The always-outstanding neuroblogger, SciCurious, put up an excellent post overnight on a presentation she saw at the current Annual Meeting of the Society for Neuroscience (SfN) in Chicago. Therein, she wrote about a poster presentation she saw on the relationship between iron, cholesterol, and Alzheimer's disease.
All was quite well until near the end of her post. That is where my writer's block of the last week dissipated and manifest itself as a blogpost-length comment.
This is a lovely post otherwise but you've obviously been drinking if you think you could get away with "an enzyme known as CYP46A1 (yeah, I don't know what that means either)" knowing that I am reading.
CYP46A1 is a member of the cytochrome P450 family of monooxygenases (look for "CYP" you young whippersnapper; there's a whole international allele nomenclature org for this). In fact, neuroscientist god and 1970 Nobel laureate, Julius Axelrod in Bernard Brodie's group first identified this xenobiotic oxidizing system in 1955 - oh, but I'm sorry - you kids don't read papers before 1966 that aren't on PubMed because you can't find the building we used to call a library. Well, rest assured, Dear Weedhopper, that the journal Science has archived their papers online and you can find one of the original papers (Science 121:603-4, 1955 - PDF here) without leaving your computer. Axelrod's original solo paper is in Journal of Pharmacology and Experimental Therapeutics 114:430-8, 1955.
But, I digress.
While we mostly think of P450s as hepatic, adrenal, renal, or pulmonary enzymes, we've known that many other tissues possess P450 activities. CYP46A1 can exist in glia and is otherwise known as cholesterol-24-hydroxylase. The product of this reaction creates a hydroxylated version (at carbon 24 if you can believe it) that cannot cross the blood-brain-barrier as you note.
And while alcohol dehydrogenase is primarily responsible for oxidizing the EtOH coursing through your veins, the higher concentrations you were likely to encounter after writing this post would be handled by CYP2E1. But that all involves things like differences in Km (yeah, I don't know what that means either.)
Have fun and say hello to all of our friends!
Yes, I closed the comment on a happy note so that she knows I'm just giving her a hard time. However, Sci is fortunate that I am not on her dissertation examining committee.
By the way, this excellent biography of Julius Axelrod by Harry Smith details Axelrod's relationship as a technician in Brodie's lab and his pursuit of a PhD at age 42. Axelrod had a tremendous influence on a generation of scientists, including one of my own professors. Smith's article quotes the philosophy of Axelrod:
- Ask simple questions. (But look beyond the obvious.)
- Do something new, but not too new. (Work just left or right of mainstream questions.)
- Talk to people and read! (Then talk more, read more. You never know where the next idea will come from.)
- Science is 99% discouragement. Stay focused!
- Do one good experiment a day.
- Find and exploit your own scientific style.
- Skimming the cream is a good thing. (But do enough science to know that the cream is real.)
- Don't sweat the details. Focus on your hypothesis and don't get swayed by complexity.
- Publish to clarify your thinking and your hypothesis. Nothing more.
That is all.
Ha! Great plug for the library, too. (I think Hopkins can talk about the dangers in not reading the pre-1966 lit). BTW for other institutions, they should probably look on JSTOR for the old Science issues (back to 1880)- that's more likely the place they have access.
Over at Physiology News we have been running an occasional feature where we get eminent scientists to pick a personal "Ten Key Papers in..." (i.e. in their own field). They give a very brief summary of the paper, and why they think it was significant for the field and also for them. Example here (sorry - large PDF).
It has not always proved easy recruiting people to write these, as it is a bit of work, but it presents one kind of solution to the problem of younger folk being unaware of any work in the field less than, say, 5-10 years old. The people that write these perspectives tend to be 50+ so they usually take a kind of "historical development" view.
Another recurring feature we do is "Living History", where we get eminent senior scientists to describe important discoveries they were involved with, or key times in their scientific career - see e.g. here.
Pubmed is sooooo web 1.0. Who uses it anymore?
I do sometimes get nostalgic as I smell the books when I walk past the library though.
One experiment per day? Eeekkk. Takes about 5 years for us.
"Science is 99% discouragement." Thus our rule, before going home set-up a reaction so you have something to look forward to in the morning.
do i detect a little get-offa-my-lawn-you-damn-kids-*fistshake* in that comment? :)
really though, it was an informative addition to Sci's post. and bonus points for Axelrod mention- his influence has been passed down through generations of neuroscientists.
Thanks for posting that, and I love most of Axelrod's aphorisms.
I too appreciate the insight of good, old literature. In my particular field it's Hodgkin and Huxley, or Katz and his colleagues. Just great old stuff. Love it!
Nat, you should check out the first link I posted above - the writer picking his ten favourite ion channel papers, Prof Peter Stanfield, was one of Alan Hodgkin's later grad students. The Hodgkin / Huxley / Katz papers from the 50s really are amazingly prescient about modern channel theories, given how little they then knew.
Another of the facts that sticks with me is that when Hodgkin and Huxley did (and published) the first squid giant axon action potential recordings, in the Summer of 1939, Andrew Huxley was a 22 yr old undergrad student doing the equivalent of a Summer lab job. Of course, the war meant they had to leave off work and only go back and pick up the threads in 1946.
David Colquhoun, whose name might be familiar to you as a patch clamper, said in his obit for Bernard Katz that he reckoned every person starting in electrophysiology ought to read all Katz's published papers from start to finish as an Intro Course.
PS Oops - forgot link for the Katz obit: