A weekend at Lake Itasca

I might be distracted for a few days — I’m at our second annual retreat, in which we drag 50 new biology students out to a field station and force them to confront biology. Me, too…I saw a tree! And a squirrel!

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How to read a scientific paper

If you’ve been wondering how the pros do it, here’s a guide to dissecting a science paper.

Don’t be intimidated: it’s a description for how to really take every detail of the paper apart, and it’s a rough outline of what I do before talking about a paper on the blog. But it’s also a little bit of overkill for most papers. I read a lot of papers, and I can’t possibly analyze them as thoroughly as that article prescribes, and I take shortcuts — often, the methods are the most boring part, and I’ll just skim over them rather than doing the thorough diagramming recommended. I’ll go back and cover them thoroughly if I find other parts of the paper provocative, though.

The other course I’m teaching this term is an independent writing course, though, in which the students have to produce a well-researched term paper. I’ll have to send them a note telling them to read this article now.

Just in time for my cancer class

In a few weeks, we’ll be having a discussion of the ethics of cancer research: what is a reasonable intervention in the case of a patient who has no hope of survival? And look at the interesting case that just appeared on my radar: two cancer surgeons who treated brain tumors by deliberately infecting them with bacteria.

Two UC Davis neurosurgeons who intentionally infected three brain-cancer patients with bowel bacteria have resigned their posts after the university found they had "deliberately circumvented" internal policies, "defied directives" from top leaders and sidestepped federal regulations, according to newly released university documents.

Dr. J. Paul Muizelaar, 66, the former head of the neurosurgery department, and his colleague, Dr. Rudolph J. Schrot, violated the university’s faculty code of conduct with their experimental work, one internal investigation concluded.

All three patients consented to the procedures in 2010 and 2011. Two of the patients died within weeks of their surgeries, while the other survived more than a year after being infected.

The premise behind their experimental procedure is probiotics, which immediately throws a warning on the play: there’s a lot of abuse of the concept out there.

Muizelaar and Schrot called their novel approach “probiotic intracranial therapy,” or the introduction of live bowel bacteria, Enterobacter aerogenes, directly into their patients’ brains or bone flaps. The doctors theorized that an infection might stimulate the patients’ immune systems and prolong their lives.

But there are some serious problems here. They didn’t have institutional review and approval of their procedure! That’s not a warning flag, it immediately calls the entire research into question and brings the ethics of the doctors under the microscope. You don’t get to do that.

And then there’s their logic. This is a disease with a median survival of 15 months. Their first patient died less than 6 weeks after the surgery, while the second lived for a year, which the report says “buoyed the doctors and seemed to bolster their theory”. That makes no sense at all — with so few trials they can’t possibly make that kind of assessment. Furthermore, their third patient died of sepsis.

At least it sounds like we’ll have something to talk about. That seems a paltry reward for three people’s deaths.

(via The Tree of Life)

It was the week before classes, and all through the house…

The faculty were melting down. It’s going to be a busy week — I have syllabi to finalize and multiple meetings to attend and cranky fish to fuss over (Morris has toxic water everywhere, full of minerals, and we’re dependent on the RO system to clean up the crap…and they’re shutting it down and flushing it with chlorine this week. What? Yikes!). And then I have other things I’m stuck with.

Tomorrow evening at 7:30 I’m doing a book event on KFAI radio. There goes my afternoon and most of the evening.

This weekend we have our Bridge to Biology program — a huge number of our incoming first year students in biology get taken out to the Lake Itasca Field Station, where we try to lose them in snipe hunts get them enthused about science and biology. I’ll be out there with a microscope and cameras and embryos (I hope, if the RO system doesn’t poison everything).

Oh, yeah, I’m preparing all my class stuff. I’m teaching cell biology and cancer biology this term. Any students reading this? You can get a jump on everything by reading the first couple of chapters of Life by Sadava et al., we shall be marching through the first third of this book in the cell biology class. In cancer biology, we’re going to focus on The Emperor of All Maladies by Mukherjee for the first few weeks, so read that whole thing now. Then once you all know what horrible things cancer does to people, we’ll dive into the mechanisms. You’re fortunate, too: last time I taught this, we used Weinberg’s Cancer Biology text, which is really aimed more at graduate level work; this time around we’re using Hesketh’s Introduction to Cancer Biology. The first two words in the title will make it a less daunting exploration, I hope.

News from the world of fish drudgery

I’ve been away from my office and computer all day doing manual labor. Our little fish facility had a problem: the tanks all drain into these custom built trays (we made them from sheet plastic with PVC angle rods glued and caulked around the edges), which then drain into the reservoir tank. It turns out they leak, not much, just a few drops an hour, but when you multiply that by two dozen tanks and 24 hours 7 days a week, it adds up. The custodians complained.

That constitutes a full scale emergency, you know. As every scientist learns early in their careers, the two groups of people you cannot ever piss off are 1) the department secretaries, and 2) the custodians.

