The fixing of nature through gene technology: empty promises, COIs, and unwanted truths

The example of gene-editing in cattle

A few days ago, Dr Giuseppe Longo, a colleague at the European Network of Scientists for Social and Environmental Responsibility (ENSSER) who many of you will know from his far-reaching and important work, alerted some of us to a perplexing video.

Titled, “Alison Van Eenennaam Edits Cattle Using CRISPR,” the video is about genome editing technologies in beef cattle production and the two “exciting projects” underway by Van Eenennaam, a geneticist at UC Davis.  The video comes with full transcripts and a summary given by Synthego – who “aim[s] to educate scientists and non-scientists about the latest CRISPR gene editing technology, CRISPR-based therapeutics, and CRISPR regulations.”

The video raises some foundational issues, even beyond the prospect of cattle gene manipulation.

The Video

The video begins with

“Why do we need genetically modified cows created with CRISPR gene editing technology? Aren’t GMOs bad for you? The short answer is a resounding no - GMOs have many uses, including preventing the extinction of species of plants and animals, and helping them be more resilient to their environment.”

I can see why the video triggered Longo’s interest. Among many others, he has long unearthed numerous issues with gene editing, appropriately naming the underlying conception of biology the “genocentric” view. The “n” here is intentional and indicates the same significance as the description of the universe with the earth at the center. Other than the little “n,” there is not much difference between these two models. Genes as the blueprint of life are the predominant description taught at all schools and universities, from K2 to the grave.

This model has been taken at face value for decades, and, as before, has taken the boldness and wisdom of some outstanding heroes to challenge the narrative that has established itself as the gospel truth. Many of the members of ENSSER fall into this category. Longo’s work challenging Jennifer Anne Doudna – who received the 2020 Nobel Prize in Chemistry for her “pioneered work: in CRISPR gene editing - is a must-read in this regard. 

Yet, the video by Alison Van Eenennaam seems to have even shocked Longo. It’s just under 26 minutes, and I found it rather astonishing indeed. Astonishing also, because many of the things proclaimed in the video have meanwhile been found to have serious flaws. The video may be a few years old but seems like a forerunner of what has been unfolding more recently, not only in terms of cattle, but gene editing more generally, how the results are presented, and who, in Van Eenennaam’s view, is to blame for some of the largest global problems of today.

I find her video shocking as it parallels so many of the developments we have seen since the COVID-19 era, and long before most of us had ever heard about “mis-, dis-, and mal-information,” the deployment of fear as a weapon, and blaming truth-tellers.

Anyone watching the video will soon discover numerous parallels to the scientific disaster that has unfolded in recent years and likewise whitewashed since the pandemic. It raises the question. Is it all from the same playbook, orchestrated by the same puppet masters behind the scenes, or is it a reflection of the thinking of most modern scientists?

I am not going to answer this. Instead, I want to highlight some of the stunning claims made in the video and the rationale surrounding this very risky work. The parallels to more recent events will become plainly obvious. Interestingly, in this case of gene-editing of cattle, notable revelations have been made, so that many things that are celebrated in the video have meanwhile proven a dismal disaster.

Van Eenennaam’s gene-editing projects in cattle

CRISPR technologies have exploded and in recent years even reached cattle.

Source: (PDF) 50. Hornless cattle – is gene editing the best solution? Available from: https://www.researchgate.net/publication/352369279_50_Hornless_cattle_-_is_gene_editing_the_best_solution#fullTextFileContent.

The figure gives an overview of the implementation of CRISPR-Cas9 gene editing in cattle. The top route shows gene editing of in vitro fertilized embryos with subsequent selection of successfully edited embryos employing a cell biopsy, followed by transfer of such embryos to recipients. The bottom route shows the gene editing of cells, e.g. fibroblasts, the selection of successfully edited cells, the use of these cells for the production of embryos by somatic cell nuclear transfer, and the subsequent transfer of the embryos to recipients.

Van Eenennaam’s 1st project: Hornless cattle 

This project is about “gene-editing” fathers of the next generation so they do not have horns. When the video was done, this had already been realized in one bull who "faithfully" passed on the gene to its offspring (6, at the time of the interview). She also envisions that if this is done to enough bulls, and if these are used for breeding, then in 20 years, there won't be any cattle left that have horns.

(Note the lofty goal: if done that way, it would essentially eradicate the natural gene pool and we would only have such gene-manipulated cattle left.) 

Why would we need to engage in such a far-reaching project?

Van Eenennaam describes it as an "animal welfare" thing - "the beneficiary is the cow," because they won't have to be de-horned. 

