00:01:57 This afternoon's program tackles the topic of the effects of recombinant DNA technology on society.

00:02:03 This DNA revolution has advanced our understanding about ourselves and the biological world at a remarkable rate.

00:02:09 And as you saw last night, it's even inspired some scientists to sing in public about it.

00:02:14 You've heard a lot about the enthusiasm about the promise of DNA technology to better our lives.

00:02:20 And you've heard about benefits already available in the form of new drugs, new tests for the diagnosis of genetic diseases,

00:02:28 plants that could help feed the world, and promises I think most exciting for preventative medicine contraception that Barry Bloom spoke about this morning.

00:02:36 This DNA technology, like any other powerful technology, has the potential to affect large numbers of people and to have effects that are both long-lived and global.

00:02:46 And like any new technology, it has the potential to produce both benefits and new unknown risks for human beings.

00:02:53 It's probably because DNA technology has such direct effects on our health that we're so personally interested in understanding its true benefits and the true risks and how to balance them.

00:03:03 This afternoon, we'll explore some difficult questions about the best way to apply recombinant DNA technology to benefit society,

00:03:10 such as how can we use DNA technology to provide medical benefits without violating our ethical principles or endangering confidentiality?

00:03:19 Can there be governmental guidance of this technology to ensure its safety without impeding potentially life-saving progress?

00:03:27 Can DNA technology be used to improve our food supply without endangering the ecosphere?

00:03:33 How can DNA technology be used in the courts and still maintain our legal principles and civil liberties?

00:03:39 Some, but although not all, questions will be raised this afternoon that don't have clear-cut answers.

00:03:45 It's clear they require a balancing act between opposing but equally justified concerns.

00:03:50 It's clear that we'll have to make some difficult choices to come up with satisfactory answers to these questions,

00:03:55 both at the individual and the public policy levels.

00:03:59 And because we'll all be affected by the results, it's critical that both scientists and the public work together

00:04:04 in the process of deciding how this technology can best be used to benefit society.

00:04:09 It's a tenet of democratic societies that good choices can be made only if people are well-informed.

00:04:15 Scientists have come to recognize more and more that it's critical that we play an active role

00:04:19 in helping the public learn the basic facts necessary to understand how science applies to their lives.

00:04:25 We realize that we need not just to spend time doing this,

00:04:29 but we also need to learn more effective ways to communicate these sometimes difficult facts and concepts.

00:04:35 It's clear, I think, from some of the previous talks, we need to learn to avoid jargon.

00:04:40 We sometimes slip into it without realizing it.

00:04:43 One of the things that locally has been quite beneficial, UCSF scientists, students,

00:04:48 and graduate students, postdocs, and scientists working with the school systems,

00:04:52 the San Francisco high school and junior high school systems,

00:04:54 have learned a lot about how to communicate by working with the teachers and the students.

00:04:59 They've really helped us learn what works and what doesn't.

00:05:03 The first two sessions of the symposium have helped provide you with some of the background

00:05:06 and the basics of DNA technology and its applications,

00:05:09 so that it can allow you to begin to deal with the ethical questions that are posed in this session

00:05:14 and in the previous sessions.

00:05:17 Now, we have four speakers this afternoon in this session.

00:05:21 Neil Holtzman will first discuss problems raised by the ability to predict

00:05:24 whether or not someone will develop a genetic disease.

00:05:29 Roger Beachy will discuss issues surrounding the development of genetically engineered agricultural products

00:05:34 and their placement in the field.

00:05:37 After break, we'll hear from Don Kennedy,

00:05:39 who will discuss the role that government plays in regulating recombinant DNA technology and its products.

00:05:44 And then Eric Lander will tell us how DNA technology can be used to trace the identity

00:05:49 of an individual person, plant, or an animal.

00:05:52 After the final question and answer session, question and answers for this session,

00:05:56 then Harold Varmus will come out and introduce Leon Letterman,

00:05:59 who will give an overview perspective of the entire symposium.

00:06:04 Now on to our speakers.

00:06:07 Victor McKusick, a well-known researcher in human genetic diseases at Johns Hopkins University,

00:06:12 lists in his book, Mendelian Inheritance of Man,

00:06:15 over 5,500 different inherited diseases, each caused by mutations

00:06:19 in one of the 100,000 or so genes that make up our chromosomes that you've heard about.

00:06:25 In addition to these so-called single gene diseases, many of which are relatively rare,

00:06:31 common disorders like heart disease, psychiatric diseases, many cancers, and many other diseases,

00:06:36 clearly have a genetic basis and many of these look like they may be caused by defects

00:06:42 in more than one gene, or the so-called multiple gene defects

00:06:45 that were referred to in the question and answer session in the last session.

00:06:50 As more and more of these genes are identified,

00:06:53 the molecular basis of each disease can be understood,

00:06:55 and we hope and expect that treatments can be devised based on this understanding.

00:07:00 However, even before we have cures, having these genes in hand immediately provides a way

00:07:04 to predict whether a person has already or will develop a particular disease.

00:07:09 What sorts of ethical concerns does this ability to predict the future of a person's health raise?

00:07:15 Our first speaker, Neil Holtzman, has considered these issues in more depth than just about anybody,

00:07:20 and has been a leader in efforts to determine how to maximize the benefits

00:07:23 and minimize the problems with being able to predict genetic diseases.

00:07:27 Neil is a professor of pediatrics at Johns Hopkins University,

00:07:30 where he's a scientist, physician, and noted teacher, and we welcome him today to our symposium.

00:07:35 Neil.

00:07:43 Thank you, Rick, I suppose.

00:07:47 You've given the beginning of my talk, so the audience will bear with me if there's some repetition.

00:07:53 Last night you heard that having a detailed map of his route across the United States

00:07:59 enabled David Botstein to find the wallet he inadvertently dropped out of an airplane east of Cheyenne.

00:08:08 The scenario may be improbable, but the point David made was not.

00:08:13 A detailed map of the human genome will enable scientists to find all of the genes, all of our genes.

00:08:23 This is the goal of the Human Genome Project, as you heard from Dr. Watson.

00:08:29 It will increase our understanding of how the body works and what goes wrong in genetic diseases.

00:08:36 At the moment, the path for applying that information to improve the outlook for those born with genetic disorders

00:08:44 is more like a maze than a map.

00:08:48 A maze like the one used in animal experiments in which hazards, shocks, are more plentiful than the reward.

00:08:55 This afternoon I will spend the first part of my talk considering what we can expect and not expect

00:09:03 from the Genome Project in improving the outlook for human diseases.

00:09:07 Then I will turn to the hazards of genetic testing to individuals and society.

00:09:13 Let me begin, and here's where the repetition comes in, by describing the two categories of disease

00:09:18 in which genes in the germline, the eggs and sperm, play a role.

00:09:23 First, diseases that occur when a single gene goes awry, as explained by Dr. Singer this morning.

00:09:29 We call them single gene or Mendelian diseases for the monk Gregor Mendel,

00:09:34 who first discovered discrete units of inheritance.

00:09:38 Second, diseases whose occurrence depends on the presence of more than one gene.

00:09:43 We call them multifactorial disorders.

00:09:47 Dr. Singer's RAS story deals with somatic cell genetic diseases,

00:09:53 you might consider cancer that way, not germline diseases,

00:09:56 and I will not discuss the somatic diseases further.

00:10:01 As you heard from Rick, there are over 5,000 human traits that can be attributed to mutations in single human genes.

00:10:08 But some of these traits simply represent normal variation.

00:10:14 This slide shows some single gene diseases for which the genes have already been identified.

00:10:20 I want to make three points about the diseases on this slide.

00:10:25 First, they include the most frequently occurring single gene diseases.

00:10:30 Cystic fibrosis affects about 1 in 2,500 white children,

00:10:35 and sickle cell anemia about 1 in 500 black children.

00:10:39 Second, the genes involved in these diseases were either discovered or well on the way to discovery

00:10:48 before the Human Genome Project officially began.

00:10:52 Third, each of these 12 diseases can be diagnosed by a laboratory test before symptoms appear, even in fetuses.

00:11:02 But for only three of them, growth hormone deficiency, hemophilia, and phenylketonuria,

00:11:08 can treatment correct or compensate for the genetic defect.

00:11:12 This pattern of being able to diagnose a disease or predict its future occurrence

00:11:18 before being able to treat its symptoms effectively,

00:11:21 will be repeated again and again as additional disease-causing genes are identified.

00:11:27 The reason is simple.

00:11:29 Once a gene is identified, it can be inserted into plasmids by recombinant DNA techniques and cloned.

00:11:36 And you've heard all that.

00:11:37 The large amounts of DNA that are manufactured in this way can then be used as a test probe

00:11:44 to determine whether a person has a disease-causing mutation in the gene.

