Memorandum submitted by
Dr Arpad Janos Pusztai
INTRODUCTION AND
BACKGROUND
In recognition that research on the effects
of genetically modified (GM) crop plant on the environment is
of fundamental importance and particularly that their dietary
use and possible impact on the mammalian gastrointestinal tract
has had scant attention without a single peer-reviewed paper by
1995 (only one since; J. Nutr. 1996), SOAEFD commissioned a 3-year
multicentre project (FF 818); Genetic engineering of crop plants
for resistance to insect and nematode pests: effects of transgene
expression on animal nutrition and the environment. The main
objective was: "To identify genes encoding antinutritional
factors which will be suitable for transfer into plants to enhance
their resistance towards insect and nematode pests, but will have
minimum impact on non-target, beneficial organisms, the environment,
livestock fed on these plants, and which will present no health
risks for humans either directly or indirectly through the food
chain". Our proposal describing the genes and plants, the
experimental designs and protocols, the tasks of each participant
and research milestones was peer-reviewed by BBSRC and approved
by leading scientists. In recognition, SOAEFD selected our proposal
against other competing tenders. The genes considered for transfer
were those coding for plant antinutrients including lectins. With
our unique previous experience of feeding rats using diets rich
in insecticidal antinutrients, it was decided that the programme
of work on the effects of GM-plants on the environment, target
pests, beneficial insects and soil bacteria at University of Durham
(UD) and the Scottish Crop Research Institute (SCRI) should be
coordinated from the Rowett Research Institute (RRI). Our most
important work task was to devise novel methods for the safety
testing of GM-potatoes which could be incorporated by the regulatory
authorities into the testing and risk assessment of GM-foodstuffs.
Our work has concentrated on tubers from GM-potato lines expressing
the gene of snowdrop (Galanthus nivalis) bulb lectin, GNA,
and our task was to carry out chemical analyses to establish whether
the parent and transgene lines were compositionally equivalent
or not and to determine in 10-day and 3-month rat feeding trials
whether the effect of GNA-GM lines on the mammalian gut and metabolism
was similar to that of parent lines or not. The selection of GNA
was not arbitrary. This gene has already been incorporated into
several crops (rice, cabbages, oilseed-rape, etc) and indeed GNA-GM-potatoes
have been grown in field-trials for several years in the UK. Moreover,
our RRI group has done 6 years of previous work with GNA in which
we demonstrated that GNA, even at much higher levels of dietary
inclusion (up to 42 mg GNA/rat/d) than the expected expression
levels in GM-plants, had apparently no deleterious effect on the
growth and health of young rats.
RESULTS—CONCLUSIONS
OF GM-POTATO
WORK CARRIED
OUT AT
RRI
After GNA gene insertion changes in protein,
starch, sugar, lectin and trypsin/chymotrypsin inhibitor levels
were observed in the tubers of two generations of two GNA-GM
lines suggesting "possible gene silencing, suppression
and/or somaclonal variation" in the potato genome. The
GNA-GM-potato lines investigated in FF 818 programme were therefore
not "substantially equivalent" to the appropriate
parent tubers or to each other.
In all three 10 day rat feeding trials with
GNA-GM-potatoes significant changes in the weights of some of
their vital organs were observed even when lactalbumin supplied
two-third of the protein in the diet (D249). Multivariant statistical
analyses indicated that although the treatment effects were small,
the number of significant differences in organ weights was more
than would be expected from Type I error rate, suggesting that,
similar to the lack of compositional equivalence, the metabolic
consequences of feeding GM-and parent potatoes were also substantially
different even though "potato GNA" in GNA-GM-potato
diets appeared to be functionally similar to "snowdrop GNA"
in GNA-spiked diets.
The growth rate of rats fed potato diets was
slightly but significantly less than that of rats fed lactalbumin
diet but the presence of GNA had no significant effect of weight
gain. However, as the protein content of GNA-GM-line 74/2T was
significantly less than of the parent line, feed conversion efficiency
of the rats with this GM-line diet was also less. Moreover, when
GNA-GM-potatoes supplied most of the dietary protein (D227 &
D242), digestion and absorption of nutrients was retarded and
the effect became significant in D242.
Feeding rats with GNA-GM-potatoes for 10 days
significantly reduced their lymphocyte responses to mitogenic
stimuli compared to parents and these differences could not have
occurred by chance. However, as on 110 day feeding the proliferative
responses of rats given potato diets were strongly suppressed,
possibly due to the cumulative effects of potato toxins, no differences
between parent and GM-potatoes could be found. Accordingly, the
existing data support our original suggestion that the consumption
by rats of transgenic potatoes expressing GNA has significant
effects on organ development, body metabolism and immune function
that is fully in line with the significant compositional differences
between transgenic and corresponding parent lines of potatoes.
THE ROWETT'S
ROLE IN
THE EVENTS
BEFORE AND
AFTER AUG
10
I am including this section in response to the
Committee's request in respect of the Rowett's role in the handling
of our results and the circumstances of my departure.
