Please, please people: stop using the naive dictionary meaning of words in place of context

I know I’m notorious for complaining about those goofy definitions of atheism (“it just means “not believing in god”, nothing more!”, the superficial mob will say) because the word has acquired much deeper resonances that we ignore at our peril, and has implications far greater than simple rejection of one assertion. But the other word that people love to abuse is “freethought”. The same superficial twits all think it means simply that you’re allowed to think whatever you want (which, it turns out, you can do even in a theocracy) and that it’s a kind of hedonism of the mind in which all things are permissible.

It’s not. It’s a word with a long history, a real meaning, and a greater substance than the poseurs know of. Alex Gabriel does a marvelous job scouring the ignoramuses on the meaning of freethought.

Objections to Freethought‘s place in our masthead are among the laziest, glibbest soundbites our critics have, but more than that display a failure to grasp even the term’s most basic history. Freethought is not ‘free thought’ or uninhibited inquiry – to think so boasts the same green literalism as thinking a Friends’ Meeting House is a shared beach hut or that Scotch pancakes contain Scotch  - though even if it were, it’s silly and inane to assume one’s critics are automatons or say loose collective viewpoints mean dictatorship. Freethought is a specified tradition, European in the main, whose constituents have by and large been countercultural, radical and leftist, everything Condell and cohorts viscerally despise.

I am so fed up with people who say that they understand the meaning of the word “free” and the meaning of the word “thought”, and therefore they understand everything they need to know about “freethought”. And these are often the same people who claim that their tradition is one of knowledge and learning and skepticism, yet they want to replace the complex world of knowledge with a kind of naive literalism.

A philosopher agrees with me

I don’t know whether this is a good thing, or a bad thing, but at least he’s agreeing for a different reason. On the question of whether we’ll someday be able to download brains into a computer, I’ve said no for largely procedural reasons: there is no way to capture the state of all the complex molecules (and the simple ions, either) of the brain in any kind of snapshot, and the excuses of the download proponents are ludicrously ignorant of even the current state of biology. John Wilkins says no for a different and interesting reasons: a simulation (and that’s all a computer version of a person could be) is not the thing itself. The map is not the territory. So even surrendering the idea of a high-fidelity transfer and saying that you’ll just develop a model of a brain doesn’t get you anywhere close to solving the problem of immortalizing “me” in a machine.

Sorry, trans-humanists. I can believe that there can be a post-humanity, but it won’t include us, so I don’t know why you aspire to it. I can sort of imagine an earth transformed by human activities into a warmer, wetter, even more oceanic place that allows more squid to flourish, and it’s even a somewhat attractive future, but it’s not a human transformation.

Some academics in literature apparently have a lady problem

So, so familiar, and so, so tiresome. Professor of literature at the University of Toronto David Gilmour:

I’m not interested in teaching books by women. Virginia Woolf is the only writer that interests me as a woman writer, so I do teach one of her short stories. But once again, when I was given this job I said I would only teach the people that I truly, truly love. Unfortunately, none of those happen to be Chinese, or women. Except for Virginia Woolf. And when I tried to teach Virginia Woolf, she’s too sophisticated, even for a third-year class. Usually at the beginning of the semester a hand shoots up and someone asks why there aren’t any women writers in the course. I say I don’t love women writers enough to teach them, if you want women writers go down the hall. What I teach is guys. Serious heterosexual guys. F. Scott Fitzgerald, Chekhov, Tolstoy. Real guy-guys. Henry Miller. Philip Roth.

Let me guess. He thinks his opinion of woman writers is an objective fact, and not at all colored by his own personal sexism.

Also, what kind of teacher only teaches the work he personally adores? Shouldn’t the point of a literature course be to broaden students’ minds, rather than imprisoning them in the limited scope of the instructor’s prejudices?

What are tumor suppressor genes?

I’m trying to raise money for the The Leukemia & Lymphoma Society, and I promised to do a few things if we reached certain goals. I said I’d write a post explaining what tumor suppressor genes are, while wearing a pirate hat and nothing else, if we raised $5000. Shiver me timbers, I did! And it’s cold!

madnakedpirate

If you want more, go to my Light the Night fundraising page and throw money at it. I’ll write about microRNAs and cancer when we hit $7500. Note that we’re also getting matching funds from the Todd Stiefel Foundation, so join in, it’s a good deal.

There’s a basic principle in biological homeostasis (and it’s also true in cybernetics) that for every process that turns something on, you have an anti-process that turns it off. When you look at what’s going on inside the cell, you’ll often get the impression that it’s spinning its wheels — every protein, for instance, is being degraded at about the same rate that it’s being synthesized. The whole cell is in a state of dynamic equilibrium, in which it might look like the concentration of some protein is constant overall, but when you look closely, individual protein molecules are being constantly made, instantly targeted for destruction, and dismantled…only to be nearly instantly replaced by a duplicate. Everything is in a state of flux, and it looks terribly wasteful, but it means that everything is fluid and flexible and the cell is incredibly responsive to subtle cues.

Last time I wrote about oncogenes, genes that are activators of crucial cellular processes like cell division, and I told you that these play a role in cancer by sending faulty signals that switch on uncontrolled cell division. Given the above principle, you might expect that if there are gene products that turn on cell division, there ought to also be gene products that turn off cell division, a kind of anti-oncogene. And there are! They’re called tumor suppressor genes.

While acting in opposition to oncogenes, tumor suppressor genes typically exhibit another difference in behavior that sets them apart. Cancer causing mutations in oncogenes are usually dominant: that is, the mutation doesn’t just knock out the gene, it has to make a hyperactive gene, and just one mutant copy gone rogue is enough to start switching on cellular activity. Tumor suppressor gene mutations tend to be recessive.

