Heterochronic parabiosis is the new name for vampirism


As Caine mentions, wealthy Libertarian/Republican scumbag Peter Thiel sees great promise in the idea of parabiosis as a way to treat aging, which is just a little too on-the-nose for an overvalued parasite.

It actually works: some markers for aging are reduced in their effects with infusions of blood from younger donors, and it’s actually a promising technique, but not necessarily as a therapeutic treatment, as Thiel seems to think.

I’m not convinced yet we’ve found a single panacea that works. It’s possible there exist single-point things that could work. I’m looking into parabiosis stuff, which I think is really interesting. This is where they did the young blood into older mice and they found that had a massive rejuvenating effect. And so that’s … that is one that … again, it’s one of these very odd things where people had done these studies in the 1950s and then it got dropped altogether. I think there are a lot of these things that have been strangely underexplored.

The reason it was dropped, I think, is that no one saw a way to carry it forward into useful information. You have to understand that those old studies weren’t about just occasionally giving an old mouse a transfusion of blood from a young mouse — they actually stitched the two mice together in a way that allowed blood exchange between them for long periods of time and got a prolonged exchange of fluids, proteins, and cells. This is not practical as a human therapy, although it is very Mad Max.

But it worked! The old mouse in these experiments experienced multiple benefits.

The old parabiont benefits from not just young blood, but also the young organs: heart, lungs, liver, kidneys, thymus, etc; and removal/neutralization by the young parabiont of negative metabolites, chemokines, etc. These together with improved blood oxygenation, normalized glucose/insulin and cholesterol profile are all likely to contribute to the rejuvenated tissue stem cells.

OK, sign me up! Any of you young bucks like to be surgically attached to me for a while, to give me a little pick-me-up? What if I were Peter Thiel and had some buckets of money to give you for this donation?

There might be some concerns. You ought to be asking, if old blood is so deficient that it could be improved by an infusion of my young blood, and if this actually transfers some effective anti-aging components, what happens to the young mouse? Remember, this is a continuous two-way exchange.

The young parabiont has to maintain an additional aged body with poorly functioning organs, inflammation, ongoing pathologies and perturbed immune responses, which could all contribute to the observed slight decline of the young stem cell responses.

Whoops. There might be a few ethical concerns here. Also, ick.

Also, these old experiments had the problem of sorting out exactly what was causing the anti-aging effect, and that was actually the intent of the experiments — to find potential proteins or cell types or other blood factors that might have a positive effect on older individuals. But the fact that these two mice were physically attached to one another also had complicated social effects.

The old parabiont has a much more stimulating environment when sutured with a young rather than an old partner. In contrast to the old and more sedentary animals, young mice are active and the old partner literally has to tag along. The pheromone landscape also becomes changed in hetero-, as compared to isochronic pairs. It is known that pheromones as well as environmental enrichment enhances, whereas environmental deprivation decreases neurogenesis and neuronal plasticity and “mock parabioses” have not been done to control for this.

So I might get the same effect from participating in youthful activities that I would from becoming a temporary conjoined twin with an 18 year old. So rather than undergoing surgery with me, maybe you should just go dancing with me? Except that even taking a grumpy old geezer to the dance club might have a deleterious effect on the poor young person I am afflicting.

So here’s the summary:

One conclusion from the heterochronic parabiosis studies is that the regenerative capacity of old tissue stem cells can be enhanced by the young systemic milieu; however, an over simplistic vision that using small volumes of young plasma or a “systemic silver bullet” will provide rejuvenation, e.g. one circulating molecule, at this point seems unlikely. Aging is a multi-genic process, the list of potential “silver bullets” is short, and some are oncogenic. Notably, while administration of small volume of young plasma to aged mice improved their cognition, the effects on brain or other tissue stem cells or health span have not been studied. Most importantly, the positive effects of young blood on old are only partial for muscle and the increase neurogenesis is nowhere near levels seen in young brain. Moreover the strong inhibition of young tissue stem cells by the aged systemic milieu in vivo and by old serum in vitro have been repeatedly reported. Summing up what is known, introducing small volumes of young plasma into an old host may not work effectively for enhancing tissue regeneration in the old, unless the inhibitory components of the aged circulation are neutralized or removed. And notably, removal or neutralization of these inhibitory systemic factors is predicted to have a positive effect on tissue repair by itself.

