So it’s been ten years now since the peak of the genomics craze in the drug industry. Hard to believe! Looking back on these things, it can be hard to recapture the mood, since regretful hindsight keeps blurring the more painful parts. I know that a lot of companies would, in retrospect, rather have back some of the huge amounts of money they spent back in that era, but for every one of those, there’s a genomics company that wishes that they had something that hot to sell again.

Well, actually, that’s not true in every case, since several of those genomics players haven’t even lasted long enough to look back from this far. But at the time, at the time they looked as if they might end up owning the world. Not everyone believed that, true, but I don’t remember many people with the nerve to say so in public. The strongest misgivings went something like “We don’t know if this is going to work or not, but we have to be ready if it does”, which is a perfectly defensible position.

But that was rare – most of the stuff you heard, at least in press releases and the like, ran to “Genomatronic Corp. announces that it has now filed patent applications (a whopping load of patent applications) on another huge, important swath of the vital human genome (remember, there’s only one!), and reminds the industry that its back walkway is open on Tuesdays and Thursdays for Big Pharma to come crawling up it”. Over at Megapharm, Inc., their opposite number, the fear was quite real that the Genomatronics of the world actually were staking out all the deposits of gold, and that all the drug targets in the world were going to end up owned by someone else – like those other big drug companies that were daily announcing huge deals with Genomatronic et al.

It was easy for panic to set in. How much of the genome could possibly be left by now? We’d better do a deal while there’s something to buy! After all, when you got down to it, these folks were right – there’s only one human genome, and we’re only going to read it for the first time once, and all the drug targets that will ever exist are in there – right? So why would you sit there and watch the competition walk off with all the good stuff? Right?

Well. . .not as right as you’d think. The big splash of cold water, at least as I remember it, was when the Human Genome Project folks announced the total number of human genes, and it came in way below what some people had been estimating – like, ten times less. If you added up all the genes that people had claimed to have filed applications on up until then, it was well in excess of the number of genes that turned out to actually exist. This embarrassing patent excess was one problem (some of which could be explained by multiple filings by different companies), but the unexpectedly small number was the other one, and the more worrisome. How could there be so few genes when we knew there there were a lot more proteins than that? And so the importance of post-translational processes finally began to be appreciated by a wider public. It wasn’t “one gene, one protein” – it was “one gene, a bunch of proteins, and we’re not sure quite how or quite how many”.

Another set of problems came on a bit more slowly. The companies that did the whopper genomic deals came to realize that (1) even 50,000 genes was rather a lot, when you had no idea what most of them did, what pathways they fit into, what diseases they might be associated with, and what might possibly happen if you found a compound that affected their associated proteins, and (2) it didn’t look as if we were going to even get a chance to find out about that last part, because most of these things came up empty when you screened against them anyway. These were (and are) all major problems. We still have only fuzzy ideas of what a lot of genes actually do, and we still have a terrible time finding useful chemical hits against a lot of our new targets – more on these later; they’re perennial topics around here.

You still see breathless articles (particularly in the alternative press) about the amount of your own DNA that’s like, patented and owned by the big corporations, man, but the people who write these articles generally don’t know enough to realize that most of that stuff is irrelevant. The patent office has tightened up severely on its requirements for gene patents, and recent court decisions have called the whole idea of patenting DNA sequences into question (more on this later, too). And at any rate, most of these things would be on track to expire without anyone yet finding out what they might be good for.

So where are we now? So, in the end, there was no genomics gold rush, at least not in the way that everyone thought. The genomics players are out of business, or if not, they had to completely retool and find something else to do. Most of their patent applications were wastes of time and money, since they never issued, were generally hard/impossible to defend if they did, and are mostly heading for expiration without having made anyone a dime. The value of the genome is real, but it’s taken (and it’s still taking) a lot longer to realize it than anyone would have believed in 1999. If anyone was predicting this ten years ago, I missed it. It wasn’t me.

Update: Keith Robison lived it from the inside, and tells the tale.

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