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Archive for March, 2011

The Quantum Choice: You Can Have either Sex or Immortality

Tuesday, March 29th, 2011

Note: A long-term study from Northwestern University (not yet in PubMed) has linked participation of young adults in religious activities to obesity in later life. Overhanging waistlines in First World societies undoubtedly contribute to the degenerative illnesses of lengthened lifespan. But it’s important to keep in mind that fat fulfills critical functions. This article, which looks at the other side of the coin, was commissioned by R. U. Sirius of Mondo 2000 fame and first appeared in H+ Magazine in September 2009.

Because of the four-plus centuries of Ottoman occupation, the folklore of all Balkan nations shares a Trickster figure named Hodja (based on 13th century Konyan Sufi wandering philosopher Nasreddin). In one of the countless stories involving him, Hodja has a donkey that’s very useful in carting firewood, water, etc.  The problem is that he eats expensive hay. So Hodja starts decreasing the amount of hay he feeds the donkey. The donkey stolidly continues doing the chores and Hodja, encouraged by the results, further decreases the feed until it’s down to nothing. The donkey continues for a few days, then keels over. Hodja grumbles, “Damnable beast! Just when I had him trained!”

Whenever I hear about longevity by caloric restriction, I immediately think of this story.

But to turn to real science, what is the basis for caloric restriction as a method of prolonging life? The answer is: not humans. The basis is that it appears (emphasis on the appears) that feeding several organisms, including mice and rhesus monkeys, near-starvation diets, seems to roughly double their lifespan. Ergo, reasons your average hopeful transhumanist, the same could happen to me if only I had the discipline and time to do the same –- plus the money, of course, for all the supplements and vitamins that such a regime absolutely requires, to say nothing of the expense of such boutique items as digital balances.

I will say a few words first about such beasties as flies (Drosophila melanogaster) and worms (Caenorhabditis elegans) before I climb the evolutionary ladder. Many organisms in other branches of the evolutionary tree have two “quantum” modes: survival or reproduction. For example, many invertebrates are programmed to die immediately after reproduction, occasionally becoming food for their progeny. In some cases, their digestive tracts literally disintegrate after they release their fertilized eggs. Conversely, feeding a infertile worker bee royal jelly turns her into a fully functioning queen. The general principle behind caloric restriction is that it essentially turns the organism’s switch from reproductive to survival mode.

Most vertebrates from reptiles onward face a less stark choice. Because either or both parents are required to lavish care on offspring, vertebrate reproduction is not an automatic death sentence. So let’s segue to humans. Due to their unique birth details, human children literally require the vaunted village to raise them — parents, grandparents, first degree relatives, the lot. At the same time, it doesn’t take scientific research to notice that when calories and/or body fat fall below a certain minimum, girls and women stop ovulating. It also takes just living in a context of famine, whether chosen or enforced, to notice the effects of starvation on people, from lethargy and fatigue to wasted muscles, brittle bones and immune system suppression, crowned with irritability, depression, cognitive impairment and overall diminished social affect.

Ah, says the sophisticated caloric restriction advocate, but much of this comes from imbalances in the diet –- missing vitamins, minerals, etc. Well, yes and no. Let me give a few examples.

All vitamins except B and C are lipid-soluble. If we don’t have enough fat, our body can’t absorb them. So the excess ends up in odd places where it may in fact be toxic –- hence the orange carotenoid-induced tint that is a common telltale sign of many caloric restriction devotees. Furthermore, if we have inadequate body fat, not only are we infertile, infection-prone and slow to heal due to lack of necessary hormones and cholesterol; our homeostatic mechanisms (such as temperature regulation) also flag. And because caloric restriction forces the body to use up muscle protein and leaches bones of minerals, practitioners can end up with weakened hearts and bone fractures.

Speaking of fat, the brain has no energy reserves. It runs exclusively on glucose. When starved of glucose, it starts doing odd things, including the release of stress chemicals. This, in turn, can induce anything from false euphoria to hallucinations. This phenomenon is well known from anorexics and diabetics entering hypoglycemia, but also from shamans, desert prophets and members of cultures that undertook vision quests, which invariably included prolonged fasting.  So caloric restriction may make its practitioners feel euphoric. But just as people feel they have comprehended the universe while under the influence of psychoactive drugs, so does this practice impair judgment and related executive functions.

