What Next?

As I contemplate more bad news in the industry, this time from local pharma giant GSK (though we don’t know yet how badly the Triangle facilities will be affected), I was thinking about a fuller answer to a question I got after my last post: What are the alternatives for a laid-off organic chemist with industry experience?

I got the decidedly non-unique opportunity to think about this first hand a year ago, so I hope I can offer some insight. Here’s the list I drew up and some thoughts on each option.

1. Get another job in medicinal chemistry.

Easier said than done. Big Pharma do still have internal research groups, but they are not growing and opportunities to find positions there are far and few between. A better bet might be in smaller companies, start-ups for the most part, or non-profit groups or academic drug discovery efforts, such as the Vanderbilt Institute of Chemical Biology or (locally to me) the UNC School of Pharmacy program. Which part of the country you are in will play a major role, as many of these companies are clustered, with Boston, San Francisco and San Diego being the main centers, though RTP and Seattle, for example, have respectable amounts of discovery going on.

2. Same field, different role.

In looking around, I found that there were jobs in the industry, just not in drug discovery. Drug development, analytical support and clinical trial management positions are more prevalent. So if you have the interest and skill set to make such a sideways move, this is certainly a possibility. The problem is, of course, anyone with direct experience in the area is automatically ahead of you in the queue and with the job market as it is, companies are able to pick and choose their candidates. Not that companies want all their analytical team to be super-experienced – that can create problems of its own when promotions need to be given out – just that you will have a fight on your hands for the more entry-level positions. Plus, you may find it is not a sideways move but a backwards one.

3. Patent law

I know several ex-chemists that have moved into patent law. It is potentially lucrative and if dealing with patents is your dream or, possibly more likely, you think you can stand all that paperwork, this is a way to go. There is an interesting post here about a chemistry professor that turned to law school after he was denied tenure. The answer to your first question: yes, you need some more schooling to do this.

4. Teaching

The most obvious alternate career for scientists, but one that is often reluctantly pursued, due to financial concerns plus the whole having to teach a bunch of high schoolers chemistry thing. I don’t think teaching should be a fall back position, this is something you have to really want to do, a vocation rather than a job. You should also realize that the subject matter is not the skill you need to master here, it is the teacher-student interaction.

If you can get by that, then you can get into teaching relatively easily. If you have an advanced degree, many educational programs will let you begin teaching while getting your teacher certification, especially in the sciences, where there is a distinct lack of teachers. If you get into teaching relatively early in your career, you do still have the option of giving it up, but for a mid-career transition, I’d recommend thinking long and hard about it before committing.

5. Consulting

If you are established enough in the field, you may be able to get enough work in an advisory capacity. This obviously requires some specialized knowledge in a hot field and a good-sized network of contacts so that you can talk to the right people to get that consulting work. Certainly a nice line of work if you can get into it and make a name for yourself, but limited to a relatively small percentage of the population.

6. Start your own company

Talking of taking the hard road, you could just start your own company. There are a great number of challenges here, but to start, you will need some niche that your company can fill, whether it is cheap drug discovery (maybe good contacts in Asia?), some amount of specialized knowledge, something that makes a larger company want to bring their work to you. Perhaps you have some idea for a product to help drug discovery. That initial idea seems key, but then the hard work begins, as you exchange working 8 hours for someone else for working 18 hours for yourself. There are resources to help entrepreneurs get started, though this is out of my own experience, I have a few colleagues who have gone down this road. Be prepared to lose money hand over fist for 2 years. At least.

7. A brand new career.

Leave behind chemistry and make your fortune elsewhere. Sounds good? But not unlike changing roles within the pharmaceutical industry, changing to something new means you are competing with people who have previous experience in the new field. Very hard in this job market. Good networking will be essential, though that applies to pretty much everything in this list.

My own experience centered on the top 4 items, as I hadn’t the experience nor the sheer will to do consulting or my own company. I did decide early on that I wanted to stay in chemistry (ruling out #7). I thougth about patent law, but felt the paperwork would get me down. I like writing papers, but then they are done and I can go back to the work in the lab. Teaching I gave a lot of thought to, people have said they think I’d make a good teacher. I got forms for the course at UNC, started on an application. But the soul-searching said it was not really for me. I kept my options open with alternate roles in drug development, or process, or analytical, but none of those came through. In the end I got my first wish, which was a role in the lab, doing medicinal chemistry at RTI.

Right Place – Wrong Industry?

As someone in drug discovery, the news that caught my eye today was that of AstraZeneca’s announcement that they are cutting 8,000 jobs over the next 4 years, including 1,800 in R&D. On top of all the other big pharma jobs that have been put to the sword in the last couple of years, that is a depressing number of people.

