 At the beginning of this decade, Dr. Brill took his skills as biochemist, microbiologist, molecular biologist, and ecologist, and moved to the industrial world of biotechnology. He now serves as vice president of research and development for agrocedis. This company focuses on ways to use plant and animal biotechnology to improve agricultural productivity. Just this past week, agrocedis has received approval to field test a product that is an application of bioengineering technology. Dr. Brill gives us the perspective of a bench scientist who has asked, how does it work? To the applied scientist who asks, how can we constructively use it? We are honored that Dr. Brill has accepted our invitation to join in this year's Nobel Conversations. He will speak on the impact of biotechnology and the future of agriculture. Dr. Brill. Thank you, Dr. Lambert. What I'd like to do this afternoon is show you or convince you that biotechnology is opening up some very exciting new approaches to improve agriculture. And not all I'll be talking about will be on the upside because there's a little bit of a problem that's occurring, and that is concerns about this technology, and I'll be spending quite a bit of time on that. In fact, you'll probably think I'm a little bit too defensive about things. I'll try to put these concerns into perspective. Before I go into the subject matter, I think it's important that I educate you and make you all molecular biologists. So if you can stand around for one minute, I'll have the first slide, please. Represents the chromosome. And the chromosome contains the genetic material of all living organisms. The chromosome is made up of a chemical called DNA, and the chromosome is segmented, made up of many segments. Each segment is a gene. And in a living cell, there are thousands, not tens of thousands, of different genes. Each gene codes for a different protein. And a living cell is living, is doing its thing because of the complement of proteins that it contains. So it is the proteins that take up food into a cell that digest the food, allow the cell to make more of itself, and become larger or duplicate. A fish cell has a different complement of proteins than a human cell does, and that has a different complement of proteins, and therefore a different complement of genes than, say, a tomato cell. So there are thousands, tens of thousands of different genes, each coding for different proteins. In the next slide, please, what exactly is a genetic engineer? Well, genetic engineering is gene splicing. That is, you saw those little segments. It's possible to take a segment out of a gene, out of a chromosome, and in fact it's possible to take a segment out of a chromosome from any animal, plant, or microorganism. And the exciting part of this technology is that one can take that gene out, can purify it, and can put it back into a different organism. Now it's possible to put genes into only a few different kinds of organisms, but the number of organisms that are becoming amenable to this technology is increasing. Very exciting developments from genetic engineering, a technique that's just a little over a decade old, include mostly in basic research. We're learning about evolution of organisms through understanding the genes and examining these purified genes. We're understanding the basis of development, how cells develop. We're learning a lot about diseases, how certain microorganisms cause disease. We're learning about how cancer, or at least how some cancers work, and how some viruses work. So that's very, very exciting. The next slide please. This place is all right. Two more weeks and I'll be a molecular chemist. The point I want to make with this is that this technology really isn't that sophisticated. That high schools have laboratories in which recombinant DNA or genetic engineering or gene splicing, they're all different words for the same thing. High schools are getting involved, and that was just recently in Cold Spring Harbor, I believe, a course for high school teachers. In many developing countries, there are laboratories involved in genetic engineering. In all of our major universities, throughout the world, there are dozens and dozens of laboratories involved in the technology, and certainly lots of industries are involved. There's even a home genetic engineering kit I hear that is for sale. So the genie is out of the bottle and probably is impossible to put it back. If somebody wanted to, they could set up a genetic engineering lab without too much trouble in their basement. Next slide please. Well, what's different from the perspective of biology, not so much for chemistry or engineering, the commercial interests in the technology as the technology is developing. And I think before I go into agriculture, I'd like to make a point of what genetic engineering can do, and I'll do it taking a healthcare example. I'll take it because it's one of the first examples, and human healthcare is really where most of the genetic engineering applications have been directed. Certain diabetics need insulin, which is a hormone. Insulin is a protein, and therefore there's a gene that codes for insulin. The diabetics are given, they generally inject themselves daily with insulin that has come from the pancreases of slaughterhouse animals, such as cattle and sheep. And in most cases, that's fine. But animal insulin is slightly different than human insulin, and there's certain diabetics who develop reactions or allergies to these animal insulins, and it would be very nice if they could treat themselves with human insulin. But there's not that big a source of human pancreases. Now, what scientists have done is to isolate the human insulin gene from human cells, put that gene into a bacterium, into a microorganism, and then grow that microorganism in a big fermenter, a fermenter such as is used in the brewing industry. You know, there's a big vat full of liquid, full of nutrients for the microorganism. So the microorganism then grows, it now has a new gene in it besides all of its other genes, and so the microorganism is pumping out insulin. And when the vat is all, when the cells are all grown up, then the laboratory harvests the material and purifies the protein, human insulin, and can end up with pounds of pure human insulin, human insulin that's exactly equivalent, exactly the same as the insulin that's in a normal body. And this is now being sold, it's called humulin sold by Eli Lillian Company. And there are a number of other proteins that are being produced, but I won't discuss those. Well, most of the early applications in agriculture, which is the focus of this talk, are going to be in the animal healthcare area just because, as I said before, almost all of the work is being done in human healthcare, and there's spinoffs that can