Blood as a Youth Potion

Could techniques that restore markers of youth to old mice have any effect on human subjects?

Blood Transfusion Experiment in Mice

Cellular senescence, a "state in which cells stop growing and dividing," contributes to the aging of various tissues in the body. In one experiment, two mice were surgically spliced together, like Frankensteinian conjoined twins. The younger mouse showed signs of aging, while the old mouse gained some of the young one's youthful health. To distinguish blood-borne factors from other effects, the blood of old mice has been transfused into young ones, causing the recipients to show "increased expression of senescence biomarkers in the muscle, kidney, and liver." They also suffered loss of strength and endurance.

Senolytic agents, "drugs that eliminate senescent cells," when infused into the blood of the old mice, reduced the ill effects on the victims of the age-to-youth transfusions.

Conversely, transfusing the blood of young mice into old ones "decreased tissue damage in the liver, kidney, and muscles of old mice."

These studies remind me of a classic quasi-vampire story from 1896 (one year before DRACULA), "Good Lady Ducayne," by Mary Braddon. The wealthy title character has a reputation for being generous to her young, female paid companions. But why have they all mysteriously wasted away and died? It turns out that her villainous personal physician has been drugging the girls with chloroform and secretly draining their blood to transfuse it into their elderly employer, maintaining vigor unnatural for her advanced years. This method of forestalling the ravages of age sounds like obsolete pseudo-science. How surprising to learn that such a method might actually work, to some extent at least.

Unfortunately, neither senolytics nor the vital fluids of vigorous young people can presently act as a fountain of youth for human patients. If healthy blood could serve that purpose, negative social consequences such as exploitation of the incarcerated or the poor could result. Money or reductions in prison time might offer an irresistible temptation to "donate" blood to the privileged classes.

Special people whose blood confers health or immortality form a long-standing science fiction trope. For instance, THE IMMORTAL, a 1969-70 TV series, based on short stories by SF writer James Gunn, features a man whose transfused blood heals a dying millionaire. However, the effect wears off after a while. Naturally the rich man wants to keep the other one as a living blood bank, so the potential victim goes on the run. in Tananarive Due's African Immortals novels, beginning with MY SOUL TO KEEP, the Immortals of the series title keep their nature secret to avoid being hunted for their blood, through which their immortality can be passed on. If a human family or subspecies with rejuvenating blood existed, it seems all too likely that they might be imprisoned and bled for the benefit of the elite.

Margaret L. Carter

Carter's Crypt

Artificial Blood

Here's an article about an artificial blood substitute being developed by a research physician from the University of Maryland School of Medicine:

Artificial Blood One Step Closer

It's not meant to replace regular blood transfusions, but as a supply in emergencies for purposes such as to "stabilize a patient’s blood pressure or facilitate blood clotting." The goal is "to develop a bio-synthetic whole-blood product that can be freeze-dried for easy portability, storage, and reconstitution." Instant blood, just add water! The main ingredient will be "ErythroMer, the artificial blood product made by KaloCyte, a company co-founded by Dr. Doctor in 2016 with bioengineer and synthetic chemist Dipanjan Pan, PhD, MSc, professor in nanomedicine at Penn State University, and Philip Spinella, MD, a military transfusion medicine expert at the University of Pittsburgh." The two other main components are "synthetic platelets and freeze-dried plasma."

Here's a Wikipedia entry about various kinds of blood substitutes:

Blood Substitute

The most difficult function to duplicate, as well as the most important, is the transportation of oxygen. Several different varieties of manufactured hemoglobin have been tried. Another potential alternative might be growing red blood cells from stem cells in vitro.

As a fan, scholar, and writer of vampire fiction, naturally I wonder whether the University of Maryland's artificial blood product could nourish vampires. Could it serve the function of True Blood in the Sookie Stackhouse series, allowing vampires to "come out of the coffin" as accepted members of society? Whole blood includes many components besides those found in present-day blood substitutes. Which of those ingredients are necessary for vampires to thrive? If the growth of stem-cell-generated hemoglobin could be perfected, that would seem the best product for both medical uses and vampire nutrition.

