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The rehabilitation of tobacco in the era of Covid-19

 

Since the 1960s, tobacco has had an increasingly bad reputation. The UK epidemiologists, Doll and Hill, had already confirmed the connection between smoking and lung cancer as early as 1950. Nevertheless, it took decades for these findings to be translated into government-sanctioned disincentives to smoke cigarettes. We all know now how disingenuous the cigarette companies were during those decades. In hindsight (which is always 20:20), it was obvious. Lung cancer was a very rare condition and most physicians did not encounter it until the end of the 19th century when smoking cigarettes became a popular habit. The epidemiology numbers and the physiological proof are so compelling, that it is surprising that this habit persists in so many parts of the world.

 

The tobacco plant is an innocent participant in this deadly habit. It is true that it produces nicotine, which is a highly addictive alkaloid. But tobacco does not produce nicotine in order to create a craving to smoke in humans. Nicotine is a naturally occurring insecticide and has evolved to protect the (originally wild) tobacco plant from insect pests and other herbivores. Older amateur gardeners will remember buying tobacco extracts containing nicotine as insecticides. These are now banned in Europe and N. America, but the use of such extracts as an insecticide dates back to the 17th century.

 

In the midst of our Covid-centric world, what has tobacco got to do with anything? True, there is a controversy raging right now about whether smokers are more- or less-susceptible to Covid-19. But this is not where I am going. Let’s look at the tobacco plant itself and see how its story strangely intersects with our current predicament.  This pariah plant has actually helped us to understand viruses and paradoxically it might help us to combat this pandemic over the coming months.

 

In the early years of the 20th century, viruses were very mysterious entities. Scientists had used the word ‘virus’ to describe any infectious agent as early as 1728. But in 1892, a Russian botanist, Dmitri Ivanovsky, described the first virus, showing that it was much smaller than any bacteria and a different type of infectious agent. The virus he described was not a human pathogen, but a plant virus called Tobacco Mosaic Virus (TMV). Six years later, Martinus Beijerinck, a Dutch scientist, independently replicated these experiments and the new science of virology was invented. For the next several decades, scientists working on viruses used TMV as their paradigm. In 1937, William Stanley first purified the crystalline form of this virus. At the time he was convinced that it was made entirely of protein, which turned out to be wrong, but he got the Nobel Prize anyway in 1946 for his pioneering work in purifying the virus.

 

Fred Bawden and Norman Pirie in 1936 working at the Rothamsted Research Station in the UK showed that the purified virus crystals contained another substance which turned out to be critical. Six percent of the virus crystals by weight was actually RNA. There continued much controversy about the transmission of this virus. Was protein really the infectious agent, was the RNA just a structural scaffold for the viral particle? Then in 1957, Beatrice Singer, performed the pivotal experiment which showed that tobacco mosaic virus RNA on its own was infectious! This proved conclusively that the genetic component of the virus was actually RNA not protein. The protein was the structural part and acts as the protective coat around the RNA. 

 

This should sound familiar. During the relentless daily news bulletins about Covid-19, we are now all amateur virologists. We have learned that Covid-19 is a spiky ball of protein, with some fat (lipid) surrounding a central core of RNA. It is the RNA that is the dangerous payload of this pernicious virus. Amazingly, up to the 1950s, most of our knowledge of viruses came from a tobacco virus!

 

If you are impressed by the botanists’ contribution to our understanding of viruses, much more recent research has been using tobacco to combat the current Covid pandemic. We have known for years that plants can ‘read’ any gene and follow the instructions contained in the gene. If we introduce a gene from mammals, insects, fungi and even viruses into plants, they will obey the instructions and make the corresponding RNA and subsequently a protein specified by the RNA. It has been known for 15 years that if we introduce genes from a human pathogenic virus like influenza into a plant, the plant will make viral protein. About 10 years ago, it was found that when this happens, the plants can make ‘viral like particles’ which look just like the virus but comprise only its protein scaffold. These are non-infectious, empty particles (with no enclosed RNA) but they are perfect as vaccines. Years before the current pandemic, this was proven for influenza virus vaccines. Amazingly, the plant of choice to make these vaccines is still tobacco!

            

There are now many university laboratories and several plant-biotechnology companies (e.g.MedicagoiBio) who are using tobacco as the production vehicle for Covid-19 vaccine candidates. A lesser known fact is that during the last Ebola virus outbreak in Africa, anti-Ebola antibodies were also produced in tobacco to tackle that epidemic. 

 

So, although our misuse of tobacco through smoking has been the cause of millions of premature deaths in the past, this is a plant that started the whole science of virology. As we hopefully move towards routine vaccination against Covid-19, tobacco could yet be the source of millions of doses of a much-needed vaccine. Let’s keep an eye on plant companies too. If you want to find out more, you can read a recent article by Paul Christou and colleagues on how plants like tobacco can help in this fight against Covid-19.

 

Maurice Moloney