Insistence of Vision, Page 5

  We may go to the stars someday. And I envy those bright souls. But we do fly.

  Next, a more serious… and scientific… tale about another kind of transcendence.

  Chrysalis

  ᚖ

  Like every person who ever contemplated existence, I’ve wondered if the world was made for me – whole and new – this very morning, along with counterfeit memories of what came before.

  Recollection is unreliable, as are the records we inherit each day. Even those we made the night before – our jotted notes or formal reports, our memorials carved deep in stone – even they might have been concocted, along with memories of breakfast, by some deity or demon. Or by an adolescent 28th Century sim-builder, a pimpled devil, playing god.

  Find the notion absurd?

  Was that response programmed into you?

  Come now. History was written by the victors, while losers passed their entire lives only to serve as brief speedbumps. And aren’t all triumphs weathered by time?

  I sound dour. A grumpy grownup. Well, so it goes, when tasked with cleaning messes left by others. Left by my former self. And so, with a floating sigh of adulthood, I dive into a morass – records, electronic trails and “memories” that float before me like archaic dreams. Ruminations of an earlier, ignorant – not innocent – me.

  It all started medically, you see. With good intentions, like so many sins.

  ᚖ

  January 6, 2023: Organ replacement. For a generation it was hellishly difficult and an ethical nightmare. Millions lingered anxiously on waiting lists, guiltily hoping that a stranger out there would conveniently crash his car – someone with identical histocompatibility markers, so you might take a kidney or a liver with less probability of rejection. His bad luck transforming into your good fortune. Her death giving you a chance to live.

  Even assuming an excellent match, there’d be an agony of immunosuppressant therapy and risk of lethal infections. Nor was it easy on us doctors. When a transplant failed, you felt you were letting two patients down, both recipient and donor.

  Sci fi dystopias warned where this might lead. Sure enough, some countries started scheduling criminal executions around the organ want-list. Granting reprieves till someone important needed a heart... your heart. Then, off to disassembly.

  When micro-surgeons got good enough to transplant arms, legs and faces – everything but the squeal – we knew it was only a matter of time till the Niven Scenario played out. Voters would demand capital punishment for more than just heinous crimes. Your fourth speeding ticket? Time to spread you around. Is it really death, when nearly all your parts live on, within a hundred of your neighbors?

  Hell gaped before us. There had to be a better way.

  And we found it! Grow new parts in the lab. Pristine, compatible and ethically clean.

  Caterpillar eat! Chew that big old leaf.

  Ugly little caterpillar, your relief,

  When you’ve chomped your fill, will be to find a stem.

  Weave yourself a dressing room, hang in it, and then

  Change little caterpillar, grow your wings!

  Now go find your destiny, nature sings.

  When we started trying to regrow organs in situ, George Stimson claimed the process would turn out to be simple. He offered me a wager – ten free meals at his favorite salad bar. I refused the bet.

  “Those are your stakes? Lunch at the Souplantation? Acres of veggies?”

  “Hey, what’s wrong with healthy eating? They have the genuine stuff.”

  “My point exactly, George. Every time we go there, I look at a plate full of greens and think: this is what real food eats!”

  He blinked a couple of times, then chuckled at my carnivorous jibe before swinging back to the main topic – building new human organs.

  “Seriously. I bet we can get away with a really simple scaffold. No complicated patterns of growth factors and inhibitors. None of this stuff.”

  He waved at the complex map of a human esophagus that I had worked out over the weekend – a brilliantly detailed plan to embed a stretchy tube of plastic and collagen with growth and suppression factors. Along with pluripotent cells, of course, the miracle ingredient, cultured from a patient’s own tissues. Some of the inserted chemicals would encourage the stems to become epithelial cells here and here. Others would prompt them to produce cartilage there and muscle-attachment sites here and here and...

  ...and George thought my design way too complex.

  “Just lace in a vascular system to feed the stems,” he said. “They’ll do the rest.”