Margaret L. Carter

Carter's Crypt

Quest for Longevity

The cover story of the January 2023 NATIONAL GEOGRAPHIC, a 35-page article titled "The Science of Living Longer and Better," explores several different approaches, both theoretical and practical, to the goal of extending the human lifespan. The genetically programmed maximum age for us seems to be around 120 years. However, very few people make it that far.

Numerous drugs enable mice to live as much as 60% longer than normal. Why don't they work on people? Why do certain animals such as naked mole rats and some bats live significantly longer, in proportion to their size, than we do? Why do Greenland sharks live at least 250 years, maybe longer? Altering a single gene in a certain species of roundworms doubles their lifespan while keeping them youthfully energetic, but we're more complicated than worms. Why do people in some societies tend to enjoy longer, healthier lives than the average? Environment? Diet? Exercise? Other lifestyle factors? Some scientists have tried promising drug therapies on themselves, with mixed results. Animal studies show life extension outcomes from severe restriction of calorie intake, but, again, such a regimen hasn't produced similar effects on human subjects. Anyway, personally, if I could lengthen my lifetime by a decade or two that way, I wouldn't bother; adding on years of semi-starvation would be no fun.

Stipulating the natural human upper age limit as about 120 years suggests that the Howard Families project in Robert Heinlein's METHUSELAH'S CHILDREN couldn't work the way the novel portrays it. By the date of the novel, the 22nd century, the typical Howard Families member lives to 150, retaining the appearance and vitality of a person in the prime of life. This situation exists before rejuvenation therapies are invented later in the story. Simply interbreeding bloodlines of naturally long-lived people couldn't extend their maximum ages past the 120-year limit if genes for such extension don't already exist. Moreover, real-life super-centenarians, however vigorous, still look their age, not so youthful they have to adopt new identities to avoid unwelcome attention. The only way the "Methuselahs" of Heinlein's novel could survive and remain young-looking to the age of 150 would be if Lazarus Long had already spread the mutated gene responsible for his apparent immortality through most of the Howard population. (Given the character of Lazarus as portrayed in the later book TIME ENOUGH FOR LOVE, that hypothesis seems not unlikely.) That explanation wouldn't work for the early generations such as Lazarus's own mother and her contemporaries, though. There's no plausible way mere selective breeding for a century or so could produce human beings who live over 100 years with the appearance of well-preserved middle age.

So if we want lifespans like Heinlein's characters, we'll have to develop futuristic technologies similar to those speculated about in the NATIONAL GEOGRAPHIC article. Even so, surpassing the natural limit of 120 years would seem to require something radically beyond those techniques, maybe direct alteration of DNA—such as the hypothetical "cellular reprogramming" mentioned in the article.

Margaret L. Carter

Carter's Crypt

Animal Regeneration

Here's an article about sea slugs that purposely decapitate themselves:

Decapitated Sea Slugs

It's believed they occasionally "jettison" their bodies to get rid of parasitic infestations. The abandoned torso (if that word applies to slugs) swims independently, sometimes for months, before eventually decomposing. The severed head, however, grows a whole new body, often within three weeks. Meanwhile, it continues to feed on algae as if it doesn't notice it has no digestive system, not to mention other essential organs such as a heart.

Self-amputation, called "autotomy," shows up in other species, such as lizards who let their tails detach to escape predators, then grow new tails. Starfish can generate new arms to replace severed limbs, and in some case a segment of a dismembered starfish can develop into a separate animal. In my high-school biology class, we bisected flatworms to watch the pieces regenerate over several days. Sea cucumbers sometimes eject their internal organs under stress and regrow the lost organs. Mammals, in contrast, have limited capacity for regeneration, but (according to Wikipedia) two species of African spiny mice shed large areas of skin when attacked by predators: "They can completely regenerate the autotomically released or otherwise damaged skin tissue — regrowing hair follicles, skin, sweat glands, fur and cartilage with little or no scarring."

