00:01:56 How a society decides to draw the line between the safety of new drugs and other products

00:01:59 has always been a highly contentious issue.

00:02:03 This issue has been highlighted in recent years by the debate over the testing process for new drugs to combat AIDS, for instance.

00:02:10 You've seen how recombinant DNA technology can be used to produce large amounts of otherwise unobtainable proteins

00:02:16 that can be used as drugs or new crop plants for agricultural use and other applications as well.

00:02:22 Should these innovations be subjected to more detailed tests than those produced with traditional technology?

00:02:29 Or will this slow down the availability of new opportunities?

00:02:33 Our next speaker is admirably suited to address these difficult questions.

00:02:37 Don Kennedy headed the Food and Drug Administration under President Carter

00:02:40 and has been hailed as one of the most effective leaders ever in that post.

00:02:44 He was president of Stanford University for 12 years and is a practicing biologist with wide-ranging interests

00:02:49 including studies of the nervous system, behavior, and the environment.

00:02:52 We're especially grateful for Don agreeing to miss the Stanford football game this afternoon and be with us.

00:03:07 Well, the rather dramatic title that we've supplied for this talk

00:03:14 summarizes a question a lot of people have wrestled with over the 17-year history of this remarkable technology.

00:03:22 Wrestled with it because not only do we have at hand a fascinating new science,

00:03:28 we have at hand an equally fascinating set of challenges to public policy.

00:03:34 How do we regulate such new technologies?

00:03:37 How do we try to balance the costs and the benefits that they will bring us?

00:03:42 I think the regulation of recombinant DNA is perhaps the ideal case study in science and public policy and for several reasons.

00:03:53 First, it offers, as you have heard for the past couple of days, an unparalleled sweep of new opportunity.

00:04:00 Those who are practicing the technology, let alone the investors, see exciting prospects of new medications,

00:04:08 new agricultural crops, new means even of remediating environmental problems.

00:04:13 It is, in short, the source of stupendous possibilities.

00:04:17 But second, each opportunity affords an array of potential problems, unwanted side effects,

00:04:23 unanticipated social costs, unforeseen public health, and environmental risks.

00:04:30 But these, not in themselves unusual because they often accompany newly introduced technology,

00:04:38 are compounded by a very special kind of drama, the specter of genetic monsters running amok.

00:04:46 And some feel, furthermore, that in undertaking this kind of work we have begun to interfere in a process so fundamental in nature

00:04:56 that we may be guilty of the sin of hubris.

00:05:00 And that reservation, so deep that at times in the history of this business it has seemed almost theological,

00:05:07 has been of profound significance in the politics of recombinant DNA regulation.

00:05:14 And third, this is one of the very few instances in which scientists themselves, the very developers of the technology,

00:05:21 were the first to recognize its potential risks and to call public attention to the need for evaluating them.

00:05:28 Perhaps partly as a result, scientists were given more than the usual amount of responsibility

00:05:34 for the early development of regulation in this area.

00:05:38 In the view of some, that's made the process more sensible, more appropriately suited to the nature of the risk.

00:05:44 And in the view of others, it has removed critical issues from public scrutiny and thereby reduced accountability.

00:05:52 So there's lots to argue about.

00:05:54 It's a fascinating exercise, and partly because it illuminates a special part of the American character.

00:06:02 On the one hand, we're a creative people bursting with entrepreneurial zeal, fearless about risk.

00:06:09 On the other, we're full of suspicion and concern about what others may do to us,

00:06:14 including perhaps especially what our government may do to us.

00:06:18 On the one hand, we believe that our leaders owe us a measure of protection against hazards.

00:06:24 But on the other, we deeply resent any intrusions on personal freedom,

00:06:29 even when those intrusions confer exactly that kind of protection.

00:06:35 Well, onward.

00:06:37 You've already heard more than I am able to tell you about the early history of the awareness of the prospect of regulating recombinant DNA technology.

00:06:49 I'll just point out that my Stanford colleague, Paul Berg,

00:06:52 had recognized the hazards of working with animal viruses like SV40 well before the issue of recombinant DNA technology itself came to the fore,

00:07:03 had organized a conference to deal with those.

00:07:06 So there was a precedent when Paul and other colleagues assembled a group of scientists first to co-sign a moratorium letter that temporarily halted their research

00:07:18 and was published in Science Magazine and then the now-famous Asilomar Conference

00:07:23 at which the issue of recombinant DNA regulation was first considered in 1975.

00:07:31 That meeting and the cloud of controversy that developed around it and lingered long afterward set the tone for much of what followed.

00:07:39 I have to remind you what the times were like.

00:07:43 Rock and roll was not a lot more than a decade old.

00:07:47 The last wisps of tear gas had barely faded from Bay Area campuses.

00:07:53 Much attention was still even being given to the democratization of science,

00:07:59 and there were still straight-faced proposals that research laboratories be converted into cadres in which everyone voted on the design of experiments.

00:08:09 Those who think that political correctness dominates campuses today either never knew or do not remember what it was like when the new left was still fairly new.

00:08:21 In that climate, the assembly at Asilomar tried to accomplish something truly ambitious.

00:08:27 Scientists engaged in a new and exciting area of research in which the biological nature of organisms could be manipulated in novel and much more directed ways

00:08:38 had sensed a difficulty and called a halt in their work.

00:08:42 The recommendations they formulated in full public view at Asilomar were regarded by many as a landmark of social responsibility in science.

00:08:53 But not everyone was happy, and how could they have been in times like those?

00:08:59 The assaults came quickly from the scientific right.

00:09:02 The argument was that the new technology presented no problems at all and that even to talk about regulating it might put notions of control into the wrong heads.

00:09:11 Let's not tell Junior not to stuff beans up his nose.

00:09:16 And from the left, from Science for the People and other organizations, the argument was that the entire premise of Asilomar was wrong,

00:09:25 that scientists had no right to assume the task of self-regulation that belonged to the public at large.

00:09:33 In the immediate aftermath of the conference, the scientists who conceived it and carried it out received praise from most quarters

00:09:43 as befitted a self-sacrificing initiative in the public interest.

00:09:47 But as time wore on, they were made acquainted with a lesson that many have learned in other contexts.

00:09:55 Those who start a revolution seldom stay to direct the new state.

00:10:00 Indeed, they are soon overtaken by the very events they start, as Gorbachev and soon perhaps Yeltsin can testify.

00:10:09 And in just the same way, those who raise difficult questions about control can expect to lose some of it in the longer run.

00:10:17 Some of the pioneers in this initiative may have expected that.

00:10:21 Others may have hoped that by raising questions themselves they could actually guarantee continued control,

00:10:28 much as some advocates of voluntary professional accreditation hoped to avoid the sterner grip of state oversight.

00:10:37 Whatever the motivation, the scientists launched something that soon eclipsed their capacity to manage it.

00:10:44 Well, what were the arguments and beliefs being brought at that time, marshaled at that time, in support of the idea of research regulation?

00:10:54 The first was surely a fear of the unknown, a concern that public health hazards of unanticipated severity

00:11:02 could result from new genetic combinations produced in this way.

00:11:07 This specter of bacterial monsters, the bug that ate Cambridge,

00:11:12 even spawned a number of local regulatory initiatives in academic communities around the country.

00:11:19 That concern has tended to disappear over time, at least with respect to the standard microbial work,

00:11:26 as various recombinant strains have been handled safely over the years.

00:11:31 But from the beginning, as I mentioned earlier, there were other less explicitly stated but often deeper worries,

00:11:37 and some of them are still with us and are still reflected in the controversy.

00:11:42 One's political, the view that certain experiments are bad science and should not be done,

00:11:47 or if done, only done under the supervision by non-scientists with the proper views.

00:11:55 Another is more theological than political.

00:11:58 It says that evolution is a process so delicate and so important that it should not be tinkered with in any way.

00:12:05 Some very distinguished biologists expressed that view early on,

00:12:10 though without explaining why and whether hybrid corn is okay.

00:12:17 Well, after Asilomar, something very like a popular rebellion grew up from a fusion of these elements that I've just mentioned.

00:12:26 The energy of that counter-reformation, I think, was added to considerably by some of the original scientists,

00:12:35 who, having blown the whistle, swallowed it later and said there wasn't a problem after all.

00:12:40 They were probably right, but that reversal didn't do much to buttress public reassurance about the stability of expert opinion.

00:12:50 I remember my own most colorful experience with that occurred at a National Academy of Sciences forum in early 1977 in Washington,

00:13:01 when a very staid and stuffy gathering was suddenly punctuated by the arrival of a noisy group called the People's Business Commission,

00:13:10 led by Jeremy Rifkin, a very colorful figure at the time.

00:13:15 I was on the stage. I thought I was in the middle of a sit-in for some time,

00:13:20 and I remember very well that they carried signs saying,

00:13:23 Don't Xerox Life, the theological theme, important then, somewhat important still.

00:13:33 Well, at exactly this time, the government was trying to figure out how to regulate this new technology, particularly research on it.

00:13:42 Most of the scientists had been supported by the National Institutes of Health,

00:13:46 and its director at the time, Donald Fredrickson, was given charge of an interagency committee on recombinant DNA,

00:13:54 on which I represented the Office of Science and Technology Policy in the White House because I was on loan to them half-time.

00:14:04 Its task, the task of the committee, was to work out the appropriate mode and jurisdiction for recombinant DNA research,

00:14:12 and although the exercise was pretty good by the normal standards of government deliberation among agencies,

00:14:20 it did resemble a feeding frenzy for turf at times.

00:14:24 There were 25 federal agencies. Some of them supported research.

00:14:28 Some of them, like the State Department, were just interested.

00:14:32 Others were regulatory agencies, and they showed a considerable appetite for doing what they were put on Earth to do.

00:14:41 Regulatory agencies regularly obey the two-year-old-with-a-hammer rule.

00:14:45 If you give a two-year-old a hammer, it is amazing how much stuff needs hammering.

00:14:50 And the regulatory agencies thirsted for this new array of nails,

00:14:59 and the Environmental Protection Agency in particular laid sweeping claims to regulatory oversight.

00:15:08 But in fact, it turned out that none of the statutes that existed, not the OSHA statute, not EPAs, not any of EPAs,

00:15:16 not the Toxic Substances Control Act, not the Public Health Service Act, provided adequate statutory authority.

00:15:24 So it was decided in the end that legislation was needed, and then the prospects really began to scare everybody.

00:15:34 The legislative course was confusing, to make it shorter than it really was.

00:15:40 The Senate Health Subcommittee, under Senator Kennedy's chairmanship,

00:15:44 drafted proposals in which a public commission would share responsibility with the Secretary of Health, Education, and Welfare, as it was then.

00:15:53 A corresponding version in the House was a plain vanilla version without the public commission.

00:16:03 As these competing visions of regulation wound their way through the legislative process of hearings and so forth,

00:16:12 meantime, concern was ebbing because research with the disabled strains of bacteria was lowering the estimates of risk,

00:16:21 and the scientific community got more and more concerned about the appetite for new legislation,

00:16:27 particularly since the subcommittee staff of the Senate subcommittee substantially rewrote the original administration bill

00:16:35 and made it much more difficult and disadvantageous from the viewpoint of the scientists.

00:16:40 Well, eventually, the legislative push simply lost its momentum,

00:16:45 and the Secretary of HEW was encouraged to use all existing statutory authorities

00:16:51 and to create the Recombinant Advisory Committee and to just go ahead and get the job done,

00:16:58 and that is exactly what happened.

00:17:01 In the end, the perception of public health risk and its gradual ebbing was the decisive political factor.

00:17:10 The other major concern, referred to by one distinguished biologist as the manipulation and deformation of nature,

00:17:18 did not eventually figure significantly in the political struggle,

00:17:23 so the NIH guidelines were left in place, and what we had at the end of the process was what Roger Noll called at the 1977 Academy Forum

00:17:34 professional self-regulation.

00:17:36 That is exactly the place in which it wound up, and I think the test of time applied reasonably says that it has worked reasonably well.

