Habits

So I’m working in the lab and all the rotavaps on my side of the lab are busy so I go to use the one on the other side. The two on my side are both hooked up to a chiller, but the lone one has a dry ice trap. As a result, this is distinctly the third choice and is not used as much. I’m first to use it today and it needed dry ice, but the water in the bath was low too. So I got a big beaker to refill the bath, added some water. It wasn’t quite enough so I head back over to my side of the lab and refill the beaker to add to the water bath, even though there was a sink right next to the water bath I was filling. So why didn’t I use that sink?

In a word, habit.

It got me thinking about habits and our routines and how we do things.

I am, to an extent, a creature of habit. I like my routine. I see it as a mental check list that gets everything done. If I stray from my usual routine, I might forget to turn on the chiller (for example) which delays the first evaporation of the day. We have by an iterative process worked out the most efficient way to do things on a daily basis. The problem with this is when something disrupts the program, so being able to adapt to the unexpected is necessary, but as chemists working with the ever fickle world of organic chemistry, most of us are used to that as well.

But it occurred to me that the habits are helpful in another way, an important way when doing laboratory work. When things go wrong, you are already doing things right. This is where good habits pay major dividends. That goes from wearing your protective equipment even when you aren’t doing anything particularly dangerous and keeping your lab area clear so a spill doesn’t escalate. Of course, this is also when bad habits come back to bite you, those things you’ve always done and got away with. Adding extra hydrogenation catalyst to push a reaction to completion might be something you can do on a small scale, but when you do that on a multi-gram scale, you have a fire. And if you have a ton of solvent sitting around in your hood then suddenly you have a bigger fire. And if you didn’t bother putting your lab coat on to do this quick little thing, suddenly you have a big problem.

Another good habit to get into is putting things on your blog regularly. Opportunity (or just making the time) has been tricky the last few weeks, but as I believe the song goes, a good habit these days is hard to find.

A Quick Update

Blogging time has been scarce the last few weeks, so I thought I’d give a quick update on where I am now and what’s been going on.

First the best news: my boss’s grant came through and I have funding on my project for a minimum of two years, most likely a full four years. Compared to most, that is serious stability, which I like a lot.

I have to say this makes me a rather lucky fellow; not that there are no job s at all in the Research Triangle, but they are hard to come by, especially if you still want to be doing synthetic chemistry. That I can at least tentatively plan on being here for the longer term is marvelous.

We’ve been busy in a couple of areas, with a new grant we are busy getting things going for that, but also making tool compounds for collaborators and also getting our data organized for publication. I have been good at getting the data but getting it into a form we can publish, especially with the number of compounds, is a challenge. All I can say is thank goodness for ACD software for managing NMR spectra.

Making tool compounds is interesting too. Sometimes it is just literature compounds that the pharmacologist wants and sometimes it is something from our collection that has better properties or that we want to compare with the established standard. But it does generally involve working on a bit bigger scale (multiple gram quantity) which is a nice change from 30 mg of compound being ample. You can see it, you can actually make a nice solid that you can see at the bottom of the vial!

I also got to contribute to another writing assignment, which I suppose where most of my spare time, “blogging time” if you will, went. That was a piece where I thought after I got the subject I would rattle off pretty quickly but then the more I read the more it grew. Don’t think I can really say much more until I know it’s OK, so look out for more about that at a later stage and it might well spawn a number of extra blog posts as well.

A final note: we had a Canada Goose decide that the employee parking lot was a good place for a goose nest this week. That is not quite as crazy as it sounds – there are a lot of trees lining the area – but still fairly unorthodox. Add to that the gander strutting around warning people off with a hiss. It made walking into work a bit more interesting!

Head Shaking Moments

I’m short of time for blogging this week, but a few things have caught my eye and made me shake my head.

A hugely wide-eyed view of the value of a Ph.D., with great comments by ChemJobber.

Sloppiness in preclinical research, a commentary in Nature. I saw this via Pharmalot, who also adds some feedback on the report. My favorite no make that most-head-shaking inducing part was the quote from one of the authors, who had talked about his finding to one of the authors of a paper which he had been unable to reproduce.

I explained that we re-did their experiment 50 times and never got their result. He said they’d done it six times and got this result once, but put it in the paper because it made the best story. It’s very disillusioning.

Disillusioning, indeed.

Another one, again from ChemJobber: C&E News reporting the worst unemployment data changed their headline from the online version when they printed it on paper. A lot of good suggestions for alternate headlines in CJ’s piece.

