Hypothesis: My headaches are caused by withdrawal from caffeine, a substance that I am addicted to.
Alternative Hypothesis: My headaches are due to some biological cause, and caffeine treats this undefined problem.

Experimental Approach: Attempt to slowly wean myself off of caffeine. If I can do this successfully and remain headache-free for an extended period of time, I will take this as evidence for a caffeine addiction. If I cannot, I will take this as evidence for a biological problem.

Today’s post explains exactly how I plan to do this, in academically painful detail (below the fold).

Figure 1: (A) My current dose is 2 packets per day. Shown are 24 packets, enough for 12 days. I later added 5 packets to the total. (B) Packets claim to weigh 20g, and my scale agrees. Packaging is included in this weight. (C) An empty, seal-able, flexible-plastic container weighs 2g. (D) The first filled container has a mass of 182g, giving 180g powder. (E) The second filled container has a mass of 202g, giving 200g powder. (F) The third and final container weighs 200g, for 198g powder.

I’ve been drinking this instant Vietnamese coffee for a long time now, because it gives me a pretty precise daily caffeine dose and has kept me more headache-free than has normal coffee. I attribute this to high variability in brewed coffee, since the amount of grounds used, water temperature, and brew time vary day-to-day and likely have large effects on final caffeine concentration. So the plan is to use this instant coffee, starting on Day 1 with the amount that I am currently using, followed by 1 gram/day reductions. This will be slow process, allowing me to adjust to the reduced caffeine intake. If during this process I hit quantities that fail to prevent headaches, I will stay on that dose until the headaches stop. If I hit a dose that causes daily headaches for at least 5 days, I will conclude that this is a biological problem.

My current dose is 2 packets per day (Fig. 1A), which should be 40g including the packaging. To more precisely determine the daily amount, I emptied 29 packets (14.5 daily doses) into 3 sandwhich bags and weighed each (Fig. 1). The results are summarized in Table 1, and were remarkably close to the expected value (39.9g actual versus 40g expected).

 
Tomorrow marks Day 0 of The Weaning, which I will begin by measuring out 40g into a tared coffee mug using the scale shown in Fig. 1. I will decrease my daily intake linearly, 1g/day, for the days following as described above, and will follow up this post with the results or with problems that I run into.

I’m writing this post on my new Asus Transformer Prime (with keyboard) and it just feels clumsy as hell. Probably that feeling comes mostly from the Android operating system, which makes text editing a difficult process. And the slowness of switching applications to find links or open other documents also makes this a pain. Perhaps I will get used to it and even begin to like this system over time, but for now I cannot recommend that anyone who wants to do any serious mobile writing (or coding) get one of these things. It seems you’re much better off with a small laptop.

While I was working away at WashU, preparing for graduate school, I imagined myself as a grad student. In that imagination land I was working my ass off, learning all kinds of things, and sharing every bit of that with others via this platform. My work would be totally open. In reality, I am doing only those first two things.

Every couple of days I have an awesome research experience or an interesting new idea and come home planning to write about it. Then I start thinking about how I can present the experience while maintaining the proper level of censorship. Perhaps unsurprisingly, my motivation always quickly evaporates. You may be wondering: why is there any censorship required at all?

Well, it turns out that biological research must remain shrouded in secrecy for at least two major reasons: [1] Just like in any other profession, there are charlatans, thieves, and liars to avoid; and [2] biological research results are potentially worth huge mountains of cash. I’m still hoping that most biological scientists really do fit my ideal image of a Scientist, but the problem is that it only takes a few jerks to make life difficult for everyone else.

There is a lot at stake for researchers, as a lot of money and time is sunk into any project. So if some other group manages to do the same or similar work, and get published first, then much can be lost. Fear of outright idea-theft is one of the huge problems, but the more surprising one is that competing researches don’t want to give each other a leg up by sharing information because sharing leads to reduction or even loss of credit. If you share, your cool idea might end up becoming a novel tool used in someone else’s Nature paper instead of your own. And then you have more trouble getting funding, and students, and tenure…

So the funding system necessarily leads to closed science, which would be true even without the explicit jerks. And then money gets involved on the other side of discovery. Universities, companies, and researchers are patenting the crap out of new biological discoveries. Mutant proteins, dead viruses, synthetic compounds, techniques to synthesize or purify natural compounds, plasmids, and so on and so on. Most of these things aren’t worth much (except for knowledge-value) and so their defenses just end up making life a little more difficult. Others are hugely useful, but are better left to companies anyway (pharmaceuticals or complicated and expensive processes, for instance). Others still are hugely useful, but only for research purposes, and have no business being tied to business. For example: plasmids (circular DNA containing a handful of genes).

I have been building a plasmid for the past few weeks (for my secret research project) and ran into a totally unexpected problem. I wanted a certain fluorescent protein in my plasmid, and we have several in the lab on different plasmids that we have gotten from other labs or companies. For those unfamiliar with cloning (the molecular kind, not the sheep kind), it’s actually a rather routine process to stick a bunch of genes together into a plasmid. In order to get enough copies of a gene to efficiently construct one of these things, a researcher will use PCR. This awesome technology lets you go from a few copies of a gene to billions (literally) in a few hours. You can PCR any gene you want, so long as you know its sequence.

So my plan was to find the fluorescent protein gene from one of our plasmids, make a bunch of copies of it by PCR, then stick it into another one of our plasmids. Simple. But then it turns out that many of our plasmids  have Material Transfer Agreements (MTAs) attached to them, and that each MTA has different requirements for what I can and cannot do with the plasmid’s components. One plasmid has three genes, each “licensed” by a different university! One of the things the MTA prevents me from doing, for example, is to make any changes to the fluorescent protein gene from one of these plasmids. This actually sucks a lot, because that was something that I needed to do. And this requirement was by a university. I understand and expect that kind of behavior from a company, as companies exist to make money in whatever way possible. Companies aren’t supposed to have ethics, or have a primary goal of advancing human knowlege. But universities are supposed to have both of those things.

In the end, I just went with a probably-slightly-crappier fluorescent protein that, I hope, is not under an MTA. And it looks like it is doing what I designed it to do. So there’s that.

In conclusion, it looks like my relationship with biological research will become the same as my relationship with software: I’ll make my work as open as I can, hope that others do the same, and generally use free-and-open slightly-crappier versions of expensive-and-closed things (whether those things are plasmids or office software).

Hopefully the likely-more-complex reality turns around again so that I will find myself back at idealism. I expect that the process of publishing my first paper (whenever that happens) will reveal a lot…

A CSS file is just a text file, at MOST a few kilobytes.

In other news, you can get 20 gigabytes of extra space from Google for $5/year…

While a total ripoff, I was tired of WordPress’ themes never being quite right, and wanted to have the standard theme I use in presentations: maroon and shades of grey.

Still a better deal than text messaging…

I’m working on a post on the awesomeness of Regular Expressions, specifically in Notepad++ and for use on FASTA sequence data. Check back soon (if you care…)!