Saturday, December 14, 2013

And on the Vitamin D front...

My latest Vitamin D blood test was perfectly normal. And yes, I've been feeling a lot better. So much better in fact, that I've been a bit surprised by how much energy I have and how much I can get done in a day. I now wonder for how long I had that deficiency.

Serious people

A colleague, here in Denmark, launched (unprovoked) into bashing US higher education, as light conversation at a party. We discussed the serious problems of student debt, lack of public funding, and the very variable standards of education. She had read something that said that US college students were just there to party, take the easiest possible courses, and "not be serious people." The young women, it was reported to me, only stay in school long enough to find a husband. The strongest evidence for the overall lack of seriousness, I was told, is that students spend a great deal of their time taking courses that have no direct connection to their major. The implication was clear: if one actually intends to do something with one's studies, one focuses exclusively on preparing oneself for that something, and no dabbling. Good biology students, Danish biology students for example, take biology and just enough math, chemistry and physics. At this point I mentioned that as a biology major, I also took classes in essay writing, ceramics, psychology, stage management, dance, etc. and that I thought it was time well spent. This was clearly not comprehensible, and the subject quickly changed.

I will not badmouth the Danish educational system, which in many ways is excellent, and certainly in some ways (particularly public funding, affordability and access) is far better than the US system. I will say that Danish students strike me as no more serious, or sober, than their US peers. As foreign as it is to most people here, I remain a believer in the liberal arts education, and I think they could benefit by allowing some breadth to accompany the focus.

To this day, those writing courses improve my manuscripts, and the stage management experience has made it possible for me to organize myself and a new scientific society. The Social Psychology course, taken concurrently with an Animal Social Behavior course, brought me to understand how barriers between social and natural science impede scientific progress, and that the fallow spaces between these fields are often where the most interesting unturned rocks remain. The dance class was, well, a useful diversion at a stressful time, was useful in wooing a very serious wife, and helps me to entertaining our two-year old. Some of my most original biological thoughts have come to me while making not-quite-round pots and not-as-expressive-as-I-had-hoped monsters out of clay. My creativity, a characteristic more than one boss has told me is my most unusual strength as a researcher, was learned by taking more than just biology classes.

So thank you, Bennington College. Bennington's educational philosophy is as fervently opposite to the Danish way of doing things as almost any school in the world. I do admit that quite a few of my peers there did not strike me as "serious people," although I'm fairly certain no one I knew was there just to find a husband1, and that most of these not serious people wouldn't have been all that serious at any school. Most of them have turned out just fine. As crazy, dysfunctional and you-can't-be-serious as Bennington sometime is (getting saner actually2) I'm still glad I went there.3

1If I remember correctly, Bennington's student body was about 70% females, 10% gay males, and 15% taking-full-advantage-of-the-ratio straight males, so the husband hunting would have been challenging.
2 Bennington has a new president. The old dysfunction had many roots, but the animosity between the president and almost everyone else didn't help.

3 This is all just a long-winded way of saying that I've started applying for jobs back in the US, and will be looking for a place with a good liberal arts educational program.

Monday, November 18, 2013

More D

Old dried fruit bits mixed with crumbs of my daughter's favorite crackers, all spilling from a torn, unmarked plastic bag: an excellent find. Pumpkin seeds scattered on the shelf along with some paprika and vegi-broth powder: perfect. The back of the pantry is just the place when the bird-seed runs low. I have these bursts of energy, enough to refill the bird-feeder, before the coughing and the need to clutch the nearest wall return. The antibiotics have basically cleared the mycoplasma out of my lungs and ears, but the underlying virus is still there.

When the vitamin D deficiency was diagnosed, the nurse told me to take 10µg of supplement a day and come back in three months for another blood test. I didn't entirely expect to continue being sick for that whole three months, but that seems to be the result. A friend at work told me he takes 70mg of vitamin D a day, which is 7,000 times as much as I am taking, so I decided to do some research about dosage. He must mean 70µg, as he is still alive. 

Different countries recommend somewhere between 10µg and 30µg per day for a healthy adult, and levels up to 100µg per day are considered entirely safe, and EU guidelines recommend this level for patients with very low serum vitamin D levels (which I have). So my piddling 10µg plus whatever tiny bits I get from my diet (they don't add vitamins to dairy here, and I'm a vegetarian) and the no sunlight I encounter probably isn't alleviating my deficiency all that fast. So I've decided to take dosage into my own hands. I'm going to start taking 50µg per day, and scale back if and when my blood test shows that I have a healthy level. I would need to take thrice that much for several months to risk vitamin D toxicity. 

In the mean time, I will slump against this wall and watch the birds on the feeder. The magpie really likes those paprika-flavored raisins.

