: The Human Age

The (3D-Printed) Ear He Lends Me

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The (3D-Printed) Ear He Lends Me

Lawrence Bonassars lab in Cornell Universitys Weill Hall sits across the street from a jewel of a tiny flower garden, now blanketed in snow. Though Weills outside walls are white as the season, its one of the greenest buildings in the country, which has earned a rare gold LEED rating, thanks to everything from recycled building debris and materials (such as the outer skins white aluminum panels) to a cooling roof planted with succulents and flowers, heat-reflective sidewalks, a giant atrium with passive solar heat, and motion sensors that turn on lights, temperature, and air flow only as needed, when people appear.

Opened five years ago, as a state-of-the-art home for the Department of Life Sciences, its been designed as an intellectual crucible with large overlapping labs. Long open sunlit rooms, running the length of each floor, share common lounges, corridors, and microscope areas, making it impossible not to bump into postdocs in related fields. Even in winter, cross-pollination is encouraged. Just as the planners hoped, many collaborations have ensued, the new field of regenerative medicine is taking wing, and bioprintmakers are crafting tailor-made body parts.

The principle of regenerative medicine is magically simple: if a heart or jaw is damaged, either teach the body to regrow another or print a healthy new one the body will embrace. What Bonassars lab regenerates is the bodys vital infrastructure of cartilage: all those cushions (the so-called disks) between the vertebrae in the spine; the easily torn meniscus in the knee; the accordion of semicircular rings that keeps the trachea from collapsing when we breathe, yet allows it to bend forward when we swallow; the external ear, prized by poets and nibblesome lovers, who often describe it as shell-like. His goal is to restore lost function to ragged physiques and fix facial defects. To that end, he mingles tools from several disciplines, including biomechanics, biomaterials, cell biology, medicine, biochemistry, robotics, and 3D printing. If your only tool is a ruler, youll tend to draw boxes. New tools create new mental playgrounds. On this playground, spare ears abound.

What could you do with a spare ear? If a patient with skin cancer has to have an ear removed, the traditional way to replace it is with a prosthetic, but that has to be donned every day. A young mother in exactly that fix lamented to CBS News, I could just see my kids running around with it, yelling I have mommys ear! Instead, surgeons at Johns Hopkins harvested cartilage from her ribs, shaped it into an ear, and implanted it under her forearm skin, where it could be nourished by her own blood vessels. Just four months later, when the ear had grown its own skin, it was removed from her arm and attached to her head. Yet, wonderful as her new homegrown ear was, the process required numerous operations, including breaking open the vault of the chest and stripping cartilage from the ribs, then shaving and shaping the ear to fit. A feat of subtractive manufacturing.

Or an ear might rescue the one child out of nine thousand who is born with microtia, a condition in which the external ear hasnt fully developed, sometimes leaving only a small peanut-shaped vestige behind for classmates to ogle and mock. A father of three young childrentwin six-year-old girls and a five-year-old boyBonassar is deeply sympathetic to the condition, and mindful of what early fixes can mean. Unfortunately, children arent able to brave an operation like the young mothers until theyre six to ten years old, because they dont have enough rib cartilage. Also, the operation is very painful and quite traumatic, and you dont really want to subject a child to it. How much simpler, less invasive, and cheaper to do an MRI, CT scan, or 3D photograph, then print the cartilage out on demand in the exact shape of each childs highly personal ear. Youd be able to do it much earlier in a childs life, and you could photograph the left ear, flip it around to make a right ear, and match the geometry perfectly.

Microtia doesnt harm hearing, but it often invites the social nightmares of bullying and shunning, just as a child is detailing a sense of self. So, although a new ear is only a cosmetic change, it has an enormous impact on a childs hope of making friendswhich in turn shapes a growing childs brain. The ability to smile is a childs coin of the realm, pleasant ears and face its passport. As I learned volunteering for a short spell with Interplast in Central America, the sooner you can repair a harelip, birthmark, or other deformity, the better chance a child has to bond with her parents, let alone strangers.

