27 June 2002

SCIENCE COMPROMISED

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
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http://www.cnr.berkeley.edu/~kenw/maize/compromised.htm
Agricultural Biotechnology Science Compromised[1]

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

© 2002 Kenneth Worthy, et al.

Excerpts from this article were published 27 June 2002 as a Correspondence in the journal Nature simultaneously with replies from several scientists. See
http://www.nature.com.  A response to those replies can be found at
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.[2] 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.[3] Yet, these flaws alone cannot explain the intensity of negative reactions: (i) Nature's near-retraction of the entire original article,[4] 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.[5] 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[6] and is demonstrated by Quist/Chapela’s DNA hybridization test, which addressed the only substantive criticism - that of PCR contamination.[7] 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".[8] 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.[9],[10] Comments from a number of scientists have diffused the impact of this finding by calling it "obvious",[11] and "inevitable and welcome", while simultaneously challenging "the methodology and results reported in the Nature paper."[12] 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.[13] 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.[14] 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,[15] and thus the stability of transgenic constructs in uncontrolled environmental samples cannot 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.[16],[17] All eight authors of the two critiques of Quist/Chapela published by 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.[18] 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".[19] 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."[20] 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.[21],[22],[23]

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.[24] 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".[25] 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.[26]

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." [27] 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.[29] 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.[30] 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.