A colleague asked me yesterday what I thought about a story she'd seen in the media regarding a virus often found in algae. Supposedly it can impair human cognition. I told her that as a matter of fact I'd been working up a brief blog post on the topic because of its implications for mass tort litigation, gave her the short version and promised to finish the post and send it along once I'd finished working on a presentation. Now I have so here it is.

A couple of weeks ago "Chlorovirus ATCV-1 is Part of the Human Oropharyngeal Virome and is Associated With Changes in Cognitive Functions in Humans and Mice" was published in Proceedings of the National Academy of Sciences. It's an excellent example of good science revealing just how strange our world really is and just how little we really know and how poor our guesses can be about the causes of human disease.

I'll get to the strangeness and the upset applecart of prior beliefs shortly but first it's important to point out that this is a classic case of scientific discovery. It's a direct observation of something never seen before followed by an experiment designed to test the implication of its discovery. It is not a case of finding a correlation between one event and another that seemingly followed it and thereafter creating a model/explanation of how the observed association might be causal. That's just generating a hypothesis. Nor is it the usual null hypothesis testing of small effects that drives most modern toxic tort litigation. That's just pretending to be surprised when a system that has been slightly perturbed turns out to be slightly perturbed.

Like most modern discoveries this one depended on a new method of observation and curious scientists deploying that new method to peer about the world around them. The new method (methods really but I'll cram them all into one category as they're evolving rapidly and besides it shortens the post) involves rapidly (and cheaply) sequencing all of the genetic material in a sample, comparing it to libraries of microorganisms, human cancer cells (see e.g. The Cancer Cell Line Encyclopedia ), etc. and thereby "seeing" the biological diversity present in the sample. The name for it is metagenomics.

Gene sequencing isn't new of course but what is new is the ability to sequence the unknown unknowns in a sample and to do so rapidly and (relatively) inexpensively. In the past you'd take a sample, culture whatever was present in a petri dish (multiple techniques here too but anyway ...) and then sequence whatever was in each of the clumps of clones you'd cultured. The problem is that not every microbe is culturable. In some cases the right medium has yet to be found. In other cases the beastie is dead - an invisible casualty of an unseen battle between the immune system and an invader. Either way we were blind to much of what was going on.

In this study scientists took throat swabs from people participating in an investigation of cognitive ability (among other things) to see what they could see with their new method. Upon comparing the genetic data they found to the libraries available they were surprised to find a match with a virus that infects algae; one that had not previously been identified as being infectious in humans. They then looked to see if there were differences between those with and without the virus and found a marked decrease in cognitive ability among those infected. To test the hypothesis that springs so readily from such a correlation they then ran an experiment on lab animals. Sure enough, cognitive ability including memory declined in those mice inoculated with the virus. But that wasn't the end of it. They next looked to see what genetic changes the virus had wrought and it turned out that it altered the expression of genes that have to do with cognition. Not quite proof but pretty compelling.

As the use of this new way of seeing, metagenomics, has expanded so have the number of discoveries. Have a look at Elevated Levels of Circulating DNA in Cardiovascular Disease Patients: Metagenomic Profiling of Microbiome in the Circulation and Pathogenic Microbes, the Microbiome, and Alzheimer's Disease (AD) to see what may await.

And along with the discovery of new causes come ways to track it back up the causal chain (at least until a deep pocket is found). See for example Seeking the Source of Pseudomonas aeruginosa Infections In a Recently Opened Hospital: An Observational Study Using Whole-Genome Sequencing .

One question raised is what duty is owed to those of your workers and customers who might come in contact with what was thought to be a harmless green algae occasionally infected with a virus nobody suspected until now to have the ability to fiddle with your brain's fine tuning. Another is whether you ought to have your cognitively impaired plaintiff who blames the landfill tested for Chlorovirus. Or how about whether there ought to be a REACh for food (since the companies will come to have, thanks to the use of metagenomic techniques to ensure food safety, vast libraries of the presumably harmless microbes and their ever evolving offspring that ride to market in and on their products)? And what about record-keeping requirements because even helpful bugs sometimes go bad? Is it foreseeable that an innocent bug shipped far from home and thrown in with a strange crowd might pick up a plasmid coded for virulence?

If scientific discoveries raise more questions than they answer then the intersection of the law and new discoveries ought to keep us busy.