I dont really need a new ear. Except for the occasional snare-drum of tinnitus or missed stage whispers, mine are working passably well. And the outer shells fit the size of my head. I could use more cartilage in my left knee, and a new spinal disk one day, but I dont fancy todays remediesa cold metal implant, or a gift from a four-legged animal.

Nonetheless, a homegrown ear is what Lawrence Bonassar offers me, extending it in his open hand, as if it were sprouting out of his palm and shaking hands were just another form of listening. Translucent white, the ear feels smooth and warm as amber, and my thumb automatically plays over its many ridges and folds. Im surprised by the level of minute detail. Its quite odd to fondle a disembodied ear. Or a prizewinning one, for that matter. His bioprinting has won first place in the World Technology Awards in Health and Medicine, the Oscars of the technology world, which celebrate inventions of the greatest likely long-term significance for the twenty-first century.

The ear he lends me is solid, yet bendy as a dried apricot, and would flex easily under the skin. But this one isnt intended for anyones head. He returns it to a glass jar of preservative and sets it back on a shelf. His lab looks like the mental crossroads it is: a chemistry lab full of microscopes, workbenches, sinks, glass, and stainless steel. But also a medical facility, complete with large incubators, sterile fields, and countless drawers of parts and molds. And also a tech center equipped with computers, robots, and of course 3D printers. All accompanied by a seemingly endless wall of windows.

Outside there is the frail enchantment of snow, and a school bus creeping by like the orange pupa of some colorful butterfly.

One long ray of sunlight like a pointing finger touches a white desktop box about the size of the first manual typewriter, but less complicated looking. Two steel syringes with nozzles float above a metal warming plate, where theyll begin hopes calligraphy. The ink may be living cells of any type, lifes pageant in a polymer. When the nineteenth-century painter Georges Seurat used a similar stipple technique with pure color, his dots seemed to blend, but that was merely sleight of eye. These dots merge because cells fuse freely; they dont need a human nudge.

As the moving pen writes, it doubles back over each line, stippling new layers, until it creates an outer ear that isnt exactly organic in the way a wart or an eyelash is. Still, when transplanted, it will twitch with life, feel embodied, and help redefine what we mean by natural. Then any tangle of flesh and blood will serve as home, making rejection obsolete. For once in our long-storied evolution, a body part isnt molded solely by evolutions blueprintwe can choose its design. And forget years. Once he receives the MRI, CT, or 3D image, Bonassar can grow an ear in fifteen minutes. The time it takes me to walk to my local coffee shop.

Bonassar has mastered the art of training materials to carry cells and deposit them like puppies exactly where he wants while keeping them alive and happy. And, just like healthy pups, the cells are agile enough to tussle without smooshing, hale enough to tug, eager to curve their tiny mouths inward and eat all the nutrients they need.

The two polymers he prefers are collagenprotein fibers the body uses as gluey twine and mortarand alginate, a gel found in the brown seaweed I held at Thimble Islands, and used by drive-ins to make milk shakes thick and creamy as they swirl out of the dispenser. My parents had one of the first McDonalds, where I sometimes poured shakes, and I know the consistency wellbetween syrup and toothpaste. Thats also the way bioprinters dispense ink, except that the carrier has clusters of living cells embedded in it.

When I ask Bonassar if he makes the scaffolds here, too, a proud smile appears, as he explains that the scaffolding is the liquid. This shake contains its own framework, so that an ear fresh from the printer is ready to go. And the ink? Water droplets wouldnt stick together. Hard marbles would roll off. Instead he uses squishy collagen marbles, which cling to their neighbors. Like eggs or blood, collagen gels when its heated and the fibers scramble together. So he stores it cold, allowing it to stiffen only when it falls onto the warming plate.

Its a technology he hijacked from Hod Lipson, and he began printing in Lipsons lab with a printer wide as a brick hearth and heavy as an iron cauldron. Now its the size of an espresso machine and shockingly simple: load whatever you want into your syringe, place it so that the motor can grab the plunger and print, then adjust the rate ink squeezes out, and set the print heads path. After that, two more steps remain.