Why do plants regularly lose limbs and grow new ones anywhere on their trunks, while most animals are much more limited in this respect? Why the difference in regenerative capacity between lizards and mammals, although they're all vertebrates? The sea slug's self-decapitation makes tales of vampires and other monsters that can re-grow lost appendages seem more plausible. The slug's independently moving detached parts remind me of a vampire novel by Freda Warrington in which a decapitated vampire regenerates a complete body from his severed head. Meanwhile, the headless corpse grows a new head; however, the resulting individual rampages mindlessly like a zombie. In the science fiction genre, I once read a story whose protagonist hosts a visiting alien at a house party. This alien's species has detachable limbs, so losing an appendage is no big deal for them. Also, this particular ET has a totally literal comprehension of English. When the protagonist compliments a concert pianist with the remark, "I wish I had her hands," the alien tries to do the host a favor by amputating those hands and presenting them as a gift. . . .

It's hoped that understanding the sea slug's remarkable ability "could one day lead to advances in regenerative medicine and other fields." Many science-fiction future technologies include medical treatments that enable injured patients to grow new organs and limbs. Maybe that vision might eventually come true.

Margaret L. Carter

Carter's Crypt

Anticipating Androids

In Mary Shelley's novel, Victor Frankenstein apparently constructed his creature by stitching together parts of cadavers. (His first-person narrative stays vague on the details.) Considering the rapid decay of dead flesh as well as the problem of reanimating such a construct, if we ever get organic androids or, as they're called in Dungeons and Dragons, flesh golems, they're more likely to be created by a method similar to this: Robotics experts at the University of Vermont have designed living robots made from frog cells, which were constructed and tested by biologists at Tufts University:

Xenobots

They're made of living cells derived from frog embryos. Joshua Bongard, one of the researchers on this project, describes the xenobots as "a new class of artifact: a living, programmable organism." The frog cells "can be coaxed to make interesting living forms that are completely different from what their default anatomy would be." Only a millimeter wide, they potentially "can move toward a target, perhaps pick up a payload (like a medicine that needs to be carried to a specific place inside a patient)—and heal themselves after being cut." They might also be able to perform such tasks as cleaning up radioactive materials and other contaminants or scraping plaque out of arteries. While this process doesn't amount to creating life, because it works with already living cells, it does reconfigure living organisms into novel forms. Although there's no hint of plans to build larger, more complicated artificial organisms, the article doesn't say that's impossible, either.

If an android constructed by this method could be made as complex as a human being, could it ever have intelligence? In an experiment I think I've blogged about in the past, scientists at the University of California, San Diego have grown cerebral "organoids"—miniature brains—from stem cells:

Lab-Grown Mini-Brains

These mini-brains, about the size of a pea, can "mimic the neural activity" of a pre-term fetus. Researchers hope these organoids can be used to study brain disorders and perhaps to replace lost or damaged areas of living human brains. At present, they can't think or feel. But suppose they're eventually grown large and complex enough to—maybe—develop sentience or even consciousness? In that case, it could be reasonably argued that they should have individual rights. The "disembodied brain in a jar" that's a familiar trope of SF and horror, is, according to the article, a highly unlikely outcome of this research. If these miniaturized brains ever became complex enough to transplant into a more highly developed version of the frog-cell "xenobots," however, the question of personhood would surely arise.

Margaret L. Carter

Margaret L. Carter

3D-Printed Organs

3D printing is now being used as an aid to cardiac surgery. The printers don't yet make actual replacement hearts. What they do is use information from ultrasound images to construct three-dimensional duplicates of patients' hearts for surgeons to practice on:

3D Print Heart Models

Here's an article about a baby in Baltimore, with a severe congenital heart defect, who's getting prepared for surgery through this method:

3D Heart Model for Toddler

This technique does, however, have the capacity to produce simpler cardiac replacement parts, in the form of 3D-printed silicone heart valves:

3D Print Heart Valves

A vital problem in growing artificial organs for transplant consists of providing them with a viable blood supply once they're implanted in the body. Creating "intricate networks of tiny blood vessels" is a major challenge. Now scientists at Rice University in Texas have made progress with "a 3D bioprinter that can print vessels less than a third of a millimeter wide in biocompatible hydrogels." They've even built an artificial lung capable of oxygenating blood:

Biggest Challenge with 3D-Printed Organs

Here's a Smithsonian article about the prospects for lab-grown and 3D-printed organs:

Printed Organs on Demand

Two obvious advantages of producing custom-made body parts on demand, of course, would be bypassing the donor shortage and avoiding any risk of rejection. Maybe in the future most of us will be cyborgs. Moreover, if such personalized replacements eventually become available to everybody, might we reach a point where people never have to die until they reach the upper limit of old age? Maybe our descendants in the near future will see the fulfillment of the biblical prophecy (paraphrased), "As the age of a tree shall the lives of my people be."

