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An Interview with Professor Manuel Varela: Who Discovered this thing we call Viruses?

Nov 3, 2018 by

Michael F. Shaughnessy –

1) Although there may be some debate on this point, apparently Dmitri Iosifovich Ivanovsky is the Soviet scientist who discovered viruses. First of all, where was he born and when, and when and where did he go to school?

While you are certainly correct regarding the debate, in many modern treatises regarding the history of microbiology, Dr. Dmitri Ivanovsky is generally regarding as having been the first discoverer of the viruses.  At the very least, he is highly regarded as having been one of the founding fathers of the virology field of interest.

The consensus seems to be that, in 1882, Dr. Adolf Mayer described the cause of the tobacco mosaic disease as consisting of a soluble infectious agent, like perhaps an enzyme of some sort. Dr. Ivanovsky is generally regarded as having propounded, in 1892, an infectious filterable bacterial cause for the tobacco mosaic disease, perhaps also being particulate in its nature; while Dr. Martinus Beijerinck definitively stated that the infectious tobacco mosaic disease agent was not necessarily a bacterium, but rather a contagious living liquid virus. Therefore, historians of science appear happy to give credit to each of these three scientists as bona fide founding fathers of the scientific discipline called virology—the study of viruses.

Another debate emerges regarding the date of Dr. Ivanovsky’s birthdate, with one source stating the 28th day of October, in 1864, while another source maintaining that the 9th day of November 1864 is the day of his birth. It has been speculated that the disparity in the birthdates is due to the change over to the Gregorian calendar from the previous Julian calendar by Russia, in 1916. Thus, October 28 seems to be the generally accepted birthdate.

Another point of contention appears to be Dr. Ivanovsky’s birthplace. One source dictates his place of birth to be a village called Niz, located within the Gdov district of the St. Petersburg region, while another source maintains that the birthplace of Dr. Ivanovsky is Gdov itself. In either case, it is clear that he was born in Russian Empire.

Incidentally, there are also variations on the spelling of his name:  Dmitri versus Dmitry, and Ivanovsky versus Iwanowski. The spelling differences apparently have to do with the Russian versus German etymologies.

The Ivanovsky family had limited finances, especially after his father, Joseph Antonovich, died when Dmitri was still young.  Dmitri attended secondary school at Larinski, where took the highest honors upon graduation in 1883. Ivanovsky then attended the University of St. Petersburg. While at university, Ivanovsky was influenced by two prominent faculty, Drs. Andrei Famintsin and A.N. Beketov.  These university faculty members encouraged Ivanovsky and made lasting impressions upon him. One of these investigators, Prof. Famintsin (also spelled Famintsyn), assigned Ivanovsky to the task of studying an outbreak of crop damage occurring in tobacco plants.

In 1887, Ivanovsky used the results of his tobacco disease investigations as a basis for starting his undergraduate thesis, which he defended in 1888 at the University of St. Petersburg.  In 1895, Ivanovsky took his master’s degree after studying alcohol fermentation as this thesis project. While teaching and working on his doctoral thesis project at St. Petersburg, the university had dismissed him for lack of progress in completing the graduate work. The story is told that his students vigorously protested the dismissal. Nevertheless, the dismissal was considered final, and he was not re-admitted to the program. One source states that Ivanovsky took his thesis project to the University of Kiev, where they accepted his tobacco work as a suitable project, whereupon his was granted a doctoral degree in 1903. The new faculty graduate committee members who accepted the tobacco thesis work of Ivanovsky were recorded as Drs. Navashin and Purievich, attesting to their propensity to see far ahead into the future regarding the importance of the topic.

2) His name seems to be linked with his study of mosaic disease in tobacco. Can you explain what this is all about?

In essence, Dr. Ivanovsky found, in 1892, that the mosaic disease of the tobacco plant was a filterable infectious microbial agent, possibly being particulate in nature. At first, he incorrectly concluded that the infectious agent was a bacterium, similar to the previous contention held by Dr. Adolf Mayer, who in 1879 had studied the plant disease in a systematic way, invoking Koch’s postulates.

In his initial experimental work, Dr. Ivanovsky essentially repeated the previous investigative work of Dr. Mayer. Here, Dr. Ivanovsky took diseased tobacco plants, with their mosaic lesions on their leaves, prepared a crushed tobacco plant slurry, and ran the preparation through a fine linen-based filter apparatus. Next, Dr. Ivanovsky applied the diseased tobacco filtrate into the veins of healthy tobacco plants, in much the same approach as Prof. Koch had conducted with his bacterial anthrax studies in lab animals. In a span of about 2 weeks, Dr. Ivanovsky observed that the inoculated healthy plants became diseased, producing the mosaic lesions on their leaves, too. In so doing, Dr. Ivanovsky confirmed the transmissibility property of the agent, from diseased plant to healthy plant, of the tobacco mosaic disease.