Compare and contrast with the local news, which at least has the novelty of being relatively good. First was the list in Fortune of companies that have never laid anyone off, headed by the Triangle’s tech powerhouse, SAS (also named as the best place to work in the country by Fortune, who are clearly fans). Notice a lack of pharmaceutical companies in those lists. British electronic device maker ACW is bringing jobs to Durham county and in general, the Research Triangle had an excellent year of new investment.

Like I said, right place, but not too much happening in the pharmaceutical area. Is it too late to become a tech geek?

My Tales of Ammonia

One of my least favorite chemicals is ammonia. Described by most as that pungent smelling gas, it is one that I would always prefer to avoid if I could. Not as downright unpleasant in aroma as numerous sulfides or mercaptans, it has instead a kind of olfactory kick in the sinuses that makes you instinctively jerk away.

What is a shame is that it is quite a useful little molecule – as the long list of producers and uses on its Wikipedia page testifies. The main use in synthesis is for dissolving metal (usually sodium) reactions, which have a characteristic (and quite beautiful) blue color. A more every day use is as an addition to chromatography solvents as ammonium hydroxide, to help the march of the amines through the silica. So my distaste for its pungency has taken a back seat to my appreciation of its utility.

My time at graduate school (at the picturesque University of St. Andrews in Scotland, by the way) was book-ended by ammonia releases that prompted evacuation of the building. I should add that I wasn’t involved in either, other than as bystander, but my understanding was that the cylinder of ammonia was only infrequently used (as would be obvious if you consider they had the same one at the end of my time there as they had at the beginning!) and had a tendency to get a bit stuck, only to open all at once and release a whole lot of ammonia in one go. Why they didn’t just get rid of the thing after the first time, I have no idea.

A more serious incident also occurred in my group while there, a grad student using ammonia got a face full after a septum popped out. It was pretty scary for a moment or two, but a colleague in the lab at the time grabbed him and got him to the sink, giving him a thorough drenching. Within a few minutes, he was all right again. It was quite shocking how suddenly something can happen in a laboratory like that. One moment as quiet as can be (given the noise of the hoods, pumps, etc), next moment bedlam breaks out.

I have done the sodium-ammonia reaction myself several times. I can’t deny it is pretty, but it is a real pain to carry out. In fact, one assignment I was given was to eliminate the sodium-ammonia step from a reaction sequence. This particular reaction was a worse pain than most, as not only was it procedurally tedious, it also didn’t give that great a yield either. But the constraints on the available space and glassware meant it could not be scaled up to any great extent either, so it became a bottle neck in the synthesis, one I was more than happy to circumvent.

Plus, it smells. Did I mention that?

Outsourcing Pharma

It seems that there has been a flurry of articles talking about the state of outsourcing in the pharmaceutical industry this week. Lilly gained a mention in the Wall Street Journal on the matter. A more general look came from Fierce Pharma and also this post from Nick Taylor.

So to summarize, outsourcing will continue to grow as a route big pharma takes to develop new products. The bad news is (for us employed in the area in the west at least) that most of that outsourcing will go to Asia and, increasingly, Central and South America, though there are indications that we will see a modest increase within the US as well. This is all, of course, driven by cost.

I noticed that a lot of these were talking about development rather than the initial discovery of drug candidates. As the latter is my particular interest, I wondered a little about what will happen to preclinical discovery. A comment by Merck CEO Dick Clark made the point that the announced closure of several Pfizer/Wyeth sites made last year: big pharma is looking to shed some more weight in research. That is pretty common, I think, in mergers and acquisitions, especially in lean times. Research is easy to cut back as it gives no immediate prospect of gain. The company trims up, gets back on a steady course, more efficient and more profitable.

The long term survival of pharmaceutical companies is based on research though, so it seems very likely that heavy cuts now will result in a need down the line when the remaining resources become over-committed. So as I see it we may not see an immediate turn around in work for drug discovery scientists, but there will likely be a need for more once they realize they still need research to succeed.

The remaining question is will this be outsourced as well? And if so, where? I think the answer will be similar to the answers above. An increasing amount of initial research will be outsourced, with a goal of keeping down costs. As for where, well, some of the new companies in Shanghai, for example, are getting increasingly proficient and (importantly) trusted at doing medicinal chemistry and so there will be companies that make use of their talents and lower prices. On the other hand, there is a large talent pool of scientists in the U.S. now that are going to be making their way independently of their former employers, but still that is where they have contacts and they will do what they can to leverage those into contracts. They will be more-or-less forced to work for less than they are used to, but I can see a number of outsourcing discovery chemistry companies springing into existence, adding to those that already are in existence. It will be challenging for them too, as they will have to react to pretenders at home and abroad, while the new kids on the block look to establish their reputation and their companies in a challenging and changing world.

