Potential plant pandemic pathogens
"On reading," by Simon Wain-Hobson, is a weekly discussion of scientific papers and news articles around gain of function research in virology.
Since January 2024, Dr. Wain-Hobson has written weekly essays for Biosafety Now discussing risky research in virology. You can read his entire series here.
On reading the United States Government Policy for Oversight of Dual Use Research of Concern and Pathogens with Enhanced Pandemic Potential and Implemental Guidance document from the plant virus perspective.
Wheat and rice feed the world. To put numbers on that reality, the ten year global average for wheat production for 2015-24 is 768 million metric tons. More than 3.5 billion people eat rice as a basic food staple. In 2024 China and India each produced around 145 million metric tons accounting for around 55% of world production. Both are huge export crops.
Without plants what would chickens and cows eat? Without plants and livestock humans would never have gotten to 8 billion and rising.
Plants are particularly vulnerable: they can be decimated by fire, withered by drought and destroyed by encroaching humans. They are preyed upon by herbivores, omnivores and insects to which must be added a bewildering array of pathogens from fungi to bacteria to viruses. Viruses often make discolored circles on plant leaves so giving a mosaic appearance. For reasons unknown most plant viruses have RNA as their genetic material. That means their genomes are small, generally less than 10-15,000 building blocks and mutate fast, every bit as fast as a human flu virus.
They exact a heavy burden: loss to pathogens of all forms can be as much as 30% for the main food crops.
This quickly feeds into hunger. WHO reported that 733 million people faced hunger in 2023, while around 2.33 billion globally faced moderate or severe food insecurity.
Plant viruses can be transmitted by a large array of insects. Aphids for example can transmit a virus stuck to parts of their anatomy. By contrast, other viruses such as Tomato spotted wilt virus can grow inside thrips, a bothersome plant pest, as well as inside tomato plants. Humans too are vectors with viruses being spread by way of soil on dirty shoes and even by feces.
Feces? A 2006 paper examined the stools of two healthy Singaporeans. They found up to a billion viruses per gram of dry weight fecal matter. Among a collection of 37 different viruses 30 were plant viruses with pepper mild mottle virus (PMMV) dominating. Intriguingly, the fecal PMMV was infectious to host plants, suggesting that humans might act as a vehicle for the dissemination of certain plant viruses. That takes us down a peg or two!
Plant viruses have contributed substantially to basic knowledge in biology. Tobacco mosaic virus (TMV) was the first virus identified back in the 1890s. Wendell Stanley showed that TMV could be crystalized. When crystals were dissolved in water, he showed they were infectious. In turn newly made virus could be crystalized. This indicated that viruses had regular structure something that was totally unknown and surprised many. For this work he shared the 1945 Nobel Prize in chemistry.
In 1955 Fraenkel-Conrat showed that naked TMV RNA when placed on a tobacco leaf abrasion could infect the plant systemically like the whole virus. This was a challenge to the newly minted DNA structure of Watson and Crick in 1953 and those that had clearly shown that bacterial DNA was the hereditary material. It transpired that RNA could also be the hereditary molecule albeit only among viruses. Everywhere else it is DNA.
Genetic manipulation of plant viruses has matched that of human and animal viruses. Everything can be done - plant virus‐based vectors have also been successfully developed for gene function studies and target gene expression in plants. Viruses can be cultured in the lab or in specialized greenhouses where nutrients, water and light rigorously controlled.
Obviously, plant viruses could be manipulated to do harm, with harm leading to hunger. Using the flawed Fouchier & Kawaoka logic some academic scientists could argue that they wished to make an inventory of mutations that confer enhanced virulence or insect borne transmission of a virus that, let’s say, infects rice, Remember, there will always be a premium on working on a virus that infects an economically important crop.
The same issues concerning predicting virus behavior come to the fore. Would the combination of mapped mutations work the same way in a different virus? This has been discussed in several essays. Lab accidents must occur, but as humans are not infected, their frequency is probably vastly underappreciated. Furthermore, there is experimentation in the close confines of a lab which will have a higher degree of biosafety compared to work in greenhouses. On reading would hope that no experiments on enhanced virulence and transmission would be performed in greenhouses.
There is not one engineered plant virus study that has made news headlines but unless discussed in the open we can’t assume that such experiments will not be performed. As mentioned most plant viruses are rapidly mutating RNA viruses so just like their animal and human counterparts, that can adapt rapidly to new environments. In fact, the highest mutation rate for any biological entity is that of Chrysanthemum chlorotic mottle viroid where a mutation occurs on average every 400 RNA building blocks copied.
In an earlier essay we discussed amphotropic bat coronaviruses, viruses that can multiply in at least two different hosts (Coronavirus biosafety levels). Tomato spotted wilt virus (TSWV) mentioned above and related tospoviruses infect more than 1000 species of plants including many important food crops and ornamental plants.