Next, Dr. Ivanovsky inquired whether the disease was inheritable.  Thus, to examine this possibility, he acquired new progeny seeds from diseased tobacco plants, and planted them. The new progeny plants failed to show the distinctive tobacco mosaic disease. Therefore, Dr. Ivanovsky’s work strongly implied that the disease was infectious, rather than genetic in its basis. With this new knowledge in hand, Dr. Ivanovsky recommend that tobacco farmers burn all infected plants and rotate crops in order to prevent the emergence of new mosaic disease.

Then, Dr. Ivanovsky used a newly developed porcelain filter, called a Pasteur-Chamberland candle, with very fine pores, through which it was believed that most, if not all, bacteria were stopped in their tracks on the front part of the porcelain apparatus.  Unfortunately, for Dr. Ivanovsky, the new filter could stop not all bacteria. In fact, when Dr. Ivanovsky repeated his tobacco mosaic plant experiments, preparing the slurry of diseased leaves with the new Pasteur-Chamberland candle filter, the filtrate material showed the clear signs of the mosaic disease in newly injected healthy tobacco plants.  Thus, he concluded that the infectious agent was either a very tiny bacterium or a soluble toxin; that is, the microbe or a secreted component, either of which could readily pass through the new Pasteur-Chamberland candle filter, was the infectious agent of the tobacco mosaic disease.  Unfortunately, Dr. Ivanovsky was wrong about both of these conclusions. The disease turned out be a virus and not a bacterium or a toxin, as we currently know each of these in much detail today. History has forgiven him, however, considering that no one in the history of science had ever actually seen a virus before.

When Dr. Ivanovsky later learned about the studies of Dr. Martinus Willem Beijerinck, published in 1899, in which Dr. Beijerinck claimed that the infectious agent was some sort of “living fluid contagion” Dr. Ivanovsky conducted another experiment.  He measured the diffusion of the infectious agent through agar, concluding that the contagion was more of a particulate entity in its nature, rather than a living fluid, as Dr. Beijerinck had postulated.

Interestingly, in his published doctoral dissertation, Dr. Ivanovsky included illustrations of diseased tobacco plant cells showing intracellular material that he had noticed. In one of these illustrations, he described so-called bacterial inclusion bodies, which appear to be highly similar to the cylindrical and helical nature of the true tobacco mosaic virus (TMV) structure, as definitively shown in later studies of Dr. Wendell Stanley, in 1935, showing photographs of the actual viruses for the first time in history. 

In 1903, Dr. Ivanovsky was to backtrack a little regarding the bacterium / toxin hypothesis as a cause of the tobacco mosaic disease, writing that the contagion was certainly a microbe, a filterable agent, and a mystery to be settled later.  Dr. Beijerinck, meanwhile, was also to acknowledge finally the contributions of Dr. Ivanovsky in correctly assessing that the agent multiplied only within the tobacco plants. 

3) Why would soviet authorities be concerned about some bacteria or insect that would damage tobacco plans in the Ukraine?

Presumably, the tobacco plants and the resulting industry connected to it were a prime source of financial wealth. Thus, damage to crops was a serious situation. Besides the Ukraine, the “tobacco pox” also affected Bessarabia and the Crimea. Still a young scientist at the time, Ivanovsky was sent to investigate the problem. First, his work focused on a fungal infection of the tobacco, a condition known as the “ashening” in which a fine powdery mildew developed on the leaves of the tobacco plants. Ivanovsky found that the plant disease manifested itself in humid conditions; and he further found that the fungus hid in thermally protected locations within the tobacco plant during the winters, making it possible for the fungus to survive the cold temperatures. Thus, he recommended that the plantation farmers remove both the afflicted leaves and the tops of the tobacco plants between seasons. Ivanovsky further recommended that the diseased parts of the plants be burned in order to stop the fungus in its tracks, preventing contamination of the next season’s crops. Lastly, he suggested that new crops be planted with a wide berth between each growing plant and that the fields be sufficiently drained to avoid excessive soil moisture.

