A decellularized small porcine liver.
Jennifer Cisneros was 18 years old, commuting to college from her family's home outside Annapolis, Maryland, when she came down with what she thought was the flu. Over the following weeks, however, her fatigue and nausea worsened, and her weight began to plummet. Alarmed, her mother took her to see a pediatrician. "When I came back with the urine cup, it was orange," Cisneros recalls. "He was like, 'Oh, my God. I've got to send you for blood work.'"
"Eventually, we'll be better off than with a human organ."
Further tests showed that her kidneys were failing, and at Johns Hopkins Hospital, a biopsy revealed the cause: Goodpasture syndrome (GPS), a rare autoimmune disease that attacks the kidneys or lungs. Cisneros was put on dialysis to filter out the waste products that her body could no longer process, and given chemotherapy and steroids to suppress her haywire immune system.
The treatment drove her GPS into remission, but her kidneys were beyond saving. At 19, Cisneros received a transplant, with her mother as donor. Soon, she'd recovered enough to return to school; she did some traveling, and even took up skydiving and parasailing. Then, after less than two years, rejection set in, and the kidney had to be removed.
She went back on dialysis until she was 26, when a stranger learned of her plight and volunteered to donate. That kidney lasted four years, but gave out after a viral infection. Since 2015, Cisneros—now 32, and working as an office administrator between thrice-weekly blood-filtering sessions—has been waiting for a replacement.
She's got plenty of company. About 116,000 people in the United States currently need organ transplants, but fewer than 35,000 organs become available every year. On average, 20 people on the waiting list die each day. And despite repeated campaigns to boost donorship, the gap shows no sign of narrowing.
"This is going to revolutionize medicine, in ways we probably can't yet appreciate."
For decades, doctors and scientists have envisioned a radical solution to the shortage: harvesting other species for spare parts. Xenotransplantation, as the practice is known, could provide an unlimited supply of lifesaving organs for patients like Cisneros. Those organs, moreover, could be altered by genetic engineering or other methods to reduce the danger of rejection—and thus to eliminate the need for immunosuppressive drugs, whose potential side effects include infections, diabetes, and cancer. "Eventually, we'll be better off than with a human organ," says David Cooper, MD, PhD, co-director of the xenotransplant program at the University of Alabama School of Medicine. "This is going to revolutionize medicine, in ways we probably can't yet appreciate."
Recently, progress toward that revolution has accelerated sharply. The cascade of advances began in April 2016, when researchers at the National Heart, Lung, and Blood Institute (NHLBI) reported keeping pig hearts beating in the abdomens of five baboons for a record-breaking mean of 433 days, with one lasting more than two-and-a-half years. Then a team at Emory University announced that a pig kidney sustained a rhesus monkey for 435 days before being rejected, nearly doubling the previous record. At the University of Munich, in Germany, researchers doubled the record for a life-sustaining pig heart transplant in a baboon (replacing the animal's own heart) to 90 days. Investigators at the Salk Institute and the University of California, Davis, declared that they'd grown tissue in pig embryos using human stem cells—a first step toward cultivating personalized replacement organs. The list goes on.
Such breakthroughs, along with a surge of cash from biotech investors, have propelled a wave of bullish media coverage. Yet this isn't the first time that xenotransplantation has been touted as the next big thing. Twenty years ago, the field seemed poised to overcome its final hurdles, only to encounter a setback from which it is just now recovering.
Which raises a question: Is the current excitement justified? Or is the hype again outrunning the science?
A History of Setbacks
The idea behind xenotransplantation dates back at least as far as the 17th century, when French physician Jean-Baptiste Denys tapped the veins of sheep and cows to perform the first documented human blood transfusions. (The practice was banned after two of the four patients died, probably from an immune reaction.) In the 19th century, surgeons began transplanting corneas from pigs and other animals into humans, and using skin xenografts to aid in wound healing; despite claims of miraculous cures, medical historians believe those efforts were mostly futile. In the 1920s and '30s, thousands of men sought renewed vigor through testicular implants from monkeys or goats, but the fad collapsed after studies showed the effects to be imaginary.
Research shut down when scientists discovered a virus in pig DNA that could infect human cells.
