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Friday, July 18, 2014

The summer of scientific missteps

What is going on with scientists this summer? Misplaced smallpox strains, contamination at the CDC? It took me over a week to decide what I really thought about all this before I could write about it. Is the media blowing things out of proportion, only increasing the public’s mistrust in science? How did this happen and is it part of a bigger problem?

First came news from the director of the Centers for Disease Control and Prevention (CDC) in Atlanta, GA, that two laboratories, working with highly pathogenic organisms would be shut down and all shipment of materials from BSL-3 and -4 level labs (high biosafety levels) stopped pending review. In one case, a low-pathogenic influenza virus, H9N2, was contaminated with the highly pathogenic H5N1 (of “bird flu” fame) and sent to the Department of Agriculture who discovered the mistake. In a separate incident the bacteria responsible for anthrax disease had been improperly inactivated before transferring it to a lower biosafety level lab. Apparently, approved sterilization techniques were not followed, nor was their a standard protocol in the lab for inactivating and transferring the anthrax bacteria to other labs.

Then in early July, 6 vials of the variola virus (responsible for smallpox) were found in a storage freezer (a freezer probably very much resembling a deep freezer) at the National Institute of Health (NIH) in Bethesda, MD. The samples were prepared and stored in 1954. Previously the only remaining stocks of virus (which was eradicated in 1981) were thought to be held at the CDC and at the State Research Center of Virology and Biotechnology in Siberia.

So how could this happen?
Upon hearing the news, I shook my head, but was not surprised. Scientists are quite fallible, especially when it comes to lab organization and thinking they are immune to lab safety practices. The fast pace required to publish and not perish can often lead to sloppiness: sloppiness in record keeping and in properly training and overseeing safety measures. I have experienced both of these first hand. It is not hard to imagine at all how 6 vials, even vials of deadly and potential agents to be used for bioterrorism, went unnoticed amidst the ~40,000 vials that fit inside a standard laboratory -80˚C freezer. Also, there is a lot of turnover in science: graduate students change every 4.5 years while postdoctoral fellows come and go as often as every year (though three is more likely). This combined with the high variability in record keeping practices often leads to loss of years of work, and in this case, a potentially deadly mistake. Because of time constraints for advisors, there is usually little oversight into the record keeping practices of the researchers actually making the samples. It is usually not until that researcher leaves that there is a mad scramble to make sure everything is in “order.” The best-case scenario is that samples will have been entered into a database. But in too many cases, there is no database and samples are poorly labeled (and anecdotally, written in another language), labels are worn off, and of course, encrusted in ice. Unless someone is immediately taking over that researcher’s work, these “orphaned” boxes of material are often shoved to the back of the freezer, apparently in some cases, waiting to cause a scandal half a century later.

Though there have been multiple calls from the World Health Organization for scientists to go through their inventories and find remaining vials of smallpox throughout the decades since it was eradicated, there was little impetus and no oversight for scientists to actually go through the arduous (and finger-numbing) procedure. Really, the virus poses little public health threat left alone at the bottom of a deep freezer. Also, on a positive note, the researcher who identified the virus notified his superior and the viral stocks were transfer to the CDC for analysis and destruction. One can imagine a worse case scenario where an unknowing researcher somehow disposed the vials in a receptacle that was not subsequently autoclaved (exposing the virus to pressurized steam that kills viruses and bacteria). However low, there was a chance for these viral stocks to make it into the environment alive.

Many scientists I talked to were frustrated by these glaring oversights because they worried it would put smallpox virus (and other “extinct” disease) research at risk. There has been an ongoing debate by countries around the world about not so much as whether to destroy the virus, but when. Why keep the virus around? Is there really a chance for smallpox to return or be used by terrorists? Well, in 2002, scientists were able to synthesize poliovirus de novo using mail-order DNA segments that were assembled using the genome sequence of the virus as a blueprint and molecular biology techniques known to any graduate student (Cello et al, 2002). There was immediate uproar from both the science community and general public and the potential creation of the smallpox virus specifically cited as a major concern. And so scientists argue, we need to keep a few smallpox stocks around just in case.

It seems like a silly response to the NIH incident to destroy the remaining known smallpox stocks when the real danger, it seems, is from the stocks we don’t know about, not from those in Russia or at the CDC…oh wait. I can understand why the general public mistrusts scientists. In 2003, the NIH accidentally sent anthrax to a Children’s Hospital in California for Pete’s sake! And the most recent investigations into the CDC discovered anthrax specimens in unlocked refrigerators in a hallway where many workers pass through. And again, record keeping was found to be inadequate. If we want to argue to keep around deadly pathogens, “just in case”, we need to get it together people.

Of course, this is easy for me to say from my budding yeast field. The worst my biological agent will do is give you a hang over (not true at all, but I couldn’t resist). And of course, I always follow proper safety precautions, never eating or drinking in lab and always wear long pants and closed shoes. But although I started off thinking the media was potentially blowing things out of proportion, I found myself in the end, angry at scientists but not really having any answers. Clearly more oversight into protocols is necessary and I believe Dr. Thomas Friedman, the director at the CDC, will do it. But as long as time is of such limited supply and demands are so high on supervisors, sloppiness will continue to contribute to incidents like these. But that's just my two cents, what do you all think?

References:
Cello J, Paul AV, Wimmer E (2002) Chemical synthesis of poliovirus cDNA: generation of infectious virus in the absence of natural template. Science 297: 1016–1018.

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