Last week, the second of two controversial papers were published announcing mutations that make the H5N1 Influenza A virus more highly transmissible between ferrets (Herfst et al. and Imai et al.) Both articles alter the H5N1 virus by site-directed mutagenesis, a common technique to change the genetic code of the virus, and the result is an altered protein structure. One group used random mutagenesis by PCR (polymerase chain reaction, to synthesize new genetic material), while another used targeted mutagenesis to disrupt known important protein residues. The modified viruses were then used in animal trials to determine if the mutations made a significant change in infectivity, particularly airborne infectivity between ferrets. Ferrets have long been used to study influenza pathogenesis.
The publication of these findings has caused significant controversy for the possible misuse of H5N1. While these studies were performed in ferrets, it is very possible that some or all of the mutations that increase transmission in ferrets may perform similarly in humans. We cannot be sure of this however, without a clinical trial, which will never be undertaken for obvious reasons. The take home message of these papers is that scientists sometimes make modified organisms, and alter their biology in order to study the fundamental properties of biological systems. Though the results of these papers suggest a way to make a more transmissible virus, the reality is that neither of these papers uses novel biological techniques; molecular biological methods developed over the last 20 years have enabled many labs to do similar work. While there is the potential of malicious use here, most scientific papers describe some aspect of biology, and dissect how DNA, RNA, proteins, cells, and whole organisms work, and how small changes can disrupt their biology. Any knowledge has the potential for abuse.