00:17:46 But now we take a great leap forward in time and also change the focus.

00:17:52 I think intervening events have done little to change the view I just expressed about research regulation,

00:18:00 but now the focus shifts and comes to the application end of the new technology, not the research and development end.

00:18:11 And here, a similar exercise in trying to coordinate federal regulatory authority got absolutely nowhere.

00:18:21 Under the Federal Coordinating Council for Science, Engineering, and Technology, an arm of the Office of Science and Technology Policy,

00:18:30 there was an effort to create a biotechnology science coordinating committee,

00:18:36 which mandated something called the coordinating framework, and then stopped agreeing and started fighting.

00:18:45 And in the end, there was never a major jurisdictional problem resolved.

00:18:51 Important bases were left untouched, and perhaps most important,

00:18:55 agencies were left free to claim their own regulatory turf, and there is no present coordination,

00:19:03 a matter that is a cause for some concern.

00:19:07 Well, why is this all exciting?

00:19:11 It's exciting for the reason that Dr. Vici and before him, Dr. Fink, have described to you.

00:19:18 It's exciting because of transgenic plants.

00:19:23 And you've heard a lot about the underlying science, and I won't even describe it to you again,

00:19:29 although there are some wonderfully ingenious things happening,

00:19:34 bombarding plant cells with tiny metal particles coated with DNA and getting them to change.

00:19:42 It's quite extraordinary to one who left active biology 15 years ago, I can tell you.

00:19:49 And now there's an extraordinary capacity to produce beneficial alterations in the agricultural economy,

00:19:59 not just of the United States but the world, but it has encountered significant obstacles.

00:20:06 The first obstacles came up when it was necessary to take the work out of the laboratory and start field trials.

00:20:18 In the first instance, this came not with transgenic plants,

00:20:22 but when recombinant DNA technologies were used to move useful genes from one kind of bacterium to another.

00:20:31 You've already heard about BT, the insecticidal protein from Bacillus thuringiensis.

00:20:38 Bear in mind, Bacillus thuringiensis, the bacterium,

00:20:42 has been used in absolutely unregulated or almost unregulated fashion by farmers for years.

00:20:50 They mix up vats of it in the barn and spray it on.

00:20:57 It is sprayed by air frequently.

00:21:00 It is a microbial insecticide that is of proven effectiveness.

00:21:06 The idea was now to get it into a soil bacterium where it could live right near the roots of some valuable crop plant

00:21:16 and then confer protection against these pest insects more directly.

00:21:23 So Monsanto incorporated the BT gene into a soil bacterium called Pseudomonas fluorescens

00:21:32 and laid plans for a field trial in St. Charles County near St. Louis.

00:21:37 Now, EPA, under the Insecticide, Rodenticide, and Fungicide Act, regulates that kind of work,

00:21:45 and EPA had to approve an experimental use permit.

00:21:52 Monsanto applied, and EPA sent it to a subgroup of their scientific advisory panel,

00:22:00 and the advisory panel recommended a few changes but said that then it could go ahead.

00:22:06 But that was not the only hurdle.

00:22:10 In the meantime, Jeremy Rifkin, who we have met before, now in coat and tie,

00:22:16 filed objections to the permit application with EPA,

00:22:20 and he also wrote to the commissioners of St. Charles County seeking their intervention in disallowing the tests in their county.

00:22:28 So there was a substantial struggle, both at the level of the county commission and at the level of EPA,

00:22:35 which they lost because the EPA administrator declined to take the advice of the advisory panel

00:22:43 and, in fact, did not approve the field trial.

00:22:49 Everybody learned something from that.

00:22:51 Now, once transgenic plants came along, there was an enormous effort at public education.

00:22:58 In the meantime, a National Academy of Sciences report on field testing of genetically modified organisms was published in 1989.

00:23:07 It concluded that, and I quote directly here,

00:23:11 crops modified by molecular and cellular methods should pose risks no different from those modified by classical genetic methods for similar traits.

00:23:20 That seems to me to be a reasonable conclusion for the field trial part of this problem,

00:23:28 but there's a more straightforward worry, and now we turn to it.

00:23:34 Please remember that we are talking about food when we're talking about transgenic plants.

00:23:40 Once the field trials are over, presuming that they're a scientific success, we have a new crop.

00:23:47 Of course, it has to be a tomato.

00:23:49 Why everybody only works on tomatoes?

00:23:52 Roger has to explain this to me, but anyway, what we got is a tomato, and now somebody has to be persuaded to eat it.

00:24:00 And that brings into play a whole new domain of regulatory authority over which my old agency, the FDA, presides.

00:24:09 Let me give you one quick piece of background about FDA's regulatory authority.

00:24:17 In the mid-1930s, when it was formulating what are the modern food safety laws, it faced an interesting dilemma.

00:24:24 Food producers were beginning to do interesting things with chemistry.

00:24:29 They could add stuff to processed food to make it last longer or look prettier.

00:24:36 There was some reason to believe that the reckless pursuit of those economic objectives might produce some adverse externalities for consumers.

00:24:43 On the other hand, the woods were full of natural contaminants, bad stuff that got into plants while they were growing

00:24:49 or into fish while they were swimming around before they were caught.

00:24:53 And Congress was fond, even fonder than it is now, of the yeoman American farmer

00:24:58 and was understandably reluctant to make life difficult for him over something he couldn't help.

00:25:03 So Congress made a judgment that I think is fundamentally right and fair,

00:25:08 though it now sometimes makes government and its laws look foolish.

00:25:12 The decision was that when food processors add something to food, they have to prove it's safe.

00:25:18 They have the prior burden of proof of safety.

00:25:21 And when a natural contaminant is present, the burden is on the government to prove that that food isn't safe.

00:25:28 So a substance that's deliberately added, even if it's something that just migrates out of packaging into the food,

00:25:34 is a food additive, must be approved by a food additive petition unless it's been out there forever,

00:25:41 in which case it is so-called generally recognized as safe until evidence is produced that says it isn't.

00:25:51 Well, the problem must be obvious to you.

00:25:54 It is that there are some natural contaminants that are more dangerous than things we add,

00:26:00 and that produces a public perception of inconsistency in the way the government is treating risks.

00:26:09 Now comes the challenge of genetically engineered crop plants.

00:26:13 Now, to be sure, the problems aren't new.

00:26:17 Traditional plant breeding has given us very analogous ones in the past,

00:26:21 but the new techniques do make possible the transfer of genes over much wider taxonomic distances than before,

00:26:28 and that prospect worries people.

00:26:31 The National Wildlife Federation speaks of, and I quote,

00:26:34 an open invitation to put any gene, human or chicken or bacteria, into our food

00:26:40 and features a cartoon of fresh produce with the questioning label fish gene above a stack of tomato sauce cans.

00:26:48 What else?

00:26:49 Well, should FDA regulate genetically engineered food?

00:26:55 Obviously, if genetic engineering produces a new additive in the food,

00:27:01 why shouldn't it be treated like a deliberately added substance that's part of food processing?

00:27:08 On the other hand, there are serious worries about that,

00:27:12 and they're quite beautifully summarized, I think, in this cartoon.

00:27:16 Look, the little shop of horrors over there has come to life under the benign auspices of this mad scientist,

00:27:27 and FDA was urged by many to worry about those crop plants.

00:27:35 In fact, it adopted a very reluctant policy, published a Federal Register notice earlier this year,

00:27:44 that said, here are some ways in which you can decide whether this might be harmful,

00:27:49 follow our decision tree, keep us informed, but we're not going to require even labeling,

00:27:56 and we're not going to require a novel regime of food safety testing.

00:28:03 So they decided against a ham-handed grasp for regulatory authority, and there the matter rests.

00:28:10 My own view is that FDA probably will be forced to extend its reach somewhat, at least to labeling.

00:28:17 But the challenge will be to do that without restricting our opportunity to reduce the dependence of our agriculture on energy and applied chemicals.

00:28:26 As always with these challenges that new science throws at old policies that last chapter has yet to be written,

00:28:34 I hope I've persuaded you that this particular challenge is complex, tricky, difficult,

00:28:40 that solving it will require much more than straightforward risk assessment or cost-benefit analysis,

00:28:46 and certainly more than simple-minded rhetorical admonitions that it's not nice to fool with Mother Nature.

00:28:54 I hope you now think regulation is a tough and tricky proposition. I certainly do.

00:29:00 But imagine how much tougher and trickier it would be if the technology had really proliferated beyond the capacity of regulatory authority to coop it up.

00:29:10 And I want to point out that that may already have happened.

00:29:14 Now, this is an actual ad from a supermarket tabloid.

00:29:20 I wish I could tell you more about it, but I haven't got my own kit yet.

00:29:25 When I produce the first hamster with antlers, you will be the first to know.

00:29:30 Thank you very much.

00:29:41 Thank you, Don.

00:29:43 Marilyn, some questions?

00:29:45 First of all, Dr. Kennedy, you just ended, all but ended your presentation with a sort of tantalizing prediction, I think,

00:29:52 that your own view is that FDA will have to eventually extend its regulatory reach on these matters that it has sort of delicately sidestepped so far.

00:30:02 Could you elaborate on that a little bit?

00:30:04 Well, it's an entirely off-the-wall prediction based on absolutely no inside knowledge,

00:30:11 but on a kind of political reading of the tea leaves.

00:30:15 I think that the argument for labeling is going to prove difficult to resist.

00:30:21 I'm not prepared to predict that the reach will extend any farther than labeling,

00:30:26 but I think it's going to be difficult to resist the argument that labeling would be required.

00:30:32 If I could follow that up, why do you think the argument for labeling will turn out to be so persuasive?

00:30:39 I have experienced several arguments about labeling,

00:30:44 and I guess I think they tend to be quite politically persuasive because the cost appears to be low.

00:30:52 It isn't always, but it appears to be low, and the benefits always look substantial.

00:31:00 There's the concern that some people have that they just want to know if they're fish genes in their tomatoes because they don't like the idea,

00:31:10 but I've also heard a possibility raised that there could be potential real hazards.

00:31:14 For example, if a person has a food allergy, there are some very serious food allergies,

00:31:19 and food allergies are generally to a protein in the food that one is allergic to,

00:31:24 and if that protein is what is transferred, say you happen to be allergic to the fish protein that gets transferred to the tomato,

00:31:31 this could be a hazard that you're completely unaware of.

00:31:34 Have you heard these arguments, and how much validity or real concern do you think they represent?

00:31:40 I think they are the best arguments on the labeling side of the question.

00:31:43 In a way, the only argument against it is that food labeling requirements now do permit,

00:31:49 under certain conditions, potential allergens to go unlabeled,

00:31:54 and so it's a larger repair job than it would seem on the surface,

00:31:59 but that's the only counterargument I've heard except for cost.

00:32:10 I have another follow-up question just to bring the discussion back around to embrace human therapeutics as well as plant science.

00:32:19 I'm wondering whether you think that gene splice therapeutic products

00:32:24 should be held to any sort of different standard of efficacy,

00:32:28 given that cytokines and proteins, hormones, often work in a subtle cascade in the body

00:32:35 in which clinical signs of improvement might be differently manifested.

00:32:42 Should there be a different yardstick?

00:32:46 I don't think that there should be a different yardstick.

00:32:50 I'm persuaded on the basis of what I know,

00:32:53 and I want to say again how reluctant I am to tread into FDA policy domains after now 13 years of absence.

00:33:05 There may have been a lot of things that have happened that would change this view if I were closely connected to them,

00:33:13 but my view is that a new drug is a new drug

00:33:18 and that the provisions that now attach to new drug applications are adequate to detect

00:33:29 or to prevent novelties of the kind that you're talking about.

00:33:33 In other words, I don't think that there's anything that can be gotten in this way that couldn't be gotten

00:33:39 and hasn't already been gotten more laboriously perhaps by other means.

00:33:57 Human beings show a wide range of physical and other features.

00:34:01 None of you, I hope, for instance, would bet on me in a one-on-one basketball game

00:34:05 against Michael Jordan or against Jim Watson for that matter.

