Yes. I think we would consider all of the crops that we have as crops that have been subjected to some type of genetic modification. Now, of course, we have the newer techniques--recombinant DNA techniques--of introducing a single gene or a few genes. . . .

From the early 1980s, these methods were applied in medicine?

			Biotechnology coordinator at FDA, he discusses the risk of allergenicity with GM technology and the challenges facing regulatory agencies if mandatory labeling is implemented. Maryanski also points out the complexity of the U.S. food supply, which makes it difficult to segregate GM food from non-GM food. (Interview conducted October 2000.)

Yes. The first product that FDA reviewed was insulin produced through fermentation. That was approved in 1982. We even had experience prior to that, because of a scientist who had first raised questions about the safe use of this technology. That led to the development at the National Institutes of Health of guidelines for research.

So when the questions started to be raised about the application of these techniques in the food sector, FDA had a lot of experience from the research guidelines through NIH and from its own experience in reviewing the first pharmaceuticals.

We've used genetic engineering in enzymes in foods without public fuss.

Yes. The first food ingredient was something called chymosin, or what people may know better as rennet. It's the enzyme used to clot milk to make cheese. That enzyme was produced in a bacteria as the first product of modern biotechnology. FDA made a decision on rennet in 1990. We had a petition with an opportunity for public comment, and we received no comments from the public at all, at that time.

That was just the first of many enzymes?

Yes. Of course, there were other things--enzymes used to make high fructose corn syrup, for example, which is used in soft drinks.

So before this current phase, what products have genetically engineered enzymes?

. . . Things like bread and cheese and soft drinks, and the vitamins and amino acids and so forth. But they are often not things that people would see in the grocery store. In other words, when you buy a loaf of bread, you may not realize that the enzymes used to produce that bread have been genetically modified. That they're very minor components of the food, I guess, is the point.

Those products have created very little public comment. The second wave is crops transformed to make more traditional foods.

Yes. . . . That's about the time that FDA was becoming aware that agriculture was going to be a big sector of the biotechnology industry. Under the mechanisms that we regulate food safety, we do not routinely review new varieties of corn and potatoes and things that one would think of as food before they go to market, even though there are several hundred new varieties developed in the U.S. every year. Nevertheless, we do have authority over the safety of that food.

But would you let those crops in, and then recall them if they're dangerous?

Yes. The law places the legal responsibility on the purveyor--the person who's selling the product--to provide a safe and wholesome product to the consumer. The law also gives FDA broad enforcement authority to take action if there is something that's unsafe about the product.

What makes you think these new genetically modified varieties will be different?

We actually spent several years at FDA looking at what would be the impact of this technology on the food supply. The government had decided that, as a matter of policy, biotechnology would be regulated under the existing statutes, which for FDA meant that we would regulate foods under the Food, Drug and Cosmetic Act. We had to be sure that in fact that statute was adequate.

So our scientists examined all aspects of this technology relative to food production--looking at how similar the products would be, how they would be different, what kinds of safety testing would be appropriate for these products. After careful consideration, we felt that we were dealing with foods that we're well familiar with, in the sense that these are new varieties of corn and potatoes, soybeans. . . .

Explain the concept of "GRAS."

Under the Food, Drug and Cosmetic Act, food additives--things like spices, flavors, preservatives, and sweeteners--are required to be approved by FDA before they can be used in food. The definition of a food additive does have exemptions for substances that are Generally Recognized As Safe (GRAS). Congress, in enacting the requirement for food additives, recognized there were many substances that had been safely used in food, and did not want a pre-market review of all of those substances, such as sugar and vinegar and so forth. They also said that . . . if it's generally recognized in the scientific community that the use of the substance is safe in food, that it would be exempt from the pre-market approval requirement.

So we have a large class of substances--enzymes, many flavors, and many common food substances, such as vinegar and sugar and salt and pepper and so forth--that are added to food, but that do not undergo pre-market approval, because they are generally recognized as safe.

Could this apply to genetically engineered enzymes, for example?