So I bought a bunch of solid strong trays (Christian trays, no less) and a pile of bulkhead fittings, and have spent most of the day with a hole saw punching tidy precise holes in their bottoms and clamping on watertight fittings and adding vinyl tubing for precision delivery of waste water, and then ripping out old trays and putting in the new ones.

Now I’m all damp and sweaty. But now water goes in, and water goes out, and I can account for every last drop, so we’re all good.

Also, by the way, we’re getting steady production of about 50 eggs a day, and I’ve got about a hundred larvae I’m nursemaiding every day, with more on the way. We’re struggling with the science side of things now that the production side seems to be working smoothly.

zebrafishembryos

Embryos at last!

Oh, look: The first embryos from our new and improved fish system!

babyfishies

We only got a handful today, but you can see why. Those are about 3½ hours old, so we collected too late and the little babies’ mommies and daddies had spent the previous few hours assiduously poking around in the marbles sheltering the eggs, and had sucked up their little brothers and sisters in a cannibal feast, as they like to do. We’ll be adjusting our schedules, as developmental biologists often have to do, to do much earlier collections starting tomorrow.

The parents look happy and comfortable, perhaps a little plump after their breakfast of caviar and shrimp, so we expect more tomorrow. Right now we’re raising these little guys at a couple of different temperatures to calibrate our staging adjustments.

Disappointment

I got up early this morning and rushed over to the lab to suck on tanks — danios lay demersal eggs that sink to the bottom of the tank, and you can just siphon them up — and…nothing but fish poop. I have a sad face. It was probably overly optimistic since we only have a few adults yet and they’ve just been plunked into the system, but I had hopes. They look so happy! (Zebrafish visibly respond to stress by going pale, and as soon as these guys hit the tanks their little stripes were vividly dark blue).

Water quality is good, but now I’m channelling my grandmother and starting to fuss over their diet. They need to eat and get fat and good rich fatty food is just the ticket. We’ve got the brine shrimp hatchery bubbling and those should be ready tomorrow, and I’m going to be giving them a range of tropical fish foods. We will plump these little creatures up so they can give me more than just feces to look at in the morning.

We’ve also ordered a couple of defined wild type lines — at $20/pair, so we expect thoroughbreds — so the colony population should climb soon, which will help. Then, observations and experiments and breeding and colony expansion.

You asked, I deliver the fish porn

Since everyone insisted, here’s a photo of our incipient zebrafish system, built by my student Josh.

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What it is is a set of ordinary plastic shelving with some custom built plastic trays to catch water overflow, and then an array of simple 2-3 liter tanks (the smallest size Kritter Keepers, if you must know — you can get them for about $2 each). There is a 110 liter reservoir tank down below, with an immersible pump that can generate a flow of about 1900 gallons/hour, currently greatly throttled down since we only have a few tanks in place. Water is pumped out of the reservoir to two places: 1) towards the ceiling, where the PVC plumbing splits — with valves, we can select to have the water pumped right out to the sink nearby, or to a bypass line that just has the water going up and back down, or in normal operation, to a line that has a big hunk of 3″ PVC pipe packed with bioballs and charcoal for filtering, and 2) to a big bucket of sand for additional filtration. Water is just flowing all over the place here.

Most importantly, the main outflow line is tapped in 3 spots to some irrigation hose leading to six of these nifty little widgets that provide a trickle of water out nine smaller drip lines, which lead to the fish tanks. It’s amazing what you can find in hydroponics gear. If ever Minnesota legalizes marijuana, I could also cycle fish water (mmm, rich & tasty fish poop) into racks of plants and pay for all this stuff.

Here’s a quick and dirty diagram if that explanation doesn’t help. Not that the cartoon will necessarily help, either. Blue circles are valves. Arrows indicate the direction of water flow.

tanksystem

It’s been running for a couple of weeks solid with no problems (I wish I could say the same for the backup system we set up yesterday, which blew gaskets all over the place and made a mess overnight), so we’ve actually put a few fish in there. With any luck, we’ll have embryos this week!

Next phase begins!

We think our fish facility is complete now. We have run it through the fishless cycling process. Now I have to drive 60 miles to get some cheap pet store danios to give it the live test, so I’m going to be offline for a bit.

Once those are thriving and we’re totally confident that everything is going to work, we’ll be ordering a bunch of defined strains and raising those up…and doing our preliminary baseline analyses on the embryos. It’s progress! Science marches on!

World conquest…slightly delayed

When we fired up all cylinders on our majestic fish apparatus today, we discovered…leaks. Nothing tremendous, no sprays of water under pressure all over the place, just a couple of slow, steady, trickling drips. We demand perfection since this will be running 24 hours a day for months on end. So joins are being resealed and retested. Damn science. Damn engineering. Damn plumbing.

Have no fear, we’re just pushing back teleostageddon a few days. But the Daniocalypse will happen! We cannot be stopped now! The device is nearly complete!