00:11:50 Finding a safe, effective treatment, on the other hand, is much more difficult.

00:11:57 I will return to the ethical consequences of this temporal gap

00:12:01 between diagnosis or prediction on the one hand and treatment on the other in the second part of my talk.

00:12:08 Now, if the genes responsible for the most frequently occurring single-gene disorders

00:12:13 have already been discovered, what is left for the genome project?

00:12:19 Most of the single-gene traits that do cause diseases, albeit rare ones, are waiting to be identified.

00:12:26 Collectively, they affect more people than the few frequently occurring diseases

00:12:32 like cystic fibrosis and sickle cell anemia.

00:12:35 Mapping the human genome will accelerate the discovery of genes for all,

00:12:40 all of the remaining rare single-gene disorders.

00:12:45 Mapping the genome will also lead to the identification of genes

00:12:49 that predispose people to multifactorial disorders.

00:12:56 Many of these disorders occur much more frequently than any of the single-gene disorders.

00:13:03 We view the discovery of these genetic predispositions akin to the discovery of risk factors for disease,

00:13:11 such as high cholesterol or cigarette smoking.

00:13:15 If you have the risk factor, your chance of getting the disease is higher than if you don't,

00:13:21 but you can have the risk factor and never get the disease,

00:13:24 or you can get the disease even if you don't have the risk factor.

00:13:29 In contrast to high cholesterol and smoking, you can't get rid of your genetic predisposition.

00:13:36 You can lower your cholesterol by diet or drugs, and you can stop smoking,

00:13:40 but you can't exchange bad predisposing genes for good ones either now or in the foreseeable future.

00:13:48 Telling people of their genetic predispositions may prompt them to get more frequent exams

00:13:54 so the disease can be caught early, or knowing they are at increased risk,

00:13:58 people may be more willing to take steps to reduce their chance of getting the disease,

00:14:04 but we still don't know many steps that will work or how frequently people will accept them.

00:14:11 The ability to map predisposing genes to specific locations on the human genome

00:14:15 is proving far more difficult than mapping single-gene disorders.

00:14:20 One problem is that the multifactorial diseases are not discrete entities, as are many single-gene diseases.

00:14:27 The chance for mistaken diagnosis is higher.

00:14:30 Another problem is that the same gene may not play a role in all persons afflicted with a particular disorder.

00:14:38 As a result of such difficulties, reports of mapping genes for manic depressive,

00:14:43 for bipolar disorder, and schizophrenia have been retracted,

00:14:48 and an association of a specific gene with alcoholism has been disputed.

00:14:56 Despite these problems, extravagant claims have been made by reputable scientists

00:15:03 for the importance of the Human Genome Project.

00:15:06 Daniel Koshland, a leading biochemist and the editor of Science,

00:15:11 had the following to say at a genome conference in 1989.

00:15:17 Koshland argued that no group would benefit more from the project than the homeless,

00:15:24 since many of them suffer from disorders that would eventually be prevented or treated thanks to the Genome Project.

00:15:31 This suggests that, contrary to fact, that the vast majority of people who find themselves out on the street

00:15:38 have diseases like bipolar affective disorder or schizophrenia.

00:15:45 Despite the hype, the fact remains that by the time the Genome Project is finished,

00:15:51 all 100,000 human genes will be located on specific chromosomes and sequenced.

00:15:57 This has a nice egalitarian ring to it.

00:16:00 Regardless of which deleterious genes any of us carries, they'll all be identified.

00:16:06 But we have no assurance that people at risk for any genetic or gene-influenced disease

00:16:13 are equally likely to derive benefit from the discoveries,

00:16:18 or that the benefits will exceed costs and risks.

00:16:22 I will consider three problems.

00:16:24 Applied research and development, pricing, and access.

00:16:30 Funds earmarked for the Human Genome Project will not be used to elucidate the function of genes as they are identified.

00:16:40 Consequently, the potential benefit to people at risk of some diseases may be delayed or never realized.

00:16:47 I doubt we'll see the same rush for capitalizing on the discovery of genes for rare diseases as we have for cystic fibrosis.

00:16:57 It did not take long after the CF gene was found, in about August 1989,

00:17:03 before the rush was on to develop a test that could detect the 1 in 25 whites in the general population

00:17:12 who were at risk of having children with CF.

00:17:14 This is from February, six months later, 1990.

00:17:19 Companies and a few medical centers are already selling such tests,

00:17:25 although they are not capable of detecting all CF carriers.

00:17:30 Seldom will knowledge of the gene for a rare disease prove lucrative enough to stimulate commercial interest.

00:17:37 One exception is the gene for growth hormone deficiency.

00:17:42 The gene for growth hormone, which causes growth hormone deficiency.

00:17:48 Growth hormone is used to treat children with the rare deficiency,

00:17:53 but it could also be used in healthy kids who are not tall enough to play basketball.

00:17:59 Professional basketball in particular.

00:18:01 This use of genetic research to enhance normal function is one ethical problem that I will not comment on further,

00:18:07 but you should think about it.

00:18:10 The next problem is pricing.

00:18:12 With patent protection, manufacturers can fix prices artificially high on genetic tests and therapies,

00:18:19 as has happened with growth hormone.

00:18:22 Originally intended to provide a reward for inventors,

00:18:26 patents may not serve the public well in the genetic arena.

00:18:31 The discovery of the genes for many diseases,

00:18:34 which is an essential step in the development of genetic tests or effective treatments,

00:18:39 is being accomplished by the investment of public funds in the Genome Project.

00:18:44 The public does not hold the patents on these genes and seldom will under existing patent law.

00:18:51 In many instances, universities hold the patents as the recipients of public grants under the Genome Project.

00:18:58 Due to changes in the patent law in 1980,

00:19:00 a university can grant an exclusive license to a company to develop a product based on the patent held by the university.

00:19:07 As a result of such a monopoly,

00:19:09 the public, who through tax revenues paid for the project in the first place,

00:19:14 could pay more than the costs justify when the product comes on the market.

00:19:20 Unless health insurers agree to reimburse for these high prices,

00:19:24 only the affluent will be able to afford the results.

00:19:29 Any reduction in price that is possible that a monopolistic manufacturer makes

00:19:37 will be to maximize profit and not to make the products available to everyone.

00:19:44 This brings me to the final one of these three problems, access.

00:19:49 Problem two is tied up with reimbursement for health care in the United States.

00:19:54 Let us return to Professor Koshland's contention about the benefit of the Genome Project to the homeless.

00:20:00 Even if he is correct,

00:20:02 how the benefit would get to the homeless under the current reimbursement scheme is puzzling at best.

00:20:10 As I will consider shortly,

00:20:12 rather than finding the fruits of the Genome Project used for their benefit,

00:20:16 those alleged to have generic predispositions may find that they are used against them.

00:20:24 Given these problems, we have to ask whether $3 billion planned for the 15-year Genome Project,

00:20:30 assuming no cost or time overruns,

00:20:33 is a reasonable allocation of scarce resources.

00:20:38 Last night, Dr. Watson said we need more money for this enterprise, not less.

00:20:45 If we could harness these discoveries to serve mankind without hazard,

00:20:49 and if there were no competing needs to be satisfied, I could not disagree.

00:20:56 I also want to make clear that I'm referring only to the Human Genome Project

00:21:01 and not questioning the development of recombinant DNA technologies,

00:21:08 which, as we heard this morning, have had far-ranging and very important applications well beyond genetic diseases.

00:21:16 If it were true that non-genetic diseases were no longer significant problems,

00:21:21 we could argue with greater conviction that the investment in expanding our knowledge of the human genome was justifiable.

00:21:27 In recent years, however, the greatest increase in age-adjusted deaths among Americans has been AIDS,

00:21:34 the 11th leading cause, and infections in the bloodstream, now the 14th most frequent cause.

00:21:40 Deaths from homicide and legal intervention have also increased and are now the 10th leading cause of death.

00:21:47 The recrudescence of tuberculosis, the emergence of other infectious diseases as public health problems,

00:21:52 such as Lyme disease and toxic shock syndromes,

00:21:55 and the pernicious problem of antibiotic resistance, as has been described by Dr. Cohen and Dr. Bloom,

00:22:02 indicates that we have not licked infectious diseases.

00:22:06 As we heard from Dr. Bloom, infectious disease looms large in the third world,

00:22:11 but when fewer, as he told us, than 10% of children in Houston have been immunized, it is still a problem here.

00:22:21 We come, finally, to the potential misuse of genetic tests.

00:22:26 Toward the beginning of the talk, I indicated that tests to diagnose diseases or predict their future occurrence

00:22:32 will be available long before effective treatments.

00:22:36 What happens in this gap between detection and treatment?

