three letters, C,T,T, encoding asingle amino acid, phenylalanine, is the cause of cystic fibrosis in avast majority of cases. About five people in this room carry thatmutation. They're not, themselves, at risk, but they could havechildren with CF if they marry another carrier. And if on the way outof this room, everyone were to spit in a test tube, we would be able toanalyze the DNA and call you back tomorrow and let you know which of youwere carriers. But there's more. If we toss the sequence of a cysticfibrosis gene into the computer and ask if the computer's ever seenanything like it before, the computer responds, yes, there are dozens ofgenes that are similar. They all reside at the cell's surface and theytransport molecules. And that's before doing even a single experiment.We have a very good guess that the cystic fibrosis gene is atransporter, which indeed turns out to be right. This shows clearly the power of transforming biology into aninformation-based science. Discoveries can be leveraged a hundred timesover. The same approach has been used to identify genes from manydiseases, including early onset breast cancer and colon cancer. And here's a provocative example. There's a gene onchromosome 19 called apolipoprotein-E. It has three common alternativespellings in the population, called E-2, E-3 and E-4. Turns out, if youhappen to have a double dose -- two copies -- of the E-4 spelling, youhave an especially high risk of Alzheimer's disease later in life --perhaps a 50 percent chance. About six people in this room have adouble dose of E-4. And if, on the way out, you spit in the test tube,we can ring you back tomorrow and let you know if you're one of thosepeople with high risk for Alzheimer's disease. Do you want to know? I certainly don't. There's no therapytoday for it. But at least the knowledge that apo-E is involved in thedisease has propelled pharmaceutical companies to search for drugs thatblock its action. Now, one consequence of the periodic table is that we canbuild detectors to follow how each gene is turned on and off underdifferent conditions in the cell. By taking such global views, we canbegin to infer the wiring diagram, the circuits and software of thecell, so to speak. Everywhere, the focus is on mechanisms. We're beginning tounderstand diseases as mechanical processes, uncovering the cellularclockwork driving the mayhem of disease. Even aging is beginning to beunderstood as a programmed, molecular process -- raising the prospectthat someday we may be able to slow its course. Nowhere will the impact be greater than on cancer. Cancertreatment today consists largely of giving poisons to which rapidlydividing tumor cells are slightly more sensitive to normal cells. It'sa blunt weapon, indeed. Now, for the first time, the features thatdistinguish cancer cells from normal cells are becoming clear. Theysuggest dozens of ways to specifically kill cancers. They go by arcanenames like angiogenesis inhibitors and telomere blockers andantibody-mediated destruction. But these rational strategies willtogether provide us with multi-drug cocktails from which tumors can'tescape. It will take patience and steady investment, but it's alreadyclear that by the end of the next century cancer will no longer be thedread scourge that it is today. And quite apart from its medical significance, the texturevariation in the human genome holds great fascination. Any two humanbeings on this Earth are 99.9 percent identical at the DNA level -- onlyone difference in a thousand letters. So as you look to your neighborto the left and to the right, you should appreciate how nearly identicalyou are. (Laughter.) On the other hand, one difference in a thousand letters in agenome of 3 billion letters still translates to 3 million differencesbetween any two individuals. So if you look to your left and your rightagain, you can also revel in your absolute uniqueness. (Laughter.) DNA also teaches us about human history. Rare spellingdifferences in DNA can be used to trace human migrations. For example,scientists can recognize the descendants of chromosomes that ancientPhoenician traders left behind when they visited Italian seaports. DNAalso tells us that we are a very young and closely related species. DNAvariation reveals a human family tree in which all 6 billion humans onthis Earth -- and I understand that last night at midnight, weofficially passed 6 billion with a little baby born in Sarajevo -- all 6billion humans on this Earth trace back to a small group of about 50,000humans that lived in Africa a mere 7,000 generations ago, about 150,000years ago. The common genetic variance in the human population todaylargely traces back to that initial family population in Africa. Andalthough the general public may imagine that there are sharp differencesamong racial and ethnic groups, most genetic variations are distributedacross all groups. Now, there is one crucial way in which my periodic tableanalogy breaks down. The chemical periodic table pertains to atoms andmolecules. The biological periodic table speaks of people. The socialconsequences of genomics will be far-reaching, and I hope we'll have anopportunity to discuss them this evening. Let me touch on one very briefly. In the short-term, the mostpressing challenges will be to deal with the flood of geneticinformation. The key issue, I think, is privacy. We must protect theprivacy of genetic information, so every citizen can get the informationessential to their health without fear of repercussions. Shouldinsurance companies have a right to know genetic information beforeproviding health insurance? What about employers? The government?Even overzealous journalists? There's been some progress in passing laws to prevent geneticdiscrimination in group health insurance, but there's currently noprotection for individual health insurance, employment and generalprivacy. There's much work to be done. Now, in the long-term, the most unsettling question will bewhether we should ever re-engineer the human genome. Well-meaningenthusiasts are sure to begin proposing ways to improve the human genome-- to prevent cancer, slow aging, enhance memory. Concerning this lastpossibility, I'm sure you've all read that Princeton University, my almamater, has expanded its educational mission. Biologists there areproducing smarter mice by adding genes for certain neurotransmitterreceptors. But the notion that we can improve humans with a quick genefix is, of course, naive. Human physiology is a delicate balance, andsimplistic efforts are likely to do more harm than good. Just imaginethe prospect of a product recall for a gene introduced into the humanpopulation that we later realized wasn't such a good idea. (Laughter.) Well, we can delay these prospects for a while by emphasizingour profound ignorance, but that's only a temporary solution. Therewill come a time when we can do such things safely, and we must discusswhat we should do. Should we ever make a human being in someone'simage, according to someone's plan? Would crossing this threshold turnhuman beings into products of manufacture? If we cross this threshold,will we ever return? And then, finally, the most important issue will be the subtleways in which genetic knowledge influences our own views of humanpotential. There is a risk that we may fall into a naive biologicaldeterminism, hewing to individuals as specified by their genes, limitedby their genes. This would be a colossal mistake. History is littered withsupposedly scientific pronouncements about the limits of women, ofAfrican Americans, of Southern Europeans, of Asians, of Jews. Sciencehas done a singularly poor job when it has sought to define limits onthe human spirit, and on human potential. Now, we need more nuanced ways to understand the role of genesand the range of human diversity. I'm particularly fond of this poster,from an exhibit at the Musee du Langue in Paris. It reads: "Toutparent, tout different." It can be translated two ways: all the same,all different; or all related, all different. And this is, of course, a central theme -- perhaps the centraltheme in the American conversation. When Thomas Jefferson wrote theDeclaration of Independence -- "We hold these truths to be self-evidentthat all men are created equal," -- the words, in fact, had a rathernarrow meaning. But they have grown with the country, reinterpretedthrough the centuries by Elizabeth Katie Stanton at Seneca Falls, byAbraham Lincoln at Gettysburg, by Martin Luther King on the steps of theLincoln Memorial. That fundamental credo that people must be judged forhow they act, not for accidents at birth, will have even greaterimportance as we develop thousands of new ways in which we could, inprinciple, subdivide a people. What a remarkable time. Genomics is opening breathtakinghorizons in scientific understanding and medical progress. At the sametime, it is presenting us with complex social choices. I know of noscientific field in which it is more exciting or more important for usall to imagine the future. Thank you very much. (Applause.) THE PRESIDENT: We have had many wonderful nights here, but Idon't think I've ever been more stimulated by two talks in my life.Thank you, Dr. Cerf. Thank you Dr. Lander. I would like to also say a word of appreciation to Hillary. Ithink that as our time here draws toward its close, it's clear that shehas been, I believe, the most active and innovative First Lady sinceEleanor Roosevelt, for, perhaps these Millennium Evenings will lastlonger in the imagination of America than virtually anything any of ushave done, and I thank her for that. (Applause.) Also, being term-limited does have its compensations.Normally, at this time of year I'd be doing something else tonight.(Laughter.) Yesterday, I called the Vice President to rub it in anddescribe what I would be doing tonight. (Laughter.) And I was having avery good time turning the screw about how fascinating this was going tobe. Finally he said, that's okay, you need to be there more than I do.(Laughter.) The jokes about my technological and scientific limitationsare legion around the White House. (Laughter.) So I have been thinking of all these questions -- do I reallywant a mouse smart enough to go to Princeton? (Laughter.) Won't it besad to have an Internet connection with Mars if there are no Martians towrite to or e-mail us? (Laughter.) I am glad to know that the totalconnection of the Internet to the nervous system of human beings is alittle ways out there in the future. I had been under the impressionthat that had already occurred among all children under 15 in America.