As the last worker of FF 818 left the programme
by June 98, RRI work on GM-potatoes was at an end. With "Increased
Flexibility Programmes" SOAEFD funding ends after the three-year
period of the contract and it is up to the Institute to incorporate
them into core-funded research. This is the normal course when
the work produced good results and fits into the Institute's research
profile. However, the Directors of RRI were not willing to allocate
core funds or allow us to use some of the moneys our group has
earned from external contracts to continue with GM research. We
would have been willing to carry on at a minimum level of input
with a PhD student till we were able to attract more external
money for scaling up the work. As we have been running four programmes
on external funds, our prospects were good. However, as the report
of the Visiting Group early in 1998 criticised the Institute's
work and its scientific management, there was no willingness to
allocate funds to a new programme till the direction of the Institute's
research will have been settled. All the same, the Director was
happy for the continuation of our work but only if commercial
funding could be attracted. For this, with the enthusiastic encouragement
of the Directors of RRI & RRS (Rowett Research Services),
the help of the PR officers of the Institute and based on our
experimental results, we started to organize a major conference
at RRI on the effects of GM-foodstuffs on consumers to which scientists
from FF 818 and others and representatives of EU, industry, grant-providing
and regulatory bodies were to be invited. The programme and even
the date was agreed. To draw the attention of possible sponsors
to the merit of our case and attract funds for the continuation
of our GM work, the main speakers were to be the senior members
of our RRI group to highlight our achievements and give details
of our (hitherto unpublished) results. First it was to be 2 October
because the Director was free. Later because of an "open
day" at RRI on 23 October, we agreed that the conference
be hosted in as part of this. Far from being against publicising
our results, the Directors were keen to promote it. It was only
after 12 August that the open day and the conference were cancelled.
My appearance on the "World in Action"
TV programme was a part of the publicity for the conference and
recorded in late June with Professor James's blessings and in
the presence of the RRI's PR. Professor James phoned my wife after
the broadcast to congratulate me on how well I handled the interview.
If the Rowett had any qualms about the content of the programme
they had seven weeks to stop it but they did not as I only talked
about the necessity of finding new methods for testing with animals
of GM-foodstuffs before they are released which was clearly based
on our short- and long-term nutritional and immunological work
with our two distinct lines of GNA-GM-potatoes. No experimental
details or even the identity of the gene used were given (transcript;
Appendix 1[1]).
I reaffirmed my belief in GM technology but only if we got it
right and handled it transparently. The Rowett was happy with
the publicity as shown by the RRI Press Releases on 10 and 11
August and another by the Governing Body Chairman to M Jacques
Santer and Frank Dobson (Appendix 2[2])
which were full of praise for our work "of strategic importance
to our country and European Union consumers". "A range
of carefully controlled studies underlie the basis of Dr Pusztai's
concerns". "The testing of modified products with implanted
genes needs to be thoroughly carried in the gut of animals and
humans if unknown disasters are to be avoided".
Unfortunately, and in my view as a consequence
of the Rowett's mishandling of the media by not consulting the
scientists of our group early enough about the accuracy of the
data which were released by the Rowett on 10 and 11 August, major
mistakes were made. Statements in the 10 August Press Release
such as that "the potent insecticidal lectin concanavalin
A obtained from the South American Jack Bean if inserted into
potatoes will . . . " was never discussed with us. Indeed,
we never saw the contents of this Press Release till 14 August
but by that time the media was full of our work on ConA-GM-potatoes
or indeed, that we have never done any GM-potato feeding experiment.
It appears that Professor James realized his error late in the
afternoon of 11 August. Apparently he thought the best way to
extricate himself from the responsibility for having mislead the
public by giving out details of a work with ConA which has in
fact never been done was to tell the world that I got "muddled"
or even that I "took" data from a colleague who was
absent at the time. He then also suspended me on 12 August and
set up an Audit. As it now transpires he had no right to have
an audit because I was never accused of scientific fraud by the
Rowett and this could have been the only legitimate scientific
reason for the audit. Even if I had drawn erroneous conclusions
from our GM-potato-work (which I had not), it is not a serious
enough offence to warrant the setting up of an audit. Moreover,
against BBSRC rules I have never been given the reasons for my
suspension and the audit in writing. All our data were confiscated.
Professor James had written to me a series of letters (copies
of these are available if needed[3])
in which he explicitly threatened me with legal action if I spoke
to anyone in or outside the Rowett about our work. He also warned
all Rowett staff of the dire consequences if anyone spoke to me.
Indeed, I was sent to Coventry; only Professor James communicated
with me by occasional warning letters. Although I was ostensibly
only suspended from GM work, all our results, people in our group,
my three PhD students and all of our funding, even the commercial,
were summarily taken by the Rowett. I was left to my own devices
in my office to fill out the remainder of my contract. I was arbitrarily
removed from all EU programmes and conferences. Because of the
confidentiality issue in my contract which was emphasized by Professor
James, I was denied any right to clarify scientific or other points
and issues which in my opinion were not right. So all information
in the media originated from the Rowett after 10 August and none
from me.
