Has food always been genetically modified?
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?
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.
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.)
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
We've used genetic engineering in enzymes in foods without public
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
. . . 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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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.