(Roughly) Daily

Adam Mastroianni on the challenges– and opportunities– facing science…

Randomized-controlled trials only caught on about 80 years ago, and whenever I think about that, I have to sit down and catch my breath for a while. The thing everybody agrees is the “gold standard” of evidence, the thing the FDA requires before it will legally allow you to sell a drug—that thing is younger than my grandparents.

There are a few records of things that kind of look like randomized-controlled trials throughout history, but people didn’t really appreciate the importance of RCTs until 1948, when the British Medical Research Council published a trial on streptomycin for tuberculosis. Humans have possessed the methods of randomization for thousands of years—dice, coins, the casting of lots—and we’ve been trying to cure diseases for as long as we’ve been human. Why did it take us so long to put them together?

I think the answer is: first, we had to stop trusting Zeus.

To us, coin flips are random (“Heads: I go first. Tails: you go first.”). But to an ancient human, coin flips aren’t random at all—they reveal the will of the gods (“Heads: Zeus wants me to go first. Tails: Zeus wants you to go first”). In the Bible, for instance, people are always casting lots to figure out what God wants them to do: which goat to kill, who should get each tract of land, when to start a genocide, etc.

This is, of course, a big problem for running RCTs. If you think that the outcome of a coin flip is meaningful rather than meaningless, you can’t use it to produce two equivalent groups, and you can’t study the impact of doing something to one group and not the other. You can only run a ZCT—a Zeus controlled trial.

It’s easy to see how technology can lead to scientific discoveries. Make microscope -> discover mitochondria.

Clearly, though, sometimes those technologies get invented entirely inside our heads. Stop trusting Zeus -> develop RCTs.

Which raises the question: what mental technologies haven’t we invented yet? What brain switches are just waiting to be flipped?…

On reinvigorating science: “Declining trust in Zeus is a technology,” from @a_m_mastroianni.

Apposite to an issue he raises: “Citation cartels help some mathematicians—and their universities—climb the rankings,” from @ScienceMagazine.

[Image above: source]

* Elizabeth Blackwell

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As we deliberate on discovery, we might send micro-biological birthday greetings to a woman who modeled the attitude and behavior that Mastroianni suggests: Ruth Sager; she was born on this date in 1918. A pioneering geneticist, she had, in effect, two careers.

In the 1950s and 1960s, she pioneered the field of cytoplasmic genetics by discovering transmission of genetic traits through chloroplast DNA, the first known example of genetics not involving the cell nucleus. She identified a second set of genes were found outside of the cell’s nucleus, which, even though they were nonchrosomomal, also influenced inherited characteristics. The academic community did not acknowledge the significance of her contribution until after the second wave of feminism in the 1970s.

Then, in the early 1970s, she moved into cancer genetics (with a specific focus on breast cancer); she proposed and investigated the roles of tumor suppressor genes. She identified over 100 potential tumor suppressor genes, developed cell culture methods to study normal and cancerous human and other mammalian cells in the laboratory, and pioneered the research into “expression genetics,” the study of altered gene expression.

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