Lecture 24 Controversial transgenic plants: risks revisited Chapter 15 Neal Stewart

Discussion questions Discuss controversies in the light of science and risks of transgenic plants—examples. What is the recipe for producing a controversy? What are the 3 eras in plant biotechnology controversy? What happened to usher each in and out? How can we critically examine risks and controversies?

Mae-Wan Ho “Genetic engineering bio- technology is inherently hazardous… which will spell the end of humanity as we know it, and of the world at large.” Genetic Engineering: Dream or Nightmare 1999 p. 1

NGOs and GMOs

The Frankenstein paradigm: man controls (perverts) nature with science. Frankenfood

The case of Arpad Pusztai’s transgenic potatoes Insecticidal potatoes expressing a snowdrop lectin gene (codes for a sugar binding gene) Not commercial product Feeding study with rats—examined gut features Compared transgenic and non-transgenic potatoes Experimental design and controls? Conclusion was that the transformation process itself or the promoter was responsible for the effect

Pusztai’s potatoes Series of events Small laboratory study promoted on national TV (in UK) by the author Feeding frenzy by: –Popular media –NGOs Scientific paper published in the Lancet (1999) 354: Scientific resolution

The case of the monarch and Bt cry1Ab corn pollen

Monarch butterfly Series of events Small laboratory study published in prestigious journal (Nature 399: 214)—a seemingly profound result. Prestigious university (Cornell) makes press release. Feeding frenzy by: –Popular media –NGOs Increased scrutiny by: –Scientists –Regulators Scientific resolution

Monarch butterfly In October 2001 PNAS– 6 papers delineated the risk for monarchs. Exposure assumptions made by Losey et al. were not relevant--far off. What’s riskier? Broad spectrum pesticides or non-target effects?

Tiered approach—mainly non- targets Wilkinson et al Trends Plant Sci 8: 208 What happens when these levels are used for risk quantification?

Figure 5.1 Corn belt Oaxaca, Mexico Illicit gene flow from, GM corn to Mexican landrace corn 2001 The case of Quist and Chapela Stewart (2004) Genetically Modified Planet

Transgenes from commercial corn to Mexican landrace corn CMV (sic) [CaMV] promoter DNA putatively found in maize landraces in Oaxaca, Mexico. Claimed transgene introgression into landraces. Used PCR (only) to make conclusions. Study was thoroughly criticized by scientific community. Paper “retracted*” in April Quist and Chapela Nature 414: *When a paper is really retracted, the authors’ acknowledge flawed science and officially retract the paper—it is as if it never existed. In this case, that did not happen. In 2002 the editor (for the first and only time when he essentially said he wish it would’ve never been published.

What is introgression? Gene flow Hybridization Introgressive hybridization Edgar Anderson “The permanent incorporation of genes from one set of differentiated populations (species, subspecies, races and so on) into another.” Stewart et al. (2003) Nature Reviews Genetics 4: 806

Stewart et al. (2003) Nature Reviews Genetics 4: 806

How many plant species introgress (interspcific)? All plant species 400, ,000 Plant species that hybridize: 10,000s Plant species that introgress: 100s? (165 proposed, 53 documented*) *From Rieseberg and Wendel 1993 Hybrid Zones and Evolutionary Processes Pp (Ed., Harrison)

And…Oriz-Garcia et al 2005 PNAS 102: No transgenic DNA was found in 153,746 Mexican landrace samples. Weak PCR signals = A few transgenic kernels Even if results were valid, Introgression was not demonstrated. Better explanation would be spurious hybridization. They should have looked at inheritance and done Southerns

Landrace maize saga continues Piñeyro-Nelson, A. et al. Molecular Ecology 18: (2009). Found evidence of 35S promoter in 2001 and 2004, but not Frequency of 35S in landrace maize= 1.1% by PCR and 0.89% using Southern blot analysis (but few samples were assayed using Southerns Schoel, B. & Fagan, Mol. Ecol. 18, (2009). Genetic ID: claimed that there was “insufficient evidence” for transgenes in landraces. Argued that qPCR should be the standard. Piñeyro-Nelson, A. et al. Mol. Ecol. 18, (2009). –Counter-argued against Genetic ID.

Who/what is Genetic ID? “Global leader in GMO detection” according to the company website assessed April Detection of transgenes using PCR and real-time PCR. In Fairfield, Iowa. Also in Japan and Germany. Founded by John Fagan (Maharishi University) in 1996.