  “But how will they know which adult cell type to turn into?” I demanded. “Without being told?”

  This was way back near the turn of the century, when we had just figured out how to take skin or gut cells and transform them back into raw stems, a pre-differentiated state that was pluripotent or capable of becoming almost any other variety, from nerves to astrocytes to renal... anything at all! Exciting times. But how to assign those roles in something as complex as a body organ? We had found specific antigens, peptides, growth factors, but so many tissues would only form if they were laid out in ornate patterns. As complex as the organs they were meant to rebuild or replace.

  Patterns we were starting to construct! Using the same technology as an ink-jet printer, spray-forming intricate 3-D configurations and hoping to someday replicate the complex vein patterns within a kidney, then a spinal cord, and eventually...

  “We won’t have to specify in perfect detail,” George assured me. “Life will find a way.”

  I ignored the movie cliché. Heck, why not try his approach in a pig or two?

  We started by ripping out a cancer ridden esophagus, implanting a replacement made of structural polygel and nutrients. This scaffolding we’d lace with the test animal’s own stem cells, insert the replacement....

  Whereupon, voila. Step back, and witness a miracle! After some trial and error... and much to my astonishment... George proved right. In those first esophagi we implanted – and in subsequent human tests – my fine patterns of specific growth factors proved unnecessary. No need to command them specifically: “You become a mucus lining cell, you become a support structure...” Somehow, the stem cells divided, differentiated, divided again, growing into a complete adult esophagus. And they did it within the patient!

  “How do they know?” I asked, despite expecting in advance what George would say.

  “They don’t know, Beverly. Each cell is reacting only to its surroundings. To chemical messages and cues from its environment, especially its immediate neighbors. And it emits cues to affect them, as well. Each one is acting as a perfect – if complicated – little...”

  “...cellular automaton. Yes, yes.”

  Others, watching us finish each others’ sentences, would liken us to an affectionate old married couple. Few noticed the undercurrent of scorching rivalry.

  “So,” I continued, “just by jostling against each other in the geometric-chemical pattern of the scaffold, that alone is enough for them to sort themselves out? Differentiating into dozens of types, in just the right geometry?”

  “Geometry, yes.” George nodded vigorously. “Geometrical chemistry. I like that. Good. It’s how cells sort themselves into vastly complex patterns, inside a developing fetal brain. But of course you see what all of this means.”

  He gestured along a row of lab benches at more recent accomplishments, each carefully tended by one or more students.

  – a functioning liver, grown from scaffolding inside a mouse, till we carved it out. The organ now lay in vitro, still working, fed by a nearby blood pump –

  – a cat whose lower intestines had been replaced by polygel tubing... that was now completely lined with all the right cells: in effect two meters of fully functioning gut –

  – two dozen rats with amputated fore-legs, whose stumps were encased in gel-capsules. Along simple frameworks, new limbs could be seen taking shape as the creature’s own cells
(with a little coaxing from my selected stem-sims) migrated to correct positions in a coalescing structure of flesh and linear bone. Lifting my gaze, I saw cages where older creatures hobbled about on regrown appendages. So far, they were clumsy, club-like, footless things. Yet, they were astonishing.

  And yes, George, I saw what it meant.

  “We always assumed that mammals had lost the ability to regenerate organs, because it doesn’t happen in nature. Reptiles, amphibians and some fish can regrow whole body parts. But mammals in the wild? They... we... can only do simple damage control, covered by scar tissue.”

  “But if we prevent scarring,” he prompted. “If we lay down scaffolds and nutrient webs –”

  “– then yes, There emerges a level of self-repair far more sophisticated than we ever imagined possible in mammals.”

  I shook my head. “But it makes no sense! Why retain a general capability when nature never supplies the conditions to use it? Only when we provide the right circumstances in our lab, only then do these abilities emerge.”

  George pondered a moment.

  “Beverly, I think you’re asking the wrong question. Have you ever wondered: why did mammals lose... or give up... this ability in the first place?”

