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interview: charles arntzen

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The first history of any vaccine goes back to China, hundreds of years ago, for smallpox. The first experimental use of vaccines goes back 200 years to Jenner in England, where he took a scab of cowpox from a cow and rubbed it on a cut on the arm of a boy, and there was sort of a reaction to it. And then--you never do this today--but he challenged the kid with authentic smallpox. And the boy did not get smallpox, so he made the correlation.


President emeritus of the Boyce Thompson Institute for Plant Research at Cornell University, Arntzen is working on making safer vaccines for viruses which kill millions in the developing world. He discusses his work developing edible vaccines (inside GM bananas, tomatoes, or potatoes). He also talks about Europe's opposition to GM foods and science's hopes for applying GM techniques to future foods, medicines, and environmental cleanup. (Interview conducted September 2000.)
That was the first model of a vaccine where you used, in that case, a related virus. Today we call them attenuated viruses, because they're like the real pathogen--a thing that causes disease--but they're either weakened, sometimes killed, chemically inactivated--or there are relatives. So it could be a virus that attacks cattle but not people, but it still triggers an immune response. So for 200 years, most vaccines have been built around this concept of using a relative of what causes disease in us, or an inactivated form.

Then along came molecular biology in the mid- to late 1970s. The first vaccine that came out of this was for hepatitis B. The scientists in that case looked at the entire genome of the hepatitis B virus. That was a pretty heroic scientific feat, with the simple techniques they had about 25 years ago. But they found a gene in the virus that encodes, or it has the information for, the surface of the hepatitis B virus.

You can picture hepatitis B like a little tennis ball. It's got a furry outside and that furry stuff on the outside is protein. That's what sticks to a human cell and causes the virus to be taken up. So these guys did take that gene, moved it to yeast, and grew the yeast in fermentation vats. Now the yeast produces a furry little tennis ball, or a virus-like particle, but there's nothing inside it, so there's no capacity for disease. They purified this furry little tennis ball from yeast, and now formulate it and put it into an injectable form. That was the first hepatitis B vaccine. That came out in 1986. It was licensed by the federal government as being very safe and very effective. That was the first of now what's appearing to be a flood of subunit vaccines that are coming in.

The molecular vaccines are really safe. Are there disadvantages?

It would be nice to solve the poverty issue.   But until we can do that, one of the accomplishments of modifying food is that we can help give these desperately poor people something better to improve their healthI don't want to emphasize that there are disadvantages to modern vaccines. But there are inconveniences, if you will, and those relate to the cost. This is a pretty high-technology process. It's not been very easy to transfer it to developing countries. The second point is that these new vaccines all require refrigeration from the point of manufacture to the point of use. If you're trying to take a vaccine to a Third World country, that adds an enormous cost, and adds a certain unreliability. If this cold chain breaks down someplace, you could lose the effectiveness of your vaccine. So those are the two biggest issues.

In addition, the World Health Organization says, "We'd really like these to be oral vaccines, because they're easier to implement." Their model for that is a polio vaccine--a simple thing that was developed more than two or three decades ago. You take the polio virus in a weakened form, but put it on a sugar cube, and just put that on the mouth or the tongue of a kid. It's an easy delivery mechanism. So the World Health Organization has been looking for the equivalent of the sugar cube delivery system.

What's wrong with syringes?

Well, syringes cost money. Because they cost money, they're often inappropriately used in developing world. People try to clean them, and they shouldn't. They should be throwing them away, but at the cost, they add significantly to the delivery system. The World Health Organization estimates that there are hundreds of thousands of deaths and disease incidents caused by inappropriate needle use. So they'd like to get away from that technology.

Given those hurdles, how can a plant get you through this?

With plant-based vaccines, we're not trying to replace the immunology side of it. We're totally dependent upon our friends who know virology and bacteriology to figure out how to find the genes and find the right components to make the vaccine. I picture myself, as a plant biologist, as a manufacturing specialist. We can put the gene now into the chromosome of the plant, so that every cell in the plant that comes back out of this has the capacity to manufacture a new protein. Then, even more, the plant itself is a delivery system.

So if you can simply eat it, now you don't have to do any complex formulation; you don't have to do purification; and you don't have to deal with some of the other issues about toxicants or other materials that could get into the formulated vaccine.