Transgenic landrace maize Series of events Quist and Chapela publish Nature paper Much criticism by science community Nature editor says paper should never have been published Ortiz-Garcia et al PNAS paper—no transgenic DNA is found Piñeyro-Nelson, et al. Molecular Ecology paper claims transgenes come and go Genetic ID claims authors misinterpret data Probably low level of transgene presence? Decision is made to allow field trials in Mexico of transgenic corn

The Rural Advancement Foundation International (now the ETC Group) renamed TPS or GURTs to TERMINATOR TECHNOLOGY and TRAITOR TECHNOLOGY Words are powerful!

The case of “Terminator” technology AKA Technology Protection System AKA Gene Use Restriction Technology

(1 of1 )(1 of1 ) United States Patent United States Patent 5,723,7655,723,765 Oliver, et al. Oliver, et al. March 3, 1998 March 3, 1998 Control of plant gene expression Abstract A method for making a genetically modified plant comprising regenerating a whole plant from a plant cell that has been transfected with DNA sequences comprising a first gene whose expression results in an altered plant phenotype linked to a transiently active promoter, the gene and promoter being separated by a blocking sequence flanked on either side by specific excision sequences, a second gene that encodes a recombinase specific for the specific excision sequences linked to a repressible promoter, and a third gene that encodes the repressor specific for the repressible promoter. Also a method for making a genetically modified hybrid plant by hybridizing a first plant regenerated from a plant cell that has been transfected with DNA sequences comprising a first gene whose expression results in an altered plant phenotype linked to a transiently active promoter, the gene and promoter being separated by a blocking sequence flanked on either side by specific excision sequences to a second plant regenerated from a second plant cell that has been transfected with DNA sequences comprising a second gene that encodes a recombinase specific for the specific excision sequences linked to a promoter that is active during seed germination, and growing a hybrid plant from the hybrid seed. Plant cells, plant tissues, plant seed and whole plants containing the above DNA sequences are also claimed. Inventors: Inventors: Oliver; Melvin John (Lubbock, TX), Quisenberry; Jerry Edwin (Idalou, TX), Trolinder; Norma Lee Glover (Quanah, TX), Keim; Don Lee (Leland, MS) Oliver; Melvin John (Lubbock, TX), Quisenberry; Jerry Edwin (Idalou, TX), Trolinder; Norma Lee Glover (Quanah, TX), Keim; Don Lee (Leland, MS) Assignee:Assignee: Delta and Pine Land Co. (Scott, MS) The United States of America as represented by the Secretary of (Washington, DC) Delta and Pine Land Co. (Scott, MS) The United States of America as represented by the Secretary of (Washington, DC) Appl. No.: Appl. No.: 08/477,55908/477,559 Filed: Filed: June 7, 1995June 7, 1995 US Patent 5,723,765; Inventors: Melvin Oliver, et al. issued March 3, 1998— licensed to Delta and Pineland Control of plant gene expression

Evolution of GMO controversies Until 1998: few controversies : “Golden age” of controversies— characterized by NGO and media frenzies. Scientists were passive until now: Fewer controversies. Why? –Over 1 billion acres and 100 trillion transgenic plants—no one has died. –Wary media –Proactive scientists (see response to Quist and Chapella).

Seralini rat tumor study Rats were fed Roundup ready corn or conventional corn over the rat’s lifetime (2 years) (Food and Chemical Toxicology 50:4221; 2012). Higher incidence of cancer and death Conclusion: the GMO corn or Roundup is toxic

Scientific response to Seralini Study criticized on the basis of experimental design (low sample size) and use of Sprague- Dawley rats (susceptible to cancer). European Food Safety Authority concluded the study was of “insufficient scientific quality for safety assessments.” Raised questions of scientific misconduct since the researchers will not release their data. Paper was retracted by the journal in 2013.

Conclusions No technology is risk-free, but plant biotechnology is not risky per se Food, corporate control, and environment causes are social issues that reach beyond science GMOs are one tool for agricultural and environmental security and sustainability

Historical global area and value of transgenic crops Marshall, A Nature Biotechnology 30:207

Global area of transgenic crops by country Marshall, A Nature Biotechnology 30:207

Big environmental benefits of today’s transgenic crops Herbicide tolerant crops have increased and encouraged no-till agriculture– less soil erosion. Over 1 million gallons of unsprayed insecticide per year.

Risks Weighed against benefits Weighed against risks of competing practices and technologies (none are risk- free) Weighed against not adopting Controversies result from oversimplifications coupled with a desire to inflame.