July 4, 2002
AGRICULTURAL BIOTECHNOLOGY SCIENCE COMPROMISED
http://www.cnr.berkeley.edu/~kenw/maize/compromised.htm
Here's the powerful full statement from Worthy et al, partially reproduced
in a letter in Nature. See also Worthy's 'Responses to Metz, Fütterer
and Kaplinsky's Correspondences in Nature, 27 June 2002' http://www.cnr.berkeley.edu/~kenw/maize/responses.htm
The international controversy surrounding the Mexican maize transgenic
introgression findings of Quist and Chapela exposes systemic problems
in the science of agricultural biotechnology. Their work served two purposes:
first, to demonstrate the presence of transgenes in maize landraces despite
a moratorium on the planting of transgenic maize in Mexico, and second,
to open a discussion on the behavior of transgenes in an ecological context.
In step with patterns of normal scientific discourse, some errors have
surfaced that went undetected in the initial peer-review process; indeed,
Quist and Chapela acknowledge several problems in their paper.
Yet, these flaws alone cannot explain the intensity of negative reactions:
(i) Nature's near-retraction of the entire original article, suggesting
that Nature's editors doubted the presence of transgenic DNA in Mexican
maize, even after Quist and Chapela supplied corroborating data from a
non-PCR method (DNA hybridization);
(ii) public accusations of basic laboratory incompetence; and
(iii) an apparent "viral marketing" effort by the Bivings Group, a public
relations firm with ties to Monsanto, that created false Internet identities
and rumors to prime the assault on Chapela on "AgBioWorld," a listserv
used by more than 3,000 scientists.
Regrettably, much of this opposition has detracted from the healthy scientific
process of improving the quality of data, sharpening analysis, and conducting
further research to answer new questions. We are confronted instead by
an atmosphere of hostility and mistrust that upstages what has become
a critical research question: When transgenic DNA moves unintentionally
into new species or new environments, what are the evolutionary, ecological,
genetic, and social consequences? This article reveals many of the political
and economic conflicts surrounding the controversy that threaten to compromise
the integrity of agricultural biotechnology as a science.
To shed light on the controversy, it is helpful to review first the scientific
claims made by Quist and Chapela and their respondents. The first finding
of Quist/Chapela-the presence of transgenic DNA constructs in Mexican
maize landraces-stands unrefuted. It is reported as confirmed by tests
run by Mexican government researchers and is demonstrated by Quist/Chapela's
DNA hybridisation test, which addressed the only substantive criticism-that
of PCR contamination.
In light of Quist/Chapela's presentation of additional data, even the
ag-biotech promotional organization AgBioWorld, which has organized opposition
to Quist/Chapela as evidenced in their "Joint Statement", agrees that
this first finding stands "undisputed".None of the criticisms of Quist/Chapela's
techniques published in Nature effectively refutes the first finding.
This may not be apparent to the casual reader, since the focus of the
critiques is to highlight flaws rather than to identify how these flaws
might affect the overall results.
Comments from a number of scientists have diffused the impact of this
finding by calling it "obvious",and "inevitable and welcome", while simultaneously
challenging "the methodology and results reported in the Nature paper."
By capitalizing on the uncertainty over the behavior of transgenes in
maize landraces, these scientists can have it both ways: the presence
of transgenes in the environment is certain, yet also doubtful. The second
finding of Quist/Chapela, establishing the genomic context of transgene
insertion using i-PCR, is far less certain due to various technical problems.
The authors admit that two sequences resulted from false priming and that
this could apply to other sequences as well. The criticism that the sequences
do not take the form expected of the protocol is also valid, but the reason
is unclear.
Many of the published criticisms are valid and welcome, though they do
not completely invalidate the results. Kaplinsky et. al suggest that all
eight sequences derived from i-PCR are artifacts of false priming, yet
AF434761 clearly has a continuation of the CaMV sequence adjacent to,
but outside of, both primers used. In the end, it is difficult to draw
any convincing conclusions about the location of CaMV in the genome. The
contention surrounding the genomic context finding has obscured the significance
of Quist and Chapela's attempt to contribute to a deeper understanding
of the vital question of the behavior of transgenes in non-laboratory
genomic contexts.
Attempts to answer important scientific questions should normally be
met with criticism and calls for additional efforts to answer those questions.
