Any biologists looking for a job?

My university is hiring for a full-time, tenure-track biology position. Take a look at our job ad:

Duties/Responsibilities: Teaching undergraduate biology courses including cell biology, genetics, electives in the applicant’s areas of expertise, and other courses that support the biology program; advising undergraduates; conducting research that could involve undergraduates; and sharing in the governance and advancement of the biology program, the division, and the campus.

We’re looking for a cell biologist who can also teach genetics…hey, hang on there. Those are the courses I teach! Are the other faculty conspiring to replace me?* It’s a cunning plan they had, then, to put me on the search committee to find a new person to bump me off. They probably thought I’d never expect it if it was happening right under my nose.

Oh, well, I’ll accept my fate gracefully. If you think you’d fit in at a liberal arts university where teaching is your primary responsibility, and you know your cell biology and genetics, apply! We’ll be reviewing applicants starting on 10 November, and will be doing initial phone interviews in early December.

*Actually, it’s more about flexibility. With a small department, everyone needs to be able to wear multiple hats, and I’m the only guy teaching genetics right now, and have been the only guy for over a decade. We like to have a backup for everything. So it’s more like I’m a potential single point of failure.

Silicon Valley creationists

There’s a wave of irrationality sweeping through the over-privileged, ridiculously wealthy world of coddled millionaires and billionaires of Silicon Valley. Some of them seem to think The Matrix was a documentary, and that we’re code living in a simulation, so they like to get together and wank over this idea.

That we might be in a simulation is, Terrile argues, a simpler explanation for our existence than the idea that we are the first generation to rise up from primordial ooze and evolve into molecules, biology and eventually intelligence and self-awareness. The simulation hypothesis also accounts for peculiarities in quantum mechanics, particularly the measurement problem, whereby things only become defined when they are observed.

No, that makes no sense. It exhibits a lack of awareness of modern biology and chemistry; “primordial ooze” is a 19th century hypothesis that did not pan out and is not accepted anymore. This guy is ignorant of what would have to be simulated, and thinks that if we were just created with the appearance of having evolved, he wouldn’t have to understand biochemistry, therefore it would be simpler for him.

And where have I seen that “created with the appearance of X” phrase before?

If we are simulated, it doesn’t make the problems go away. This would have to be such a complete simulation that it includes all of physics and chemistry and biology; that models quantum chemistry and the mechanics of all the chemical reactions that produced us; that includes viruses and bacteria, and includes all the evolutionary intermediates; that has such a rich back story that it would be easier to have it evolve procedurally than to have some magic meta-universe coder generate it as some kind of arbitrary catalog. It just doesn’t work. It definitely isn’t a simpler explanation — because it would require all of the complexity of the universe plus an invisible layer of conscious entities running the whole show.

I’ve also heard that phrase that “creation is a simpler explanation than evolution” somewhere before.

I hesitate to say this because I’m no physicist myself, but I don’t think this Terrile fellow understands physics any better than I do, either. The observer effect does not imply a conscious, intelligent, aware observer, as he claims. The observer effect does not mean that there had to be some super-programmer watching over every physical process in order for it to occur.

I don’t think these yahoos even understand what a simulation is.

According to this week’s New Yorker profile of Y Combinator venture capitalist Sam Altman, there are two tech billionaires secretly engaging scientists to work on breaking us out of the simulation.

I think there must be some scientists somewhere who are milking a couple of gullible billionaires out of their cash.

This makes no sense. If we are, for instance, code programmed to respond to simulated stimuli and emit simulated signals into an artificial environment, how can you even talk about “breaking us out”? We are the simulation. Somehow disrupting the model is disrupting us.

If you don’t think this sounds like febrile religious crapola, let’s let Rich Terrile speak some more:

For Terrile, the simulation hypothesis has “beautiful and profound” implications.

First, it provides a scientific basis for some kind of afterlife or larger domain of reality above our world. “You don’t need a miracle, faith or anything special to believe it. It comes naturally out of the laws of physics,” he said.

Second, it means we will soon have the same ability to create our own simulations.

“We will have the power of mind and matter to be able to create whatever we want and occupy those worlds.”

I’ve written some simulations myself — I have some code lying around somewhere that models the interactions between a network of growth cones. We already have the ability to create our own simulations! These guys are all gaga over increasingly complex video games; those are simulations, too.