Some local news: I had mentioned the acquisition of Icagen by Pfizer before. Well, now they have changed their name to Neuventis. Uh huh.

We need a chuckle after that lot, so why not undermine professorial dignity with ChemBark’s look at some portraits? Or seek career advice from a Corellian smuggler?

Most Read in the Journal of Organic Chemistry

I have been getting a series of emails from the ACS journals I follow the most showing the Most Read articles of 2011. I found the one from Journal of Organic Chemistry most interesting.

While I think of JOC as the place for total synthesis and synthetic methodology, there is only one total synthesis in the list (Total Synthesis of Iejimalide B), although there is also a more philosophical discussion of total synthesis by Phil Baran. The majority of articles are of a more generally useful nature, such as a list of chemical shifts for NMR reagents (I have the table taped up in my office), a look at the effective drying of solvents and the evergreen article on flash chromatography by Clark Still.

The synthetic methods have a greater showing, with the ubiquitous reduction amination, hypervalent iodine and trifluoromethylation via copper catalysis. In fact there is another copper catalyzed reaction (an Ullman coupling) but no palladium cross coupling. Is palladium just another discarded reagent now?

The last article that made the list is an oddity, as it is the description of the NanoPutians, more or less a paper describing the drawing of stick figures (in mono-, di- and polymeric forms, no less) with chemical structures.

I suppose the take away here is that if you want your paper widely read, it needs to be practical and generally useful no matter the kind of project your readers are working on. Though that Still’s 1978 paper is still making the “top 10 most read in 2011” is very impressive.

I Wouldn’t Do That New Reaction Today If I Were You

One for Friday the 13th.

A subject that comes up from time to time is that of scientists with superstitions. Is it surprising that supposedly rational scientific people would subject themselves to irrational superstitions? Clearly they do: ChemJobber had a post on this very thing (with some great comments) and before that Nature Chemistry covered it.

I’ve known some reactions that really did seem like you should check the phase of the moon before you ran them. I’ve known people with a lucky separatory funnel (one guy took it with him when he left!). I can’t say that I’ve noticed my reactions working less well on Friday 13th and I do try to dissuade myself from having such foibles, though I share ChemJobber’s preference to not assume a reaction has worked until the NMR is in hand. And it does seem that saying a reaction will be easy is asking for trouble.

It looks like not wanting to tempt fate is a natural instinct though. A TierneyLab column in the New York Times covered it quite well: the reaction to a negative outcome is much greater than the alternative. So if you don’t take your umbrella and it doesn’t rain, you forget about it, but it you get soaked, you remember it vividly. So that becomes an instinct to take the umbrella or else it will rain. Or in other words, it is best to be prepared for the worst.

But good luck with that tricky palladium cross-coupling today anyway.

Merry Christmas!

Blogging will be a little light over the holiday season, but I wanted to take the opportunity to thank you all for reading and to wish you a relaxed and happy Christmas.

Nobel Curmudgeon

The 2011 Nobel Prize for Chemistry will be announced tomorrow and some people around the web seem to be pretty excited about it, including the always entertaining ChemBark who is live-blogging the event. I am sorry to say I don’t share that level of enthusiasm.

I’m not big into awards anyway. I might notice who won the Oscars but I will certainly not be sitting through the broadcast. (“Sitting through” is suggestive, is it not, like it is something to endure rather than enjoy). So there is that strike against it. But like the Oscar winners, I notice the Nobel winners, think “neat!” when I hear what they did (as I am not often au fait with their work prior to the announcement) and then carry on with life. Even when the palladium cross-coupling guys won last year (who’s work I most definitely did not need to look up first), I was pleased for them (especially Heck who had to retire due to lack of funding). But I did not think they were better scientists because of it. Lots of other scientists will never win the Nobel. But so what? Their work is still good and interesting. Official recognition from the Nobel committee is merely icing, albeit icing worth a fair bit of money.

Perhaps I am just a Nobel curmudgeon.

A Decade On

It has been hard to avoid reflecting on what happened in New York and Washington DC 10 years ago. It really is one of the times you remember where you were.

I was at work, the company I worked for (Scynexis) was just over a year old and I had been there for maybe 6 months. All chemistry was in one big lab with offices along one side. I remember coming out of my office heading for my hood when I heard someone say that someone had flown a plane into the World Trade Center. I still remember thinking that sounded like a sick joke. Because it couldn’t possibly be something that really happened. I also remember later that morning, standing with a bunch of other people, watching a television – I don’t even know where it came from – with scenes from the tragedy unfolding.