Yes. FDA has said that, in looking at modifications by genetic engineering, there can be new substances in the food, such as a protein or an enzyme. To the extent that those substances are similar to proteins or enzymes that we have consumed safely, we would consider those to be essentially similar to substances that have been accepted as GRAS, and so we will not require pre-market approval for those substances.

We do have the legal tool to require pre-market approval if genetic modification is used to introduce a substance that's very different, and we don't have a basis to believe that that substance is generally recognized as safe. . . .

So a potato is a potato is a potato, if it's not checked.

Yes. There is the possibility that someone could change the potato in a way that would be significantly different. If, for example, through gene technology, a protein were introduced that was very different from proteins that we've safely consumed, FDA has authority to require pre-market approval for that protein as a food additive. . . .

Is a variety of BT corn of interest to the FDA?

We have felt from the beginning that when there is a new technology--and we consider recombinant DNA or modern biotechnology to be a new technology--it's prudent practice for developers to discuss products that are produced by this new technology with FDA before they enter the marketplace. Then we can be sure that there's nothing about this technology that has not been resolved in terms of food safety. . . .

In terms of a product like BT corn, where the corn is modified to produce a substance that is a pesticide, that pesticide substance is evaluated by EPA under the pesticide laws and regulations. But the corn itself, in terms of its use in human food, still falls under FDA.

If it was "substantially equivalent," would you allow it?

"Substantial equivalence" is a difficult term, and it's not a legal term in the U.S. . . . We use that concept as a way of comparing the new product with its counterpart, in terms of how similar, how different it is, so that we can focus the testing on making sure that any differences in the product are also safe.

How similar is BT corn or Roundup Ready soy to other varieties?

In terms of the testing that we have seen, those products, except for the introduced trait, are similar in all other aspects that have been measured. In other words, the corn is still the same corn in terms of its starch content and its other nutrients. Whatever is typical of that particular plant has not been altered.

Given that there was little public comment on enzymes, were you surprised when this issue recently became of greater public interest?

We had what we thought was quite a bit of interest in this in the early 1990s, when we were in the process of reviewing the first products, including the Flavor-Saver tomato. We had a very open public process, and FDA did receive many comments about this technology at that time. Once we completed that public process and made the decision for the first products to go to market, there were then several years when we really received very little input from the public. It's only been within the past couple of years that the level of concern has once again been raised. . . .

In terms of allergenicity, is there anything new because of the process by which these products are made?

Allergenicity is not a new topic, and it's something that we do take very seriously. Because genetic material can be moved from different sources--from one plant to another, or from one non-food source to another--there is the possibility of introducing new proteins into the food. We know that there are, of course, many proteins that make up the food supply. A few of those proteins are allergens. . . . So one has to be very cognizant of possible allergenicity when a new protein is introduced into a food, whether that's by a gene transfer modification, or whether it's by a simple addition in the manufacturing process.

FDA indicated in its early policy that we would be particularly concerned if genetic material were transferred from a food that we know causes allergic reactions, such as peanuts or fish or soybeans. In that case, we actually feel that developers should assume that they have transferred an allergen, unless they can scientifically demonstrate that they have not. . . .

Would you say there's more risk of allergenicity with this technology?

We actually think the risk is very low, based on our discussions with scientists who are expert in the field of food allergy. The reason is that there are ways to scientifically assess the possible allergenicity of a protein that's derived from a source, where we know that individuals are allergic to that food. We've actually had an example where a soybean was developed with a protein from Brazil nut. There are individuals who are allergic to tree nuts, including Brazil nuts. The scientific procedures did demonstrate that that protein was an allergen, and that product was discontinued.

In terms of proteins that would come from sources that are not known to be allergens--bacteria, for example--the feeling from the scientists was that, while there's always some chance that a protein could be an allergen, it wasn't very likely that most proteins would be allergens, particularly if they did not exhibit characteristics that are typical of food allergens. Food allergens, for example, tend to resist digestion. The proteins that have been introduced into foods, to this point in time, have all been shown to be readily digestible, and not similar to any known toxins or allergens. . . .

Would you say that was the biggest of the issues? What about toxicity?

There are two aspects to that. One is the genetic material that's introduced that produces a new substance, such as a protein. That's where we can determine what the protein's function is, whether it's digestible, and whether it has any similarities to known toxins and allergens.

