The search for the source of the E coli contagion in Germany has heated up in the past 24 hours. Focus was initially on a restaurant in Lubeck but has now shifted to a farm which supplied sprouts to this restaurant and others associated with illness. We should know within the next day or two what evidence German officials have that this farm is the source of the contamination. However, even if it is, it does not address the broader questions of how this novel strain of E coli came to exist.
As discussed in my previous blog, determining whether the current outbreak comes from a natural or man made source is difficult because E coli exchange genetic material in nature but are also easy to modify in a laboratory. If this outbreak was due to a well-characterised pathogen that had caused similar outbreaks in the past, there would be no reason to suspect anything but a natural source. However, early evidence suggests that this is an unusual bacteria, both in terms of its genetics, but also in the large number of people infected and in the severe symptoms it causes. Indeed, recent stories suggest that hospitals in Northern Germany are under severe pressure. This event is likely to go down as the worst E coli outbreak in recorded history. Thus, perhaps it is not surprising that the very novelty of the bacteria and the severe symptoms have raised suspicions:
From The Windsor Star, June 4, 2011:
A senior German doctor last night called for an investigation into the possibility that the bacteria had been spread deliberately.
Klaus-Dieter Zastrow, chief doctor for hygiene at Berlin’s Vivantes hospital, said: “It’s quite possible that there’s a crazy person out there who thinks ‘I’ll kill a few people or give 10,000 people diarrhoea’. It’s a negligent mistake not to investigate in that direction.”
Interestingly, there was a report that German authorities had launched a criminal investigation (The Daily Mail, June 4, 2011 ). The basis for this investigation has not been revealed.
However, it is important to note that given the unusual nature of this pathogen, it is unlikely that a solitary criminal is responsible for this outbreak. Further, given the rarity of at least some of the genetic material, stateless terrorists are probably not responsible for the production of this pathogen. The fact that there has been no claim of responsibility also undermines this hypothesis.
If this bacteria was made in the laboratory, it was likely produced by a well-funded group with extensive resources and skills. This could only be supported by a State. If such resources were available, is it possible to determine that this new E coli strain was not natural? It depends.
As I mentioned in my previous blog, genetic material from E coli can be manipulated using restriction enzymes. In common lab strains, there are specific and readily identifiable sequences called restriction sites which facilitate splicing different bits of genetic material together. The presence of such sequences at the junctions of unusual combinations of genetic material in this new strain would be a dead give away that this bacteria was a biological weapon. Currently, raw sequence is available from at least one isolate. However, to identify incriminating restriction sites, a high-quality, finished assembly of these sequences is necessary. Although a number of groups are working hard on this, only rough, incomplete drafts have been made public thus far. We should have more information on this next week.
If suspicious restriction sites are not found, can we conclude that this bacteria must be natural? Unfortunately, no. Molecular biology has advanced greatly in the last decade and there are now many ways to manipulate bacteria in a laboratory without leaving tell-tale signs. Indeed, if this new strain of E coli was made in a sophisticated laboratory, leaving restriction sites in would be tantamount to announcing that it was a bioweapon.
There are a number of ways the current investigation will end. I won’t pretend to know which is the most likely. However, one possibility is that we will be left in an ambiguous situation. The genetic analysis may point to an extremely odd configuration of genes, but no smoking DNA may be found. Detective work may find that agricultural products were contaminated, but may not find out where the bacteria that contaminated them came from. If this is the outcome, should we regard any consideration of the possibility of a laboratory origin as “inappropriate”, “paranoid”, or “irresponsible”?
No, in my opinion. We should not.
From: Yi, et al 2010
Among the pathogenic E. coli strains, EHEC O157:H7 has been recognized as one of the most notorious pathogens featuring the properties of an extremely common and virulent serotype, and is responsible for a series of severe gastrointestinal illnesses with life-threatening consequences in North America, Europe, China, and Japan, , , . Considering its high pathogenicity, EHEC O157:H7 has been listed as a potential bio-weapon in many countries.
Indeed, enterohaemorrhagic E coli has an official BioWeapon designation: WB3.
Yesterday, it was reported that the Centre for the Protection of National Infrastructure in the UK has issued a warning to manufacturers and retailers to be on the alert for attempts to poison food by politically motivated groups (The Telegraph, June 4, 2011).
It is true that Nature has killed many people. It is also true that humans have killed many of their own species. When someone dies in an unusual way, there is usually an investigation to determine whether or not foul play was involved. People in Germany are dying of an unusual pathogen which was explicitly listed as a possible Bioweapon. Maybe they are dying of natural causes. But assuming this, without an investigation which considers the other possibility, would be reckless, in my opinion.
Yi et al. (2010) Crystal structure of EHEC intimin: insights into the complementarity between EPEC and EHEC. PLoS One. 5: 15285.