Margaret L. Carter

Carter's Crypt

Beliefs, Facts, and Action

Sometimes it doesn't matter whether one has accurate beliefs about facts as long as one's beliefs have a correct or useful effect in practice. In one STAR TREK novel in which the crew brings aid to a planet suffering from an epidemic, they advise the local healers of the importance of cleanliness. One of them says something like, "Yes, we know dirt attracts disease demons." Later Spock gives her a medication with the statement that disease demons can't abide it. Whether the healers believed in disease demons or germs, what mattered was the treatment being applied. The British Navy realized lime juice prevented scurvy long before vitamins were discovered. Likewise, cooks knew food would spoil if not stored in the proper conditions, even though they knew nothing about bacteria. During medieval epidemics, the spread of disease was controlled by quarantine when doctors still thought illness came from unbalanced humors or malign astrological influences. The heroine of Henry James's short novel DAISY MILLER dies of malaria, which the story attributes to the miasma emanating from the swamps near Rome. Although people then didn't know malaria was spread by mosquitoes, they knew hanging around swamps and other sources of stagnant water often led to catching the disease. Of course, as a literary symbol of ancient, corrupt Europe destroying a young, naive American girl, a swamp works better than a mosquito.

Before astronomers accepted the Copernican model of the planets revolving around the sun, they believed Earth was the center around which the planets (including the sun and moon) and the sphere of the fixed stars revolved. People still managed to navigate by the stars, and astronomers and astrologers could use the incorrect model to predict the movements of heavenly bodies. The triumph of the Copernican model, however, allowed more elegant predictions and opened the way for the revelation that the planets and stars obeyed the same Newtonian gravitational laws as objects on Earth. Contrary to popular belief, by the way, the Earth-centered universe theory didn't mean people thought Earth and the human race were special in a good way. Unlike the heavenly bodies outside the sphere of the moon, Earth was flawed, the lowest point in the cosmos, where the dregs of creation ended up. The moon was imperfect, too; it changed on a monthly schedule, and it displayed visible spots. The planets, sun, and stars were thought to be composed of different, perfect material. The main shock of the Copernican revolution wasn't that we lost our place at the center. It was that the heavens were as changeable as Earth and the objects on it, made of the same kind of matter. Speaking of Newton, the classical laws of physics worked fine in practice for centuries, despite the fact that theories of relativity and quantum mechanics eventually revealed the inadequacies of classical physics on the macro and micro levels.

Often, of course, erroneous beliefs about facts do make a practical difference. Long before Mendel and the later discovery of DNA, farmers knew how to breed animals and plants for desirable traits. However, they also believed in prenatal impressions—that the experiences of pregnant mothers left their marks on the offspring. According to the book of Genesis, Jacob induced his father-in-law's flocks to produce spotted offspring by placing spotted twigs in front of the breeding animals. Columbus was mistaken about the size of the Earth. If he hadn't bumped into a previously unknown land mass by sheer luck, his expedition would probably have been lost long before getting near Asia. When medical science discovered the risks of excessive cholesterol in the bloodstream, authorities assumed dietary cholesterol should be restricted. People unnecessarily reduced their intake of innocent, nutritious eggs, until new studies identified trans fats as the main dietary villain. Pediatricians used to recommend that babies sleep on their stomachs or, later, face up in an inclined rather than flat position, for fear they might spit up and choke. Better understanding of the physiology of sudden infant death has led to a complete reversal, so that babies now sleep on their backs. Ideology drives policy on matters such as punitive incarceration of drug offenders versus treating addiction as a medical problem or what kind of formal sex education (if any) adolescents should be offered in schools—issues in which mistaken beliefs about real-world effects can result in undesired actual outcomes.

What factual beliefs might our present-day culture hold that will be disproved in the future, maybe with real-life consequences? What universally held assumptions of ours might future generations or visiting extraterrestrials consider as absurdly wrongheaded as we consider the heliocentric cosmos or the "humors" theory of disease?