Get it? The parabiosis experiments that Thiel is thrilled by were not and cannot be part of a direct treatment approach; they were part of a series of experiments that hoped to identify blood proteins and cells that modulate the effects of aging. They are a first step to figuring out what is going on, and maybe, far down the road, figuring out how to treat the symptoms of aging. It’s a method for studying causes of aging, not necessarily treating them.

Let’s hope privileged billionaires don’t start strapping up young people to their veins to get imagined rejuvenation on the basis of their misunderstanding of science.

The mystery of the orgasm

Perhaps we need to think more about human psychology. There’s an interesting phenomenon that goes on all the time when people read about evolution: they shoehorn the observations into some functional purpose. There’s just something so satisfying to our minds to be able to say “that thing exists for this particular reason”, and we find it frustrating to say, “there is no reason for it, it’s just chance and circumstance”. It shouldn’t be so, but our minds just try to fit everything into that particular mold.

Now watch: some people — maybe even you — are going to now try and develop an adaptive scenario for why having brains that work that way is a good thing. We try to build a teleological framework around everything, and so it must have a purpose that is being fulfilled, and we rarely stop to think about whether it may be actually limiting us. Maybe it’s not good. Maybe there are other ways that brains can work, and this particular mode of thinking is just a clumsy kludge that resulted from the gradual agglomeration of stuff, mostly unselected, that built up the substrate for human cognition.

A case in point: the female orgasm. There’s a new paper out on the subject, and there are lots of articles being written on it, and they generally start out by pointing out that there’s something puzzling about the phenomenon: shouldn’t it have, you know, a reason for existence? It can’t just be, it has to do something useful for women, or reproduction, or pair bonding, or any of dozens of hypotheses that have been proposed.

So NPR finds closure in an explanation.

A pair of scientists have a new hypothesis about why the female orgasm exists: it might have something to do with releasing an egg to be fertilized.

Nope. That’s not what the paper says. It says it might be a relic of a historical endocrine function, not that it plays any role in women today.

Carl Zimmer sets up a mystery.

An eye is for seeing, a nose is for smelling. Many aspects of the human body have obvious purposes.

But some defy easy explanation. For biologists, few phenomena are as mysterious as the female orgasm.

I would challenge his analogy: what’s so obvious about a nose? Nostrils and an olfactory epithelium, sure — that does have a clear functional role, and we can see signs of selection in the signal transduction apparatus, but why do we have this bony projection with a knob of cartilage on the end? We think we’d look weird without it (like Voldemort), but there’s a wide range of shapes within our species, and related species — chimps and gorillas, for instance — don’t have much in the way of a nose. It doesn’t affect their ability to smell.

(Note: both of those links take you to good summaries. I’m just weirdly conscious of how much we all take adaptive thinking for granted.)

This is the point where I tell you all to go read The Case of the Female Orgasm: Bias in the Science of Evolution by Elisabeth Lloyd, in which she takes apart a collection of adaptive scenarios that simply do not hold up. We ought to face facts: orgasm in women has nothing at all to do with reproduction. It doesn’t facilitate transport of semen, it doesn’t make them want to lie down horizontally, it doesn’t compel them to pair bond with men (since masturbation is a more effective path to orgasm than intercourse, why aren’t we arguing that the clitoris is the devil’s tool to drive women away from men? Oh, some do.)

Fortunately, this new paper by Pavlicev and Wagner, The Evolutionary Origin of Female Orgasm, doesn’t succumb to the fallacy of the spurious adaptive explanation. Instead, it’s following a much more useful evolutionary tradition: everything is the way it is because of how it got that way. Every living thing has a line of ancestry, and we inherit with modification the traits of our lineage, and the necessary way to study these traits, since our ancestors aren’t generally available for examination, is to take a comparative approach. So they do the evolutionary biology thing and ask what functions female orgasm have in related species, and try to infer an ancestral role in pre-humans.

