Validity of Botulinum Neurotoxin Serotype H

TO THE EDITOR—I write in reference to the publication of the articles and commentaries regarding the purported new botulinum neurotoxin serotype H [1–4]. For the past 30 years, the genetics and physiology of Clostridium botulinum, particularly the properties of serotypes and subtypes of botulinum neurotoxins, have been studied in my tier 1 select agent laboratory. I also have a dual use research of concern issues (DURC) program in place, including a risk-mitigation plan, whereby my laboratory's work and publications, including those on recom-binant botulinum neurotoxins, must be rigorously approved by the University of Wisconsin–Madison Office of Biological Safety, the Centers for Disease Control and Prevention, and the National Institute of Allergy and Infectious Diseases. Although developing a program to satisfy DURC requirements has required much effort, time, and extensive communications , we feel it represents the opinion of the majority of researchers in the field of C. botulinum and its neurotoxins that the presentation and sharing of new information and results of important findings is integral to advances in this important field. I was dismayed by the publication in the Journal of a purported new serotype of botulinum neurotoxin (" serotype H "), wherein critical data were intentionally omitted because of presumed " DURC issues. " In addition, there are significant scientific concerns in the studies, in that certain strategies and experiments did not yield decisive and definitive findings for defining a new serotype of botulinum neurotoxin. Specifically, in dual toxin– producing strains, it is extremely difficult to distinguish the lethal effects in mice between the high-titer toxin (BoNT/B) and the low-titer toxin (BoNT/H). It is unclear whether the antitoxins used by the authors were validated for efficacy and whether death was due to nonneuro-toxin mouse lethal compounds that can be observed in C. botulinum cultures grown in complex medium. In the " sero-type H " study, protection in the appropriate mouse lethality assay was observed by combinations of antitoxins A, B, and F, supporting the conclusion that the new serotype is primarily a hybrid between A and F serotypes. These results resemble the mosaic botulinum toxins observed between serotypes C and D, for which an-titoxins to C or D alone do not neutralize " by the conventional serotyping method " [5, 6]. It has been discussed that such C/ D-hybrid toxins constitute a new sero-type, but molecular understanding of the hybrid nature has not provided support for designating a …