00:22:41 Let us answer this first for tests that are intended to predict future disease

00:22:47 or an increased risk of disease in the person being tested.

00:22:51 Consider Huntington disease, a single gene neuropsychiatric disorder that begins insidiously at about 40 years of age

00:22:59 and follows a progressively cruel course to death in 10 years or so.

00:23:04 There is no treatment, but there is a predictive test.

00:23:09 Would a person at risk, that is someone who has a mother or father with the disease,

00:23:14 want to know that he or she will get Huntington's?

00:23:20 A positive test could be like a death sentence for some,

00:23:25 while for others it could relieve the anxiety generated by uncertainty.

00:23:30 A positive result also means that each of the person's children has a 50% chance of having the disease.

00:23:38 Because the disease is untreatable, people with Huntington disease or who have a positive test result for it

00:23:45 cannot obtain health insurance in the United States.

00:23:49 Employers who know a person is at risk are unlikely to employ that person,

00:23:54 partly because care will raise the cost of the employer's health benefits.

00:24:00 A person with a negative result, on the other hand, may now be able to get health insurance

00:24:05 whereas he or she was uninsurable when the insurer knew the risk was 50%.

00:24:12 Insurance underwriters call this fair discrimination.

00:24:18 A person who has a greater chance of getting sick or of dying soon, they say,

00:24:23 has to pay more for protection.

00:24:26 There may be some merit to this for life insurance,

00:24:29 but if we are all entitled to health care, it is hardly fair for medical insurance.

00:24:35 For Huntington disease and many other conditions for which tests will be available,

00:24:40 the person with a positive result will be denied insurance

00:24:44 or have the disease for which he or she will incur the greatest cost excluded from coverage.

00:24:52 This problem is not unique to genetics.

00:24:57 Health insurers, for many years, refused to insure people

00:25:01 because the occupations in which they work increased the risk of disease.

00:25:10 Getting group insurance is progressively harder, as this story talks about,

00:25:15 for those who are or have been sick.

00:25:19 Now, 60 years ago, when Blue Cross started,

00:25:23 private insurance provided broad coverage to many people

00:25:28 because their individual risks could not be predicted.

00:25:32 Almost everyone could be charged the same amount for health insurance.

00:25:36 As it became increasingly possible to distinguish risks,

00:25:39 some by predictive tests, others by epidemiological information

00:25:43 about the hazards of different industries,

00:25:46 private insurance became affordable for fewer and fewer people.

00:25:51 That is what we see today, and we need something better.

00:25:56 Let me now turn to the gap between detection and treatment

00:26:00 for tests that are used to predict untreatable disease,

00:26:04 not in the person being tested, but in unborn children by prenatal diagnosis.

00:26:11 Although couples may elect to continue the pregnancy

00:26:14 when the fetus is found to be affected,

00:26:17 I think it's fair to say that the technologies for prenatal diagnosis

00:26:20 would not have been and continue to be developed

00:26:23 if the alternative option of abortion was illegal.

00:26:28 Under the Supreme Court's decision in Roe v. Wade, which still stands,

00:26:33 the mother has the right to decide whether she wants

00:26:36 to terminate the pregnancy for any condition prenatally diagnosed

00:26:40 by about the 24th week.

00:26:43 One concern is that couples will use prenatal diagnosis

00:26:48 and choose abortion for disorders that do not appear until late in life,

00:26:52 are not very severe, or for which the prenatal diagnosis

00:26:55 cannot be made with certainty, and as a result of the proliferation of tests

00:27:00 as the genome is mapped, there will be more and more disorders

00:27:03 in those categories.

00:27:06 In our culture, women's acceptance of prenatal diagnosis and abortion

00:27:11 from some of our studies and the work of others

00:27:14 correlates with the severity of disease and the certainty of prenatal diagnosis.

00:27:19 Prenatal diagnosis, for instance, to select the sex of one's fetus,

00:27:23 not in situations dealing with X-linked disease, is seldom requested.

00:27:29 Some scientists and others believe that women should not have

00:27:34 this right to bring children with disabilities into the world

00:27:38 if that's what they choose to do.

00:27:40 The reasons they give are either because their life will be too miserable

00:27:43 to be worth living, a contention that is disputed by many people with disabilities,

00:27:49 or because the support of care for such people is too costly.

00:27:54 Although it seems unlikely that abortion for severe genetic defects

00:27:59 could be mandated in today's climate, a woman's right to choose freely

00:28:05 could be eroded if insurance companies refuse to pay for the care of infants

00:28:10 with diseases that could have been detected prenatally,

00:28:13 or if public programs to assist parents in caring for children with disabilities

00:28:18 are dismantled.

00:28:20 In addition, if research to find treatments for such disorders is not supported,

00:28:25 prenatal diagnosis and abortion as an interim solution until treatments are found

00:28:31 could become the final solution.

00:28:36 In conclusion, the Genome Project has been accompanied by a resurgence of interest in genetics.

00:28:43 This is evidenced by the headlines that illustrate this talk.

00:28:49 No doubt the project will greatly improve our understanding of how the human organism functions,

00:28:54 but the project and the hype surrounding it may lead to exaggerated expectations

00:28:59 that could undermine our social values.

00:29:03 I've already mentioned the portrayal of homelessness and alcoholism as genetic problems,

00:29:09 and now I'm going to talk briefly about something that apparently a number of people in the audience,

00:29:14 you people, had raised this morning.

00:29:21 Here is a front page New York Times report of Department of Justice data

00:29:27 claiming a family link to criminality.

00:29:31 Although the article pointed out that the link need not be genetic,

00:29:35 according to a more recent story in the Times,

00:29:38 scientists working in the government are developing, and I quote,

00:29:42 a violence initiative which, among other goals,

00:29:47 would seek to find biological correlates of violence in males,

00:29:52 detecting them early in life and seeking to prevent their expression, end quote.

00:29:58 Do we really believe that if there were genetic predispositions to homelessness,

00:30:02 alcoholism, or criminal behavior, and companies marketed tests to detect them,

00:30:08 that we could eradicate the problems?

00:30:11 By looking for genetic solutions, we are coming dangerously close to the eugenics

00:30:16 of the early 20th century in this country and elsewhere.

00:30:21 The emphasis on genetic causes is victim blaming of the worst sort.

00:30:26 It absolves the rest of us of social responsibility.

00:30:31 The Human Genome Project will provide a map for progress

00:30:34 and also introduce a maze of problems.

00:30:38 How the project is conducted, who will profit from it,

00:30:41 what might be foregone as a result of the public investment,

00:30:45 and how individuals in society could suffer are some of the questions I've addressed.

00:30:51 We are fortunate to have the opportunity to consider these questions

00:30:54 at a relatively early stage in the quest for the complete genome.

00:30:58 We should not take this task lightly.

00:31:02 Thank you.

00:31:12 Neil will answer questions from the panel of journalists.

00:31:15 Marilyn, if you'd start, please.

00:31:17 Dr. Holtzman, I'd like to start off by asking you to comment.

00:31:20 This picks up some of your remarks about cystic fibrosis screening.

00:31:27 The Federal Office of Technology Assessment released a report last month

00:31:32 that contained results of a survey of insurers,

00:31:36 and they disclosed that although few of the insurers expected

00:31:40 to require genetic screening in the next five to ten years,

00:31:44 most of those responding to the survey said they felt it was fair

00:31:49 for insurers to use genetic tests in evaluating health risks of applicants.

00:31:54 They also felt they should have the option of determining how to use such information,

00:32:00 and moreover stated that they felt genetic information was no different

00:32:04 from other kinds of information to be used in calculating a person's insurability.

00:32:09 Can you comment on this?

00:32:11 Who was surveyed in this study?

00:32:13 The Federal Office of Technology Assessment surveyed insurers.

00:32:16 Who did they survey?

00:32:17 Insurers.

00:32:18 Well, I think that's pretty clear from what I said,

00:32:22 that insurers, private companies, need a test.

00:32:26 And it goes a little beyond what I explained.

00:32:29 Because if a person knows that he or she is going to develop a disease,

00:32:34 one of the tendencies that many of us would have might be to go out and buy insurance.

00:32:38 And if the insurance company did not know that we were at increased risk,

00:32:42 they would sell us that insurance at the standard premium.

00:32:45 If many of us who are at increased risk did that,

00:32:48 the whole actuarial basis of insurance, at least life insurance, would be thrown off,

00:32:52 and the insurance company would lose money.

00:32:55 Their profits would not be as great.

00:32:57 So that once it becomes possible for people to know more about their risks,

00:33:01 the insurance companies have to know it as well.

00:33:04 It's called adverse selection.

00:33:07 Pending the establishment of national health, how do we balance privacy...