So what about those glowing reports which purport to have demonstrated that caloric restriction doubles the lifespans of mice and rhesus monkeys, as well as giving them glossy pelts? Surely we can put up with a bit of mental confusion, even failing erections, in exchange for a longer life, as long as it’s of high quality –- otherwise we’ll end up like poor Tithonus, who was granted immortality but not youth and dwindled into a shriveled husk before the gods in their whimsical mercy turned him into a cicada. And it does seem that caloric restriction decreases such banes of extended human lifespan as diabetes and atherosclerosis. Well, there’s something interesting going on, all right, but not what people (like to) think.

In biology, details are crucial and mice are not humans. In Eldorado Desperadoes: Of Mice and Men, I explained at length why non-human studies are proof of principle at best, irrelevant at worst. Laboratory mice and monkeys are bred to reproduce early and rapidly. They’re fed rich diets and lead inactive lives –- the equivalent of couch potatoes. The caloric restriction studies have essentially returned the animals to the normal levels of nutrition that they would attain in the wild. Indeed, caloric restriction of wild mice does not extend their lives and when caloric levels fall below about 50%, both lab and wild mice promptly keel over, like Hodja’s donkey. In the rhesus studies, lifespans appeared extended only when the investigators counted a subset of the deaths in the animal group they tested.

On the molecular level, much attention has been paid to sirtuin activators, resveratrol chief among them. Sirtuins are a class of proteins that regulate several cell processes, including aspects of DNA repair, cell cycle and metabolism. This means they’re de facto pleiotropic, which should give would-be life extenders pause. As for resveratrol, it doesn’t even extend life in mice –- so the longer lives of the red-wine loving French result from other causes, almost certainly including their less sedentary habits and their universal and sane health coverage. That won’t stop ambitious entrepreneurs from setting up startups that test sirtuin activators and their ilk, but I predict they will be as effective as leptin and its relatives were for non-genetic obesity.

This brings to mind the important and often overlooked fact that genes and phenotypes never act in isolation. An allele or behavior that is beneficial in one context becomes deleterious in another. When longer-lived mutants and wild-type equivalents are placed in different environments, all longevity mutations result in adaptive disadvantages (some obvious, some subtle) that make the mutant strain disappear within a few generations regardless of the environment specifics.

Similarly, caloric restriction in an upper-middle class context in the US may be possible, if unpleasant. But it’s a death sentence for a subsistence farmer in Bangladesh who may need to build up and retain her weight in anticipation of a famine. For women in particular, who are prone to both anorexia and osteoporosis, caloric restriction is dangerous –- hovering as it does near keeling over territory. As for isolated, inbred groups that have more than their share of centenarians, their genes are far more responsible for their lifespan than their diet. So does the fact that they invariably lead lives of moderate but sustained physical activity surrounded by extended families, as long as they are relatively dominant within their family and community.

Human lifespan has already nearly tripled, courtesy of vaccines, antibiotics, clean water and use of soap during childbirth. It is unlikely that we will be able to extend it much further. Extrapolations indicate that caloric restriction will not lengthen our lives by more than 3% (a pitiful return for such herculean efforts) and that we can get the same result from reasonable eating habits combined with exercise. Recent, careful studies have established that moderately overweight people are the longest-lived, whereas extra-lean people live as long as do obese ones.

So what can you really do to extend your life? Well, as is the case with many other quality-of-life attributes, you should choose your parents carefully. Good alleles for susceptibilities to degenerative age-related diseases (diabetes, heart disease, hypertension, dementia) are a great help — as is high income in a developed country with first-rate medical services, which will ensure excellent lifelong nutrition and enough leisure time and/or devoted underlings to make it possible to attend to suchlike things.

Baby, You Were Great!

Saturday, March 26th, 2011

– title of a story by Kate Wilhelm

Everyone who meets me inevitably finds out that science fiction and fantasy (SF/F) occupy a large portion of my head and heart: I write it, read it, review it and would like to see it discard the largely self-imposed blinkers that impoverish it. For a while, Strange Horizons (SH) magazine thrilled and captivated me. So it’s doubly hearbreaking for me to see it regressing into “normality” and losing sight of what made it stand out in the first place.

My relationship with SH has long been ambivalent. I was happy it was a major SF/F venue brought to vibrant life by female founders: Mary Anne Mohanraj and Susan Marie Groppi after her. I was pleased it published many works by women and Others and contained significant numbers of women in its masthead (as editors, not gofers or dishwashers). I was glad it showcased non-famous writers from the get-go and cast its net wide. My second major SF article appeared there when I was relatively unknown in the domain.