00:34:10 Even within a family, individuals have different faces and personalities.

00:34:14 This diversity occurs mostly because the sequence of DNA in our chromosomes is slightly different from person to person.

00:34:19 We've heard about this earlier in the symposium.

00:34:22 Recent advances in DNA technology make it possible to measure at least enough of these DNA differences

00:34:27 so that unique DNA fingerprints can be established from even a single cell,

00:34:32 without identifying the cells as coming from a particular person.

00:34:35 Our next speaker, Eric Lander, will tell us about some of the fascinating applications of this technology

00:34:41 in criminal and civil cases and will give a dramatic example of how it was used

00:34:45 to reunite children and grandparents separated by political violence.

00:34:49 Eric is an unusual biologist.

00:34:51 He was initially trained as a mathematician and has even taught mathematics and statistics

00:34:55 at Harvard University Business School.

00:34:58 The field of genetics was lucky enough to have piqued his interest a few years ago

00:35:01 and since that time he's been a major player in genetic research,

00:35:04 the Human Genome Project, and multi-genic diseases that you heard about earlier.

00:35:08 Eric is currently a professor in the Department of Biology at MIT

00:35:11 and the director of the MIT Center for Genome Research.

00:35:15 Eric.

00:35:22 Well, thanks very much, Rick.

00:35:24 As Rick said, I'm really a human geneticist

00:35:27 and I work on DNA applications to medical problems,

00:35:31 but what Rick and Harold Varmus asked me to talk about today is a non-medical use.

00:35:37 It's the use of DNA in identification,

00:35:40 and I think it does a marvelous job of illustrating the unexpected consequences

00:35:45 of discoveries in basic science.

00:35:47 Rick's already alluded to the tremendous diversity amongst human beings.

00:35:52 My favorite slide to illustrate that is this.

00:35:57 What a spectacular illustration of the marvelous range of human diversity

00:36:02 in height, in weight, in skin color, in faces.

00:36:06 It's what makes life wonderful, what makes the human species so wonderful.

00:36:11 And it makes us wonder what underlies this tremendous diversity in physical appearance.

00:36:16 We know, in fact, that in large measure,

00:36:19 physical appearance is genetically determined

00:36:22 or genetically influenced in strong measure.

00:36:24 We know this by looking at identical twins.

00:36:27 When you look at identical twins, it's not hard to see striking similarity between them.

00:36:31 You do indeed see difference, but the similarity is really much more striking.

00:36:36 And that tells us that identical DNA tends to produce identical physical appearance, at least.

00:36:42 Now, when it became possible to read DNA sequences directly,

00:36:46 it was natural to wonder how this diversity would be reflected

00:36:50 at the level of DNA spelling, DNA sequence itself.

00:36:53 And, in fact, when it was possible to read,

00:36:56 one found such things as single base changes,

00:37:00 a C here on this chromosome and a T here on that chromosome,

00:37:04 indicating that there were some spelling differences.

00:37:07 Now, in what I really do, which is applications of DNA to medicine,

00:37:11 these are the stuff we work with,

00:37:13 because these spelling differences are what we use to trace the inheritance

00:37:17 of either the black or the striped chromosome in a family

00:37:20 and see if it correlates with a disease.

00:37:22 But, in fact, I'll talk to you about a different use of all those spelling differences.

00:37:27 How much spelling difference is there?

00:37:29 Well, there is almost complete identity between any two human beings.

00:37:37 Look at the neighbor to your left and to your right.

00:37:39 You're 99.9% identical.

00:37:43 That should make you feel very common and part of a common species.

00:37:48 But, of course, in a genome of 3 billion letters,

00:37:52 even a tenth of a percent difference translates into 3 million separate spelling differences.

00:37:58 And so, again, I invite you to look to the left and look to the right

00:38:01 and notice how unique you are.

00:38:03 There is no one in this audience who has the same DNA sequence as anyone else.

00:38:07 And, indeed, your DNA sequence is unique amongst all DNA sequences

00:38:12 of any human that has ever lived and will live for quite some time to come,

00:38:17 unless you have an identical twin,

00:38:19 in which case you do have someone who has the same DNA sequence.

00:38:22 But, apart from that, your DNA sequence is yours and yours alone.

00:38:25 Should you choose to leave your DNA sequence behind here

00:38:28 in some form in some biological tissue,

00:38:30 in principle I ought to be able to look at it

00:38:33 and by its uniqueness know whose it was.

00:38:36 Thus is born the notion of DNA identification.

00:38:40 And it was quickly realized that this DNA identification

00:38:43 would be especially useful in legal cases, in the criminal courts.

00:38:48 Of course, law enforcement officials have, over the course of many years,

00:38:52 looked for things that uniquely identify individuals

00:38:56 so as to find evidence that links a criminal to the scene of a crime.

00:39:00 It is, in fact, this year, 1992,

00:39:03 the 100th anniversary of the use of fingerprints as an identifying tool,

00:39:09 begun in 1892.

00:39:11 They're extraordinarily powerful.

00:39:13 They are essentially felt to be unique,

00:39:15 and they're now computer databases of fingerprints

00:39:17 that are online across the country and are used.

00:39:19 They're great, except that for many crimes, no fingerprints are left behind.

00:39:23 A very common example, and an important example, is rape.

00:39:27 Property crimes, you may find fingerprints,

00:39:30 but for many violent crimes, it's harder sometimes to find fingerprints.

00:39:33 So scientists have looked for other markers, biological markers,

00:39:36 for example, things you might find in a semen sample from a rape,

00:39:39 to look for other signs of diversity.

00:39:42 And there has been success over the century

00:39:44 looking for protein differences, cell surface differences,

00:39:47 things like the HLA complex in blood groups.

00:39:50 But, in fact, the variation is nowhere near as spectacular

00:39:53 as in fingerprints of this sort.

00:39:55 That is, until it was possible to read DNA.

00:39:58 DNA gives as rich and as detailed a fingerprint in principle.

00:40:03 You might think that what we ought to do

00:40:06 is take a sample and just read out its DNA text in its entirety.

00:40:10 Now, this is one-sixth millionth of the human DNA text here.

00:40:15 It would be a wonderful thing if we could get that from a sample,

00:40:19 but that is the business of the Human Genome Project,

00:40:21 not the business of the local constabulary yet.

00:40:24 And so, in fact, when we do DNA comparisons,

00:40:28 we can't read all three billion letters.

00:40:31 What is done instead is a very small handful

00:40:34 of sites of variation are examined.

00:40:36 A site of variation here on this chromosome perhaps,

00:40:39 or one here, or one here, or one here.

00:40:41 And one picks enough sites of variation

00:40:43 to be able to pick up enough markers of difference.

00:40:46 We actually, at least in the forensic applications commonly done today,

00:40:51 people don't actually read out the sequence.

00:40:53 They, for economic reasons,

00:40:55 for being able to do this more quickly and more cheaply,

00:40:57 look instead at regions that have spelling differences

00:41:02 that are due to repetitions of some sequence.

00:41:05 There are repeat sequences all over the genome.

00:41:07 And in any particular region,

00:41:09 let's pretend this is on chromosome number one,

00:41:11 you might have three copies.

00:41:13 I might have four copies.

00:41:14 Someone else, five copies.

00:41:15 Someone else, one copy.

00:41:17 Typically an unimportant repeat that has no biological function,

00:41:20 but we all might differ.

00:41:21 And by taking that DNA

00:41:23 and the process of cutting it with an enzyme

00:41:25 that recognized a distinctive site here,

00:41:27 running it out by electrophoresis

00:41:30 to be able to separate these fragments by size,

00:41:32 and probing it with a piece of radioactive DNA from this region,

00:41:36 one can visualize bands corresponding to the lengths of these fragments.

00:41:40 And thus each of these different chromosomal configurations,

00:41:43 each of these different spellings,

00:41:45 due to different numbers of repeats,

00:41:47 can be visualized as different size bands on a ladder,

00:41:50 much like a barcode.

00:41:52 And so a forensic scientist examining an evidence sample E here

00:41:57 might do that operation

00:41:59 and probe it first with probe number one

00:42:01 for the first site of variation and see the pattern,

00:42:03 probe it for the next site, the next site, and the next site,

00:42:06 and compare it to the DNA patterns taken from two suspects,

00:42:09 suspect number one and suspect number two.

00:42:13 I hope even in the back it's very clear

00:42:15 that suspect number one has a different DNA pattern than the evidence.

00:42:19 And so suspect number one is completely excluded from having committed,

00:42:23 well, no, from having left this evidence.

00:42:26 It's another question how the evidence relates to the crime.

00:42:28 But that evidence sample of DNA cannot possibly suspect one's.

00:42:31 Suspect two, however, corresponds and corresponds perfectly

00:42:35 at each of the four places of variation on the human chromosomes examined.

00:42:39 Does this mean that suspect two is indeed the person who left that evidence sample?

00:42:45 What does it mean to say suspect two is included amongst those who could have left it?

00:42:49 Well, of course, to know how strongly we should take this evidence,

00:42:53 we need to know how rare that pattern would be.

00:42:55 It is a question of population genetics.

00:42:57 And for that purpose, databases have been assembled

00:43:00 of how frequent these patterns are in the population.

00:43:03 These are tricky questions. We'll return to them very briefly.

00:43:06 But those are basically the simple ideas underlying DNA fingerprinting,

00:43:10 as it's called popularly, or DNA typing or DNA identification, as we prefer to call it.

00:43:15 From this basic idea of DNA spelling differences, it was rapidly put into place.

00:43:19 Within five years of the notion of DNA spelling differences being used for medical purposes,

00:43:25 there were already private companies called Cellmark, LifeCodes, and others,

00:43:30 which grew up to provide DNA typing services to law enforcement officials.

00:43:34 By 1989, the FBI had its own DNA typing lab in the Hoover Building in Washington.

00:43:40 There were dramatic ads in the appropriate press, such as this one here from Cellmark.

00:43:46 DNA fingerprinting links the criminal to the crime,

00:43:49 with the handcuffs here being a double helix.

00:43:54 For the most part, this has been a dramatic and a broad success.

00:43:58 Increasingly in rape cases, there is no need for a victim to testify about whether a sexual act took place.

00:44:03 There's no question, typically, about mistaken identity being a problem,

00:44:08 because DNA from a semen sample can be, when appropriately analyzed,

00:44:12 used to link, convincingly, a suspect to that semen sample.

00:44:17 It has, in fact, been useful for excluding innocent people.

00:44:20 The FBI says that of many test results that they could never exclude with standard blood markers,

00:44:26 nearly a third of those people are exonerated immediately upon DNA testing.

00:44:30 Many rapists, because of this, now plead guilty.

00:44:35 In essence, DNA evidence is rapidly becoming, although it hasn't quite become yet,

00:44:39 in principle, an irrebuttable proof of identification.

00:44:43 That is to say, in principle, if the DNA says, this is yours, it's yours.

00:44:48 But of course, nothing is ever so simple.

00:44:50 Scientists are a demanding lot, a skeptical lot, a rigorous lot.

00:44:54 It's not enough to say it's okay in principle, it must be okay in practice as well.

00:44:58 And although everyone agrees that this is a spectacular technology,

00:45:01 controversies have erupted in the scientific community from time to time

00:45:05 over whether it's really being done right.

00:45:07 Fights erupt over DNA fingerprinting, and because it is such an important technology,

00:45:11 it is one where the fights have really, indeed, been rather vigorous.

00:45:16 What have they been about?

00:45:18 They've not been about how to do it in principle.

00:45:20 They've been about how to do it in practice and how well-regulated the practice is.

00:45:24 For example, DNA types should look, DNA fingerprints should look,

00:45:27 like the barcodes I showed you on the first slide.

00:45:30 I'll show you an example from an early case,

00:45:32 just to show you that they don't always have to look like this.

00:45:35 Here is a not-very-good example of a DNA fingerprint,

00:45:38 which was used in a criminal case in New York.

