A while back I was lucky enough to be accidentally selected to take a big shot from big pharma out to lunch while she was visiting. I say accidentally, because I’ve been a very vocal critic of big pharma’s business model, going so far as to actually do a seminar on the subject the first year I was in graduate school (kids, don’t do that.) My position isn’t that Big Pharma is evil and they’re out to get you, it’s that they’re big, stupid useless machines that pump out gobs of fluorinated shit for metabolic syndrome and boners and buy up little companies before their quarterly reports are up. None of them are hiring like they were a few years ago. Indeed, getting a job at these huge companies isn’t likely going to be the outcome for most people, regardless of the lab you work in. So, I took this lunch time opportunity to propose my own, rather arrogant opinion: It’s because they keep recruiting from Dave Evan’s lab. And Barry Trost’s lab. And Sam Danishefsky’s lab…. you know… as I so politely put it, the Legends of Total Synthesis. Of course, this doesn’t mean that all drug companies have stalled. Some how, we continue to get new drugs – they’re just not being made “in house” by big pharma. Look at my gheto-graph of New Drug Applications by year:

If you’ll forgive the gayness of my chart, I pulled that data here, from the very government those drug companies have worked so hard to create for us. The blue line indicates the number of NDAs approved and, apparently, the only people that can really tell the difference between “the good years and the bad years” are John Lechleiter, Richard Clark, Jeff Kindler and/or any other douche bag that is lucky enough to be promoted to “transient CEO of big pharma for a few months.” An average of 90 ± 20. With a huge boom in the late 90′s where, I presume, most of those are still covered by the more realistic “25 year patents”.

I remember back in 2002ish at Lilly when Big Syd Taurel got on the jumbotron in building 78 (there really is a huge screen and projector in the atrium – at least there was at the time) and announced that Lilly was going to enter into a hiring freeze because someone fucked up and lost the patent to Prozac before they could wring a few last good years out of it. Since then, it’s been a litany of unproven excuses like “It costs a BILLION dollars to discover a new drug and the Canadian reimportation/corporate taxes/generic competition/short patent/turrists/life is just draining all our money away and we’re operating on PENNIES, PENNIES I TELL YOU” and so on, yet – we can see from our friend the graph, that apparently some companies are doing just fine.

But I was discussing the legends of total synthesis contribution to this. Pardon the digression. The problem, as I see it, is that people who work in these labs go on to fill the ranks of big pharma, who have done nothing, while little upstarts, which are filled with people from “lesser groups” at “lesser schools” appear to be doing alright. WTF gives? Is it… possibly… that total synthesis MAY NOT be the best training for drug discovery (heresy!). (Tip: the stock excuse is that you hear more from little companies because they’re more likely to announce their discoveries faster. Apparently, Big Pharma sits on ALL news, not just the bad news.) Or has Big Pharma academically inbred it self into Appalachian style banjo plucking retardation? It could be both, of course.

I don’t think it’s just me, but it could be: does it seem like the groups with the largest anti-bio vibe are either material groups or total synthesis groups? While the obvious pitfalls of not appreciating the delicate biochemistry of the organisms you intend on eradicating may become apparent all too soon to the material folk, being anti-bio in a total synthesis lab is stupid, counter productive, and very prevalent. The new “multidisciplinary” action that compose 30% of Big Pharma powerpoint slides isn’t coming through in their hiring practices as they keep recruiting from labs that wouldn’t be able to find the active site of a protein if it were docked to the fatty part of their ass. It would be more logical to approach people who work in multidisciplinary labs, that make and model enzyme substrates – people who think like a biochemist but are trained as an organic chemist. The target in drug discovery is never known at the onset – if it were, the discovery process would be a lot easier. This is clearly not the case in total synthesis, where the target you’re synthesizing is known from day one and your mission is to make it, live or die trying.

So I dropped these things on her and got back the stock responses which I’ve heard before (she is a proud alumni of the Evan’s lab, unsurprisingly)- “we need people who can think critically about chemistry.” To which I obviously replied, “I would think anyone obtaining a PhD in chemistry should have that ability.”

Her answer was glib. “You’d like to think so…” suggesting, some how biochemists lack a certain part of their brain that performs these advanced critical thinking tasks and are awarded PhDs on the basis of “good, honest hard work if not pointless work.” Or, if I were to be even more cynical, that people who are in these legendary groups are always going to be critical thinkers and everyone else is too questionable to spend time interviewing. Which is bullshit, of course, but I’m just being cynical here.

Obviously, if you want synthetic chemists, you’ll want to hire people with bench experience, but there’s no need to hire people from the same 10 or 15 groups. Apparently, anyone can use SciFinder now, so it’s largely unneeded to get people with broad encyclopedia knowledge of reactions and, at any rate, at some point companies need to look internally to determine why they are failing and, amongst other atrocious practices (including over use of direct-to-consumer marketing, out sourcing R&D and process to developing countries with governments that are blind to intellectual property theft, excessive executive compensation packages and top heavy managment structures… so on and so forth) they need to consider that they’re recruiting researchers poorly and their hiring strategy is pulling a homogenous pool of people and they’re doing it because 1. the people hiring were from those groups and 2. trying new shit is just not something huge, stupid drug companies do well or do quickly.

I’ll end this rather long post with a cautionary disclaimer – I don’t do total synthesis but I’m also not interested in working for Big Pharma. I have no outward interest in these companies suddenly recruiting from… say… oh… some lab at Cal Tech. I also think TS is a great area to prepare chemists for work in drug companies – the issue is homogeneity and inbreeding, not that they’re failing to find quality people.