Another affliction involving the tobacco plants was, of course, the more famous tobacco mosaic disease, in which their leaves developed white spotty mosaic-shaped lesions, soon thereafter leaving the plants to wilt and rot, making it impossible to use for the tobacco industry in an effective manner. Ivanovsky found that in old plantations, the mosaic disease was transmitted via contaminated leaves and roots of the tobacco plants. Further, he recorded that in relatively newer plantations, the mosaic lesions spread to susceptible plants from contaminated tobacco leaves of diseased plants. When he examined the optimal conditions that brought about the mosaic contagion in the tobacco plants, Ivanovsky noticed that high relative humidity, warmer than usual weather, and moist soil were all necessary. Thus, he made the connection that when the tobacco plants were growing at their fastest rates, the contagion made its mosaic disease overtly known, producing worthless material for the financially important tobacco industry. As he had suggested potential preventative measures with the fungal pox, Ivanovsky recommended measures to address the mosaic disease. He suggested that the afflicted tobacco plants also be burned and that crops rotated on a routine basis. Lastly, Ivanovsky recommended that the diseased parts of the plants, with their mosaic lesions, be vigorously excised.

3) Apparently, he later studied photosynthesis- now for the uninitiated, what exactly IS photosynthesis- and why is it important?

In 1901, Dr. Ivanovsky had moved to Warsaw, Poland, becoming a faculty member, an associate professor, at the University there, where he studied photosynthesis later, in 1903. Dr. Ivanovsky had noticed a correlation of sorts between the starch content of tobacco leaves and the plant-associated pigment compound called chlorophyll. Working together with his younger protégé Dr. Michael Tsvett, they examined the relationship between the levels of starch and chlorophyll in the presence of light.  They found that chlorophyll was present in the plant leaves in a manner akin to a laboratory-based colloidal solution, making both plant and lab versions stable in the presence of light, a condition known as photostability. They also found that the chlorophyll content in plants was highly concentrated, suggesting that these concentrated amounts had something to do with their observed photostabilities. They also found that yellow pigmented compounds from tobacco leaves played a role in the protection of the chlorophyll from the photo-bleaching effects of light that belonged to the violet and blue spectra.

Photosynthesis in plants is a metabolic process that’s aimed at producing biosynthetic organic material from inorganic matter by converting the energy stored in light (sunlight) into a chemical version of that energy. The newly produced chemical energy is then used to conduct an important conversion of carbon dioxide gas from the air into newly made sugars. The biosynthesis of sugar molecules using the carbons extracted from the atmospheric carbon dioxide gas is referred to as carbon fixation.

During the photosynthetic processes, electrons are removed from molecules of water and incorporated into plant sugars, making these molecules rich in their electron content and thus making them rich in their energy content. The process of photosynthesis occurs in two general steps. First, a set of so-called “light reactions” take place. Here, the energy stored in sunlight is exploited by the plants to produce biological forms of energy, namely, ATP and sometimes NADPH. 

In the second step of photosynthesis, a set of so-called “dark reactions” take place. The term “dark reaction” is historical, and in modern times, the process is referred to as “light-independent” reactions in order to denote the fact that the reactions may not always necessarily occur only in the dark. In this second phase of photosynthesis, the carbon atoms present in carbon dioxide molecules from the air are now used to make sugars using the ATP and NADPH energies that had been generated during the first step. During this sugar making process, electrons are moved from NADPH to the sugars, thus reducing them, and ATP is hydrolyzed, expending the energy stored in these molecules. This second stage of photosynthesis is also known to biochemists as the Calvin-Benson cycle, and it is the system that performs the carbon-fixing process I mentioned earlier.

4) His work in photosynthesis led to work in chloroplasts (which are apparently chlorophyll-bearing structures). Why are chloroplasts important in the big scheme of things?

Chloroplasts are cellular structures that are devoted to performing the light-harvesting processes found in photosynthetic eukaryotic organisms, such as in green plants, plus in certain fungi, protozoa, and algae.  While chloroplasts are capable of biosynthesizing protein, they function primarily to collect the energy stored in light and use it to make ATP and sugars using carbons taken from the carbon dioxide in the air—often the same carbon dioxide that we humans, other animals, and many other organisms expel during respiration. The internal structure of chloroplasts are quite intricate, consisting of many membrane-lined sacs called thylakoids, which are utilized to conduct their photosynthetic sugar-making pathways of plant metabolism, using sunlight energy to do so.  

Interestingly, chloroplasts seem to be largely absent in prokaryotic organisms. Yet, photosynthetic bacteria are certainly present on the planet, they nonetheless use sunlight to make sugars, just as well. In these cases, prokaryotes harbor thylakoids, which are also membranous structures containing chlorophyll and other pigments embedded within a matrix system of protein and constituting a so-called photosystem.  The thylakoids of photosynthetic bacteria are composed of the plasma or cytoplasmic membranes.  Thus, certain photosynthetic bacteria play an essential role in nutrient cycling, such as in the nitrogen cycle, providing nitrogen atoms in the form of ammonia back to plants and other organisms so that they can perform needed protein synthesis.  These cycles form an integral basis of the Earth’s ecosystem. 