easily be applied to animal problems. The next slide, please. And the next slide. Here are some headlines of some of the things, I'm not going to be sure, I don't shift over anything, okay. Some of the things that are going on, here is bovine interferon. Interferon is a protein that's made in extraordinarily small amounts in animals, in this case the cow, and it's been impossible to purify enough to do any kind of substantial studies with it. Through genetic engineering, the bovine interferon gene has been isolated, been thrown into a microorganism, the microorganism has grown in fermenters, and pure bovine interferon is produced and is being tested now as a possible protective agent to be used in cattle to protect them from shipping fever, a commercially important disease. Another example is vaccines, some vaccines are being produced, and one of the first genetic engineering products sold is a vaccine against pig scours, a disease of baby pigs made through genetic engineering, not the pigs, the vaccine. Here's another vaccine, a foot and mouth vaccine, there's a virus that is potentially very, very bad virus for cattle, and good vaccines aren't available through genetic engineering, they are groups trying to make very effective and safe vaccines against this disease. Here's another gene, or another protein, bovine growth hormone, again there's a gene that makes this hormone, the hormones of protein, and the proteins are made in extremely small amounts. Now one can make pounds of this bovine growth hormone, and in fact this hormone has been injected into cattle, in a test of a Cornell, and it turns out that cattle grows substantially faster when injected with the bovine growth hormone, and they also produce, I think it's 30 or 30 or 40 percent more milk than the controls. So all these examples, we're talking about taking a gene, putting that gene into a microorganism, and growing that microorganism in a fermenter. What about genetically engineering the animals themselves? The next slide please. Okay, these are mice, and the smaller mice are normal mice, and the larger mice, in one case, has been genetically engineered, so it hasn't been injected with a growth hormone, it's been engineered with the gene that produces growth hormone, in one case it's been genetically engineered with a human growth hormone, and in another case with a rat growth hormone, and you can see these mice are larger than the ungenetically engineered controls. The way this is done is by injecting the foreign gene into a freshly fertilized embryo, and then putting that embryo into a female that will give birth to the genetically engineered animal. In many cases the animals are sterile, but in some cases now the animals are fertile, and the progeny from these animals retain the foreign gene. This is far from an art, there are tremendous complications in all of these, so it's not a simple matter to get something like this, but obviously there have been some successes. The United States Department of Agriculture has genetically engineered pigs and sheep with growth hormones, and there's no data yet on whether these animals are bigger, there's no data I know about yet. There are obviously some problems that people are thinking about from these types of experiments. For instance, faster growing animals require more feed, and so milk producing areas that have milk producing cattle, or areas that have these animals, these cattle, if we're trying to genetically engineer cattle, that are close to the feed growing areas will have a competitive advantage over the areas where feed has to be shipped. In Australia there's activity where they're trying to genetically engineer sheep to grow larger, and there's concern whether these sheep, now that they're larger, will put a greater strain on the very fragile environment by compacting the soil more and creating potentially more erosion. These are questions that are being discussed. I want to put a little bit of perspective. Traditionally, we have been breeding and applying nutritional science to increasing the weight and increasing the rate of growth of our farm animals, so that the end products are really the same. There's some concern that this ought not to occur, this technology ought not to occur. It's unnatural, which it is, because a population, let's say eventually of cattle that have been genetically engineered to grow faster would not have occurred without man's intervention. But the cattle of today, in fact, all animals that we use, whether it's our pets or our farm animals, are all the products of human intervention, and you wouldn't see herds of any of these animals looking anything like they are now if it weren't for man's agriculture. I'm going to slip back into a healthcare situation, but I want to make a point, and I think the best way of making that point is with the next slide. What is, I mean, I'm trying to focus on the unnaturalness of this. What is natural is opposition to a certain extent to every new technology. This is a picture, this is our satirical cartoon about 1800, and it's a cartoon of Edward Jenner in England who is injecting people with smallpox, the smallpox vaccine. You can see that, first of all, vaccine pot from the cow, it's labeled on this little pot here. But it is, it's pus from the cow that has cowpox, and so he's injecting this into people. At the time he was doing this, approximately 30% of English babies died from smallpox. Now nobody in the world dies from smallpox because of this vaccine. This cartoon is just an example of the problems that Edward Jenner had. He was ridiculed, and he was almost thrown out of his physician society, medical society, because he was doing this. Because people thought it was unnatural, and you can see little cows coming out of people's arms and legs. The next slide, please. I'll now start talking about plants because that's the area that I'm mostly involved with. The next slide, this is how plants are genetically engineered now. It's possible to isolate a single plant cell, let's say from a leaf, and this rod represents a chromosome. And one can add a foreign gene to a single cell, and the foreign gene can be incorporated now as one gene, remember, into tens of thousands of genes in this cell, and it's possible to take a cell like this, give it certain nutrients and hormones, and you can have that cell grow and eventually become a normal plant, a normal fertile plant, and seeds from this plant now will contain the foreign gene, and so the gene will be transferred from generation to generation through the seed. The kinds of genes or properties people are now trying to put into plants include genes that will make the plants more resistant to diseases, genes that will allow the plants to require less applied fertilizer. You know a lot of the fertilizer that's added to