++5. REVIEW OF DATA ON POSSIBLE TOXICITY OF GM POTATOES Agnet May 18, May
18, 1999 The Royal Society http://www.royalsoc.ac.uk/st_pol54.htm
The Royal Society published a review of what was known scientifically
about the suitability of GM plants for food use in September 1998. Because
of the current controversy, we are looking again at several issues, and in
particular we have reviewed all available data related to work at the
Rowett Research Institute on the possible toxicity of genetically modified
POTATOES. Our main conclusions are as follows.
ŠŠ.1. The safety of GM plants is an important and complex area of
scientific research and demands rigorous standards. However, on the basis
of the information available to us, it appears that the reported work from
the Rowett is flawed in many aspects of design, execution and analysis and
that no conclusions should be drawn from it.
2. We found no convincing evidence of adverse effects from GM
potatoes. Where the data seemed to show slight differences between rats fed
predominantly on GM and on non-GM potatoes, the differences were
uninterpretable because of the technical limitations of the experiments and
the incorrect use of statistical tests.
3. The work concerned one particular species of animal, when fed
with one particular product modified by the insertion of one particular
gene by one particular method. However skilfully the experiments were done,
it would be unjustifiable to draw from them general conclusions about
whether genetically modified foods are harmful to human beings or not. Each
GM food must be assessed individually.
4. The whole episode underlines how important it is that research
scientists should expose new research results to others able to offer
informed criticism before releasing them into the public arena.
1 BACKGROUND In April 1999 the Royal Society convened a Working Group
to examine whether newly publicised research required changes to our
September 1998 statement GM plants for food use. This report deals with the
apparent evidence that genetically modified potatoes adversely affected the
health and growth of rats. The report has been endorsed by the Council of
the Society, and was prepared by a group chaired by Professor Noreen Murray
FRS, FRSE (University of Edinburgh). The other members were Professor Brian
Heap FRS (Foreign Secretary and Vice-President of the Royal Society),
Professor William Hill FRS, FRSE (University of Edinburgh), Dr Jim Smith
FRS (National Institute for Medical Research), Professor Michael Waterfield
FRS (Ludwig Institute for Cancer Research and University College London)
and Dr Rebecca Bowden (Secretary).
2 METHODOLOGY We sought information from all possible sources about
the work at the Rowett Research Institute and obtained the following:
* Report of project coordinator, Arpad Pusztai FRSE, on data
produced at the Rowett Research Institute (RRI), 22.10.98 * Audit of data
produced at the Rowett Research Institute, 21.8.98, SOAEFD (Scottish Office
Agriculture, Environment and Fisheries Department) flexible fund project
RO818 * Response to request for clarification from the Rowett Research
Institute
* Response to request for information from Dr Susan Bardocz
* Information provided by Advisory Committee on Novel Foods and Processes
(including correspondence with Dr Stanley Ewen)
* Statistical analysis carried out by Biomathematics and Statistics
Scotland of experiments on genetically modified potatoes conducted at the
Rowett Research Institute, 1.3.99
* Minutes of evidence - Science and Technology Committee of the
House of Commons, 8.3.99
* Response to request for information from Dr Vyvyan Howard of
Liverpool University
* Response to request for information from Mr G Horgan of BIOSS
* Response to request for information from Professor John
Gatehouse of Durham University
* Response to request for information from Professor Michael
Wilson, Scottish Crop Research Institute
* Information from SOAEFD on rationale for research Dr Pusztai
indicated to us that further information existed, but did not provide it.
We sent the available information to six independent, impartial
reviewers whose expertise included statistics, clinical trials, physiology,
nutrition, quantitative genetics, growth and development, and immunology.
Their remit was to examine the data that we gave them and advise us, in the
usual way of referees, about the scientific merit of the work described.
They were not asked to give an opinion on the actions of any individuals
involved in this work.
This report is based on the responses from the six reviewers. The
responses were copied to Dr Arpad Pusztai, who was given the opportunity to
comment. In accordance with normal scientific practice, the reviewers
remained anonymous. Dr Pusztai suggested to us that his reports were
internal Institute documents and that it was therefore not appropriate to
peer review them. However, since they were released into the public domain,
both through the media and on the Internet, it seems to us entirely
appropriate that they should also be subjected to expert scientific
scrutiny - all the more so because of the importance of this area.
We now examine two specific claims that have been made as a result of
the Rowett work.
3 DID THE GM POTATOES TESTED HAVE A SPECIFIC EFFECT ON ORGAN
DEVELOPMENT AND METABOLISM OF THE RATS?
The experiments set out to investigate whether potatoes genetically
modified to contain a lectin gene from a snowdrop affected the development
of organs or the metabolism of the rats to which they were fed, in the
short (10 days) or long (110 days) term. The structure of the experiments
was changed as they progressed, which made comparisons between rats fed on
modified potatoes and those fed on unmodified POTATOES more difficult. Some
results showed differences in the overall body weights and in the weights
of individual organs in the two groups of rats. However, such results as
were statistically significant did not fall into a readily discernible
pattern.
A particular difficulty is that the experiments were not well
designed. For example, there is very little information about how the GM
and control diets differed in their detailed composition, and in particular
about differences other than those attributable to the inserted gene. These
differences should have been fully analysed, and addressed by using several
distinct strains of GM potato in the feeding trials. Second, the GM
potatoes used contained almost 20% less protein than unmodified potatoes.
Therefore, in the long-term feeding study, rats being given GM potatoes
were also given additional protein to meet Home Office requirements
intended to avoid starvation: observed effects could have been caused by
this supplementary diet being inadequate or incomplete. Third, when a rat
is underfed many organs are likely to be affected, so that separate
measurements on the same specimen will turn out to be interrelated.