The NPCs in World of Warcraft do not have rich inner lives and immortality. They do not have an ‘afterlife’ when I switch off the computer. My growth cone models are not finding meaning in their activities because they are expressions of a higher domain of reality.

I, however, am wondering why the Great Programmer in the Sky filled my virtual reality with so many delusional idiots and oblivious loons. The NPCs in this universe are incredibly stupid.

I’m sure there’s a connection between Trump and fossilized soft tissue

I went down the rabbit hole for a little while this morning. It started here: I was sent a link by Trey Smith about the TRUMP: the COMING LANDSLIDE. ~Ancient Prophecy Documentary of Donald Trump. With a click-bait title like that, I had to start watching the video. And then Trey Smith is mesmerizingly weird: his technique is to stick half his face right into the camera, and make lots of hand gestures with a computer screen in the background. It was effective at first just because his tics and odd movements and emphatic phrasing were engrossing, but I didn’t last long, because there’s no substance there. He seems to think Trump is destined to be president, but his main argument is numerology and ‘because the Bible’ with lots of finger stabbing at the video screen behind him.

So I switched to some of his other videos, and of course he’s a Young Earth Creationist, and he’s very impressed by something that has become a veritable obsession with YECs in the last decade or so: preserved soft tissue in fossil dinosaur bones. And that led him to Mark Armitage.

[Read more…]

If everyone from Yong to Zimmer says it’s true, it must be

You must have already read the tragic news: scientists have determined that I am doomed to die by 2072, when I turn 115, if not sooner. This was figured out by analyzing demographic data and seeing that people seem to hit a ceiling around age 115; the mean life expectancy keeps shifting upwards, but the maximum age seems to have reached a plateau. Carl Zimmer gives the clearest explanation of the methodology behind this conclusion, and Ed Yong gives a good description of the phenomenon of death in the very old.

The ceiling is probably hardwired into our biology. As we grow older, we slowly accumulate damage to our DNA and other molecules, which turns the intricate machinery of our cells into a creaky, dysfunctional mess. In most cases, that decline leads to diseases of old age, like cancer, heart disease, or Alzheimer’s. But if people live past their 80s or 90s, their odds of getting such illnesses actually start to fall—perhaps because they have protective genes. Supercentenarians don’t tend to die of major diseases—Jeanne Calment died of natural causes—and many of them are physically independent even at the end of their lives. But they still die, “simply because too many of their bodily functions fail,” says Vijg. “They can no longer continue to live.”

I agree with all that. I think there is an upper bound to how long meat can keep plodding about on Earth before it reaches a point of critical failure. But I’m going to disagree with Yong on one thing: he goes on to explain it in evolutionary terms, with the standard story that there hasn’t been selection for longevity genes, because all the selection has been for genes for vigor in youth, which may actually have the side effect of accelerating mortality.

This is true, as far as it goes. But I think it’s a different phenomenon, that we’re seeing a physico-chemical limitation that isn’t going to be avoided, no matter how refined and potent ‘longevity genes’ become.

When organized pieces of matter are stressed or experience wear, their level of organization decreases. You simply can’t avoid that. Expose a piece of metal in a car to prolonged periods of vibration and it will eventually fail, not because it was badly designed, but because its nature and the nature of its activity dictates that it will eventually, inevitably break.

Likewise a soap bubble is ephemeral by its nature. The same fluid properties that enable it to be blown doom it — the film will flow over time, it will tend to thin at the top, and eventually it will pop. There’s no way to suspend the physics of a soap bubble to let it last significantly longer, shy of freezing it and defeating the whole point of a soap bubble.

In people, we have a name for this wear and tear and stress: it’s called “living”. All these different things we do that make it worth existing are also fundamentally damaging — there’s no escaping the emergence of an ultimate point of failure.

115 years sounds like a reasonable best estimate from the current evidence. I’d also point out that this does not imply that we won’t find a common critical failure point, and find a way for medical science to push it up a year or five…but every such patch adds another layer of complexity to the system, and represents another potential point of failure. We’re just going to asymptotically approach the upper bound, whatever it is.

That’s OK. I’ll take 115 years. It also helps that it’s going to really piss off Aubrey de Grey and Ray Kurzweil.