the farms after a heavy rain ends up in our streams and rivers to pollute their major sources of water pollution. People are trying to improve the nutritional quality of crop plants, also trying to make plants more resistant to drought and a number of other properties, so we're at the very early stages of plant genetic engineering, but there's more and more activity, and certainly over the next decades there will be some very exciting and applied results. The next slide please. Well people are, including my company and even before I was involved in the company, people are making discoveries in laboratories that pertain to agriculture, and it's very important, and I think people who don't really think about agriculture don't realize this, but it's very important that as soon as somebody has a discovery that they feel tested as soon as possible, and the reason for that is that if you see something that looks as if it's let's say disease resistant in a laboratory or greenhouse, more often than not when it's out in the field the resistance doesn't pan out, and the reason for that is that there's no way to mimic even in the best of greenhouses, there's no way to even closely approximate all the environmental activities that are going on with the plants in the outside in nature, so it's crucial that plants or microorganisms go out into the field before one wastes more money finding it up so it just works in the greenhouse and won't be used in the field, and these are genetically engineered plants, but this is just a small plot, these are just soybean experimental plots, these are very important and a number of laboratories and companies have been frustrated by the difficulty in trying to get experiments, get permission to put experiments out in the field. The next slide please. Well there have been some concerns about putting organisms out in the field because up to now the organisms, let's say the organisms that produce insulin, these are grown in fermenters and they're contained, the organisms themselves, the genes aren't put out into the field. Nobody's really concerned, at least I haven't heard any concern about putting a genetically engineered cow out in the field, but people are concerned about putting plants and microorganisms out in the field, and in some cases there's some degree of rationality in the discussions and it's concerns in some cases there are not. The fears I think are mostly due to fear, well the concerns are mostly due to fear of the unknown. The next slide please. It says if you can't read this, not only am I against evolution, but I'm not so sure about gravity and relativity either. I'm not really, well I am making fun of politicians but I don't mean to in this manner. What's happening is that some of the more vocal concerned people have triggered politicians to be excited about this area and the politicians don't have the background and also don't seem to have the patience, I'm talking in general terms, to listen to all sides of the arguments. In other words they're concerned potentially with this could be dangerous and that's all that they, at least some of them, may need to trigger holding hearings and to potentially come out with some laws and regulations that may not eventually benefit the country. So it's very important for people involved to talk to the politicians or somehow talk to the people who work with their politicians to educate them on any issue that's where they have some expertise. And it's important for people involved to discuss the issues, to be sure that irrationality does not take the day, carry the day. And what I will try to do is to convince you that putting such organisms out into the environment is no concern for, should be no special concern. And what I'll start doing is comparing what we are, what's going on now from traditional agriculture to what might occur from a planned genetic or microbial genetic engineering experiment. The next slide please. Okay, this is a normal Midwestern corn, quite sure looks big up here. And this is a plant called Teosinte. This is presumed by some to be the progenitor of corn. These two plants would not cross naturally. This is found growing wild in Central America. But there are scientists around the world that are growing this plant and are trying to breed characteristics from Teosinte into corn. For instance, disease resistance is that this plant has that we'd like to have in our corn. Crosses between crop plants and exotic species have been going on for many, many decades. So people are crossing commercial tomatoes with little black berries that nobody here would ever recognize as being a tomato. But it happens to be a relative of tomato to try to improve these crops. Okay, the next slide please. This is what occurs in a cross. And each one of these represents, this represents, let's say, a corn. This represents Teosinte. It's chromosome. And each segment represents a gene. And remember, there are tens of thousands of genes. And when you cross a corn with a Teosinte, you can see that you're mixing up genes randomly. One cannot predict what the progeny would look like until the experiment is done. And all the progeny are different from each other. Now in a genetic engineering experiment, one, let's say we have this corn here, one could take a gene and splice it in right here. And of course, the big difference is that gene can come from any organism. Whereas in a cross, they have to be somewhat related. But you see, when you put that gene in, it's very specific. You can predict. In fact, that's the purpose of doing the experiment. So you can predict what the progeny would look like. Somebody went through all the work of isolating the gene. They know where it comes from. They know where it does. So one could predict what the progeny would look like. The progeny would all be the same. And it isn't random as it is in crosses. Now, even in the case of crosses, breeders aren't concerned when they cross Teosinte and corn. No precautions are taken. Even though somebody can argue, well, how do you know that if you cross the Teosinte and corn, you won't come out with some very terrible weed? And the reason breeders aren't concerned is because of all the decades and decades of experience with innumerable crosses done in many, many countries by sophisticated, not so sophisticated people that problems have not occurred. Serious problems in the order of something that would really frighten us that has not occurred. There have been problems from breeding, and there will be problems from genetic engineering. And examples would include, say, breeding or genetically engineering, an organism, a plant for resistance to a disease. And we may turn out later, and there are examples of that, that all of a sudden now it's susceptible while you are made in resistance, you've made it