So plants offer a less expensive production system, and also, we believe, a more efficient and effective delivery system. Coupled with growing a plant and using food-processing technology to prepare the vaccine, we can now take existing technology that's in the developing world--agriculture and food processing that exists around the world--and adapt that to making a pharmaceutical.

Is it in a safe form in the plant?

When we started thinking about delivery systems, the one that I began focusing on about eight years ago was bananas. When you start peeling a banana, the minute that peeling comes off, you are exposing a sterile environment inside. There are no bacteria. There are no fungi in there. This is a self-contained sterile container that also contains protein. So you can think of it as a sterile protein-manufacturing system. If we can put genes into bananas and cause them to produce the protein we want--in this case, a vaccine--in that sterile compartment, then all we have to do is pop it open and deliver it.

What is the process, from start to finish, of how you transform a plant?

. . . We've spent the most time working on diseases caused by viruses or bacteria that . . . cause diarrhea. . . . Diarrheal disease is an enormous problem in the developing world. It causes deaths of about 2 million children every year. That comes from a variety of reasons: inadequate water purification, public hygiene systems, etc. That's one part of solving this problem in the long term. But in the short term, vaccines would be the best route to prevent the disease.

Because the disease is endemic?

It's an endemic problem. Diarrheal disease re-occurs, especially in the developing world. Whenever they enter the monsoon season and other problems like that, it spreads more rapidly. Enormous loss of life occurs from diseases like cholera, enterotoxic E. coli, rotovirus outbreaks.

You've identified a pathogen you're interested in?

. . . Let me try to describe how we make a vaccine for Norwalk virus. Norwalk virus causes diarrhea. You get it in contaminated food, and we in the U.S. would think of it as a case of food poisoning. The Norwalk virus, when we take it in with contaminated food, has a surface protein that binds to cells in our gut, primarily in the intestine. Once it binds, the viral material--which is genes from the virus--is injected into the epithelial cells in our gut. So, essentially, the virus takes over and does genetic engineering in the cells in our gut. The result is massive diarrhea, with its inconvenience, discomfort, etc.

We in the U.S. generally do survive this, because we have rehydration therapy, etc. If you survive that, your immune system has been triggered, and the immune system now starts producing antibodies that are secreted into the gut. If that disease-causing agent comes along again, we're prepared for it. The antibodies bind to the virus and prevent the infection process.

What we wanted to do was take the gene for that surface protein, put it into plant cells, and ask whether the plant would make a virus-like particle. It's a mimic, or a decoy, that looks like the virus, but with none of the genes inside, so it can't cause disease. First of all, we found that we could do that. We did that in collaboration with Mary Estes at Baylor College of Medicine, who's an expert in this stuff.

Do you use a gene gun technique to get them in?

We use one of two routes to put the gene for Norwalk virus into plants. We can use the gene gun, so we essentially are shooting the piece of DNA into a plant cell, where it gets integrated into the chromosome. Or we use another approach, called agrobacterium-mediated transformation. That's where we first take the gene out of the virus and move it into a plant pathogen. Then the plant pathogen is a bacterium, and that moves the gene into a plant cell.

Each system has some advantages. We can use either one. But we end up with an individual cell, which now has this new gene. From that cell, we regenerate a plant back. So the first part of this has just become absolutely routine. There's so much molecular biology going on around the world today. We can bring in a high school student and have them do the first part of putting the genes into the plants for us.

The more complicated side of it then is to regenerate plants back out of this, look at each one and say, "Is it producing the vaccine in the form we want it? Is it producing it in the right place?" For instance, we initially focused on potatoes, and then tomatoes, and later banana fruit. We want to make sure that it's in the proper cells, that it's forming the right vaccine.

So the first one you did was the potato? That was the easiest to transform?

. . . For a variety of reasons, the potato was simplest. You can put the genes in relatively easily. More important for us, we knew how to cause the genes to work in the potato tuber. There'd been a lot of work by collaborators of ours. So essentially, we had a good toolbox to work with, a molecular toolbox, so we could create the gene we wanted.

The other nice thing about potatoes is that we can regenerate a lot of edible plant material back quickly. In about four to five months, we can have a pot full of potatoes, and each pot will give us probably about a kilogram of material. That's enough to do a lot of mouse feeding studies.

In these potatoes, everything else is the same, but there's an additional molecule being generated?

