Update on “Extra DNA” and Other Problems with Crop Genetic Engineering

I received an email recently from a distinguished professor of plant sciences who encouraged me to update my knowledge of the “extra DNA” problem I mentioned in an article published in the January 2018 issue of Comstocks magazine. He sent me a copy of “Bringing New Plant Varieties to Market: Plant Breeding and Selection Practices Advance Beneficial Characteristics while Minimizing Unintended Changes“–a paper published in the latter half of 2017 and authored by 13 people (Glenn et al.), 10 of whom were employees of Monsanto Company–to help me do that. He indicated that Glenn et al. “describes all of the procedures, checks and tests that are done on commercialized transgenic traits to address the problem” that I had told the author of the Comstocks article has not been solved in 25 years.

Monsanto’s Current Selection Practices, According to Glenn et al.

I have to admit that I am pretty impressed with the procedures, checks and tests carried out on potential genetically engineered (GE) crop products as documented by these (primarily) Monsanto authors. For example, they indicate that molecular analyses are conducted “to ensure: (i) that only one copy of the DNA insert was in the selected events, (ii) the intactness and integrity of the DNA insert, (iii) the absence of any undesired DNA from the transformation process (e.g. the vector backbone), and (iv) that the DNA insertion had not interrupted endogenous genes.” Additional RNA and/or protein analyses “to confirm that the intended gene products were being produced” are also mentioned in the paper.

I think it should be mandatory for all developers to conduct all of these tests, and for any GE “event” (i.e. individual GE plant) being brought to market to have successfully passed them all.

The “Extra DNA” Problem is Still a Problem

But the bottom line is that the “extra DNA” problem is still a problem. Vector backbone sequences (and other unintended DNA, see below) can still get unintentionally inserted into GE crop plants. Therefore, this problem has not been solved; Monsanto still has to check to ensure “the absence of any undesired DNA from the transformation process (e.g. the vector backbone),” and that is the “extra DNA” problem I referred to in the Comstocks article. In fact, according to Glenn et al., Monsanto checks for “extra DNA” not just once, but twice during the course of bringing a new GE plant variety to market. At Calgene, Inc., back in the early 1990’s, we also checked for “extra DNA” in our tomato, cotton and brassica GMOs, and then threw out any of those GE plants that had any. Based on Glenn et al., Monsanto is doing the same thing…25 years later.

Hopefully, all other developers of GE crop plants designed for human consumption: 1) know about this problem, and 2) are doing the same.

But Monsanto’s Selection Practices Were Not Always This Strict

Take selection criterion (ii) from Glenn et al., for example: to ensure “the intactness and integrity of the DNA insert.”  In the past, Monsanto Company has commercialized multiple GE corn varieties in which the intactness and integrity of the DNA insert was not maintained during the genetic engineering process; the DNA that ended up in the GE crop after the genetic engineering process was not the same as the DNA that was intended to be inserted.

And one of the best examples of a Monsanto GE corn variety in which the integrity of the DNA intended for insertion was not maintained in the final GE corn product is NK603. NK603 is the GE corn tested by Séralini and colleagues in a long-term rat-feeding study, a study that raised concerns–and subsequently controversy–regarding possible toxic effects of NK603 (and of glyphosate-containing herbicide) on animals (see, e.g., this article on the subject in Nature). NK603 GE corn was not only commercialized as an individual GE corn product; according to a report out of Purdue University, it also has been bred into at least half a dozen other GE corn products, some of which are associated with DowAgrosciences and Pioneer Hi-Bred as well as Monsanto.

The Lack of Integrity of the DNA Insert and Intended Gene Products in NK603

The integrity of the DNA inserted into NK603 was not maintained during the genetic engineering process used to create NK603. And that lack of integrity at the DNA level resulted in a lack of integrity of the RNA expressed from the inserted gene(s), and to lack of integrity in the form of a mutation in one of the foreign proteins produced in the GE corn varieties carrying the GE locus from NK603.

According to Monsanto, in addition to a single complete copy of the DNA the company intended to insert into the recipient corn plant (which comprises two versions of genes designed to convey resistance to the herbicide glyphosate), NK603 also includes an “inversely linked 217 bp piece of DNA containing a portion of the enhancer region of the rice actin promoter at the 3’ end of the inserted DNA.” This is another type of “extra DNA” that developers of GE crops do not intend to insert into GE crops: an extra copy of a random chunk of the DNA they do mean to insert, placed randomly adjacent to the intact complete copy of the DNA they do mean to insert.

And as a result of sequencing the inserted DNA to verify its “integrity” in NK603, Monsanto identified not only the extra, inverted piece of the rice gene promoter, but also two point mutations in one of the genes conveying glyphosate resistance, “one of which results in a change of the amino acid leucine to proline at position 214 in the protein.” The other point mutation did not change the amino acid sequence of this protein. Nevertheless, the integrity of the introduced foreign protein had not been maintained.

Additionally, and perhaps of most concern in terms of understanding how the lack of integrity of the DNA insert might affect the biology of the recipient corn plant, Monsanto scientists found that expression of the inserted gene(s) in NK603 produces an RNA transcript comprised of not just information stored in the inserted DNA but also information stored in the corn DNA adjacent to the position in the corn genome into which the insert was randomly placed. That is, “mRNA transcription was detected to initiate in either one of the two promoters of the NK603 insert and…continue into the corn genomic DNA.” RNA is an intermediary molecule that conveys the information stored in DNA to the cellular machinery; some RNAs translate the information coded in DNA into a protein that, in this case, provides resistance to glyphosate; other RNAs are now known to play roles in regulating how other genes are expressed. The upshot is that an unintended gene product, a chimeric RNA molecule comprised of intended insert-DNA-associated sequences plus sequences derived from the corn DNA that just happened to be adjacent to the spot in the corn genome where the foreign DNA insert landed, is produced in NK603 GE corn and any other GE corn varieties into which NK603 has been bred using traditional breeding methods.

More Safety Studies of NK603 are Needed

 We do not know whether the lack of integrity of the DNA inserted into NK603 results in any physiological changes in GE corn plants comprised of this GE corn event.

But we do know that if NK603 had been put through the procedures, checks and tests described in Glenn et al., it would have failed them.

In the meantime, we also know that Séralini and colleagues documented problems in rats fed NK603 over their lifetimes in a study that passed peer-review and was published in a reputable international journal (Food and Chemical Toxicology), but was retracted–more than a year after it had been in print–by the journal’s editor-in-chief after he deemed it “inconclusive.” We also now know that Monsanto played a behind-the-scenes role in the public attack on that study that resulted in its retraction.

What we need now is for that study to be replicated “by a truly independent laboratory using appropriate sample sizes” (David Spiegelhalter, a statistician at the University of Cambridge, UK). We need an update on NK603.

I, for one, would like to know–conclusively–the safety status of NK603 GE corn.

I would hope that the United States Food and Drug Administration, and its counterparts in other parts of the world, would want to know as well.


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3 Responses to Update on “Extra DNA” and Other Problems with Crop Genetic Engineering

  1. Pingback: Food Evolution Film Neglects to Mention Important Facts…Like Glyphosate is a Probable Human Carcinogen | Biotech Salon

  2. Pingback: Golden Rice: Of Good Intentions, Insertional Mutants, Human Error, and the Need for Better Regulation of GMOs | Biotech Salon

  3. Pingback: New Salk Institute Study Reveals More Detailed Picture of “Scrambled Nature” of Gene Insertions in GMOs | Biotech Salon

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