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Musings of a Cancer Doctor
Wide-ranging views and perspective from George W. Sledge, Jr., MD
Wednesday, January 25, 2012
On Orthobunyaviruses

I spent the summer between my junior and senior years in medical school in an externship in Memphis. I have two regrets about the summer: I did not go to Graceland (Elvis was still alive, and not taking visitors) and I did not spend enough time listening to blues music on (the then fairly decrepit) Beale Street. But I did see my first case of Kaposi’s sarcoma.

 

I was rotating with an oncologist at the time.  One day he called our ward team together and told us that he had a patient -- or rather, a patient’s legs -- he wanted us to see.  The patient was a delightful 90-year-old Jewish tailor, a survivor of the Holocaust, and his feet and lower legs were covered with indurated purplish plaques. Did any of us know what this patient had?

 

We all professed ignorance. “I’m not surprised”, he said. “It’s Kaposi’s sarcoma. You’ll probably never see another case of it in your life.” He explained how this was predominantly a disease of elderly patients, mostly of Mediterranean descent, with compromised immune systems. It was, as cancers went, a somewhat indolent disease, and rare as hen’s teeth. This was only the second one he had ever seen.

 

Four years later, now an oncology fellow, I saw two cases of Kaposi’s in a week. The AIDS epidemic had arrived, and suddenly the formerly rare and indolent had become common and vicious. And now, three decades later, HAART has made Kaposi’s rare once again. Diseases can spring up out of nowhere, identified, knocked down and then replaced in record time: whack-a-mole medicine.

 

I was thinking of this last week when I read a story about a new viral illness that has emerged in northern Europe. Called “Schmallenberg virus,” after the German town where it was first noticed, the infection causes malformations and stillbirths in cattle, sheep, and goats. So far the virus has been detected in Germany, Belgium, and the Netherlands. (For an interesting story on Schmallenberg virus, see

wired.com/wiredscience/2012/01/new-animal-virus.)

 

The virus is transmitted by midges and belongs to an obscure grouping called the orthobunyaviruses. So far there is no evidence that the virus can spread to humans, and let’s hope it never does: as many as half of the fetuses carrying the virus will develop congenital malformations such as scoliosis or hydranencephaly (the brains being replaced with fluid sacs). Jumping species to the human population would be a nightmare. Midges don’t care for humans to the extent, say, of mosquitoes, so for the moment we appear safe.

 

There was a time, in the 1960s and ‘70s, when we thought that we lived in an era of essentially stable disease patterns.  The time when a new infection, a Yersinia pestis, could wash over a continent in a year or two, killing half the population, was a relic of the Middle Ages, of a pre-scientific, pre-antibiotic era best characterized by ignorance of scientific principles and the unavailability of basic public health measures.

 

We now lived, we were told, in the era of chronic disease, and in particular of diseases of aging. Diphtheria had been replaced by adult onset diabetes, polio by heart attacks and stroke. These chronic diseases were inexorable and often lethal, but being age-related they were essentially predictable.  The causes of these might be unknown, but they would eventually become knowable, and controllable.

 

Paralleling this transition from acute infectious diseases to the slow diseases of aging was the idea that biological evolution had been replaced by cultural evolution. We now lived essentially outside of the historical constraints imposed by nature, in a world where Malthus and Darwin no longer mattered. A popular book anthropologic treatise of the time was called Man Makes Himself.

 

One immediate benefit of this cultural evolution was that we could now control reproduction and eliminate sexually transmitted disease with penicillin. These twin and virtually simultaneous discoveries drove sweeping social changes.  The Seventies were, as a result, a fun decade. Unless you were a nerdy pre-med and medical student.

 

Pretty much everything I’ve lived through since that time has demonstrated the fallacy of those views. The past few decades have been rife with sweeping demographic and epidemiologic changes, punctuated by sometimes shocking black swan events. Add to this the unfolding picture painted by modern genomics and it is clear that we never escaped our biologic past.

 

Those first few cases of Kaposi’s, along with the Pneumocystis carinii infections that accompanied them, changed everything. A disease once confined to Sub-Saharan primates emerged from Africa, carried around the world on Boeing’s wings (Patient Zero in the AIDS epidemic being a lethally promiscuous flight attendant), demonstrating the ability of modern technology to spread rather than halt disease. And with it came the growing realization that the age of epidemic disease was not over. We had fooled ourselves based on a brief respite.

 

It also became apparent that other sweeping changes, consequences of modern social and economic forces, were washing over healthcare, one after another. Our ability to control reproduction came at a price, as the side effects of steroid hormones piled up like medical journals on my desk, patiently waiting to be opened. An epidemic of diabetes, which has not yet peaked, was brought on by inertia and cheap calories, pushed by the constant television brainwashing of young children.

 

The era of chronic disease has not been an era of stability. Far from it. The tide can come rushing back up the shore.

 

‘Anthropocene’

Serious scientists now predict the rise of tropical diseases in once temperate zones, as global warming continues unabated, ignored by politicians who glory in their scientific illiteracy. A new term, the anthropocene, was coined to describe a period in geologic history where earth has reached a potentially dangerous tipping point, possibly a death spiral.

 

We never escaped evolutionary forces, as we now have been painfully reminded by the natural world. Bacterial and viral infections that believe in Charles Darwin kill patients who don’t, as resistance mechanisms outwit last year’s wonder drugs. Regions cleared of malaria by DDT relapsed as resistance mechanisms kicked in.

 

But this was evolution in lesser species. Surely cultural evolution had placed our own genes outside evolution? But this was not the case. Our evolutionary history, written in our genes, tells us that we are still little boats tossed about in the sea of biologic history. 

 

When, last decade, researchers took a close look at the human genome, they were astonished to discover that 7% of it was made of retroviruses. Any passing infection, apparently, can insert itself into our germline. The vast majority of these are nonfunctional, but who knows? And multiple genetic mutations affecting modern humans have occurred within recent millennia. The BRCA mutations, for instance, are all relatively new.

 

And culture itself, we now know, drives human evolution. The anthropologist John Hawks of the University of Wisconsin, examining human SNPs, calculated that the rate of mutational change in the human genome is accelerating. Not stable, not declining, but increasing as the human population increases and is exposed to diverse and numerous new environmental pressures.

 

It is easy to find all this rather frightening. We don’t care much for chaos.  The very thought of an orthobunyavirus cross-dressing its way into humans, creating pediatric neurology wards full of hydranencephalics, is scary to contemplate.

 

Still…

But I’m also impressed by the ability of modern science to respond, and respond quickly, to these new challenges. Metastatic melanoma having six well-described resistance mechanisms before vemurafenib came on the market means we can start working on emerging problems before they become widespread. Characterizing the Schmallenberg virus genome early on diminishes the likelihood it will be the next medical catastrophe.

 

A patient of mine getting adjuvant chemotherapy for breast cancer recently told me that the most important lesson she had learned from the experience was “knowing when to duck.” It’s a pretty good lesson: lots of stuff heads our way, much of it unpredictable, so knowing when to duck may be the best we can hope for.

 

The race will never come to an end: we are still Nature’s creatures. But we’ll keep running. And if we don’t exactly know where we are going, we’ve finally got decent running shoes.

 

About the Author

George W. Sledge, Jr., MD
GEORGE W. SLEDGE, JR., MD, is Chief of Oncology at Stanford University. His OT writing was recognized with an APEX Award for Publication Excellence in the category of “Regular Departments & Columns.”