susceptible to another disease. And those kinds of problems will occur, have occurred, and in fact, that's the breeders profession is to look for these problems and to field test in first small plots in a couple of locations and then larger plots and many more locations. And so this field testing has to occur before any crop is acceptable. And that will continue even though plants have been genetically engineered. So there are no special concerns and there are also no special regulations for traditional breeding. So what's the why am I so excited about all of this? Well, people have mentioned and pointed out the fact that some organisms are dangerous, they cause tremendous problems. And some people have said that those organisms can be considered as models from what might occur through a genetic engineering experiment. For instance, the Japanese beetle, and here's an organism that's caused tremendous commercial problems. Dutch elm disease, the elm bark beetles cause tremendous problems. The hydrilla in the south that's been clogging waterways. The next, next slide. Here's a hillside in Pennsylvania that's been wiped out by the gypsy mark. Another very serious problem. The next slide please. This is the kudzu vine in the south where this plant is a terrible weed and here you can see it killing, choking out trees. So as everybody knows that organisms, some organisms can wreak havoc. Well, what's the relevance of these types of organisms to what might occur from a genetic engineering, from genetic engineering work? Well, these organisms are not, are not problem organisms because man has genetically manipulated them. These are problem organisms because they were imported from another country. They came into the United States. In their native country, they had evolved over eons to be competitive, that's why they survived, but they didn't take over because there were natural limiting factors such as other plants, weather pathogens and so on. They became problems when they came into the United States. In the case of kudzu, it was China, I guess China, Japan and then United States. They became problems when they came into the United States and one or more of the natural limiting factors was missing. And so in these cases they took over and have caused and continue to cause serious problems. I think it's important to tell you that almost every crop we grow in the United States and almost every plants that you have as an ornamental plant in your house were imported from, from outside of the United States. So that very, most plants imported have been valuable, but there have been examples of serious problems. Now there's scientific basis to believe that by genetically engineering a corn or a wheat or a rice that one wouldn't inadvertently come up with a plant that could cause as much damage as teosinte. In other words, it's become a serious problem weed. A serious problem weed isn't, isn't a serious problem weed because it contains a single gene. It can, it has to have a variety of problems and I'm being very general, but it has to have problems such as for instance the seed would have to overwinter or survive for a long time. The seed has may have to be dispersed over long distance. The plant would have to grow fast and be more vigorous than other plants around it so it can take over. This isn't, these properties aren't due to one gene. They're due to hundreds if not thousands of genes. And it's not just the presence of these genes, but it's these genes interacting in a very, very orderly specific fashion. So how could one imagine that by taking one or several genes from any organism one could convert corn into a real problem weed like this? It's my view that the chance of producing a problem weed through genetic engineering is less than the chance of producing a problem weed in a Tocente corn cross which nobody is concerned about. Okay, next slide please. Okay, here's a, I'm switching topic now, topics, I'm talking about microorganisms. This is the first page of an advertising brochure put out by the National Nitro Culture Company in Pennsylvania. And they're advertising bacteria specific for alfalfa in this case that do nice things for alfalfa in the field. This claim, it says the greatest discovery of the century. This claim really isn't as great as it seems since this was printed in 1904. And so it's no big deal I guess to have the greatest discovery in four years. It's a much bigger deal to have the greatest discovery now. But I'm using this just to demonstrate that microbes have been added to our fields in the United States since the turn of the century. The next slide please. Here's an alfalfa field treated with such a microbe, it's called rhizobium in this case. And here's one that wasn't treated. So it's apparent that some microorganisms have dramatically benefited agriculture. The next slide. These are canisters of inoculants, microorganisms. This is for soybeans. This was made in 1918. This is for clover, 1938. And here's one against for horticultural crops that was about seven years old. In the United States since the turn of the century there have been hundreds of products, microbial inoculants that farmers have put out in their fields. And they put on the order of a billion of these microbes per acre. In some cases the products are good and some not good. And one could imagine for the hundreds that have been used commercially one can say that perhaps 10 times or even 100 times more have been used experimentally. So that over the last 80 years just in the United States there have been thousands and thousands and thousands of microbes that have been grown up in fermenters and have been applied in very large numbers to farmers' fields. In India the inoculant business and in Russia the inoculant business was even greater than in the United States. In no case and in many cases the microorganisms were mutated. In no case that I know of is there an example where any of these organisms has caused any kind of problem. The purpose of this is just to tell you not to be afraid of microorganisms just because they're microorganisms. The next slide. Here's an example of a rhizobium. This is soybean. This part had been inoculated with a rhizobium that has been used commercially in the Midwest for more than a decade. And it's possible to isolate the organism and genetically manipulate it and make the organism do better what it normally does which is fixes nitrogen for the plant. And here are plants that are more vigorous, they fix more nitrogen and these are the organisms that are added to these plants have been genetically altered. So it's possible with genetic engineering to improve useful organisms. Hey the next slide please. This says uh-oh there have been fortunately there have been debates on this issue and I think more and more the people who were