The world changed that day but it has changed a lot since then too. We’ve really had to put that behind us because there are an ever increasing number of other things to worry about. We were told at the time the terrorists would win if we didn’t just try to live our lives as best we could and so we do, because there isn’t really any other way to go on.

So I took my moment to remember. Now it is time to get on with the rest of our lives.

Lab Wishlist

I have what I need to do my job. There’s always something else though. I found myself wishing today.

What I’d like is something to monitor my rotavap so I can see when it is done. So I know when it is time to get up from my desk and add more solvent or take it off. I don’t know how many times I’ve been about ready to go home, but not until this stuff has had all the solvent removed. I’m imagining a little web cam type thing, with a feed to my computer. I can look to see if it has bumped or if it is actually removing the solvent properly. Anyone else ever done that? Left a flask on the rotavap over a seminar and come back to find it has removed precisely 3 mL out of the 250 mL in the flask. And if I increase the vacuum just a tiny bit, it is suddenly flying off.

And when it is done (but not before) I can spring into action, do what needs to be done and then get back to updating my note book or reading papers or other important business that I conduct from my desk.

Oh, and a way to alert me when my TLC is done. That would be great too.

(and right after I pressed submit on this post, I went into the lab and found my solvent had hardly gone down at all – see how useful this invention would be?)

The Future of Small Molecules

First, a potential-rambling-post warning. Normally, I like to cogitate on a post for a while before writing, forming something akin to a beginning, middle and end. But in this case, i am not quite sure of the structure. I’m going to just write and see where it leads. Hopefully somewhere interesting.

The initial spark for this post came from a suggestion from a coworker. He showed me an article about a man who had received a bone marrow transplant which had effectively cured him of AIDS. The donor is one of those few that is naturally resistant to HIV and the bone marrow transplant effectively passed on this resistance as the patient’s CD4 cells were free of disease. When the transplant was done, it was posited that this might happen, but now, 3 years later, the patient has no detectable sign of HIV in his system.

We are not about to give every AIDS patient a bone marrow transplant, but the goal of actually curing AIDS is beguiling. The drugs available for HIV have been an unqualified success for the pharmaceutical industry, but all of them suppress the virus, not eradicate it. This is a difficult task due to the nature of the virus, as it inserts its genetic code into the DNA of the host cell, so you can’t kill the virus completely without killing all the cells that carry its genetic information. Some progress toward a vaccine has been made, and it starts to beg the question – how much longer will people pay for the pills? How much will things like bone marrow transplants and vaccines hurt pharma profits?

There has generally been a progression of the standard of care for diseases. Perhaps there was once none but rest and prayer, then some vile concoction that might kill or cure. Slowly the quality of the drug got better and things moved on. That is happening in AIDS now, a disease we did not even know about until 30 years ago. With AIDS in particular, the ability to treat the poorest people in the world has long been a problem, with some companies donating or reducing prices for those parts of the world that cannot afford the regimen of pills that people take here in the USA. What I got to thinking about is this: how much more can small molecule drugs do for human health?

Coincidentally, as I was pondering this, everyone’s favorite pharma blogger Derek Lowe posts on the Failure of Modern Medicine. He highlights an article on the Atlantic about this subject and how Alternate Medicine is growing due to regular medicine not meeting our needs. And Matthew Herper at Forbes posted a counterpoint, saying there has been progress in the chronic illnesses like heart disease and cancer, it is just very difficult. Which is true.

The further truth though is that we live much longer than we used to and the main causes of death are what people used to call “old age”, the body slowly breaking down. There are treatments for cancer, cholesterol lowering agents for heart disease. They do some good. But how much more good can they do? Are we not reaching a point where the cost of living a few more months is such a burden on the rest of society that it hardly seems worth it? Or maybe the way forward now is not with small molecules, which can never really be truly without side effects, the work now becoming the domain of the biologic, with the pharmaceuticals we already have doing what good work they already do.

I don’t really have an answer. There are certainly some disease areas where some kind of therapy is needed – recent announcements about successful candidates in HCV show that there are areas that still need some kind of improved therapy and medicinal chemists will have a role to play in that. And maybe there is some advance in the world of cancer therapy that will open up whole new possibilities for medicinal chemistry.

I just can’t help wondering if there is not that much more to find.