(Laughter.) This is an amazing set of topics. Let me say just one otherthing. I really loved seeing, on a slightly sad note, I loved seeingthat wonderful, famous picture of Wilt Chamberlain and Willie Shoemaker.Some of you may know the great Wilt Chamberlain passed away today, oneof the greatest athletes of the 20th century. So I hope you will havehim and his family and friends in your thoughts and prayers tonight. This is a fitting thing for us to do in the White House,because innovations in communication and technology are a very importantpart of the history of this old place. In 1858, the first transatlantictelegraph transmission was received here in a message that QueenVictoria sent to President Buchanan. Later, the first telephone inWashington, D.C., was located in a room upstairs and we now have areplica of that telephone in the same room upstairs. The first mobilephone call to the moon was made here by President Nixon, 30 years ago.Even these Millennium Evenings have made their own history. This iswhere we held the first ever cybercast at the White House. So I want to thank the speakers for building on all of thisand telling us what we can look forward to in the future; and forreminding us that as we unlock age-old mysteries and make what we canthink more possible to do, there are ways to do it that bring ustogether as a society. So I would like to begin the questioning, if I might, with aquestion to Dr. Lander, because it bears on a great deal of the workwe've done. You talked about how we were 99.9 percent the same, but how ifyou looked at how many permutations there were in the one-tenth of apercent left we could still be very different. I think it's veryinteresting -- and I talk about this all the time -- that as we're onthe age of this new millennium and we have these evenings and we imaginethis future that you have sketched out to us, this is what we all liketo think about, how exciting, how wonderful, how unbelievable it can be. The biggest threat to that future is how many of us on thisglobe are still in the grip of the most primitive of human limitations-- the fear of the other, people who are different from us. And we seeall over the world -- from Bosnia and Kosovo to the Middle East toNorthern Ireland to the tribal wars in Africa, how easily the focus onour differences -- that one-tenth of one percent -- as what matters canlead first to fear, and then to hatred, and then, ultimately, todehumanizing people who are different. And it's very interesting -- as someone who grew up in thesegregated South and lived with the whole terrible and, yet, beautifulstruggle of the civil rights years, to think that there were in myhometown people who were dehumanizing other people because of theone-tenth of one percent difference between them is quite an awesomething to contemplate. So I would like to ask you, if you could say in ways thatwould make sense to us, explain to us a little bit what is it that makesus the same and what is it that makes us different? And how could wecommunicate this scientific knowledge to people in a way that woulddiminish the force of racism and other bigotry in the world in which welive? DR. CERF: You're not asking for a whole lot there.(Laughter.) A minor little detail, right. (Laughter.) DR. LANDER: No, but what a wonderful question and what animportant thing. I even want to point out that when you speak about theone-tenth of a percent difference between two groups who might bewarring with each other, there isn't a one-tenth of a percent differencebetween those groups. DR. CERF: It's even less than that, isn't it? DR. LANDER: In fact, the variation in the human population isreally that ancient variation we had back a long time ago. Most genescome in about two or three flavors, two or three spelling differences.And those flavors of the genes weave themselves through the humanpopulation like a tapestry. You and I have one-tenth of a percentdifference. But two ethnic groups don't have one-tenth of a percentdifference. Most of the variation is not between groups, it's withinthe individuals within the group. In fact, since we all left Africa 7,000 generations ago, therejust hasn't been a lot of time to build up large amounts of geneticvariation. We do see differences. In fact, we're cued into seeingdifferences between people. That's very misleading about what is reallygoing on at the genetic level. You may think two humans look verydifferent from each other, but the truth is they're much moregenetically similar than two chimpanzees are. Chimps have much moregenetic difference within their species than we do, because we are sucha new, young, small species. And so, in fact, there are not significant genetic differencesbetween warring parties in most parts of the world. A geneticist goingin could not find those differences. Indeed, it may help -- I don'twant to be naive about that -- but it may help for folks to know thatthe differences that are out there are woven in every population. Maybethey're at slightly different frequencies, but they're throughout thewhole population. I don't imagine that will solve prejudice and that will solveracism, but, in fact, I don't see a scientific basis for drawing linesbetween people there. DR. CERF: So you're saying that racism isn't a spelling error? DR. LANDER: No, no, no. DR. CERF: It's not anything as simple-minded as that at all. DR. LANDER: Sure, there are genes that control differences inappearance and some of them have been selected over the years. But, infact, they don't represent the majority of variation in the genome. AndI, as a geneticist, and I think most of my colleagues appreciate thatthose are not the places to draw lines. DR. CERF: So, therefore, that's not an excuse. That'swonderful. DR. LANDER: No, I think the interesting variations that arethe variations of things like the number of color receptor genes youhave. Some folks have two red receptors or three red receptors, and dothey see the world differently? There's a lot of wonderful texture ofvariation out there, but it's not a variation that ought to be dividingus. MS. LOVELL: I'm going to bring this back to the Internet withOmar Wesso (phonetic). You started, as a youth, playing around withcomputers and now you're an Internet analyst and entrepreneur. Q Thank you. I wanted to ask, basically, we have seennumerous wonderful and unanticipated uses of information technologydeveloped. You mentioned electronic commerce. I wonder, how can weencourage more young people and adults to move from being consumers ofthese future innovations to being creators? DR. CERF: Actually, based on what the President observed, I'mnot sure we have to encourage too much. I think that most of theinnovation that's happening in my field is happening among young peoplebetween the ages of nine and 20. One of the sons of an FCC Commissioneris already teaching his third grade class how to make web pages. And Ithink -- don't look behind you, there is a 13-year-old gaining on you. I honestly believe if you're looking to understand where thefuture of the net is going and all of this technologies, don't ask anold fart like me, go talk to the kids that are teenagers or in juniorhigh school because they are the ones that are going to decide whatthings they want to buy, what services they want, what new productsthey're going to build, and a lot of them will do it themselves. So in a funny way, I'm not sure that we have to work very hardto achieve the objectives you're suggesting. These kids have adoptedthe net, it's theirs. The one message I get from them is, this is ournetwork, don't screw it up. (Laughter.) MS. LOVELL: Well, Mrs. Clinton, let's go to the Internet. MRS. CLINTON: All right. This is one of the real joys ofbeing able to have these evenings is to have questions that come in.And so, do we have a question that we can put on my screen? Do I haveto -- Ellen, if it's on that screen, why don't you read it? MS. LOVELL: Yes, that was supposed to happen. Well, here we go. DR. CERF: By the magic of technology. (Laughter.) That'sit. How many engineers does it take to -- MS. LOVELL: Somebody just said one of the postcards got lost.(Laughter.) This is from Seattle, Washington, and it's to Vint Cerf, andit says: At our current pace, do you think we'll gradually lose ourinterpersonal skills and become more and more isolated from each other?Are we losing our tribal or village human experience, in exchange for apurely impersonal, technical one? Thank you, Uncle Dave. (Laughter.) DR. CERF: You know, this reminds me of the glass windowsyndrome. Whenever we get into an automobile and we start driving,we're isolated from the world by a sheet of glass. And boy, what doesthat do to change our behavior. Well, I don't agree with the proposition that the Internetisolates, or dehumanizes, or separates us. I don't think it does anysuch thing. I think that it connects us in ways that we never could beconnected before. I see preservation of culture. I see the sharing ofexperience. I see the sharing and preservation of history in thatmedium. I discover people and places that I never would have discoveredbefore, were it not for the spread of the net. And I think, frankly,the travel industry is going to benefit more than any other segment ofthe population, because people discover other people with commoninterests, that they otherwise could not have encountered. And thenthey want to go and meet them. And so my guess is that the net is actually going to create afar greater, global conversation than we ever had before. And it willcreate virtual villages of people with shared interests that couldn'texist except in the world of cyberspace. MS. LOVELL: Yumedas Chikas (phonetic) is a student fromWheaton High School who participated in the National Institute of Healthpilot program, teaching genetic literacy so young people would be ableto make informed choices in the future. Q Good evening. Both the Internet and genomics gatherbillions of pieces of data. Who owns information gathered about me? Isthat information secure, in the database or on the Internet? Do I havea right to keep my information, including genetic information, private? MS. LOVELL: That's really for both of you. DR. CERF: I think you do. And it seems to me that it's nodifferent than any other personal information that might be about yourincome, or your financial situation, or other personal activities. Ofcourse, the problem is not the technology. And don't let anybody tellyou that, well, the solution to this problem is cryptography. It'sactually a powerful tool, and it's a good, useful tool to have. But what is really at issue here is how we decide as a societyto treat that information. How do companies and other organizations whoobtain it in the normal course of work -- if it's medical transactions,medical treatment and things like that -- how do we decide, as asociety, to treat that information? And in my view, that information is just as private asanything else that we would consider personal information. But in orderto protect it, we have to decide that's what we're going to do. DR. LANDER: Now, Vint, you say he has a right to that. Andthat's because you recognize his right, but I don't know that at law wedo recognize that right yet. I think, in fact, we have to go quite aways to protect the right that we feel you should have to control yourown genetic information. Do you have a right, right now, to stop someone who takes yourblood for a particular test, medical test, from doing 10 other tests toit? It's not at all clear in the law you do right now. Do you have theright to stop me from taking a cocktail napkin that you might have wipedyour face with and do a DNA test on it? It's not clear you do rightnow. I think, in fact, if we're going to make sure that you have anopportunity to seek genetic information for your own benefit, we'regoing to have to protect it. And I think we're going to have to protectit with a lot -- to recognize that right, to let you sue for that rightand to make sure that