  “Of course I have! The answer is obvious. With our fast metabolisms, we have to eat a lot. No mammal in the wild can afford to lay around for weeks, even months, the way a reptile can, while waiting for a major limb or organ to regrow. He’d starve long before it finished. Better to concentrate on things mammals are good at, like speed, agility and brains, to avoid getting damaged in the first place. Mammalian regeneration probably vanished back in the Triassic, over a hundred million years ago.”

  He nodded. “Seems a likely explanation. But what’s puzzling you –”

  “– is why the capability has been hanging around all this time! Lurking in our genome, never used!”

  George held up a hand. “I think we’re getting ahead of ourselves. First, let’s admit that humans have now changed the balance, the equation. We are now mammals who can lie around for weeks or months while others feed us. First family and tribe, back in the Stone Age, then town and nation –”

  “– and that increased survival rates after serious injuries,” I admitted. “But it never resulted in organ regrowth!”

  Abruptly I realized that half a dozen grad students had lowered their tools and instruments and were sidling closer. They knew this was historic stuff. Nobel-level stuff. Heck, I didn’t mind them listening in. But shirking should never be blatant! I sure never got away with it, back when I served my time as a lab-slave. My withering glare sent them scurrying back to their posts. Oblivious, as usual, George simply blathered on.

  “Yes, yes. For that to happen, for those dormant abilities to re-awaken, it seems we need to fill in all sorts of lost bits and pieces. Parts of the regrowth process that were mislaid across – what’s your estimate, again?”

  “A hundred million years. Ever since advanced therapsids became fully warm-blooded, early in the age of dinosaurs. That’s when major organ regrowth must have gone dormant in our ancestors. Heck, it’s not surprising that some of the sub-processes have faded or become flawed. I’m amazed that any of them – apparently most of them – are still here at all!”

  “Are you complaining?” he asked with an arched eyebrow.

  “Of course not. If all of this holds up,” I waved around the lab, now quadrupled in size, as major funding sources rushed to back our work, “the therapeutic implications will be staggering. Millions of lives will be saved or improved. No one will have to languish on organ donor waiting lists, praying for someone else to have bad luck.”

  I didn’t mention the other likely benefit. One more year of breakthroughs and the two of us would be shoe-ins for Stockholm. In fact, so certain was that starting to seem, that I had begun dismissing the Nobel from my thoughts! Taking for granted what had – for decades – been a central focus of my life, my existence. It felt queer, but the Prize scarcely mattered to me anymore. I could see it now. A golden disk accompanied by bunches of new headaches. Pile after pile of distractions to yank me from the lab.

  From seeking ways to save my own life.

  But especially from finding out what the heck is going on.

  The cicada labors seventeen years

  Burrowing underground,

  Suckling from tree roots,

  Below light or sound.

  Till some inner clock commands

  “Come up now, and change!

  “Grow your wings and genitals

  “Forget your humus range.”

  So out they come, in adult form,

  To screech and mate and die.

  Mouthless, brief maturity,

  As generations cry.

  We dived into the genome.

  One great 20th Century discovery had been the stunning surprise that only two percent of our DNA consists of actual codes that prescribe the making of proteins. Just 20,000 or so of these “genes” lay scattered along the forty-six human chromosomes, with most of the rest – ninety-eight percent – composed of introns and LINEs and SINEs and retro-transposons and so on...

  For a couple of decades all that other stuff was called “junk DNA” and folks deemed it to be noise, just noise. Dross left over from the billion years of evolution that has passed since our first eukaryotic ancestor decided to join forces with some bacteria and spirochetes and try for something bigger. Something more communal and organized. A shared project in metazoan life.

  Junk DNA. Of course that never made any sense! It takes valuable energy and resources to build each ladder-like spiral strand of phosphates, sugars and methylated nucleic bases. Darwin would have quickly rewarded individuals who pared it all down. Just enough to do the task at hand, and little more. Redundancy is blessed, but efficiency is divine.