After the first successful human organ transplant in 1954—of a kidney, passed between identical twin sisters—the limited supply of donor organs brought a resurgence of interest in animal sources. Attention focused on nonhuman primates, our species' closest evolutionary relatives. At Tulane University, surgeon Keith Reemstma performed the first chimpanzee-to-human kidney transplants in 1963 and '64. Although one of the 13 patients lived for nine months, the rest died within a few weeks due to organ rejection or infections. Other surgeons attempted liver and heart xenotransplants, with similar results. Even the advent of the first immunosuppressant drug, cyclosporine, in 1983, did little to improve survival rates.
In the 1980s, Cooper—a pioneering heart transplant surgeon who'd embraced the dream of xenotransplantation—began arguing that apes and monkeys might not be the best donor animals after all. "First of all, there's not enough of them," he explains. "They breed in ones and twos, and take years to grow to full size. Even then, their hearts aren't big enough for a 70-kg. patient." Pigs, he suggested, would be a more practical alternative. But when he tried transplanting pig organs into nonhuman primates (as surrogates for human recipients), they were rejected within minutes.
In 1992, Cooper's team identified a sugar on the surface of porcine cells, called alpha-1,3-galactose (a-gal), as the main target for the immune system's attack. By then, the first genetically modified pigs had appeared, and biotech companies—led by the Swiss-based pharma giant Novartis—began pouring millions of dollars into developing one whose organs could elude or resist the human body's defenses.
Disaster struck five years later, when scientists reported that a virus whose genetic code was written into pig DNA could infect human cells in lab experiments. Although there was no evidence that the virus, known as PERV (for porcine endogenous retrovirus) could cause disease in people, the discovery stirred fears that xenotransplants might unleash a deadly epidemic. Facing scrutiny from government regulators and protests from anti-GMO and animal-rights activists, Novartis "pulled out completely," Cooper recalls. "They slaughtered all their pigs and closed down their research facility." Competitors soon followed suit.
The riddles surrounding animal-to-human transplants are far from fully solved.
A New Chapter – With New Questions
Yet xenotransplantation's visionaries labored on, aided by advances in genetic engineering and immunosuppression, as well as in the scientific understanding of rejection. In 2003, a team led by Cooper's longtime colleague David Sachs, at Harvard Medical School, developed a pig lacking the gene for a-gal; over the next few years, other scientists knocked out genes expressing two more problematic sugars. In 2013, Muhammad Mohiuddin, then chief of the transplantation section at the NHLBI, further modified a group of triple-knockout pigs, adding genes that code for two human proteins: one that shields cells from attack by an immune mechanism known as the complement system; another that prevents harmful coagulation. (It was those pigs whose hearts recently broke survival records when transplanted into baboon bellies. Mohiuddin has since become director of xenoheart transplantation at the University of Maryland's new Center for Cardiac Xenotransplantation Research.) And in August 2017, researchers at Harvard Medical School, led by George Church and Luhan Yang, announced that they'd used CRISPR-cas9—an ultra-efficient new gene-editing technique—to disable 62 PERV genes in fetal pig cells, from which they then created cloned embryos. Of the 37 piglets born from this experiment, none showed any trace of the virus.
Still, the riddles surrounding animal-to-human transplants are far from fully solved. One open question is what further genetic manipulations will be necessary to eliminate all rejection. "No one is so naïve as to think, 'Oh, we know all the genes—let's put them in and we are done,'" biologist Sean Stevens, another leading researcher, told the The New York Times. "It's an iterative process, and no one that I know can say whether we will do two, or five, or 100 iterations." Adding traits can be dangerous as well; pigs engineered to express multiple anticoagulation proteins, for example, often die of bleeding disorders. "We're still finding out how many you can do, and what levels are acceptable," says Cooper.
Another question is whether PERV really needs to be disabled. Cooper and some of his colleagues note that pig tissue has long been used for various purposes, such as artificial heart valves and wound-repair products, without incident; requiring the virus to be eliminated, they argue, will unnecessarily slow progress toward creating viable xenotransplant organs and the animals that can provide them. Others disagree. "You cannot do anything with pig organs if you do not remove them," insists bioethicist Jeantine Lunshof, who works with Church and Yang at Harvard. "The risk is simply too big."
"We've removed the cells, so we don't have to worry about latent viruses."