everyone respects that right. And I know there's a lot of effort to do that right now. AndI think it's one of the most important remaining works to make sure thatthe Human Genome Project itself delivers a society that citizens canreally use. And I really, for my part, endorse the efforts to pass suchlegislation. I really call on everyone to get to it. DR. CERF: Could I ask for you -- we've got two very prominent -- DR. LANDER: Right. You guys have more to say about this than-- (laughter.) THE PRESIDENT: Let me just say this. We've been working onthis, and it's very important to me because I'm a fanatic about thisissue. I want unlimited scientific discovery, and I want unlimitedapplications. But I think we don't want people to lose their sense ofself and the fragility of their personhood here in some sort of assault.So we've been working on this. What you said sounds great, but it's not as easy to do as itsounds. So I think it might be helpful, if I could just ask SecretaryShalala, who is in charge of one piece of this, which is our efforts toprotect the privacy of medical records, just to talk a little bit inpractical terms about what we're doing to respond to this young man'squestion. Donna, would you -- there's a mike. SECRETARY SHALALA: I think the most important thing I shouldsay to this young man -- actually, the answer to his question is, itdepends on what state he lives in whether his medical records -- DR. CERF: Euphoria. SECRETARY SHALALA: But the one thing I can tell you is thatthere are more federal protections on your Blockbuster card than thereare on your health information. And that is, no one can go to yourlocal Blockbuster and ask what movies you rented because they'reactually is a federal law that protects your Blockbuster record and thevideos that you rent. What we're trying to do is to set out a set of principles --and we'll probably end up putting in place some regulations if Congressdoesn't act. The President has been urging Congress to act. But thefundamental principle is that health care information ought to be usedfor health care purposes. And anyone that doesn't ought to be heldaccountable; that you ought to have the right to get access to yourhealth records to make corrections, if necessary, but that there arelarger public purposes. The President cares deeply about research, for example, andthat all of us have to agree as a society that our health records can beused for research purposes but, at the same time, protect our privacy. So we have to have a set of principles and the fundamental oneis that health care information for health care purposes -- they can'tbe used to deny you a job or access to college or to deny you insurance. THE PRESIDENT: But let's deal with two hard questions here,real quick -- I think this is important. Question number one, prettysoon if the genome project is brought to fruition, according to what Dr.Varmus has told me when I spent a day out there, it will become normalin the not too distant future for young mothers to go home with theirbabies from the hospital with a map of their genetic future. You maynot want to know about Alzheimer's, but you could know about things thateven if you can't cure you could delay, defer or minimize. So you getthat. Now, the mother and the father are employed by someone andthey provide family health insurance. Since private insurance is basedon a reasonable approximation of risk -- I don't agree with the way wefinance health care in this country, you all know that. But that's afight I didn't win here in the last seven years -- if it's based on anassessment of risk, what should the insurance company have a right toknow? And if the insurance company doesn't have a right to know,haven't you undermined the whole basis of privately-funded insurancebased on risk -- question one. Question two for you. DR. CERF: We don't get to answer that one. THE PRESIDENT: Yes, I want you to answer that, but I want youguys to talk. Question two: This is the problem we face in a much moregrave sense in dealing with the prospect of cyberterrorism or something.It's one thing for us to write laws that protect privacy of records.But you just got through -- in answering Omar's question, you weretalking about how, well, but all these kids are always figuring out --well, among the things they're figuring out is how to break into varioussystems all the time. So even if we had perfect laws, how are we goingto protect privacy when we're dealing with all of these creativegeniuses out there working through the net? Respond to those twoquestions. DR. CERF: Now, let's you and him fight. Okay. DR. LANDER: No, no, it goes right to the heart of the problemhere. At some level, is insurance about matching rates to risks, or isit about sharing risks that none of us chose? And what happens is thatat the beginning where we don't know that much about our future, there'snot so much tension between those two. As we learn more and more aboutspecific risks -- that you might be at risk for cancer and someone elsemight be at risk for diabetes, we could make exclusions or put inspecial rates for your cancer risk there -- we can, in fact, tear apartthe basis for pooling the risk and sharing the risk. But I think the important point to recognize there is if oneinsurance company won't wish to forego that information when itscompetitors had that information -- well, it wouldn't do very welleconomically. But if all couldn't use that information, they wouldn'thave any disadvantages relative to each other. There is still the question -- what I guess economists call"adverse selection," people who know they need more insurance for someparticular risk going out and buying more. But for some basal level ofinsurance, I think, in fact, we ought to have a way where some insurancepackage -- and we probably don't disagree much on this -- has to beavailable to people quite independent of those risks. And maybe then, if you want to get an extra million dollarpolicy on some cancer thing, you might have to consent to it, becausethat's a different kind of economic bargain. But at some basal level,no, we've got to decide that we mean this is a social way to share risk;to say with respect to all the things that could happen to you, therebut for the grace of God go I, and decide that that's the basis for oursystem. And I think we can by making sure that we uniformly don't usethat across all companies, make an economically viable system thatdoesn't. But there's obviously a lot of work to be done, and I don'tmean to over-simplify any of that. You get the other half. DR. CERF: I get the other half. Thank you. Okay, I want tocome back to this question of privacy, though, but we'll do thatafterwards. The question about how we protect ourselves against allthose really smart kids out there is that some of them are helping us dothat, in fact, already. (Laughter.) But I don't want to understate thechallenge that this poses. You'll recall, Mr. President, that your Information TechnologyAdvisory Committee not too long ago recommended that we increase thelevel of research and fundamental software principles that will allow usto build much more robust systems than we can today. There's a lot ofvery basic research that needs to be done to make software more reliableand more resilient. And that's not something that you just do on aweekend's work. It means serious and sustained effort in the computerscience departments here and elsewhere to understand how to cope withthe billions of pieces of software that are interacting in networks inthese little slices of computing that are everywhere imbedded in thewoodwork. So the answer is, there's no easy solution to that. But it'snot going to require a breakthrough of huge magnitude; it just takessome very sustained work. And we have to make sure that that work getssupported. MS. LOVELL: You know, I think Carol Greider (phonetic)actually had the perfect follow-up question to the President's question.Carol is a geneticist with John Hopkins University, with an expertise in-- as you will see -- a very special interest in genetic information. Q To pick up the question that you raised yourself, a questionof Dr. Lander, and that is that, given that a lot of different diseaseshave both a genetic component and an environmental component, and thegenetic component may be made up of a number of different genes, whatmight be the advantage to parents knowing the complete genotype of theirchildren as they go home, knowing that there are environmental as wellas genetic influences? DR. LANDER: Well, goodness, today, sending parents home withcomplete genome type information, even if we could do it, wouldoverwhelm them -- would overwhelm them because they couldn't possiblydigest that information; and because nobody could help them digest thatinformation. Genes interact in a complex way in an interactiveenvironment. We're going to have to think very carefully about how tosupply information that represents what we really know and what peoplecan act on. There are going to be places where we can make a bigdifference. We know there are genetic predispositions to juvenilediabetes. We don't know quite how to prevent that, but there arestrategies that people might use if you knew a child was going to be athigh risk for juvenile diabetes. And that's something that you'reprobably have to do before the age of five, to intervene then. So aparent is going to have to know that information and do something aboutit and make a choice. And they may be strategies that you wouldn'tapply to everyone in the general population because there is riskinvolved. So we're going to have to match the information to being ableto act on that information and to the responsibilities of parents do it.I think the gaping hole right now is education. And I don't just meanthat in the form of the American people don't know enough about geneticsand they should pick up genetics text books. I mean that we don't knowhow to explain it. But a tremendous amount of research has to go on onhow to communicate this in a way that people can hear and understand.It's easy to talk around statistics and nucleotides and things likethat, but I don't think it connects for people. And so I think we have a huge amount of work to do, every bitas important as the scientific work, to connect up with the generalpublic and expectant mothers and fathers. DR. CERF: Can I come back to one very interesting thing aboutthis privacy question? Often, when we're trying to do scientificresearch, it's really valuable to have a pool of information about thehealth conditions of the entire population that we can deal withepidemiology and all these other things, we can see how certaintreatments are doing in a large population. Now, normally, the way we deal with this is we decouple thepersonal information, the identifying information, from the medicalinformation. And that sort of works for almost all of the cases I canthink of except genetic information, and here's why. The completegenetic sequence of a person is the most definitive fingerprint I canthink of. It defines the person. So if complete genetic information isavailable to you and that's associated with any of the other medicalinformation, somehow or other that's the ultimate fingerprint, you can'tdecouple the personal information because it is the