The Truth behind Bad Bugs

Soob did me the courtesy of pointing me to this Slate article about the past E. coli outbreak in spinach that caused so much trouble in 2006. In the article, the author suggests that this case should demonstrate that it isn't so easy to genetically engineer new biothreats as some would have us believe.

The scientists concluded that at some point in the not-too-distant past, this strain of E. coli O157:H7 evolved rapidly into a far meaner pathogen than its ancestors. Natural selection altered its genes quickly, thanks to the ability bacteria have to reproduce in as little time as 20 minutes. Speeding up their evolution even further was their ability to take in DNA from other microbes, even from species that are only distantly related. The genomes of bacteria are being continually rejiggered into new combinations of genes. Some bacteria become better at capturing sunlight, others at resisting antibiotics. And, in the case of the spinach strain of E. coli O157:H7, the introduction of viral DNA has made them far nastier.

It is chilling to think just how quickly a new, more dangerous form of E. coli has emerged—and it's tempting to think that its quick arrival bodes ill for synthetic biology. After all, if it just takes a few years for a dangerous strain to evolve in the wild, just think how easy it will be for people to build them in the lab.

In fact, the spinach outbreak teaches a very different lesson. The Michigan State scientists have no idea what is making the new strain so mean. It's a straightforward task to identify the hundreds of new genes in its genome, but the researchers can't say precisely what all those new genes are doing. The same goes for the hundreds of missing genes as well as for the other genes tweaked and fine-tuned by natural selection.

This sort of ignorance is par for the course in the world of microbes. And if a new strain of an intensely studied species is so mysterious, it's hard to believe that bioterrorists could just type out a new plague on their keyboards. Our deep ignorance also raises some doubts about how far synthetic biologists can go with the good applications of the science. In the most ambitious projects, scientists have inserted only a few genes. They've had some spectacular successes, such as making E. coli produce jet fuel and precursors to malaria medicine. But the notion that we might add hundreds of genes to bacteria to do something useful, like turn microbes into solar power generators, may be hubris for a long time to come.

Inventors don't always design their inventions from scratch, though. Perhaps someone could create a new pathogen simply by mimicking nature: combining different sets of genes, mutating a few of them, and using trial and error to find ones that worked? Probably not. Nature's lab bench is colossal. Millions of cattle and other animals are carrying around E. coli O157:H7, and an incalculable number of viruses are invading them, trying out new combinations. Many of those combinations turn out to be failures, but natural selection can give rise to a few spectacular successes. Even if a government built a giant lab just for the purpose of stumbling across a new pathogen, it might take centuries or millenniums to hit on something like the spinach strain.

But this ignorance is not cause for much comfort. Even if we don't need to worry about synthetic bacteria just yet, we do need to worry about new pathogens evolving right in our own backyard (or, rather, our own feedlots and factory farms). As things stand, we become vaguely aware of these bacteria only once they've been sickening and killing for years. One way to speed up the search for nature's new bioweapons would be to set up a monitoring network. If public-health workers were equipped with cheap, fast testing devices, E. coli and other microbes might not be able to surprise us so often in the future. And if some evil genius does someday figure out how to unleash a bioweapon, we will have had an excellent rehearsal.

This is an interesting and I think effective article - certainly our government scientists and DHS leadership like to fret and worry about this supposed future threat of designer biowarfare agents, and sure, it COULD happen some day, just like a giant asteroid the size of Texas COULD actually hit a land mass on Earth some day. We do need to temper our imaginations with risk management and logical priorities.

I also note the author's desire to use public health as the testing ground for potential terrorist bioweapons - this is a popular statement from public health advocates who don't think the federal government is spending enough money in their sector. On the one hand, they're right to say that the public health system is the right response to any imagined future terrorist BW incident (much more than projects BioWatch and BioShield are). On the other hand, if your intent is to focus on specific terrorist BW scenarios, sending the money to a broad responsive effort like the public health system isn't always the best use of money either.

Comments

[BGG]

Predictably, this post brings me out of my cave. The thing about articles like the one from Slate (and I really enjoy Carl Zimmer's stuff so I'll be nice) is that they tend to focus on the most unlikely molecular biology scenarios (i.e., "evildoers" applying full-blown synthetic biology), rather than the most likely scenarios by today's level of technology. Today it's more likely someone would engineer multiple antibiotic resistance into a bug of their choice, or transfer pathogenic plasmids from a dangerous organism (obviously, anthrax springs to mind) to a common nonpathogenic organism. Or both. There are simple manipulations that could be done today to cause problems...although I think the important question is would a terrorist bother with all that?

The article is correct in its assertion that we don't need to worry about synthetic biology yet, and natural mutations in known pathogens present the much greater threat. But the article doesn't portray the whole picture. True, scientists can't describe the host of interactions going on between dozens of genes in a new strain of E. coli, but this does not mean that they haven't identified oodles (that's technical jargon) of pathogenic sequences from dozens of organisms and can easily insert them into foreign genomes. While the threat from true synthetic biology is a couple of decades away, the threat from a molbio "tinkerer" is here today.

Now, don't take this to mean that I argue some minimally modified pathogen will be released into the population. I personally think it's not that likely some "evildoer" would go to the trouble -- I agree totally with you that, "We do need to temper our imaginations with risk management and logical priorities." And frankly, our current crop of terrorists appear to be dumber than a 10-lb. ball bearing when it comes to science. I only want to make the point that some naughty person could do a variety of troublesome things with today's technology, and that many articles seem to gloss over that and go straight for the "brand new organism" idea, which is more sensational.

[Gwyn]

I'd recommend Domaradskij's comments in his Biowarrior book on the difficulty of splicing different attributes onto pathogens to create a super agent and the subsequent interactions. His take on it was that once you introduce one new section it tends to have a reaction on another part of the existing agent, generally making it less potent. Admittedly his experience is 15 years old, but the fundamentals would seem to be the same.