Meanwhile, over the past decade, other approaches to xenotransplantation have emerged. One is interspecies blastocyst complementation, which could produce organs genetically identical to the recipient's tissues. In this method, genes that produce a particular organ are knocked out in the donor animal's embryo. The embryo is then injected with pluripotent stem cells made from the tissue of the intended recipient. The stem cells move in to fill the void, creating a functioning organ. This technique has been used to create mouse pancreases in rats, which were then successfully transplanted into mice. But the human-pig "chimeras" recently created by scientists were destroyed after 28 days, and no one plans to bring such an embryo to term anytime soon. "The problem is that cells don't stay put; they move around," explains Father Kevin FitzGerald, a bioethicist at Georgetown University. "If human cells wind up in a pig's brain, that leads to a really interesting conundrum. What if it's self-aware? Are you going to kill it?"
Much further along, and less ethically fraught, is a technique in which decellularized pig organs act as a scaffold for human cells. A Minnesota-based company called Miromatrix Medical is working with Mayo Clinic researchers to develop this method. First, a mild detergent is pumped through the organ, washing away all cellular material. The remaining structure, composed mainly of collagen, is placed in a bioreactor, where it's seeded with human cells. In theory, each type of cell that normally populates the organ will migrate to its proper place (a process that naturally occurs during fetal development, though it remains poorly understood). One potential advantage of this system is that it doesn't require genetically modified pigs; nor will the animals have to be raised under controlled conditions to avoid exposure to transmissible pathogens. Instead, the organs can be collected from ordinary slaughterhouses.
Recellularized livers in bioreactors
(Courtesy of Miromatrix)
"We've removed the cells, so we don't have to worry about latent viruses," explains CEO Jeff Ross, who describes his future product as a bioengineered human organ rather than a xeno-organ. That makes PERV a nonissue. To shorten the pathway to approval by the Food and Drug Administration, the replacement cells will initially come from human organs not suitable for transplant. But eventually, they'll be taken from the recipient (as in blastocyst complementation), which should eliminate the need for immunosuppression.
Clinical trials in xenotransplantation may begin as early as 2020.
Miromatrix plans to offer livers first, followed by kidneys, hearts, and eventually lungs and pancreases. The company recently succeeded in seeding several decellularized pig livers with human and porcine endothelial cells, which flocked obediently to the blood vessels. Transplanted into young pigs, the organs showed unimpaired circulation, with no sign of clotting. The next step is to feed all four liver cell types back into decellularized livers, and see if the transplanted organs will keep recipient pigs alive.
Ross hopes to launch clinical trials by 2020, and several other groups (including Cooper's, which plans to start with kidneys) envision a similar timeline. Investors seem to share their confidence. The biggest backer of xenotransplantation efforts is United Therapeutics, whose founder and co-CEO, Martine Rothblatt, has a daughter with a lung condition that may someday require a transplant; since 2011, the biotech firm has poured at least $100 million into companies pursuing such technologies, while supporting research by Cooper, Mohiuddin, and other leaders in the field. Church and Yang, at Harvard, have formed their own company, eGenesis, bringing in a reported $40 million in funding; Miromatrix has raised a comparable amount.
It's impossible to predict who will win the xenotransplantation race, or whether some new obstacle will stop the competition in its tracks. But Jennifer Cisneros is rooting for all the contestants. "These technologies could save my life," she says. If she hasn't found another kidney before trials begin, she has just one request: "Sign me up."
The process of finding the right gift for your favorite life science lover can be daunting. Here's a roundup of the coolest bio-products related to health, nutrition, gaming, lifestyle and more.
AYO Circadian Light Therapy Wearable
We don’t hear it tick, but we have our own clock inside our body–more precisely, circadian clocks. Our cells contain tiny molecular clocks that keep track of our circadian rhythms, or our sleep and metabolism pattern and activity levels, on a daily basis. Chronic circadian disruptions can lead to sleep disorders, poor energy levels, weight gain, lousy mood, and sped-up aging, as well as increased risk for every “modern” disease out there, from diabetes to cancer.
Now, high-tech glasses have been developed that attempt to mimic the benefits of sunlight. In the morning and afternoon, these glasses shed blue light into your eyes to stimulate the master clock at the base of your brain for less drowsiness. The technology's design draws from an area of research, chronobiology, that received a Nobel Prize in 2017 and has become increasingly active in recent years.
