NOTE: Below Dr. Doug Gurian-Sherman, Senior Scientist at the Union of Concerned Scientists and former biotech specialist at the U.S. government's Environmental Protection Agency (EPA), comments on a recent letter attacking a study published by the journal, Proceedings of the National Academy of Sciences (PNAS).
The Rosi-Marshall et al study - funded by the National Science Foundation - found consumption of Bt corn byproducts produced increased mortality and reduced growth in caddisflies, an important food resource for higher organisms like fish and amphibians.
The letter attacking the study is from the 'usual suspects' - Alan McHughen, Henry Miller, Klaus Ammann, C. Kameswara Rao, Ingo Potrykus, Piero Morandini, Chris Leaver, S. Shantharam, Mark Sears, and C. S. Prakash. With the exception of Sears, none seems to have any especial expertise in the area they're commenting on, and nearly all can be found in the GM Watch profiles (or by searching at www.gmwatch.org) of ardent GM promoters.
As you know, the recent paper in PNAS that shows possible harm to stream insects was attacked by a group of scientists in a letter to the journal editor. Most of the points that they raise in their letter are misleading, even while some of them are technically correct. Because of the subtleties involved, I have written rebuttal points that I sent to some friends. I thought that they may be useful to others. My points are in caps following the relevant sections of the letter written by the pro-GE scientists.
Comments and letter to the editors of PNAS
A consortium of scientists signing this comment in a letter to the editors has analyzed the paper and came to critical conclusions, which seriously question the conclusions of the paper.
We are deeply concerned by the appearance in PNAS of a recent article, 'Toxins in transgenic crop byproducts may affect headwater stream ecosystems,' (10,1073 (2007)), by Rosi-Marshall et al., apparently funded by NSF. We recognize that it is not unusual for papers to be published with minor flaws or infelicities, even after peer review and revision, but the article by Rosi-Marshall et al. contains egregious methodological flaws and omissions, and presents conclusions not supported by the data.
We call your attention, in particular, to the following:
1) There is extensive evidence in the literature that corn pollen produced by currently available Bt corn varieties contain extremely low amounts of Bt toxin. This was shown in a series of six papers by top scientists published in PNAS after the Losey Bt corn pollen-Monarch debacle, an intensive and time-consuming effort to try to set the science straight (1). How many busy scientists and how much scarce money will we need to divert to calm this new scare?
IT IS SAD THAT THESE SCIENTISTS, ONE OF WHOM (MARK SEARS), WAS APPARENTLY HAPPY TO RECEIVE FUNDING TO PARTICIPATE IN THE MONARCH STUDIES (MAYBE HE WOULD SAY IT WAS HIS DUTY!), CANNOT APPRECIATE THE VALUE OF THE ADDED AGROECOLOGICAL KNOWLEDGE THAT THOSE STUDIES CONTRIBUTED. IN ADDITION (SPEAKING AS AN EPA SCIENTIST WHO WAS THERE AT THE TIME) THOSE STUDIES WERE NECESSARY TO INFORM EPA ABOUT ACTUAL RISKS FROM Bt CROPS IN THE FIELD. THE LOSEY PAPER ON MONARCHS WAS A PERFECTLY REASONABLE ONE. IN ANY CASE, THERE ARE SEVERAL ASPECTS OF THE MONARCH BUTTERFLY INCIDENT THAT ARE MISREPRESENTED HERE. FIRST, THERE WAS IN FACT A VARIETY OF Bt CORN, Bt176, THAT COULD INDEED KILL MONARCH BUTTERFLIES IN THE FIELD DUE TO HIGH LEVELS OF Bt TOXIN IN ITS POLLEN. IT WAS FORTUITOUS (I.E. HAVING NOTHING TO DO WITH EPA RISK ASSESSMENT) THAT THIS VARIETY WAS NEVER GROWN ON MORE THAN ABOUT 5% OF U.S. CORN ACRES, AND THEREFORE DID NOT HAVE A MAJOR IMPACT. THIS VARIETY WAS NOT RE-REGISTERED AFTER THESE RESULTS WERE DISCOVERED. SECOND, THERE WAS ENOUGH TOXIN IN THE POLLEN IN THE OTHER MORE WIDELY-PLANTED VARIETIES (MON810 AND Bt11) TO KILL MANY MONARCHS - UP TO ABOUT 24% ACCORDING TO A LATER STUDY (DIVELY ET AL. 2004). THE REASON THAT MORE MONARCHS WERE ACTUALLY NOT THREATENED WAS THAT THE CATERPILLARS WERE USUALLY NOT PRESENT IN CORN FIELDS WHEN POLLEN FROM CORN WAS PRODUCED. THESE DATA WERE NOT KNOWN BEFORE THE FIELD STUDIES REFERRED TO BY THESE LETTER WRITERS, AND THEREFORE ACTUAL RISKS TO MONARCHS WERE NOT WELL KNOWN BEFORE THOSE STUDIES WERE CARRIED OUT. THAT THE LETTER WRITERS SUGGEST THAT THESE STUDIES WERE A WASTE OF TIME REVEALS THAT THEY REALLY DON'T HAVE AN INTEREST IN MAKING SURE THAT THE RISKS FROM GE CROPS ARE MINIMAL.
