Researchers pocket $500,000 of taxpayer money to turn edible plants into mRNA vaccine factories. Report: Claire Robinson

The US National Science Foundation has given University of California Riverside scientists $500,000 of taxpayer money to try to turn edible plants like lettuce or spinach into mRNA vaccine factories. But it’s highly unlikely that the technology will work as intended – and it poses serious contamination risks.

While UC Riverside does not directly claim that the researchers are trying to develop COVID-19 vaccines in the target plants, it is seemingly trying to exploit public fear of the pandemic to gain acceptance for these genetically modified (GM) pharmaceutical crops, pointing out in its press release that “messenger RNA or mRNA technology” is “used in COVID-19 vaccines” (with those produced and marketed by Pfizer and Moderna being of this type). UC Riverside’s hope is apparently that no one who cares about combating the SARS-CoV-2 virus could possibly complain about vaccines in their lettuce.

The aim

The mRNA vaccines currently in use work by instructing our cells to produce SARS-CoV-2 spike proteins, one of the key parts of the virus that makes it so highly infective in humans. The aim is to teach the cells to produce and release SARS-CoV-2 spike protein, which then stimulates the individual’s immune system to produce antibodies against it. These antibodies will then bind to, and interfere with, the ability of the "wild" SARS-CoV-2 virus to infect people and thus protect against serious COVID symptoms.  

One of the challenges with these mRNA vaccines is that they must be kept cold to maintain stability during transport and storage. The new project aims to enable plant-based mRNA vaccines to be stored at room temperature. They would then be eaten by the person who wants to be vaccinated.

The project led Michael Flynn, the former National Security Advisor under former US President Trump, to comment, “Somebody sent me a thing this morning where they’re talking about putting the [COVID] vaccine into salad dressing, or salads.”

It’s not quite accurate, but you get the gist.

The mechanics

The idea is that the genes encoding the mRNA vaccine would be delivered into plant cells via genetically engineered plant viruses. The vaccine gene construction is designed to ultimately end up in the plant’s chloroplasts (structures in the cell) where they produce the desired mRNA. Then the person to be vaccinated would eat the lettuce or spinach containing the mRNA, the mRNA would instruct the person's cells to make the SARS-CoV-2 spike protein, and an antibody immune response will occur, just as with the injected vaccines.

Will it work?

We asked London-based molecular geneticist Dr Michael Antoniou whether the plan would work. He was unconvinced and raised the following question: “Even if the mRNA is produced in the chloroplasts of the food plant, how will it end up intact inside the body of the consumer, be taken up by cells and be expressed? mRNA molecules in food are highly unstable and degrade rapidly on cooking and in the gut.

“I can understand genetically modifying plants to produce a protein vaccine, as has been attempted on numerous occasions in the past, albeit unsuccessfully. But mRNA vaccines in plants? I just don’t see how this could work.”

Dr Antoniou was also puzzled by the statement in the grant proposal that the aim is “to turn chloroplasts of edible plant leaves like spinach or lettuce into biomanufacturing devices for vaccine production”. He said, “Biomanufacturing usually involves the extraction of the desired protein in specialised equipment. Yet the UC Riverside press release implies that people can simply eat the vaccine-containing lettuce or spinach and get a dose of vaccine that way. It’s not clear which of these scenarios is intended.”

Dr Antoniou told us that he had submitted questions on these aspects to the lead researcher, UC Riverside professor Juan Pablo Giraldo, but did not receive any reply.

How would dose be controlled?

A key aspect of how pharmaceutical drugs (including vaccines) work is getting the dose right. But how will dose be controlled in the case of mRNA-containing lettuce, when the concentration of mRNA is likely to vary widely between plants and even between the various parts of a single plant?

And even if this problem were solved, how would dose be controlled when every Tom, Dick and Harry can grow vaccine-containing lettuces in their backyard? Because that, according to Giraldo, is the aim of the project, as we discuss below.

With pharmaceuticals, too much or too often can be disastrous and lead to toxic effects from overdosing. In the case of vaccines, too many doses can lead to immune system exhaustion – meaning that instead of the desired immune response, the immune function is reduced or even blocked completely, leaving the patient at risk of more severe illness. Who would be liable for the outcomes of overdoses from lettuce-gobbling enthusiasts?

Contamination

According to Giraldo, the goal of the research is to have a crop that could be grown almost anywhere, including in people’s gardens and farmers’ fields. In other words, there would no control over the conditions under which it is grown, and whether the crop bolts and cross-pollinates ordinary lettuce and spinach. Lettuce is mostly self-pollinating, but reportedly, some pollen “gets where it shouldn't, so there is always cross pollination”.

Spinach is wind-pollinated and it “can be difficult to keep pure if others in the vicinity are allowing their spinach to flower. Commercial seed growers isolate by as much as 15km”.

Worrying history of GM “pharma” crops

There are worrying precedents for accidental contamination from “pharma” crops. For instance, during a project in California involving genetically engineered corn producing proteins for pharmaceutical uses, including an experimental vaccine for hepatitis B, inspectors found conventional corn sprouting within 15 metres of the pharma corn in a zone that should have been completely clear of crops. Corn, which is wind-pollinated, produces enormous amounts of pollen that typically travels at least 20 to 40 metres beyond where it is being grown, and under windy conditions much further.

And a project in Nebraska came so close to sending plants carrying an experimental pig vaccine into the food supply that it was dubbed the Three Mile Island of Biotech. Over half a million bushels of soybeans and over 150 acres of corn had to be destroyed in the effort to contain the damage.

Following such incidents, even the staunchly pro-GM science journal Nature Biotechnology was moved to point out that “we should be concerned about the presence of a potentially toxic substance in food plants. After all, is this really so different from a conventional pharmaceutical or biopharmaceutical manufacturer packaging its pills in candy wrappers or flour bags or storing its compounds or production batches untended outside the perimeter fence?”

The journal’s editors lamented the fact that “It seems that an industry in which the PhD is the intellectual norm is either incapable of learning a simple lesson from the past or cannot bring itself to act appropriately, despite what it has learned previously.”

So how do Giraldo and his colleagues plan to prevent contamination from their pharma lettuce and spinach? As yet, they have failed to publicly address this critical issue, which has also not been raised by any of the mainstream media outlets reporting their research

In our view, this project is reckless and irresponsible and in backing it, the National Science Foundation is putting the public and the environment at risk.