concerned at least about putting plants out in the environment are becoming much less concerned but there's a little bit more concern about putting microorganisms, genetically engineered microorganisms out into the environment because microorganisms are invisible and they don't cause terrible diseases and people who haven't had experience of microbiology uh naturally are somewhat more concerned. What's the chance by genetically engineering an organism that we would consider safe or safe enough to put out in the field uh by converting that organism into a problem pathogen? I think the chance is extraordinarily low and again the scientific basis for this somewhat parallel to the argument I used for the weed situation. A pathogen talking about microorganisms yeast I mean fungi and bacteria uh pathogens are pathogens not because they contain a single gene on the a pathogen give you an example is a pathogen because it may contain a gene for a toxin but that's not sufficient it may need a gene or genes so that the organism can overcome host defense mechanisms or it may be genes so it can survive in between hosts and as we're learning more and more about microbial ecology and about the molecular basis of pathogenesis uh it's not a single gene it's again a complex of genes very specific genes interacting in very specific ways to make an organism into a problem pathogen in other words one that could spread readily and cause grief by either infecting animals us or or plants in fact uh one of the leading scientists at Stanford, Stan Falco who who studies the molecular biology of pathogenesis says that he couldn't even with lots of resources available he couldn't purposely convert an organism to be considered safe into one that could be a problem pathogen so to do it accidentally by taking genes from any organism for the purpose of trying to make an organism into a agriculturally useful organism the chance for converting it into a problem pathogen is extraordinarily low it's something I wouldn't worry about there are 20 million on the average there are 20 million cells per cubic inch of soil and these cells these are microorganisms and these cells are continually dividing they're continually mutating they exchange genetic material uh with with uh their cousins with their related organisms and there's more and more evidence now that that there's some exchange of material even with unrelated organisms so there's evidence that genes may be exchanged between say animal and bacteria and a bacteria to a plant and so on in most cases where let's let's say a bacterium has taken up a plant gene in most cases that plant gene won't do anything good for the organism it won't give it a selective advantage and so that organism will not predominate in some rare cases where there is a selective advantage then the organism can predominate and that's called evolution well I believe that what what will happen through genetic engineering is going to be minuscule and ecologically insignificant compared to what occurs naturally or continually and randomly in nature now there have been some the press has been bad at this they say uh genetic they're it's a it's a nice story uh people are concerned about genetic engineering because they don't want another Bhopal three mile island or love canal could have the next slide please this is just a picture of Bhopal of the union carbide plant in India and Bhopal well here am I a representative from industry telling you that my technology is safe and certainly the builders of the Bhopal plant signed off saying that that the plant was safe what is the relevance of these chemical problems uh including a three mile island it's the chemical problems are radioactive chemical what's the relevance of these problems to what might occur through genetic engineering well all of these cases we're dealing with a dangerous chemical and everybody involved would agree that they're dealing with a dangerous chemical in the case of of uh Bhopal the chemicals called methyl isocyanate and everybody knows that methyl isocyanate is dangerous so there's a real there's a potential for a problem by uh producing methyl isocyanate by utilizing it by storing it by disposing it or by transporting it in other words if you were on a truck carrying methyl isocyanate and somebody bumped into the rear of the truck I would be very very concerned whereas there's no apparent danger that can come from a recombinant organism would say a truck full of organisms that have come out of a fermenter it's I believe it's quite a different situation quite a different situation the next slide please well it's ironic that I think most of the activity going on in genetic engineering of uh with regard to agriculture is aimed to replace some of the pesticides we we use or if not replace them give us the option of using smaller amounts of pesticide or using safer pesticides I just read that 20 percent of Illinois farmers assume the same thing as true Minnesota 20 percent of Illinois farmers have gone to their physician at least once due to a pesticide related problem there are 400 species of agricultural pests that have become resistant to pesticides we're learning more and more that these pesticides get into our food in other words we eat the pesticides and there's evidence or indications that some of these pesticides may have potential to cause things like cancer well if we're worried the people are worried about putting genetic putting gene genetically altered organisms into the environment let's see what happens let's compare genetic engineering what happens to genetic engineering with what happens with the use of pesticides when millions of acres are treated with insecticides and one routinely finds insecticide resistant insects millions of acres are year after year sprayed with herbicides and we always see herbicide resistant weeds also with the use of herbicides that one gets mutant microorganisms in the soil all kinds of microorganisms that are mutated so that they can degrade the pesticide the herbicide more effectively and in this way that herbicide can't be used the following year or if it is used the farmer has to use more of it so in all of these cases the organisms the insecticide resistant insects the herbicide degrading bacteria the the herbicide resistant weeds they can be disseminated by their normal natural means and they can also exchange their genes with guys they normally exchange genes with so by the use of pesticides you will get uncharacterized genetic changes in problem organisms with genetic engineering you get characterized genetic changes in safe organisms again quite a difference well to summarize the safety issue i believe that the chance of producing a problem organism through recombinant DNA technology through genetic engineering is going to be less than the