00:45:41 It's one I know well because it was one where I was asked to serve as an expert witness,

00:45:45 which is how I, from my medical genetics background, got briefly involved in this.

00:45:49 It was an interesting case because it showed what scientists can do when they put their heads together.

00:45:54 Halfway through this case, when all the evidence was being considered,

00:45:57 all of the scientists who had testified as witnesses for the prosecution

00:46:01 and all the scientists who testified as witnesses for the defense

00:46:04 met outside the courtroom without the lawyers present and talked about the evidence,

00:46:09 and at the end of the day agreed the evidence was terrible,

00:46:12 they went back to court with a joint statement from the witnesses on both sides saying the evidence was no good.

00:46:17 It was the first case in which DNA fingerprinting was actually thrown out

00:46:21 because of the way it was practiced in particular.

00:46:23 It was also an example, I think, to the legal community

00:46:25 that scientists are not necessarily hired guns who'll say whatever you tell them to say.

00:46:30 The other controversy that has arisen is about how to interpret a match.

00:46:35 What frequency should you put on it?

00:46:37 How rare is a pattern? How odd is a match?

00:46:40 And for this, the controversy is a technical one and a complex one,

00:46:43 but it has to do with the fact that the frequencies of different DNA patterns of different genes

00:46:47 vary across the population.

00:46:49 This is actually a blood group frequency distribution.

00:46:52 Similar things are known for other types of DNA differences.

00:46:56 And so there is active controversy, or has been active controversy,

00:46:59 about exactly what weight we should put on samples.

00:47:02 Are the odds being quoted 100-fold too high, 10-fold too high?

00:47:06 Are they exactly right? Maybe they're 1,000-fold too high?

00:47:09 Scientists are arguing very actively about all of this.

00:47:12 And there is a good mechanism in the scientific community for focusing such argument,

00:47:16 and it is and was in the form of a National Research Council committee

00:47:21 from the National Academy of Sciences that was put together.

00:47:24 For my own sins in that New York case, I served on this committee for a period of three years,

00:47:29 which finally culminated in the production, after a very, very long gestation,

00:47:34 in an NRC report called DNA Technology in Forensic Science.

00:47:37 It's actually on sale out back, should you happen to want one.

00:47:40 The important things of the report, which just came out this spring,

00:47:44 was that the Academy called for defined standards for laboratory work.

00:47:49 It called for new standards for statistical calculations.

00:47:53 And most importantly to my mind, it called for mandatory proficiency testing,

00:47:57 that the laboratories that are doing this work should be subjected regularly

00:48:01 to blind proficiency testing to ensure that they did the work well on a regular basis.

00:48:06 It is in some sense appalling that there are no mandatory standards

00:48:10 for something as important as forensic testing.

00:48:13 There are higher standards indeed for the laboratory practices of someone

00:48:16 who will diagnose strep throat than for the laboratory practice of someone

00:48:20 who will create a DNA fingerprint that could be used to send someone to death row.

00:48:25 Another point that we talked about, it's not on the slide, is about databases.

00:48:30 There has been discussion about creating national databases of everyone's DNA type.

00:48:35 That way when a rape is committed, there's no need to find a suspect.

00:48:39 We could take the semen sample and get its DNA pattern

00:48:43 and compare it to a database of everyone's DNA pattern and find out whose it was.

00:48:47 There are many people who feel understandably uncomfortable about such a national database.

00:48:52 So legislatures have instead decided in some states to set these up,

00:48:56 not for all citizens, but for only those convicted of, say, sex offenses.

00:49:00 In other states, for those convicted of any felony.

00:49:03 There's a lively controversy over what sorts of databases should be set up.

00:49:07 And there are those who say, why should you matter?

00:49:10 Why should you care if you're in a database?

00:49:12 Because after all, if you're innocent, there's no chance the technology will do you any harm.

00:49:16 Well, even as standards are being discussed and worked out, and I'm an optimist,

00:49:20 I feel the standards are being worked out very well.

00:49:22 I think the Academy's report and many other steps are doing a great job

00:49:25 of putting this on the most rigorous possible footing.

00:49:28 New developments occur at just a dizzying pace.

00:49:31 For example, this advertisement from Cetus Corporation says,

00:49:34 DNA typing will never be the same again.

00:49:37 And it heralds the use of PCR, the polymerase chain reaction in forensic DNA typing.

00:49:43 PCR is a marvelous technology to amplify DNA.

00:49:47 It allows you to take a specific region of DNA on the chromosome,

00:49:51 and by using little black primers here and copying back and forth, back and forth,

00:49:56 just the particular region you want to copy,

00:49:58 making 2, then 4, then 8, then 16, up to millions of copies of a particular region.

00:50:04 And so, in principle, it is possible to, and people do indeed,

00:50:07 start from the DNA of a single cell and get enough DNA to analyze with PCR.

00:50:12 That makes it possible not just to analyze bloodstains of the sort that were seen before,

00:50:17 in which you could get one microgram, one millionth of a gram of DNA,

00:50:21 or semen swabs from a rape, some of which, many of which,

00:50:23 give you enough to analyze by standard techniques,

00:50:26 and, in fact, even a shed hair has enough DNA at its root.

00:50:30 A urine sample, saliva sample, will have enough DNA in most cases.

00:50:36 It's possible, then, that by licking an envelope,

00:50:38 you deposit enough DNA to trace who sealed the envelope.

00:50:42 Obviously, a technology that is that powerful and that is that sensitive

00:50:46 must be used even more carefully because, as you can imagine,

00:50:49 if I sneeze on something, my DNA is there, too.

00:50:52 And so there's tremendous need to avoid contamination.

00:50:56 Whether laboratory practice is up to that,

00:50:58 whether proficiency tests have to be put in place,

00:51:00 the guarantee that they're up to that, these are questions under debate.

00:51:04 Let me shift gears and talk about a different application

00:51:07 than in the United States criminal courts.

00:51:10 An application to a human rights problem,

00:51:13 not my own work, a work of a colleague who I'll describe,

00:51:16 but she was kind enough to share these slides and her information with me

00:51:19 so I could share it with you.

00:51:21 In 1975, the military in Argentina overthrew the government of Isabel Perón.

00:51:27 A very rigid ideological military it was.

00:51:31 It was a military which said such things as the following quote

00:51:37 from the military governor of Buenos Aires,

00:51:40 direct quote from a speech to the public.

00:51:43 First, we will kill all the subversives.

00:51:45 Then we will kill their collaborators.

00:51:47 Then their sympathizers.

00:51:49 Those who remain indifferent.

00:51:50 And finally, we will kill the timid.

00:51:53 They had a lot of enemies indeed.

00:51:56 As shown in this tree of subversion.

00:52:01 This is in fact a tree of subversion, all the subversive groups,

00:52:05 based upon a similar drawing that was made in Germany for the SS

00:52:09 during the Nazi regime.

00:52:11 I note for you just briefly, I can't read everything,

00:52:13 the roots of the tree of subversion are Marxism, Zionism, and Freemasonry,

00:52:17 but other important branches include the liberals, the evangelicals,

00:52:22 the Anglicans, and the Rotary Club.

00:52:25 It's on there.

00:52:28 The military junta set out in a systematic fashion to eradicate the opposition

00:52:32 and to terrorize its society,

00:52:34 and did so with sweeps through neighborhoods,

00:52:36 picking up subversives and non-subversives rather indiscriminately,

00:52:39 taking at times whole families, young families.

00:52:42 In fact, many people disappeared,

00:52:44 and no one knew, because of lack of coverage, the scope of what was going on.

00:52:48 They knew their own children had disappeared.

00:52:50 Eventually, after the fall of the government,

00:52:52 the Commission on the Disappearances of Persons

00:52:54 found 9,000 documented cases of disappearances.

00:52:58 Correcting for underreporting and the lack of documentation,

00:53:01 it's estimated that about 15,000 persons were disappeared.

00:53:05 Well, as these cases began to build up,

00:53:09 older women, grandmothers typically,

00:53:12 of young men and women in their 20s and 30s,

00:53:16 began to get together in the main square, the Plaza de Mayo in Buenos Aires,

00:53:20 and began to talk as support groups for one another,

00:53:23 looking for their lost children.

00:53:25 They began to talk, and they began to march, and they began to protest.

00:53:28 And as they did, people came to the square and shared with them stories,

00:53:31 and the stories said,

00:53:33 we've heard of cases of children appearing in military families

00:53:38 who were previously childless, and the wife wasn't pregnant.

00:53:43 They would occasionally have stories from people released from prison

00:53:46 saying that they had a friend,

00:53:49 or that one of their children had been seen alive in prison

00:53:52 and had given birth.

00:53:55 Midwives and obstetricians were at times kidnapped and blindfolded

00:53:59 from the streets of Buenos Aires, taken to military prisons,

00:54:02 forced to help in the delivery of children,

00:54:04 and then blindfolded and put back on the streets.

00:54:07 Sometimes during a delivery,

00:54:09 a woman might say to such a midwife or obstetrician,

00:54:12 my name is, please tell my mother.

00:54:15 And in one case it's documented the midwife did,

00:54:18 and she was later killed for it.

00:54:20 Phony birth certificates began showing up at the schools about five years later,

00:54:24 and registrars quietly told the grandmothers of the Plaza de Mayo,

00:54:28 or told someone who told the grandmothers,

00:54:30 and the grandmothers took notes.

00:54:33 By 1983, when the Malvinas War, the Falklands War,

00:54:38 led to the fall of the military junta and Alfonsín took over,

00:54:41 the grandmothers contacted the AAAS,

00:54:43 the American Association for the Advancement of Science,

00:54:46 and asked for help in identifying and proving that these were their children.

00:54:49 And they demanded that genetics must be able to do it.

00:54:52 They knew genetics somehow would be able to do it.

00:54:55 And through a route got in touch with Mary Claire King,

00:54:58 a professor at the University of California, Berkeley,

00:55:00 a true hero to me, and a good friend and a colleague.

00:55:03 And I'm describing, indeed, her work past here.

00:55:06 Mary Claire King went and worked with the grandmothers of the Plaza de Mayo

00:55:10 to begin, as they say, we are searching for two generations,

00:55:15 to begin to try to get court orders for some of the children taken into military families

00:55:19 to do some sort of genetic typing and show that, indeed,

00:55:22 they belonged to these biological grandparents

00:55:25 rather than to the adoptive parents.

00:55:29 Originally, simple HLA typing was used,

00:55:32 typing of cell surface markers,

00:55:34 but this was not terribly powerful in these cases.

00:55:37 DNA fingerprinting of the sort I described before was used,

00:55:41 but again, for technical reasons I won't go into, was not as powerful.

00:55:45 Very much more powerful, almost unique sequences of DNA would be needed.

00:55:50 And so Dr. King's group turned to looking at a particular bit of DNA

00:55:55 called the mitochondrial DNA.

00:55:57 It exists in a little ordinal, a little package outside the nucleus of the cell.

00:56:02 It's a small bit of DNA.

00:56:03 And what's important to know about it is you only get it from your mother.

00:56:06 It's only passed on in the egg and not the sperm.

00:56:08 And so mom passes it on to all her kids,

00:56:11 and every female passes it on to all her kids.

00:56:13 If I can read snippets of unique variable sequence in mitochondrial DNA,

00:56:19 I can trace maternal lineage.

00:56:24 The older woman at the top is Heidi Lemos,

00:56:28 and these are two of her grandchildren.

00:56:31 She and her adult daughter and her son-in-law were all kidnapped by the military.

00:56:37 She was tortured and eventually released.

00:56:40 Her adult daughter and adult son-in-law were eventually killed.

00:56:43 But the daughter was two months pregnant when she was picked up,

00:56:46 and a prisoner told Heidi that her daughter had been kept alive and gave birth in prison.

00:56:52 Heidi Lemos spent 10 years looking for that grandchild of hers.

00:56:57 She eventually found a child living with a woman

00:57:02 who had been the military guard in charge of female prisoners at the prison,

00:57:07 and it was quite plausible that this child was not hers,

00:57:10 and she demanded of the courts DNA testing.