The reactions to Quist/Chapela seem to have become suspended in an extended
criticism phase, with little expressed interest for more investigation
into transgene behavior in the environment (an opportunity missed in Nature's
Editorial Note). Paul Christou's harsh critique of Quist/Chapela illustrates
this interest in dwelling on the faults, rather than moving beyond them.
He takes Quist and Chapela to task by saying that the chances that recombination
caused irregularities in their i-PCR data is infinitesimally small, but
he neglects to mention that his own lab has discovered that the CaMV promoter
has a recombination hotspot implicated in illegitimate (low homology)
recombination between plasmids and genomes.
If such recombination were occurring after CaMV is integrated into genomes,
it would be cause for concern indeed. Intensive investigation of the behavior
of transgenes is clearly needed, as evidenced by the fact that even the
molecular mechanism of transformation remains unknown, and thus the stability
of transgenic constructs in uncontrolled environmental samplescannot be
assured. Unfortunately, this scientific debate takes place within webs
of political and financial influence that compromise the appearance of
objectivity (and possibly the actual objectivity) of scientists such as
the Quist/Chapela critics.
All eight authors of the two critiques of Quist/Chapela publishedby Nature
either currently or recently have had all or part of their research funded
by the Torrey-Mesa Research Institute (TMRI), a progeny of ag-biotech
firm Novartis (currently Syngenta). The affiliation of seven of those
authors with TMRI is a result of that company's $25-million "strategic
alliance" with the University of California, Berkeley's College of Natural
Resources.
Wilhelm Gruissem, formerly of U.C., Berkeley and architect of the strategic
alliance, whose current laboratory is in partnership with TMRI, is the
supervisor of the eighth author, Johannes Fütterer. None of the eight
authors declares this funding from an ag-biotech firm as a competing financial
interest. Such a funding arrangement might be less noteworthy had Chapela
not been the leading faculty critic, and Quist a leading student critic,
of the strategic alliance and its implications for scientific freedom
and balanced science.
Their vocal opposition to the alliance jeopardized a large flow of financial
support for these same scientists who, out of the thousands of biotechnology
researchers qualified to evaluate their research, have now become their
chief critics. These competing interests would be less striking, however,
had some of these critics not resorted to publicly accusing Quist and
Chapela of incompetence and ideological bias; Metz called their paper
a "testament to technical incompetence" and suggested that "an ideological
conflict encouraged this lapse in scientific integrity".
One would hope that Nature would look farther afield for critics in the
future. Compromised positions extend beyond those of these critics. Nature
Publishing Group actively integrates its interests with those of companies
invested in agricultural and other biotechnology, such as Novartis, AstraZeneca
and other 'sponsorship clients', soliciting them to "promote their corporate
image by aligning their brand with the highly respected Nature brand."
These attachments presumably challenge Nature's ability to provide a
neutral forum for scientific debates on ag-biotech. Nature's Editorial
Note was unorthodox and unnecessary-the normal scientific process of contestation
should have been permitted to proceed, using Quist/Chapela's claims and
data to repeat, verify or refute their findings, without additional editorial
comment. Because of its potential effect on regulatory policy, the timing
of Nature's disavowal of Quist/Chapela and its publication of critical
responses, immediately before the sixth meeting of the UNEP Convention
on Biological Diversity and discussions of the legally binding Cartagena
Protocol on Biosafety (7-19 April and 22-26 April, respectively) further
undermines the journal's quest to be perceived as uncompromised by commercial
and financial interests.
Such commercial connections are not unusual for scientific journals and
their editors and authors, as elucidated by Sheldon Krimsky and others
quoted in Nature's recent News Feature on conflicts of interest.Unfortunately,
peer reviews and requirements for disclosure of "competing financial interests"
provide scant counterbalance to the webs of interests surrounding ag-biotech
science. Direct influences are only part of that environment. Biotechnology,
it must be noted, represents a prominent and seductive pathway for biological
scientists into technology, industry, and financial and professional rewards.
Current, outright "competing financial interests", even when disclosed,
do not sufficiently account for the progressive levels of interest many
scientists have in ag-biotech, when they work for ag-biotech firms, or
hope to do so in the future, or are funded by those firms, or are ideologically
committed to the proposition that industrial solutions are essential for
agricultural problems.