We have a whole suite of things that need to be done in agriculture.  Using the best of new genetics is just part of the solution.  It's not a silver bullet that's going to work by itself.  It's just part of the overall solution.Right. When they put a gene into a potato, essentially all we've added is one new protein. For all practical purposes, that's invisible. You don't see any effect of it. The way we determine that it is, in fact, there, is to do a bioassay. That means taking a piece of the potato and feeding it to a mouse, and then taking blood samples from the mouse and saying, "Does it get new antibodies? Does it get an antibody against this protein we're interested in?"

Once we'd shown that that works with potatoes and what the advantage of the system was, we could save some of the potatoes and just cut them up into pieces, replant them. Now we get identical plants coming back out. So we had uniformity of our experiment.

The next step for us has been to move the same type of work into tomatoes. That took a bit more work to build a toolbox, if you will, so we can create the genes that will work in the tomato fruit.

Before that, how were you sure this is working in the potato?

The question is, "How do we know that the vaccine is there?" The answer is pretty simple. We just peel it, cut it up into cubes, and feed the potato to a mouse. We then take blood samples from that mouse on a periodic basis, and we ask if the mouse has serum antibodies, or is he now making antibodies against that protein? The answer was yes, we found them. . . .

In all mammals, we're producing secretory antibodies all the time--in our lungs, in our saliva, throughout the gut. We can detect those antibodies in fecal pellets. Sure enough, after eating our genetically designed potatoes, the mouse would start making secretory antibodies.

Is the mouse a good model then for humans?

Mice are the traditional model for human vaccines. Once we had pre-clinical data with mice, we then went to the U.S. Food and Drug Administration and asked for permission to try the same experiments with people. They went through all the regulatory issues, and the first time we tried this, it took about eight months for us to get approval to guarantee safety for the volunteers. But we then had human volunteers eat some of our potatoes, and sure enough, got the same result. They got antibodies in the blood serum and secretory antibodies. So we can tell that the human immune system can also be triggered by simply eating raw potatoes that contain our vaccine that we've designed into them.

Do they have to eat raw potatoes?

Well, raw potatoes aren't bad. I sat and ate raw potatoes when my mother was peeling them. I remember that as a kid. Now, we perhaps did a bit more, because some of the volunteers had to eat up to 100 grams of raw potato, which is about the size of a tennis ball or so. That's a big bowl of some starch. But they did it, and we thanked them for it, and sure enough, they got the proper immune response.

You were thinking that, because it was raw, this might not be the ideal delivery?

Yes. The reason we do raw potatoes is because many of these antigens or vaccines that we're interested in would be destroyed by heating. So if you boiled the potatoes, if you made a mashed potato or a french fry, we anticipate that all the activity would be gone.

So then you moved on to other plants?

Well, because you can't process or cook a potato easily, we decided that we're going to try the same experiments in other plants. The next step was to go to tomatoes. . . . One of the big reasons to try tomatoes is that they are easily processed. We can now start taking food-processing technology ... and just make tomato juice, or more important for us, we're trying to freeze-dry the tomato juice and just get a dry powder.

I want to emphasize, why should we go and make a dry tomato powder? The answer is really that this is a medicine. We're not trying to make a new V8 juice. We're trying to make a medicine. If we're going to be successful, we have to deal with things that are part of the pharmaceutical industry. They talk about proper dosage. They talk about lot-to-lot variation, meaning, if you make up 100,000 doses at one time, the next lot has to be comparable in activity.

The only way I can deal with that from a plant side of things is to start using food-processing technology to get a dry powder, or ultimately, when we get to bananas, I think something like a baby food puree. You can make tens of thousands of little containers of a banana baby food, and you can sample each one and verify that the dosage is uniform--that they're free of any sort of bacterial toxins or anything else--the standard sort of stuff that has to be done with any pharmaceutical product. Our switch on this is we can use food-processing technology, which is available in the developing world, and apply it to a medicine.

Assuming everything goes well, what is your vision?

Let's say we want to deliver vaccines against diarrhea in Africa, where they're needed. I'll tell you what I do not see: I don't see a village banana tree with vaccines in it, where everyone goes up and takes one when they want to. That, for a variety of reasons, would be impractical. You wouldn't control dosage, etc. What I do see would be a company or a government organization established in a country--maybe South Africa initially, because they have a very good infrastructure. I see them having their own vaccine companies in South Africa, where they would take some of the plant material that's generated, begin to grow it under confined, regulated conditions, and manufacturing an herbal medicine of sorts. It's very acceptable and they're accustomed to it in Africa, and they're used to taking a dried plant material.