Here, we note that most hypotheses are seeking an explanation for the presence of female orgasm within the human or primate lineage, whether due to direct or correlated effects of selection. Yet we will argue below that female orgasm, as male orgasm, predate the primate lineage, and the orgasm of human females likely evolved from an ancestral and adaptive trait, which might not have all the characteristics of human orgasm and may also have had a different function. We propose that explanations focusing on primate mating system and behavior thus address the primate-specific (or sometimes human-specific) modifications of a previously existent trait rather than its origin (Amundson, 2008). Our focus here will be the question what that ancestral trait may have been. As the lineage-specific modifications or secondary cooption (“exaptation,” in terms of Gould and Vrba, 1982) can take extreme forms under different, internal, or external selective forces, we therefore do not expect to find in animals a female orgasm as we know it in human, but are rather seeking its homologue in other species.

They also place it in the context of more general theories about the basis of the female orgasm.

The field addressing the role of female orgasm is by no means short of hypotheses. The evolutionary hypotheses align in two groups: one group argues that it is not quite true that female orgasm has no effect on reproductive success (e.g., enabling female choice, bonding, etc.), and the other group argues that it may indeed have no reproductive value in the females, but rather its existence is explained as a correlated effect of another selected trait, or a different developmental stage. For example, one well appreciated among the later hypotheses describes female orgasm as a fortunate consequence of the shared developmental basis of clitoris and penis, and therefore a consequence of reproductive necessity of the male orgasm (by-product hypothesis, Symons, 1979). A critical review of the existing hypotheses has been published in Lloyd (2005) and will not be attempted here.

So the two general hypotheses are that it has an as-yet-undetermined reproductive function (this is so far unsupported by the evidence), or that it is a byproduct of other properties. Pavlicev and Wagner are, I think, adding some other nuances to the story, but their explanation is actually orthogonal to those two explanations.

Pavlicev and Wagner point out that induced ovulation is common in mammals, and is probably a basal trait of the clade, although it has been repeatedly gained and lost. It’s an energy saving measure; why should the female spontaneously ovulate all the time, in the absence of an opportunity to become pregnant? We take it for granted — nuns continue to menstruate, after all — but many mammals do not ovulate unless they receive an endocrine signal that announces to their ovaries that hey, you’re actually mating, this might be a good time to drop an egg for fertilization. In these species, the clitoris seems to be the trigger — stimulating it induces an endocrine surge that induces ovulation. So the idea is that humans have female orgasms because our distant mammalian ancestors had all this complex hormonal machinery coupling ovulation and coitus, and we’ve lost the necessity, but the apparatus is still there. We’ve dismantled the factory, but the remnants still make a fine playground.

Another interesting pattern they see is that when ovulation is uncoupled from clitoral stimulation, there is a tendency for the clitoris to waner farther from the vaginal opening. Induced ovulators tend to have the clitoris positioned right near or even within the vaginal opening, but in animals like humans, it’s quite far away and is poorly stimulated by vaginal thrusting. This may be another of those byproducts: the opening of the urethra happens to be between the vagina and the clitoris, so the increasing separation of the clitoris and vagina may be a consequence of increasing the separation of the urethra and vagina.

I do have some slight reservations about the paper, though. One is that the explanation is insufficient. Here’s their diagram of the phylogenetic distribution of induced ovulation.

Phylogenetic distribution of (A) modes of ovulation, (B) the presence of the urogenital sinus (UGS; in basal species: cloaca), and (C) the position of clitoris relative to the vaginal orifice (in, border, out). Note the phylogenetic correlation between spontaneous ovulation with the reduction of the urogenital sinus, and the external position of the clitoris. This correlation is suggestive of an ancestral role of clitoral stimulation for the initiation of pregnancy in induced ovulators and the loss of this function in spontaneous ovulators.

Phylogenetic distribution of (A) modes of ovulation, (B) the presence of the urogenital sinus (UGS; in basal species: cloaca), and (C) the position of clitoris relative to the vaginal orifice (in, border, out). Note the phylogenetic correlation between spontaneous ovulation with the reduction of the urogenital sinus, and the external position of the clitoris. This correlation is suggestive of an ancestral role of clitoral stimulation for the initiation of pregnancy in induced ovulators and the loss of this function in spontaneous ovulators.