Poetry, to the limited extent I understand it, is about conveying more than is said

Mickey mouse/ Band-Aid
Deck chairs

Monday, September 16, 2013

Thinking while sick

Back when I watched TV, which is many years ago, I would sometimes watch Star Trek. My least favorite character was Mr. Spock. My objection to Spock was that he was extremely foolish in a way that he should have been smart enough to recognize and correct. His foolishness was based in his refusal to admit the importance of understanding emotion and psychology. He would respond to any statement about feelings influencing actions with, "That's illogical," without considering the fact that these statements were also true. Feelings do influence behavior, and to deny that fact, or fail to act on it is illogical.

I was thinking about this last night in the context of the placebo effect. The placebo effect is surprisingly powerful, very easy to demonstrate convincingly, and I've never heard a plausible argument for how the physiology behind it works. There is also good evidence for a negative placebo effect, that believing something will harm you can make it somewhat harmful.

This was on my mind because I have been sick for the last two weeks, with a cold bad enough to keep me from getting much of anything done, and people have started to suggest various home remedies that I am sure don't work. However, because of the placebo effect, I wish I did believe they worked. My inherent skepticism keeps me from gaining the demonstrable benefits of almost any worthless snake-oil. On the other hand my previous experience of frequent and lengthy sickness convinces me that I am likely to stay sick, surely contributing to a negative placebo effect.

It was these thoughts, plus snippets of the Norse myths Iris has been reading to me before bed, that I went to sleep. And what a strange pair of dreams I. First, I dreamed I was in a bar or hall with long wooden tables. Some of my deceased male relatives were there, as were many other people I didn't know. I knew I had only been there long ago, as a child. A man at another table stood, called for attention, and pointed at me. "Look who's come back," he announced mockingly, "Why if it isn't Daniel, the heir to a long proud line of atheists!" I was going to argue, but I woke.

Next, I dreamt that my left thumb-nail had gotten very long and ragged. As I tried to cut it, it started to expanded, unfold and then unroll itself, until it was as big as a post card. It had been tightly folded and wrapped, growing into itself. I cut it off amazed that it could have gotten so big and ingrown without my realizing, and at how compactly wrapped it had been. Looking at my thumb I saw a slot under the skin, maybe a half inch deep just above the nail where the furled and folded nail had rested. Inside the hollow there were areas where minute green plants had started to grow, and areas with many small bloody scabs. I was happy to be able to rinse it clear, and with that I again woke, feeling well rested and fully awake for the first time in weeks.

How do I interpret this? I've decided that simply believing that the placebo effect is helping should be enough to cause the placebo effect to actually help, and that something as simple as a dream of cleansing should be enough to trigger this positive cycle. At present, I am not interested in hearing alternative explanations.

Wednesday, February 20, 2013

A strange sort of consolation

Last year about this time I was working feverishly on a grant application to the National Institute on Aging (NIA), one of the National Institutes of Health. The specific grant I and my collaborators applied for is called an R21 (Exploratory/Developmental); it is sort of a starter grant for people who need money to do the background work to develop the proven methods and concepts you need to apply for their main type of grant, the R01. We submitted the application last winter, and got the fairly positive feedback from the scientific committee in the summer. They ranked it as being in the top 13% of applications in terms of scientific merit. Not wonderful, not terrible. By far the best (I am told) of the R21s reviewed by this particular scientific committee. This roughly means that if they funded 13% of the applications (all R##s combined), we would likely get funded.

In the fall we heard that our application had undergone final administrative review, but we didn't get any yea or nay answer until January, after the grant would have started, when they told us that we wouldn't get the grant this year but please improve a few things that the reviewers complained about and resubmit.

In preparing the application last year, I read a blog post saying that applications for R21s and R03s (another smaller grant) were pretty much a waste of time. The way the review process works, they are in direct competition with R01s, which are by their nature more mature projects, and are given 12 pages instead of 6 to make their case. Less money+less space+less mature project= very small chance of a small payoff was the argument. We decided the type of work we were proposing was exactly what the R21 was intended for, and was exploratory/developmental enough to have little chance at an R01, so we would go ahead and just try to beat the odds. (He may have run out on his last three wives, but surely he'll change for me!)

Even this rather fierce looking hawk wouldn't have gotten an R21

As of the beginning of this year, and as of now, all US federal agencies don't know what their budget for the current year is. What do you do when you don't know if you have money to spend? You don't spend it. So it turns out the NIA funding rate for R03s and R21s for this years is a whopping 0%. Yep, every single application for those types of grants was rejected. Some R01s were funded, but not so many. I try not to think of the absurd amount of time I put into writing my 0% chance of success application. We won't be resubmitting our R21 grant this year, and I don't plan to submit more applications to NIH in the near future. I do hope Congress gets their act together some time soon. There are an awful lot of American scientists in Europe these days.