“We have been developing and testing the AYO Circadian Health solution for the past five years in collaboration with some of the world's leading experts and researchers in chronobiology, light therapy and health,” said Alexander Dimitrov, co-creator of AYO. “We have done studies with over 25,000 participants, and over one million light sessions,” Dimotrov continued, partnering with institutions such as Mount Sinai Hospital, City of Hope and the U.S. Department of Defense.
The technology could fundamentally reshape the way we view sleep, health and our daily calendars. And, when connecting to a mobile app, the glasses could minimize circadian disruptions for travelers between conflicting time zones.
($269)
myDNAge Test
It's not easy for many people to break free of their attachment to the concept of chronological age, which counts years by how many times we’ve circled the sun since the day we were born. Society lumps us all into one age bracket according to our date of birth but, lately, research is suggesting that we should do some serious deconditioning. According to these studies, the more accurate measure is your biological age, a measurement based on various biomarkers of the body’s overall health and resilience, regardless of your calendar age.
If you want to find out your “true” biological age, myDNAge is a test that focuses on epigenetics, or patterns of changes in DNA methylation, with some initial research pointing to its accuracy. It offers a snapshot of your epigenetic age as well as key biomarkers related to your metabolism, risk of Alzheimer's and more, according to Xiaojing Yang, group leader of epigenetics at myDNAge. “You can perform tests six to 12 months [apart] to track the impact of lifestyle changes,” Yang said. The kit could be a useful tool both for citizen scientists and biohacking veterans.
($299 for one kit–Use code NEWYEARNEWME to receive 50% off a second kit)
Prairie Sky Yak Cheese
Do you love cheese? Do you love exotic cheese? Do you have an interest in preserving biological and genetic diversity? If you answered yes to all three questions, yak cheese was made for you. This type of cheese typically comes from a free-range yak living 13,000 feet above surface level in the Tibetan Himalayas, a relative of the endangered Wild yak. (North America is home to at least 5,000 registered yaks.)
“When I learned that we had a piece of rare biodiversity to be preserved for future generations, I realized that the yak in North America needed a job,” said Nicole Geijer Porter, president of World Heritage Yak Conservancy (WHYC), an organization formed to protect heritage yak “If an animal cannot be beneficial to the rancher in some way, exclusively as pets and lawn ornaments, they will go extinct. Raised for meat they are often hybridized with cattle to grow bigger and faster, so they will also go extinct,” said Porter, an epigeneticist turned yak herder.
Each slice of cheese and piece of butter supports the genetic testing and tracking of Tibetan yak. (You can become a member of WHYC through the Adopt-A-Yak program). “This project is also of biological importance because of the low methane emission research on yak, and the high nutritional content of the milk and cheese,” said Porter.
As for flavor, the Prairie Sky Yak Gruyere is a semi-hard cheese with a nutty taste sometimes compared to chocolate; Tomme de Savoie is a semi-soft Alpine cheese reminiscent of a washed rind muenster; and the Yak Cheddar is made with yak milk following the classic English recipe from Wells Cathedral, with earthly and pungent flavors.
(Various prices; $59.95 for the Three Yak Cheese Flight Gift Box, $139.95 for the Regional Himalayan Yak Cheddar Gift Basket and more)
Bite Toothpaste Bits
The price of a healthy smile is steep. Each year over one billion plastic toothpaste tubes are thrown out, over 50 Empire State Buildings worth of these tubes end up in landfills or oceans, and many animals suffer and die each year in cruel tests for improving oral care in people.
Sustainable oral care is both an act of self-love and giving back to the environment. Bite is a toothpaste that boasts about its green practices for a reason: it uses recyclable glass bottles with aluminum lids that break down into sand after they’ve been used. For shipping, Bite uses kraft envelopes padded with recycled and compostable newspapers, and its boxes are made of fully recycled, corrugated cardboard and sealed with paper tape. Bite refills come in 100% home compostable pouches every four months (still no plastic).
Sustainability aside, there may be an element of fun to Bite – as you brush, a mint foam forms “like magic,” the company claims.
Fractional Laser Treatment for Skin
The environment is hard on our skin: from ultraviolet rays to pollution, a constant oxidative war is waged upon it, leading to loss of collagen and damage to the barrier function of the skin. A fractional laser treatment is a type of laser skin resurfacing procedure that essentially traumatizes the skin – in a good way - through subjecting a small area of it to tiny amounts of laser energy. The laser penetrates the second layer of skin, the dermis, leading to skin exfoliation, which stimulates collagen and elastin production.
The treatment may help with soothing acne scarring, correcting uneven skin tone and texture, and reducing wrinkles and fine lines, sun damage and age spots. Recent research suggests the fractional laser can help with improving skin elasticity and reducing the amount and depth of wrinkles, though there’s little to no evidence for any benefits for eyebags, dark circles, discolorations within the eye area and water retention.
(Typically, a single fractional laser treatment costs $750 for a small area, $1500 for a full facial treatment, and $2000 for full face.)
Gadgets and Apps to Measure Your Heart Rate Variability
Heart rate variability may sound like a condition that requires immediate medical treatment, but the more you have of it, the better for your health. Although you may think of the heart as a steadily beating metronome, there are actually small differences in the amount of time between each beat. These differences are called HRV, and having more HRV has been linked to better fitness and fewer diseases.
HRV is easy to measure with a range of gadgets on the market, including Fitbits and Oura Rings. Which product floats your boat is a matter of personal preference, but the Polar H10 chest strap offers some advantages. For example, you can measure your HRV with the Polar H10 while walking around, unlike some devices that require you to stay still while taking a reading.
Plus, the Polar sensor pairs with free apps such as Elite HRV that are great for tracking how your HRV changes over time. "HRV really helps you gauge if you're moving in a positive or negative direction" with your health, says Jason Moore, the CEO and founder of Elite HRV and Spren. Have fun experimenting over the holidays with different lifestyle habits that are associated with higher HRV, some studies show, such as intermittent fasting, regular exercise and just getting more sleep.
($89 for the Polar H10, $0 for the Elite HRV app)
FoodMarble AIRE2
Its predecessor, FOODMarble AIRE1 was a pocket-size breath-testing device that measured hydrogen on the breath. More hydrogen means less digestion, and the AIRE1 used advanced breathalyzer technology to figure out what exactly is going on with the gut. Now, the company has launched FoodMarble AIRE2, which also measures methane alongside with hydrogen. High levels of methane in the body may cause abdominal pain, bloating and constipation, cirrhosis of the liver and chronic pancreatitis. The AIRE2 also comes with haptic feedback to make it easier to use.
Research suggests that these breath tests are valid as at-home diagnostic tools for many digestive conditions. To get the most accurate results, though, it’s important to closely follow the recommended protocol - for example, you can’t eat or drink anything for 10 to 12 hours before the test.
($229)
Adventurist Backpack’s Classic Backpack
The Classic backpack is a perfect option for life science aficionados who enjoy getting outside and exploring in nature. Padding in the front and back provides extra protection for camera gear, laptop, and other electronics, and it's completely water-resistant so you can get outside in winter weather.
Nobility points: Adventurist Backpack Co. is partnered with national non-profit Feeding America, and every backpack sold helps provide 25 meals to families in need across the U.S.
($65)
This Saves Lives
Speaking of nobility points, you could load your new backpack with a food choice that helps feed others as well. In 2013, actors Kristin Bell, Ryan Devlin, Ravi Patel and Todd Grinnell teamed up to start This Saves Lives, which makes power bars full of vitamins and nutrients, and the company has a unique business model: for every bar you buy, a packet of food is sent to a child in need. In addition to offering essential nutrients, the bars are non-GMO, kosher and gluten-free. Note: This Saves Lives is owned by the same company, GOOD Worldwide, that owns Leaps.org.
(Wild Blueberry & Pistachio bars, $23.99)
NADI X Pants
Even if you’re a yoga zealot enjoying the benefits to your strength, balance and flexibility, chances are you're performing the movements sort of askew. Wearable technology wants to improve your yoga posture and these sleek yoga pants called NADI X have subtle electronic sensors that track how you place your hands, rotate your hips, and align your back. The leggings use haptic feedback (or vibrations on your skin) to slowly guide you into correct alignment. You can also combine the wearable with an app that contains 40 poses and fitting music. Even if you aren't into yoga, you could use the pants for a perfect stretching session. If you do use it for yoga poses, the pants will “speak” to you, letting out a soothing "om" sound once everything is perfect.