Van Eenennaam’s 2nd project: “All Boys”. This is even more insane, if at all possible. It involves gene editing to change an animal’s sex. The motivation is to reduce the "environmental footprint" of cows to reduce the chance of having female offspring - the justification is that females take longer than males until they produce more beef and bring a monetary return.

To achieve this, Van Eenennaam is using CRISPR to create a gene called SRY and then use artificial insemination. The argument is that the presence of SRY can make a female turn out to be essentially male. 

“The overall hypothesis is that there's a single gene, SRY, that determines maleness. Hypothetically, if we were to duplicate that gene and integrate it into the X chromosome of a male, then we will get X carrying SRY gene and Y males. The Y chromosome bearing semen from a bull like that would be normal, but the X chromosome semen would be carrying the SRY gene.”

And the risks and challenges? Van Eenennaam is indeed concerned about several —- in her view, it is achieving high enough efficiency of the process, to get these “knock-ins working efficiently” in eggs or embryos. 

“In cows, you have to get the eggs from somewhere too; we get ovaries from dead cows. We aspirate immature follicles out of those ovaries, put them in maturation media to make them receptive to fertilization, fertilize them, inject with our editing reagents, and then they have to go through seven days of culture after which we biopsy them. If they survive that, and if they have what we want, then we freeze them, defrost them, transfer them into synchronized cows, and that's only a 15% success rate, and that's just to test if what we think is true is actually true.”

It’s a huge process, and expensive, to get the knock-in cows pregnant, and then they have to carry them to term. In her opinion, if the gene-edited egg/embryo does not lead to a pregnancy, it's a huge waste of time and resources...

Ironically, she is never talking about the health risks of the gene-manipulated animals, those consuming them/their products, or risks to the ecosystem at large. (Some may think this could, in turn, benefit BigPharma; and why would that not create any environmental cost?!)

The Promises of Gene Editing

Van Eenennaam does not want to use the term genetic modification, because it is "just gene editing."

"Often, there is no difference between modifications being made using editing vs. conventional breeding."

Yet, she argues, the potentials of such processes are numerous and great. The two main ones are:

“Many ‘sustainability goals’ can be achieved this way.”

“Genetic engineering enables us to introduce useful variations into our breeding programs in a very targeted way that really accelerates ... genetic improvement...”

“Using gene editing to minimize the loss of livestock ‘to diseases and other environmental factors:’”

“Our group specifically isn't working on this, but there are groups working to produce tuberculosis-resistant cattle, Avian Flu-resistant chickens, and African Swine Fever-resistant pigs.” 

(Note: she does not see any risks. Many of us are wondering now, a few years down the road, about the emergence of avian flu and other diseases that seem very mysterious indeed!)

The future that Van Eenennaam envisions? To optimize cattle genetics via gene-editing to minimize the carbon footprint, to make them resistant to infections, etc. She maintains it would be a "win-win" situation, because farmers would not lose all those animals to disease and, with the optimal genes, they would need fewer resources and time to grow and mature. 

(Note: again, this presumes that there is no biological cost or risk whatsoever to such gene-altered animals, something that is not justified). 

Van Eenennaam’s concerns

In Van Eenennaam’s view, the main challenges are regulations, and that you have “competing industries towards this technology.” To her, the main question will be

“whether they're going to monetize fear around this technology in the same way they have with the GMOs.”

Assured of the benefits, she further argues:

“Regulations make it difficult to get these products to market, mainly due to the GMO scare and the plethora of misinformation being put out into the common world that all GMOs are bad for you.”

Her next worries are even more bizarre.

In contrast to all the wonderful things that she argues she could do, if there were not these regulatory obstacles (which still prohibit her from doing this at scale) she sees two other difficulties (Side-note: contrary to what she is saying, there are risks!)

In her mind:

• People only talk about risks, and never about benefits.

• "Others have monetized fear around gene-editing to sell their own products."

• "The natural food industry sees there is a money-making opportunity to cast fear around gene editing."

To sum it all up: to her, the greatest problem is all this misinformation about gene editing and all the fear about it. 

Hornless cattle gene-editing errors only discovered years later

The gene-edited cattle have been widely celebrated, touted as a poster child of the success of “precision breeding.”

It was only years later that scientists at the Food and Drug Administration who investigated the genome sequence of one of the edited animals discovered what was regarded as impossible. Contrary to the terms “precision” and “editing,” the hornless cattle actually had foreign DNA.

In their publication in Nature Biotechnology, they explain why it had taken years until these unintended effects of the germline genome-edited cattle were discovered, highlighting a concern that has become even more prominent since the pandemic years:

“Each screening approach carries assumptions and biases that may allow alterations of unexpected types to go undetected.”