Happy New Year

A slightly belated Happy New Year to one and all. I hope you have a good 2010.

I gave myself a little break from the blogosphere for the holiday period, so this is little more than a note to say I am back at the keyboard again. The main stories of the week seem to be about outsourcing in the industry and I should have a post on that particular subject in the very near future, plus a few other subjects that caught my eye.

For now I will remind readers of my Twitter account and LinkedIn profile, plus my email address dperrey at verizon dot net. Not sure if writing it like that really does deter spammers, but it is worth a try.

It’s a Busy Busy Christmas

There are a lot of distractions at this time of year. With all the holiday pressures, it is hard to get your regular work done at its usual pace. But (and this maybe just me) work has a tendency just before a break to turn it up a notch, the to-do list gets a little longer and the urgency for things to get done a little greater. It is funny how your chemistry that refused to work for a month suddenly cooperates and you now have a week before you go on vacation to get somewhere with it.

Actually, I think part of that is just me. I like to take off for a break feeling I had reached a natural place to pause. Sometimes the point you want to reach is a little further down the road than perhaps you might have reached without the added incentive to be done for a spell. Plus you add in the holiday pressures – mailing gifts is a hassle or a long wait in line if you go at the wrong time of day. There is also the desire to go for lunch with friends once more before 2009 is gone for good. Those extra little tasks cut into your time and put added stress on your day.

The truth is that some of these deadlines are self-imposed – sorting out which are really important and which are just you pushing yourself can help you regain some perspective. It will still be there after the break. A little stress is good – slow days at the office are much worse (for me at least) than busy ones, because the day feels a lot longer and less productive when you have little to do. But like a lot of things that we do over the holiday period – moderation is the key.

Merry Christmas, enjoy your winter break and I’m looking forward to 2010.

The Blogging Chemist

Once again, Derek Lowe at In the Pipeline has put me onto an interesting article, this time about chemistry communication and collaboration via the web. The essence of the article is that many sciences make great use of web-based collaboration, but chemistry as a whole lags behind and discusses why this is.

There are many reasons – a lot of chemistry is secret and as a result difficult to talk about, a lot of the work is away from a computer so it does not allow it to be incorporated into the work-flow. Another point is that a lot of chemistry projects are about making something and not working on a theory as such, so are inherently less collaborative. A final point they make is that relatively few chemists are bloggers and it is really this point that I want to discuss further in this post.

I think it would be fair to say that the pharmaceutical industry and chemistry industry have not really embraced social media to the extent other industries have. A few companies have accounts on Twitter and a presence on Facebook. There is a bit more representation on LinkedIn but that really reflects the individuals working at companies that want to network and connect with old colleagues.

Blogs are more a personal undertaking, providing a relatively conversational environment to discuss topics on the mind of the blog creator, often commentary on current events in the industry or personal diaries of life in the labs. For the chemist, a lot of the things we could talk about come under “should we talk about that on the world wide web?” Often their quick reply is negative. So the list of things to talk about shrinks and we talk about other people’s work or in more general terms about trends in the industry.

From a personal standpoint, as one of the supposedly rare chemistry bloggers, starting a blog was a way to talk about my experience as a chemist especially as one looking for employment in these uncertain times. Continuing the blog after employment was found is a way to keep myself engaged with the wider world (also known as looking out for things to blog about) and giving my take on things that are going on, all while keeping my writing skills sharp and keeping up with the developments in social media (a subject I am woefully behind on). The time it takes to create a post is tricky (time is short), but I slot it in, mostly over my lunch break, which I generally spend at my desk anyway (often while the Isco is running and so work is still progressing). Sometimes I wonder how other keep up with daily posts, but I am happy with my one-to-three times a week efforts.

Other blogs clearly incorporate aspects of their work into their blogging – whether it is following kinase inhibitors, interesting synthetic papers or reporting pleasing procedures . And various others, some of which I have links to from here, which is definitely a partial list. So there is plenty of life in the chemistry blogging circuit. Despite our apparent reputation, we do like to talk about our subject.

Peaking into the Drug Pipeline

As a constant during the news stories covering mergers and takeovers between pharmaceutical and biotech companies, people tend to talk about their drug pipeline, how they need to combine their pipelines in order to meet their financial goals for the quarter/year/decade. Often, they talk about how their combined efforts will result in a sruge of new drugs for a variety of diseases and shareholders and patients will rejoice.

Strangely, these optimistic predictions don’t seem to ever quite pan out. But they know what went wrong and the next one, they assure us, will do it.

Well, it turns out that it won’t. Or it hasn’t so far at any rate.