Meta Quest Pro VR headset
When it comes to perfecting virtual reality (VR), the Meta Quest Pro VR headset is one step ahead the rest. In a vibrant 3D virtual space, your Meta avatar has the ability to translate your real-life facial expressions into the virtual realm so the experience can feel more personal, while controllers track your movement and use haptic feedback to translate your hand gestures and finger actions into VR as well. Unlike its Quest 2 headset, Meta markets this Quest Pro headset, which was just released in October, as a great tool for work and business meetings, but you can also use it to play games, watch movies, or download fitness apps or mental-health related apps – some of which are designed to help you get boxing workouts with long-distance friends, fight your fear of heights or meditate in outer space.
Rouge Sur Mesure Custom Lip Color Creator
Beauty and artificial intelligence (AI) complement each other well in the new Yves Saint Laurent lip personalized color – which wants to put the final nail on the coffin of generic lipsticks. This is a lipstick printer at its core. You pair a device to your smartphone and then insert three lipstick cartridges into the base, each of which comes with a color palette (all four could create up to 4,000 lipstick shades). Particularly charming is the fact that you can take a photo of your outfit, and the app will suggest shades that match or clash it.
($299, cartridges $89 each)
Dairy-Free Cream Cheese and Meatless Breakfast Patties
On the environmental front again, meatless patties and dairy-free cream cheese constitute conscientious and delicious choices for vegans, vegetarians and pretty much anyone else. Chicago-based Nature's Fynd is worth checking out. It uses a microbe named Fusarium strain flavolapis, which has origins in an acidic hot spring at Yellowstone National Park.
“We use this remarkable microbe to grow Fy — a nutritional fungi protein that’s made into a wide variety of delicious and sustainable foods,” says Karuna Rawal, Nature’s Fynd CMO. Fy is grown via a breakthrough fermentation process using a fraction of the water, land, and energy compared to traditional protein sources.
It’s a sustainable way to grow food for Earth’s population,” but Nature’s Fynd isn’t just concentrating on Earth. The company recently partnered with NASA to send Fy to space. “As long as there’s an appropriately controlled environment, we can grow Fy anytime, anywhere. It could be a nutritious food source for astronauts on deep space missions," said Rawal.
CBD Oil
Biologically curious people may be especially interested in trying cannabinoid (CBD) oil. CBD is a natural and safe substance found in cannabis, which has been found to tackle anxiety and depression, reduce symptoms of post-traumatic stress disorder, help manage chronic pain and migraines, improve sleep patterns, and keep panic attacks at bay. Kanibi’s Isolate CBD Oil Tincture is a good choice as it is cinnamon-flavored and made in an FDA-inspected facility.
($109--25% off on your first order)
Govee RGBIC Floor Lamp
Another winner for anyone who's been hearing about the health benefits of obeying your circadian rhythms: "RGB" lights, or red-green-blue lights that can be operated by remote control to shine bright blue light during the day and then, with a few touches of your phone, bathe you in warmer, red light to get you ready for bed. Look for RGB bulbs to stick into the light fixtures you already have, or you could opt for the Govee floor lamp that syncs with an app on your phone (or Alexa) for circadian color changing. You can also put it on party mode and watch it shift across 16 million color shades in response to the rhythms and beats of Cuddle Up, Cozy Down Christmas and Hanukkah Oh Hanukkah.
($99)
PackPoint
If you suffer from packing anxiety (or incompetence), an app may take away the pain. PackPoint is an app that builds your packing list according to trip type, activities and weather. You add your trip details, select activities (fancy dinner, business meeting, or even workout are some examples), and PackPoint tells you what you need to bring to your destination. The app is free, but upgrading to Premium for a small fee lets you add your own activities and packing list items.
(Free, Premium Package $2.99)
Eternity Rose
Roses symbolize love, passion, innocence, friendship, and the disarming power of natural beauty. They wilt fast, though, and their spectacle is an unsettling reminder of the fragility of beauty and existence. Unless you dip the rose in 24 karat gold.
The Eternity Rose is put through an intricate three-month process of electroplating, or coating the rose with copper and then with other metals in micro-thin layers. You won’t have to see your flowers sag after a few days because these roses never die. The glitter of gold atop the natural rose (or platinum or silver–whatever you prefer) will fit right in with the Christmas Eve ambiance.
($169 for the gold rose)