00:33:11 I'm sorry, I can't question.

00:33:12 I'm sorry.

00:33:13 How do we balance privacy, civil rights, and progressive programs of diagnosis and prevention

00:33:19 barring establishment or pending establishment of a system of national health?

00:33:25 Well, I don't think we do.

00:33:28 At least in terms of access and in terms of genetic discrimination.

00:33:34 Nevertheless, I think it's clear to say that a universal health insurance

00:33:39 where everybody has access to care is not going to resolve a number of the problems that I've talked about.

00:33:46 It could be equally as possible for a government, perhaps even more so,

00:33:51 who is interested in reducing costs to want to know about the genotype of individuals

00:33:59 and to put certain restrictions on those individuals,

00:34:03 even going to the extreme of requiring prenatal diagnosis

00:34:07 or, as there are still laws in the book and books in a number of states,

00:34:11 of requiring sterilization for people who may be at risk.

00:34:13 Those laws that came out of the eugenics movement in this country in the early part of this century

00:34:19 are still on the books in a number of states.

00:34:23 So I think one has to be wary that while universal health insurance and national health insurance

00:34:28 might solve the problem of access, that we have to be extremely careful still

00:34:33 about problems of privacy and confidentiality

00:34:36 and of deciding how we want to use the results of genetic tests.

00:34:42 Just to follow that up, do you have a mechanism in mind,

00:34:47 an organization, a governmental body, an ombudsman who should be addressing these issues?

00:34:51 How should they be tackled?

00:34:53 The concern that you raise is obvious, but the mechanism by which to address it is not quite clear.

00:34:59 Well, there are a number of mechanisms.

00:35:05 I did not mention in a direct sense that there is a small portion of genome project funds

00:35:13 that are set aside for considering ethical, legal, and social issues.

00:35:18 And at the moment there is a committee of that group that is looking into the problems of insurance.

00:35:26 Now Congress, or at least one of the committees in the House,

00:35:31 is becoming rather arrestive about whether there will ever be recommendations

00:35:37 that come out from this particular means

00:35:42 and has called for an independent commission to look into questions of privacy

00:35:47 and consequently genetic discrimination.

00:35:50 There is a committee of the Institute of Medicine

00:35:53 that has been supported by the ELSI program that does not have the restraints

00:35:57 that, say, a committee that directly operates under NIH may have,

00:36:00 and this committee may come out with some recommendations.

00:36:03 As I indicate, there is already considerable interest in Congress,

00:36:06 and one privacy bill was introduced last year.

00:36:11 It did not go anyplace, but I expect that if the problem materializes

00:36:18 or in anticipation of it, that we may see more activity.

00:36:26 I just wanted to follow up with a point that Marilyn brought up.

00:36:30 There is another survey that's just coming out this week by Lewis Harris of just average Americans

00:36:36 who also surprisingly agree that others should have the right to know genetic information

00:36:43 from an individual, including insurers and employers.

00:36:48 I'm wondering if there isn't some idea that once something is known,

00:36:53 that the information, once it's tested and once the answer is found,

00:36:58 that that somehow puts it into a new category.

00:37:01 There's something known, whereas if something wasn't already known,

00:37:05 we wouldn't be grappling with this issue.

00:37:08 I'm just concerned that once we go ahead with the testing,

00:37:11 that therefore it should be made available,

00:37:13 and that a lot of people actually agree that if something's known,

00:37:16 you shouldn't be allowed to conceal it.

00:37:19 Well, let me answer the question on two levels.

00:37:23 First, the matter of insurance companies, government agencies,

00:37:28 organizations unrelated to the person having access to that kind of information.

00:37:33 I would argue here that genetic information is not much different than a lot of other information

00:37:39 that is usually inadvertently and unknown to each of us released to a variety of organizations.

00:37:49 Our medical records, though we might like to think they're confidential,

00:37:52 really have many ways in which information on them can be released to a variety of organizations.

00:38:00 There are ways through your driver's license,

00:38:03 and many states require a social security number on the driver's license.

00:38:08 Social security numbers are used widely by a large number of organizations,

00:38:14 and access to social security numbers and your identity through your driver's license is possible.

00:38:21 Once people get that, they have access to a wide range of information about you that is non-genetic

00:38:27 and can make marketing decisions, can pitch things directly to what they learn

00:38:31 or your particular needs, your likes and dislikes.

00:38:35 So in that area, I think genetic information may exacerbate a problem

00:38:40 that is becoming very acute in this society,

00:38:43 and that is that many organizations are having access to information about us that we don't know

00:38:48 and in many cases don't want them to have.

00:38:51 Now, on the matter of families, I mean, there genetics becomes more unique

00:38:59 in that the information that I am a carrier for a disease says something about the increased chance

00:39:07 that my brothers or sisters might be carriers or might be affected with a disease.

00:39:12 And there is a real serious ethical debate that is not easily answered

00:39:17 about whether that information should be made available.

00:39:19 Now, I think we have very little empiric information here,

00:39:22 and I think we're going to find that in many instances, particularly as people understand genetic disease,

00:39:27 that this is nothing they had control over and that it should not be stigmatizing,

00:39:31 that most people will be willing to share that information with relatives.

00:39:37 If they do not, the question then comes up is what responsibility does the physician

00:39:42 who administers the test have to share that information?

00:39:47 And the President's Commission on Ethical Issues in Medicine in the early 1980s

00:39:53 examined that quite closely and laid out some fairly stringent criteria

00:39:58 that this really was life-threatening or life-saving information,

00:40:03 and only in such extreme cases should physicians share that information with relatives

00:40:10 if the person tested did not want that information given.

00:40:15 Time for one more.

00:40:17 All of this discussion seems to be sort of going around the question of a technological imperative

00:40:23 in the sense of if you can get information, then if you have the ability to obtain it,

00:40:28 then it will be obtained, and then the question is who can know it and what will come of it.

00:40:32 And while society is debating the ethics of this, the technology marches on,

00:40:38 and I wonder if there's any, what you think of the issue of whether there are points

00:40:43 at which maybe one should put the brakes on until the ethical questions are resolved

00:40:48 and how one does that or who does that.

00:40:50 Well, I guess I wasn't too clear, but I was suggesting that as we march down the genome project

00:40:57 that I think we need, and Mr. Hall raised this question about what policies might be developed

00:41:04 and how they'd be developed, but I think we do need to develop those policies

00:41:08 before we go much further along down that pathway.

00:41:26 I warned you that the questions wouldn't be easy.

00:41:29 This morning Jerry Fink told us about some ways DNA technology is being used to produce plants

00:41:34 with resistance to disease in insects and with better growth characteristics.

00:41:39 What sorts of issues arise when we begin to manipulate plant crops by recombinant DNA technology

00:41:43 and introduce these crops into the field?

00:41:46 How do we reap the benefits of improved plants and still maintain an ecological balance?

00:41:50 Our second speaker this afternoon, Roger Beachy, will tackle some of the concerns

00:41:55 about applications of recombinant DNA technology to agriculture.

00:41:59 Roger's a professor and head of the Division of Plant Biology

00:42:02 at the Scripps Research Institute in La Jolla, California.

00:42:05 His technique for producing tomato plants resistant to a particular viral disease

00:42:09 has been used by other researchers to produce many types of plants with resistance to a variety of viruses.

00:42:14 Roger.

00:42:22 Thank you.

00:42:24 I'm here, as Rick said, I'm here to give the talk that Jerry Fink earlier said he wanted to deliver,

00:42:30 and I'd like to thank him for leaving it to me because I don't know what I'd talk about

00:42:33 if I didn't have my own talk.

00:42:35 The topic that Harold asked me to deliver today was really cause for reflection on a few issues.

00:42:43 I'll avoid the strict scientific presentation in favor of a general discussion of the needs of agriculture

00:42:49 for biotechnology, a few examples of success stories,

00:42:53 and then a brief discussion about how we can assure the safety of the consumer

00:42:57 as well as the ecology of our environment.

00:43:00 I'll say at the outset that I am grateful to the colleagues at both private and public institutions

00:43:05 for much of the content of my lecture.

00:43:07 Truly, the science is a result of not only basic research,

00:43:10 much of which you have heard about this morning and yesterday,

00:43:13 but also a product of research interactions.

00:43:16 As you have heard said many times throughout this short symposium,

00:43:21 we're talking about interactions that are truly productive.

00:43:25 If we hope to apply our laboratory science outside.

00:43:30 I want to talk about transgenic plants and whether they are really super plants

00:43:34 or if they're monsters.

00:43:35 We've all seen the movie titles,

00:43:38 and the unfortunate part is that some of our colleagues

00:43:41 serve as intellectual resources for some of those movies.