Then there's a second area of question, which is about the food itself. Foods contain many different substances, some of which would be harmful to people if they were present in levels that are higher than what is typical of the crops that we now have. So we do make sure that companies run the analyses to make sure that substances that are typical of the food are present at levels that are acceptable. . . .

What about the neutrality of the agency as to whether this technology has succeeded or failed?

Our responsibility is to protect the American public. In terms of products that are developed by a technology--whether it's a new technology or a conventional technology--our role is to ensure that the products are safe. Our role is not really to make a judgment about whether they should be placed in the marketplace or not. . . . We are not here to impede products from being developed and introduced into the market if they are safe. We are here as the gatekeeper to close the gate if a product is not going to be safe for consumers. . . .

You're not interested in the process by which a food is made, but in its safety?

That's an important question, because yes, it is the characteristics of the ultimate food product that we're interested in, in terms of whether that product is safe for consumers. But it is important to know how a product is produced, because that often gives you a window into questions about safety. Different processes may raise different issues.

. . .

As a regulator, does the term "genetically modified food" give you any definitional problems?

I don't think it really gives us problems. It's just that it's been difficult to find terminology that everyone can understand and accept around the world. We have always thought about genetic modification as something that applies to all methods of altering plants, animals, microorganisms, that are used for producing goods, such as foods and agriculture. Today that term is being applied more specifically to the modern techniques of biotechnology. . . .

If we were labeling something as genetically modified, we'd have to label a lot of things.

In our view, we'd have to label all the foods in the market if we just simply said the broad definition of "genetic modification."

Clearly, that's not what people are talking about. . . . Europeans are talking about food made with recombinant DNA techniques.

That is really the main issue. The actual legislation in Europe is a little bit broader than just recombinant DNA. It includes some other sort of modern techniques, but excludes from their definition the more traditional kinds of techniques, such as hybridization. . . .

Mandatory labeling is very complex. What kinds of problems would you have to wrestle with?

First of all, you have the plant that has been developed for a particular purpose, and there may be several varieties of that plant that have been developed by recombinant DNA techniques--several varieties of BT corn, for example. But there may be other varieties of corn, and there are other varieties of corn, that have been developed by different methods of plant breeding. All of those varieties of corn will be processed together. They will be shipped together. Then the processed products will then be introduced into many different kinds of products. So it's very difficult to distinguish which products contain material from modern biotechnology or any other particular technology.

In terms of the food label itself, it can be very complicated, because you have many ingredients in the food. An ingredient such as an oil, for example, may or may not contain DNA or protein, depending on whether that oil is highly refined or only partially refined, and whether it's a composite of many different varieties that were used to make that oil. . . .

What about labeling food derived from animals that have eaten GM foods as feed?

We have considered that issue. We do regulate animal feeds. The feeds, of course, in some cases, contain new proteins. Those proteins, as I've mentioned earlier, have been shown to be readily digestible. So we would not expect any new material or different material to accumulate in the meat or in the milk of animals that are fed feeds that are derived from plants that have been developed by modern biotechnology.

Would you like to be faced with mandatory labeling?

For us, it's more a question of the law that we have. We do, of course, have mandatory labeling for significant changes in the food. If there's a new allergen in the food that people would not expect, that must be labeled. If a consumer needs to know how to cook or prepare the food differently, that must be disclosed on the label. If the food has a different nutritional value, those kinds of changes have to be disclosed for a food developed by modern biotechnology, just as they do for other foods.

But the question about the method--which is really the question that many people would like to know--is a difficult one. Under our law, we are required to make information available if it's material to the product. We have looked very carefully at the use of recombinant DNA techniques, and we do not have any information that the simple use of the techniques creates a class of foods that is different in safety or quality from foods developed by other methods of plant breeding. So we don't have a legal basis to require manufacturers to disclose that information on the label.

The manufacturers are free to disclose whether the product is developed by modern biotechnology or not developed by those processes, as long as they do so in a way that is truthful and doesn't mislead the consumer.

Does that mean that the companies can't make claims about good or bad aspects?

