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Biotechnology Consultation
Note to the File
BNF No.
000049
January 2, 1998
Potato, insect resistant (Colorado Potato Beetle), virus resistant (Potato Virus Y), kanamycin resistance (nptII), Bacillus thuringiensis subsp. tenebrionis (BTT)
In a submission dated July 31, 1997, Monsanto provided summary information to support their safety assessment of genetically modified potatoes, specifically lines NewLeaf Y cv. Russet Burbank (RBMT15-101), New Leaf Y cv. Shepody (SEMT15-02, SEMT15-07 and SEMT15-15) and NewLeaf Y cv. Hi-Lite (HLMT15-3, HLMT15-15 and HLMT15-46). This data was further supported by three previous summaries of NewLeaf potatoes. Potatoes containing the CryIIIA BTT protein have been on the market since 1995.
The intended technical effect of this genetic modification of potato is to confer tolerance to the Colorado Potato Beetle (CPB) and Potato Virus Y in a single plant. Potatoes are grown to be consumed mainly as fresh vegetables. Potatoes are not in widespread use as an animal feedstuff (Memo - Nov. 25, 1997- Michaela Alewynse, CVM).
According to Monsanto, their NewLeaf varieties of potato have been modified to express neomycin phosphotransferase type II (for selection), the cryIIIA gene which encodes the BTT protein (for resistance to CPB) and the PVYcp gene from PVY (for resistance to PVY).
The use of the BTT protein and the PVYcp protein as pesticidal substances and the use of the selectable marker NPTII as a pesticidal inert ingredient in the development of the virus and insect resistant potato are under the regulatory purview of the Environmental Protection Agency (EPA). EPA regulates the use of the introduced genetic material encoding the viral coat protein, insect resistance protein and the selectable marker (including associated sequences required for expression) as well as the expression products. Therefore, in the consultation, we did not address the safe use of the viral coat protein and insect resistance protein as pesticides or the safe use of NPTII in potato as a pesticidal inert ingredient. The main focus of the consultation with FDA was the compositional analysis of the transgenic potato as compared to the parental variety.
Monsanto described the identity and function of the genetic material introduced into the potato lines by the Agrobacterium tumefaciens/Ti plasmid-mediated transformation system. The introduced genes were transformed into potato using the vector PV-STMT15, derived originally from a standard plant transformation disarmed pTi58 plasmid.
It was reported by Monsanto that the three chimeric genes introduced between the right and left border regions of the plant transformation vector included: 1) the chimeric gene for the selection of transformed plant cells which consisted of the promoter region of the nopaline synthase gene from the Ti plasmid of A. tumefaciens, the nptII gene and the nontranslated 3' region of the nopaline synthase gene referred to as NOS 3'; 2) the chimeric gene responsible for the control of the CPB which consists of the Arabidopsis thaliana ribulose-1,5-bisphosphate carboxylase small subunit ats1A promoter, the CryIIIA gene which encodes the BTT protein and the nontranslated 3' region of the nopaline synthase gene (NOS 3'); 3) the chimeric gene responsible for control of PVY which consisted of the 35S promoter region of the Figwort mosaic virus, the full length PVYcp gene from a naturally occurring PVY and the nontranslated 3' region of the pea subunit of ribulose-1,5-bisphosphate carboxylase referred to as E9 3'.
Three proteins, the nptII protein, the CryIIIA CPB control protein, and the PVY coat protei) are expressed in the NewLeaf Y potatoes. The nptII protein which is used as a selectable marker, was approved for use as a processing aid in several crops in 1994. Monsanto also received an exemption from the requirement of a tolerance for this protein as a pesticidal inert ingredient from the EPA on September 28, 1994 in all crops.
Monsanto stated that the CryIIIA protein from Bacillus thuringiensis subsp. tenebrionis (BTT) introduced in these NewLeaf Y potato varieties is identical to that found in nature and in commercial BTT formulations available since 1988. The EPA approved Monsanto's request for an exemption from the requirement of a tolerance for this protein in 1995.
According to Monsanto, the PVY coat protein confers resistance to the Potato Virus Y. Monsanto presented evidence that virus infected plants, including PVY-infected potatoes, tomatoes and peppers, have been part of the human and domestic animal food supply without detectable adverse health effects. The EPA in 1994 proposed to exempt all viral coat proteins from a requirement of a tolerance. Monsanto stated that the PVY protein is not known to be an allergen nor does it have any significant homology to known allergens.
Monsanto presented data concerning the level of total solids, sugars, vitamin C, soluble protein, and natural glycoalkaloid toxicants. Monsanto also performed proximate analysis and measured total protein moisture, fat, ash, crude fiber, carbohydrates and calorie content. Monsanto reported that the levels of all components analyzed were statistically identical to those in the control potatoes or were within the levels reported in the literature for commercially available Russet Burbank potatoes. These data allowed the firm to conclude that the composition of the NewLeaf Y potato varieties is equivalent to the composition of traditional potatoes.
Monsanto has concluded that NewLeaf Y potatoes containing the transformation are not materially different in composition, nutrition and safety from potatoes currently grown, processed, marketed. and consumed as human food. At this time, based on Monsanto's description of its data and analyses, the Agency considers Monsanto's consultation on NewLeaf Y potatoes to be complete.
/s/
Vincent Zenger, Ph.D.
