Details of new botulinum toxin censored to stop ‘misuse’

By Siouxsie Wiles 15/10/2013


Clostridium botulinum,* the bacterium that turned out not to be contaminating a heap of New Zealand made infant formula a few months ago, is at the centre of a new scare. This time it’s the discovery of a strain of the bacterium for which there is no treatment.

C. botulinum produces neurotoxins that prevent acetylcholine from being released from the motor nerve endings causing flaccid paralysis and symptoms of blurred vision, drooping eyelids, nausea, vomiting, diarrhea and/or constipation and cramps. In severe cases it leads to paralysis of the breathing muscles and causes respiratory failure. Until recently, seven different neurotoxins had been identified to date – known by the letters A-G. Toxin types A, B, E, and F cause disease in humans while types C and D cause disease in cows, birds, and other animals but not in humans. Treatment for patients with botulism is the delivery of the corresponding antitoxin to neutralise the particular toxin type causing their disease.

In two papers just published in the Journal of Infectious Diseases (alas, they are behind a paywall), Jason Barash, Stephen Arnon and colleagues from the California Department of Public Health describe a strain of C. botulinum (IBCA10-7060) isolated from an infant with botulism** (1, 2). IBCA10-7060 was found to produce two toxins, toxin-type B and a novel toxin which the authors have called type H. What first led them to suspect they had something new was when the antitoxins used to treat mice injected with either faecal extract or culture filtrate failed to save any of the animals.

The researchers have since sequenced the 2 botulinum toxin gene clusters of strain IBCA10-7060 and found that the sequence of the type H toxin differs substantially from the gene sequences for the 7 known toxin types A–G. But we are going to have to take their word for it, as the authors have taken the unusual step of censoring any genetic information about the novel toxin that could allow it to be misused as a biological weapon.

This from the accompanying editorial by David Hooper and Martin Hirsch:

It is general JID policy that gene nucleotide sequences must be submitted to the International Nucleotide Sequence Databases and that the accession numbers must appear in the final revision and published version of the manuscript. However, in this case, we made an exception. Because no antitoxins as yet have been developed to counteract the novel C. botulinum toxin, the authors had detailed consultations with representatives from numerous appropriate US government agencies (see Notes), as well as the JID editors, and received approval to publish both manuscripts, while withholding the key gene sequences until appropriate countermeasures were developed.

The worry is that someone could easily use the genetic sequence to synthesise the toxin gene DNA which could then be used to make a toxin for which there is currently no known antitoxin. So the gene sequence of the toxin is going to be withheld until an antitoxin has been produced. It’s worth at this point noting that, according to Wikipedia, botulinum toxin A is one of the most toxic substances known to man – 1 kilogram of it would be enough to kill the entire human population.

As an aside, its interesting to see that in this case the manuscripts were reviewed by a committee representing various branches of the US government***. Missing from the committee was anyone from the US National Science Advisory Board for Biosecurity, the very committee charged with providing advise and guidance on the potential of research to be misused to pose a biological threat to public health or national security. Curious.

So if the research is so dangerous, why publish in the first place? This is the first new botulinum toxin type to be identified in more than 40 years, so its discovery serves as a reminder that there are an awful lot of dangerous microbes that we don’t even know exist yet. But it also serves to tell the scientific and medical community that there exist novel and potentially untreatable strains of C. botulinum in the environment. It would be interesting to now find out how prevalent this new toxin type is, but to carry out studies like that will require the genetic information.

I understand why the genetic sequences are being withheld in this particular case, but all the same it makes me uneasy. Who gets to decide which other researchers around the world can have the censored information to help progress the discovery of an antitoxin, or look into the toxin’s prevalence? The country currently being held hostage by it’s own elected representatives?! That’s scary.

References:
1. Barash JR, Arnon SS (2013). A Novel Strain of Clostridium botulinum That Produces Type B and Type H Botulinum Toxins. J Infect Dis.
2. Dover N, Barash JR, Hill KK, Xie G, Arnon SS (2013). Molecular Characterization of a Novel Botulinum Neurotoxin Type H Gene. J Infect Dis.

*As a quick reminder, C. botulinum is a spore-forming bacterium that doesn’t like oxygen. It can cause a rare but sometimes fatal illness called botulism, a result of the microbe’s ability to produce neurotoxins which are produced when C. botulinum spores germinate and the bacterium starts to actively grow, which it can only do in an environment with no oxygen. There are three main forms of illness caused by C. botulinum:
1. Foodborne botulism, caused by consuming food or drink contaminated with botulinum toxins,
2. Infant botulism, where the gastrointestinal tracts of babies becomes colonised by C. botulinum spores before their protective gut microbes establish are established (This is why parents are advised not to give honey to children under the age of 1),
3. Wound botulism, when wounds become infected with C. botulinum spores present in the environment.

**It’s not disclosed if the infant lived or died.

***1. Drug Development Section, Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH);
2. Enteric and Hepatic Diseases Branch, NIAID, NIH;
3. Bacteriology and Mycology Branch, NIAID, NIH;
4. Office of Biotechnology Activities, Office of Science Policy, NIH;
5. National Counterproliferation Center, Office of the Director of National Intelligence;
6. Office of the Assistant Secretary for Preparedness and Response, Department of Health and Human Services (DHHS);
7. Biomedical Advanced Research and Development Authority, Office of the Assistant Secretary for Preparedness and Response, DHHS;
8. Threat Characterization and Attribution Branch, Chemical and Biological Defense Division, Science and Technology Directorate, Department of Homeland Security;
9. US Army Medical Research Institute of Infectious Diseases;
10. Division of Select Agents and Toxins, Office of Public Health Preparedness and Response, Centers for Disease
Control and Prevention, DHHS;
11. Biological Countermeasures Unit, Federal Bureau of Investigation Weapons of Mass Destruction Directorate,
Department of Justice.