An added deficiency of the study was that, as far as we can tell, the
measurements were not conducted 'blind' as is normal practice for trials of
this kind (a protocol in which the scientists making the measurements are
not aware of how the animals have been treated). Unconscious bias is well
known to be a source of invalid results.
Because of the poor experimental design, it is simply not possible to
be sure about the causes of the small effects obtained in the study.
4 DID THE GM POTATOES TESTED HAVE A SPECIFIC EFFECT ON THE IMMUNE
SYSTEM OF THE RATS?
It had been claimed that the consumption of GM potatoes had
significant effects on the immune system of rats in the feeding trials,
because of some effect of the genetic modification itself rather than
because of the particular gene inserted. Reviewers were asked to consider
if this conclusion was valid.
One of the immune reactions in the body can be mimicked in the
laboratory. Antigen-reactive white blood cells (lymphocytes) are
transformed into dividing lymphoblasts when they are stimulated by specific
antigens. This provides a means of testing for effects on the immune
system.
The claim that the Rowett data show evidence that the inserted gene had
a different immune effect from simply adding lectins to unmodified POTATOES
does not stand up. Inappropriate statistical tests had been applied to the
data and, when the appropriate comparisons are made , there are no
interpretable differences. Moreover, the experimental data in this area are
beset by the same sources of inconsistency noted in section 3 above.
5 CONCLUSIONS OF REVIEW OF DATA
The work on feeding trials with GM and non-GM potatoes attempted to
cover too much ground with the resources available. In the form currently
available, the data reviewed provide no reliable or convincing evidence of
adverse (or beneficial) effects, either of lectins added to unmodified
potatoes or of potatoes genetically modified to contain a lectin gene, on
the growth of rats or on their immunological function.
In summary, the data presented to the reviewers and Working Group are
inadequate for the following reasons:
* poor experimental design, possibly exacerbated by lack of
'blind' measurements resulting in unintentionally biased results;
* uncertainty about the differences in chemical composition between
strains of non-GM and GM potatoes;
* possible dietary differences due to non-systematic dietary
enrichment to meet Home Office and other requirements;
* the small sample numbers used in experiments testing several
diets (all of which were non-standard diets for the animals used) and which
resulted in multiple comparisons;
* application of inappropriate statistical techniques in the
analysis of results;
lack of consistency of findings within and between experiments.
The uncertainty and ambiguity of the data urge great caution in the
interpretation of the results presented. A much improved experimental
design, with stringent controls, would have been needed if the claims made
for the study were to be convincing. Even if the results of the particular
study had supported the claims that have been made for them, it would have
been unwise to use them for making statements about the safety or otherwise
of all GM foods.
Although we have no evidence of harmful effects from genetic
modification, this of course does not mean that harmful effects can be
categorically ruled out. This issue can be resolved only by the necessary
research carried out to a high standard and by full use of the regulatory
mechanisms for dealing with safety of food.
6 FUTURE RESEARCH Reviewers were asked to give advice on the
necessity of future research arising from the data presented.
The only way to clarify the current situation would be to refine the
experimental design of the research done to date and to use this as the
basis for further studies in which clearly defined hypotheses were tested,
focused on the specific differences already claimed. It would be necessary
to carry out a large number of extremely complex tests on many different
strains of GM and non-GM potatoes. It would be important to ensure that
these studies had sufficient statistical power (in the sense that numbers
in each experimental group were sufficient to deal with the variability in
individual response) to come to a clear conclusion. It would also be
important to take adequate account of the age and the susceptibility of the
animals and the wholesomeness, completeness and adequacy of the entire
diet. Careful thought would have to be given to the specific targets for
any hypothesised damage.
7 RECOMMENDATIONS In view of the public interest in this case
we recommend that the results of any future studies on testing GM food
safety, when completed, should be peer reviewed and then published. This
would provide an opportunity for the international scientific community and
the public at large to have access to the information.
The Royal Society has recommended in its September 1998 statement GM
plants for food use that any over-arching body analyse the current
regulations, giving particular consideration to whether long-term animal
feeding studies are necessary to provide greater information on
allergenicity or toxicity. We now reiterate this recommendation.
++6. UK DOCTORS REPORT ON OMEN -- GLICKMAN Agnet May 18, May 18/99 Reuters
Washington
U.S. Agriculture Secretary Dan Glickman was cited as telling a a U.S.
consumer group Tuesday that a new report by the British Medical Association
that calls for a moratorium on the planting of genetically-modified crops
could be a sign of things to come, calling the report "a little bit of an
omen" and predicted a public debate over the "next five, 10, 15 or 20
years" on biotechnology. Glickman was further quoted as saying that
although the United States has taken the lead in the approval of
genetically-modified crops, it can't force those products "down consumers'
throats. Dismissing the skepticism that's out there is not only arrogant,
it's very bad business strategy," noting that biotechnology will only
succeed if it has the confidence of consumers, and that, "My confidence in
biotech, or industry's confidence in biotech, is ultimately irrelevant."
Glickman added that there also has been concern that requiring the
labeling of genetically-modified crops could open a "Pandora's box" of
labeling, such as one that says "this item has been produced by a farm that
treats its cows nicely. You could get to the point where every social
engineer(ing) concept would be disclosed in the label" which, he said,
would causes chaos in the food production system. Even so, Glickman
acknowledged that the debate over such issues won't be driven by "pure
science. If consumers don't buy the product, all the science in the
world... is for naught."
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