00:43:46 But focus indeed on some of the assumptions that we do need to take about the future

00:43:54 and why biotechnology can play an important role in meeting some of the needs.

00:44:02 It's been well documented, at least the projections are,

00:44:05 that the world population will in fact double, reach the 10 million by the year 2030.

00:44:10 Many of us in our research initiatives talk about the 2030 or 2040 prediction

00:44:17 and the problems that we will face in terms of how much food will be required.

00:44:21 This will demand that food resources double

00:44:25 and that dietary intake be upgraded in both quality and quantity of the intake.

00:44:32 And the third factor that is absolutely with us

00:44:35 is that society is going to become increasingly environmentally sensitive

00:44:39 to the issues that agriculture presents.

00:44:42 With that in mind, the biotechnologist has to address

00:44:45 not only the mandate for new science in his research,

00:44:50 but also to begin to look for ways to apply biotechnology

00:44:54 to the applications of food production.

00:44:58 What it means is that we're going to need worldwide productivity increased

00:45:01 by quite dramatic amounts by the year 2030.

00:45:05 We all know of the famines that are in Somalia and this year, at least, described.

00:45:12 Less well-reported are the famines also that are in Zimbabwe

00:45:19 and other parts of the areas of Africa just below the tropical zone.

00:45:26 So farmers need to produce a lot more calories.

00:45:28 The basic need in many developing countries is in fact

00:45:32 not simply concerned for quality of food, but quantity.

00:45:35 Calories are simply missing in many of the countries where need is the greatest.

00:45:42 This is not new to us as humankind and societies.

00:45:47 Rather, it's been with us a long time.

00:45:49 I think the mandate that we face is that these applications of new technologies

00:45:55 be in fact developed not only for the tropical regions,

00:46:00 the temperate regions of the agricultural world,

00:46:03 but the tropical regions as well.

00:46:06 The key technologies that have served for very many years in agriculture

00:46:10 are those that are listed here on the slide.

00:46:13 Plant breeding has played a tremendous role in improving and increasing food production.

00:46:21 One can't say enough about the efforts.

00:46:25 If you look at the increase in corn, for example, over the last 40 years

00:46:30 after the advent of hybrid corn seed production,

00:46:34 you see that the yields have been startling.

00:46:38 The use of agricultural chemicals have increased quite dramatically over the years.

00:46:43 They have also played an important role in our maintaining a relatively level cost of goods

00:46:49 or cost of food that we've had.

00:46:51 There's a question now that we all raise of the question of efficacy

00:46:56 versus environmental impact that now needs to be faced, now more than ever.

00:47:01 The growing use of biological control for pests and pathogens

00:47:06 is gaining increasing awareness amongst not only the farmers,

00:47:12 but also among the consuming public as well.

00:47:16 One way to address all of those issues is, of course, good farm management.

00:47:22 Farmers are as concerned about this issue as all of you in the audience are.

00:47:28 What role then is there left to be played?

00:47:32 Clearly there's a role for biotechnology, as you heard discussed by other speakers during this symposium.

00:47:38 The possibilities of doing things with agricultural biotechnology or plant biotechnology

00:47:43 that you couldn't do by plant breeding or agrochemical discovery

00:47:48 certainly has not escaped the laboratory door.

00:47:52 People address issues not only because they're scientifically interesting,

00:47:55 but in order to solve problems that have applied implications as well.

00:48:00 When biotechnology came to the fore a few years ago,

00:48:04 you read, as well as I did, either in the Wall Street Journal

00:48:08 or in other investor-related publications,

00:48:14 that the biotech industry was going to work to deliver new crops

00:48:18 and new plant species or new plant varieties that are better.

00:48:22 They didn't tell us what better was because, in fact,

00:48:25 the biotech industry didn't know what better was.

00:48:27 They only knew they could do things.

00:48:29 You heard earlier the discussion of we know what DNA sequences are.

00:48:33 We know what protein amino acid sequences are derived from those sequences of nucleotides.

00:48:39 We don't know the biology related to the expression of those proteins.

00:48:43 That's the same situation that the plant scientist found himself in over the last 10 years.

00:48:50 The target of plant biotechnology is, of course,

00:48:55 to deliver genes into preferred cultivars

00:49:00 without changing the advantageous qualities of the crop that you're dealing with.

00:49:06 Jerry told you about the vagaries of wide species crosses or wide varietal crosses,

00:49:13 which introduce not only the good genes or good traits in a cross,

00:49:18 but also those that are not so good.

00:49:20 Plant biotechnology has a characteristic of being much more accurate in that sense.

00:49:25 That is, you start with a plant variety that you prefer

00:49:28 because of its size, its shape, its color, its fragrance,

00:49:31 and introduce a single gene that you want to have a dominant phenotype

00:49:35 or dominant effect on the plant.

00:49:38 So the specificity of the technology is a large measure of its assets.

00:49:46 The technology is straightforward.

00:49:48 It's a matter of introducing a gene into a single cell

00:49:51 and regenerating that cell into an aggregate of cells

00:49:56 from which we'll develop a shoot, if you're lucky, with leaves,

00:50:01 and then eventually with roots.

00:50:03 Those roots will then make that plant self-sufficient in the soil.

00:50:06 It grows nicely then outside of a growth box.

00:50:10 It can grow in a greenhouse as well as it can in a growth box.

00:50:14 This technology has been widely applied in a large number of crop species,

00:50:18 and this list keeps growing almost monthly.

00:50:23 We see descriptions of new crops come along all the time.

00:50:27 I saw a preprint of one on fescue grass, another on turf grass.

00:50:32 This list will continue to enlarge as scientists continue their laboratory efforts.

00:50:38 What you see in yellow are those crops where the greatest amount of effort

00:50:42 is being placed towards commercialization.

00:50:44 You see it in the case of soybeans and cotton and canola.

00:50:47 This is the source of rapeseed oil that is a good cooking oil.

00:50:52 Maize or corn, tomatoes, and potatoes.

00:50:55 Not to say that lettuce, peas, carrots, cabbage, celery, etc. are not important.

00:50:59 They are simply not the focus of most of the basic research.

00:51:03 The first commercializable products of plant biotechnology

00:51:06 are likely to be cotton, a fiber crop,

00:51:09 and perhaps some of the vegetable crops, including tomatoes,

00:51:13 and perhaps melons and cucumbers.

00:51:17 The plant traits that have been introduced into plants by genetic transformation

00:51:21 include a number.

00:51:23 It's important to recognize that not all the problems are solved.

00:51:26 There are examples in each of these categories that I want to tell you about

00:51:30 and let you know where the state of the art is.

00:51:33 There is resistance to disease caused by some but not all viruses,

00:51:37 to some but not all fungi,

00:51:39 and I think bacterial disease has been now protected by plant genetic transformation.

00:51:46 There is resistance to attack by some insects, not all, but some, a very limited few.

00:51:51 There is tolerance to environmentally friendly herbicides,

00:51:54 those herbicides that have less chemical impact on the environment,

00:51:57 on the soil flora, and other organisms than plants.

00:52:01 And there are examples of improved quality traits.

00:52:04 You'll see a little bit more of the delayed softening

00:52:07 during ripening of tomato fruit,

00:52:09 the application of that to crop plants such as papaya,

00:52:14 at least from my perspective, would be excellent.

00:52:16 I'm a papaya lover, and when I go to a market

00:52:19 and find only soft, mushy ones that are overly ripe rather than perfectly ripe,

00:52:23 it makes me not want to buy a papaya that day.

00:52:26 There are modified starches and modified oils.

00:52:28 These are examples of things that have happened.

00:52:31 Let me tell you a little bit about why the technology is needed,

00:52:34 then some examples.

00:52:36 What you know about plant breeding is that it's done a marvelous job

00:52:39 in delivering crop plants that are able to withstand

00:52:43 biotic stresses in their environment.

00:52:45 Also some abiotic stresses.

00:52:47 There are varieties of tomatoes that have been developed in Egypt, for example,

00:52:51 that do very well under saline conditions or salty soils.

00:52:56 There are other examples where diseases are not prevalent on some kinds of crops

00:53:01 because of disease resistance genes that have been incorporated.

00:53:04 I should remind you that most plants are resistant

00:53:08 to most of the organisms in the environment,

00:53:10 but there are cases of parasitism where there are simply not examples

00:53:15 of genes in relatives of a crop plant

00:53:20 that can be incorporated into that preferred crop plant.

00:53:24 Three examples are shown here.

00:53:26 The first is a slide that I received from

00:53:29 the International Rice Research Institute in Manila,

00:53:33 and that is a disease called rice-tungro disease.

00:53:36 It's responsible for reducing rice yields in the southeast part of Asia

00:53:41 as well as the Indian and Burmese area of Middle Asia

00:53:47 by as much as 80%.