Margaret L. Carter

Carter's Crypt

Trusting the Experts

I'm rereading FOR HER OWN GOOD: TWO CENTURIES OF THE EXPERTS' ADVICE TO WOMEN, by Barbara Ehrenreich and Deirdre English (actually, the first edition, titled "150 Years of..."):

For Her Own Good

The book deconstructs medicine and psychology in particular, as one would expect, but also new disciplines such as "domestic science" (aka home economics, invented in the late nineteenth century). The venerable doctrine that overuse of the mind, especially in pursuit of "masculine" fields of study, ruined women's physical health and rendered them unfit for their natural purpose, reproduction, is only the most blatantly appalling of the now-discredited theories exposed in this historical survey.

The book serves as a reminder of how "science-based" recommendations offered to the public can change from century to century, decade to decade, and sometimes year to year. Around 1900, American housewives were encouraged to protect their families' health by obsessive cleaning in an attempt to make the home germ-free (an impossible goal in a normal household anyway). Nowadays, it has been discovered that an excessively clean environment in childhood promotes allergies. In the first half of the twentieth century, some doctors recommended smoking as a weight-loss strategy (as mentioned in Stephen King's novella "The Breathing Method"). In the same period, mothers were urged to put their babies on rigid schedules and told that picking up a baby between feedings or cuddling and playing with him or her would lead to all sorts of mental and moral ills. At the time of my first pregnancy, obstetricians badgered pregnant women to starve themselves into a weight gain of twenty pounds or less (not only almost impossible for most women but unhealthy). Eggs used to be considered evil because of their cholesterol content. Now we know dietary cholesterol has little or no direct effect on blood cholesterol; the main culprits are trans fats.

That's what we know now, at least. What guarantee do we have that the latest findings of modern science will remain THE authoritative truth instead of being superseded as many earlier truths have been? Yet the average layperson has to trust the experts, since she doesn't have the background to evaluate the research herself. (And then there are pseudo-scientific fads, which the Internet sometimes makes hard to distinguish from legitimate science.) The best we can do is exercise critical reading and thinking skills as we compare claims—which a liberal education is supposed to teach us to do, as mentioned in last week's blog post. Faith in the pronouncements of authorities is often scorned as a fallacious mode of thought, but we all accept authority as the basis for many of our beliefs. Even the most widely educated genius can't be an expert in everything.

I once came across mention of a story (don't know the author or title) in which the magicians of the world "came out" and revealed that all the alleged technological marvels of modern society were, in fact, created by magic. For many of us in relation to many fields of technology, "a wizard did it" would sound just as plausible as the scientific explanation.

Margaret L. Carter

Carter's Crypt

Good Out of Evil?

In Barbara Hambly's CRIMSON ANGEL (which I reread last week), the protagonist of the series, Benjamin January, a free colored resident of antebellum New Orleans trained as a surgeon in France but making his living as a musician, unearths the notebooks of a physician known as "Dr. Maudit" ("Accursed"). The doctor drugged and vivisected hundreds of slaves, many of them bought for the purpose. The quandary of whether to benefit from the information in those notebooks addresses an ethical problem still relevant. The situation brings to mind Dr. Mengele, the Auschwitz "Angel of Death," who performed cruel experiments on concentration camp inmates, especially twins. If Mengele's studies had yielded any useful knowledge, would it have been morally right to preserve that information? In the case of Mengele, the question is moot, because by all accounts his methods were flawed and his "experiments" useless. In Hambly's novel, however, given the state of medical science in the 1830s, the doctor's dissection of living bodies yields a wealth of knowledge unobtainable in any other way. January is strongly tempted to keep the notebooks, recognizing many instances where the discoveries recorded therein could have saved patients' lives if he'd had that knowledge in the past.

Is it simply wrong to profit from the evil actions of another, even if the result would contribute to the welfare of many people? Or would preserving the knowledge gained by vivisection of unwilling victims salvage some good out of the original evil? Couldn't it be argued that failure to use the information would mean their deaths have been completely wasted? One character in CRIMSON ANGEL says "it is wrong to keep the profits of a crime" because such behavior "is an incentive—a permission—for others to commit crimes for the sake of the rewards." In the end, January decides he must destroy the notebooks despite his bitter regret for the loss of the knowledge in them.