2) The authors extrapolated from a laboratory test to a field system based on a single study. Such extrapolation is problematic to begin with; not only did the authors lack the statistical confidence necessary for a valid extrapolation, in another venue (2) they reported they did not find these effects in the field, a salient fact not mentioned in the PNAS paper. This discrepancy should have been disclosed and discussed. In addition, earlier relevant studies concluded that Bacillus thuringiensis (Bt) endotoxin concentrations in aquatic systems are extremely low and are metabolized rapidly in water (3,4).
THEY DID NOT EXTRAPOLATE TO THE FIELD. THEY NOTED AT LEAST FOUR TIMES IN THEIR PAPER THAT THEIR RESULTS 'MAY' HAVE IMPLICATIONS FOR THE FIELD. THIS TERM OF CONTINGENCY CLEARLY IS USED TO QUALIFY THE POSSIBLE FIELD IMPLICATIONS. THE EARLIER 'RELEVANT' STUDY (( http://www.benthos.org/database/allnabstracts.cfm/db/Columbia2007abstracts/id/370 , ONLY AN ABSTRACT) WAS ONLY ABOUT POLLEN - IT DID NOT CONSIDER LEAVES! THE CURRENT STUDY USED HIGHER LEVELS OF POLLEN, AND THE AUTHORS ACKNOWLEDGED THAT THE POLLEN AMOUNTS WERE HIGHER THAN WOULD OFTEN BE FOUND IN STREAMS. HOWEVER, THE MORE RELEVANT ISSUE IS EXPOSURE TO LEAVES AND OTHER SIMILAR MATERIAL BECAUSE 1) IT WAS FOUND TO BE PRESENT IN STREAMS AT MUCH HIGHER LEVELS THAN POLLEN, AND 2) THE AMOUNT OF Bt TOXIN IN LEAVES AND SIMILAR PLANT TISSUES IS MANY-FOLD HIGHER THAN IN POLLEN. AS TO THE OTHER CITED PAPERS, IT IS NOT UNCOMMON FOR DIFFERENT RESEARCH USING DIFFERENT METHODS TO GET DIFFERENT RESULTS. IT SHOULD BE NOTED HOWEVER, THAT EVEN THOSE OTHER STUDIES FOUND MEASURABLE Bt TOXIN IN RIVERS.
3) The title implies transgenic crops are the only source of Bt toxins, but endotoxins in commercial Bt insecticides such as Dipel, Xentari, Foray, and Thuricide are also used by farmers, including organic farmers, to control insects, and in some areas intensively If the authors are measuring the effect of Bt toxin at all, how do they know the toxin comes from the transgenic Bt crops rather than from these organic Bt insecticides? If they lack data to distinguish the sources, isn't the term `transgenic' in the title simply gratuitous and sensationalistic?
THE LAB EXPERIMENTS USED Bt CORN, NOT Bt MICROBIAL PRODUCTS (NATURAL Bt), AND THEREBY SHOWED THAT BT CORN COULD BE TOXIC TO CADDISFLIES. IN TERMS OF EXPOSURE IN THE FIELD, THE AMOUNT OF Bt FROM Bt CORN GREATLY OVERSHADOWS THE AMOUNT OF MICROBIAL Bt USED. IN AREAS WHERE CORN IS HEAVILY GROWN (MANY MILLIONS OF ACRES), THE AMOUNTS OF Bt MICROBIAL WOULD BE INSIGNIFICANT COMPARED TO Bt FROM FIELD CORN. SO THIS IS ONE OF THOSE POINTS THAT IS TECHNICALLY CORRECT, BUT MEANINGLESS IN PRACTICE.