00:53:50 Those are areas of the world that can't afford that kind of loss in crop yield.

00:53:54 There are no disease resistance markers known for rice-tungro disease.

00:53:59 There are examples of tomato crops both in Mexico and in Asia

00:54:04 which simply don't bear fruit

00:54:07 because of a new class of virus diseases

00:54:10 which have developed over the last 50 years,

00:54:13 perhaps because of our agricultural practices

00:54:16 or perhaps because of the movement of viruses

00:54:19 from native plants into cultivated plants,

00:54:21 but they simply have no way to control these diseases

00:54:24 by classical plant breeding.

00:54:27 In the developing countries,

00:54:29 we anticipate that the need for such technologies will be quite enormous.

00:54:34 This is a picture from a colleague of mine at Scripps.

00:54:39 He gave me his name is Claude Fouquet,

00:54:41 and Claude worked in the Ivory Coast for many years with cassava.

00:54:45 What you see is a very sick cassava plant,

00:54:48 one that's been invaded by a virus disease

00:54:50 called African cassava mosaic virus.

00:54:53 This disease is also not controllable by standard technologies

00:54:57 and standard plant breeding.

00:54:59 This is what a cassava plant should look like.

00:55:01 If you know cassava, it grows at large roots,

00:55:04 sometimes weighing as much as 1 to 2 kilos.

00:55:07 That's a lot of starch and a lot of calories

00:55:09 for those who would normally eat them,

00:55:11 but in fact, less than 10% of the cassava

00:55:14 grown in all the African continent is free of the virus disease.

00:55:18 So plant breeders at the International Institute in Nigeria

00:55:23 and other regional laboratories are trying to solve problems

00:55:26 by classical approaches in plant breeding.

00:55:28 The question is, does biotechnology play a likely role

00:55:33 in diseases like this one?

00:55:36 An important part of disease control, of course,

00:55:40 relates to how viruses are spread,

00:55:43 and many viruses are spread by white flies.

00:55:45 We've seen the infestation of the Imperial Valley of California

00:55:48 by white flies in the last year or two.

00:55:52 Their ingress into Florida and into Texas has also been noted.

00:55:58 These flies are responsible for carrying

00:56:01 a large number of plant diseases, including many viruses.

00:56:06 If we can develop...

00:56:08 Many of the adverse effects of the infestation

00:56:10 are not due to the white fly only,

00:56:12 but by the virus disease that they carry.

00:56:16 Much of the impact of disease resistance

00:56:19 should be, in fact, to reduce the need for chemical sprays

00:56:22 to control insects like the white fly, like the aphid, like the leafhopper.

00:56:27 There are upsides of the technology

00:56:30 that are inherent in delivery of disease resistance

00:56:34 that also should be noted.

00:56:36 If our goal is to develop disease-resistant crops,

00:56:39 one of the benefits will be that it should reduce

00:56:42 the need of the farmer on chemicals

00:56:45 that would normally be used to control the vectors

00:56:48 of those diseases, the white flies and the aphids.

00:56:52 I want to tell you about a disease-resistant strategy

00:56:55 that we developed as an example of what's being done in the field.

00:56:59 It's only one of two or three strategies

00:57:02 that in the last several years have been applied

00:57:04 for the control of plant virus diseases.

00:57:06 It applies something called pathogen-derived resistance,

00:57:09 a term that was coined in the early 1980s.

00:57:14 In fact, the strategy that we adopted

00:57:17 was the result of basic work that was done

00:57:19 at a number of fundamental laboratories

00:57:22 in the U.S. and in Europe

00:57:24 on the disease-resistant reactions

00:57:27 and on how to cross-protect plants.

00:57:29 The strategy that we employed is relatively straightforward,

00:57:32 and that is we created transgenic plants

00:57:37 that contained genes that were derived

00:57:41 from the plant pathogen itself.

00:57:43 Now, by cutting the virus up into small pieces, of course,

00:57:46 we destroy its pathogenicity,

00:57:48 and we look only at the role of a single gene product.

00:57:52 Plant virus is a little bit of a scientific lesson here,

00:57:55 and I promise not to bore you with too many details,

00:57:58 is that plant viruses are relatively simple in nature.

00:58:02 They contain, in these cases, they encode only three proteins,

00:58:06 and one of the major proteins that the virus encodes

00:58:11 during its infection or disease cycle is the capsid protein.

00:58:15 It's a protein that wraps around the genetic information

00:58:18 to give a structural stability,

00:58:20 to protect it from the insect gut

00:58:22 as it's transmitted from one plant to the next, etc.

00:58:26 So we derived the genetic information

00:58:30 of the gene for the capsid protein or coat protein from the virus,

00:58:35 attached it to these regulatory elements

00:58:37 that you heard discussed yesterday,

00:58:39 promoters, these are the sequences that turn the gene on or off

00:58:42 or tell it where to be expressed,

00:58:44 a terminator sequence as well.

00:58:46 Now, you recognize, of course, that with the choice of a promoter,

00:58:50 you say, well, do I want this turned on in the leaf,

00:58:52 or do I want the gene only in the root,

00:58:54 or do I want it only in certain cells in the leaf,

00:58:56 or do I want it in all cell types?

00:58:58 So you have the capacity to design

00:59:00 the expression pattern of that gene

00:59:02 in the genetically transformed plant as well.

00:59:05 Then simply introduce that gene

00:59:07 by the standard conjugation methodologies

00:59:09 into a biological vector that Jerry talked about this morning,

00:59:13 agrobacterium-related plasmids,

00:59:18 and then using this simple transformation system

00:59:21 and regeneration system,

00:59:23 using the totipotency characteristic of the plant cells,

00:59:26 regenerate whole plants.

00:59:27 Now, you recognize that every cell in that plant

00:59:30 will contain the implanted gene,

00:59:33 and depending upon the promoter or regulator that you use,

00:59:36 that gene will be expressed in specific or all cell types.

00:59:40 The phenotype of disease resistance

00:59:42 was shown in tomatoes is relatively dramatic,

00:59:46 at least from my eyes,

00:59:48 and that is that those tomato plants

00:59:51 that carry the gene for that virus

00:59:53 are resistant to infection,

00:59:55 whereas those plants that did not carry

00:59:57 that implanted gene were susceptible.

01:00:00 And this has been termed

01:00:02 capsid protein-mediated resistance,

01:00:04 so we derived resistance by expression

01:00:06 of the capsid protein gene,

01:00:08 and it has since been used to develop resistance

01:00:12 in a wide variety of crops

01:00:13 against a variety of different virus diseases.

01:00:17 In this case, work done at Monsanto Company

01:00:20 introduced two different virus resistance genes

01:00:23 from viruses that belong to two different groups,

01:00:27 and they planted those in the field,

01:00:29 and the results are evident.

01:00:31 That is, those tubers on your left

01:00:34 were derived from plants that were not resistant,

01:00:36 and those on the right were resistant.

01:00:39 An important part about this experiment

01:00:41 is that, as you know,

01:00:43 potatoes are propagated or planted the next year

01:00:46 as pieces of seed potatoes,

01:00:48 and if those potatoes are infected,

01:00:50 then the next generation or the next plant

01:00:52 will also be infected.

01:00:54 The virus is not present

01:00:55 either in the leaves of this plant

01:00:57 nor in the roots,

01:00:58 which meant that the progeny

01:01:00 went on to the next,

01:01:01 were present in the next generation.

01:01:03 How does this virus do its thing?

01:01:06 The translation of virus particles

01:01:09 is relatively,

01:01:11 or the infection and replication of viruses

01:01:14 is reasonably well known for some pathogens.

01:01:17 What we've discovered is that

01:01:20 the protein that's found in the cell

01:01:23 as a cellular protein

01:01:25 recapsidates or blocks the uncoating of the virus

01:01:28 as it enters the cell.

01:01:29 Therefore, there's no translation

01:01:31 of the genetic information,

01:01:33 and therefore, no replication.

01:01:35 This model of what resistance is like

01:01:39 or what its resistance is caused by

01:01:41 is developed out of a series of basic research experiments

01:01:44 that are done in the laboratory.

01:01:46 We're excited about the application

01:01:48 and use of this technology.

01:01:50 There are lots of insects, however,

01:01:52 that are not carrying viruses

01:01:54 that cause very severe diseases.

01:01:56 Beetles, larvae of a variety of insects.

01:02:01 This is the larvae of the cotton bull worm,

01:02:04 which is a major problem.

01:02:06 Insects such as the Colorado potato beetle

01:02:10 or the insects that have larval forms

01:02:14 in the leopard-opterus category

01:02:16 have been controlled for a number of years

01:02:18 or at least attempts have been made

01:02:20 to control these insects by a variety of agrochemicals.