I hear that women are made of exotic matter

The Nobel in Physics has been awarded for research on exotic matter, but I think you’d be better off looking for a physicist to explain it. I’m sure it’s good work and that the three scientists are deserving, but I just have to leave this fact on the table.

No Nobel Prize has come close to being equitably distributed by gender, but physics has the worst record of them all. Zero women have won it in the past 50 years. Exactly two women have won it ever.

Again, this does not detract from the accomplishments of Thouless, Haldane, and Kosterlitz, but it does make one wonder how much further physics would have progressed if it didn’t have a culture that discouraged half of humanity from participating.

Can I come in and tell you about the cult of Danio?

Now I know how a Mormon or Scientologist or Baptist feels when some heathen tries to earnestly explain their religion. This video is well done, but gives me a bit of the heebie-jeebies.

I started working on zebrafish in 1979 (I wasn’t the first, or even particularly close — that honor goes to the crew in George Streisinger’s lab), and all through the 80s our lab group had a reputation: at every meeting in every talk, we’d recite what was called the Zebrafish Litany, a listing of all the virtues of this quirky new model organism that nobody else knew much about. In fact, at the Friday Harbor lab meetings in developmental biology there was a kind of tradition where the students would linger in the auditorium late at night and mock the speakers and professors with imitations on the podium, and one year a group made fun of us by having a series of students march robotically to the lectern and recite the exact same series of words. And those words are in this video. How dare the unbelievers speak our catechism!

The video doesn’t quite capture the true nature of the Cult of Danio, though. Everything in it is about how zebrafish research contributes to the study of human diseases, which is a nice perk of the system, but we study the fish because the fish are fascinating, not because we are wannabe human disease researchers. Also, the part where he explains the flaws of the zebrafish, that they have many duplicated genes (so do we) and that they have unique genes not found in humans? Those aren’t flaws.

It is nice to see, though, that our orison is now part of the general public awareness of the zebrafish. That’s why we were saying it so often. Soon, you too shall be a believer. All praise George!

Autophagy wins a Nobel

Well, actually, Yoshinori Ohsumi has won the prize for his work on autophagy, a cellular process you may have never heard of before. The word means “self eating”, and it’s an important pathway that takes chunks of the internal content of the cell and throws them into the cell’s incinerator, the lysosome, where enzymes and reactive chemicals shred them down into their constituent amino acids and other organic compounds for reuse. What makes it interesting is that the cell doesn’t want to just indiscriminately trash internal components; there are proteins that recognize damaged organelles and malfunctioning bits and packages them up in a tidy little double membrane bound vesicle that fuses with the lysosome and destroys them.

At least, most of the time it’s selective. It was first characterized by Ohsumi in yeast, where, if you starve the cells, they start self-cannibalizing to survive. If you use mutant yeast that lack some of the degradative enzymes, they are unable to break down the materials being dumped into the lysosome, and the vacuoles just get larger and larger, making it relatively easy to screen for changes in the machinery for autophagy.

Autophagy in yeast. In starvation-induced (non-selective) autophagy,  the isolation membrane mainly non-selectively engulfs cytosolic constituents and organelles to form the autophagosome. The inner membrane-bound structure of the autophagosome (the autophagic body) is released into the vacuolar lumen following fusion of the outer membrane with the vacuolar membrane, and is disintegrated to allow degradation of the contents by resident hydrolyases. In selective autophagy, specific cargoes (protein complexes or organelles) are enwrapped by membrane vesicles that are similar to autophagosomes, and are delivered to the vacuole for degradation. Although the Cvt (cytoplasm-to-vacuole targeting) pathway mediates the biosynthetic transport of vacuolar enzymes, its membrane dynamics and mechanism are almost the same as those of selective autophagy.

Autophagy in yeast. In starvation-induced (non-selective) autophagy, the isolation membrane mainly non-selectively engulfs cytosolic constituents and organelles to form the autophagosome. The inner membrane-bound structure of the autophagosome (the autophagic body) is released into the vacuolar lumen following fusion of the outer membrane with the vacuolar membrane, and is disintegrated to allow degradation of the contents by resident hydrolyases. In selective autophagy, specific cargoes (protein complexes or organelles) are enwrapped by membrane vesicles that are similar to autophagosomes, and are delivered to the vacuole for degradation. Although the Cvt (cytoplasm-to-vacuole targeting) pathway mediates the biosynthetic transport of vacuolar enzymes, its membrane dynamics and mechanism are almost the same as those of selective autophagy.