Let's say it was a banana. Making a dried banana chip and delivering that in a little package, saying, "This is a medicine" would be normal. They have dried banana chips around the world. If we could just do that, or grind up this dried banana chip and spike it into a little milk and give it to an infant--that's something that could be done at a local level, without a lot of high technology. It would take an educational activity. But this is something that would be consistent with a type of medicine that they have today.

Would it be cheap?

The question is, what would it cost to do this in a developing country? I think it's pretty obvious that the actual production of the material could be extremely cheap. The next step, having some sort of quality assurance, is tougher for me to estimate. You would want to make sure that you have the systems in place, that the dosage is accurate and reliable, and that the processing . . . is reliable. It's hard for me to anticipate the cost to this.

But clearly it's something that's doable. There has to be a will to accomplish this. First of all, it doesn't have to be expensive. It simply has to be something that's built into an organization in the developing world.

It's for these sorts of reasons that our goal isn't necessarily to take this first to a very poor country in Africa. In fact, we've built our first connections with extremely good, sophisticated scientists in Mexico. There is a demand for diarrheal disease vaccines in Mexico, and they have very good in-country vaccine companies. Some of these are already making and distributing vaccines. They have a very good public health system. So our goal is to try to collaborate with people in Mexico, transfer this technology, test it there, demonstrate that it works, and do that in parallel with what we're doing in the U.S. I should emphasize--we're trying to do this first in the U.S., not because I'm nationalistic, but because I don't want to be accused of taking this technology and testing it on poor people someplace else in the world.

We've had the rise of this controversy over genetically modified foods. Did this surprise you when it happened? Has it affected your work?

The controversy over genetically modified foods really hasn't had any direct impact on our research activities. And I'm happy about that. I keep emphasizing, we're producing medicines. Materials that generate as an edible vaccine will never be in the grocery store, and we're building in controls to ensure that that won't happen.

But in the broader issue, am I surprised at what has happened? Perhaps not, because I think this has been a surprise to the public. They haven't seen all this background science and technology being developed. It's been something that is so common to us in the scientific community. I haven't seen anything that's shocking or that concerns me about any sort of safety issue, but I've seen it coming for the last 20-plus years. It seems obvious and routine to me.

But I certainly am aware, just from my conversations with family and relatives, that they find it shocking that all these changes are possible. It's sort of science fiction stuff, and I guess whenever something comes along that you hadn't thought about, it raises some concerns.

What potential in this technology people should be aware of?

Well, clearly the next generation of plants that are genetically modified are going to be enormously different from the first generation that came out. We're seeing a lot more activity that's focused around human health. There are a variety of reasons for that, but probably the greatest reason in the U.S. is that we've got excess food today. There's less return in just increasing yields.

What we have to focus on is how we make our foods better. We can keep reminding ourselves that we can do things that will improve the human health value, that we're going to add value to society and to the products that farmers are producing, and we're going to have a good economic impact all throughout this food chain.

My own special interest is this area of producing actual pharmaceuticals in plants. Because of the institute where I am, it really hasn't been a focus on the U.S. in particular. It's been more a focus on the Third World. How can we deliver . . . a very effective vaccine, but make developing countries less dependent upon philanthropy and big industry and things of that nature? How can we provide the technology so that a Third World country can make the vaccines themselves?

Is this technology useful because it allows you to grow plants in inhospitable soils? What about the "golden rice" argument?

Well, if you start looking at specific examples of where genetically modified foods have a value in the developing world, I think number one is the issue of food security--protecting plants against disease, so that they grow better. Also, perhaps, virus resistance, sort of immunizing plants against viruses as the number one example. It's going to have the biggest effect in the developing world.

But secondarily, as we have seen with the golden rice story, you can also change the qualities of the plant itself. We can put things like vitamin A into a rice plant, as Dr. Potrykus and his colleagues did. That's quite incredible, and it's going to solve major problems in the developing world, as to the availability of food materials for good nutrition.

I know that a standard response is, "Well, they should just be eating more green leafy vegetables." I've been to India. I've stayed in a very nice hotel in the center of New Delhi. And you see families living on the sidewalk on an old patch of blanket out there. This is part of this global migration of families to the cities, as populations grow. They no longer have a little garden plot to grow their materials. They're stuck in a concrete jungle someplace. They don't have access to green leafy vegetables and things that they need, and they're living on a handful of rice every day.