01:02:23 There is, however, a biologically-based material.

01:02:29 The names of some of which you see here,

01:02:31 Dipel is one, Thuracide is another.

01:02:35 These are products derived from a bacillus,

01:02:38 a soil bacteria,

01:02:41 which produces in a normal metabolic pathway

01:02:44 its own growth and development.

01:02:46 It develops a protein that's called the BT

01:02:49 or bacillus thuringiensis endotoxin.

01:02:51 Applying that to the leaves of the plant

01:02:53 can control the insects.

01:02:55 The trouble with that is that these molecules

01:02:58 are sensitive to UV inactivation, the sunlight.

01:03:01 Transgenic plants have been developed

01:03:03 to carry that gene or a portion of it.

01:03:06 The plants that contain that protein

01:03:09 are resistant to a specific larvae

01:03:13 of specific leopard-opterus insects.

01:03:15 For example, this is a tomato hornworm on tomatoes.

01:03:18 Obviously, the plant on your left is a transgenic.

01:03:21 This has been applied also in field trials.

01:03:25 It's very effective to control these larvae

01:03:27 under field conditions.

01:03:29 In the last several years,

01:03:31 these have been in the advanced stages of evaluation.

01:03:35 More recently and even more exciting

01:03:37 for the farmers in the Midwest

01:03:38 is how do you control the European corn borer,

01:03:41 that insect that decreases the yield of corn plants

01:03:45 by destroying the core of the maize plant

01:03:50 and making it fall over or lodging,

01:03:54 as the farmers would call it.

01:03:56 Whereas those plants that are genetically transformed

01:03:59 to express that gene are able to eliminate

01:04:04 or decrease the damage by the larvae.

01:04:09 The cotton bullworm is the pest

01:04:12 that has been most studied in the last several years

01:04:15 as biotechnology has developed cotton plants

01:04:18 that carry the gene for one of these

01:04:22 Bacillus thuringiensis endotoxins

01:04:25 to control that insect.

01:04:28 I'll remind you that as much as 40%

01:04:31 of the insecticides used in the U.S.

01:04:34 are directed toward cotton.

01:04:36 40%.

01:04:38 10% of that is to control this insect.

01:04:43 Genetic transformation has developed

01:04:45 cotton bulls, cotton plants,

01:04:49 that are able to resist the infestation

01:04:52 by that insect.

01:04:54 On your right, you see a crop

01:04:57 that is non-transgenic.

01:04:59 And on the left, being examined

01:05:01 by one of the researchers from Mississippi,

01:05:03 you see that these cotton plants

01:05:05 are in fact doing very well,

01:05:07 even without any sprays.

01:05:10 The lint produced out of cotton is obvious.

01:05:12 It's obvious that the one on the left

01:05:14 is from a transgenic plant

01:05:15 and the one on the right is not.

01:05:17 The Bt, the use of the Bacillus thuringiensis gene

01:05:23 has been looked at in a variety of ways

01:05:26 and we know that there's much less insecticide

01:05:28 required to control this insect

01:05:32 if there's the presence of the Bt gene.

01:05:35 Now, the use of transgenic plants

01:05:38 to develop resistance to environmentally

01:05:41 friendly herbicides, as they're called,

01:05:43 has also been discussed quite widely.

01:05:46 There are a number of examples of this

01:05:48 and I'll only show you one.

01:05:50 This is resistance to the herbicide

01:05:52 called Roundup.

01:05:53 It's been used in fields for more than 20 years.

01:05:56 It's known as a safe herbicide.

01:05:58 Those soybeans that are standing, of course,

01:06:00 are transgenics and those little stubs

01:06:02 in the center are not, obviously,

01:06:04 resistant to the disease.

01:06:07 There are other examples of quality issues

01:06:10 that Jerry mentioned today,

01:06:12 the capacity of fruit to remain firm

01:06:14 and healthy longer on the shelf.

01:06:17 There are examples of developing plants

01:06:19 that make polyhydroxybutyrate.

01:06:21 These are polymers that can be used

01:06:23 in making plastics.

01:06:25 It's a very exciting discovery by researchers

01:06:27 at James Madison University

01:06:29 as well as Michigan State University

01:06:31 in a collaboration.

01:06:33 The only problem so far is the plant only grows

01:06:35 to about an inch and a half tall,

01:06:37 so it doesn't make very much plastic,

01:06:39 but those are only genetic technical difficulties.

01:06:42 But the point is there is an advance out there.

01:06:47 There are also experiments going on

01:06:49 to try to change the structure of starch,

01:06:52 to encourage starch to have a different structure,

01:06:56 a different side chain,

01:06:58 so that polymers of plastic can be made

01:07:00 out of starches in the future.

01:07:02 We can look at plants as a renewable resource

01:07:04 for some of our commodity chemicals.

01:07:07 The kinds of traits that we'd like to look at

01:07:09 for the future are shown here.

01:07:11 Some are simply more of the same,

01:07:13 but at the bottom you see that

01:07:15 the likelihood of using plants as sources

01:07:18 of medicinal components,

01:07:20 including vaccines, either oral or IV,

01:07:23 depending upon how the production scheme is set up,

01:07:26 anti-cancer agents, antiviral agents.

01:07:28 Plants as renewable resources for commodity materials,

01:07:31 including polymers and oils and other compounds

01:07:34 that will find plants being used as factories,

01:07:37 not for new things,

01:07:39 but simply modifications of existing components

01:07:41 in those plants.

01:07:44 The ability of plants to tolerate

01:07:46 the environmental stresses

01:07:48 have become an increasing target of plant scientists,

01:07:51 how to make them grow in drought or in saline soils

01:07:54 or in high temperature, low temperature,

01:07:56 under high metal toxicity conditions, etc.

01:07:58 Those are in the future,

01:08:00 and I think we can expect them at a specific time frame.

01:08:03 The time frame is estimated here.

01:08:05 We can imagine that improvements in food processing

01:08:08 we'll see by the year 2000 to 2010.

01:08:11 Chemicals and polymers will be developed

01:08:14 somewhat after that.

01:08:16 All of this first requires a much finer

01:08:19 and detailed basic understanding of plants,

01:08:22 the biochemistry of their metabolism,

01:08:24 and how the enzymes are responsible

01:08:26 for the pathways in those plants,

01:08:28 how they can be switched up, switched down,

01:08:30 how the plant can be used as a renewable resource.

01:08:35 The issues that remain, of course,

01:08:38 as shown on this slide,

01:08:40 are not unheard of or unknown

01:08:42 to most of you in the audience

01:08:44 who are concerned about not only health

01:08:46 but the environment.

01:08:48 Who is the one to govern this kind of material?

01:08:51 The USDA governs and examines plant health.

01:08:54 They want to make sure that the plant

01:08:56 that the farmer puts in the field

01:08:58 is able to withstand a cycle, can be fruitful.

01:09:01 The EPA judges whether or not

01:09:03 this plant has pesticidal properties.

01:09:06 So plants that carry the Bt endotoxin gene

01:09:09 are being examined by the Environmental Protection Agency

01:09:12 and asking if this is a good thing,

01:09:14 not only from the standpoint of the plant

01:09:16 but from the standpoint of the environment.

01:09:18 Some of the questions that are raised

01:09:20 are what happens to the population of insects

01:09:23 that normally would be susceptible

01:09:25 to those insecticides or those insecticidal proteins,

01:09:29 the natural proteins,

01:09:31 and how might the use of transgenic plants

01:09:33 affect the availability of those biopesticides?

01:09:36 How do you manage the genetic resource

01:09:38 of genetic engineering?

01:09:40 If there are four or five genes here

01:09:42 that control a lepidopteran insect,

01:09:44 how do you deploy them?

01:09:45 Do you deploy them one at a time,

01:09:46 two at a time, three at a time,

01:09:48 or do you stagger them in different years

01:09:50 so that you control the population of the pest?

01:09:54 How do you not waste the genetic resource

01:09:57 that the genetic engineer has developed?

01:09:59 Confirming environmental safety

01:10:01 is an issue that lies both

01:10:03 with the regulatory agencies as well as the scientists.

01:10:06 And we as responsible scientists

01:10:08 need to continue to focus on the questions

01:10:10 that the public might raise

01:10:11 because eventually and ultimately

01:10:13 consumer acceptance is what's going to govern

01:10:15 whether or not this technology

01:10:17 will in fact be deployed

01:10:18 other than for making cotton

01:10:20 or for making new polymers or new starches.

01:10:22 Our goal has to be to continue to work

01:10:26 towards the goal of 2030,

01:10:29 and that is looking to face the population

01:10:32 at that point in time.

01:10:34 Agricultural agencies that look at these rules

01:10:37 and regulations are trying to learn as they go along.