However, there were some worms in the tasty apple. One was that SH seemed to have adopted a stance of “science hurts our brains” – perhaps to distinguish itself from the scienciness of Analog and Asimov’s. This was true not only (increasingly) for its stories but also for the non-fiction articles which steered determinedly clear of science, concentrating instead on literary and social criticism. There’s nothing wrong with that, of course, especially when SF/F is still struggling for legitimacy as literature. But other speculative magazines – Lightspeed, for one – manage to include interesting science articles without shedding cooties on their fiction.

So I read SH fiction less and less but continued to browse its columns and reviews. Then in the last few years I noticed those shifting – gradually but steadily. They were increasingly by and about Anglosaxon white men and showed the tunnel vision this context denotes and promotes. The coalescent core reviewers were young-ish British men (with token “exotics”) convinced of their righteous enlightenment and “edginess” along the lines of “We discovered/invented X.”

I caught a whiff of the embedded assumptions that surface when these self-proclaimed progressives relax, safe from prying eyes. One of them recently reviewed a story on his site and characterized its protagonist by the term “cunt”. He used the word repeatedly, as a synonym for “empathy-lacking sociopath”. Having accidentally read the entry, I remarked that, feminism bona fides aside, the term doesn’t ring friendly to female ears and even the canon definition of the term (“extremely unpleasant person, object or experience”) is not equivalent to psychopath. Perhaps not so incidentally, I was the only woman on the discussion thread.

The reviewer’s first response was that only Amurrican barbarians “misunderstand” the term. I replied (in part) that I’m not American, and presumably he wishes to be read by people beyond Britain and its ex-colonies. At that point he essentially told me to fuck off. His friends, several of them SH reviewers or editors, fell all over themselves to show they aren’t PC killjoys. They informed me that US cultural hegemony is finally over (if only), that “cunt” is often used as an endearment (in which case his review was a paean?) and that women themselves have reclaimed the term (that makes it copacetic then!).

So this is the core group that has been writing the majority of reviews at SH for the last few years and is now firmly ensconced not only in SH but also across British SF/F venues. This may explain the abysmal gender percentages of the latter, which haven’t really budged even after the discussions around the not-so Mammoth Book of Mindblowing SF or the handwringings over the Gollancz aptly named Masterwork Series. The recent epic fantasy debate showcased the prevailing attitudes by discussing exclusively works of (repeat after me) white Anglosaxon men. Not surprisingly, the editor of SH just revealed that roughly two-thirds of recent SH reviews were by male reviewers and two-thirds discussed works of male authors, adhering to the in/famous “one-third rule” that applies to groups helmed by men.

People will argue that SH still has “a preponderance” of women in its masthead and pages. That’s mostly true — for now. However, it is significant that the percentages of works by women in SH consistently reflect the ratios and clout of women within each of its departments. Too, it’s human nature to flood the decks with one’s friends when someone takes over a ship. The problem is that, given the makeup of the current editor’s inner circle, an echo chamber is all but assured. To give one example, a new SH column does blurbs of online discussions relevant to SF/F. Although the editor in charge of it asked for input and admitted he got an avalanche of responses, its entries so far have come almost exclusively from members of the in-group.

So SH is inching towards a coterie of white Anglosaxon men as arbiters of value, a configuration Virginia Woolf would have found depressingly familiar. People are fond of repeating that publication ratios reflect the fact that women submit less than men. What I increasingly see at SH are stances that need not be in-your-face hostile to exert a chilling effect. If someone smirks at you constantly, the passive-aggressive condescension will eventually stop you from going to his parties as effectively as if he had explicitly barred you entry (check out The Valve to observe this dynamic at work).

It grieves me to see SH slowly but inexorably become literally a neo-Victorian club. It grieves me that one of the few SF/F venues once genuinely receptive to women’s work is resorting to smug lip-service. Perhaps the magazine is a victim of its success: once women had nurtured it to prominence, men could take over and reap the benefits – a standard practice.

I see developing patterns early, so much so that I often joke I should be called Cassandra, not Athena. Yet this once, for the sake of the genre and the women who painstakingly watered the now-vigorous SH tree, I fervently hope I’m proved wrong. Otherwise, given the attention span of the Internet, a handful of us will wistfully recall (to hoots of incredulous derision, no doubt) that once there was a verdant oasis in SF/F that women created, shaped and inhabited.

Remedios Varo, Nacer de Nuevo (To Be Reborn)

Note to readers: I am aware this will lead to polarizing and polarized views. I will not engage in lengthy back-and-forths, although I made an exception for the expected (and predictable) response by Abigail Nussbaum. People are welcome to hold forth at whatever length and pitch they like elsewhere.

