The evolution of drug resistance and the curious orthodoxy of aggressive chemotherapy

Andrew F. Read, Troy Day, Silvie Huijben

Research output: Contribution to journalArticle

144 Citations (Scopus)

Abstract

The evolution of drug-resistant pathogens is a major challenge for 21st century medicine. Drug use practices vigorously advocated as resistance management tools by professional bodies, public health agencies, and medical schools represent some of humankind's largest attempts to manage evolution. It is our contention that these practices have poor theoretical and empirical justification for a broad spectrum of diseases. For instance, rapid elimination of pathogens can reduce the probability that de novo resistance mutations occur. This idea often motivates the medical orthodoxy that patients should complete drug courses even when they no longer feel sick. Yet "radical pathogen cure" maximizes the evolutionary advantage of any resistant pathogens that are present. It could promote the very evolution it is intended to retard. The guiding principle should be to impose no more selection than is absolutely necessary. We illustrate these arguments in the context of malaria; they likely apply to a wide range of infections as well as cancer and public health insecticides. Intuition is unreliable even in simple evolutionary contexts; in a social milieu where in-host competition can radically alter the fitness costs and benefits of resistance, expert opinion will be insufficient. An evidence-based approach to resistance management is required.

Original languageEnglish (US)
Pages (from-to)10871-10877
Number of pages7
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue numberSUPPL. 2
DOIs
StatePublished - Jun 28 2011

Fingerprint

Drug Resistance
Drug Therapy
Pharmaceutical Preparations
Public Health Schools
Intuition
Expert Testimony
Insecticides
Medical Schools
Malaria
Cost-Benefit Analysis
Public Health
Medicine
Mutation
Infection
Neoplasms

All Science Journal Classification (ASJC) codes

  • General

Cite this

@article{ae192375c31a43d1ab465e220580fd01,
title = "The evolution of drug resistance and the curious orthodoxy of aggressive chemotherapy",
abstract = "The evolution of drug-resistant pathogens is a major challenge for 21st century medicine. Drug use practices vigorously advocated as resistance management tools by professional bodies, public health agencies, and medical schools represent some of humankind's largest attempts to manage evolution. It is our contention that these practices have poor theoretical and empirical justification for a broad spectrum of diseases. For instance, rapid elimination of pathogens can reduce the probability that de novo resistance mutations occur. This idea often motivates the medical orthodoxy that patients should complete drug courses even when they no longer feel sick. Yet {"}radical pathogen cure{"} maximizes the evolutionary advantage of any resistant pathogens that are present. It could promote the very evolution it is intended to retard. The guiding principle should be to impose no more selection than is absolutely necessary. We illustrate these arguments in the context of malaria; they likely apply to a wide range of infections as well as cancer and public health insecticides. Intuition is unreliable even in simple evolutionary contexts; in a social milieu where in-host competition can radically alter the fitness costs and benefits of resistance, expert opinion will be insufficient. An evidence-based approach to resistance management is required.",
author = "Read, {Andrew F.} and Troy Day and Silvie Huijben",
year = "2011",
month = "6",
day = "28",
doi = "10.1073/pnas.1100299108",
language = "English (US)",
volume = "108",
pages = "10871--10877",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "SUPPL. 2",

}

The evolution of drug resistance and the curious orthodoxy of aggressive chemotherapy. / Read, Andrew F.; Day, Troy; Huijben, Silvie.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. SUPPL. 2, 28.06.2011, p. 10871-10877.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The evolution of drug resistance and the curious orthodoxy of aggressive chemotherapy

AU - Read, Andrew F.

AU - Day, Troy

AU - Huijben, Silvie

PY - 2011/6/28

Y1 - 2011/6/28

N2 - The evolution of drug-resistant pathogens is a major challenge for 21st century medicine. Drug use practices vigorously advocated as resistance management tools by professional bodies, public health agencies, and medical schools represent some of humankind's largest attempts to manage evolution. It is our contention that these practices have poor theoretical and empirical justification for a broad spectrum of diseases. For instance, rapid elimination of pathogens can reduce the probability that de novo resistance mutations occur. This idea often motivates the medical orthodoxy that patients should complete drug courses even when they no longer feel sick. Yet "radical pathogen cure" maximizes the evolutionary advantage of any resistant pathogens that are present. It could promote the very evolution it is intended to retard. The guiding principle should be to impose no more selection than is absolutely necessary. We illustrate these arguments in the context of malaria; they likely apply to a wide range of infections as well as cancer and public health insecticides. Intuition is unreliable even in simple evolutionary contexts; in a social milieu where in-host competition can radically alter the fitness costs and benefits of resistance, expert opinion will be insufficient. An evidence-based approach to resistance management is required.

AB - The evolution of drug-resistant pathogens is a major challenge for 21st century medicine. Drug use practices vigorously advocated as resistance management tools by professional bodies, public health agencies, and medical schools represent some of humankind's largest attempts to manage evolution. It is our contention that these practices have poor theoretical and empirical justification for a broad spectrum of diseases. For instance, rapid elimination of pathogens can reduce the probability that de novo resistance mutations occur. This idea often motivates the medical orthodoxy that patients should complete drug courses even when they no longer feel sick. Yet "radical pathogen cure" maximizes the evolutionary advantage of any resistant pathogens that are present. It could promote the very evolution it is intended to retard. The guiding principle should be to impose no more selection than is absolutely necessary. We illustrate these arguments in the context of malaria; they likely apply to a wide range of infections as well as cancer and public health insecticides. Intuition is unreliable even in simple evolutionary contexts; in a social milieu where in-host competition can radically alter the fitness costs and benefits of resistance, expert opinion will be insufficient. An evidence-based approach to resistance management is required.

UR - http://www.scopus.com/inward/record.url?scp=79960648350&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960648350&partnerID=8YFLogxK

U2 - 10.1073/pnas.1100299108

DO - 10.1073/pnas.1100299108

M3 - Article

C2 - 21690376

AN - SCOPUS:79960648350

VL - 108

SP - 10871

EP - 10877

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - SUPPL. 2

ER -