5) This famous microbiologist also studied plant anatomy and physiology.  How does the study of plant anatomy and physiology contribute to the field of microbiology?  

I think it is interesting to note that these two seemingly disparate fields of study, plant biology versus microbiology, contribute to each other. Both of these areas are of benefit to each other in several ways. Let us discuss a few of these plant-microbe relationships.

First, plants serve as suitable hosts for microbial pathogens. Members from several classes of microbes, such as the bacteria, viruses, and the protozoa, are known to act as causative agents of plant pathology. This is a very large and important field of study. As we saw in the case of the tobacco mosaic disease, caused by a virus, the regional economy during the time of Dr. Ivanovsky could have been in serious trouble, had it not been for the recommendations by him and others to address the problem. In addition to the tobacco plants and its associated industry, food crops may also be severely affected by microbial pathogens. Some of the most important crops that may be susceptible to microbial pathogens also include avocados, corn, coconuts, cucumbers, legumes, potatoes, and sugarcane. Many of these crops are acutely tied to the economy, and destruction of these crops and others may correspondingly affect their economic productivities.

One important historical incident that comes to mind is the so-called Irish potato famine. The infecting water mold, an alga called Phytophthora infestans, essentially devastated the entire country’s supply of potatoes, which had been their main food staple. It caused massive starvation and movement of huge waves of Irish immigrants to other countries, where permanent alterations were made in the sociologies, cultures, music, politics, economies, etc., to both groups of hosts and migrants involved, not to mention to each of their descendants. In the U.S., for example, because the Chinese and Irish immigrants built the transcontinental railroad, the U.S. economy flourished, eventually making the U.S. a superpower.

Another important relationship between plants and microbes has to do with the transfer of nutrients from soil to plants with the help of microbes. For example, certain species of bacteria, such as those of the genus Rhizobium live on the roots of plants and provide needed ammonia molecules that plants may use to synthesize proteins, permitting plants to grow in the soil.

In another case, when plants die and decompose, it is with the help of various microbes that they conduct the plant decomposition process, thus recycling elements and minerals back to the soil so that other organisms may use for their own growth purposes.  Without microbes the dead plants would simply accumulate, tying up important biomolecules that could have otherwise been used for other plants and organisms in order for them to live, as well.

Microbes can be used in the modern biotechnological field to make useful products. For example, by using microbes and recombinant DNA technology, certain crops can be genetically engineered to be resistant to the destructive effects of insect predation. In one particular instance, a bacterium called Bacillus thuringiensis (Bt) is a potent predator of several types of crop-destroying insects; and by using recombinant DNA technology, one can use the engineer the crop plants to harbor certain Bt proteins to confer the insect predation resistance. These engineered crops using microbial proteins are then able to enhance the crop yields, producing efficient harvest on a yearly basis. Such practices can improve the economic status.

6) What other contributions did this famous microbiologist make, and what other things is he known for?

In addition to the study of tobacco plant diseases and photosynthesis, Dr. Ivanovsky had interests in yeast-based alcohol fermentation and in soil microbiology.

Dr. Ivanovsky was keen to better understand the roles of elements oxygen and nitrogen in alcoholic fermentation. In the laboratory, Dr. Ivanovsky built an apparatus that permitted him to continually culture alcohol-producing yeasts. He fed the cultured yeasts a carbon source, namely sugar, plus peptone, which is rich in nitrogen-containing molecules. He showed that as the peptone concentrations were increased in the experimentally growing yeasts, their growth rates were enhanced but their alcohol fermentation rates were reduced. Dr. Ivanovsky was also leery to make the connection between oxygen depletion and alcoholic fermentation rates, believing instead on the importance of nutrient availability rather than on oxygen availability as being one of the prime drivers of fermentation.

While not necessarily conducting research studies in the field of soil microbiology, as a professor Dr. Ivanovsky was nonetheless instrumental in the education and training of its students, as he had developed a series of lectureships on the topic. His observations on the subject had influences, especially in Russian science. For instance, he pointed out to his students and trainees the importance of soil microorganisms on the roles they played upon decomposition of dead decaying matter, especially in the recycling of minerals and other elements back to plants. Further, he advocated the involvement of nitrogen-containing substances in soil as playing important roles in fertilizers for crops. He also encouraged the importance of soil microorganisms in agriculture, an insight that is still relevant in modern times. 

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