Note that our lineage seems to have lost this property at the separation of rodents and primates! One estimate is that this divergence occurred about 96 million years ago, so our ancestors had to have lost the requirement to link clitoral stimulation to reproduction deep in the Cretaceous, yet still maintained the association between clitoral stimulation and orgasm to the modern day.

That retention is still best explained by the byproduct hypothesis — the pleasure circuitry is maintained by ongoing selection for its operation in males, and there’s no purpose to untangling it and removing it from females, and in fact, selecting for anorgasmia in females might have unfortunate reproductive side effects in males.

I’d also suggest that it doesn’t answer another question: why does sex feel good? We have other urges that our physiology doesn’t address by inducing super-charged sensations — I mean, why don’t we have wild orgasms every time we urinate? Why doesn’t my thyroid send ripples of joy through my body when I balance my salt intake? If you’ve ever watched cats mating, you also know that sex for them is more a matter of compulsion than an opportunity to revel in pleasurable sensations by choice. Do salmon enjoy thrashing themselves to death? I might also argue that to some human males sex isn’t a matter so much of feeling good as it is conquest, expressing dominance, and flaunting their social potency to their peers, so there are clearly alternative mechanisms to make sure males mate with females.

I might suggest that the mystery isn’t the female orgasm, but the orgasm, period. But it’s only a mystery if you insist on demanding a direct adaptive explanation for its existence.

Yay! I’m going to live forever!

I’ve got one of those sedentary jobs, and my hobbies are all rather sedentary, too. That’s bad for my health. But now Steven Novella reports on the latest analysis of the effects of exercise, and it’s good news.

The authors looked at the two variables of interest, exercise and sedentary time. Sedentary time includes driving, sitting at a desk, watching TV, and similar activity. Moderate exercise could be just taking a brisk walk, and they mostly considered the total time of exercise.

Not surprisingly, they found that exercise was associated with decreased risk of death from all causes in the 14 year follow up period, while time spent being sedentary was associated with increased risk of death.

But then they also looked at people who had sedentary jobs and hobbies, but also exercised. They found a decreased risk of death in this group. In fact, the risk of death in this group was lower than for those who did not have sedentary habits, but also did not exercise.

That describes me exactly. For the past year or two, I’ve been ramping up my exercise program, and now walk about 5 miles a day, and this is confirmation that I’ve got “decreased risk of death”.

I just need news that there’s something to offset my bad genetics next. I’m hoping that drinking beer and eating chocolate cake might do something to patch up some ugly genes.

Stop teabagging science, Scott Adams


Scott Adams, the cartoonist and professional self-promoter, is undermining his brand and marketing himself poorly, again. He is complaining about the DNC in ways that demonstrate that he’s an insecure man and profoundly ignorant.

It’s all about the men, don’t you know.

But if you’re an undecided voter, and male, you’re seeing something different. You’re seeing a celebration that your role in society is permanently diminished. And it’s happening in an impressive venue that was, in all likelihood, designed and built mostly by men. Men get to watch it all at home, in homes designed and built mostly by men, thanks to the technology that was designed and built mostly by men. I mention that as context, not opinion.

Don’t thank technology, guy. Thank sociology for the fact that men build and design things, while women and minorities are relegated to serving the dominant white men, and thereby have their roles diminished. Being the beneficiary of a long history of discrimination does not make you a better person. If you actually worked with women, rather than sitting alone drawing cartoons designed to prove your point, you’d know that they are just as capable as men.

But it takes a special kind of wanker to see other people getting their due and think that acknowledging other people’s achievements somehow diminishes your own. Scott Adams must be fun at children’s birthday parties; he probably goes around reminding the kids that he has birthday parties, too, and he’s had more of them and they’re better than this stupid party.

I’m especially peeved at Adams’ continuing abuse of science, though. This is not science.

I watched singer Alicia Keys perform her song Superwoman at the convention and experienced a sinking feeling. I’m fairly certain my testosterone levels dropped as I watched, and that’s not even a little bit of an exaggeration. Science says men’s testosterone levels rise when they experience victory, and drop when they experience the opposite. I watched Keys tell the world that women are the answer to our problems. True or not, men were probably not feeling successful and victorious during her act.

Apparently, we men are terribly hormonal, and dependent on our testicles to appreciate happiness. Unfortunately, Adams has taken a tiny grain of scientific evidence and mangled it into something unrecognizable.