4) The authors seem unaware that there are several variant forms of Bt endotoxin, as they failed to disclose which one(s) they were seeking and measuring. Toxicological studies use known quantities of known toxins, and look for a dose response. If their study included specific assays, they were not reported. If they were not conducted, the report was, at best, premature.
THE AUTHORS MENTION IN THE PAPER THAT THEY USE CRY1Ab CORN, SO UNLESS THEY WERE MISTAKEN, THEY DO IDENTIFY THE TYPE OF Bt CORN.
5) The authors do not disclose which Bt-corn isolines were tested. Different hybrids can differ significantly in both secondary metabolites and in antinutrient quantity (as well as in kind and amount of Bt toxin expressed). By not using isolines, they could have been seeing the effect of different concentrations in different hybrids of antinutrients or of other factors unrelated to Bt toxin. Similarly, the authors do not disclose quantitative measurements of tissue sampled, e.g., 'Leaves were added. as needed.' This lack of detail precludes others from replicating their study.
ALTHOUGH THIS IS ANOTHER TECHNICALLY VALID POINT, IT IS NOT LIKELY TO BE CORRECT IN PRACTICE. THE AUTHORS OF THE PNAS PAPER WERE IN FACT TRYING TO ACCOUNT FOR AN ALREADY KNOWN UNINTENDED EFFECT, THAT OF HIGHER LIGNIN IN Bt CORN, IN ODER TO GET MORE RELIABLE RESULTS. THEY DELIBERATELY MATCHED THE Bt AND NON-Bt CORN LINES BY LIGNIN CONTENT IN THEIR EXPERIMENTS. IN ADDITION, ALTHOUGH IT IS POSSIBLE THAT DIFFERENCES IN THE CORN VARIETIES, INDEPENDENT OF Bt, HARMED THE CADDISFLIES, THAT IS NOT THE MOST PARSIMONIOUS EXPLANATION. THIS IS BECAUSE HARM WAS SEEN FROM TWO VERY DIFFERENT CORN TISSUES - POLLEN AND LEAVES. IF THERE WERE HARMFUL COMPOUNDS OTHER THAN Bt CAUSING THE EFFECTS, IT IS NOT VERY LIKELY THAT THEY WOULD BE PRODUCED AT SUFFICIENT LEVELS IN THESE TWO VERY DIFFERENT TISSUES. ON THE OTHER HAND, Bt TOXIN IS PRESENT IN LEVELS THAT ARE KNOW TO BE ABLE TO KILL SOME INSECTS IN BOTH THE POLLEN AND THE LEAVES. Bt TOXIN IS A KNOWN COMMON DENOMINATOR OF BOTH TISSUES. ON THE SECOND POINT, ALTHOUGH (AGAIN) TECHNICALLY TRUE THAT THE PAPER'S AUTHORS DON'T QUANTIFY THE AMOUNT OF Bt Cry TOXIN, THEY ADEQUATELY DESCRIBE THE FEEDING FOR A QUALITATIVE ECOLOGY PAPER (WHICH IS WHAT IT IS - NOT A TOXICOLOGY PAPER). THEIR FEEDING METHODS FALLS UNDER THE GENERAL APPROACH OF AN 'AD LIBITUM' FEEDING STUDY (I.E., YOU LET THE BUGS EAT AS MUCH AS THEY WANT BY MAKING SURE THERE IS A CONTINUOUS SUPPLY) - WHICH IS FINE AS A FIRST APPROACH.
6) The authors conclude that growing Bt-corn may cause downstream adverse effects in waterways, but they fail to consider alternative explanations. Moreover, they analyze their results in a vacuum. In the real world, the choices are not 'Bt-corn' versus 'no intervention', and to imply that that is the case displays a remarkable ignorance of agriculture. Farmers grow more than one species and cultivar, and often use more than one pesticide strategy. For example, if a farmer were to control insects using conventional pesticides (that is, absent Bt corn plants), how would those pesticidal treatments affect caddisflies? For all we know, Bt corn may be environmentally preferable to traditional pesticides or other strategies to control insects. The authors imply otherwise without providing the comparative evidence.
APPARENTLY, ACCORDING TO THESE AUTHORS, WE NEED ONLY TO BE CONCERNED ABOUT THE MOST EGREGIOUS HARMS - LESSER HARM IS OK. FORTUNATELY, U.S. REGULATION OF PESTICIDES DOES NOT WORK THAT WAY. THE LETTER MIS-REPRESENTS THE REGULATORY MANDATE OF EPA - THE AGENCY RESPONSIBLE FOR Bt CROPS. THE LAW IS SUPPOSED TO REGULATE A PESTICIDE SO THAT IT CAUSES 'NO UNREASONABLE HARM' TO THE ENVIRONMENT. IT IS NOT A COMPARATIVE STANDARD (I.E., IT DOES NOT BASE ITS RISK ASSESSMENT ON WHETHER SOMETHING ELSE MAY CAUSE GREATER HARM). IF Bt CAUSES UNREASONABLE HARM, THEN IT IS IN VIOLATION OF U.S. REGULATIONS. OTHER HARMS NEED TO BE ADDRESSED ON THEIR OWN MERITS (OR DEMERITS).
The points above illustrate sloppy experimental design and interpretation that should have been detected by even a cursory peer review. Where were the crucial qualitative and quantitative data on source tissue, distinction of diverse types of Bt toxins, and discussion of alternate explanations for their results? We are at a loss to explain how qualified reviewers and editors could be unaware of flaws of this magnitude. Publication of this flawed paper has seriously jeopardized the credibility of PNAS as a high quality, scientific forum.
INSTEAD OF ATTACKING THE RESULTS OF THIS PAPER, MORE WORK IS NOW NEEDED TO BETTER UNDERSTAND THE POSSIBLE IMPACTS ON AQUATIC ENVIRONMENTS FROM Bt CROPS. THE PAPER RAISES VALID ISSUES THAT REQUIRE MORE RESEARCH SUCH AS: HOW SENSITIVE ARE STEAM INSECTS TO Bt TOXINS; HOW QUICKLY DO THESE TOXINS DEGRADE AND DISSIPATE IN THE STREAM ENVIRONMENT; HOW MUCH ACTUAL IMPACT OCCURS IN THE STREAMS? THE PAPER POINTS TO A REAL GAP IN EPA'S RISK ASSESSMENT OF Bt CROPS THAT NEEDS TO BE LOOKED AT CAREFULLY. IT IS UNFORTUNATE THAT THE LETTER AUTHORS APPARENTLY WOULD RATHER NOT FIND OUT IF HARM IS ACTUALLY OCCURRING IN THE ENVIRONMENT.
Alan McHughen, Professor, University of California, Riverside.
Brian Federici, Professor, University of California, Riverside.
Henry Miller, M.D., The Hoover Institution, Stanford University.
Klaus Ammann, Prof. emerit. Delft University of Technology, the Netherlands C. Kameswara Rao, Professor. Foundation for Biotechnology Awareness and Education,Bangalore, India.
Prof. Dr. Ingo Potrykus, Chairman, Humanitarian Golden Rice Board & Network Dr. Piero Morandini, Dept. of Biology, University of Milan, Italy C. J. Leaver, CBE, FRS, FRSE, Sibthorpian Professor of Plant Science, University of Oxford, UK S. Shantharam, Director, Biotechnology Education Programs, Asian Institute of Technology, Bangkok, Thailand Mark Sears, University of Guelph, Ontario, Canada.
C. S. Prakash, Professor, Plant Molecular Genetics, Tuskegee University, USA
1. PNAS 2001. 98: 11908-11912; 11913-11918; 11919-11924; 11925-11930; 11931-11936; 11937-11942.
3. Douville, M., F. Gagné, L. Masson, J. McKay, and C. Blaise. 2005. Tracking the source of Bacillus thuringiensis Cry1Ab endotoxin in the environment. Biochemical Systematics and Ecology 33(3): 219-232.
4. Douville, M. and F. Gagné. 2003. Tracking the Source of Bacillus thuringiensis Cry1Ab Toxin in the Environment. Scientific and Technical Report ST-226. Environment Canada - Quebec Region, Environmental Conservation Branch, St. Lawrence Centre.
Doug Gurian-Sherman, Ph.D.
Food and Environment
Union of Concerned Scientists
1707 H Street, NW
Washington, DC 20006-3962