Science as Social Enterprise

This topic is such fun, I could log in each day and all the ideas I’ve had for thirty years would start lining up on the framework of hologenomics.

In the last few years our lab has been getting more deeply into Type IV Secretion Systems. We set out some years back to ‘re-invent’ the Agrobacterium tumefaciens plant gene transfer capability in other families and genera of bacteria.

The reasons were twofold. First to invent around a very egregious and complex patent ‘thicket’.

Agrobacterium had been discovered to be capable of transferring genes from itself into higher plants, using a mechanism that is very similar to that used by virtually all bacteria to transfer genes (and proteins) from one bacterial cell to another, and often from one bacterial species to another. This observation was the first prominent inter-kingdom gene transfer described, and was the foundation of plant genetic engineering. So of course, it was patented up and down, backwards and forwards; every improvement, every species of plants…obscene greedfests of patenting. Until no one could actually use Agrobacterium to create crops (not just plants) that were improved. Except of course for a very few multinationals that had acquired strong portfolios and were willing to cross license them narrowly.

Anyway, we found that all the patents referred to this biologically unique (now there’s an oxymoron) capability of Agrobacterium tumefaciens. We reasoned that nothing in biology is unique. (Or as Jeff Goldblum’s darkly prescient character in Jurassic Park opines “Nature finds a way”). So we looked at moving this capacity to diverse bacteria and thus rendering the patents interesting and informative, but not legally restrictive.

It was surprisingly easy! And every one of the bacteria we tried it in worked, and in every plant species combination. Hmmm… so interkingdom gene transfer wasn’t hard? Well….

The other reason we set out to do this work-beyond, which we called Transbacter, was to make the process better. To use bacteria that had evolved a benign and symbiotic relationship with plants (and hence did not induce a pathogenesis response) to do our gene transfer, nicely.

Well, all that is pretty well described. But as we get more into these natural gene transfer capabilities, which are loosely clustered as ‘Type IV secretion systems (T4SS)’ I start to realize that the movement of genes between bacteria and likely, between bacteria and fungi, protists, plants, animals, you name it, is probably hugely more common than previously supposed.

The antibiotic resistance factors that are so promiscuously shared on broad host range plasmids (like the ubiquitous RK2) are moved around with T4SS’s, and of course the first system I cut my teeth on – the E. coli ‘F’ factor (fertility factor) is yet another of these. No self-respecting bacteria seems to lack such a capability.

If our observations about how the Ti-encoded Agrobacterium system can be so effective inother bacteria can be generalized, I think it may mean that a very serious force in metazoan and plant apogenome evolution will be from horizontal gene transfer from microbes. Note I say ‘microbes’ not bacteria, because I bet these types of systems pop up in fungi, protists, archae…etc.

Ok…my fingers are sore from typing this little blog. But there’s the convergent evolution in my scientific thinking – from glucuronide metabolism (and GUS the Wonder Gene) to horizontal gene transfer…now coming full circle.

What fun this period of life sciences could be. I really find 99% of molecular biology boring as bat shit these days. I can’t bear reading journals. But these ideas are much more envigorating, as they seem to smell of a pervasive logic. And as usual, I adore going where the metrics are tough. If you can’t see it and measure it, its not there? No way.