First, we have to appreciate the fact that testosterone levels fluctuate a lot. There is circadian and seasonal variation, and also individual variation in testosterone levels.

Male   Female  
Age: T Level (ng/dL): Age: T Level (ng/dL):
0-5 months 75-400 0-5 months 20-80
6 mos.-9 yrs. <7-20 6 mos.-9 yrs. <7-20
10-11 yrs. <7-130 10-11 yrs. <7-44
12-13 yrs. <7-800 12-16 yrs. <7-75
14 yrs. <7-1,200 17-18 yrs. 20-75
15-16 yrs. 100-1,200 19+ yrs. 8-60
17-18 yrs. 300-1,200    
19+ yrs. 240-950    
Avg. Adult Male 270-1,070 Avg. Adult Female 15-70
30+ yrs. -1% per year    

I almost certainly have much lower levels of testosterone now than I did when I was 20, but I don’t know, because I’ve never had them measured. Scott Adams did not have his testosterone levels measured, either, but he felt free to claim a nonexistent measurement validated his perception of how science works. Also, despite likely declines in my testosterone over the years, I’m happier and more secure and confident now than I was in my 20s; it’s almost as if environmental circumstances have a greater effect on the cognitive perception of my life.

But also, Adams left out a significant point in those scientific studies, as explained in this paper: Effects of victory and defeat on testosterone and cortisol response to competition: evidence for same response patterns in men and women.

In this study, we report evidence from sport competition that is consistent with the biosocial model of status and dominance. Results show that testosterone levels rise and drop following victory and defeat in badminton players of both sexes, although at lower circulating levels in women. After losing the match, peak cortisol levels are observed in both sexes and correlational analyses indicate that defeat leads to rises in cortisol as well as to drops in testosterone, the percent change in hormone levels being almost identical in both sexes. In conclusion, results show the same pattern of hormonal responses to victory and defeat in men and women.

So, if he were correct (he’s not), then all across America men were experiencing a decline in testosterone, while women’s testosterone levels were rising. Since women outnumber men, that translates into a net gain in American T levels!

Please also note that these hormonal effects are not about “happiness”, but about dominance. I know that to the normal clueless guy dominance is equated with happiness, but it’s simply not true — mammalian hierarchical behavior also increases stress, so it’s not as simple as testosterone being the happy chemical. Testosterone also drives feelings we don’t regard as “happy”.

Throughout vertebrate phylogeny, testosterone has motivated animals to obtain and maintain social dominance-a fact suggesting that unconscious primordial brain mechanisms are involved in social dominance. In humans, however, the prevailing view is that the neocortex is in control of primordial drives, and testosterone is thought to promote social dominance via conscious feelings of superiority, indefatigability, strength, and anger. Here we show that testosterone administration in humans prolongs dominant staring into the eyes of threatening faces that are viewed outside of awareness, without affecting consciously experienced feelings. These findings reveal that testosterone motivates social dominance in humans in much the same ways that it does in other vertebrates: involuntarily, automatically, and unconsciously.

So maybe watching Alicia Keys also made American men less angry and less arrogant…if the song had the purported effect on testosterone levels, which, I emphasize again, was not measured. Personally, I did not feel threatened or diminished by a woman singing a song, so I don’t have any reason to think my testosterone levels were affected at all…but then, I should not deny Scott Adams his perception of the experience. Maybe he felt totally crushed and defeated by a woman musician and his balls actually shriveled.

The song might have had other positive effects.

Elevated levels of testosterone have repeatedly been associated with antisocial behavior, but the psychobiological mechanisms underlying this effect are unknown. However, testosterone is evidently capable of altering the processing of facial threat, and facial signals of fear and anger serve sociality through their higher-level empathy-provoking and socially corrective properties. We investigated the hypothesis that testosterone predisposes people to antisocial behavior by reducing conscious recognition of facial threat. In a within-subjects design, testosterone (0.5 mg) or placebo was administered to 16 female volunteers. Afterward, a task with morphed stimuli indexed their sensitivity for consciously recognizing the facial expressions of threat (disgust, fear, and anger) and nonthreat (surprise, sadness, and happiness). Testosterone induced a significant reduction in the conscious recognition of facial threat overall. Separate analyses for the three categories of threat faces indicated that this effect was reliable for angry facial expressions exclusively. This testosterone-induced impairment in the conscious detection of the socially corrective facial signal of anger may predispose individuals to antisocial behavior.