Monday, February 11, 2013

Better measures of tiny bits of living jelly

My student and I had a paper accepted last week. I like this paper a lot. First some official details, then a short story about how the paper came to be.

Forthcoming in "Marine and Freshwater Research" 

The consistent, non-destructive measurement of small proteiform aquatic animals with application to the size and growth of hydra 

Daniel Levitis and Josephine Goldstein

Abstract: Hydra (Cnidaria), the basal metazoan most often studied in cellular, molecular and developmental biology, is difficult to measure because it is small, proteiform and aquatic. To facilitate broader organismal and ecological study of Hydra, we evaluate three methods whereby a polyp's body column can be measured by means of photomicroscopy. The volume, cylindrical surface area and surface area corrected for changes in body shape are all highly repeatable methods (r=0.97) when shape varies little. However, shape changes alter volume and cylindrical surface area. Repeated corrected surface area measures of the same individuals in markedly different positions yield standard deviations that are less than 5% of the mean measured area. This easy, non-lethal means of individual size measurement explicitly accounts for the flexible morphology of a polyp's hydrostatic skeleton. It therefore allows for the elucidation of how growth and size vary over time, age and food intake. We find that hydra change size dramatically day to day, and that while food level influences adult size, it has little effect on the early growth of recently detached buds. Finally, we discuss ecological and biological applications of this method. 

Part of why I like this paper so much is that my student did most of the hard parts, and the reviewers didn't ask for a lot of changes, and the editor (Dr. Russell Death) moved things along quickly and efficiently, so it is the first paper I've published that didn't feel like pulling my own teeth. It is a solid methods paper. It says, "here is a method for doing something that many scientists may want to do, that we didn't know a good way to do before."

In particular, it is a simple way to accurately and easily measure a tiny transparent aquatic animal with no hard parts or consistent shape without harming it.  Take a picture of it and with a bit of simple math calculate its surface area. Simple, elegant, inexpensive, non-invasive, biologically meaningful, everything I hoped it would be.

But the method presented in the paper is a substantially different, and better, method than the one we started out with. In fact, we were almost ready to submit the paper when we changed the method drastically.

I started out just wanting to measure a hydra polyp because it was necessary for another research project. Nobody had a method that worked halfway decently without killing the hydra. A hydra's body, although it shortens and lengthens, bends and twists is almost always roughly a deformed cylinder. So I said, "Hey Josi" (that's my student), why don't we develop a method to measure a hydra by photographing it and estimating its volume as though it was cylinder?" She agreed, and off we went, taking photos of hydra during our whole research project, for almost two years. We finished gathering our data, and found that indeed we could measure hydra this way. It didn't work great, but it kinda worked. You could use it to tell the difference between a really huge hydra and one that was just kind normal. Viola, unimpressive but probably publishable methods paper.

We wrote it up and were pretty close to submitting when I decided to see what hydra focussed papers had come out recently, and found that someone else had just published almost the exact same method in a nice paper with an interesting biological point. Our formulation of that method didn't work any better than hers did, and we had no point beyond "here is how to measure." We couldn't publish the same method again, even if we came up with it independently. After some cursing and self-recriminations for being so slow, I decided to see if it was possible to salvage anything of the methods paper. Josi took another set of photos and I used them to repeatedly adjust my formula, with limited biological reasoning, until something worked better than the formula just published. In fact, one formula I came up with by eyeballing my graphs worked much better than the method just published. So much better that the calculated value hardly changed at all even when the shape of the hydra changed drastically.

Now you are probably saying to yourself that this is blatant cheating. Trying different formulas (perhaps 100 of them) until something gives you the result you want is a pretty sure way to get the result you want, if you are persistent enough. But two things combined to make this not just okay, but beautiful. First, the formula I stumbled upon made obvious biological sense, even before I knew it worked. This formula represents a hydra as a roughly cylindrical bag whose skin stretches as it elongates itself, or folds and ripples as it contracts. In other words, it describes a hydra accurately and reveals something I didn't previously know about the way a hydra moves. Secondly, and as importantly, when I applied the formula to the main data set, which I didn't use to develop the formula, it still gave a highly consistent measurement for any individual, even as the shape of the individual changed. The method in fact works for completely different populations of hydra. You could take two hydra that looked the same size under the microscope and conclusively decide that one was bigger than the other. You could tell how much a young hydra grew each day. You could really measure the buggers, eliminating most of the noise inherent to previous methods.

Still more lovely, the method Josi and I had just developed could make use of the photos and measurements we had already taken, so redoing all our calculations and figures required Josi to write only a few extra lines of code (Thank you Josi, thank you R). We did a little rewriting to compare our method favorably to our other method, blamed attributed the other method on to the person who had just published it, made our biological argument to explain why the method worked, and we had a drastically improved paper ready to submit. There is a lesson in this somewhere about the scientific method.