  Eventually, we found out that much of the “junk” was actually quite important. Sequences that served a vital function, regulating when a gene would turn on to make its protein, and when it should stop. Regulation turned out to take up heaps of DNA. And much of the rest appeared to be recent infestations from viruses – a creepy thing to think about, but of no interest to me.

  For a while, some folks thought we had the answer to the “junk DNA problem.”

  Only, vast stretches remained mysterious. Void of any known purpose, they didn’t seem to do anything at all. And they were much too big to be just punctuation or spacers or structural elements. The junk theory came back as colleagues called those big, mystery patches meaningless relics...

  ... till George Stimson and I made our announcement.

  Fish are fish are funny folk,

  They never laugh and never joke.

  When mating, there is no romance,

  Just a throng, a whirling dance.

  Then commence...

  ...the winnowings –

  Ten billion sperm, ten million eggs,

  Produce a hundred thousand larvae,

  Hundreds survive, become fish,

  For maybe two to start it over.

  CBC - The Q: Welcome back, I’m Sandra Oh and this is the Q, coming to you live and in 4-D from the Great Plains Theater in Winnipeg. We’ll get back to tonight’s fantastic noppop group, The Floss Eaters – yes, let it out for them! Only now let’s all calm down and welcome onstage our special guests. Give a warm welcome to Manitoba’s brightest science stars – Beverly Wang and George Stimson.

  Professor George Stimson: Thank you Sandra.

  Professor Beverly Wang: Yes, it’s good to be on your lively show. My, that last song was... Can-Do Invigo-Rating.

  Sandra: Ha ha! Totally with-it. You’ve won the crowd over, Madame Professor. It’s not grampa’s rock’n’roll, eh? Now hush you folks in the seats. We only have Bev and Geo for a few minutes before they must go back to changing our world. So let me start with Beverly, on behalf of folks here and in our audience around the globe. We’ve all been amazed by the success you both sparked in re
-growing individual organs and body parts, giving hope to millions. Is it true that you’ve also done it yourselves?

  BW: Yes, I have a new kidney and liver, grown in a vat from my own cells. I was offered regular transplants – they found a match. But it seemed more honest and true to use our methods myself. As one of the first volunteers. So far, the new parts have taken hold perfectly.

  Sandra: And you, George?

  GS: My own grafts were less ambitious... mostly to deal with widespread arthritis. Joint and tendons. Reinforcement and replacement.

  Sandra: How’d that go?

  GS: Shall I juggle for you?

  Sandra Hey now, doc, those water bottles are... wow! That’s some talent. Let’s hear it for Circus Stimson!

  GS: Well, I used to show off in college... it’s been years... oops!

  Sandra: No sweat, we’ll clean it up. That’s an impressive demonstration of restored youth and zest! Still, we’re always wondering on the Q... what’s next? What’s beyond grow-your-own-organs? I have to tell you we hear rumors that you’ve got something even bigger brewing. Called the Caterpillar Cure?

  GS: Well now, Sandra, that’s not a name we use. It arose when we described taking a deathly ill test subject and wrapping or encasing the whole body in a protective layer –

  Sandra: A cocoon!

  GS: Hm, well yes. In a sense. We then trigger processes that have long lain dormant in the mammalian tool kit. We’ve become quite adept at extrapolating and filling in lost or missing elements. Whereupon we give the body every chance to repair or regrow or even replace its own component parts without surgical intervention, in a way that’s wholly... or mostly... natural.

  Sandra: Wow... I mean, wow! I haven’t heard applause that wild from a live audience since we had both Anvil and Triumph on the show, playing together in Ottawa. Settle down folks. Professor Wang, may I ask how you feel about the way pop culture is interpreting some of this? A cluster of quickie-horror pollywood flicks have suggested that this awakening of long-dormant traits might go awry in spectacular ways. Have you seen any of these cable-fables?