00:57:13 Mitochondrial DNA sequences were obtained under court order

00:57:17 and were found to match perfectly between this granddaughter she never knew and Heidi Lemos.

00:57:23 They went to court and demanded the return of the granddaughter.

00:57:27 The military family made the argument,

00:57:29 how can you return this grandchild to a family she's never known?

00:57:33 It's not in the child's best interest. She doesn't know Heidi Lemos.

00:57:36 The grandmothers of the Plaza del Mayo said,

00:57:39 When the society knows that these people she's living with were the murderers of her parents,

00:57:45 how can you not? Because when she becomes an adult, she will know this.

00:57:49 How is it worse for her to move families now

00:57:53 or to find out when she's an adult that she's been raised all her life by her parents' murderers?

00:57:58 The Supreme Court of Argentina agreed.

00:58:01 This is simply the sequences of Heidi Lemos and her granddaughter.

00:58:07 Sometimes the stories are about things that are less happy.

00:58:11 The Manfull family was abducted in 1979 from their home in the middle of the night.

00:58:17 Eventually, the mother, the father, and this son were all murdered.

00:58:23 Karina and Christian were wounded but survived,

00:58:27 and Graciela was actually sleeping over at a friend's house when her parents were taken in the night.

00:58:33 The bodies of the parents and the son were not found, at least not for many years.

00:58:40 Then mass graves began to turn up, and there was a mass grave site

00:58:43 that was a plausible site to contain the remains of the Manfull family.

00:58:47 And so one was faced with the prospect of multiple skeletons and skulls,

00:58:52 such a skull here from such a mass grave,

00:58:55 and trying to identify which were the remains of the Manfull family,

00:58:58 of the parents and of the son.

00:59:02 And so Dr. Kingsgrove at Berkeley worked out ways to sequence DNA,

00:59:06 to obtain DNA from the teeth of a skull by sawing a tooth and a half

00:59:11 under sterile conditions and extracting DNA and sequencing mitochondrial DNA.

00:59:15 They tried it out first at Berkeley with the baby teeth of lots of residents at Berkeley.

00:59:20 And then when they found they could do it with baby teeth, they began to do it with skulls.

00:59:24 And in fact, briefly, the skulls of male childs and female childs here are matching a sister,

00:59:33 and here the father, sorry, the skulls of the male child and the mother match the sister.

00:59:39 They should all have the same mitochondrial DNA.

00:59:41 And here the DNA sequence from the molar of the presumptive father matches his grandmother.

00:59:48 And these mitochondrial DNA sequences establish that they are indeed the Manfull family.

00:59:54 Their remains have been reburied in the family grave.

00:59:57 It's unlikely much justice will come in the case,

01:00:00 because the military has declared an amnesty at this point for crimes committed during the period.

01:00:06 Overall, about 51 living children have been identified as belonging to some appropriate family,

01:00:12 and most of these have been restored to their natural biological family.

01:00:16 Many of the children are now reaching the age of majority

01:00:19 and so are able on their own to look for their natural families when they know that something was amiss.

01:00:25 And even as the grandparents are dying, they are leaving behind their DNA in a DNA databank

01:00:31 so that the children, as they come to ask, will have it.

01:00:37 It's a remarkable story, and Mary Claire and the work she's done and other colleagues have done is quite remarkable,

01:00:43 and I appreciate her sharing the slides with me, and I'm a tremendous fan of what DNA has done in those cases.

01:00:49 Let me briefly in the closing minutes tell you about two other applications of DNA technology.

01:00:55 Very briefly, it can be applied not just to humans,

01:00:59 but DNA technology turns out in its DNA identification form to be very useful in agriculture as well.

01:01:07 One of the great uses of DNA fingerprinting turns out not just to be in the criminal courts,

01:01:11 but in the civil courts, and not just for human cases, but for corn cases and tomato cases,

01:01:17 because in fact, people spend a tremendous amount of time developing strains of corn by standard old breeding,

01:01:23 like Jerry Fink told you about this morning,

01:01:25 and they can never gain intellectual property protection of it, never gain patent protection over it,

01:01:29 because there's no way to prove that this corn plant was theirs.

01:01:33 So they put all this work into developing the strain, someone steals the strain,

01:01:37 and there are ways to do that, and you can't prove anything about it.

01:01:40 Well, in fact, you can do DNA fingerprinting on corn plants,

01:01:43 and Pioneer Seed and many other large seed companies routinely maintain databases of the DNA fingerprints

01:01:48 of all their important varieties so they can go to court and prove you stole one.

01:01:52 It, in fact, is a good thing because it then creates the economic protection

01:01:56 to give people an incentive to develop things.

01:01:59 And then very briefly, the ultimate in DNA paternity testing.

01:02:03 As I was getting on the plane yesterday to come here, I found in the New York Times

01:02:07 and quickly photocopied and made a slide of the ultimate DNA paternity test,

01:02:13 DNA taken from a 40 million year old extinct insect, actually kind of termite, notwithstanding the headline,

01:02:22 preserved in amber, shades of Jurassic Park for those of you who have read it.

01:02:27 And DNA sequencing by PCR has been done on this to answer questions about

01:02:32 who is the parent of the modern day cockroach, and was it really the termite?

01:02:37 This is a termite, and they are comparing and finding all sorts of novel things

01:02:41 about whether the termite really was or wasn't the evolutionary ancestor of the cockroach.

01:02:46 Indeed, if we take DNA paternity testing way back, it brings us back to our common origin as a species

01:02:53 and brings us back to the common unity of life.

01:02:57 In closing, basic science, where does it lead us?

01:03:02 It leads us in unexpected directions that have social consequences.

01:03:06 No one developed DNA technology, DNA identification, the looking at DNA spelling differences,

01:03:11 for the purpose of criminalistics applications.

01:03:16 No one developed it to help settle paternity suits or to resolve human rights abuses.

01:03:20 No one developed it for intellectual property protection.

01:03:24 DNA technology wasn't driven by the questions of evolution.

01:03:27 It was driven by a wholly different set of questions,

01:03:29 and yet the ability to read and interpret DNA spelling differences

01:03:32 has had consequences for all of these areas.

01:03:36 As a society, we can be pleased and proud that our technology,

01:03:42 that our sciences have such social applications,

01:03:45 but what we must do together as scientists and as a society

01:03:49 is to make sure to insist at all times with the criminalistics, etc.,

01:03:54 that we apply these technologies with the highest of standards.

01:03:59 And we must strive to apply them, as with Argentina, to the highest of purposes.

01:04:05 Thanks very much.

01:04:07 Thank you.

01:04:20 We must have two questions for Eric directly,

01:04:22 and then we'll have the panel address the whole panel.

01:04:26 Okay, a quick one.

01:04:28 Granted that quality assurance and lab standards for DNA criminal labs is a good thing

01:04:33 and should be pursued with all speed,

01:04:36 but I'm still left a little bit confused in the wake of a great flap last spring

01:04:40 over what Victor McKusick and his panel did or didn't say

01:04:45 in terms of just how serious is the problem of PCR false positives and the like.

01:04:53 What is your opinion about how great this problem is at the moment in real time?

01:04:58 I think on anything that has to do with whether something that is wonderful in principle

01:05:04 is being practiced well in practice,

01:05:07 it's foolhardy for me to give any sort of a probability statement

01:05:11 of what fraction of them are being right or wrong.

01:05:13 I think it requires case-by-case analysis,

01:05:15 and I won't wade into trying to guess how well things are done.

01:05:19 I've had an opportunity to look at only a tiny fraction of cases.

01:05:22 As I said, I apply DNA to very different purposes,

01:05:25 and my involvement has been to raise some of these questions in one case

01:05:29 with the National Academy.

01:05:31 There's a much greater database.

01:05:32 I'm going to decline to give you those numbers.

01:05:34 Courts, I think, are rightly sensitive to the need to look carefully at these.

01:05:38 In a number of states, there are very strict guidelines governing admissibility

01:05:42 that require you to check whether the work was done correctly.

01:05:46 I think that's a wonderful thing.

01:05:48 I think things should go to juries only when, in fact, the work has been done correctly,

01:05:52 and I support those sorts of evidentiary rules.

01:05:55 Beyond that, I think science and law both work well by cases

01:05:59 rather than in the abstract and in general.

01:06:02 Yes?

01:06:03 This brings up a specific case that a member of the audience is asking about.

01:06:07 Roger Coleman was executed in Virginia.

01:06:11 Governor Wilder refused clemency,

01:06:13 partly on the basis that he said he believed the DNA evidence incriminated Coleman.

01:06:18 Do you believe that DNA evidence was sufficiently reliable to put Coleman to death?

01:06:23 Again, I take all criminal cases and DNA cases as such serious matters

01:06:28 that I won't venture as specific in the Coleman case,

01:06:31 which I'm aware of generally from the media and from some conversations,

01:06:34 without having had an opportunity to review the evidence myself.

01:06:37 What I do know is there was substantial controversy

01:06:40 over whether the evidence did or didn't suggest

01:06:43 that there was another DNA pattern involved in a rape murder.

01:06:48 I know that it was not a clear-cut case.

01:06:51 There were other things seen in the sample

01:06:53 suggesting the possibility of another person involved,

01:06:56 not necessarily, although I don't know the facts, excluding Coleman.

01:07:00 And so it's a very delicate and a complicated case.

01:07:02 I think what's fair to say is that there wasn't a great deal of enthusiasm

01:07:09 for retrying that case or having another hearing on the evidence.

01:07:12 I think many people felt more upset about that,

01:07:15 that there was a certain speed with which the execution proceeded

01:07:18 when questions had been raised.

01:07:20 I think there was a concern that the public would be very upset

01:07:23 if executions were delayed while people quibbled over details

01:07:27 like guilt and innocence and DNA.

01:07:30 So I certainly can't comment on the merits.

01:07:33 All I can say is that as a bystander and someone reading the press,

01:07:36 there were questions raised left and right,

01:07:39 and it would seem to me that unless there were many facts I don't know,

01:07:42 they might have merited more attention in the scientific forum than they got.

01:07:45 But again, these are such important questions.

01:07:48 You must deal with them on a case-by-case basis.

01:07:50 And since I'm not privy to all the facts,

01:07:52 my opinions are really uninformed, much more so than they ought to be.

01:07:57 Thanks very much.

01:07:59 Can I get one more question?

01:08:01 Why don't we have them just one more question?

01:08:04 Just one quick question.

01:08:06 Could you address more generally the idea of society always having to chase

01:08:11 after technology once it's been developed?

01:08:14 You're talking about creating standards.

01:08:17 It takes time to create standards, but technologies get used right away.

01:08:24 That they do, and it's usually a good idea to create standards

01:08:27 after you've had some experience with things.

01:08:29 And so you pose a valid problem.

01:08:32 You can't write good rules until you've done certain things,

01:08:34 and you shouldn't be doing those things until you've written good rules.

01:08:38 Life is rather imperfect that way.

01:08:40 I have no solution to it.

01:08:42 It means we will bumble through somehow initial periods of all new technologies

01:08:46 as we begin to get information and regulation in place.

01:08:49 I think it's important that we know that we're doing that,

01:08:52 that we therefore proceed with great caution at the beginning,

01:08:55 but then again we have to press on with important things.

01:08:57 It wouldn't be right to withhold benefits of technologies

01:09:00 in favor of long, long delays for speculative regulation either.

01:09:03 I think a balance has to be struck.

01:09:05 We have to know what we're doing.

01:09:06 I am one who very much favors a cautious approach,

01:09:09 and yet I'm not one to declare willy-nilly moratoria.

01:09:13 Thanks again very much.

01:09:16 Thank you.

01:09:23 And now we have a few minutes for questions for all four speakers

01:09:27 before Leon Letterman speaks.

01:09:33 I have a question from the audience for Dr. Beachy.

01:09:37 It says you mentioned several genetic traits that are being introduced into plants,

01:09:42 one being the quality of being resistant to friendly herbicides.