So even if everything was fully worked out for a GOF 2.0 engineered TSWV strain infecting tomato plants, it is not at all sure the same dynamics will pertain to another plant. Yet more uncertainties.
Despite the GOF 2.0 controversy, no discussion of the plant equivalent was undertaken. Fortunately, in 2023 the US National Science Advisory Board for Biosecurity (NSABB) noted the following in the executive summary of a long report. Finding 7. The focus of the current P3CO policy on pathogens that are likely to cause disease in humans is appropriate. However, an analogous oversight framework is lacking for research involving enhanced animal or plant pathogens.
This was adopted by USG in its 2024 policy document on DURC along with work on animal viruses. In Section III-D-5-a. BL3-P (Plants) or BL2-P + biological containment is recommended for experiments involving most exotic (see Section V-M, Footnotes and References of Sections I-IV) infectious agents with recognized potential for serious detrimental impact on managed or natural ecosystems when recombinant or synthetic nucleic acid molecule techniques are associated with whole plants.
In Section V-M we learn that In accordance with accepted scientific and regulatory practices of the discipline of plant pathology, an exotic plant pathogen (e.g., virus, bacteria, or fungus) is one that is unknown to occur within the U.S. Determination of whether a pathogen has a potential for serious detrimental impact on managed (agricultural, forest, grassland) or natural ecosystems should be made by the Principal Investigator and the Institutional Biosafety Committee, in consultation with scientists knowledgeable of plant diseases, crops, and ecosystems in the geographic area of the research. Emphasis added.
Given the need for highly specialized knowledge, the decision is left to the experimenter. Finally, there is a 12 page annex entitled Physical and biological containment for recombinant or synthetic nucleic acid molecule research involving plants. They have made a considerable effort.
However, we’re in a dilemma for:
• We know that scientists overestimate the benefits of their work and underestimate the risks.
• The plant virology community is far smaller than that for animal of human viruses while they have plethora of different viruses and viroids to cater for. Accordingly, specialist knowledge is far less abundant.
• It quickly comes down to trust. In the GOF 2.0 bird flu controversy trust was lost with players flip flopping as they chose and backtracking over time. The COVID origins mess saw calls for by establishment scientists for censorship of dissenting opinion, aka the lab leak which was disgraceful. Loss of trust in fellow scientists makes life so much more complicated for scientists, and leaves the public wondering, to be polite.
• The 13 year old GOF 2.0 controversy is still not resolved.
• We can’t even agree in writing on what should be the lowest common denominator; first, do no harm.
Terry Pratchett’s one-liner is worth mulling over. I’ll be more enthusiastic about encouraging thinking outside the box when there’s evidence of any thinking going on inside it.
Conclusion
This needs open discussion and if that takes time, so be it. For plant virologists who may not have followed too closely the GOF 2.0 controversy, trust today means applying the very simple rule, ‘first, do no harm.’ Otherwise, the legislator will step in. Which they may well do.
Aside 0
This essay was up and waiting to be posted when on Monday May 5, President Trump signed an Executive Order stopping dangerous GOF research in the US at the federal level. We will dwell on this end to gain of folly in next week’s essay.
In defining the scope of dangerous GOF research, among eight activities we read conferring to the agent or toxin resistance to clinically or agriculturally useful prophylactic or therapeutic interventions against that agent or toxin or facilitating their ability to evade detection methodologies. Someone was thinking and realized that a novel plant or animal virus could wreak havoc on a world that has more than enough problems.
Aside 1
Imagine if someone developed a novel highly pathogenic GOF modified rice virus. As rice is a huge food staple and an important export commodity, hopefully SE Asian governments would go ballistic. Lest On reading is accused of suggesting a noxious idea, this was the cornerstone of the 1956 sci-fi book The Death of Grass which was made into the film No Blade of Grass in 1970.
Aside 2
The oral-fecal route results in a myriad of different infections from bacteria to reoviruses, rotaviruses and picornaviruses such as polio, none of which have a membrane. Those with a membrane, think HIV, flu, herpesviruses and more are chewed up by stomach acidity.
Aside 3
In a fascinating review of Chinese contributions to plant virology, we learn that studies have shown that two geminiviruses, TYLCCNV and tobacco curly shoot virus (TbCSV), can enhance the fecundity and longevity of invasive whiteflies (Middle East‐Asia Minor 1, formerly known as B biotype) when they feed on infected plants. Viruses manipulating their vectors!
Aside 4
Fortunately, plant viruses don’t infect mammals although there is one curious observation that suggests this is not entirely impossible.
Aside 5
Mention of Watson and Crick provoked a flashback to a detail that has been largely forgotten. In the 1953 structure of DNA the bases A and T pair with each other by way of two hydrogen bonds. These are looser bonds than those linking oxygen to hydrogen in a water molecule, for example. Remarkably, the bases G and C are also shown to be paired by two hydrogen bonds. However, as any biologist knows G and C are held together by three hydrogen bonds, a correction that emerged in 1956.