He leads me through an open doorway into a tiny room packed with large machines, including a sterile culture hood with a large window, in which the whole bioprinter can be placed, safe from dust, fungi, and bacteria. It looks like an incubator for preemies.

No, this is the incubator, he says, turning to peer through a glass door into dimly lit shelves. Look there. Can you see them?

Rising on tiptoes, I see two petri dishes holding small strange buttons or perhaps tires. The odd items are spinal implants destined for a bouncing, braying fluff of a dog. Canine arthritis is a big problem for frolicsome dachshunds, hounds, and especially beaglesdogs with short necks and long bodies wear out their cervical disks and develop joint pains just as we do. Working with Cornells Veterinary School, Bonassars lab created implants with a gel-like core that pushes against a tougher outside ring, pressurizing it very much like blowing up a tire. Its also a true organ, two different kinds of tissue that work together seamlessly.

In osteoarthritis, cartilages cushion wears out like an old pillow, and bone rubs bone raw, producing inflammation and pain. Almost everyone has a creaky-jointed sufferer in the family. Todays back operations usually remove a damaged disk and fuse the vertebrae together with a metal plate, which creates the rigidity of a poker up the spine, doesnt always work, and can make adjoining vertebrae weak as loose teeth. An alternative to fusion would be a godsend to sixty or seventy million people in the United States alone. Starting small, Bonassar replaced spinal cartilage in rats with his own lab-grown variety, and the rats lived normal lives, apparently pain-free. Next in line are larger animalsa dog, sheep, or goatand if that works, then human volunteers will follow.

Bending to examine a smaller chamber alongside the incubator, I spot the next stage in the life of bespoke disks. Since all tissues in the body are weight-bearing and thrive under stress, his lab toughens the tissues, squeezing the implants over and over, as if they were pumping iron. This also quickens their metabolism, squooshing food in and smooshing waste out, making it more efficient. Such bioprinted implants could last longer than natural ones.

Its quite realistic to assume, Bonassar says, hazel eyes sparkling, that the first stages of the human clinical trials could happen within the next five years.

When I ask about printing out hearts, lungs, and livers, he leads me to a large computer screen where he summons up a pair of gloved hands holding what look like pieces of sushi: thick white slices with a thin halo of pink. A closer look reveals a rarer delicacy: ear implants fabricated from 3D photographs of Bonassars daughters ears. He smiles at them with a love pure as starlight. Then he points out the blood vessels in the thin rind around the implants, and the thicker comma of white tissue thats quite bare. Yet those bare cells prosper, too.

The challenge with organs isnt their size, its the plumbing. The bigger organs are like Venetian cities, fed by elaborate water streets afloat with gondolas. Many labs around the world are hunting the best ways to mirror those supply lines, and the elusive aha moment could be one week away or ten years. But its scent is in the air, and no one doubts it will soon revolutionize medicine with clean, healthy organs on demand. A touch of mental whiplash is to be expected.

Its a hallmark of the Anthropocene that science and technology are galloping at such a pace that Bonassars field didnt even exist when he was in high school or college. Now hes among those ringing the biggest changes, including a dramatically new view of the human body and the jostles of cells that inhabit living tissueseven what a cell is and how a cell behaves. Not only do we know about stem cells, were starting to wield them in clever ways to mend the body, and its not arduous to do; it can be as simple as exposing cells to the right chemicals or stimuli. Theres been a stunning paradigm shift from the rule of phenotypeone cell type fated for one job and nothing elseto phenotypic elasticity, the idea that cells are far more versatile and can be repurposed, like a hammer used to anchor a kite.

We now grasp that a wafer of skin can be retrained to do just about anything. Its a new category of raw material, like wood or stone, with potent gifts. An ebony tree growing in Africa may provide shade to humans, and a lofty haven for a leopard gnawing a carcass, but its dark grain also gives rise to clarinets, piano keys, violin fingerboards, and music. The old idea of skin as a sacred cloak with two main jobsto seal off the vulnerable organs inside us and define our individualityhas given way to a sense of how mingling, malleable, and porous the body really is. At the cellular level, were stunningly mutable, not just in our lifestyles, which we always knew, but in our bits and pieces. A butler can change his mind, via his neurons, and become a gandy dancer. A dash of skin can become fresh neurons for a Parkinsons-stricken monk. What to do with cells is increasingly more a question of imagination than material.