This scenario relates to perennial hot topics in medical research and bioethics, especially nowadays with issues surrounding experimentation on embryos and stem cells.

The episode mentioned above isn't a true spoiler for CRIMSON ANGEL. You can still enjoy plenty of suspense in reading the book, which takes place in New Orleans, Cuba, and Haiti, and discovering the deeper secrets behind the murders. I highly recommend this long-running series, which begins with A FREE MAN OF COLOR. Hambly has done in-depth research about New Orleans and the South in the 1830s, and through the experience of a mixed-race (but mostly black) protagonist, she explores the nuances of race relations in the former Spanish and French colony where Americans are seen as brash interlopers who don't understand the subtle distinctions of the racial caste system and the free "colored" demimonde.

Margaret L. Carter

Carter's Crypt

Unintended Consequences

I recently saw an article about wildfires in Oregon, which are much worse than they would have been naturally because of the conscientious efforts to prevent forest fires in past decades. (Remember Smoky the Bear?) Without human interference, forests burn frequently enough to clear out underbrush and make room for new growth. Without periodic fires, the underbrush keeps accumulating to build up a copious supply of fuel, so when fire does eventually break out, it's disastrous.

That phenomenon is only one example of how human good intentions in manipulating the natural order can generate unforeseen negative consequences. Back when wolves were considered dangerous pests that ravaged livestock and attacked people, wolf packs were systematically eliminated in the U.S. More recently, they've been restored to their old habitats, thus repairing (many researchers believe) damage done by their removal. There's a theory that reintroduction of wolves to Yellowstone Park, through predatory pressure on elk, allows the growth of certain trees (whose young shoots and saplings elk graze on) that beavers need to thrive:

Wolf Reintroduction

Everybody knows about the rabbit overpopulation in Australia, where introducing bunnies as a food source for colonists seemed like a good idea at the time.

Proper hygiene to eliminate disease-causing germs has saved millions of lives. Yet it's recently become known that a too-clean environment in infancy and early childhood makes children more likely to suffer allergies, asthma, etc. in later life. Apparently a little dirt is good for kids! Doctors used to recommend postponing introduction of potentially allergenic foods such as peanuts and wheat until well after the first year of life. On the contrary, new studies suggest that early exposure to such substances actually reduces the risk of becoming allergic later. The same principle seems to apply to pets; it's nice to know for sure that a lifetime surrounded by cats hasn't harmed our offspring.

Many decades ago, some doctors recommended that pregnant women take up smoking to lose weight! In the early twentieth century, feeding babies formula from bottles was the modern, "scientific" thing to do. My first obstetrician, an elderly man in the mid-1960s, must have been trained when this attitude prevailed, for he actually tried to discourage me from breastfeeding. (We moved to a different state in the middle of that pregnancy, and I'm glad I stuck to my plan even though nursing instead of bottle-feeding was still rather rare then.)

In the American Southwest, goodness knows how many millions of gallons of water are poured onto lawns to make people's yards resemble eighteenth-century English gardens, rather than cultivating plants native to the climates and ecosystems of those regions.

To paraphrase an old TV commercial, it's not nice to mess with Mother Nature—or, at least, we should investigate all possible angles before we do. Something to keep in mind when we eventually colonize other planets.

Margaret L. Carter

Carter's Crypt

Latest Cyborg Leap Forward

Medical researchers at Ohio State University have invented a device called NeuroLife, which enables a quadriplegic to move his hand:

Brain Implant

One end of the device is implanted in his brain, with external cables that run down to his hand, bypassing the damaged spinal cord. NeuroLife transmits nerve impulses generated by algorithms based on recordings of activity in the motor cortex (if I understand the explanation correctly). The experimental subject has regained enough precision control of his hand muscles to pick up objects and even play video games. I wonder whether he can use a keyboard; the article doesn't say. That would really be a leap forward. (I know about speech-to-text programs, of course, and many people seem to love them; if I were paralyzed, though, I would have a lot of trouble "writing" by dictation and would wish for the ability to type.)

This technique took a decade of development, and the patient had to undergo months of training to get the full benefit. So it won't be an instant fix, even when it becomes publicly available (and the article doesn't mention when that might happen). Still, it's a wondrous achievement.

Margaret L. Carter

Carter's Crypt