David Kennedy and Andrew Read have kindly supplied the following teaser for their latest paper in Proceedings Of The Royal Society B. As they point out, this “armchair speculation” has elicited a gamut of reactions ranging from awe to scorn and so we are sure they would welcome commentary on this paper from the readers of Evmedreview!

Andrew Read

Dave Kennedy and Andrew Read

Center for Infectious Disease Dynamics, Departments of Biology and Entomolology, Penn State

David Kennedy

Evolution is perhaps the world’s greatest problem solver. It has found innumerable solutions to blistering environmental insults. Nowhere is this clearer than for drug resistance. Pathogen evolution has undermined virtually every known chemotherapeutic drug. Yet rubbing a cowpox pustule into a person’s open wound somehow confounded evolution. Most modern vaccines have done so too: they work as well as they did when they were first introduced. Why can evolution rescue pathogens from drugs but not from vaccines?

When we first discussed this question, we were surprised not to agree on an answer. It seemed that any of a laundry list of features might help explain why vaccines are more evolution-proof than drugs. We were also surprised to find barely any discussion of the problem in the literature. A few people had asked why resistance to measles or smallpox vaccines failed to evolve, but the answers were specific to those viruses. What was the general answer?

We disagreed for months before one of us (DK) persuaded the other (AR) that, ironically, the most plausible answer lay in processes well known in agricultural resistance management. This solution—which we just published after a grueling time with reviewers—is essentially armchair speculation. We cannot yet know whether it is correct. Reactions from colleagues have ranged from ‘that is obvious’ to ‘that is wrong’ and have involved adjectives like ‘superficial’ and ‘stimulating’, as well as the opinion that our article reads like an undergraduate essay. We hope that the simplicity of our argument breeds the kind of skepticism that leads to new data and new theories. The problem seems important. Will next-generation vaccines fail? Can drugs be made as evolution-proof as vaccines? Which cancer therapies have the greatest potential to work?


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