01:09:51 This writer says,

01:09:53 I've also heard that fertilizer companies are purchasing major seed-producing companies

01:09:58 with the intent of genetically engineering plants requiring larger and larger quantities of fertilizer,

01:10:05 thus increasing profits of those companies.

01:10:08 Is this happening?

01:10:13 The latter, not that I'm aware of.

01:10:18 If I had stock in a phosphate company, I might not even answer if I knew,

01:10:22 but I have no knowledge that anyone's working on.

01:10:26 There is a lot of research to increase the capacity of plants

01:10:30 to take up certain kinds of minor elements more efficiently

01:10:34 so that plants can live in, say, phosphate-deficient soil more readily

01:10:40 by being in association with microbes that convert the soil minor element into a form that's usable.

01:10:48 Those kind of things I think are under investigation,

01:10:51 but those are ones that reclaim limited amounts of fertilizers or elements from the soil

01:10:59 and mobilize them into the plant.

01:11:01 There's also work going on to develop plants that are able to live in toxic soils,

01:11:07 but I don't know of anyone who is working on increasing dependency,

01:11:13 rather we're trying to transfer genes such as those that are important for fixing nitrogen and taking up elements.

01:11:20 The question of the herbicide question is one that is an important one

01:11:25 and one that will continue to raise the interest of the public

01:11:30 and it comes still to the question of what is the best way to grow our food

01:11:36 and we have come to depend on some very important and very useful agrochemicals

01:11:40 and those will continue to be used for the foreseeable future

01:11:44 until we have bona fide alternatives that can produce the same level of product,

01:11:50 have the same level of productivity, result in the same level of productivity without increased cost.

01:11:55 And if that's the case, then we certainly must use those that are the most friendly to the environment

01:12:00 and for that kind of data we rely on the scientists and universities

01:12:04 and the regulatory agencies to inform us and keep us abreast of what's the latest in safe and friendly herbicides.

01:12:15 I have a question here that's addressed to Dr. Beachy,

01:12:18 but it deals with Bacillus throgensis toxin which Dr. Kennedy also mentioned

01:12:24 and this person's concern, this question, is that they're asking if there's validity to the,

01:12:30 or they're saying that Dr. Bruce Ames of UC Berkeley points out that endotoxins produced by plants

01:12:36 for their own protection can sometimes be dangerous to humans

01:12:39 and I think the point being raised here is that just because something's natural doesn't necessarily mean that it's safe

01:12:45 and the question is, is Bt is a natural toxin that has been applied for a long time

01:12:50 but generally in a way that humans probably don't ingest huge amounts of it.

01:12:54 Is there any reason to be concerned that if plants are engineered to produce Bt

01:12:58 that could increase the risk over the long term for humans consuming those products?

01:13:03 It's a valid question because in fact as companies such as Ecogen and Microgen

01:13:08 search through the thousands of strains of Bacillus,

01:13:11 they find those that have efficacy against some insects and those that don't

01:13:15 and their goal is to find those that are the most likely safe in the environment.

01:13:19 Remember that these Bacillus thuringiensis endotoxins are especially specific.

01:13:24 They work on certain sets of insects or species or even subspecies

01:13:29 so that they are highly, they are indeed specific.

01:13:34 There are none that I know of that have proven effects on

01:13:38 other than the insect cells that are targeted in the guts of the insects.

01:13:43 It's not, one could raise the possibility however that there are,

01:13:47 that if this protein is in a plant it would break down into a different form

01:13:50 and have a different activity than it would have had if it had been applied to the surface of the leaf

01:13:54 and that's an issue that would have to be addressed by additional testing and additional proof.

01:14:02 I forgot the other part of that question.

01:14:04 I think that was basically it, that people are going to be exposed to it much more

01:14:09 if it's in plants that they're eating all the time

01:14:12 and perhaps they have been up to this point and there could be long term consequences.

01:14:15 The other point that I want to raise on that is that in fact

01:14:18 with the level of specificity and gene regulation

01:14:22 one can eliminate the presence of the Bt endotoxin in the edible parts.

01:14:27 If you want to protect a tomato plant, you protect, here we are again,

01:14:34 if you want to ask me the question of why tomatoes, this is a good time.

01:14:38 You have the protection of the fruit, you have the protection of the plant by protecting the leaves

01:14:43 and specific transcriptional or regulatory sequences

01:14:46 will give you the expression in the leaves rather than in the edible parts.

01:14:49 So there are ways around an issue if there is indeed a safety issue that needs to be raised.

01:14:55 There are ways that with molecular genetics you can address each of those.

01:15:00 Of course, just to add something quickly,

01:15:03 that does not help you, however, in leafy vegetables where you and the bugs like the same parts.

01:15:14 We should also remember that the application and use of Bacillus thuringiensis

01:15:20 is in fact by dusting plants as a natural insecticide is to dust leaves

01:15:29 and most of that insecticide or residue of the Bacillus is washed off during the preparation of the food.

01:15:38 But it's likely that you have been ingesting some.

01:15:41 The question of whether or not you will ingest more in a transgenic plant than in a dusted plant

01:15:46 is one that has not yet been fully addressed.

01:15:50 Several people talked about world hunger and so forth.

01:15:54 A member of the audience asked,

01:15:56 isn't world hunger a problem of distribution rather than production?

01:16:02 Can I hit that one first and then it's yours?

01:16:05 It absolutely is.

01:16:06 There are parts of the world where distribution is in fact limiting.

01:16:11 And we all know about those.

01:16:13 On the other hand, I can't give up what I know how to do

01:16:18 in favor of letting a politician make a decision later.

01:16:22 That might or might not impact that food supply.

01:16:25 It would be immoral, I think, for me not to do what I can do

01:16:29 to alleviate the areas that I can

01:16:31 and allow the economists and the politicians,

01:16:34 if they have the same moral standards that the rest of us espouse,

01:16:37 reach their solutions.

01:16:40 I can't sit and wait.

01:16:41 It's important that I do what I know how to do

01:16:43 and they do what they know how to do

01:16:44 only they need to do their job better while I do mine.

01:16:53 I think the whole issue of food distribution versus production

01:16:59 depends upon whether you have the notion or don't have it

01:17:06 that somehow, sometime we're going to have a perfect world economy

01:17:10 that puts enough cash in the hands of poorer persons

01:17:13 because the biggest part of the distribution problem

01:17:16 is the availability of sufficient resources

01:17:21 to purchase food in those parts of the world that are short of it.

01:17:25 You're never going to have a perfect distribution system.

01:17:29 Therefore, you ought to plan a system that can produce more

01:17:33 than a perfect distribution system would require.

01:17:36 So to say it's a distribution problem and thereby wish it away,

01:17:41 I think is just not rational.

01:17:46 Thank you.

01:17:51 This is a question that deals with something

01:17:54 that's been danced around a little bit.

01:17:56 This speaker says,

01:17:58 several speakers talked about the importance of basic research,

01:18:01 its contributions, and the necessity to support basic research.

01:18:04 Could someone elaborate on the difference

01:18:06 between basic and directed research?

01:18:09 I'd like to add that some of us know that there's a debate going on right now

01:18:13 in the Congress and in the government funding agencies

01:18:16 about whether the way that research has been funded should be reconsidered

01:18:22 and there should be more emphasis placed on directed research

01:18:26 and less on basic research, broadly speaking.

01:18:30 And I wonder if anyone wants to address that,

01:18:32 whether that's a good idea.

01:18:34 I'll take a crack at that.

01:18:40 Directed research is the easier to define.

01:18:42 It's research aimed at producing a particular result

01:18:45 in a particular way at a particular time.

01:18:48 It's very important.

01:18:50 Development of many types of drugs and other things

01:18:56 are highly directed operations.

01:18:58 But the basic fundamental breakthroughs in science

01:19:01 that have created entire new industries,

01:19:03 the biotechnology industry, the computer industry,

01:19:06 have depended on the serendipitous work of basic science,

01:19:11 which is to say investigators following their nose

01:19:14 as to what's interesting,

01:19:16 what are good questions to ask and answer,

01:19:18 what nature happens to be selling in the way of answers these days,

01:19:22 where it's yielding.

01:19:24 These are very hard things to define,

01:19:26 and Congress hates that.

01:19:28 They hate the idea because they call it,

01:19:29 and perhaps the press will call it,

01:19:31 lack of accountability.

01:19:33 Investigators, I must admit,

01:19:35 write grant proposals to study something interesting

01:19:38 and then halfway along the way find an unexpected surprise

01:19:42 and go study something else instead because of that surprise.

01:19:45 God help us when the Office of the Inspector General catches on to this

01:19:49 and says,

01:19:50 how could it be?

01:19:51 You said you were going to do X research for the next five years,

01:19:54 and look, you didn't.

01:19:55 You're committing fraud not to have done precisely what you said

01:19:59 in Doltish fashion.

01:20:01 These things pay very long-term returns.

01:20:04 They're very speculative.

01:20:05 They're very uncertain.

01:20:06 But they are the very foundation of science.

01:20:09 We need a portfolio of basic research and applied research.

01:20:13 What my concern is,

01:20:14 there are great constituencies in Congress

01:20:17 for things like Alzheimer's disease, cancer,

01:20:21 and many other disease states.

01:20:24 But in fact,

01:20:25 tremendous progress against those disease states

01:20:27 has come through things like molecular biology

01:20:30 in most unexpected directions.

01:20:32 There are not constituencies demanding more funding

01:20:35 for these basic areas,

01:20:37 and so I fear that Congress naively will be funding cancer,

01:20:42 Alzheimer's disease,

01:20:43 many other things,

01:20:44 and expecting chop-chop,

01:20:45 let's see results on this quickly.

01:20:47 They're going to be very disappointed.

01:20:49 I've read the report, too,

01:20:50 out of Congressman Brown's subcommittee

01:20:53 and a task force of his committee

01:20:55 that expresses frustration

01:20:56 that science isn't solving all our problems

01:20:58 and that maybe we ought to redirect science funding

01:21:01 so science solves all our problems.

01:21:03 I think it's always a good idea

01:21:05 to look carefully at the basis of funding science.

01:21:08 I'm in favor of such reexaminations.

01:21:10 But I think if, in fact,

01:21:11 the goal of them is that science

01:21:13 should be solving many social problems,

01:21:15 I think it's misfounded.

01:21:17 I think, in fact,

01:21:18 science has been a remarkably successful enterprise

01:21:20 in this country,

01:21:21 more successful in this last 50 years

01:21:23 and in this country than at any time in history.

01:21:26 And so I would be at least cautious

01:21:28 about tampering with it.

01:21:30 This is a human genome project.

01:21:37 I agree with Eric

01:21:39 that we have to protect basic research,

01:21:42 and certainly this challenge from Congress

01:21:44 is one direction.

01:21:45 Let me, perhaps as a footnote,

01:21:47 suggest that basic research

01:21:50 may be challenged elsewhere,

01:21:52 and that is through the universities.

01:21:54 I alluded in my talk

01:21:55 to the change in the patents

01:21:57 which have made universities

01:21:59 more interested in applied research,

01:22:02 that is, research for which

01:22:03 there may be some immediate payoff

01:22:05 in terms of royalties from granting licenses.

01:22:09 And there has already been some work,

01:22:11 not enough,

01:22:12 to suggest that at least some of the investigators

01:22:15 who are involved

01:22:16 and some of the universities who are involved

01:22:18 have turned from basic research

01:22:20 to applied research

01:22:21 because this is an immediate gain

01:22:23 not only to the investigators

01:22:24 but to the universities.

01:22:25 And I think we have to begin, if you will,

01:22:28 to think about whether there is some danger

01:22:32 to a growing university industrial complex.

01:22:37 Okay.

01:22:38 In the interest of time,

01:22:39 we'll have to stop the session.

01:22:40 And thank you to the speakers.

01:22:42 And Harold Varmus will introduce Leon Letterman.