Taking out the trash is a vital procedure for cells, as well as for maintenance of your household, and there are cases where autophagy is implicated in human diseases. For instance, mitochondria are intensely active metabolically, and experience a lot of wear and tear. Your cells take old, busted mitochondria, tag them with proteins, and recycle them with a specific subset of autophagy called mitophagy, or mitochondria-eating. Some forms of Parkinson’s disease seem to be caused by defects in the mitophagy machinery, causing defective mitochondria to accumulate in the cell and impairing normal function.

Autophagy also seems to have some complex roles in cancer. It can be a good thing, in that early on if defective proteins and organelles accumulate, they can be sensed and destroyed, so autophagy in that case is a defense against cancer. However, cancer can also subvert that machinery and route the cell’s defenses right into the trash.

But also, autophagy seems to be involved in every step in cancer metastasis. This shouldn’t be a surprise, since autophagy is used to regulate the activity of the cell in all kinds of behaviors.

Schematic illustrating roles of autophagy in the metastatic cascade. Autophagy increases as tumor cells progress to invasiveness and this in turn is linked to increased cell motility, EMT, a stem cell phenotype, secretion of pro-migratory factors, release of MMPs, drug resistance and escape from immune surveillance at the primary site in some tumors. Many aspects of these autophagy-dependent changes during acquisition of invasiveness also likely contribute to the ability of disseminating tumor cells to intravasate, survive and migrate in the circulation before extravasating at secondary site. At the secondary site, autophagy is required to maintain tumor cells in a dormant state, possibly through its ability to promote quiescence and a stem cell phenotype, that in turn is linked to tumor cell survival and drug resistance. Emerging functions for autophagy in metastasis include a role in establishing the pre-metastatic niche as well as promoting tumor cell survival, escape from immune surveillance and other aspects required to ultimately grow out an overt metastasis.

Schematic illustrating roles of autophagy in the metastatic cascade. Autophagy increases as tumor cells progress to invasiveness and this in turn is linked to increased cell motility, EMT, a stem cell phenotype, secretion of pro-migratory factors, release of MMPs, drug resistance and escape from immune surveillance at the primary site in some tumors. Many aspects of these autophagy-dependent changes during acquisition of invasiveness also likely contribute to the ability of disseminating tumor cells to intravasate, survive and migrate in the circulation before extravasating at secondary site. At the secondary site, autophagy is required to maintain tumor cells in a dormant state, possibly through its ability to promote quiescence and a stem cell phenotype, that in turn is linked to tumor cell survival and drug resistance. Emerging functions for autophagy in metastasis include a role in establishing the pre-metastatic niche as well as promoting tumor cell survival, escape from immune surveillance and other aspects required to ultimately grow out an overt metastasis.

It may also affect Crohn’s disease and other inflammatory syndromes. There are mutated proteins associated with Crohn’s that are part of the autophagy pathway; macrophages carrying these mutations deliver bigger doses of inflammatory cytokines when stimulated. Selective autophagy plays a role in regulating the balance of exports from the cell.

Those are the mild diseases caused by defects in this pathway. Look up Vici syndrome, a heritable disorder that causes devastating problems for those afflicted. It’s caused by mutations in the EPG5 gene, which is an important regulator of autophagy.

It’s not just about human diseases, though. Autophagy is universal in eukaryotes: yeast have it, plants have it, animals have it. Genes in the pathway are studied in yeast and nematodes and flies and mice, so this is a common mechanism of regulating the internal traffic of the cell.


Jiang P, Mizushima N (2014) Autophagy and human diseases. Cell Res 24(1):69-79.

Nakatogawa H, Suzuki K, Kamada Y, Ohsumi Y (2009) Dynamics and diversity in autophagy mechanisms: lessons from yeast. Nat Rev Mol Cell Biol 10(7):458-67.

Mowers EE, Sharifi MN, Macleod KF (2016) Autophagy in cancer metastasis. Oncogene doi: 10.1038/onc.2016.333.