The composition of the Audit Committee in my
view was inappropriate. Despite having many nutritionist staff
members, a chemist (Chairman) and a microbiologist were appointed
from RRI plus a potato biologist from SCRI. There was only one
outside expert who had work experience with animals. The whole
audit was over in less than 10 hours. Practically none of the
data in the Audit Report was primary and no independent statistical
analyses were carried out to validate the analyses which were
done by the Committee or other staff at the time. This has come
to light in the last two months as we managed to recover some
of the laboratory and animal house books and data sheets to be
passed on to Dr Horgan for independent statistical analysis. Had
this been done at the time or had the Committee consulted me,
the serious flaws in the Audit Report could have been avoided.
According to BBSRC rules some, but not all,
of my data were returned to me on 19 October that I could comment
on the Audit Report. For example, the immunology data were only
recovered on 26 February 1999! The deadline set by Professor James
was 7 pm on 22 October. This I did using the data available at
the time by writing an alternative (Co-ordinator's) report. The
two reports were complementary, to be read together and were not
papers or meant to be published as public disclosure of data usually
jeopardize their publication as papers. Despite this the Rowett
published the Audit Report to coincide with Professor James' and
Dr Chesson's appearance in the House of Lords' Select Committee
on GM-related matters on 28 October. However, neither of them
gave any indication that the data in the Audit Report were contested
by me or that there was an alternative report. The secrecy went
so far that even the scientists who participated in FF 818 were
not given a copy of my report. However, after the publication
of the Audit Report scientists who knew me and took a keen interest
in our work started to ask for my side of the story. As the BBSRC
staff code does not prohibit exchange of views and data between
scientists, I sent my report (plus the Audit Report for comparison)
in confidence to about 30 UK, European and American scientists
but only those requesting it and only if they promised to send
back their evaluation. The results are well known. At the end,
24 of them published a Memorandum (without giving away confidential
data) and asked for my re-instatement to carry out further work.
THE ADEQUACY
AND QUALITY
OF SCIENTIFIC
ADVICE AT
PRESENT
As referred to above, I regard the scientific
evidence on record of the possible biological and nutritional
effects of GM-foodstuffs, a single paper in a peer-reviewed journal,
as wholly inadequate. The results of "in house" work
by Companies introducing new GM crops are unpublished as regards
the public although they may have been submitted to the appropriate
regulatory authorities for scrutiny. Clearly, even if they give
excellent accounts of the work done, they fall down on the public's
(and other scientists') desire of transparency.
THE ROLE
AND FRAMEWORK
OF ADVISORY
COMMITTEES
With the predicted onrush of genetically modified
crops in the next decade, the role and the framework of the advisory
committees will be severely tested. As I understand, the scope
of their ability to give advice can be restricted by their apparent
limitation in commissioning GM-food testing of their own or basic
work underpinning GM-research. Their judgement is therefore mainly
based on information received from the companies. Although they
can ask for more work to be done when, in their opinion, this
is needed, this may not be the best solution, nor is it conducive
to the transparency demanded by the public. It also appears that
the lines of communication between advisory committees and active
scientists working in GM-related fields may not be adequate. The
committees' advice is likely to be dependent to some extent on
the personal knowledge of what is going on in the labs and fields
and by whom. This in view of the members' high workload leaves
too much to chance. In a European context the situation becomes
even more acute, particularly considering the number of possibly
relevant papers published each year. In fact, if nothing else
was demonstrated by our case with the GM-potato work, it showed
that once I was gagged, the results of our work could not reach
the Advisory Committees. There is a clear need for a route through
which, when needed, results could more directly be passed on to
the Committees without permission from Institute Directors. Scientific
secretarial help may also be needed for pre-assessment of relevant
papers which need to be passed on to overworked Committee members.
As the forte of most of the members is scientific administration,
the Committees should not only be strengthened by the presence
of consumer and environmental pressure groups but also by the
appointment of active scientists.
THE ABILITY
OF THE
CURRENT SYSTEM
TO RESPOND
RAPID SCIENTIFIC
DEVELOPMENTS
This more or less follows on from above. It
is unlikely in my opinion that due to the slow publication of
scientific papers, members of the Committees, without a network
of contacts with workers at Institutes active on the field, will
be able to keep up with scientific progress. Whether it is liked
or not, they will have to be more proactive/interactive with scientists
and get information about unpublished work in confidence as early
as possible.
OVERARCHING BODY
TO ADVISE
ON AND
OVERSEE GENETICALLY
MODIFIED FOOD
I think above I have made a compelling case
for just such a body. Perhaps as part of FSA it may be possible
to set it up. However, it has to be able to fund research of its
own, be independent and, most of all, its work must be fully transparent.
I am confident that under such conditions the Government will
be an "intelligent customer" for the advice.
My final sentiment as I expressed in the World
in Action programme: "I actually believe that this (GM) technology
can be made to work for us. And if genetically modified food will
be shown to be safe, then we have really done a great service
to all our fellow citizens".
NOTE
This Memorandum (with tentative recommendations
for GM-food testing; Appendix 3[4])
was compiled by Dr Pusztai, dated 1 March 1999. No contribution
from the Rowett, SOAEFD or scientists who have participated in
FF 818 Programme was received and none implied.
1 March 1999
1 Not printed. Back
2 Not printed. Back
3 Not printed. Back
4 Not printed. Back
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