01:10:41 Their rules are not perfect.

01:10:42 They're being instructed not only by scientists,

01:10:45 unfortunately not enough by scientists,

01:10:47 more by lawyers and policymakers,

01:10:49 than by the facts.

01:10:50 We need to continue to encourage

01:10:52 our regulatory agencies to learn the facts

01:10:54 of the science that they regulate

01:10:56 because in fact that will be probably

01:10:58 the single largest deterrent

01:11:00 to whether or not some of the products

01:11:02 that are being developed and tested in greenhouses

01:11:04 will in fact meet the market.

01:11:06 It's you the consumer that is given information

01:11:09 by the federal agencies and the press

01:11:11 that will make a decision

01:11:12 and let's make it in an informed way

01:11:15 because in fact feeding the next 5 billion people

01:11:18 is not going to be as easy as feeding the first 5 billion.

01:11:21 We have a lot of work to do

01:11:23 between now and 2030 and 2040.

01:11:26 The applications of these technologies

01:11:27 in developing countries are obvious.

01:11:29 It's our moral responsibility

01:11:31 not only to look at the possibilities for their use

01:11:34 and maintaining a clean environment in our agriculture

01:11:37 but making sure that what we deliver

01:11:39 has got the chance of reaching those who need it the most

01:11:42 and very often as you've heard

01:11:44 in the case of medicinal components, vaccines and so forth,

01:11:48 that need is going to be greater or as great,

01:11:50 if not greater, in developing countries

01:11:52 than it is going to be in the developed.

01:11:55 Thank you very much.

01:11:56 Applause

01:12:04 We have time for about two questions.

01:12:07 Dr. Beachy, it's hard not to be dazzled

01:12:10 by the utopian potential of the designer plants that you described

01:12:15 but there's a concern I've heard expressed

01:12:18 that plant genetics companies might in fact downplay

01:12:23 the traits such as famine-ending growth yields

01:12:28 in favor of traits that tickle the yuppie consumer's palate

01:12:32 such as blue roses or anti-sense tomatoes

01:12:38 or things that boost corporate profits

01:12:40 by simply extending shelf life.

01:12:43 What I'd like to know is

01:12:44 how do we get your values into the corporate boardrooms?

01:12:51 Talking to the corporate boards.

01:12:53 There are many corporate groups

01:12:58 who are in fact interested in not only the good of their profits

01:13:03 but also seeing their technology move out.

01:13:06 We see it with small European biotechnology companies.

01:13:10 We see it with the giant industries in this country.

01:13:12 There are examples where science fellows

01:13:15 are being taken into corporate laboratories

01:13:18 to learn plant genetic engineering

01:13:20 and then testing those improved crops

01:13:25 back in their home countries when it's appropriate to do so.

01:13:28 I know of at least one company that's doing so.

01:13:31 There are also ways to encourage those companies

01:13:35 to release the pressure of corporate profits.

01:13:39 That is, enable these technologies to be used

01:13:43 free of intellectual property rights.

01:13:46 The greatest thing that we could do

01:13:48 is make it possible for India to grow all the peanuts that they can

01:13:52 so that they can feed their own economy

01:13:55 without interference from American patent law.

01:13:58 In China, the need to develop increasing food production

01:14:02 is absolutely evident.

01:14:04 They don't have enough and they won't have enough

01:14:06 in the next 30 years to maintain feeding capacity.

01:14:09 Indonesia is another example.

01:14:11 These countries don't always maintain intellectual property rights

01:14:14 or have them that are satisfactory to many of us in the West.

01:14:18 The answer is to find a way that intellectual property rights

01:14:23 are waived whenever necessary

01:14:26 to encourage the development in those countries.

01:14:28 There are a growing number of scientists, such as myself,

01:14:30 who are interested in the interactions of our laboratories

01:14:34 with those from Latin America, Asia, and Africa.

01:14:37 We bring students in as well.

01:14:39 The problem is finding support for those

01:14:41 because it's not an inexpensive science.

01:14:43 I think there are ways to do so.

01:14:45 Resources are required,

01:14:47 but I believe that corporate sponsors are possible

01:14:51 and they are making themselves known

01:14:53 through making technologies available

01:14:59 that can be used in those countries.

01:15:01 That's a very important first step.

01:15:04 APPLAUSE

01:15:10 When people who express concerns

01:15:13 about the genetic engineering of plants

01:15:15 often say that this is not necessarily going to be good for the environment,

01:15:19 one of the examples that is often given

01:15:21 is herbicide-resistant plants,

01:15:23 saying this is going to encourage the greater use of herbicides.

01:15:26 You said that it will encourage the use of safe herbicides.

01:15:31 First of all, what is an environmentally safe herbicide?

01:15:34 Could you give us an example of how a farmer

01:15:36 growing a particular crop would have to use herbicides

01:15:39 if that crop were or were not genetically engineered

01:15:42 with herbicide resistance?

01:15:44 Just a little bit of a reminder,

01:15:46 American agriculture has become dependent

01:15:48 on a lot of agrochemicals.

01:15:50 We've seen the ones that are not good,

01:15:53 the atrazines, for example, that went out of usage here,

01:15:56 were detrimental herbicides,

01:15:58 those that leached into groundwater

01:16:00 and caused problems in the Midwest.

01:16:02 We've also become dependent on cheap sources of food.

01:16:05 We don't like to pay more than 12%, 13%, 14% of our annual income for food.

01:16:09 If we really took it at what its actual cost might be,

01:16:16 we might see it go to the level that it is in Europe,

01:16:19 which is substantially higher, perhaps double what we pay.

01:16:22 We're used to cheap food, and the consumer demands that.

01:16:25 What that means is that we will continue to depend upon agriculture chemicals

01:16:30 unless a biocontrol methodology or mechanism is in place

01:16:34 to provide equal levels of yield at the same low cost.

01:16:39 So far, that's not with us.

01:16:41 So if you have a choice, then, of no chemicals or chemicals,

01:16:44 the choice is going to be some chemicals.

01:16:46 That's to keep the price of our food down.

01:16:49 So what chemicals do you choose to use?

01:16:51 You choose those that have the longest history of safety,

01:16:54 and there are a few chemicals that are like that.

01:16:57 There are other chemicals that are being developed by chemical companies

01:17:00 that have high safety.

01:17:02 That means they don't have any impact on fungi, on earthworms,

01:17:07 or on birds that eat the plants that might have been exposed.

01:17:10 They have simply very limited levels of toxicity,

01:17:13 only to organisms that carry chloroplasts, only green things.

01:17:18 So if you have a target to go for, that's what you would use.

01:17:23 The downside is that it's non-selective.

01:17:27 The upside is that's the way you make profit

01:17:29 because you have a corn crop that is transgenic for herbicide resistance,

01:17:33 and it grows well.

01:17:34 The farmer then has to manage how he applies that.

01:17:37 If he applies it too widely,

01:17:39 then he has a possibility of contaminating foreign fields or other fields.

01:17:44 If he uses, however, a safe herbicide,

01:17:46 one that turns over within, say, 24 hours after application,

01:17:49 turns over in the soil,

01:17:51 then he has a limited impact on other crops or other plants in the area,

01:17:56 less contamination by simply walking or moving between fields.

01:18:00 The farmer's information then will come from the fellow who sells them the seed.

01:18:05 The guy who sells them the seed will say,

01:18:07 here's a new corn variety.

01:18:10 Now if you use it with this herbicide,

01:18:12 you'll have less need to till your field.

01:18:16 You'll use less resources to spray it.

01:18:18 You'll use less resources to keep it cultivated or weed-free,

01:18:23 and you'll make use of a new set of information.

01:18:26 I hope that answers your question.

01:18:28 What kind of herbicides would he have to use

01:18:30 if the plant weren't resistant to these safe herbicides?

01:18:33 If it was not resistant to safe herbicides,

01:18:35 there are other kinds of chemicals that can be used.

01:18:39 For example, corn will be resistant to herbicide A, B, C, or D.

01:18:43 If the farmer wants to use A

01:18:46 and wants to use a safe herbicide for it,

01:18:48 he can get better control with A

01:18:51 because it won't affect the plant.

01:18:53 If he chooses to use B,

01:18:54 he may have to use a different set of procedures.

01:18:58 He may have to treat the soil in advance,

01:19:00 or he may have to treat the plant only when it's very young,

01:19:04 or he may suffer a small yield decrease

01:19:07 if he sprays his adult corn plant with herbicide letter B

01:19:12 because that's the nature of how that herbicide affects it.

01:19:15 He'll simply manage his resources as he has in the past.

01:19:18 If he wants to get the best control,

01:19:21 he may choose to use one that is effective against all crops

01:19:25 except for his corn.