Blastocysts Feel No Pain

Monday, March 14th, 2011

In 2010, the recipient for the Medicine Nobel was Robert Edwards, who perfected in vitro fertilization (IVF) techniques for human eggs in partnership with George Steptoe. Their efforts culminated with the conception of Louise Brown in 1978, followed by several million such births since. The choice was somewhat peculiar, because this was an important technical advance but not an increase in basic understanding (which also highlights the oddity of not having a Nobel in Biology). That said, the gap between the achievement and its recognition was unusually long. This has been true of others who defied some kind of orthodoxy – Barbara McClintock is a poster case.

In Edwards’ case, the orthodoxy barrier was conventional. Namely, IVF separates sex from procreation as decisively as contraception does. Whereas contraception allows sex without procreation (as do masturbation and most lovemaking permutations), IVF allows conception minus orgasms and also decouples ejaculation from fatherhood. Sure enough, a Vatican representative voiced his institution’s categorical disapproval for this particular bestowal. However, IVF has detractors even among the non-rabidly religious. The major reason is its residue: unused blastocysts, which are routinely discarded unless they’re used as a source for embryonic stem cells.

Around the same time that Edwards received the Nobel, US opponents of embryonic stem cell research filed a lawsuit contending that this “so far fruitless” research siphoned off funds from “productive” adult stem cell research. The judge in the case handed down a decision that amounted to a ban of all embryonic stem cell work and the case has been a legal and political football ever since. The brouhaha has highlighted two questions: what good are stem cells? And what is the standing of blastocysts?

Let me get the latter out of the way first. Since IVF blastocysts are eventually discarded if not used, most dilemmas associated with them reek with hypocrisy and the transparent desire to curtail women’s autonomy. A 5-day blastocyst consists of 200 cells arising from a zygote that has not yet implanted. If it implants, 50 of these eventually become the embryo; the rest turn into the placenta. A blastocyst is a potential human as much as an acorn is a potential oak – perhaps even less, given how much it needs to attain viability. Equally importantly, blastocysts don’t feel pain. For that you need to have a nervous system that can process sensory input. In humans, this happens roughly near the end of the second trimester – which is one reason why extremely premature babies have severe neurological defects.

This won’t change the mind of anyone who believes that a zygote is “ensouled” at conception, but if we continue along this axis (very similar to much punitive fundamentalist reasoning) we will end up declaring miscarriage a crime. This is precisely what several US state legislatures are currently attempting to do, with the “Protect Life Act” riding pillion, bringing us squarely into Handmaid’s Tale territory. It is well known by now that something like forty percent of all conceptions end in early miscarriages, many of them unnoticed or noticed only as heavier than usual monthly bleeding. A miscarriage almost invariably means there is something seriously wrong with the embryo or the embryo/placenta interaction. Forcing such pregnancies to continue would result in significant increase of deaths and permanent disabilities of both women and children.

The “instant ensoulment” stance is equivalent to the theories that postulated a fully formed homunculus inside each sperm and deemed women passive yet culpable vessels. It is also noteworthy that the concern of compulsory-pregnancy advocates stops at the moment of birth. Across eras, girls have been routinely killed at all ages by exposure, starvation, poisoning, beatings; boys suffered this fate only if they were badly deformed in cultures or castes that demanded physical perfection.

Let’s now focus on the scientific side. By definition, stem cells must have the capacity to propagate indefinitely in an undifferentiated state and the potential to become most cell types (pluripotent). Only embryonic stem cells (ESCs) have these attributes. Somatic adult stem cells (ASCs), usually derived from skin or bone marrow, are few, cannot divide indefinitely and can only differentiate into subtypes of their original cellular family (multipotent). In particular, it’s virtually impossible to turn them into neurons, a crucial requirement if we are to face the steadily growing specter of neurodegenerative diseases and brain or spinal cord damage from accidents and strokes.

Biologists have discovered yet another way to create quasi-ESCs: reprogrammed adult cells, aka induced pluripotent cells (iPS). However, it comes as no surprise that iPS have recently been found to harbor far larger numbers of mutations than ESCs. To generate iPS, you need to jangle differentiated cells into de-differentiating and resuming division. The chemical path is brute-force – think chemotherapy for cells and you get an inkling. The alternative is to introduce an activated oncogene, usually via a viral vector. By definition, oncogenes promote cell division which raises the very real prospect of tumors. Too, viral vectors introduce a host of uncontrolled variables that have so far precluded fine control.