I see the Rockefeller Foundation and others recognizing this, and seeing that we've got these global shifts in people stuck in desperate poverty, and the few foods they can eat. They have focused on issues like, how can we change the quality of that food that they do have available, and improve the nutrition of these people?

Because the people aren't getting a balanced diet?

Because they can't get a balanced diet. They're desperately poor. They're part of this urban migration that is just dragging people into a situation where they have no choice. It would be nice to solve the poverty issue. That would be great. But until we can do that, one of the accomplishments of modifying our food is that we can help give these desperately poor people something better to improve their health as they try to dig their way out of the situation that they're in.

Greenpeace says that there's enough food to feed the world already--that the problem is distribution.

Yes. The argument that there's enough food in the world, but it's in the wrong place at the wrong time--that's a real argument. But a lot of the food sources we have are not easily shipped. A fresh tomato isn't going to be shipped from Iowa to Bangladesh. Grains can be shipped--cereal , grains, and legumes and things like that.

But we tried some experiments of just shipping food and giving it away. For instance, in India and Bangladesh in the 1960s, when there was famine, if a country like the U.S. comes in and just provides food, it further degrades the capacity of the country itself to stimulate its own agricultural economy. I think we saw when we made those mistakes at one time, and then we shifted our emphasis on providing the technology to people to produce their own food. That's been much more successful.

In a sense, we haven't even been involved in it so much in China, but you can see the enormous advancements in China in feeding their own people. It's been through an implementation of good agricultural policy, using the best of the new technologies that are available, and moving very rapidly. If you travel in China today, you don't see the starvation that is prevalent in other parts of the world, especially in the poorer parts of the world today.

Is it your sense that India and China see a lot of potential in this technology?

It's very interesting to compare India and China. China has moved very aggressively in all aspects of food technology, emphasizing things like infrastructure for transport of foods, but also rapidly mobilizing to use new genetic engineering techniques. Essentially, they don't take just one part of it. Biotechnology is not a sole solution, but a whole structural analysis is a solution.

I've traveled a fair amount in India. India has apparently just taken more of a piecemeal part. It's a highly democratic country, and some of the disadvantages of democracy have come in not having China's sort of overall planning system. But India has done a remarkable job of feeding a population that has doubled in the last several decades. They're still feeding their people. They have been slower to adopt technology for genetic engineering, and in part, maybe that's because they haven't had the demand yet. They haven't had the food demands that China has seen.

We have a projection over the next 100 years of a doubling of world population. Without new agricultural technologies, is that going to be impossible?

Well, it's hard for me to talk about what's going to happen over the next 100 years or 50 years. It's easier to picture what's going to happen over the next two decades. Now, we have the young people born on the ground today, who are going to produce an additional 1 billion people each decade. That many new people every ten years is the size of India. When you start thinking of this massive food need that we have--and largely the population is increasing where we don't have an adequate food supply--we're just going to exacerbate all the problems we have today.

Of course we need new technology. We can't just continue to plow up forests or try to find new prairies to convert into farmland. That doesn't exist in the places we need it, and we don't want to shift the remaining natural areas of the world that we have today and destroy them to get more farmland. All we can do is increase the productivity of the land that we have today, to meet this enormous coming increase in population.

The other argument is that a more efficient type of organic farming should be instituted, rather than developing new technology.

It's really baffling to me how anyone can say that we just don't need new technology. India is largely an organic farming nation today. As they try to take on new technology, the most successful has been genetic technology. It's the improved rices that came out of international research activities, and the improved wheats. Taking genetically improved materials is what's allowed them to feed their population.

Some of that has been coupled with use of fertilizer, for instance, in India, which has dramatically increased the rice yields. What's missing in places like India, for instance, is a lot of additional technology--like post-harvest storage of the material, drying of the material, packaging of it, so they don't have losses to insects or disease problems in the stored material.

So I think people are fixated right now on, "Oh, my God, they're doing something with genetics, and that's the problem." But we have a whole suite of things that need to be done in agriculture, and using the best of new genetics is just part of the solution. It's not a silver bullet that's going to work by itself. But it's just part of the overall solution.

We see the moratorium in Europe, and labeling laws. And you see a few companies in this country, like Gerber and Frito-Lay, deciding not to produce these. Do you have any concerns that this might be delayed, or stopped in its tracks?

