SIDS History, Cloning Tip, and LB Problems

Today I Learned:

1) There's a tragic story about SIDS, sudden infant death syndrome, with a valuable lesson for scientists like yours truly.

Back when SIDS was first, uh, I guess "discovered" as a distinct thing, doctors were very confused about it (they still are). One of the first things they tried to do was autopsy a bunch of infants who had died from SIDS. This was before SIDS was *defined* as any infant death still unexplained after an autopsy, so there was hope that they might find some obvious cause.

They found one. It turned out that babies with SIDS had massively enlarged thymuses (thymi?). Researchers (doctors? I'm honestly not sure who did the autopsies) reasoned, reasonably, that something was causing the infants' thymuses to become grossly enlarged, blocking their airways and choking them to death. The treatment? Shrink the thymus. How? Blast it with radiation.

Bear in mind that this was before we knew much about the effects of radiation on biology. Radiation was new and miraculous and had the kind of mystique around it that I would argue quantum mechanics and antioxidants have today. This was back in the day when many scientists thought radiation was a promising way to make crops grow bigger. *Exactly* how they figured radiation would shrink a thymus without also thinking it might be bad for you, I'm not really sure, but the point is that nobody understood that blasting radiation into a baby was a dangerous proposition. Nevertheless, it was, and an estimated 20,000 babies died as a result before they figured out that thymus irradiation was a bad idea (specifically, thymus irradiation tended to cause cancer of the thyROID, which is quite close to the thymus).

But at least the radiation kept thymus swelling down, saving babies from SIDS. Right? Wrong. Here's where the important lesson comes in. I could just go ahead and state it right here, but this story is more entertaining told in the order Radiolab presented it (thanks to Radiolab, by the way!), so I'm going to tell it that way.

To understand what went wrong here, we have to go back to the late 18th century, right around the American Revolution. This was a time of exploding interest in medicine, and it was when the first medical schools were established, at least in America. One of the rather important and rather valuable raw materials required to run a medical school is corpses. Human corpses, in particular. It's hard to properly learn human anatomy without them. So there was a huge demand for cadavers, which was met for quite some time by freelance acquisition specialists known as "resurrectionists". These resurrectionists would find corpses wherever they could, dig them up, and sell them to scientific establishments and medical schools. People soon caught on to this, and the wealthy started investing in resurrectionist-proof burial coffins to protect their bodies. Anyone who couldn't afford it remained at risk. To stop wanton looting of graveyards while ensuring that scientific institutions would still have a steady source of bodies, the government stepped in and established that a) resurrectionists could no longer sell any corpse they could get their hands on, and b) that anybody who died in a poor house would have their body donated to science/medicine.

This worked for quite a while. There's a problem, though. Tenants of poor houses are not random members of the population. Tenants of poor houses tend to be, well, poor. Also stressed, and malnourished. As it happens, poor, stressed, malnourished people tend to have abnormally small thymuses, particularly poor, stressed, malnourished *infants*. This wasn't understood until well after the first SIDS autopsies. When researchers had autopsied SIDS victims, they had been seeing healthy, normally-sized thymi for the first time. The rest is history.

So, today I learned to USE GOOD FRACKING CONTROLS.

2) When designing pieces for cloning, it's worth doing a virtual (i.e., in silico) digest before starting to build the parts. Learned this the hard way. *sigh* More positively, I learned a nice trick when making linear DNA for cloning. If you're making a bunch of linear pieces with the same cloning ends (say, biobrick ends), it can be worth it to extend those ends until you can amplify the piece with a primer that can be shared between all the pieces. This lets you use one pair of primers to amplify all of your parts.

3) More reason to use that M9 minimal media I mentioned yesterday. This from Andy Halleran's comment on my last TIL: "I've heard weird things about people trying to get reproducible promoter strength and variability measurements in LB. Basically it's not reproducible at all unless you use a minimal media and then it's really nice. Especially true if you're driving multiple things under strong promoters. The general idea is that strong promoters hog a huge amount of cellular resource. Put a few of those into one cell and you're siphoning off a large % of metabolic flux and this causes problems." This is good to know! Thanks, obviously, to Andy Halleran.