When we look at labeling, we don't just look at the specific words, such as "produced using modern biotechnology." We have to look at the whole food label. What image does that convey to the consumer? What message will a consumer take away from that food label? So if the product says, "This product was not produced using modern biotechnology," but it has a happy face or sunshine or something that conveys that this product is better than its competitor, then we think that would be misleading to the consumer. If it's simply a factual statement that this product was or was not produced by modern biotechnology, then we would think that would be suitable labeling.

. . .

What about the taco shells that Taco Bell used? How could something like this happen, given our regulatory structure?

This was a case of a product that was not approved for use in food. It was approved by EPA for use in animal feed. The company that developed this particular plant believed that they had a management program that would ensure that the growers of this corn would channel that product into feed use, and keep it out of the food supply. In fact, the company did explain that plan to FDA. Obviously, it didn't work.

We did begin to receive reports that there had been some methods of detecting the Cry9C, the name of this protein, in taco shells. We initiated a full investigation into the matter. . . . As a result of that investigation, we did determine through analytical methodology that in fact the Cry9C protein was present in the taco shells that had been provided by the Kraft Company.

How widespread was this?

I don't think we know that exactly. . . . Nevertheless, Kraft recalled the products. . . .

Was a potential allergen released into the food supply?

We have no information to suggest that there is a health problem with this product. At the same time, it had not completed the review process. There were questions about whether this particular protein might have some of the characteristics that are similar to food allergens.

How would you reassure an anxious consumer? How could you make this less likely to happen?

We have to be very cognizant about the complexity about the food supply, that it's very difficult to separate something that's used in feed from something that may also be used in food. That's something that all the agencies will be looking at very carefully.

It's not terribly reassuring to hear that.

What we want to have in place is a process where products complete the regulatory system before they go to market. I think that's the most important thing, from FDA's perspective. That's why we're moving to a mandatory notification system, to make sure that we are in fact informed about all products before they go to market.

The mandatory system exists under existing law? Or would you need new laws?

We think we have the authority. We're going to publish a proposal and explain the legal basis that we believe that we can require companies to notify us, under the existing law.

So if I'm a company producing a product with new genes, what do I have to do to comply with mandatory notification?

The process that's been in place since the early 1990s is based on the 1992 policy, which provides comprehensive guidance to developers about the kinds of issues that should be taken into account during the development and testing of these products. What FDA has said right from the beginning is that we want companies to come in and talk to us about these products early on, early and often, even when they're on the drawing board. . . .

That gives an interchange between the FDA scientists and the company scientists about the design of tests. So when the company then goes forward with the testing, they have FDA's advice in the beginning. Once they've completed all the testing, then we ask them to provide information to us, so that we can evaluate whether in fact they have done the correct testing and whether they've answered the relevant safety issues before these products go to market. . . .

Why should we trust a system like that?

We don't have the resources to do product development kind of testing. On the other hand, as I said, our scientists do interact with the company scientists. They look at the company scientists' data. That's our first line of making sure that the data is sound. Under our system, the data that supports a safety of product is always available, under the Freedom of Information Act, to anyone who would like to review it. So all scientists who are interested--or others, for that matter--can review that data. Of course, there is a federal law against defrauding the government. So it's not in anyone's interest to provide false information to the agency. . . .

What do you say to those people who say we've rushed headlong into this technology?

It doesn't seem that way to those of us that have been working in this area for many years. Our scientists have spent many hours reviewing data on the technology as well as the specific products. . . . In reaching our decision on the Flavor-Saver tomato, we discussed the scientific approach that had been used by the company. That was the approach put forward in our 1992 policy, with our Food Advisory Committee, which is a committee of experts from outside FDA consisting of academic, industry, and consumer representatives.

One of the things that the committee concluded was that the product did not raise substantial public health issues. They felt that it was appropriate for the company and FDA to have gone through this elaborate process over several years of review of this product, but in fact they suggested that we find a simpler way, if there were going to be products that would be similar to that. . . .

But you don't think this has been rushed?

No. This is something that FDA has done in a very deliberate manner: looking at the science first; looking at the types of products and our regulatory system; and really trying it out through the consultation process. It's been a very deliberative and publicly open process.

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