Clearly, the attitudes about genetically modified foods in Europe have delayed its implementation in Europe. I think their perceptions are based upon a series of other things that don't have any relevance to genetic engineering per se.

Such as?

Such as, they have problems with BSE, the mad cow disease, which has caused in England in particular a lack of confidence in their regulatory system. A whole series of other events in Europe has just caused people to be concerned about safety of their food supply. None of these have any relevance directly to genetic engineering, but it's caused the public to question their governments and what their governments can do. In addition, the Europeans are affluent. They have an excess supply of food, and they're subsidizing their farmers to reduce production. And I can understand this. The whole notion of adding new technology to add more food seems bizarre.

. . . Why is it different in the U.S.? Well, in part, I believe, even though we have more food than we need, most folks here recognize that the food supply from the U.S. is part of the global economy. It's good for our economics, but it's also good for the rest of the world. Because if we just stopped exporting food, it would have an enormous impact on other parts of the world. So I see a fundamental difference there in the acceptance of the technology.

Let's say that the U.S. and Europe would decide, "We're never going to do genetically modified foods." . . . I don't think it's going to stop the technology. It's so essential for China, for India, for other parts of the developing world to increase their food supply to meet their burgeoning populations; it's going to happen. We can't be so arrogant to think that we determine what sort of science is going to be done on a global basis.

We can be pleased with ourselves that, in the U.S., we've really been the leaders in developing the new technology and implementing it safely in this country. We haven't had so much as a headache from any genetically modified food, and I think that's because we thought about these things. We go back to something called the Asilomar Conference, back in the 1970s. Back in the 1980s, I was involved in government committees that dealt with safety issues, about what type of genetic engineering we could do, how we would move genetically modified plants into the field. We've been working on this stuff since the technology was developed.

In the U.S. it's been science-driven. We have had great cooperation between federal agencies. But we've had the scientists who understand this and who developed it, working on this all the way through.

So, people who say that regulatory agencies are giving this a free ride--are they wrong?

I think we've got a very efficient regulatory system in the U.S. I believe it's because we've focused on science, and we've had the scientists who understand this, engaged from the beginning--back from the 1970s. The idea that the U.S. government is just letting things fly through--I can guarantee you that it's not the case. The amount of time we've spent in the last two years just dealing with regulatory issues to test our plant-based vaccines . . . at times, as a scientist, I'm ready to pull my hair out, saying, "Why don't these people just let us move ahead? Let's get on with it." We've got something that can solve a world problem, and they want us to write another form to prove that this is safe, etc.

At the same time, as a rational scientist, I've seen this stuff evolving, and I also know that we have to do this. While I'm absolutely convinced that the products we're testing for vaccines are safe, I know that perception is a crucial issue. If we ever did something that would cause the public to lose confidence in what we're doing, what I've spent the last nine years on could just collapse. Then I'd really be frustrated. So I want to make sure that we do this right.

In spite of how frustrated I get with government folks at some times, I'm so pleased they're there, because I know that, in the U.S., we have this process in place. I can always refer back to it and say, "Yes, we've done all these things, we've considered all these things, and it works."

Are you concerned about safety and ecological issues?

Well, I'm very concerned about the perception issues. From a scientific standpoint, I don't see anything inherently unsafe about what we're doing in putting genes into, say, a tomato, that would cause a tomato to produce a vaccine. But I am extremely concerned that someone might say, "Oh, he's putting hepatitis B in tomatoes." Well, we're not, of course. But it's so easy to make an incorrect assumption about this. So what we're trying to do is build in safeguards right now.

We have funding from the U.S. Department of Agriculture for a project that I think is pretty neat. We are taking our tomatoes, which now contain genes for a vaccine. We're crossing them into other genetic varieties that are male-sterile--that means they don't produce pollen. Furthermore, with these plants now, we're crossing them so that we will produce seedless tomatoes. . . . So we can grow tomatoes now--and I would expect this would be done in greenhouses, because that's pretty standard production system--but there would be no pollen, no seeds. There's no way that this stuff can inadvertently escape into the environment.

It's going to add a little bit of cost to the production, because we'll have to make cuttings of our tomatoes to get the next generation, rather than collecting seeds. But I believe that to prevent misperception is much more important. So even though I don't see the safety need for this, I firmly believe that we should move in this direction, to give the public confidence that our vaccine-containing tomatoes are never going to show up in the marketplace in their grocery store.

