We interrupt our scheduled series of posts to bring you the case of the crazy postdoc (for those of you outside the scientific research community, postdoc = postdoctoral researcher, which is the status you attain after receiving your PhD but before anyone wants to pay you a real salary). The San Francisco Chronicle first reported this case on Nov 12. The basic summary of the case is that a UCSF postdoc (Benchun Liu) decided, for no apparent reason, to poison his labmate’s (Mei Cao’s) drinking water. There does not appear to be a motive, but the case is still unfolding and there still seems to be a lot of confusion about the facts. For instance there’s the mysterious identity of the poison. Initially the Chronicle quoted UCSF police Capt. Paul Berlin:
“He told investigators that in both attempted poisonings, he had used a buffer agent designed to control acid in lab solutions, Berlin said.
The agent turns water blue, but Cao drank it anyway, Berlin said.”
Well, pretty much anyone with any chemistry or biology lab experience can make an educated guess that the blue pH buffer is most likely bromothymol blue. Bromothymol blue is used in a lot of loading buffers (think those agarose gels with bright blue bands you might see on CSI when someone is running a DNA test) – it’s yellow when pH is low, blue when pH is high. At first glance bromothymol blue doesn’t seem like the worst thing to digest – after all its use as a pH indicator suggests it’s relatively inert (as in we add it to our solutions because we don’t expect it to do anything but inform us about our solution pH and who cares if your stomach turns yellow if it’s not doing anything bad?). On the other hand we also use bromothymol blue at very low concentrations (i.e. 0.001%), and pretty much anything is toxic at high concentrations. We can check the MSDS (material safety data sheets: the papers that contain all the basic information about the chemicals you work with in lab) to see what’s known about bromothymol blue. This MSDS suggests that ingestion of large doses can cause upset stomachs, this one suggests inducing vomiting immediately after any accidental ingestion. My guess is that no one has really explored what happens when you swallow bromothymol blue because a) it’s a horrible drug candidate so no one’s done toxicity tests and b) no one has ever accidentally swallowed the contents of the very conspicuous, very blue, tube on their bench. Still all the evidence would lead me to believe that, while it’s not good for you, swallowing bromothymol blue is also not the worst thing in the world.
However, this story took a completely different turn on Nov 25, when the Chronicle reported this:
“Liu is accused of trying to poison co-worker Mei Cao, 44, by putting a laboratory chemical, ethidium bromide, into a cup near her work station.”
Ethidium bromide (EtBr) is vastly different than bromothymol blue. For one thing, it’s red not blue (although it dissolves colorlessly into large volumes). It’s also a carcinogen (cancer causing chemical) and teratogen (causes birth defects). In a lab the most common use of EtBr is to visualize DNA. Remember those CSI gels? Well, when you load DNA into them you don’t actually see it running through the gel. You need to put it under a UV light so that it will fluoresce. But DNA by itself is not easily visualizable so we treat the gels with EtBr and visualize the DNA indirectly through EtBr. We can do this because EtBr is an intercalating agent – that means it inserts periodically into DNA strands. That’s great for looking at DNA on a gel. It kind of sucks when it’s intercalating in the DNA in your cell. These insertions will cause a lot of DNA damage (breaks, mutations, etc) that can cause cancer or cell death. In fact when we handle EtBr in the lab we have special disposal for anything that touches it (gloves, pipette tips, gels), because we don’t want it sitting around in landfills.
As an aside and general note of interest, a lot of chemotherapeutic agents are also intercalating agents. Take a look at the structure of EtBr and a doxorubicin, an anticancer drug:
EtBr
Doxorubicin
See those rings in the middle of both structures? Those will give the molecules a nice, flat, shape that allow them to slip into a pocket that is inherent in the famous double helix structure of DNA, causing it to unwind. When dealing with cancer this is an acceptable but risky treatment, because the cancer cells have a greater chance to be effected (since they’re the cells undergoing rapid division and therefore are making lots of DNA). However, any cell is susceptible to this mechanism of action, so in cases where there’s no cancer, all you’re doing is hurting normal cells and possibly introducing cancer causing mutations (I may give cancer treatments their own post in the future as there’s plenty to say about them, independent of this case). But, it’s an interesting point that most cancer drugs are also carcinogens.
Anyway, back to the crazy postdoc case: EtBr is considerably worse than bromothymol blue, and looks nothing like it, making me wonder if it’s confusion by the reporter about the science, or if the postdoc is just that crazy and keeps making up different stories (or used both!). In an even weirder twist on the case, the postdoc has been released while awaiting trial – that seems odd to me in an attempted murder case. Anyway, the whole case is extremely crazy, and we’ll be following it here as updates come. So far, I think the best line (pointed out to me by a friend) comes from the most recommended comment on the sfgate story:
“It’s the urology department, so his motive is obvious. He was pissed off.”
Update 11/30/08: Liu has pleaded not guilty, claiming EtBr is not a poison. He might have a case. See my update post on why EtBr, even with its intercalating properties, is not as bad as you might believe.
Tags: cancer, crazy postdoc, EtBr, UCSF, University of California
