Molecular genetics of gene expression

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Transcript Molecular genetics of gene expression

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

1998 1999 1999-2000

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: 1353-54. • Scientific resolution

The case of the monarch and Bt cry1Ab corn pollen

1999 1999-2000 2001

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

What’s riskier? Broad spectrum pesticides or non-target effects? In October 2001 PNAS – 6 papers delineated the risk for monarchs.

Exposure assumptions made by Losey et al. were not relevant--far off.

Tiered approach —mainly non targets

What happens when these levels are used for risk quantification?

Wilkinson et al. 2003 Trends Plant Sci 8: 208

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

Transgenes from commercial corn to Mexican landrace corn Quist and Chapela 2001. Nature 414: 541-543.

• 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 2002.

*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 1949. “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)?

Plant species that hybridize: 10,000s Plant species that introgress: 100s? (165 proposed, 53 documented*) All plant species 400,000-500,000 *From Rieseberg and Wendel 1993 Hybrid Zones and Evolutionary Processes Pp70-109 (Ed., Harrison)

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 And…Oriz-Garcia et al 2005 PNAS 102: 12238 No transgenic DNA was found in 153,746 Mexican landrace samples.

Landrace maize saga continues

• Piñeyro-Nelson, A. et al. Molecular Ecology 18: 750-761 (2009).

Found evidence of 35S promoter in 2001 and 2004, but not 2002. 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, 4143-4144 (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, 4145-4150 (2009).

– Counter-argued against Genetic ID.

Who/what is Genetic ID?

• “Global leader in GMO detection” according to the company website assessed April 13 2010. • 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.

2001-2002

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 2005 2009-2010 • 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 http://cls.casa.colostate.edu/TransgenicCrops/terminator.html

US Patent

5,723,765; Inventors: Melvin Oliver, et al. issued March 3, 1998 — licensed to Delta and Pineland

Control of plant gene expression 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.

Evolution of GMO controversies

• Until 1998: few controversies • 1998-2001: “Golden age” of controversies— characterized by NGO and media frenzies. Scientists were passive.

• 2002 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. 2012. Nature Biotechnology 30:207

Global area of transgenic crops by country Marshall, A. 2012. 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.