So maybe the hypothetical reduction in men’s testosterone levels made them less angry, more sensitive to the social cues of their loved ones, and less antisocial? These sound like good results that are not at all in conflict with happiness!

If the Scott Adams Castration Effect* were real, that would argue that maybe we ought to be broadcasting Alicia Keys everywhere. Maybe more Beyoncé is the path to World Peace.

*The Scott Adams Castration Effect is what I’m calling the fearful sensation of diminishment that some men experience when faced with strong women. The poor man. He’s got it bad.

That’s a very useful quote

Larry Moran cites a great quote from Bill Martin.

Life is an exergonic chemical reaction. It’s the energy releasing redox reaction at the core of metabolism that makes life run, and throughout all of life’s history it is one and the same reaction that has been running in uninterrupted continuity from life’s onset. Everything else is secondary, manifestations of what is possible when the energy is harnessed to make genes that pass the torch.

If you need any of that explained, read Larry’s summary.

I teach cell biology, and that could be the theme for the entire class. The course has a strictly enforced prerequisite of general chemistry, and students typically take it concurrently with organic chemistry. I tell them from day one that this is basically a chemistry course that focuses narrowly on the reactions that go on inside cells, and yes, life is all about electrons getting cycled through reactions that provide the energy that drives other reactions — it’s mostly redox chemistry.

Focusing on that is also helpful in understanding the origins of life, because it really is just a transition from geochemistry to self-contained bags carrying out continuous redox reactions. I teach the first half-year of our second year core curriculum, and we really do emphasize metabolism and the energetics of the cell, while the second half is basic molecular biology that focuses on DNA/RNA. That makes a lot of sense, because as we all know, metabolism came first, information came second.

Cancer is old, news at 11

In a mildly interesting discovery, a toe bone from a 1.7 million year old hominin has been found to bear an osteosarcoma. The poor individual would have been suffering with pain when they walked, it might even have killed him (not the toe, but the possibility of metastatic cancer) and it’s suggestive that there might have been some social care for them.


But you know what’s not interesting at all? That cancer has been around for millions of years. That’s old news.

The precise origins of cancer have been a source of debate due, in part, to the scarcity of historical evidence. Possibly the earliest reference to the disease is attributed to the great Egyptian physician Imhotep, who lived around 2600 B.C. In his writings, Imhotep describes an affliction characterized by a “bulging mass in the breast” that was resistant to any known therapies.

Errm, Dogs get cancer. Mice get cancer. Whales get cancer. Reptiles get cancer. Sharks get cancer, despite myths you may have heard. Insects get cancer.

That an old mammal got cancer is not surprising at all. And while the subtitle might claim that the observation “could have important implications for modern medical research”, the article doesn’t say what those implications are. It can’t, because there aren’t any.

I just find myself annoyed that here is a thought-provoking but ultimately anecdotal datum that humanizes our distant ancestors and might have some implications for the history of human social behavior, but it’s getting shoe-horned into the trite and pragmatically false paradigm that it’s a discovery that could lead to the Cure for Cancer. Stop the hype, please.

A tree poll!

I mentioned that one of the dignified trees in our yard was marked for death — we got the detailed diagnosis. It’s Dutch Elm disease. We have some guys coming by on Monday to hack it to death and haul away its dismembered limbs.

But it’s not all sad and grisly news. We’ve also talked to the city, and they’ve given us their list of trees to be planted around town this fall (the number is how many of each they have on hand), and we can get on the list and name a preference.

10) Accolade Elm
10) Acer Sienna Maple
5) Hackberry
5) Deborah Maple
5) Thornless Hawthorn
10) Cathedral Elm
5) Ivory Silk Japanese Tree Lilac
10) Siouxland Poplar
5) Ironwood
5) Bur Oak
10) Northern Acclaim Locust
5) Silver Maple
5) Willow Weeping

We’re going to do some research ourselves, but I thought I’d be lazy and ask all of you readers — which ones do you like and why?