Former genetic engineer says imprecision of GM techniques is nothing new and must not be denied or downplayed.
Below is an excellent and insightful article by Dr Belinda Martineau, the former genetic engineer who developed the Calgene GM tomato in the early 1990s.
by Belinda Martineau
Biotech Salon, July 15, 2023
The following is a piece I wrote which was published in the July 15, 2023 edition (online; July 16 in print) of The Davis Enterprise.
A critical detail was omitted from Rich Rifkin’s Forum article published June 28 in The Davis Enterprise. In the interest of reducing the “mountains of misinformation” related to regulation of genetically engineered/modified (hereafter GE) organisms to which he referred in that piece, that omission should be corrected.
Rifkin pointed out that TALENs, the process UC Davis professor Alison Van Eenennaam and colleagues used to edit a gene responsible for the development of horns in cows, is “more precise [at] editing [the genes of] live cells than CRISPR.” But he failed to mention the imprecision of TALENs that led to the bovine offspring resulting from Van Eenennaam’s research containing more than just the edited gene they had intended to insert into those animals.
That’s right. Despite Rifkin’s statement that “Everything else about the offspring [other than the allele the scientists had intended to insert] … was the same as any other Holstein,” in reality those GE bovine offspring also contained bacterial DNA sequences — including a gene conferring antibiotic resistance — that had been inserted during the gene-editing process. Not only did Van Eenennaam and her colleagues not intend to insert that bacterial DNA into those offspring, but they didn’t even know they had inserted them until a scientist at the FDA informed them about it (after FDA scientists had analyzed the genomic data generated and provided to them by Van Eenennaam and her colleagues).
This type of GE-associated imprecision isn’t unique or new. In fact, unintended insertion of “extra” DNA into genetically engineered organisms has been happening for over 30 years. I know because my colleagues and I at Calgene, Inc. found that we had inadvertently inserted bacterial DNA into the Flavr Savr tomatoes we were analyzing and preparing for commercial sales back in the early 1990s.
In the Flavr Savr case, FDA scientists asked us to prove our contention that only the DNA we intended to insert into our tomatoes had been inserted. The fact that our subsequent experiments revealed bacterial DNA had been inserted into 20-30% of our tomatoes shocked me, and we published our results in a peer-reviewed journal soon thereafter so as to let the scientific community know about this imprecision of genetic engineering. The FDA scientists who found the bacterial DNA in Van Eenennaam’s de-horned GE cows published their results as well and cited additional examples of this “extra DNA” problem that had surfaced in the years since my colleagues and I had identified the problem in our tomatoes.
UC Berkeley professor Jennifer Doudna, who was awarded the Nobel Prize in Chemistry in 2020 for her research on CRISPR, is another peer-reviewed scientist who is concerned about imprecision associated with gene-editing. She gave the keynote address at the UC Davis Krebs Symposium held a couple of months ago during which she cited examples from the peer-reviewed literature of large DNA deletions and translocations, chromothripsis and chromosome loss associated with use of CRISPR and referred to this precision problem as a “bottleneck” to “What’s Ahead for Genome Editing” (the title of her talk).
Being concerned about unintended consequences of using new technologies is not — as Rifkin implied in his article — fomenting “unscientific folly.” In order to make the most informed decisions possible about how best to regulate the products of these new technologies we need to admit to their imperfections that we (should) know about, like the “extra DNA” issue that contributed to abandonment of Van Eenennaam’s hornless cow research, not make boldfaced lies of omission regarding them.
We also need to recognize that it is possible there are additional imprecisions associated with the new technologies that we just don’t understand yet (like the possibility of interfering with dynamic genomic processes in organisms, perhaps), and throw a little precaution into the mix.
I’m all for reforming the “archaic regulations used by the FDA” to regulate GE animals. But we should start by admitting that the selective breeding process humans have been using for more than 10,000 years — a process Charles Darwin called “artificial selection” — is substantially different and significantly more “tried and true” than the GE processes humans have been using for the last 30-plus years.
There have been examples of “troublesome” GE products in those three decades (like StarLink Corn, glyphosate-tolerant crops that contributed to build-up of glyphosate-resistant weeds, NK603 corn, etc.) and they should be dealt with as red flags, not denied, downplayed or ignored. We need an honest process for reforming U.S. regulations of GE organisms, one in which the truth, the whole truth, and nothing but the truth prevails. No lies of omission allowed.
— Belinda Martineau is a Davis resident, plant geneticist and former genetic engineer; she reports and comments on biotechnology on her blog: biotechsalon.com and elsewhere.