personalinformation. So what are we going to do about that? DR. LANDER: We're going to sign you up for the committeesthinking about how, in fact, you parcel out that information in waysthat we can still do research and still protect the privacy. I think both are important. We default on being able to doresearch because of an undue fear that information will leak out, Ithink we will disadvantage people. If, on the other hand, we let thatinformation leak out, we will also do a great disservice. And we'regoing to have to chart a course down the middle and it's going to take acombination of information scientists and genomicists to think about howto do that job, so we'll find out. DR. CERF: That's great. There's at least one PhDdissertation hiding in there. MS. LOVELL: And to get to some more of that information, Iwanted to acknowledge Stephen J. Gould, the biologist who, as Presidentof the Association for the Advancement of Science, helps the publicfathom issues in science. Dr. Gould. Q I wanted to ask you two quick questions -- broad inimplication. First of all, what is the human genome, given all thatvariation? Admittedly, not much between any two, but integrated overthe genome, what's it going to look like when it's finished? Is everyposition going to be ACGFT, ACGFT? Secondly, given the reductionistic traditions of the way wethink in Western science, how are we going to get people to understandand recognize that that little CD of yours is not a human being, andthat humanity and humanness is very different from the blueprint that'sonly a grand average of all of us -- never going to explain what makes aYankee versus a Red Sox, which is arguably the most important questionin America today. (Laughter.) DR. CERF: Certainly will be in the days ahead. DR. LANDER: Oh, goodness. Well, the first one -- what is thehuman genome -- sort of a first-order approximation, it will be a listof As, Ts, Cs and Gs, just like you've got lists of ones and zeroes.And it will be an arbitrary sequence from one person -- actually, aharlequin of sequences from different people. And we won't fuss muchover the one letter in a thousand. As time goes on in the years ahead, each of those letters willget annotated to say, this is a spot of variation. This is a spot whereyou've got a gene that frequently comes in a couple of different forms.And that will get layered on and on. Every single nucleotide of thehuman genome does vary in somebody in the population, but the ones we'reinterested in are the common ones, where we might stand a chance ofunderstanding medical significance. With regard to the other question you ask -- how do we makesure that people don't get the view that the CD is the person -- I thinkthat scientists have a real obligation in their choice of metaphors. Ithink metaphors are tremendously powerful things. We can call the humangenome "the blueprint," the "Holy Grail," all sorts of things -- it's aparts list. It's a parts list. If I gave you the parts list for theBoeing 777, it's got 100,000 parts on it, but I don't think I couldscrew it together on the basis of that and I certainly wouldn'tunderstand why it flew because of that, and I wouldn't understand allsorts of things because of that. We've got to understand that the Human Genome Project istremendously exciting, but it is a piece of infrastructure. It isinfrastructure building like we build roads in this country, to helpcommerce. It is an infrastructure-building project like the Internet,which is not the information, but a backbone, and we've got to makepeople understand that despite all the wonderful, highfalutin talk aboutgenomics, it is the beginning, not the end. And I don't expect to beable to read out human nature in that code, and I certainly don't seeany evidence of anything distinguishing between Yankees fans and Red Soxfans. DR. CERF: Could I just ask one question about this? It'salways bothered me that people use the phrase "blueprint," for example,to describe the human genome or any genome. And I don't think I thinkof it that way and I'm hoping that you will agree. It really feels morelike it's a program that gets interpreted, and you start out with onecell, and then it gets fertilized and then things start to happen. Andit's that sequence and portions of it that get interpreted and produceproteins and create -- so it's more like executing a program and thenhaving a result as opposed to simply being blueprint. DR. LANDER: It's both the data and the program itself. ButI've got to emphasize that when you get the CD, you don't know how toread the program any more than if you got a CD of ones and zeros for awhole bunch of computer programs written in a language that you couldn'tunderstand. DR. CERF: Or didn't know -- right. DR. LANDER: -- or didn't know. And so, in fact, we'redealing with a language here that is three billion years old, and it'sgot patches and patches on the code by evolution. It's never beendocumented very carefully -- you think you've got problems withdocumentation -- (laughter) -- this stuff hasn't been documented -- DR. CERF: Wait a minute -- is there a Y2K problem with thehuman genome? (Laughter.) DR. LANDER: There's a Y-3 billion problem. That's the issue.(Laughter.) DR. CERF: I'm not worried about that. (Laughter and applause.) DR. LANDER: No, no, I mean that quite seriously. If you havetrouble sorting out Y2K problems in a piece of Fortran code written inthe 1960s, just imagine the issues in trying to decipher the workings ofsoftware that's the product of 3 billion years. DR. CERF: You know, I used to think we were going to getpeople angry at us for the Y10K problem, right, when they'll say, "whydidn't those jerks 8,000 years ago fix it with an extra fifth digit?"Now, you're wondering why didn't that stupid bacterium -- (laughter) --three billion years ago -- why didn't you do it the other way? MRS. CLINTON: I have to ask Stephen J. Gould, since he sortof alluded to this by raising the Red Sox and the Yankees, how would youanswer the question about what genetics will tell us about behavior? Isa Red Sox or a Yankee fan bred in the DNA? What is it we're going tofind out about behavior? DR. GOULD: Certainly not. There is a basic human naturebased on the very minor extent of the differences that Eric so wellspecified. But most of what interests us is the enormous culturaloverlay, which is obviously permitted by our common genetic nature, butthat's not a particularly informative statement. Thank goodness therichness of our differences in our cultures is not so specified, and iswhat is influenced is enormously flexible and that will preserve ourdiverse humanity and so biology will join culture and even give us someliberty, thereby. MS. LOVELL: Mary Davidson. As executive director for theAlliance of Genetic Support Groups, you represent people withgenetically based conditions. Q Yes. I have a question for you, Dr. Lander. I'm speakingfrom the perspective of families that look to genetics with suchtremendous hope, but still with their eyes open for the undertow thatwe've been talking about. So let's put ourselves in a very personalposition. Do I really want to know if I have a predisposition for adisease for which there is currently no medical treatment? And if Iknow that I'm already -- if I already know that I'm at risk for adisease, what happens to me and my family, then, in the lag time betweenobtaining this knowledge, having it on my medical record, and then atreatment certainly being developed in the, I hope, near future? DR. CERF: Boy, science is a lot easier than policy, isn't it? DR. LANDER: Yes. Your first question, do you want to knowabout genetic information concerning traits where you can't do anythingtoday, at least where there's no treatment today -- well, in some casesyou might. There might be instances -- for example, people withHuntington's disease or at risk for Huntington's disease may still wantto know because it will affect their reproductive decisions, or mayaffect their reproductive decisions. And so there can be instanceswhere that would be useful. There may be instances where early screening might still be ofsome benefit -- you don't have very good treatments, but there might bepurposes with regard to some cancers where early screening might be ofvalue. But now, if we can't do anything about it, on the whole it'snot clear to me that that information really does anyone any good --although I must say that if the person wants to know, they have everyright to know. We're going to have -- as you point to -- this veryuncomfortable lag period between when we can predict and when we canprevent, or cure. It's going to vary tremendously. For some diseases, it mightbe a couple years, and for other diseases it could be a century, becausewe might not have a way to get into the right cell in the brain to beable to do something. We have to be honest about that. Genetics holds tremendous promise, but it doesn't guaranteethat understanding is a cure. It's just that ignorance is usually atremendous obstacle to the possibility of a cure, and that's all thatscience can hold out. We are going to have to help families get the information tomake the choices about what they want to know. We clearly want to knowit as scientists. We want to be able to race as quickly as possible topreventive therapy. But this is going to have to be a conversation, anda multi-textured conversation, because every genetic disease isdifferent with regards to its risks, with regards to the people itaffects -- young children or older people in life. That's why I thinkit's so important that we have a dialogue between scientists and thegeneral public on this. DR. CERF: Could I just find out something here? Now, I thinkabout how difficult it is for us to understand the behavior of theInternet and all the computers that are on it, and all the softwarethat's on it. And yet that system, in some ways, is not even as complexas the interactions that happen in our human bodies, as our bodiesdevelop and as the DNA is interpreted. People sometimes must get theidea that this is like clockwork, and it isn't. We don't actually knowwhat will happen. We know what might happen, but we don't know deeplyexactly what will, and we can't predict it. So people who get this genetic information and misunderstandit to be a prescription, a prediction, would be terribly misled. And,in fact, I don't even know if you can quantify how little we actuallycan say about what the outcomes are going to be. It's so complex. DR. LANDER: But it varies for each disease -- DR. CERF: That's the point. DR. LANDER: -- and in some cases we do know things. You know,we can't deny the fact that there are genes that confer a risk of earlyonset breast cancer. And we can statistically measure the population,and say with some statistical certainty, even if we don't know the wholecircuitry of how it happens -- although a great deal of progress hasbeen made on that -- that a young woman who's diagnosed -- who is toldthat she has a particular mutation has a particular risk in life. Now, it may be that some environments will push it one way orthe other, and we don't know enough about it, and that we're giving anoverall average number to everybody. But that number's still verydifferent than the background risk. DR. CERF: Well, I understand that -- DR. LANDER: So we struggle our way up with very imperfectinformation. But it's valuable information. DR. CERF: Are there cases where there isn't any doubt? Inother words, a genetic mistake will absolutely, 100 percent, guaranteethere's something broken? Can you give us some examples? DR. LANDER: Many examples of that. Huntington's disease,that I alluded to briefly, has a virtually 100 percent penetrance -- theword we use for a probability of effect -- in the course of life. Thereare a handful of cases where it might be put off rather late. There aremany relatively rare genetic diseases where a gene is just plain broken,and it's clear that every individual who inherits that broken copy ortwo broken copies from each parent, will indeed have that geneticcondition. The tough cases are the ones -- the ills that afflict mostof us: heart disease, diabetes -- DR. CERF: Okay, those have variations -- DR. LANDER: Those are the ones that are multifactorial, thatdo interact a great deal with environment. Those are the ones mostpeople will be interested in in the long run, and those are the oneswhere we have the most work ahead to do. But there's the whole range,from certainties to things that, in fact, can be completely modified byenvironment. Let me give you one small example. We test every child inAmerica today for a genetic disease. It's called phenylketonuria.Babies are tested with a heel stick at birth to see if they have thisrare genetic disorder called phenylketonuria. Those few babies thathave it lack an enzyme for digesting a nutrient, phenylalanine. Ithappens to be in NutraSweet, so every Diet Coke can -- I saw thePresident drinking Diet Coke -- if you look on the side, it says,"Warning to phenylketonuric: contains phenylalanine." It's a geneticwarning on your Diet Coke can. DR. CERF: Oh, and you can't digest -- DR. LANDER: My point is, they can't digest that nutrient.And if they have it from birth, it will build up and poison their brain.And it's a 100 percent form of mental retardation -- except that if youknow it, you can put them on low-phenylalanine diets from birth andthey'll have normal intelligence. You've got there an instance wherewe've got something that's completely genetic, but, of course, it'scompletely changeable with environment. That's the range of complexitywe're talking about. DR. CERF: So let's follow up on that, if it's okay. What --suppose we know this. We know that we've got that broken gene. Now,you said, let's change the diet to deal with the side effects. DR. LANDER: As long as we're lucky, in this case, we could. DR. CERF: Now, is there anything else that we mightanticipate? Can you actually imagine genetic therapy that goes and doessomething that will correct the problem? DR. LANDER: Sure. You can imagine pharmaceutical companiesdeveloping a small molecule, a drug, that tickled some other gene tomake up for that deficit. And that actually happens. There arestrategies like that. You can imagine gene therapies, where some kindof a viral vector restores the missing gene -- a clotting factor, forexample, into some cells in the body. There's a whole myriad of possibilities. The thing about thegenome project is it gets you that basic information, but then it splaysout in a hundred directions of possible therapies that we may have todo, and there's just a century of biomedical research that's going tohave to follow on to be able to deliver on the possibilities for each ofthose. DR. CERF: To draw the informatics and genomics together for amoment, we wouldn't be able to do some of these things if we didn't havethe computing horsepower and the memory and the ability to share theinformation that we have now. That's fascinating. DR. LANDER: Not a chance. That's right. MRS. CLINTON: We have also with us Dr. Francis Collins, and Iknow you've thought a lot about this question about the gap betweeninformation and treatment. And I wanted to ask you what you thought. DR. COLLINS: Well, it's an interesting discussion we'rehaving. And I think from the perspective of individuals who currentlysuffer from some of these diseases, or they exist in their families,there's a great sense of impatience -- where are the cures, where arethe end points to this very promising research? As a physician I'm verysympathetic with that. I think what we're talking about here is working on a pathwaytowards the top of the mountain. The top of the mountain is curingdiabetes, curing hypertension, curing cancer, curing schizophrenia. Butto get to the top of the mountain you have to travel a certain path.The excitement we're talking about this evening is the genetics ofgenomics provides us with a path that we didn't have before. It's avery powerful way to get to the top of that mountain; but we shouldn'tfool ourselves that by building this base camp called the human genomewe're already up there and have solved all of those disorders. But itis the best way going right now to get to that point. And there is already good news around us with some of thehills nearby beginning to be scaled. We talked about various examples.I put forward the example of colon cancer, where we now know how toidentify the roughly half a million people in the United States that arevery high risk for colon cancer. There is a circumstance where it's nota diet or a drug, it's surveillance. If you know that you're in that category, you get yourcolonoscopy beginning at age 40 and do that every couple of years;you're going to find that polyp while it's still small enough to beremoved, and you'll save that death from metastatic colon cancer, whichis an awful one. So there is a circumstance where the diagnosis itself can belife-saving. But to be honest, the diseases won't all be like that.And then we have to keep climbing up the mountain. And some of thethings we'll find at the top of the mountain will be gene therapies andsome of them will be drug therapies. And if you're a family with thatdisease, you don't care as long as it's one of those and as long as itworks. Cystic fibrosis was mentioned by Eric earlier on. I had theprivilege of being part of the team that found that gene, and it's 10years on and we haven't cured it yet. But, you know, there are now adozen drugs in clinical trials for cystic fibrosis that have come aboutbecause we understand how the gene works. We wouldn't be at that pointnow if we hadn't had that basis, that foundation, that infrastructure ofunderstanding the genetics of this disease, which was a total puzzleuntil 10 years ago. So one should be both optimistic about where we're headed toand realistic about what the challenge involves and how much moremedical research we need. MS. LOVELL: Now, we are going to go back to the Internet, andit's for you, Mrs. Clinton. MRS. CLINTON: This is a question from Danella Bryce(phonetic) from Sydney, Australia. And the question is: Obviously thepower and the concept of the modern information technology istremendous. The fact that I can sit here in my office in Sydney andsend this question is a remarkable thing. However, for the past 25 years, I have been working with poorcommunities in developing countries trying to assist them just to reacha reasonable, sustainable level of development. How can the newtechnologies which are such a powerful information tool be harnessed toassist in the global battle to alleviate the growing numbers of peopleliving in very disadvantaged circumstances? DR. CERF: Well, let's see. First of all -- THE PRESIDENT: Can I give -- you said that we got 6 billionpeople last night. Half of them live on $2 a day; 1.3 billion live on$1 a day or less. Those are the numbers behind what Ms. Bryce isasking. DR. CERF: The first problem is that you can't take thistechnology and just put it someplace and expect it to solve all theproblems that poverty and lack of infrastructure and lack of sanitationand lack of education and everything else visit upon us, so thebeginning of all this is that you have to make investments ininfrastructure in those countries where there isn't any in order to getthem to the point where these new technologies can actually be of use. There are pockets of times when the technology can beinstalled and used immediately. For example, in medical treatment -- inobtaining important information about economics and how to operatecountry, that information can be made available immediately, but insmall places -- at university, within the administration. But for thegeneral population, the first problem is getting them to the point wherethis technology actually is useful. I can remember an effort at one time to send personalcomputers to Africa in the hope that somehow, this would help themleapfrog into the 21st century. Well, the first thing you discover is,there isn't any electrical power, or if there is, it's not veryreliable. Then you discover that the physical housing available forwhere you put the equipment is leaky and rain comes in, and even moreamazing, there are a lot of bugs that crawl around and they're not thesoftware, they're the real kinds that crawl into the machines and theydo funny things to the equipment. So then you don't have enough people who are trained in orderto maintain and operate the gear. So this -- it's not true that everycountry in the world that is still unable to take maximum advantage ofthis has to go through everything we can before they can get there, butthere are some basic things that have to happen. Just as a small example, the World Bank says that for everydollar invested in telecommunications infrastructure $3 of grossnational product can be expected to arise from that. There are formulaslike that that people can begin to work with, but believe me, this is along, hard process. A good piece of news is that all of the costs of this gear isdropping dramatically. You hear about the $200 computer. These are --consumer prices, by our standards, they're still sky-high by thestandards of countries that President Clinton mentioned. But the factis, the technology is rapidly becoming less and less expensive. Someday, Eric, we may actually be able to grow our computersbecause they'll be molecular in nature, and we'll use something verylike a string of DNA to describe what's supposed to happen, and thething will actually get created. So at some point, we'll be able todeliver these things at very low cost, but it's going to take anothermountain to climb like the one we talked about earlier. THE PRESIDENT: If I might just interject, I don't know theanswer to this, but I've spent a lot of time thinking about it. Thiswoman, Ms. Bryce, she works and she's talked about she works insustainable development. A big problem in poor countries, they totallydestroy the environment to try to develop and then they don't haveanything upon which to develop. The biggest problem in our hemisphereis Haiti -- if you fly over the island of Hispaniola you know whenyou're going from the Dominican Republic to Haiti because in all theyears when it was governed by dictatorships they just tore down all thetrees and -- if any of you know anything about it, know this. The real question is, we used to have certain assumptions abutdevelopment in a poor country; that if you wanted ever to build a middleclass life for a substantial number of the people, yet have X amount ofelectric generating capacity, and you had to have Y number