Saturday, November 24, 2007

21st century festering wounds - cinco

I have been involved with science as boss or worker for 17 years now.

Some days have passed leisurely, because a big paper from my group had come out and I knew that was a guarantee that I'd make the next promotion or get the next grant. At other times I was unable to sleep before I heard whether our latest hypothesis could be backed up with reliable data. Naturally, this was especially true when funding was bad.

But all of that was rubbish compared to this current matter matter of Samuel Vespucci. With every passing hour I was so thankful to the gods or Buddha or the blind forces determined by Newton and friends that I was not an MD.

To be a medical doctor would have caused me to die of a heart attack or some other stress-induced malady. There's something about my mind that makes me able to project my mind into the body of someone in pain. Call it extreme empathy, or whatever you call it, it was so unsettling for me to have seen Sam have another break in the bacterial colony that had spread from his leg back into his bloodstream.

My good friend Dr. Kim was handling that with severe treatments reserved generally for cancer patients--small molecules called "cytokines" were added to Sam's i.v. that provoked his immune system to get to work and kill the bacteria had bought Sam some time, but we all knew that if he lost consciousness, he would be gone. The DNR was signed and none of his family could convince him otherwise.

And so I got to the lab a bit earlier than usual, and hoped we could find something.

As it happened, my graduate student Karen had already been working on analyzing the genes from Sam.

To do this, we used some powerful technology where every gene in the body can be identified in terms of whether it was turned on or turned off. This was done using a small chip, hence the name gene chip.

She was sitting at the computer with a frown. Turning to me, she said, "I'm sorry Andrew, but I think our gene chip has a problem. If you look at all of the genes, they are all pretty consistent between the healthy patient sample, but it seems like a bunch are a bit lower in expression. I think there was some sort of a smudge on the chip that made Sam's cells look like genes were turned off."

"Yeah, but all we have to do is look at the chip and see if that's true. And what do you mean, a bunch? And didn't you run replicates to be sure things like this didn't mess up your experiment?"

"Oh yes, yes, of course", she replied somewhat defensively. I had trained her well enough to do this but things seemed so odd that I had to ask.

"Ok, well, can I see this list of genes, and see what you mean?"
There were over 30,000 genes in the study, and they were listed in terms of how much they were expressed.

This was the list on the screen that she showed me that day:

In every instance, Samuel's cells had for some reason lowered the amount of expression of these genes. It was like those genes were somehow muted compared to cells from you or me.

"So Karen, you think these chips, which run several thousand dollars for each one, were all smudged in the same spot?? Come to think of it, where are those genes on the chip? Are they even in a row????"

"Hm.....let me see." She took the list of genes and organized them based on where they were on the little chip, and suddenly the grouping was lost.

It was then that we realized that those genes weren't in a row on the piece of plastic used to measure them.

"Wait a minute--I'm going about this all backwards....what if you sorted based on location in the human genome?"

With a few clicks and a few more seconds, we realized what was wrong----
The chip wasn't broken, affecting the genes in one row---to our shock, the genes were all in a row, if you looked at where they actually were on one part of one chromosome.

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