The extensive presence of industry in private and public research laboratories
biases many laboratories against producing work that might jeopardize
the future of ag-biotech. Some people who perceive a lack of research
that challenges the progress of ag-biotech in the pages of prestigious
scientific journals (such research is certainly not lacking in social
science publications) look to these industrial influences as a contributing
factor. Scientists committed to the goal of impartiality cannot dismiss
the effects of such influences on the signers of AgBioWorld's "Joint Statement
in Support of Scientific Discourse in Mexican GM Maize Scandal".
To illustrate the point, all seventeen of the U.C., Berkeley researchers
who signed that statement are funded by ag-biotech firm TMRI, as described
above. The pervasiveness of industry and financial biases certainly places
the idea of completely eliminating them beyond the realm of possibility.
Disclosure policies are created with the intention of mitigating the most
obvious of those influences by allowing readers to make an informed judgment
about their significance.
Yet, closer examination of the financial interests and choices of Nature
and its Quist/Chapela critics with respect to this controversy reveals
a breakdown even in this limited protection. Nature's policy defines competing
financial interests as "those of a financial nature that, through their
potential influence on behavior or content or from perception of such
potential influences, could undermine the objectivity, integrity or perceived
value of a publication."
The policy defines multiple ways that researchers may be linked financially
to companies that stand to gain or lose from their work and publication,
including the following: support for research, including equipment, supplies,
etc.; recent, present or anticipated employment; and personal financial
interests such as stocks in a company. Quist/Chapela critique authors
Kaplinsky, et. al., who actively declared that they have no competing
financial interests (as opposed to making no declaration, which Nature
leaves as an option), stand in clear violation of Nature's guidelines
on at least one count: co-author Michael Freeling's research laboratory
is funded by ag-biotech firm TMRI as noted above; beyond that, all six
authors do research in laboratories funded by TMRI and some of them are
graduate students whose educations are partially funded by TMRI. In our
judgment, critics Metz and Fütterer violate the spirit of Nature's policy
due to the recent, undeclared funding of Fütterer's research by ag-biotech
firm Novartis.[28] Until last year, Metz also benefited from TMRI funding
as a Berkeley graduate student, and has been an outspoken proponent of
the CNR/TMRI strategic alliance, as demonstrated by his testimony before
the California legislature.
Determination of whether there are any other competing financial interests
among these authors would require additional investigation. Also troubling
is Nature's failure to follow its own disclosure policy as it applies
to publishing. Nature's stated policy is to disclose its commercial or
financial interests or specific arrangements with advertising clients
or sponsors when such arrangements create "any risk of a perception of
compromise" in publishing and editorial decisions.
Nature publishes ag-biotech advertisements and its "sponsorship clients"
historically include firms with ag-biotech interests, such as Aventis
(makers of "StarLink" corn) and Novartis (though these companies' turbulent
genealogy makes tracking their interests challenging). These clients stand
to lose from the findings of Quist/Chapela because their findings challenge
the idea that ag-biotech firms can safely control transgenes in the environment-a
challenge that raises the potential for increased regulation of transgenic
organisms. Nature's decision to publish a potent disavowal of Quist/Chapela,
without attendant disclosure of its financial relationships to ag-biotech
firms, has created actual-not just potential-perceptions of compromise
on the issue. In such an environment, it is difficult to imagine fair
and equal consideration being given to work that challenges the commercially
vested interests of ag-biotech and the assumptions of reductionist molecular
biology.
Quist/Chapela obviously represents such a challenge. That fact-not the
quality of their work-together with the politics of university-industry
relations, remains central to their paper's troubled reception. Ironically,
the ag-biotech industry ultimately undermines its own credibility by not
aggressively evaluating the health and environmental implications of its
products. The public will remain skeptical until it does so. We call on
scientists, Nature, and other scientific journals to re-examine their
commitments to and interests in ag-biotech and to open up spaces in laboratories,
journals, conferences and classrooms for a more balanced and critical
evaluation of the ecological and health effects of the flow of transgenes
into the environment. Statement of Competing financial interests:
The authors of this Commentary are recipients of educational grants from
and/or employees of the University of California, Berkeley, which could
lose financially from this Commentary as a result of its strategic alliance
with ag-biotech firm TMRI/Syngenta. [1] Portions of this document are
published as a Correspondence in Nature 417, 897 (2002). See http://www.nature.com.