Even though gene editing is promoted as reliable and predictable, the process itself is much more error-prone and can lead to many unintended genetic alterations.  

The FDA scientists who had discovered that the hornless cattle contained in their genome a stretch of bacterial DNA even suspected that gene-editing errors are under-reported, overlooked, and a potential blind spot in standard genetic screening methods.

One of the main blind spots remains to this day, very similar to the DNA contamination of the mRNA vaccines, involving the integration of the repair template plasmid!

This DNA needed for the gene editor is usually introduced into the cells of plants and animals, often by using additional tools such as genes from bacteria. With the hornless cattle, it was precisely such bacterial DNA that was unintentionally being inserted into the genome of the cattle. Notably, the insertion even included a gene conferring antibiotic resistance. Luckily, these animals were never used for conventional breeding – remember, the genetic modifications and unexpected adulteration involved the germline! They also barely escaped being sold as meat animals, a practical option that Van Eenennaam had considered for financial reasons (it costs 60 cents a pound to incinerate experimental animals).

For another detailed description of the screwup involving the gene-edited cattle, see an MIT Technology Review article and the report by TestBiotech.

Yet, Alison Van Eenennaam’s current webpage still promotes the dismal failures as a huge success, writing that

“it is possible to splice the 'hornless' gene from Aberdeen Angus cattle into the widespread black-and-white Holstein dairy cows so that they are born without protrusions.”

Listed are also 5 awards she has been granted since 2019. The section “Fact Sheet” does not list anything recent, in contrast to her presentations, over 800 globally, as recent as 2024. Specifically, her February 27, 2024 presentation focused on “Animal health and food safety analyses of six offspring of a genome-edited hornless bull,” presented at a National Academy of Sciences workshop.

The dark side of gene editing

The integration of foreign DNA into gene-edited animals is just one of the known problems with gene-editing — which persists to date. There are numerous others. This post cannot do justice to the many misunderstandings, distorted ideas, unsubstantiated claims, and scientific untruths that have been made.

Rather than attempting to give a synopsis of the overall published results, I would like to point my readers to the in-depth work in this regard made by members of The European Network of Scientists for Social and Environmental Responsibility (ENSSER) alone. A succinct summary of the known risks of CRISPR/Cas gene editing can, for example, be found in an ENSSER position statement of 2023. More recently, and specifically related to new GM plants, serious problems are summarized, among others, here, here, here, and here.    

Most recently, on October 7, 2024, Michael Antoniou, Professor of Molecular Genetics and Toxicology Co-Director at King’s College London, and Claire Robinson, Co-Director at GMWatch, sent an open letter to U.K. Minister Daniel Zeichner where they exposed critical shortcomings of the government’s intention to proceed with secondary legislation to implement the Genetic Technology (Precision Breeding) Act. They conclude with the most recent summary of the state of the art of gene-editing technologies:

“There is now an extensive body of reviews and other articles by scientists independent of the agricultural GMO industry providing evidence that new genetic engineering techniques such as gene editing are neither precise nor predictable and that their products can pose risks to health and the environment that are different from those posed by traditional processes....”

As one of the reasons why previous concerns raised have been ignored, they make it clear that regulatory bodies such as DEFRA and the Food Standards Agency 

“are compromised in their independence by the dominant presence of people with conflicts of interest with the agricultural GMO industry...”

These claims are supported by a long list of references (depicted in the figure below).

Conclusion

Over the years, many have tried to expose various COIs as well as regulatory and agency capture by numerous 3-letter agencies and other (self-declared) global leaders. In addition to scientists being bribed, pressured, and intimidated, the above interview indicates another problem: the arrogance of the scientists themselves.

The more experienced researchers, and those with a huge media presence, seem to find it easy to impress young audiences, in particular. In the case of the interview, I find the comprehension given by the young interviewer just as troublesome as the presentation itself – see the figure below for a summary. She bought into everything Van Eenennaam had told her, through and through.

What a stark contrast to the actual findings reported by independent researchers mentioned above!

Will the the hornless cattle debacle trigger some rethinking?

The contrast between the promises and reality could not be more pronounced. Is there any reckoning?

In a different context, former Centers for Disease Control and Prevention Director Robert Redfield is concerned about the arrogance of scientists – which he regards as the most serious form of bioterrorism”

“I do think we can see isolated bioterrorism from radical groups that want to cause havoc. But I think it’s more likely we’ll see accidental consequences of scientific arrogance will cause us biological difficulty.”  

I don’t know when the arrogant mindset among scientists became so prevalent. To me, it is shocking and a warning – to all of us. Most importantly, may global politics catch the significance of this and once again encourage scrutiny and open debate! If not, the dark sides of scientific audacity and hubris may have no end.