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To err is human

The recent furor over the mishaps at the CDC and FDA storage facilities have caught the attention of the scientific community and the indignation of Congress.

The incident at the CDC that precipitated the outcry was the shipping in mid-June of live anthrax cultures (which were supposed to be killed) to a laboratory not equipped to safely handle Bacillus anthracis. This, of course, was a potentially deadly error.

The FDA mishap involved the discovery of viable smallpox virus, dated 1954, stored in an unused portion of a storage room in an FDA laboratory located on the NIH Bethesda campus; dengue virus, Rickettsia (spotted fever group) and Coxiella burnetii (the cause of Q fever) were also found in storage in the same location.

Not the first time

This was followed by disclosure of four other events at the CDC during the past decade. The first occurred in March 2014, when a low-pathogenic avian influenza virus sample sent to a Department of Agriculture Research laboratory was found to be contaminated with highly pathogenic avian influenza A(H5N1). The second event occurred in 2006 when a CDC laboratory sent samples of anthrax DNA to outside laboratories with the contents supposedly inactivated. In fact, live B. anthracis were present. The third event also occurred in 2006, when samples sent from a CDC laboratory were found to contain live Clostridium botulinus. The fourth event occurred from 2001 to 2009 and involved live, virulent Brucella being shipped to outside laboratories under the mistaken impression it was a vaccine strain.

Donald Kaye

Clearly, these are all serious lapses that had the potential to cause severe illness in laboratory workers and in some cases to cause widespread disease. However, let us first distinguish the difference between the storage error involving smallpox virus and the laboratory errors. In the 1950s, people in industrialized countries were immunized against smallpox, as the disease was active in many parts of the world. In fact, I saw cases in South America in the 1960s and Africa in the 1970s. WHO estimated that 15 million people worldwide developed smallpox in 1967. It would have been easy for interested scientists to obtain samples of virus, and in fact, samples of the virus were undoubtedly widespread in laboratories at the time. Furthermore, at that time, laboratory operations functioned differently, and inventories were not as rigorously kept up as they are today.

Smallpox was declared eradicated in 1979, and all virus was supposed to be destroyed except for samples in high-security facilities at the CDC and in Russia (now at the Research Institute for Viral Preparations in Moscow). With the breakup of the Soviet Union, there have been questions raised about the fate of some samples. Furthermore, the finding of smallpox virus at the storage area in the NIH begs the question of whether there are samples buried in other forgotten storage areas in other scientific facilities in the United States and around the world.

Serious consequences

The episodes at the CDC are of recent vintage and of a different nature than human error. The consequences are already serious. A moratorium was placed on any biological material leaving any CDC Biosafety Level (BSL) 3 or BSL-4 laboratory. The Bioterrorism Rapid Response and Advanced Technology (BRRAT) Laboratory was closed until further notice.

While there are alternative sources for the reagents provided, this laboratory is the prime source. According to an authority writing in ProMED-mail, this closure created a vacuum in the CDC Biological Laboratory Response Network (LRN-B). The BRRAT Laboratory was responsible for producing direct fluorescent antibody and real-time PCR reagents for the entire LRN-B, including B. anthracis. Diagnostic laboratories have switched over to PCR diagnosis of B. anthracis, which is quick and very reliable. And now these events have the potential to push them back into glassware technology, sheep blood agar, and differentiating B. anthracis from B. cereus based on the former being non-hemolytic and usually penicillin sensitive (3% to 6% are naturally resistant).

Accidents a rare occurrence

The CDC is the cornerstone of US public health and its laboratories function at extremely high levels. It is unfortunate that these laboratory lapses occurred, and efforts should be made to have the best quality control possible. However, any of us who have worked in laboratories know that lapses will occur, because even in the best of worlds, humans make mistakes. Just think about infection control in hospitals and lapses in hand-washing by high level professionals. The aim of the congressional investigation seems to be to exact punishment for errors, which is somewhat ironic. The issue is that all that punishment does is create an atmosphere of fear in which cover-ups occur, with more regulation and paperwork. This is the exact opposite of what is desired, ie, prompt reporting of mistakes so that appropriate damage control can occur with better everyday supervision.

Despite the revelations of these laboratory lapses, standards today are higher than ever before, and laboratory accidents, which were common 20 to 30 years ago, are rare today.

For more information:

Donald Kaye, MD, is a professor of medicine at Drexel University College of Medicine, associate editor of the International Society for Infectious Diseases' ProMED-mail, section editor of news for Clinical Infectious Diseases and is an Infectious Disease News Editorial Board member. Disclosure: Kaye reports no relevant financial disclosures.