ESCs are not tampered with in this fashion, although long-term propagation can cause epi/genetic changes on its own. Additionally, recent advances have allowed researchers to dispense with mouse feeder cells for culturing ESCs. These carried the danger of transmitting undesirable entities, from inappropriate transcription factors to viruses. On the other hand, ASC grafts from one’s own tissues are less likely to be rejected (though xeno-ASCs are even likelier than ESCs to be tagged as foreign and destroyed by the recipient’s immune system).

Studies of all three kinds of stem cells have helped us decipher mechanisms of both development and disease. This research allowed us to discover how to enable cells to remain undifferentiated and how to coax them toward a desired differentiation path. Stem cells can also be used to test drugs (human lines are better indicators of outcomes than mice) and eventually generate tissue for cell-based therapies of birth defects, Alzheimer’s, Parkinson’s, Huntington’s, ALS, spinal cord injury, stroke, diabetes, heart disease, cancer, burns, arthritis… the list is long. Cell-based therapies have advantages over “naked” gene delivery, because genes delivered in cells retain the regulatory signals and larger epi/genetic contexts crucial for long-term survival, integration and function.

People argue that ASCs (particularly hematopoetic precursors used in bone marrow transplants) have been far more useful than ESCs, whose use is still potential. However, they usually fail to note that ASCs have been in clinical use since the late fifties, whereas human ESCs were first isolated in 1998 by James Thomson’s group in Wisconsin. Add to that the various politically or religiously motivated embargoes, and it’s a wonder that our understanding of ESCs has advanced as much as it has.

Despite fulminations to the contrary, women never make reproductive decisions lightly since their repercussions are irreversible, life-long and often determine their fate. Becoming a human is a process that is incomplete even at birth, since most brain wiring happens postnatally. Demagoguery may be useful to lawyers, politicians and control-obsessed fanatics. But in the end, two things are true: actual humans are (should be) much more important than potential ones – and this includes women, not just the children they bear and rear; and embryonic stem cells, because of their unique properties, may be the only path to alleviating enormous amounts of suffering for actual humans.

Best FAQ source: http://stemcells.nih.gov/info/basics/

Alien Life in Chondritic Meteorites (Not)

Sunday, March 6th, 2011

I received word of yet another NASA-funded claim of “alien lifeforms”: one more case of shadowy squiggles in a meteorite, it appeared in the Journal of Cosmology (JoC). Rosie Redfield and PZ Myers dissect this in detail, but essentially we have a recap of the “arsenic bacterium” debacle minus (thankfully) the NASA-directed media blitz. Briefly:

1. The author, Richard B. Hoover, has been presenting the same evidence without change since 1997.
2. The only CV I can find for Richard Hoover does not list a PhD in anything (it does say “he authored four species of bacteria” which gives new meaning to the term “conjuring”). [Update: NASA confirms that Hoover has a BSc, not in biology.]
3. The evidence itself is so weak, stale, shoehorned and artifact-prone as to be non-existent. The presentation is also misleading: it juxtaposes suggestive pictures at different scales. It doesn’t meet the criteria for publication in a reputable journal, let alone the justifiably high bar for such claims — which may explain why the author approached Fox News instead.
4. The editors of JoC say that the paper will be peer-reviewed post-publication (file this under “unclear on the concept”).
5. The executive editor of JoC for Astrobiology is Chandra Wickramasinghe of the Hoyle and Wickramasinghe “viruses from space” panspermia theories – enough said.

Memo to NASA: hire bona-fide biologists who can conduct solid research or shut down the Astrobiology division.

Update: NASA has stated that the Hoover paper was published without the required internal NASA critique and approval; it also failed external peer review three years ago.

“As Weak as Women’s Magic”

Tuesday, March 1st, 2011

Ursula Le Guin is one of the speculative fiction authors I respect and admire. Her imagination seems endless, her capacity enormous. I’ve read her novels, her stories, her essays — even her poems. I’ve written reviews of her books and she’s the SF/F author I most often reference and hold up as an example in my essays.

However, some of her stances make me uneasy as a woman, a feminist and a scientist. One of them is her insistence that magic must be gender-specific. When she recently reiterated this credo (in the context of ridiculing the idea of a female Prospero or Lear), my views on this aspect of her outlook crystallized.

The result of these reflections just appeared in Crossed Genres: “As Weak as Women’s Magic”.

Image: Cover of Tombs of Atuan: Yvonne Gilbert/Gail Garraty.