chance of producing problem organisms through practices that we now accept and manage regulations are evolving with how to handle putting recombinant organisms out into the field there's a tremendous amount of activity going on by the environmental protection agency the united states department of agriculture food and drug administration and the national institutes of health i'm hoping that the regulations that do evolve will take rational arguments by the scientists by public advocacy groups environmentalists etc and should not be led by the vivid imaginations that any new technology especially one that's kind of sexy like this is any new technology inspires i'd like the next slide please that's in a newspaper maybe that could be a good topic of the next Nobel conference and the next slide please and the next slide well this is a very exciting time the technology is at an early stage and we're beginning to utilize its first products i predict that our future will be considerably improved by use of this technology and as i said before it will be safer than technologies that will be displaced it's kind of back to nature thank you thank you dr brill for taking us into the world of agriculture and genetic research as the lights come back up perhaps our other participants would come to the front and we can begin our discussion professor professor brills talk has taken us into the world of genetic research and agriculture following up on professor kevlar's talk which was about genetic research in human beings and applying genetic research to the human animal i'd like to elicit comments from the panelists but but i'd like to begin with a question myself if dr brill will allow me i wonder winston how how you account for the persistence of the concern on the part of ecologists many of whom have considerable number of degrees in in microbiology it seems to me who persist in not accepting your argument in suggesting that that in fact there there are dangers here and i suspect maybe it comes down to the danger as as one of my colleagues said to me what if you're wrong okay that's let me just write that and what if you're wrong that's important i don't think it's it's not it's not a matter of genetic engineer versus ecologists they are there are a few ecologists probably no more than a handful that i know of who have expressed concern i know many more than a handful who who aren't concerned they're interested but they haven't they're not afraid and they they i think have the same kind of sense that i have and but there are also some recombinant dna people who have expressed concern again it's been a minority so it's not ecologists versus versus molecular biologists at all the ecologists basically the ecologists that have expressed concern are ecologists who who have been studying some of these upsetting things i mean they all have their different system but uh starling the the uh the gypsy moth and so on and really haven't considered what happens at the genetic level and so what they've been focusing on for their most of their careers have been problems that can occur from a live organism and they're very very sensitive to that and and we need we definitely need that population uh that's basically it and and part of it is what if i'm wrong but anybody can say that about any technology uh i'm quoting other people now but we inject our children with millions of doses of certain vaccines and some people have said well how do we know that with those vaccines we're not also including some virus or agent that will cause cancers perhaps even cancers don't catch 20 years from now and as we as we've had more and more experience with these we can't say well we know for absolutely sure that these vaccines are safe but based on our experience and our best estimates at the time we feel that we're we're safe and we're doing some very important things for people while while we're pursuing that but every technology one i mean the disadvantage we have in arguing the case especially with politicians is that they're sensitized that what if you're wrong and that's all they mean that's where it stops and they really don't have the patients to listen to the arguments uh you can say what if you're wrong with the t-osinte corn cross and that's that's the level i think of where we are we have experience with recombinant DNA technology of over a decade certainly uh laboratory organisms have gotten out into the environment probably millions of different kinds of laboratory organisms have from a laboratory even if you wear a lab coat you can get a little droplet can contain hundreds of thousands of organisms which can get in your shoe on your hand and you go out into the environment so we do have some experience with recombinant DNA technology in all kinds of organisms and i think more importantly we have experience with the traditional practices that the recombinant DNA isn't going to be isn't going to change organisms that radically or if it does change the organism that radically it's a dead organism thank you uh professor kevelis has a comment apropos your last point uh my understanding was that in the case of microorganisms recombinant DNA at least in the beginning uh a strain of E. coli was used that was known not to have tremendous chance of survival outside the laboratory environment it seems to me the case with um plants is different i mean you do want to survive outside the laboratory environment for openers but secondly it would seem to me to be difficult to predict given their survivability outside the laboratory environment just what uh impact they might have upon the overall ecological balance of the given environment i'm curious to know first of all how you actually assess that uh in a concrete case i don't have the slightest idea i think maybe our audience would be interested to know that at not too technical level and secondly how do you think decisions about whether these things ought to be released into the environment plants and uh genetically engineered plants how should those decisions be made where should uh uh the nexus of power and authority and society lie should it lie with you folks entirely or or us or or or how well how how does one of the first question is really how does one assess whether you what the potential for problems will be with a plant that you've just genetically engineered to do presumably to do something useful it's no different from the traditional practices which is the business of the plant breeder who takes a plant and runs a small plot and compares that to to the best plant around to its controls and a plant and and this this continually uh experiments in fact sometimes take a decade because they first try it they first try their new plant whether it comes from a teosynthetic cross or two different varieties of corn they try it in a