杏吧原创

EARLIER this year, Britain was rocked by claims that genetically modified
foods are dangerous. Arpad Pusztai, a biochemist who used to work at the Rowett
Research Institute in Scotland, said he had shown that GM potatoes were harmful
to rats because of their genetic modification alone.

Were the GM potatoes toxic? On the basis of Pusztai鈥檚 evidence, it鈥檚
impossible to say. In fact, his results support only one obvious conclusion:
rats hate potatoes.

Pusztai fed separate groups of rats on normal or GM potatoes to see if the GM
food had different effects. That鈥檚 good, basic toxicology. Unfortunately he
couldn鈥檛 make the animals eat enough potato, so they were malnourished no matter
which kind they were eating.

According to toxicologists who examined the data, changes in their organ
weights and immune reactivity showed no unambiguous association with genetic modification
(This Week, 6 March, p 13). Starvation or known toxins in raw
potato were the most likely culprits for any changes seen in the rats.

These experiments reveal a serious problem that is only now being grasped by
the biotechnology industry: standard toxicology tests don鈥檛 work for food. It is
often difficult to feed lab animals enough GM fodder, whether or not they find
it palatable, to see if it has undesirable effects compared with unmodified
food. Essentially, animal models are not sensitive enough to reveal small
differences between modified and unmodified foods.

Nonstarter

Even if you manage to get animals to eat enough test food, you risk changing
their diet so profoundly that even those eating unmodified food will be
abnormal. For all but the most blatantly toxic GM foods, this may make it
impossible to draw meaningful conclusions from such experiments.

Politicians, taken aback by huge public mistrust of 鈥淔rankenfoods鈥�, are also
realising that safety testing of these foods is not straightforward. In Britain,
the Cabinet鈥檚 biotechnology committee has commissioned a report on the human
health implications of GM foods from the government鈥檚 Chief Medical Officer and
Chief Scientific Adviser, due to be published this month. A Cabinet Office memo,
leaked by Friends of the Earth, asks: 鈥淲hy don鈥檛 we require a
pharmaceutical-type analysis of the safety of these foods, with proper trials?鈥�
But as the problems to date have shown, the proposition is a nonstarter.

So how can we check the safety of GM food? 杏吧原创s from the 29
industrialised countries of the OECD concluded at a meeting in Paris in December
that a whole new approach is needed. In September, they will meet again to start
drawing up ways of carrying out such checks.

They are up against some serious logistical problems. Harry Kuiper of the
State Institute for Quality Control of Agricultural Products in Wageningen,
Netherlands, tested a GM tomato by freeze-drying it and feeding so much to rats
that each got the equivalent of 13 of fresh tomatoes a day. Any more, and they
would have been poisoned by the basic nutrients, such as potassium, in the
tomato powder.

鈥淏ut toxicologists still said we hadn鈥檛 fed them enough to get a meaningful
result,鈥� says Kuiper. The usual approach for testing a new food additive, for
instance, is to feed it to a rat until a toxic effect is observed. That way, you
get an idea of the nature and threshold of any toxicity. But with tomatoes, the
researchers never managed to reach that threshold. In standard toxicological
terms, says Kuiper, they have not been adequately tested. Others would argue
that if such large amounts are harmless, the food cannot reasonably be called
toxic.

Nonetheless, these difficulties mean that GM food developers usually avoid
testing whole foods. Instead, they try to isolate the changed portion and test
that. As an example, Roy Fuchs, head of scientific affairs at Monsanto, one of
the world鈥檚 biggest developers of GM food, quotes potatoes carrying a gene for
the Bt toxin, an insecticide normally produced by Bacillus thuringensis.
Monsanto sells its Bt potatoes in the US and is applying for a European
licence. Fuchs says that the potatoes, like all genetically engineered plants so
far, do not produce enough of the product of the novel gene for it to be
isolated from the plants themselves and tested. 鈥淪o we put the novel genes in
bacteria, produce the gene product and test it by conventional methods.鈥�
However, the protein made by the bacteria may not be the same as that made by
the plant, especially in its potential to cause allergy.

The production of a novel protein is only one of the potentially harmful
changes that occur in when a foreign gene is inserted into a plant. Because the
positioning of the novel gene within the plant鈥檚 DNA is essentially random, it
may alter the plant鈥檚 expression of its own genes鈥攚ith unpredictable
effects. It is this kind of change that stymies conventional toxicology. Food is
a complex mixture of substances that occur in different quantities in different
varieties of crops and in the same variety grown under even slightly different
conditions. When is a change in one or several of those substances a
problem?

Unfortunately, says Kearns, no one has ever tested conventional food for
toxicity, so no one quite knows where to start. One exception is potatoes.
Conventional plant breeders in the US and the Netherlands test new potato
varieties for elevated levels of known toxins such as solenines. French breeders
do not鈥攁nd there are no legal requirements in any country to do so. And
that still leaves toxins in GM foods that we may not yet know about. 鈥淲e have to
think through these things case by case,鈥� says Kearns, starting with a better
understanding of what is in normal crops.

Kuiper鈥檚 institute is working on a screening test that detects differences in
the pattern of messenger RNA molecules produced by normal and transgenic
tomatoes. The hope it that this will provide a fast way to see if there have
been large changes in gene expression. The method can reliably detect
differences between red and green tomatoes鈥攚hich is encouraging, says
Kuiper, because green ones produce more toxins.

Key differences

The team has also compared the chemicals synthesised by normal and transgenic
plants by looking at their nuclear magnetic resonance (NMR) spectra. Nearly
every chemical compound in the plant produces a characteristic 鈥渇ingerprint鈥� of
peaks. The screening test revealed that there were up to eightfold differences
in concentrations of sugars, amino acids and various unidentified compounds.
Impressive as this sounds, it may not be significant: Kuiper notes that there
were greater differences between unaltered tomatoes grown in different
conditions than there were between GM and normal tomatoes grown in identical
conditions.

A better way of exploiting NMR might be to use it to find substances that
differ in transgenic foods and then to test these substances in, for example,
cell cultures, to see if the changes could be harmful. The need for such tests
may be soon be pressing. But when crops are engineered to produce a number of
desired nutrients or 鈥渘utraceuticals鈥�, changes in the plant鈥檚 own gene
expression could become much more complex and their potentially toxic effects
harder to test.

However, proponents of GM foods point out that whichever direction food
testing goes, the subtly altered products on our plates will have been tested
far more thoroughly than any conventional food. After all, even ordinary kidney
beans are poisonous if undercooked. Dozens of people die each year from cyanide
from peach seeds. Manioc, the staple diet of millions, had to be grated,
squeezed and cooked to drive off the cyanide before improved varieties became
available. And some of the most notorious food-linked poisons, such as
aflatoxins in grain, do not come from the food but moulds that infect it. In the
comparison between modified and unmodified foods, nothing is clear cut. And
testing is never simple.