Spearheaded by pioneers like Bonassar and Lipson, Anthropocene engineering has penetrated the world of medicine and biology, revolutionizing how we regard the body. In these vistas, electricity, architecture, and chemistry slant together and tell tales never heard before.

We baby boomers grew up with a cartload of absolutes, handed down from generation to generation of biologists, the most daunting one, perhaps, being that were born with all the brain cells well ever have, because the brain doesnt mint new cells. Yet now we have proof that it does, even in old age. Weve spent the last decade blowing up a lot of similar assumptions, and I wonder what other rigid ideas will topple. Bonassar offers me another quite mysterious one.

We were told, over and over, he says with relish, that the heart is an organ that positively cant regenerate. Yet an amazing study has turned that idea upside down.

In this study, he explains, heart transplant patients received hearts from a donor of a different gendermostly men receiving womens hearts. In theory, one should be able to examine the heart recipient, look at the cells in his borrowed heart, and find female cells from the donor. But it turns out that, on autopsy, if these men bore their transplanted hearts for more than a decade, almost half of the heart cells were mysteriously replaced by male cells. The mechanism isnt clearbut the new paradigm is. The hearts metronome tissues, which we always believed couldnt regenerate, actually can. No one knows if the cell-swap is a fusion or whether the female cells were forcibly displaced. Either way, its overturned the handcart of possibility, and furrowed many brows. If organs as elemental as brain and heart can be persuaded to regenerate, and others, like ears and corneas, can be fashioned from living ink, how will that change us as a species? Will the printing of organs affect our evolution? Could it alter our genes? Im curious to know what Bonassar thinks.

The possibility intrigues him, too. The real question, he says, is what the evolutionary pressure of these therapies might be. Would faulty genes become more prevalent, because they could be fixed? I wear contact lenses, but if I were a caveman and my eyesight was as bad as it was when I was five, I would have been in serious trouble. Now it doesnt matter. We could replace our defective parts, live longer, and feel healthier. Then he adds a provocative afterthought: Yet physically we could be much weaker and more flawed genetically.

Suppose we dont just repair and enhance ourselves, suppose we live longer as a result? The primary focus of the work in Bonassars labcartilage for arthritis, cartilage for traumatic injury, disks for back painis medical solutions for ailments that tend to afflict people long after theyve had children, when evolution has stopped bedeviling them to breed. Would the ability to be fit for a decade longer present an evolutionary advantage? Would people take more risks? How will we regard the bodys bits and pieces, and safeguard them, if we know we can cheaply replace them? We replace heart valves or heart tissue to extend life, but what if you can cure arthritis, and keep people active and sexual well into their seventies and eighties?

Think geriatric cyborgs and chimeras. Grandpas going to be saying a lot more interesting things than Where are my teeth! Just staying active for an added decade may alter our society as a whole far more than fixing a particular defect in the heart, liver, brain, or kidney.

The ninety-year-olds Ive known havent run marathons, even with gleaming new hips and knees, but theyve inhaled a lot of sky on daily walks. Even bioprinted cartilage needs exercise. Looking forward to a walkabout through drifting avenues of snow, I say good-bye to Bonassar and slip into my parka. As I stride down the hallway and into the atrium, the buildings smart sensors work and a little breeze runs before me like an invisible serpent. Hail begins lightly rattling against the windows. A vague thought, as elusive as the smell of violets, nags at me. A dark cloud passes over, and I feel aware of how aging, like winter weather, can chill the bones. For a moment, that thought hangs like an icicle, tapering and cold. Then my mind reels through hopeful images: an incubator full of spinal disks, the flexible necks of dachshunds, the long open labs of students with eager minds, the children with new ears, and the warming plate where collagen marbles land on their way to reshaping our future biology, and I swear I hear spring buzzing like a red-winged blackbird.

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