My blog posts around Thanksgiving are predictably dull: Turkey Genetics 101, The Peaceable Genomes of Pumpkins. But 2020 is like no other…
It’s hard to imagine anything worse than the horrors at our hospitals right now. But in a recent JAMA webinar, Nicholas Christakis, Yale Sterling Professor, put the fatality rate of COVID-19 into historical perspective:
“Bad as it is, the fatality rate, at .5-.8%, isn’t as bad as bubonic plague, which would kill 50% of a population in a few months. Or Ebola at 80%. Or smallpox at 95%. It could have been so much worse.” He’s a physician, scientist, public health expert, and sociologist.
It’s an unusual viewpoint to downplay the horror of this moment in time, but Dr. Christakis’s new book, “Apollo’s Arrow: The Profound and Enduring Impact of Coronavirus on the Way We Live,” takes a broader look. He said at the webinar:
“This way we’re living right now seems alien and unnatural, but plagues aren’t new to our species, just new to us. People have struggled with plagues for thousands of years. The Iliad opens with a plague on the Greeks and Apollo reigns down, the Bible, Shakespeare. What’s different about our current experience is our time in the crucible happens to be occurring when we can create a vaccine in real time. The fact that we have the technological capability to respond within a year with phase 3 trials of active agents is mind-boggling.”
We aren’t the only species subject to unseen pathogens, including the viruses that aren’t even cells or technically alive, just borrowed bits of our own genomes turned against us. With Dr. Christakis’s wider view in mind, I noticed a new article about an infectious cancer in Tasmanian devils. It combines two terrors.
A Transmissible Cancer
A Tasmanian devil, the size of a small dog, is a carnivorous marsupial. The endangered animals live only in the state of Tasmania, an island off the southern coast of eastern Australia. Introduction of dingoes to the mainland four centuries ago is thought to have driven the devils to their disappearing island home.
The full scientific name of the Tasmanian devil is Sarcophilus harrisii, perhaps best knows as Looney Tunes character Taz.
The cancer “devil facial tumor 1” (DFT1) first appeared in 1996 and has been rocketing through the population ever since.
DFT1 hideously disfigures the animal, with large tumors around the head and in the mouth. Normal biting behavior transmits it. In a new host the tumor explodes, cells rapidly dividing, easily overriding the animal’s immune response.
Worse, live cancer cells go from animal to animal, as if the cells are themselves infectious organisms, pathogens. But this isn’t the same as passing a sexually transmitted infection from person to person, such as HPV, which is a virus that predisposes to cervical cancer.
DFT1 is deadly, decimating the Tasmanian devil population and driving its extinction. Breeders are trying to establish a colony in New South Wales to save it.
Only three naturally-occurring transmissible cancers are known. Joining DFT1 are canine transmissible venereal tumor and a widespread cancer of soft-shell clams, according to the Transmissible Cancer Group in the Department of Veterinary Medicine at the University of Cambridge. Their study just published in PLOS Biology, with colleagues from Australia and France, reveals the odd genomes of the cancer cells that cause DFT1.
Exploring Strangely Stable Genomic Changes
“In cancer, the genome is shot to hell,” a prominent researcher once told me.
Cancer cells, even within an individual, often display an array of the ways that DNA and chromosomes can go off-kilter as they lose control of their division cycle. Healthy human cells growing in culture famously divide 40 to 60 times, the so-called Hayflick limit. Cancer cells, given enough space and nutrients, hormones, growth factors, and transcription factors, divide forever.
A cancer cell that’s been in a body longer has more mutations than a more recently generated one. Mutations accrue, their patterns holding the history, the narrative, of that particular cancer in that particular body.
The utter constancy of the genome changes in facial tumor cells in the devils, echoed in laboratory culture, is puzzling. The cancer genomes are much more alike, from devil to devil, than are the cancer cells in a single human.
What’s going on?
The genomic similarity of the tumors in different animals suggests that the disease began in a single “founder” Tasmanian devil, transmitted by the biting behavior. More typically, a cancer just vanishes when the host dies. The constancy, the sameness, in evolutionary terms means that whatever the persistent genome is, it offers an advantage that somehow stabilizes the cancer cells so they survive and thrive, through body after body after body – but whatever that advantage is, isn’t clear.
Calling the infectious cancer “a natural experiment for observing the evolution of cancer cell adaptation,” the researchers analyzed the genomes of cells from 648 DFT1 tumors, collected from 2003 through 2018.
Over that time the tumors mutated into five groups, or clades, dropping to three. Mapping the clades with geography showed how the cancer has spread, in the diseased devils, throughout their shrinking habitat. The findings remind me of a recent paper in Science, “Transmission heterogeneities, kinetics, and controllability of SARS-CoV-2,” that traces the early spread of COVID-19 in China.
The facial cancer cell genomes plucked from Tasmanian devils have several oddities.
• They accumulate copy number variants – short DNA sequences repeated a varying number of times.
• The telomeres – chromosome tips – that are typically elongated in cancer cells, which keeps them dividing indefinitely, are short.
• One particular small chromosome tends to be lost when the cells divide.
• Genes or entire chromosomes duplicate or disappear.
• Genomes double, producing four copies of each of the 14 chromosome types.
Cells from devils sampled decades and kilometers apart are remarkably similar. When cultured in the laboratory, the cancer cells proceed through the same choreography of genomic mayhem as they do on Tasmanian devil faces. Whatever is happening in the animals is recapitulated in glassware.
“DFT1 has acquired relatively few mutations during its thirty-year history. This research illustrates how a comparatively simple and stable cancer can colonize diverse niches and devastate a species,” said study leader Elizabeth Murchison.
Is there a link to, or message about, COVID-19 in the plight of the Tasmanian devils? Probably not; sometimes I’m just drawn to biological mysteries, and this one reverberated against the constant hum in my brain that comes from reading the technical papers on the pandemic nearly every waking moment. But I can’t help making comparisons. Here’s one.
We humans are capable of reasoning, of foreseeing consequences. We can choose to alter our risk of contracting COVID-19 with behavior – mask-wearing, social distancing, testing, avoiding situations that take us near others.
As far as I know, carnivorous marsupials rely more on instinct than reasoning. And so Tasmanian devils will keep on biting, and keep on dying, as the strong and persistent cancer cells flit from animal to animal, easily taking root and flourishing, until their hosts simply vanish. Perhaps we will learn something about ourselves from their unusual cancer.