The Opposing Thumb

An opinionated digit leafs through the biological literature
Media Roundup

Magic Words

The chimps in the genus Homo display many worrisome tendencies, among them a tendency to groupthink. Groupthink will often creep into the most unexpected places, and do quite a bit of damage. A sure sign of cultish behaviour is the spread of mantras that are repeated over and over again by acolytes. “Magic words” are used by practitioners as if they had intrinsic power, like a spell out of a Harry Potter book, and they pop up uninvited in discussions. “Magic words” substitute critical thinking and a richer vocabulary (and the ability to express subtle but important differences that comes with it). In the European science policy community, these words are “excellence” and “translational”. We’ll deal with “excellence”, and its infantile underlying notion that it is easy to quantitatively evaluate scientific output in a way that identifies work (and people) of real value, later.

For now let’s have a brief look at “translational”. First, note that it substituted a perfectly good term, “applied”.  “Applied” left much less room for bullshit- it signified that your research was directed to a practical problem. “Applied” to me clearly labelled engineering or medical research programs. “Translational” gives a skilled con artist a lot more to work with. It does not necessarily imply that you are working on a practical problem now, but you have a dictionary or interpreter that will turn your research program into something that can be sold or rented (the public good has been banished from applied science funding by another magic word, “entrepreneurship”). The spread of this notion of “translating” to the clinic has coincided with massive failure and a reproducibility crisis in scientific research (indicating that perhaps these words do have power after all).

Why am I ranting about this now? Because a trio of examples I read over the last week brought home another very important point, obvious to anyone with even a passing familiarity with the history of science: it is very difficult to predict which basic science will lead to important new applications. These examples motivated this post because they illustrate three different aspects of this essential unpredictability.

1) The first case, in this week’s Nature, is the most obvious. Someone is working in a general field that regularly spawns applied breakthroughs, but is toiling away in their own little esoteric little corner of it when lightning strikes. In Biology, the archetypical application-spawning field is Biochemistry.

Beta-lactams are the oldest and most widely used class of antibiotics. The first antibiotic, penicillin, which was discovered by Alexander Fleming in 1928, is a beta-lactam. But the oldest antibiotic proved no match for the infectious disease that has been plaguing mankind for at least 3,000 years3. By the mid-1940s it became clear that penicillin could not treat tuberculosis, and in the 1960s, scientists began to understand why. M. tuberculosis naturally produces an enzyme that chops off the beta-lactam ring that gives the class its name, rendering the drugs useless. However, this enzyme, called beta-lactamase, can be irreversibly blocked by a drug inhibitor such as clavulanate. For decades, researchers have asked whether using an inhibitor to stall the beta-lactamase enzyme could free up beta-lactams to do their job of disrupting bacterial cell wall production, and recent data point to a firm ‘yes’.

The authors of the 2009 paper that ultimately saved Payen’s patient did not originally set out to find a new tuberculosis drug. “My lab is a basic science lab,” says John Blanchard, a biochemist at Albert Einstein College of Medicine of Yeshiva University in New York, who authored the study with his student Jean-Emmanuel Hugonnet. Once they saw how effectively meropenem and clavulanate killed XDR-TB in culture, Blanchard knew the data would have major clinical implications. “I’m not a physician, but I was convinced of the biochemistry,” Blanchard says.

2) The second case is more complex. Biology studies many divergent organisms, and a frequent question is “what’s the use of studying ferns, fruit bats, or phoronids?” You know all those CSI episodes where somebody analyses DNA from a crime scene? The technique that made that possible relies on an enzyme made by a bacterium discovered in geyser in Yellowstone National Park. Without it, all those skin cells are just fish food for the crime lab aquarium. Life has evolved many wonderful solutions to the problem of survival and reproduction in strange and extreme environments. Right now there is apparently something alive and growing on the outside of the international space station. Plankton specialists are now suddenly in the aerospace application business.

Understanding bat ecology may hold the key to the Ebola spread pattern in the current epidemic, and bat genomes are helping to explain not only why they are such great virus vectors- they are also suggesting interesting reasons bats can harbor so many lethal pathogens without any detectable (so far) disease.

We are lucky that specialists have been toiling away in these far-off branches of the tree of life. Taxonomists and field biologists are favorite targets of the “translational” hysteria, and many families, or even phyla (the thickest branches in the tree) are losing their last specialists as funding is steadily drained to whoever can write CANCER in the largest font on their grant application. The vector for the next epidemic could be an animal that no one alive has any scientific experience with.

3) The last case, which I ran across reading Stanley Prusiner’s autobiography, “Madness and Memory” is the discipline that gets no respect. This is different from example #2: there, the validity of the approach and the data are not in question- just the object of study they are applied to. In this case I’m referring at disciplines like sociology or, in this specific case, anthropology.

Prusiner deservedly received a Nobel prize for his discovery of prions, infectious proteins, infamous for causing lethal neurodegenerative diseases. The disease that caught Prusiner’s attention as neurology resident was known as Creutzfeldt-Jakob (CJD). Rare, progressive, relentless, CJD was a poor candidate for an infectiously transmitted illness. The missing piece of the puzzle was an epidemic malady very similar to CJD. It was called Kuru (meaning “to shake”), and it afflicted the Fore people of Papua New Guinea. A detailed study of social and gender structure in the Fore people as it pertained to cannibalism was the first solid epidemiological link.

A new epidemic caused by prions hit the West in the 90s, bovine spongiform encephalopathy (BSE), sometimes known as variant Creutzfeldt-Jakob Disease (vCJD) in humans, but more commonly referred to as Mad Cow Disease.  BSE and vCJD were quickly identified and efficiently contained, in no small part because at some point an anthropologist went to study cannibalism in the South Pacific.

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