of roads, andyou had to have Z number of manufacturing companies, no matter what theydid to greenhouse gases, and that eventually you get around to buildingschools and universal education -- and then 30 or 40 years later youstart letting the girls go to school with the boys and there is thissort of thing that would happen. I do believe that the question, the real question is if you'rerunning a country like this, should you put this sort of infrastructuredevelopment first? That is assuming you've got a base level ofelectricity necessary to run a system. Should you do this first becausethis gives you the possibility to skip a whole generation of developmentthat would otherwise take 30 years in the economy and in education. AndI think the answer to that at least is, maybe. That I think is reallythe question that this woman is asking. DR. CERF: I have an example. A few weeks ago I got ane-mail, and the e-mail was an offer to do work. Basically, it said ifyou have web pages that you want to have formatted and put on a website, for $125 I'll do 10 of these pages. Send me a Microsoft word fileor a text file -- and, oh, by the way, if you don't have a web site, for$250 a year I'll provide that for you, as well. This was signed by aguy in Bangalore, India. Now, I was very impressed when I read that because this guyhad figured out how to virtually export the talent in the country --graduates of the Indian Institute of Technology -- to do work and tobring in hard currency into India from outside. And so that notion ofbeing able to outfit a population with the ability to work not onlylocally, but elsewhere in the world through the net, is a very appealingone. I find it's taking hold in other places -- in Ireland, inScotland, in Costa Rica, in Israel, in South Africa, and in Russia,where there are programmers working for Sun Microsystems, exportingtheir results through the net. So I think the maybe -- it may be even alittle stronger than that. We'll have to see how this turns out. THE PRESIDENT: If I could just give you one example, becauseI think this may have also relevance for remote, physically remote areasin America -- Appalachia, the Native American reservations, things ofthis kind. We were talking before we came in here tonight -- I was out innorthern California the weekend before last. And I was talking with alot of people who work for E-Bay, and they were telling me that thereare now, in addition to the employees of E-Bay, over 20,000 people whomake a living on E-Bay, buying and selling and trading -- and that afair number of these people were actually people who once were onwelfare, who moved from welfare to work. That is, from -- andpresumably a lot of them work -- didn't have a lot of formal education.They had made this jump, and a market had been created for them, wherethey lived, that otherwise would be alien to their own experience. Theywouldn't have been able to go down to the bank and get a loan, and onand on and on. Now, last year we made -- and this year we will make, throughour aid programs in foreign countries -- over 2 million microenterpriseloans to poor people, to help them start their businesses in Africa, andLatin America, and Asia. If you could somehow marry the microenterpriseconcept to setting the infrastructure of the Internet out there, I dothink it's quite possible that you could skip a generation in economicdevelopment in a way that would reinforce rather than undermine theenvironment. DR. CERF: The operative word here is "infrastructure." Andyou do have to have a certain minimum amount of it in order to make thisstuff function reliably. And, of course, it has to be reliable, or youcan't make a living out of it. MS. LOVELL: Well, this is the perfect jump to Dr. VanessaGamble's question. She's from the Center for the Study of Race andEthnicity at the University of Wisconsin. And as someone who worked toright the wrongs of the original Tuskegee study, I know you have a veryspecial concern for access and for fairness. Q This is a follow-up question that goes into inequities.We've talked about some of the benefits of these technologies. And Ithink the question we have now is about the inequities and lack ofaccess not just around the world, but in our own country. And how do wemake sure that as we move forward, that all communities in this countryare involved in the debates, and also get the benefits of these newtechnologies -- that you've talked about the benefits, to make sureeveryone is included? MS. LOVELL: That's really for both of you. DR. CERF: Well, here we go -- two things. First of all, it'sbeen possible to make things like Internet accessible in places where ithasn't normally been available, or it's not affordable, by putting itinto public institutions, into publicly accessible kiosks and things ofthat kind -- in libraries, in schools. There's a major program, as youknow, that has been undertaken called NetDay, to try to wire various ofthe schools up and provide them with access to the system. We have to pay attention, just like Andrew Carnegie did 100years ago, to making these facilities accessible to everyone who wishesto take advantage of them. And I remind you again of the horse towater; not everyone is willing to take advantage of these things. Butwhere they will, we should make them accessible. The other good news is that the cost of doing these things isdropping very rapidly. Not only is the cost of the equipment dropping,but the cost of telecommunications as well. And so, as time goes on,these things will become more and more in the reach of everyone. That'sbeen true of most of the advances in technology that I can think of. Inmy own lifetime, color television -- which used to cost $1,000 in 1950-- is a lot less expensive now, in today's dollars, than it was in theequivalent dollars 10, 20 or 30 years ago. So that's a simplistic answer, and I'm not trying to arguethat that's all there is to it. But the fact is that the thrust of allthis is actually in our favor. The costs are coming down, and makingthings much more accessible than they would otherwise be. THE PRESIDENT: Did you say you expected the penetration ofthe Internet to equal that of the telephone by 2006? DR. CERF: It will exceed the penetration -- now, notnecessarily -- it will be the same size as the telephone system by 2006.But I believe Internet will actually penetrate more deeply than thetelephone or the television have. And the reason is those little tinychips that I showed you a picture of before, they will penetrate intoproducts that people just buy without thinking about them beingcomputers. They're simply devices that do things for you. THE PRESIDENT: I want t get to the genes, but I think weshould answer that question, too. This whole question of whether we'regoing to develop a digital divide in our country I think is a very, veryserious one. Our administration, especially the Vice President, when werewrote the Telecommunications Act, we fought very hard not only to getpeople to participate in NetDay to hook up every classroom and libraryto the Internet by the year 2000 -- I think we'll get there by the endof the year; functionally, we'll be just about there -- but also, to getthe Federal Communications Commission to adopt an E-rate which wouldsubsidize the cost to poor schools and poorer hospitals in poor areasand isolated rural areas, so that everyone could have access in theschools. Now, but the divide won't be bridged until the parents ofthose children have that in their home. So I think we ought to have asa goal at least to make access to computer technology and to theInternet as universal as telephone access is. And I think until weachieve that, there will be a digital divide, so we ought to try tohasten that day and promote whatever policies we can afford or we canachieve to hasten that day, because until we do, there will be a digitaldivide. DR. CERF: I agree with that. In fact, it's a goal, apersonal goal of mine, is to see, literally, Internet everywhere. THE PRESIDENT: Now, what about the gene? That goes topatenting and all that, doesn't it? DR. LANDER: Well, I think in a sense, the differentcommunities and how they're going to be affected by this and what accessthey really have is much less with respect to genetics as a question oftechnology or infrastructure or cost than it is a question ofunderstanding and education. I think, in fact, those whole genetictechnology can look exceedingly complicated. And in its detail for eachdisease, it is very complicated. You've really got to know. But there is a level of basic understanding about genetics andthe choices and a few examples that everyone ought to know, because youcan use them as reference points, as touchstones, for the other choicesto come ahead. And I think every community, every ethnic community,every state, all of the different types of communities we have in thiscountry ought to be having conversations about those basic fundamentalchoices, those basic fundamental examples, because as problems come up,we're going to need to refer back to them. In a sense, it's easier than your problem. I don't have towire up everything. In a sense, it's harder, because we have topenetrate people's understanding and their consciousness. We've got toget the different perspectives of different communities on the sorts ofchoices we're going to have. And different communities -- and I knowyour work, particularly with regard to examples in the African Americancommunity where, in fact, failing to pay attention to that really wasquite a mistake. We've got to get that conversation going. I think, infact, we can afford to do that, but it's going to take very active workto make sure we do do that. DR. CERF: You know, the good news is that we have shown inthe last 20 years that we can affect people's behavior, right? Look atsmoking. Look at eating habits. DR. LANDER: We should have done better on smoking. DR. CERF: The point is that -- I mean, you can't smoke in therestaurants anymore, right? I mean, you can't smoke on an airplane. Sowe've managed to get people to pay attention to things that areimportant, and it seems to me we can do the same in matters related togenetics. DR. LANDER: But we've got to understand how it is that -- wecan't just get them to pay attention; we've got to understand how it'sgoing to make a difference in their lives. We've got to listen, also.And it's that back and forth that we've really got to be doing. DR. CERF: Amen to that. MRS. CLINTON: You know, one of the issues that your question,though, raises, which is a larger one, is how this conversation thatwe're having tonight gets translated into decision-making at levels ofgovernment and within the private sector as well as the public. And itdoes strike me that there are some issues that have to be addressed now,even though we don't know the full implications of what's going tohappen later, And how we create a climate in which what happens to yourgenome is as important as what happens to your taxes -- (laughter) -- isa very challenging question. And the President said something that -- he used the word"patent" -- there's a big debate about who will own this information andhow will that information be used. Because in order to have the kind ofopenness of discussion that can lead to creating a climate that wouldinfluence