The Null Hypothesis

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I REALLY liked this post. I was actually proud of it, and proud of how I explained the null hypothesis. My wife, on the other hand, called it ‘boring.’ Go figure. I am sorry for you folks who don’t like science. Maybe read it during HGTV. Or maybe during reruns of Gilligan’s Island (a show that deserves a blog post of its own). Or read it in sections. Or skip it. This was going to be a lead-in to my post about CTEPH, and why I developed such a rare affliction. Then it got away from me, as often happens. Maybe one of you can use it for a school paper? That would be nice. I feel like Napoleon Dynamite’s friend Pedro right now. I’ve watched the movie a dozen times so I am prettymuch an expert on acting and num-chuks and cool dancing.

Pedro and Napoleon

So a scientist walks into a bar and comes up with a hypothesis, a proposal, or an educated guess about an object of study. Here comes the boring part…. For my PhD my hypothesis was that arginine vasopressin, a systemic hormone, functioned as a neurotransmitter in the brain. I searched for and found receptors for vasopressin, that were involved in autonomic responses. That is a fancy way of saying something that I found fascinating, that the molecule that works on the kidney to increase water reabsorption also acts in the brain, to increase thirst. There is much more… it also increases the sensitivity of the baroceptor response, which constricts blood vessels after hemorrhage. When a person loses blood, receptors in arteries sense it and respond by narrowing blood vessels and increasing the rate and forcer of heart contractions. Vasopressin also increases clotting of the blood by activating receptors on platelets. Is it a coincidence that vasopressin is stored and released by the posterior pituitary, where the only other hormone is oxytocin? Oxytocin aka Pitocin, the hormone/medication used to induce and stimulate labor? Did the two hormones end up in the same gland, in part, because of evolutionary pressure caused by millions of years of blood loss when animals give birth?

I don’t have a clue.

I studied the actions of brain vasopressin: The characterization, solubilization, and purification of arginine vasopressin receptors on rat brain neural membranes. If you like that title, look up ‘Cloning and characterization of cDNA encoding canine alpha-L-iduronidase. mRNA deficiency in mucopolysaccharidosis I dog.’ I know the person who did THAT! And she said it wasn’t all that hard.

My studies were crude by today’s standards. My tool to give me an edge was vasopressin that contained tritium, a radioactive isotope of hydrogen that allowed me to tag those receptors and then count them using a machine that detects radiation, called a ‘scintillation counter’. A molecule of tritium would decay, releasing a beta particle – a type of radiation that won’t pass through skin (but CAN cause problems if enough is swallowed).

When a sample was placed in scintillating fluid, the beta particle would hit another molecule, triggering a cascade of other reactions that created a brief flash of light, which was counted by the machine. I could then use ‘Avogadro’s number’, 6.02 times ten to the 23rd power, to calculate the number of vasopressin molecules in the sample.

Gosh, that sounds hard! But it is just math, calculations, and killing rats, grinding up their brains, and adding stuff. In short I was a ‘grind and bind’ guy. Anyone who works in a machine shop could do it if we walked it through once or twice. Seriously. And again, I am sorry for ‘science mode’. Docs study science for a LONG time. I was fortunate because I found it so interesting, which made reading enjoyable. The people who go to med school and don’t like biochemistry have it very tough.

A ‘null hypothesis’ is the opposite of what a scientist WANTS to prove. So let’s say I want to prove MY idea. MY idea is that vasopressin and oxytocin are in the posterior pituitary, together, because blood loss during birth creates an evolutionary advantage for animals with that anatomy. Evolution is caused by genetic mistakes that are better, in some ways, than the original. The animals with ‘mistakes’ are more likely to survive and reproduce BECAUSE of the genetic mistake. In other words, my hypothesis is that ‘mutants’ have both hormones in the same gland, and that ended up being a good thing for those mutants. The null hypothesis would be that MY IDEA is nonsense. Still with me? Maybe read it again because I may not be explaining it that well.