You’ve usually got two copies of every gene. A tumor suppressor works to shut down renegade activity, and a cancer-causing mutation in one is most often simply going to be a mutation that destroys the gene — but since you’ve got two copies, it has a backup. Cancer needs to kill both copies of the tumor suppressor to escape from its anti-tumor actions.

The best known tumor suppressor gene is BRCA1, and it exhibits this behavior. BRCA1 is a good gene — it’s working to protect you from breast cancer. For most of us, every cell in our body has two functional copies of BRCA1. It’s like having two cops patrolling the beat, prepared to fight off any cancer threat, and for cancer to succeed, it has to kill off both. Even one left functional can suppress any effort by the cell to go hyperactive and proliferate. A mutation that knocks out one copy is rare, but two mutations that knock out both are even more rare — it follows two-hit kinetics, which means you multiply the probability of the two events together.

You will occasionally hear about someone being at high risk of cancer because they carry a bad allele of BRCA1 — Angeline Jolie was in the news about this recently. What has happened here is that the person was born inheriting one broken copy of the BRCA1 gene — their cells only have one cop on the beat. They aren’t born with cancer — that one copy of BRCA1 is sufficient to keep them safe — but now they are at much higher risk of an accidental mutation taking out their sole protector than if they had two.

Another well known tumor suppressor gene is Rb, the gene that when mutant can lead to retinoblastoma, or cancers of the eye. It also exhibits two hit kinetics, in that familial retinoblastoma is caused by inheritance of one mutant Rb allele, so that all it takes is one mutation later in life to lead to cancer. Sporadic retinoblastoma, that is retinoblastoma without previous examples in the family, is much rarer, because it requires a first somatic mutation and a second mutation later to take out the second copy.

famRb

Having an enabling mutation in one copy at birth so greatly increases the chance of retinoblastoma that afflicted individuals are likely to have bilateral cancers affecting both eyes, while it’s so rare in sporadic cases that it is almost always unilateral, affecting only one eye.

OK, you understand the principle. Last time, I wrote about the oncogene Ras, which, to make it simple switches on the mitotic machinery and promotes cell division. Does it have an anti-gene product that opposes Ras and switches off cell division?

Of course there is. Several actually. One example: recall that I told you that Ras is activated by binding GTP, and deactivated by converting GTP to GDP, and that Ras itself has GTPase activity and therefore works to switch itself off. There are also tumor suppressor proteins that are called GAPs, or GTPase activating proteins, that enhance Ras’s GTPase activity. One of them, called NF1 or Neurofibromin, binds to Ras and elevates its potency as a GTPase approximately 1000-fold — it basically makes Ras ultra-good at shutting down and doing nothing.

nf1gap

Oncogenes and tumor suppressors are the yin and yang of cellular regulation. Cancer cells often contain hyperactive oncogenes, and have shut down tumor suppressors…which suggests that one strategy for treating cancer is to develop inhibitors of oncogenes, and to repair, replace, or elevate expression of tumor suppressors. And that’s a rather pat explanation of some viable general strategies that of course encounter all kinds of additional complexities.


Donovan S, Shannon KM, Bollag G (2002) GTPase activating proteins: critical regulators of intracellular signaling.. Biochim Biophys Acta 1602(1):23-45.

Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646-74.

Weinberg, RA (2014) Biology of Cancer. Garland Science, New York.

Wincing…and applauding

Oh, man, I can’t endorse this action by Lakota and Dakota women. I think people have a right to do as they please (as long as it doesn’t harm others) on their private property — that goes for worshipping Jesus or Thor, desecrating Bibles, or even flying Nazi flags. (All bets are off if the Nazi sympathizers in Leith, ND, who were trying to stage a takeover of the local government, were flying that flag as representative of the city.)

So I can’t support seizing the Nazi flag and burning it, if it were someone else’s private property. But I still look at this picture and think…whoa, but they are badass.

Lakota and Dakota grandmothers captured the Nazi flag hanging in Leith, ND and burned it. Warriors!

Lakota and Dakota grandmothers captured the Nazi flag hanging in Leith, ND and burned it. Warriors!

There is no contradiction

It’s still driven by greed and pure self-interest. Ayn Rand rests easy in her grave.

In an effort to further Ayn Rand’s message critiquing altruism and promoting the virtue of selfishness, rejecting all moochers who would dare claim your money by tears, the producers of the third Atlas Shrugged movie have launched a Kickstarter campaign asking for donations, predicated on reminding supporters of the critics who have hurt it. As reported earlier this year, despite the free market repeatedly determining it would rather not have any Atlas Shrugged movies, producers Harmon Kaslow and John Aglialoro boldly refused to relinquish their rational self-interests to a world that would dare take their ideas from them, chiefly by not paying to see them. And because of their indefatigable commitment to film Atlas Shrugged: Who Is John Galt? by the fall—and thus propagate its titular character’s manifesto to “never live for the sake of another man, nor ask another man to live for mine”—Kaslow and Aglialoro have turned to asking other men to give them $250,000.

My mistake, it must be racist millennium

Out there in awesomely racist Pennsylvania, Coatesville Area School District superintendent Richard Como and Director of Athletics and Activities Jim Donato were just swapping knee-slapping text messages back and forth, as rednecks are wont to do on phones they barely understand how to use. One catch is that they were using phones issued by their employers, and when their IT assistants went about upgrading their phones, they discovered the messages. And whoa, the messages…don’t read them unless you really want to learn just how racist and sexist state employees in Pennsylvania can be.

Como has retired. Donato has abruptly resigned.

It’s the ugly season, I guess.