On Wednesday night, I headed down to the beautiful Bell House, in the Gowanus section of Brooklyn, for this month's Secret Science Club lecture featuring evolutionary biologist and virologist Dr Paul Turner of Yale University. Dr Turner titled his lecture Viruses: Good, Bad, and Ugly, in homage to his favorite spaghetti western.
Dr Turner began his lecture by addressing the amazing biodiversity of the planet, displaying first a list of North America's 'big five' charismatic megafauna- grizzly bears, caribou, moose, bighorn sheep, and wolves, contrasting it with an invisible 'big five' of North America- the Giardia protozoan, the influenza virus, the HIV retrovirus, a bacteriophage, and the Cordyceps fungi. He posed the question, are microbes nasty? His answer was that this was not necessarily true, that microbes can benefit human health. In humans, the microbiome, the community of bacteria, fungi, and viruses within the body, outnumbers the body's own cells. The microbiome can affect one's risk of heart disease, cancer, and other illnesses- it also plays a role in an individual's weight. It is currently believed that childhood exposure to microbes may help prevent autoimmune diseases, a concept known as the hygiene hypothesis. In experimental helminthic therapy, irradiated hookworm eggs are introduced into subjects in order to reduce autoimmune diseases. Dr Turner summed up this part of the lecture by noting that we live in a microbial world.
He then posed the question: What is a virus? After repeating his theme of ugly, good, and bad viruses, he posed another question: Might a virus save your life someday? Cellular life can be divided into three broad categories- bacteria, archaea, and eukaryotes... all of which form cells enclosed by a membrane. In contrast, viruses do not form cells, they characteristically have genetic material, DNA or RNA, surrounded by proteins. Viruses come in many forms- typical bacteriophages have tail vanes (Dr Turner facetiously compared them to the lunar lander). Influenza viruses contain RNA in the center of a protein shell. Viruses have a non-cellular life cycle. In order to reproduce, a virus enters the proper cell type, injects its genetic material, the viral genetic material hijacks the cell metabolism to copy itself, and the viral offspring are released from the cell.
Viruses are biodiverse, most are sub-microscopic... an electron microscope is needed to observe them. Influenza viruses and rhabdoviruses come in many shapes. Virus size does not correlate with host size- a whale can be infected by small viruses, a bacterium by large ones.
The evolutionary origin of viruses is a mystery- viruses appeared billions of years ago. Dr Turner posed a multiple choice question. A. Did viruses evolve before bacteria, being inhabitants of an RNA-based world that existed before DNA evolved? B. Did viruses evolve as parasites within cellular organisms? C. Are viruses 'devolved' cellular information? D. Did viruses arrive to Earth from space? Dr Turner jocularly illustrated these last two options with a picture of Devo and a picture of the lunar lander juxtaposed with a bacteriophage. Dr Turner indicated that A, B, and C are the three leading ideas.
Viruses reproduce very quickly, while bacteria can reproduce rapidly through binary fission, viruses can grow even faster as their progeny are formed in the cells of other organisms. Viruses are very abundant, they thrive in all environments, and they outnumber all other organisms. They are the most numerous of Earth's inhabitants. The human global population is approximately 7.2 billion, while the global virus population is estimated to be 1031. If the genes of all of the Earth's viruses were laid end-to-end, they would stretch to the Perseus Cluster, approximately 250 million light years away.
We live in a viral world- the bad viruses make the news, they are the viruses that are researched. There is evidence of ancient viral diseases- the Pharaoh Siptah had a clubbed foot that suggests polio, which is probably depicted on an image of a priest on a stele dating to 3700BCE. The mummified remains of Ramesses V indicate that he had suffered a case of smallpox. The polio virus is common in soil, it is usually harmless to humans, but becomes extremely dangerous when it enters the human nervous system. The smallpox virus was rendered extinct in its natural environment, the human body, and exists only in labs at the CDC and in Russia.
Dr Turner then took us on a tour of deadly epidemics- the 'Ugly' viruses. The 1918 flu killed 50 million to 100 million victims, a single flu strain managed to infect approximately 500 million individuals before the advent of commercial air travel. In our modern era, where travel is common, a flu epidemic may be just as deadly if the available vaccines don't match the flu strain. The Great Plague of the 14th century, which killed approximately 40% of Europe's population, is generally blamed on the bacterium Yersinia pestis, but other pathogens may have contributed to the death toll, hygiene and sanitation being sub-par at the time. The smallpox epidemic which began in 1520 in the New World decimated the Native American populations, but there are no estimates of the death toll. The AIDS epidemic, which is generally considered to have started in 1981, has claimed 39 million lives, with 78 million likely infected.
Virus emergence is a continual process- viruses can 'jump into' humans from other organisms. Bats commonly harbor viruses, which are often transmitted to pigs, then from the pigs to humans. HIV has jumped from other primates to humans, with HIV1 originating in chimpanzees and the less lethal HIV2 originating in monkeys. The HIV strains were probably introduced to humans between the 1920s and 1940s. Flu viruses are commonly transmitted by birds, especially waterfowl. The human immune system is 'naive' to bird flus- infection is easy, and we don't have the money and time to prevent 'fires', just to put them out. The mosquito born Zika virus was first identified in a rhesus monkey, only recently emerging in humans.
After dealing with the positively ugly viruses, Dr Turner focused his attention on the merely 'bad' viruses. Some viruses make you sick but don't kill you. He repeated the 1969-vintage quip: "We can put a man on the moon but we can't cure a common cold." Colds are caused by a variety of rhinoviruses. If an individual has respiratory problems, such as asthma, a cold can be serious, but many people are healthy enough to go to work with a cold, becoming links in the chains of contagion. Rotaviruses can kill children, but generally don't kill adults. Approximately 5% of child deaths in the developing world can be attributed to rotaviruses, which cause severe, dehydrating diarrhea.