To prove my REAL hypothesis, I have to try to prove the null hypothesis and fail. I need to ‘disprove’ it. I would look for examples where an entire line of evolution in animals with gross, bloody, labors were not associated with similar pituitary glands. I would look for the opposite, like animals with very easy labors that DID have those pituitary glands.

And I would look at mammalian development to see when and how the posterior pituitary develops. After all, ‘ontogeny recapitulates phylogeny’. That is NOT, btw, a good pick-up line. I’ve tried it. It does NOT work – not at all. It means that the processes that occur in a developing embryo are similar, and summarize, the course of evolution. I know – Why didn’t they just say that??

I already know about the posterior pituitary from anatomy class. Unlike the anterior pituitary, the posterior one develops from brain tissue that sticks out from the brain’s protective membranes in order to release hormones into the blood. Will it be safe out there? Yes, because both halves of the pituitary sit in the ‘Turkish Saddle’ – the sella turcica. People with pituitary tumors are often diagnosed because of a classic pattern of vision loss caused by pressure on the optic chiasma – where nerves from each eye join and cross each other. That’s only if the person has a curious doctor. I know of a person who saw an ophthalmologist multiple times, complaining of a ‘homonymous hemianopsia’. (That line actually works for some reason!). Homonymous menianopsia is the classic pituitary symptom where the person sees only one half – the same half – of the visual field in each eye. A good doc picks it up. Her doctor didn’t. Instead, at each appointment he told her that she must be confused. “It probably happened in just one eye.” She didn’t learn the truth and have surgery (they go through the roof of the mouth and nasal cavities) until her anterior pituitary was destroyed, denying her wish to eventually have children. It is a shame that such complex cases never go to a courtroom.

Jargon… where would we all be without it?

Speaking or sexism, no lie… when I became an anesthesiologist in Wisconsin, the hospital had two locker rooms: the doctor changing room (for men) and the nurse changing room (for women). The Doctors’ Lounge (probably should be capitalized for obvious reasons) was connected to, and part of, the ‘doctors’ changing room.’ The hospital eventually hired a female OB/GYN who never entered the doctor’s lounge – at least not before I left in 2001. But that was Wisconsin in 1992. Now most new doctors in the United States are women.

Where was I? So we try and try and try to ‘prove’ that anterior and posterior pituitary glands MUST develop and stay together. I have ‘prove’ in quotes because one can never prove anything completely. But… then say I find a species that releases vaopressin from the posterior half, but oxytocin is released by the thyroid. That helps ‘prove’ our ‘null hypothesis’, and suggests that the idea that ‘oxytocin and vasopressin are always together’ was a STUPID, STUPID, STUPID idea.

Or, maybe we can’t find a single species or stage of development where oxytocin and vasopressin were released by separate glands,. That would support our original hypothesis, and suggest that the null hypothesis was not supported. It would ‘disprove’ that dumb null hypothesis. “What idiots!!” it would basically say. “You fools!! How DARE you try to cross me with the exact opposite of what I was thinking!! A pox on all of you!!”

Man that’s good stuff. I love science. Although the older I get, the fewer people who appreciate my humor. One of my nurses in San Diego, Xyrus, told me to “read the room” when I joked about being psychotic. He’s not here to help me now.

You folk had no idea science was so fun. And ME? Apparently those six hours without blood flow to my brain unleashed my inner med student. Ever see Jessica Jones?? That was a great series! She was exposed to experiemental chemicals, went into a coma, and came out with superhuman abilities. Plus she can block mind control.

That’s all for now. Next time, I want to propose some hypotheses of my own about ‘why me’? Maybe tomorrow — if I don’t get distracted.


2 Comments

Stephanie · September 20, 2022 at 2:33 am

Well, I found that very un-boring lol. Now if only we could apply the null hypothesis to the way we think about politics and society we’d all be a bit more humble and a lot less certain (less certain is a good thing).

    J Junig MD PhD · September 20, 2022 at 11:25 am

    Good point! I’d have to get into a discussion about bias, but I’m too biased (I’m sure) to go there!

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