01:22:56 On the past day and a half,

01:22:58 we've described for you

01:22:59 what we call the golden age of biology

01:23:02 and some of the ways in which

01:23:03 the products of that golden age

01:23:05 are going to affect our health,

01:23:07 our crops,

01:23:08 our laws,

01:23:09 our economy,

01:23:10 and many other aspects of our lives.

01:23:13 How is our culture

01:23:14 going to accommodate to these changes?

01:23:17 What should we be doing as citizens

01:23:19 to respond to them?

01:23:22 Education is obviously important.

01:23:24 But where do we begin?

01:23:26 With schoolchildren?

01:23:28 With the general audience

01:23:29 such as the one assembled here?

01:23:31 Or with those who wield power,

01:23:33 congressmen who make national policies

01:23:35 and set priorities for government spending?

01:23:39 Few people have taken such a passionate interest

01:23:41 in this question

01:23:42 as our next and final speaker,

01:23:44 Leon Letterman.

01:23:46 Those who happen to read his recent op-ed

01:23:49 Those who happen to read his recent op-ed essay

01:23:51 in the New York Times

01:23:53 will know that half a century later,

01:23:55 he continues to savor his own high school education

01:23:58 in the New York public school system.

01:24:00 In fact, he has been inspired by it

01:24:02 to build several innovative programs

01:24:04 for teaching science to high school students

01:24:06 and their teachers in the Chicago area.

01:24:09 Just last night,

01:24:10 the Science Education Center at Fermilabs,

01:24:13 where he is a director emeritus,

01:24:16 named a building in his honor

01:24:18 to recognize these achievements.

01:24:22 At the banquet following his receipt

01:24:24 of the Nobel Prize in Physics in 1988,

01:24:26 Leon spoke directly to the question

01:24:28 of making his own science comprehensible

01:24:31 to the general public

01:24:32 and even to his co-recipients in other fields.

01:24:36 This is a dilemma and an anguish

01:24:38 for all scientists, he said,

01:24:40 because the public understanding of science

01:24:43 is no longer a luxury of cultural engagement.

01:24:46 It is an essential requirement for survival

01:24:49 in our increasingly technological age.

01:24:52 How does society respond to technology?

01:24:55 Leon, thank goodness, is here to tell us.

01:25:09 Thank you very much.

01:25:11 Listening to the wings,

01:25:14 I realized that Eric Lander gave my talk

01:25:17 much shorter and much better.

01:25:20 I was back there and rather nervous about,

01:25:22 as I was told,

01:25:23 speaking to 4,272 molecular biologists

01:25:27 distributed up and down the coast of California.

01:25:32 I was pacing there and a young lady said,

01:25:35 Why are you nervous?

01:25:36 And I said, How do you know I'm nervous?

01:25:38 And she said, You're in the ladies' room.

01:25:41 I'm always nervous when I come to California

01:25:49 because it's such a challenging place.

01:25:52 For example, the ocean here,

01:25:54 as opposed to where I grew up,

01:25:55 is on the wrong side of the beach.

01:25:59 New York visitors frequently dive into the parking lot.

01:26:03 Just as well, because they'd freeze otherwise.

01:26:06 In California, particle accelerators

01:26:08 come in straight lines.

01:26:09 That's weird.

01:26:13 And I noticed there are two different kinds of professors.

01:26:17 There's the Stanford types,

01:26:19 who are so rich that many of them

01:26:21 have unlisted telephone companies.

01:26:26 And there are University of California types,

01:26:29 who more recently are so credit unworthy

01:26:32 that even their cash is refused.

01:26:40 Zeroing in on this meeting,

01:26:43 I do agree that the 20th century

01:26:46 could quite readily be divided in half

01:26:49 with the first half belonging to physics

01:26:52 and the second half yield to biology.

01:26:54 I think that this is well illustrated by this meeting.

01:26:59 My invitation to this rather spectacular meeting

01:27:01 described the meeting as a presentation

01:27:06 of the history, the science,

01:27:09 and the social impacts of recombinant DNA.

01:27:12 And as a physicist,

01:27:13 I began to imagine similar meetings in my field.

01:27:17 What wouldn't we give to have a record of such meetings?

01:27:20 Say, 1700, the history, science,

01:27:23 and societal implications of Newtonian physics.

01:27:27 Or Faraday's discovery of electricity, say, in 1840.

01:27:32 Or in 1890, the history, science,

01:27:35 and social impact of Maxwell's discovery

01:27:38 of electromagnetic radiation.

01:27:40 Or in 1950, discovery of the quantum theory.

01:27:43 Or in 1970, of the invention of the transistor.

01:27:47 Or in 1980, of the discovery of the maser principle

01:27:50 and the laser, and so on and so on.

01:27:53 And I'm sure that there are colleagues

01:27:55 and friends in chemistry.

01:27:56 We have friends in chemistry.

01:28:01 In geology and so on,

01:28:03 who can sponsor similar conferences.

01:28:07 History, science, social impact.

01:28:10 How appropriate are these topics?

01:28:12 And yet, in September 1992,

01:28:15 I read in a very articulate quote

01:28:18 report on the health of science

01:28:19 issued by the staff of the

01:28:21 House Committee on Science, Space, and Technology

01:28:24 the following sentence, quoted approvingly

01:28:27 from a very prestigious source.

01:28:29 Quote, there is no evidence of a positive correlation

01:28:32 between the strength of our academic basic research capability

01:28:35 and our economic vitality.

01:28:39 Through my affiliation with the

01:28:41 American Association for the Advancement of Science,

01:28:45 I've been concerned over the last few years

01:28:48 more intensely with the general problem

01:28:50 of the health of research that's carried out in America.

01:28:53 And indeed, the report from which I just quoted

01:28:55 was in fact stimulated, at least in part,

01:28:58 by a report I wrote in 1990

01:29:01 to the board of the AAAS,

01:29:04 which was entitled

01:29:06 Science, End of the Frontier?

01:29:08 For those of you who were on sabbatical

01:29:10 in Lower Slovenia,

01:29:12 the report had to do with the issue

01:29:14 of whether U.S. science was healthy.

01:29:17 No one who attends a meeting like this

01:29:20 or so many other assemblies of scientists

01:29:22 can avoid a conclusion that science

01:29:24 in the United States is a robust, vital activity.

01:29:28 What I would like to insist, however,

01:29:32 in my original AAAS collection of anecdotes,

01:29:36 massive as these were,

01:29:38 has since been supported by numerous other

01:29:40 more scientific surveys.

01:29:42 What I want to insist is that there is stress

01:29:44 in the scientific community.

01:29:46 There are indicators of deep trouble,

01:29:48 so serious that the very infrastructure of science

01:29:51 dependent, as it is,

01:29:53 on a constant influx of young and bright

01:29:55 and engaged recruits

01:29:57 may be threatened.

01:30:02 Let me list some of the factors

01:30:04 contributing to stress.

01:30:06 In the AAAS report, I concentrate on funding.

01:30:08 I concentrate on funding

01:30:10 since that seemed to be the major concern

01:30:12 of the hundreds of scientists

01:30:14 who responded.

01:30:17 And it is clear, this is point one,

01:30:20 funding, point two.

01:30:22 If you take a photograph of any graduate school,

01:30:24 it's clear that fewer and fewer Americans

01:30:27 are opting for science careers.

01:30:29 And our strenuous efforts to recruit

01:30:32 from minorities and women

01:30:34 is moving painfully slowly, if at all.

01:30:37 Three, industries are increasingly reluctant

01:30:40 to invest in research

01:30:42 that has long-term payoffs or high risk.

01:30:45 And our once great industrial laboratories

01:30:48 are going, going, or they're gone.

01:30:51 Four, universities are increasingly being forced

01:30:55 to contract and change.

01:30:58 This is true of the great research universities

01:31:01 like MIT and Yale and Chicago and Columbia

01:31:03 and very likely most of the others.

01:31:06 And these institutions are the glory

01:31:09 of American research.

01:31:11 Five, increases in sheer bureaucracy

01:31:14 and regulatory burdens,

01:31:16 which I was concerned a lot about in this meeting.

01:31:18 Pressures of these on research don't help,

01:31:22 as well as the growth of militant fundamentalism

01:31:25 and their attacks,

01:31:27 varying from creationists, animal rights extremists,

01:31:30 fundamentalist distortions of the environmental movement,

01:31:33 and so on.

01:31:35 Now, I wouldn't characterize all regulatory problems

01:31:37 as fundamentalist,

01:31:39 although it isn't a bad description for some of them.

01:31:41 Another threat to science

01:31:43 comes from what I see as a simple political opportunism,

01:31:46 such as the now-discarded Senator Proxmire's

01:31:50 Golden Fleece Awards

01:31:52 or the excesses of Congressman Dingell's committee.

01:31:55 Bad as these pressures are, however,

01:31:57 the greatest danger

01:32:00 I see may well come from people who are our friends,

01:32:04 who profess to be, and in their own rights probably are,

01:32:07 pro-science.

01:32:09 These are a motley group,

01:32:11 which I would collectively call

01:32:13 science policy experts.

01:32:15 If you go to Washington and you lean against the wall,

01:32:17 out of a small crack will emerge

01:32:19 a science policy expert.

01:32:21 They include congressional staffers,

01:32:23 science agency bureaucrats,

01:32:25 people who are, or once were,

01:32:27 more actively connected to the research community,

01:32:30 but are now Washington-wise.

01:32:33 They are permanent committee members

01:32:35 of all kinds of communities,

01:32:37 some university presidents,

01:32:39 and a few scientists

01:32:41 who spend too much time in Washington

01:32:43 and are somehow distorted

01:32:45 by the effluvia

01:32:47 from the Potomac River.

01:32:49 They work for the GSA

01:32:51 and the OTA and CSA

01:32:53 and other agencies.

01:32:55 Now part of my fear

01:32:57 and resentment of these relatively new actors

01:32:59 in the science stage is that they have time

01:33:02 and they have research facilities,

01:33:04 that is, research on research.

01:33:06 And they can, and they have,

01:33:08 pick very effective holes

01:33:10 in arguments that amateurs like myself

01:33:12 will devise on airplanes

01:33:14 on the way to Washington.

01:33:16 The mischief that these friends can make

01:33:18 arises, in my mind,

01:33:20 from the fact that for the most part

01:33:23 they do not really understand

01:33:25 the research process.

01:33:27 Certainly they are on firm grounds

01:33:29 when they criticize the way the government

01:33:31 makes science budgets

01:33:33 and the way Congress deals with science.

01:33:36 Clearly that's a situation

01:33:38 that has grown like topsy

01:33:40 and should be reviewed

01:33:42 and revised.

01:33:44 Surely we can be more accountable

01:33:46 for bad science and more agreeable

01:33:48 to critical review of how scientists

01:33:50 and engineers manage research.

01:33:52 Although we have to

01:33:54 pause here and maintain

01:33:56 the right to do a certain amount

01:33:58 of, quote, bad science

01:34:00 or unsuccessful science.

01:34:02 If we don't do unsuccessful science

01:34:04 then we're doing it wrong.

01:34:06 Science, by its nature, has to have

01:34:08 a certain amount of lack of success.

01:34:10 That's what we mean by research.

01:34:12 Of course we should try

01:34:14 to find better ways of achieving

01:34:16 a reasonable balance between, say,

01:34:18 centrally shared facilities, that's called

01:34:20 big science, versus the individual

01:34:22 investigator, that's called small science.

01:34:24 Between basic and applied research.

01:34:26 Between research

01:34:28 and commercialization.

01:34:30 And, although all of these things

01:34:32 are difficult, even between atmospheric

01:34:34 chemistry and high temperature

01:34:36 superconductivity, there are always

01:34:38 people who say they know and they will

01:34:40 help you set these priorities.

01:34:42 And there's another

01:34:44 problem that as the current

01:34:46 comments you heard

01:34:48 increasingly about what's happening

01:34:50 to the problem of teaching versus

01:34:52 research. That has to be faced.