A recent paper appeared in Nature Reviews Drug Discovery by Bernard Munos, from Lilly. It states, basically, that the rate of new drug introduction has remained pretty much constant since 1950 and that the huge amount of money thrown at the problem hasn’t really improved things, especially not to the point where drug companies are producing multiple new molecular entities (NME, basically newly approved pharmaceutical products).

It is a remarkable read. I am still taking it all in. For more discussion, I point you to Derek Lowe’s In the Pipeline (his initial post is here and there are several others) and another blog post by Eric Milgram, who are both doing a great job as commentators.

Danger in Familiarity

As a chemist, I use hazardous materials every day and that is OK because I know they are dangerous so I treat them with the proper handling and respect they deserve. But are we underestimating the danger of some things we use regularly? Possibly a case of familiarity breeds contempt leads to trouble?

The first time you use a chemical, especially one you are aware is dangerous, you take special care. But it is often the case that a successful reaction will be revisited several times, by which time the chemical that you handled so carefully upon that first meeting is an old friend that never did you any harm before.

Clearly there are exceptions to this – I still feel a little nervous whenever I have used sodium cyanide or osmium tetroxide – and I am not suggesting anyone is neglecting their personal protection, just that you might not be treating it with quite the respect it perhaps deserves.

My classic example for this: concentrated acids. They are ubiquitous in laboratories everywhere. Everyone uses them, a standard chemical – and yet I bet a significant number of working chemists own clothing that has an acid spot or two on it somewhere, which is not exactly an indication of all due care being taken. I recall an undergraduate laboratory I did, where I noted to one of the professors that the chemicals we were using we all pretty dangerous. I don’t recall which ones, but I think sodium azide was in there. The professor regarded me with fond concern for my welfare and commented that he felt that the concentrated acids were the most dangerous things in the laboratory.

Another candidate for underappreciated dangers would be that entire cabinet of flammable solvents. We see that fiery symbol on it every day and it has been more years than I care to mention since I saw a bunsen burner in an organic lab, so those should be pretty safe, right? Even disregarding the additional dangers presented by ethers (peroxide formation) and possible carcinogens nestled in with the flammables (I’m looking at you, dichloromethane), the simple danger of fire in an organic lab cannot be overstated. I recall a story (which my Google skils were not able to pull up) where a faulty shelf in a flammable cabinet collapsed, causing a huge fire and destroying the lab. [UPDATE: a colleague knew the answer - it was at Ohio State University - C&E News story here] Less drastic war stories are not uncommon.

What other chemicals do you think are thought too familiar to be dangerous?

Predicting Pharmacokinetics

There are a lot of challenges in drug discovery and medicinal chemistry, but it is safe to say that most of them stem from trying to make these compounds work inside human beings. Not surprising as we are putting small molecules into a highly complex system that no one fully understands and expect them to work to cure what ails without messing anything else up.

Well, no, that is not strictly true. We don’t expect that. We’d like it to happen, but it never does.

As the established wisdom goes, efficacy is easy, but PK is hard. With the cost of developing drugs, it is not surprising that people have tried to come up with some kind of predictor to help point us in the right direction. The most well known in medicinal chemistry circles is Lipinski’s Rule of 5, which even has its own Wikipedia entry. That gives me a warm and fuzzy feeling for some reason. Other examples exist, such as Gleeson’s ADMET rules of thumb. What they share is a relative simplicity and a way to relate what you are trying to achieve to something a chemist in the lab can control – in other words, what changes you can make to your molecule to make it more acceptable.

This came up with me now because, while tiudying my desk (yes, it does occasionally happen), I came across an article out of Pfizer from Ted Johnson on the Golden Triangle to optimize clearance and oral absorption. In the spirit of the previous mentioned, it attempts to bring properties of the molecule (in this case log D and molecular weight) and find trends to indicate how these relate to the important pharmacokinetic properties of clearance and oral bioavailibility. In fact, they did find some trends and call it the Golden Triangle Rule, where the compounds that display the best PK properties fall within a triangular area of a graph of MW against log D, with an apex at MW=450 and log D ~1.5 and a baseline at MW=200 with log D between -2.0 and 5.0. So again, we need low molecular weight compounds of just the right polarity, though it is interesting that a lower molecular weight gives you more leeway on the range of polarity you can get away with. Though the authors do point out there are compounds within the triangle that fail. This is just a guideline, despite the name.

These are all only predictions and the trend of screening compounds for undesirable properties earlier in the drug discovery program will continue, despite how practical results often ruin a perfectly good hypothesis.

Of course, the problem with a lot of these techniques is that in order to reach an optimum molecular weight you have to remove the parts of the molecule that give it its potency, making it perfectly acceptable but also perfectly useless. But that is what makes a medicinal chemist’s life so interesting.