Dr Turner then posed the question, can viruses be used in biocontrol of pests? He brought up the use of myxomatosis, the dreaded 'white blindness' of Watership Down, to control the invasive rabbit population of Australia in the 1950s. While partially successful, this introduction generally failed because the virus tended to kill rabbits before they had a chance to transmit it. Dr Turner chalked this up to yet another example of the folly of introducing invasive species to Australia.
Dr Turner then focused his attention on the 'good'- are viruses good for ecosystems? He noted that an absence of predators tends to throw biological systems out of balance, citing the absence of the wolf in most of North America, and the resultant explosion of the deer population, as a factor in the spread of the bacteria that cause Lyme disease... fewer deer, less Lyme. Viruses indirectly regulate the photosynthetic activity of cyanobacteria in the oceans. Cyanobacteria evolved about 3.5 billion years ago, and altered Earth's atmosphere by elevating oxygen levels. Cyanophages outnumber cyanobacteria by a factor of ten to one, regulating the cyanobacteria population. The cyanophages carry the genes which code for photosynthesis. Dr Turner noted that viruses infect other organisms and continually 'churn' genes. Approximately one in twenty of a person's daily breaths contain oxygen produced by virus genes.
Dr Turner then posed us a riddle: What would you trade 36 bushels of wheat, 72 of rice, 4 oxen, 12 sheep, 8 pigs, 2 barrels of wine, 4 barrels of beer, 2 tons of butter, 1000 pounds of cheese, a bed, a suit of clothes, and a silver cup for? The answer, of course, is a tulip bulb, but not just any tulip bulb, but a bulb infected by a tulip 'breaking' virus which resulted in fantastic mixtures of colors.
Dr Turner then posed the question, can viruses solve health problems? He brought up the topic of antibiotic resistence, citing MRSA and XDRTB as worrisome diseases- the drugs used to treat them pose dangers to the body. Antibiotic resistance is a global problem, and will be implicated in hundreds of millions of deaths worldwide by 2050. Bacteriophages are viruses that only kill bacteria- they could be used as an alternative to chemical antibiotics. Bacteriophages could be used as a self-amplifying drug- they multiply, find and kill new bacteria. In the mid-twentieth century, the Russians and Poles invested more heavily in phage therapy than in antibiotics. Phage therapy was used to treat field wounds and cholera. In the case of cholera, patients were rehydrated and given anti-cholera phages. Bacteria can evolve phage resistance. Dr Turner asked, can we develop a strategy that works even with the evolution of resistance? He indicated that the best strategy would be to discover phages which attack bacteria by binding to virulence factors- by binding to these sites, the phages would force the bacteria to evolve phage resistance by compromising virulence. Resistance would be achieved by becoming more dangerous. OMK01 (PDF link),a recently discovered bacteriophage, found in a Connecticut lake, effects the efflux pumps that bacteria use to remove antibiotics. OMK01 forces bacteria to trade phage resistance for antibiotic resistance. Dr Turner referred us to the 6/3/2016 edition of NPR's Science Friday. In 2006, the USDA approved the use of phages to combat bacteria which can taint deli meats.
Dr Turner then posed the question, would you be here without viruses? He indicated that 10% of our DNA comes from viruses which entered the genetic germ line- these genes are known as endogenous retrovirus genes. Syncytin, a protein produced by endogenous retroviral genes, is crucial to the formation of the placenta- the protein is necessary for the proper reaction of the immune system, which does not treat the fetus as a parasite. All placental mammals are made possible by viral DNA, which is a really good note on which to end a lecture.
The lecture was followed by a Q&A session. Some Bastard in the audience asked if viruses could be used in gene therapy to combat genetic diseases. While viruses are good at swapping out genes, CRISPRs are better tools, simple enought to use on multicellular organisms for correcting genomes. Another member of the audience asked, are viruses alive? Viruses are often conceived as 'quasi-living', but Dr Turner considers them living because they can reproduce and they are subject to natural selection. Asked whether viruses could jump from one 'domain' of life to another, Dr Turner indicated that this is unlikely, because cross-domain protein recognition tends to be rare, though it has often been attempted in the lab. Dr Turner then brought up the topic of bacteriophage prospecting becoming a growth industry- there is an illimitable supply of viruses out there, some of which may have therapeutic value. He then pondered whether or not humans co-evolved with phages to welcome them into the body. Asked about tips in case there's another dangerous flu outbreak, he noted that people should have a home preparedness kit so they can stay home until the epidemic wanes... I guess I need to download more ebooks!
Dr Turner delivered a top-notch lecture, informative and entertaining. I'm biased toward biological subjects, so this lecture was definitely in my top tier. Dr Turner, an extremely nice guy, lingered for an 'adult beverage' afterward, and I had a brief conversation with him about OMK01, which he told me was located in Dodge Pond, a polluted body of water not far from Lyme.
Kudos to Dr Turner, Dorian and Margaret, and the staff of the beautiful Bell House for yet another fantastic lecture. Here's the first of a three-part video series on viral biology by Dr Turner:
Crack open a beverage and soak in that SCIENCE! Be sure to watch the other two videos in the series- more videos, more drinking, more learning.
Oh, and this month's lecture was the annual Lasker Foundation collaboration with the Secret Science Club. Special thanks to the good folks at the foundation for their support. The foundation was giving out these great T-shirts with the slogan: If you think research is expensive, try disease.