01:34:54 The scientist as

01:34:56 teacher has been a unique American

01:34:58 invention and I think it's a

01:35:00 key part of the success

01:35:02 of American science over the last

01:35:04 four or five decades.

01:35:06 But stress on young investigators

01:35:08 making over and over again

01:35:10 applications for research funding

01:35:12 is hurting their ability and their enthusiasm

01:35:14 for teaching at the undergraduate level.

01:35:16 And this whole process

01:35:18 of how we're doing on the undergraduate level

01:35:20 must be measured and understood.

01:35:22 So these are all

01:35:24 valid criticisms of the science

01:35:26 process.

01:35:28 What bothers me is that there have been

01:35:30 several very influential new reports

01:35:32 and they really scare me.

01:35:34 These are policy

01:35:36 analysts. And if policy

01:35:38 analysts really take control of the science

01:35:40 process, and I think we've heard about this,

01:35:42 we heard a bit of this in the question

01:35:44 period just before,

01:35:48 then I think we have a serious

01:35:50 problem.

01:35:52 In particular, I'm referring to a report

01:35:54 by the very competent

01:35:56 Office of Technology Assessment, OTA,

01:35:58 called Federal Funded Research

01:36:00 Decisions for a Decade.

01:36:02 And a very recent report I received by

01:36:04 again a friendly group,

01:36:06 chaired the House Science and

01:36:08 Space and Science

01:36:10 Technology Committee under

01:36:12 George Brown. And that's

01:36:14 called a report of the Task Force on the Health

01:36:16 of Research.

01:36:18 In both reports, in spite of many

01:36:20 pages of thoughtful analysis,

01:36:22 these reports reflect

01:36:24 a view, which was

01:36:26 raised a little while ago,

01:36:28 and which is all too

01:36:30 prevalent in this country, the importance

01:36:32 of fixing things and fixing them quickly.

01:36:34 And thus

01:36:36 the recent appointment of a commission to

01:36:38 review the state of the National Science

01:36:40 Foundation is causing a lot

01:36:42 of concern among those who

01:36:44 depend on the National Science Foundation

01:36:46 for their research, for voting.

01:36:48 Efforts to convert the National Science Foundation

01:36:50 to a quick fix agency have been

01:36:52 made in the past with near disastrous

01:36:54 consequences.

01:36:56 This isn't a problem of really basic research

01:36:58 versus applied research.

01:37:00 As was mentioned, we need a balance between these.

01:37:02 They're both essential ingredients

01:37:04 in a healthy research enterprise.

01:37:06 But this is increasing

01:37:08 pressure on research to be relevant

01:37:10 to national goals.

01:37:12 A very sound, seductive,

01:37:14 and almost unarguable

01:37:16 criterion to place on research.

01:37:18 So long

01:37:20 as research practitioners

01:37:22 or the citizens

01:37:24 or who

01:37:26 can have a statement or a role

01:37:28 in what we mean by national goals.

01:37:30 Who will set national goals?

01:37:32 If you think back over the last five decades,

01:37:34 do we really want national goals

01:37:36 set by transient

01:37:38 sort of political

01:37:40 fashion

01:37:42 to control and drive

01:37:44 research?

01:37:46 It would take

01:37:48 a very deep understanding of the nature

01:37:50 of research to make such a policy.

01:37:54 Do the policy

01:37:56 analysts realize that research can,

01:37:58 for example, create new national goals

01:38:00 and change old goals?

01:38:02 And that in some broad way, all

01:38:04 good research advances

01:38:06 rational goals of the nation?

01:38:08 That is, of course, goals that

01:38:10 you and I would all agree upon.

01:38:12 What I want to do

01:38:14 is to proceed to a

01:38:16 plan of action, which

01:38:18 sort of came out of

01:38:20 two activities I've been involved in.

01:38:22 One is,

01:38:24 again, following up on

01:38:26 the problem of stress in the

01:38:28 research community

01:38:30 and its pressures. And the other

01:38:32 has to do with the general

01:38:34 problem of education in this country.

01:38:36 The plan

01:38:38 of action, I think, is a good one, independently

01:38:40 of the question or arguments that I've

01:38:42 just used to set the stage.

01:38:44 The action plan

01:38:46 really requires

01:38:48 the enthusiastic collaboration

01:38:50 of this community I'm addressing

01:38:52 if it's to

01:38:54 succeed at all.

01:38:56 The proposal is that

01:38:58 the science and engineering community,

01:39:00 at some three million strong,

01:39:02 engage in a coherent,

01:39:04 altogether,

01:39:06 and sustained, years and

01:39:08 years, effort to raise

01:39:10 the science literacy of the American public.

01:39:14 Well, I mean, these are big

01:39:16 tasks. I'm working with the Chicago Public Schools.

01:39:18 That's probably harder.

01:39:20 There are lots of encouraging

01:39:22 things going on,

01:39:24 which give me some

01:39:26 confidence. Increasingly,

01:39:28 if you go to a best-sellers table, you'll find

01:39:30 three or four books on science.

01:39:32 Science writing

01:39:34 in the United States has achieved a much more

01:39:36 sophisticated level.

01:39:38 You've heard the questions from science

01:39:40 journalists, and you see that

01:39:42 science journalism

01:39:44 in this country is in a very good state.

01:39:46 The problem is not with the journalists,

01:39:48 it's with the editors and publishers

01:39:50 and the limited amount of space

01:39:52 they give to science. TV.

01:39:54 A lot of good science

01:39:56 on TV, cable, public television,

01:39:58 but

01:40:00 what you see on network TV, where you

01:40:02 have the tens and tens

01:40:04 of millions of people, is the standard

01:40:06 prototype of the scientist

01:40:08 as nerd, as white

01:40:10 coated with thick glasses, scoping

01:40:12 a cat and saying, tomorrow we destroy the world.

01:40:14 Laughter

01:40:16 Laughter

01:40:18 Science

01:40:20 societies have been sensitive to these

01:40:22 issues, in particular, especially

01:40:24 the biomedical community, but all the others,

01:40:26 the larger societies, are putting resources

01:40:28 into telling their story.

01:40:30 But what I'm proposing is something

01:40:32 vastly more ambitious.

01:40:34 Perhaps an order-of-magnitude greater

01:40:36 effort carried out by

01:40:38 a united science technology

01:40:40 community. Now, maybe science community

01:40:42 is an oxymoron. We'll see.

01:40:44 I don't know.

01:40:46 This should be public education

01:40:48 in the best sense.

01:40:50 And while we're at it,

01:40:52 this must include the whole problem of education

01:40:54 as an integral ingredient

01:40:56 because education and science

01:40:58 are entwined.

01:41:00 And without education, science would die.

01:41:02 And science can help education,

01:41:04 which

01:41:06 all of you know

01:41:08 is in pretty bad state

01:41:10 in this nation. And it's a good

01:41:12 metaphor, it's a good example

01:41:14 of science. Science today

01:41:16 is healthy, but there are symptoms.

01:41:18 And maybe 30 years ago, or 25

01:41:20 years ago, or I don't know when,

01:41:22 education in this country was healthy.

01:41:24 But something happened.

01:41:26 And in spite of 10 years of

01:41:28 rather significant

01:41:30 attention, propaganda,

01:41:32 reports, efforts,

01:41:34 the science education and

01:41:36 education in general in this country hasn't moved

01:41:38 very much. Once the infrastructure

01:41:40 collapses, it's extremely difficult

01:41:42 to reassemble.

01:41:44 In a recent retreat, sponsored

01:41:46 by the AAAS,

01:41:48 and attended by presidents, president-elects,

01:41:50 and the executive offices

01:41:52 of probably half of the larger societies,

01:41:54 we

01:41:56 raised this issue, and

01:41:58 heard from experts on

01:42:00 television, and magazines, and newspapers,

01:42:02 advertising executives, and

01:42:04 public relations firms, telling us

01:42:06 how you do this, how do you communicate

01:42:08 with science.

01:42:10 The assembled societies,

01:42:12 after listening to all this, agreed

01:42:14 to designate

01:42:16 some sort of an ad hoc group

01:42:18 to make a plan for all the societies

01:42:20 to consider. This is a sustained,

01:42:22 coherent program.

01:42:24 A successful program would use TV,

01:42:26 hopefully primetime network TV,

01:42:28 LA science,

01:42:30 science nightline,

01:42:32 and so on. Movies,

01:42:34 op-eds, full-page ads, Sunday supplements,

01:42:36 the Reader's Digest, Parade

01:42:38 Magazine, cereal boxes, and

01:42:40 skywriting, if you know somebody.

01:42:42 We would need continuing

01:42:44 advice from the professionals, from the science

01:42:46 journalists and experts on how to

01:42:48 transmit our science to the general public.

01:42:50 What we're proposing is a

01:42:52 massive program of educating the general

01:42:54 public in matters of science, engineering,

01:42:56 and education.

01:42:58 All such ventures have risk,

01:43:00 but I believe there's a greater risk to

01:43:02 not doing anything. If national

01:43:04 goals are to determine research policy,

01:43:06 we'd better try to have a more

01:43:08 literate public. Obviously

01:43:10 when you do such things, it's done in full view

01:43:12 of science policy makers.

01:43:14 Perhaps we can achieve

01:43:16 in less time than a decade

01:43:18 a new view of the value

01:43:20 and importance of science education,

01:43:22 science and education.

01:43:24 I don't accept the notion

01:43:26 that basic and applied research,

01:43:28 plus federal contributions

01:43:30 to education, totaling perhaps

01:43:32 3% of the federal budget

01:43:34 is the correct fraction

01:43:36 that should be invested in these human resources.

01:43:38 I also believe that if we can act

01:43:40 as a community, we will

01:43:42 become more aware of the many defects

01:43:44 in our system, and perhaps

01:43:46 having that conviction

01:43:48 we'll have the will and the

01:43:50 spirit to help make

01:43:52 these changes. I want to conclude by

01:43:54 urging three courses of action

01:43:56 on this dancing with DNA

01:43:58 community. First,

01:44:00 if you're young,

01:44:02 to quote

01:44:04 Isaac Newton in the period of

01:44:06 maximum fitness for invention,

01:44:08 then ignore everything I've said

01:44:10 and stay in your laboratory. That's where you belong.

01:44:12 However, for those with a few

01:44:14 streaks of gray,

01:44:16 become

01:44:18 far more active in the public understanding

01:44:20 of science. Contact

01:44:22 your society

01:44:24 offices. Get involved

01:44:26 maybe in joining in this

01:44:28 sort of joint community

01:44:30 action.

01:44:32 Get involved

01:44:34 with science writers.

01:44:36 They're the keys, I think, to this

01:44:38 crucial goal of elevating the public

01:44:40 understanding of science, of how

01:44:42 it works, how scientists think, of the history,

01:44:44 the substance, and the societal

01:44:46 consequences of the contribution

01:44:48 of science

01:44:50 to the quality of life,

01:44:52 to survival

01:44:54 of a lonely

01:44:56 and fragile planet.

01:44:58 Tell them what science can do

01:45:00 and what science can't do.

01:45:02 It's marketing,

01:45:04 but it's also the enhancement

01:45:06 of our culture, the appreciation of the beauty

01:45:08 and diversity of nature

01:45:10 to the best extent we can.

01:45:12 I have another

01:45:14 task, and that is

01:45:16 to join in the growing number of scientists

01:45:18 who are actively involved in pre-college

01:45:20 science and math education.

01:45:22 This is a terribly difficult

01:45:24 problem. I think scientists can

01:45:26 have an enormous impact on the

01:45:28 school system if they

01:45:30 take some effort and some energy.

01:45:32 In fact, both tasks are related

01:45:34 because we'll never achieve

01:45:36 the kind of educational system

01:45:38 we need if we can't get

01:45:40 the general public, the great general public

01:45:42 on our side. We're lousy

01:45:44 in science because the public and the

01:45:46 parents don't know how

01:45:48 bad it is and too often don't care.

01:45:50 And the third task I set upon

01:45:52 you is to proceed to the nearest bar

01:45:54 and have an aperitif. Thank you very much.