In addition to using plants for food, what are the things we might use in the future?

We're just at the tip of the iceberg of an enormous number of things that will be technically possible to do with plants. Some folks are talking about how they are going to change the qualities of plants so that they'll be able to do bio-remediation and clean up toxic sites. To some extent, that is a viable technology, and it's a sustainable way of dealing with complex issues. We're clearly going to use plants to produce more nutritious foods, or actually medicines themselves, as I've talked about.

I see that we're going to also very rapidly move into biological systems to produce industrial precursor chemicals. Growing switchgrass, for instance, a very easy, high-productive grass to make chemicals, which will substitute for petrochemicals coming out of the petrol industry. Now that petroleum is upwards from $30 a barrel, this sort of interest gets more interesting.

All of these things . . . don't have to depend on genetic modification. But what we're going to find is that more and more examples will appear where, if you could switch off a gene or an enzyme in a plant, or you could add some new component, it's going to make it much easier to do. If we can just cut down the amount of lignin in the poplar trees that we're growing for paper pulp to make newspapers, and get less lignin contamination in streams and waterways, that makes a lot of sense.

As time goes on, as we try more and more systems over the next two decades, we're going to see a gradual replacement to using the power of genetics, a sustainable modification of a biological resource, as the much preferred avenue over using cost-intensive industrial processes to do the same things.

What's the idea in taking a quality from one organism into another?

. . . An example that's used a lot was the flounder gene into tomatoes. The background of it, from a scientific standpoint, is that we have a good understanding of why some fish can tolerate cold, like the flounder. We'd like to have some of our fruits and vegetables tolerate cold, like strawberries, so they don't get nipped by an early frost, or by a late frost. So scientists have done experiments trying to mimic the cellular environment of a flounder in a strawberry.

These are really excellent basic science studies, and I should emphasize, they've never gone beyond that. No one's ever started a commercial development of anything from it. But I think the public responds negatively to that. My perception, after talking just to family members and others, is that you can almost see their nose wrinkling up, because there's something about a fishy smell to a strawberry. It's a mental image. More than anything else, it's just, "Ooh, I wouldn't like that." It has nothing to do with the science, I believe. It's just the way we're wired in our brain. A fish is supposed to smell like a fish, and a strawberry like a strawberry. And just superimposing words on each other--we back off. We don't like that. . . .

People don't see the connection between humans and the tomato in terms of the shared genetic heritage. Do you think we have a big educational job here?

Genetics is a really complex issue for public acceptance, because almost all the things we think about with regard to genetics have been bad. It somehow goes back to Hitlerism and something that has a negative connotation. When the positive stories about genetics have come out, about increasing the yields of our crops or making larger tomatoes or strawberries that taste good, that's genetics. But those stories aren't linked to genetics. We just have the wrong connection of negative images, and I think that persists at the present time.

How do you educate the public? That's being a little bit arrogant on the scientific standpoint. They should know as much as we do. I'd say it's more like, how do you interest the public in genetics, causing the public to want to inquire more and understand more about it? And I think that's going to be one of the positive outcomes of all this genetically modified food, because once the initial potentially negative response occurs, I think we have an intelligent public overall. They want to know more about this.

As they begin to understand that it's just a continuation of what we've been doing in crop improvement for the last 100 years, it's Burpee's tomatoes, you know, the old seed catalogues that our parents used to buy. It's just in a new formulation. Once people realize this, then I think all of this is going to calm down.

We had this controversy in medical research in the 1970s, and most people now accept that genetically engineered insulin is a good thing. Do you think we'll get to that stage with agriculture? It's not controversial anymore in medicine.

I don't think in general that the public is concerned about the use of biotechnology to make products for medicine anymore. Clearly, there are still issues with regard to the origin of stem cells for treatment. There will be more controversies that will come along in human medicine, but they're not focused on the process of biotechnology. I believe that's because of the profound benefits that we've seen from some of the new products. I believe, as a new generation of products appears in the agricultural side, as the public sees the immediate benefit and value from these things, we will slide into this same sort of acceptance.

Essentially what we're going to move to, rather than focusing on how it was done, we're going to focus on, "What's the outcome? What is the material that we're going to get in the end of the day? Is it better for my health? Is it better for the way we treat the environment? Is it good for the developing world and for solving problems of global importance?" . . .


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