[2] Quist, D. & Chapela, I. H. Nature 414, 541-543 (2001). [3] Quist,
D. & Chapela, I. H. Nature 416, 602 (2002). [4] Editor, Nature 416, 601
(2002). [5] Monbiot, G. "The fake persuaders: Corporations are inventing
people to rubbish their opponents on the Internet." The Guardian (May
14, 2002). [6] Brown, P. "Mexico's vital gene reservoir polluted by modified
maize." The Guardian (April 19, 2002). [7] Quist, D. & Chapela, I. H.
Nature 416, 602 (2002). [8] http://www.agbioworld.com/biotech_info/articles/mexmaizeresource.html
. [9] Kaplinksy, N., Braun, D., Lisch, D., Hay, A., Hake, S., Freeling,
M. Nature 416, 601-602 (2002). [10] Metz, M., Fütterer, J., Nature 416,
600-601 (2002). [11] http://bric.postech.ac.kr/science/97now/02_4now/020404b.html.
[12] http://www.agbioworld.org/jointstatement.html. [13] Christou, P.
Transgenic Research 11: iii-v (2002). [14] Kohli, A., Griffiths, S., Palacios,
N., Twyman, R. M., Vain, P., Laurie, D. A., and Christou, P. The Plant
Journal 17 (6): 591-601 (1999). [15] Granger, C. "Transgenes by no easy
means." ISB News Report. Information Systems for Biotechnology. http://www.isb.vt.edu/news/2002/news02.Feb.html.
[16] Kaplinksy, N., Braun, D., Lisch, D., Hay, A., Hake, S., Freeling,
M. Nature 416, 601-602 (2002). [17] Metz, M., Fütterer, J., Nature 416,
600-601 (2002). [18] Novartis/Syngenta received first right to negotiate
for research results from the Department of Plant and Microbial Biology
(PMB) and strong representation on the committee which disperses the funds
to laboratories in PMB, in exchange for $25 million. Contrary to recent
journalistic reports, the strategic alliance remains in full force. [19]
Yoon, C. K. "Journal Raises Doubts on Biotech Study." The New York Times
(April 5, 2002). [20] http://npg.nature.com/npg/servlet/Content?data=xml/10_sponsor.xml&style=xml/
10_sponsor.xsl. [21] Nature's Editorial Note was in fact invoked at the
Biosafety meeting by the delegate from Australia. See http://www.i-sis.org/contamination.php
. [22] United Nations Environment Programme, "Governments to advance work
on Cartagena Protocol on Biosafety." Press Release. http://www.biodiv.org/biosafety.
[23] The protocol "aims to ensure the safe transfer, handling and use
of living modified organisms that result from modern biotechnology that
may have adverse effects on biological diversity". [24] Van Kolfschooten,
F. "Conflicts of interest: Can you believe what you read?". Nature 416,
360-363 (2002). [25] http://www.agbioworld.org/jointstatement.html. [26]
For UCB PMB-TMRI funding allocations, see http://plantbio.berkeley.edu/PMB-TMRI/Projects.html.
[27] http://www.nature.com/nature/submit/competing/index.html. [28] See
acknowledgements in Rothnie, H., Chen, G., Fütterer, J., Hohn, T., J.
Virol. 2001 75: 4184-4194. [29] California Senate, Senate Natural Resources
Committee/Senate Select Committee on Higher Education, Impact of Genetic
Engineering on California's Environment: The Role of Research at Public
Universities (Sacramento, CA, May 15, 2000). See also Metz' letter on
the strategic alliance: Metz, M. Nature 410, 513 (29 Mar 2001). [30] http://www.nature.com/nature/submit/competing/index.html.
Kenneth Worthy Department of Environmental Science, Policy and Management
University of California, Berkeley 135 Giannini Hall #3312, Berkeley,
CA 94720-3312 Correspondence may be addressed to kworthy@nature.berkeley.edu.
Richard C. Strohman Emeritus, Department of Cell and Molecular Biology
University of California, Berkeley 229 Stanley Hall #3206, Berkeley, CA
94720-3206 Paul R. Billings Department of Anthropology University of California,
Berkeley GeneSage, Inc. 589 Howard Street, San Francisco, CA 94105