The recent furor over the mishaps at the CDC and FDA storage facilities have caught the attention of the scientific community and the indignation of Congress.

The incident at the CDC that precipitated the outcry was the shipping in mid-June of live anthrax cultures (which were supposed to be killed) to a laboratory not equipped to safely handle Bacillus anthracis. This, of course, was a potentially deadly error.

The FDA mishap involved the discovery of viable smallpox virus, dated 1954, stored in an unused portion of a storage room in an FDA laboratory located on the NIH Bethesda campus; dengue virus, Rickettsia (spotted fever group) and Coxiella burnetii (the cause of Q fever) were also found in storage in the same location.

Not the first time

This was followed by disclosure of four other events at the CDC during the past decade. The first occurred in March 2014, when a low-pathogenic avian influenza virus sample sent to a Department of Agriculture Research laboratory was found to be contaminated with highly pathogenic avian influenza A(H5N1). The second event occurred in 2006 when a CDC laboratory sent samples of anthrax DNA to outside laboratories with the contents supposedly inactivated. In fact, live B. anthracis were present. The third event also occurred in 2006, when samples sent from a CDC laboratory were found to contain live Clostridium botulinus. The fourth event occurred from 2001 to 2009 and involved live, virulent Brucella being shipped to outside laboratories under the mistaken impression it was a vaccine strain.

Donald Kaye

Clearly, these are all serious lapses that had the potential to cause severe illness in laboratory workers and in some cases to cause widespread disease. However, let us first distinguish the difference between the storage error involving smallpox virus and the laboratory errors. In the 1950s, people in industrialized countries were immunized against smallpox, as the disease was active in many parts of the world. In fact, I saw cases in South America in the 1960s and Africa in the 1970s. WHO estimated that 15 million people worldwide developed smallpox in 1967. It would have been easy for interested scientists to obtain samples of virus, and in fact, samples of the virus were undoubtedly widespread in laboratories at the time. Furthermore, at that time, laboratory operations functioned differently, and inventories were not as rigorously kept up as they are today.

Smallpox was declared eradicated in 1979, and all virus was supposed to be destroyed except for samples in high-security facilities at the CDC and in Russia (now at the Research Institute for Viral Preparations in Moscow). With the breakup of the Soviet Union, there have been questions raised about the fate of some samples. Furthermore, the finding of smallpox virus at the storage area in the NIH begs the question of whether there are samples buried in other forgotten storage areas in other scientific facilities in the United States and around the world.

Serious consequences

The episodes at the CDC are of recent vintage and of a different nature than human error. The consequences are already serious. A moratorium was placed on any biological material leaving any CDC Biosafety Level (BSL) 3 or BSL-4 laboratory. The Bioterrorism Rapid Response and Advanced Technology (BRRAT) Laboratory was closed until further notice.

While there are alternative sources for the reagents provided, this laboratory is the prime source. According to an authority writing in ProMED-mail, this closure created a vacuum in the CDC Biological Laboratory Response Network (LRN-B). The BRRAT Laboratory was responsible for producing direct fluorescent antibody and real-time PCR reagents for the entire LRN-B, including B. anthracis. Diagnostic laboratories have switched over to PCR diagnosis of B. anthracis, which is quick and very reliable. And now these events have the potential to push them back into glassware technology, sheep blood agar, and differentiating B. anthracis from B. cereus based on the former being non-hemolytic and usually penicillin sensitive (3% to 6% are naturally resistant).

Accidents a rare occurrence

The CDC is the cornerstone of US public health and its laboratories function at extremely high levels. It is unfortunate that these laboratory lapses occurred, and efforts should be made to have the best quality control possible. However, any of us who have worked in laboratories know that lapses will occur, because even in the best of worlds, humans make mistakes. Just think about infection control in hospitals and lapses in hand-washing by high level professionals. The aim of the congressional investigation seems to be to exact punishment for errors, which is somewhat ironic. The issue is that all that punishment does is create an atmosphere of fear in which cover-ups occur, with more regulation and paperwork. This is the exact opposite of what is desired, ie, prompt reporting of mistakes so that appropriate damage control can occur with better everyday supervision.

Despite the revelations of these laboratory lapses, standards today are higher than ever before, and laboratory accidents, which were common 20 to 30 years ago, are rare today.

For more information:

Donald Kaye, MD, is a professor of medicine at Drexel University College of Medicine, associate editor of the International Society for Infectious Diseases' ProMED-mail, section editor of news for Clinical Infectious Diseases and is an Infectious Disease News Editorial Board member. Disclosure: Kaye reports no relevant financial disclosures.