STAT has a pretty wild story (for subscribers) about Laronde, a Boston/Cambridge area biotech firm that seems to have had some major problems reproducing the data that helped raise them hundreds of millions of dollars last year. It’s quite a read, but at the same time you can’t help but feel that you’ve read this story before. Let’s go into that.
Without tearing up the paywall, the outline of the story is that Laronde had what looked like promising results for a circular-mRNA technology. The hope was that this “endless RNA”, as the company promoted it, would be more stable, have better distribution upon injection, and lead to longer-lasting protein expression as (in theory) a ribosomal complex might just keep circling around it translating all the way. There are other companies working in this area, but Laronde had spoken of some really strong results in animal model experiments, as generated in one of their research groups.
But it looks like no one else could get this to work. And when colleagues pressed the lab head involved for more details and for a chance to go over the raw data (much of which appeared to be missing), she refused to share it. Key figures in management took the line, though, that any problems with replication were obviously the fault of those other losers who just didn’t have what it took to bring the magic. Sadly, the story develops in just the way you think it does after hearing that part, and if I were an investor in the company’s $440 million Series B round last year, I would be hopping mad to read about what was really happening while that money was being collected.
At this point you may be reminded of the entire corporate culture of the late and unlamented Theranos, and with good reason. But that spectacular example is not the only one of its kind out there – Theranos differed in its scale and thoroughness, but the same habits of mind, the same research and managerial climate, those have come up many times before. They rarely get to the point of taking down an entire company, but the warning signs are all very similar, and here are some of them laid out in a handy reference format. You should start to check things out carefully if:
Only one person can get this great stuff to work. Now, there are certainly a lot of funky procedures in both chemistry and biology work with ill-defined variables, and a lot of new stuff needs taming before it works reliably. I remember a tricky anion reaction years ago that One Guy could get to work the best; he seemed to have a feel for the stirring and rate of addition. But there’s a limit to this sort of thing – the rest of us could make that alkylation work, albeit often in lower yield. A situation where no one else can get a great big career-and-company-altering result to happen again is an alarm bell. It demands attention, but (as can be seen with the STAT piece), sometimes the opposite happens. As in. . .
Legitimate questions are met with stonewalling. People whose careers depend on the great stuff working as advertised may decide instead that they Simply Do Not Want To Hear anything disturbing about it and adopt a “Shoo, little people! Out of my way!” attitude. That is not how to do science – hell, that’s not how to do anything, and the number of times people have come to grief via that attitude are beyond counting. The questions at Laronde were random noise from disgruntled employees. These were questions like “Hey, we can’t see that species at all by mass spec that’s supposed to be in those blood samples” or “Hey, we can’t reproduce those ELISA results, not even a little bit” These are legitimate scientific questions, pretty darn concerning ones, too, and they deserved real answers, not the high-handed brush-off.
Important data are missing or kept secret. There’s really no excuse for this, and there’s especially no excuse for it in an industrial research lab. You’re not making notes on paper towels; everything is damn well supposed to be documented electronically and to be accessible on demand, from the raw data on up. From the article, it seems that folks at Laronde had very sound reasons for wanting to see the data for these killer RNA experiments, because they weren’t reproducing. Finding then that these results were missing from the electronic notebooks should have set off sirens, and the refusal of the lab head involved to share data should have set off even more. You’re all working for the same company. I have never heard of an “I don’t want to show you that data” situation that ended well.
You’d think that these points would all be obvious. They are obvious. But people will find all sorts of ways to believe what they want to believe, to avoid hearing things that they don’t want to hear, and to avoid thinking about things that are too worrisome to contemplate. We all do that sort of thing once in a while; it’s human nature. But you don’t want to handle hundreds of millions of dollars that way. Nor your career.