decisions, there has to be a lot of give-and-take, and peoplehave to have some interest in creating awareness among the public andnot hoarding information. So what do you say to the question about, well, what's goingto happen to this genome information? Is it going to be the proprietaryinformation of certain companies that then will be able to basicallycontrol information about it and the use of it, or not? And, if that'san open question, what do people in positions like the President andothers sitting in this room have to begin doing to make sure that wekeep the climate open enough so that when decisions have to be madewe're able to do it? DR. LANDER: I think there are two answers to that. One, it'sunambiguously the case that information about the human genome has to befreely available to everyone in the world, to scientists, tonon-scientists. It has to be viewed as a public right to have thatinformation. Now, we can guarantee that right. The way we guarantee thatright is we, as a country, pay to get that information and put it in thepublic domain. That is, indeed, our policy now and we're doing it. Idon't for a moment say that companies also shouldn't be gathering thatinformation and doing good things with it because, in fact, they need todo that in order to deliver on the promise of cures and therapies. But the core information at the heart of the genome, thegenes, the variation, the circuitry ought to be out on the web for allto see -- for all these nine-year-olds who are going to be inventing newgenetic circuits. We can guarantee that. We do have a question about patents. Patents are a separatequestion, of course, than access to information. In essence, to get apatent, you do have to disclose your invention. So the second questionis, what's the state of patent policy and are there issues there? Well,yes, I think there are. It is important to say that there is a role forpatenting. If a pharmaceutical company wishes to develop a drug andinvest $100 million to do so, it sure wants to know that when it comesto market, its competitor can't free ride on the clinical trials theydid and bring the same drug to market. So we clearly need to be able toallow patents on some things to protect intellectual property andinvestment. But I do think we're creating a thicket of patents right now.We're giving out patents willy-nilly for very, very slight investments.And I think in the long run that's a big mistake. In the 1800s, whenyou wanted to get land in the Homestead Act you had to work it for awhile, you really had to do something important -- you couldn't justwalk the boundaries and go file a claim. What we have a situation right now is we have genericinvention. You can discover all sorts of things pretty easily bycomputer and our patent policy hasn't yet caught up with that. And Ithink we are giving patents away and -- sort of a social contract -- weincent inventors to invent by giving them monopolies. But then we, associety, ought to get a good deal for that, and so we want to be certainthat we set the bar high enough. And I think that's actually an important thing, if I can sayto people in a position to do something about it, to go back and look atour patent policy and ask whether this kind of generic discovery,generic invention really ought to meet the standard -- because I thinkit will create a set of boundaries and fences that are going to make ithard in the decades ahead for a pharmaceutical company that really wantsto put the hard work into finding a therapy and a cure to operate,because they're constantly going to be bouncing up against boundaries ofintellectual property. So I think it's not an absolute question. There's a role forintellectual property. But it is one of a degree and I, for one, thinkwe're a little bit off on that and it would bear some thinking. MS. LOVELL: I think, actually, Arthur Holden has a goodfollow-up question on that. He's the CEO of the newly formed SNIPconsortium. That is a group of 10 pharmaceutical companies that will beposting their research in the public domain, as the government is doing. Q Very much a complementary activity to the public activitiesthat are going on. Let me build on Francis's analogy of a base camp.We've essentially -- in completion of the sequence of the human genomewe've created a base camp. And with that, as we've alluded to in thedialogue, a whole series of potentially fairly important questions.What are the few critical questions you think as over the next few yearswe get this base camp established, how should we begin to move up thatmountain, number one. And, number two, the collaboration between thepublic and the private sector, which has been so critical inestablishing that base camp -- how do you see that changing? DR. LANDER: Two good questions. With regard to theinformation to come, the work to be done -- when we have that basicdescription of all the letters of the human genome there's a huge amountof work to be done. And I think it's going to look something like this.You've got to run through those letters and figure out where the genesare. That's not so trivial to do. We've got little bits, but no morethan you can figure out exactly where one program starts and stops ifyou don't know the computer language, can we figure out where the genesare. We have tricks for doing that and a lot of progress has beenmade, but we'll be using all sorts of things like sequencing otherorganisms. It turns out if you line up the human and the mousesequence, almost all the genes have been conserved. The mouse also has3 billion letters of genetic information and 100,000 genes. We are, infact, not that different from mice, if you think about it -- (laughter)-- in terms of body plan. We've got all the same organs that prettymuch has got to have the same instructions, and it does. When you lookat the genetic code our best way to find out how it functions is youline up the human sequence, the mouse sequence, and you look at whatbits match . And that's the stuff that matters. About 4 or 5 percent of your genetic code matters a greatdeal. Evolution has conserved it, and we can pick out the codingregions and the regulatory regions. And it's at the core of all geneticresearch today. I say this advisedly because, at the same time, Kansas thinksevolution is such a shaky theory we shouldn't even mention it in thecurriculum -- (laughter) -- and it's at the core of what we're doing totry to figure out how to understand how the genome works. Second off, we're going to take movies of how all the geneswork. These detectors I briefly showed of how the genes turn on and offand different cells and different diseases, they'll be classificationsof every tumor. There are already projects to do things like that.Classifications of what happens when a cell develops, when an organismdevelops. And all that data showing up on the web already -- people arewriting programs to figure out how it all interacts and pick up theregulatory regions. We're going to annotate those genes by the commonvariants in the population and all of that is public data that needs tobe out there. At the same time, take any one disease, and the work needed toproduce a therapy or a cure is monumental. It is going to requireprivate investment. It's going to require the possibility of profit onthat. And so I'm pleased to see things like this consortium that arepre-competitive efforts of industry to try to lay that commoninfrastructure, and the role for the private sector in this is to takeparticular targets and deliver on them in a way that, as a publiceffort, we can't possibly do. DR. CERF: Once we know, for example -- there is this littletransparent worm called synarabditis elegans (phonetic.) DR. LANDER: Bob Waterston, over there, was responsible inlarge part for the sequence of that organism. DR. CERF: Okay, so now -- thank you. Once we now have thesequence -- (laughter) -- now we have the sequence of this littlehalf-inch organism, and now is it possible for us to actually watch howthat sequence of genes gets interpreted so we can understand thecomplete development of that little worm? And if we know that, how doesthat help us with the bigger problem of understanding development in thehuman -- DR. LANDER: The answer in short is, yes, for the most part.we can know all the genes, we can figure out in what part of the bodythey're expressed. It takes work to do that. We can figure out underwhat circumstances they turn on and off. All of that gets us a kind ofa program for how the worm works. And that's the work of another twodecades ahead, but it's clear how that's going to happen. But how doesit help us? It helps us in a remarkable way. You see, the shock of genomics is this point about evolution.The same genes that lay out body plans in, for example, a fruit fly, orthe genes that lay out the body plan in the developing human embryo, infact, we look very different. but that same set of genes were inventedabout half a billion years ago, and they've been used and reused to dothe same thing. Now, if you want to understand birth defects, go do it in amanipulable system like fruit flies, or go look at the way thatdifferent pathways of signaling in the development of that clear wormyou referred to work, because there are pathways of signaling in thatworm that are the same as the pathways of signaling in human cancercells. DR. CERF: See, now this is starting to get really cool. Isit possible -- (laughter) -- DR. LANDER: We think so. This is good stuff. DR. CERF: Have I got enough computing power so I couldsimulate that whole thing? DR. LANDER: No. DR. CERF: No? You want to bet? (Laughter.) DR. LANDER: Okay, you've got a deal. DR. CERF: I've got a bet. Okay, we've got a bet. We'regoing to work on this one. (Laughter.) DR. LANDER: We'll get back to you on this one. (Laughter.) DR. CERF: I mean, that could really be something if we couldsimulate the whole thing. MRS. CLINTON: You mentioned one of the words that I think isin people's minds when they hope about what can come from this, andthat's cancer. And we have somebody with us who has committed his lifeand his career to understanding and working on issues like that, andthat's Harold Varmus, who is the outgoing head of NIH, and has been forthe last six years -- and I think, by unanimous agreement, has done asuperb job. And I wanted to ask Dr. Varmus -- you know, we've committedhuge resources to trying to find a cure for cancer, and there certainlyhas been progress that's been made. But what major gains lie in thenear future, and how will the Human Genome Project get us closer to acure? DR. VARMUS: I assume by "outgoing" you meant I'm leaving, asopposed to my social behavior. (Laughter.) THE PRESIDENT: You mean, as if an outgoing head of NIH werean oxymoron? (Laughter and applause.) DR. VARMUS: Let me take this back to the direction youintended to go. (Laughter.) Well, indeed, the genome project is going to affect ourapproach to many different kinds of diseases. But you've heard the wordcancer appear many times tonight. And let me explain why that is. Cancer is essentially a genetic disease. And by that I meannot that it's simply oftentimes inherited, but it's a disease thatresults from accumulation of genetic variation. Some of that variationmay be, in some cases, inherited. But much of it occurs during ourlives when -- during the natural division of cells, mistakes occur, orcells are exposed to environmental agents that cause genetic damage werefer to as mutations or variation, and it's an accumulation of thosechanges that results in the alterations of normal cell behavior tocancer cell behavior. The constellation of changes that occur in the different typesof cells give rise to lung cancer and pancreatic cancer and breastcancer and others, varies from organ to organ, and it may even varywithin one tumor type and another -- that is, within a single tumortype. Knowing which genes are affected, what the actual variations are,how those variations change the pattern of expression that Eric referredto that we can now visualize by putting all the genes on the chip andlooking at the patterns of expression, revolutionizing every aspect ofour approach to cancer. We're now in a position to evaluate individual susceptibilityto a number of cancers. Francis referred to one example, colon cancer,but many other examples exist in the skin, breast and elsewhere. Secondly, we have options for much better definition ofcancer. Cancer that may look the same -- two cancers that may look thesame to a pathologist may look very different to someone who manipulatesgenes and looks at the patterns of expression. We now know that makingthose kinds of assessments can actually predict the right kind oftherapy to use and predict the likelihood of a favorable or unfavorableoutcome. Finally, knowing which genes are affected is changing ourapproaches to designing preventive and therapeutic strategies. This issomething which is going to come to fruition over the next 20 or 30years, but already we're seeing harbingers of good news. There aretherapies for breast cancer, for example, which are based on ourknowledge of the few genes we already have in hand that we know to beimportant in cancer, knowing something about the kinds of proteins thosegenes make, what those proteins do, where they are positioned on cells.And it's this kind of tremendous bounty of information that's going tocome from the genome project when we know all genes and know about theirmutations and know about the behaviors of the proteins they make, which,in combination with the kind of information technology that is nowavailable, will create a new world in cancer. Now, this doesn't come without a cost. Some of the costs havebeen alluded to with respect to privacy and protection againstdiscrimination. The investment we've got to make as a nation and aworld to achieve these goals and very importantly, to refer to the issueof equity that was mentioned before, some of these things are going tocost a lot of money. We have to protect our citizens so that all arebeneficiaries of the research and the products of research the nationhas invested in it. MRS. CLINTON: Dr. Varmus, is it likely that we will find outthat every one of us is susceptible to something? DR. VARMUS: Absolutely. We're talking about risks and thereare relative risks. Eric mentioned a couple of diseases that we knoware almost inevitable given a certain variation in the genetic code.But the vast majority of diseases that you and I are heir to are goingto be contributed to by a large number of variations. Even the cancers that we now understand to be influenced byinherited mutations are likely of different frequencies in differentpeople, because of our environmental exposures and because of othergenes that we've inherited that modify the effects of those centralplayers. So this is very complicated stuff. And because we do have --I mean, Eric and I may look somewhat similar, but we probably have 3million differences between us. Some of those differences don't amountto a hill of beans, because they're differences that are in DNA thatdoesn't matter very much -- junk DNA. But some of those differences arequite important. And some of them are going to make him more likelythan me to have one set of diseases, and me another set. It's going to be a long time before we have enough informationto say what real risks accrue to each of us, but no doubt that -- thisgets back to the insurance problem. And I agree entirely with Eric,that we should think of insurance as a way of providing pooledprotection for the population, and not a system that is based on againing that allows individuals to seek the genetic information and thenprovide special protection for themselves based on that information. THE PRESIDENT: Before we go on, I just want to say -- we sortof glided over this -- this man has done a magnificent job at the NIHfor a long time, and I am very grateful. Thank you for that, for yourservice. (Applause.) MRS. CLINTON: I think we have time for one last question fromthe Internet, and this is from Kristin Janger (phonetic) from Vienna,Virginia. And the question is: What are some potential commercialapplications or products that may emerge from advances in informationtechnology and genetic research? DR. CHEF: Together? Together? Wow. Well, some obviousones, right? We've already touched on them. The ability to understandhow the genome works allows us to simulate a lot of the therapies thatwe otherwise would have to test in more primitive ways. And so, Eric, I would pose for discussion the possibility ofbeing able to analyze and design therapies based on enough computingpower to simulate what the effects would be. It's sort of like drychemistry in a way. Is that a reasonable thing to consider? DR. LANDER: Well, not only is it reasonable, it's happening.So when I gave you a hard time about being able to simulate the wholeorganism, well, that's a very complicated problem there, but there is atremendous amount of work already, trying to simulate little bits andpieces of it to understand when we're not dealing with genes that arecompletely broken, but ones that might be just twofold down-regulatedand we'd like to goose it up -- whether or not that would be a good ideaor a bad idea. Because there are all sorts of feedback loops. That'sthe thing about the body, it's a very complicated, homeostatic feedbackmechanism. So there's a lot of computer modeling going on already to tryto understand what are the sensitive points to intervene at. Does itmake any sense to make a drug against this step of a pathway, or willthe body, in fact, regulate to that? What are the points that arereally vulnerable and efficacious to intervention? We're going to needa lot of computer modeling because you get very surprising answers whenyou look at the whole system functioning together, rather thanindividual parts alone. DR. CERF: So, now, it's occasionally tempting to fall intothe trap of thinking of therapies that are genetic in nature. And I'mgoing to argue that, in fact, there's a much broader set ofopportunities here. This is all about understanding. It's all about depth ofknowledge about how the body works. If we understand that well enough,then we can intervene in various ways that may be rather mechanical.For example, someone who has diabetes, we can actually sense the sugarlevels in the blood. We can build little machines -- these alreadyexist. These are devices that measure what the current state of sugarintensity is, and delivers a dose of insulin as needed -- rather thanhaving to take a shot once or twice or three times a day. So there mustbe a bunch of things like that -- DR. LANDER: You said the key word. It's understanding. Thereason we have public investment, the reason why science has progressedso tremendously in the past decades is that we have common publicinvestment and understanding. The more we understand the process, themore we can then set it free to lots of creative forces in industry andacademia everywhere to fix it. The understanding, though, is a public good. It's a publicknowledge. And that's what we have to keep investing in. And I thinkthe one thing we can never slip into is thinking that because we'vereached this particular milestone, the human genome -- DR. CERF: That we're done. DR. LANDER: -- that we're done with understanding at all.There is a tremendous need for this continual reinvestment, by thepublic -- and I've got to say, the American people have been spectacularin investing, recognizing that this is one of our best publicinvestments. And we've got to keep that up. DR. CERF: Actually, this particular project is a wonderfulexample of the combining of informatics and genomics. The placement ofall of that genetic information in one database, where it's accessibleover the net, means that any researcher who finds a fragment ofinformation can go to that database and find out if anyone else knowsanything about that particular sequence. Is this a pattern that's beenseen before, and if so, where, and what does it mean? And that wouldn't have worked if we didn't have the ability tohold all that data in one place and process it. So now what we've gotis a rapidly increasing rate of discovery -- because every time someonecontributes something to that database, in a sense it interacts withevery other piece of information in the database, and allows us touncover the secrets much more quickly. MS. LOVELL: I think you just summed up the whole evening.And I'm going to give the President the last minute. THE PRESIDENT: Well, you know, that great humorist Ogden Nashonce said, progress may be all right, but it's really gone on too long.(Laughter.) And I was thinking that if he were here tonight, he wouldhave to revise his opinion. This has been an astonishing evening for me, and for Hillary,and I hope for all the American people and the people throughout theworld who have been a part of this. I want to thank you both. I want to just leave you with onethought: There are public responsibilities involved here, particularlyfor basic research. We have been very successful, and never moresuccessful, than under the leadership of Dr. Varmus, in getting strongbipartisan, non-partisan support for investments in health. And I thinkthat it's obvious that we can all see that as in our self-interest andas in the public interest. We want to live forever, and we're getting there. But I thinkit's quite important also not to forget our responsibilities for basicresearch in other areas as well. And one of the things that we willcome to know as the intersection of your two disciplines, informaticsand genomics, come together, then we will have to study even moreclosely how all this that we know about the human body and itsdevelopment interacts with changes in the environment. So other areas of research will be also important, into thingslike global warming and climate change and the sustainability of theenvironment. And what I hope we can do is to build a broader consensus,as we look into the new millennium, for the whole research enterprise inthose areas where it will never be productive in the beginning, orprofitable for people like you, to do the beginning. And then we canfind these things, and then the American entrepreneurial genius willtake off. And so I leave here with a renewed commitment to trying tohelp people like you get started. We may not understand it, those of usin politics, but we have an obligation to help you find it. And when the first mouse graduates from Princeton, I willinvite you both to deliver the commencement address. (Laughter.) Thank you and good evening. (Applause.) END 9:40 P.M. EDT