small plot and hopefully they see something that that makes it better then they try it in a larger plot then they try it in over many seasons over many environments and really that's that's the experience they get sometimes mistakes are made and a plant becomes a commercial plant and it turns out to be susceptible to a major disease so there was a corn blight in 1970 that caused havoc in the Midwest but that was easily overcome i mean it was an economic problem for a year but but there was nothing ecological really when you're talking about ecological every plant every crop we grow in fact just the growing of crops does something ecologically changes the types of insects that hang around these crops the kinds of microbes that hang around the crops uh and that's accepted and no problems have occurred from that kind of practice uh similarly i think because we're going to make even less of a change in the plant that the chance for anything unexpected is going to be much much less so the testing is a testing that the that agricultural communities have been involved with for for many many decades and universities all state universities have extension programs to look at some of the new varieties and farms and so that's the traditional way and perhaps the only way i think there's been some talk about let's come up with a laboratory test to see if organism x has potential for causing problems and while that would be very desirable i think we're decades and decades away from the there's a question to my mind about the economics and sociology of these new technologies and i thought it might be interesting to ask if in your view and and the view of people are working in this area whether you see these new technologies as as say accelerating the demise of the traditional family farm or is it going to be a sort of technology that will be equally available to everyone you know what sort of economic and sociological effects will this thing have i i'm not an expert in this area but there's a lot of discussion going on in this area and especially with the increased uh with cattle with growth hormones is predictions that in fact it will displace the small farmer and uh there's no question that agriculture will change will change with or without genetic engineering uh i think that's really all i can say is i i i know there are people involved in and looking at the impacts of this and certainly since the big companies are very involved with this uh there after the money of the big of the major farmers i think it will be basically directed towards the big farmer but it's you can look at it another way and say that it may be useful for the small farmer because one problem the small farmer has is purchasing the pesticides and the chemicals that they use and hopefully the plants that will be generated in the microorganisms that will be generated will decrease the need for these for these materials so it's it's i think it's complex and i can't give you a proper answer let me answer Dan's second question who should make the decisions well until now uh first of all there are no regulations that govern industries uh and there are a number of industries who had the opportunity to put genetically engineered organisms out into the environment and every industry has tried to comply with the guidelines that uh Dan mentioned the NIH recombinant DNA guidelines that was mentioned earlier uh everybody's complied the decisions should be made by by everybody in uh being involved really so it's it's the uh it's the economists and the and the regulatory agencies and the industries the scientists it should be based on knowledge not one person going off half cost which is my biggest concern professor luria well i just wanted to reinforce something that dr brills said which i don't think is often understood by in the public or short every newspaper what is important in genetic engineering as applied to whether to animal husbandry or to plant breeding and so on or to protection against plant diseases that in general what one aims to do is in a sense much more selected and precise than when you do for example when you breed two varieties in order to select a more resistant to these and so on what you're trying to do and what you can do is to bring in one gene that is the one that interest you with the minimum amount of complication of the genetic structure as a whole the less of course extraneous genetic material you bring you are sure you are that you have only affected the characteristic it's in general i think i would feel in principle much safer in using material which has been produced in this way than in trying for example to breed varieties of animals as has been done for hundreds for hundreds and thousands of years in order to find one which is more suitable we know very well what this has happened to sheep and so on in many cases in which people have rushed to put hybrids into the field much too soon in this case i think one has at least a confidence that the minimum amount of genetic and so on has been accomplished. Dr. Nelson i think you have a comment tonight. Yes i want to raise a question which is also sociological also economic and political in the slide you showed headlines from newspapers i was struck by the headline that says genentech foot and mouth vaccine could find major markets after third world trials and i was all puzzled about the third world here does that mean because that is where the foot and mouth disease is found that is outside the u.s congress where it's often referred to but is it only in the third world where this is a problem if so then the headline would be unexceptionable i think however i've heard it often said by various kinds of critics that the that companies in the united states are more likely to go to africa to south america to asia to try out their products whether they be pharmaceuticals or any other kind of genetically engineered product in order to see whether they work because in this country the fda or the epa or the other agencies won't allow them to trial here now is that a real problem in agricultural genetics okay well i can't really speak for genentech but uh first of all it is not a problem in the united states but it is a problem in other many other countries in the world it's it's a disease that can spread readily so it's a concern of the united states and has a special island on the east coast called plum island where research foot and mouth disease the only place in the country where research for foot and mouth disease can occur where they where they are working on the organism because they want to have a vaccine available should it come into the united states so the incentives are both within the country and outside of the country is europe i think is also very concerned about the foot and mouth disease and i think there have been some major outbreaks as a matter of testing it in in uh third world countries i think this is a slightly different issue first of all these vaccines made through recombinant DNA are i think 100 percent i mean except for an allergic reaction potentially they either aren't going to work or if they work they should be totally safe because there's no chance of getting a disease from it as you do with vaccines that are currently used in fact that's one of the beauties of some of the vaccines that are made through recombinant DNA where all you inject into a into an animal a person is a single protein uh whereas that will replace a vaccine where what you inject is a virus that's either he killed is either killed in some manner or has been mutated so it's not very lit and there have been a number of cases where these have not been perfect where people have been killed by vaccines or virus vaccines not being killed totally or not or reverting to uh to become pathogenic the question that you raised from us is very important the fact is that the rules for putting materials on the market in the united states are fortunately the strictest of any countries except possibly switzerland but it is fact that has nothing to do with genetic engineering that our large pharmaceutical companies have always tried their new drugs in countries that have more lax regulations before trying them before putting them on the market this country the recent scandal of order flex is only the most recent one of a long story in which companies do uh tiles wherever they are allowed to do that's some of the fact that the large companies have a power that goes in a sense beyond that of the wish to work of governments and they can do this because there are other parts of the world in which governments do not protect their people as strictly as our tries to we have received a number of interesting questions from the audience we won't get an opportunity to answer all of them right now many of many of them for not only this but the other lectures that we heard will be able to answer in the panel discussion tomorrow but uh professor brill i know has a question before him that he'd like to address so let me turn attention that way okay the question is how do you change the genetic structure of an entire tree or plant on the cell by cell basis okay well you have one cell as i said in the slide and you insert your foreign gene into the chromosome and the cell will then grow become larger and become two cells and now you've got two copies of the chromosome each with a foreign gene and then as you keep on multiplying cells a tree or plant consists of millions and millions of cells now you have millions and millions of cells all with the foreign gene if that foreign gene is let's say to make some uh insecticide then the insecticide will be produced in the plant tissues and insects that chew on the plant will will die hope that answers it let me just list a series of questions if you will Winston and i'll just sort of fire them out here at you questions we've received from the audience and you can perhaps give brief replies to them all right for instance do you feel that the frost resistant microbe should be field testing i believe yes i do i've heard many people discuss that microorganism and i haven't seen any basis to believe that it could create any kind of problem what are your answers to the questions raised by those opposed to field testing well they have to say why they're opposed and if they're opposed because of bull pile then i say what i said before if they're opposed because of gypsy moth and i give them what you've heard and that's basically been it somebody who's opposed to it because it's unnatural uh that's their prejudice or whatever and it's very hard it's it's more difficult to argue okay what about anhydrous ammonia placed on fields to produce nitrogen for our crops hydrogen ammonia kills all the worms which are here to disseminate the soil and hold and renew the elements will not our soil become dead i don't think there's evidence that treating soil with anhydrous ammonia really kills the soil it certainly kills insects and microorganisms but they it doesn't kill them all in the field and they readily come back all right to what extent can a morally responsible scientist in industry refuse to carry out research he finds contrary to his ethics without getting fired if his non non science superiors consider the research financially advantageous that's a very good question i think uh as dr loria really mentioned it's it's an individual morality has to should take precedence uh some people are stronger than others and i guess in some cases they can change the way things are going if you if you don't say anything uh you don't have much character but i'm not sure what that says okay do you see potential military abuses of recombinant dna research say in bacteriological or chemical warfare uh that's there've been quite a few discussions on that uh in fact i went to the state department a couple of years ago and listened to a debate on that and my belief is that if somebody wants to if one wants to get involved in germ warfare there are a whole lot of germs out there that are readily available and one doesn't have to use recombinant dna technology for uh as i said in my talk that i think it's going to be extremely difficult to make an organism worse than any organism that we now have where i think the i mean there were some articles in the wall street journal saying that russia has an active germ warfare program getting using recombinant dna or at least their laboratories that are into this um that hasn't been substantiated and i i don't predict success and from what i've heard the kinds of experiments that they're trying to pursue for instance putting a very bad toxin gene into a microorganism there are reasons to believe that if one did so that microorganism wouldn't just grow and multiply in the environment and be very prevalent what it would do is die very quickly and so if you want to spray the it's easier just to spray the toxin than the microorganism with the toxin where there is some activity going on seems to be defensive in other words i think countries are saying what might another country do and the other thing and what they might do is not uh not involve the genetic engineering experiment for instance if somebody wants to spray a toxin around just throw it out in the environment uh this way there may be a vaccine produced here against that toxin so people are talking about that but i think i i can't imagine using genetic engineering to make an organism worse than any organism i can get right now thank you before i turn the microphone over to chaplain elvi uh i'd like to thank dr bril for a stimulating talk uh and our other panelists as well for their cooperation