Ordinary people are living better with chronic conditions thanks to a recent explosion of developments in medical implants.
Beware, cyborgs walk among us. They’re mostly indistinguishable from regular humans and are infiltrating every nook and cranny of society. For full disclosure, I’m one myself. No, we’re not deadly intergalactic conquerors like the Borg race of Star Trek fame, just ordinary people living better with chronic conditions thanks to medical implants.
In recent years there has been an explosion of developments in implantable devices that merge multiple technologies into gadgets that work in concert with human physiology for the treatment of serious diseases. Pacemakers for the heart are the best-known implants, as well as other cardiac devices like LVADs (left-ventricular assist devices) and implanted defibrillators. Next-generation devices address an array of organ failures, and many are intended as permanent. The driving need behind this technology: a critical, persistent shortage of implantable biological organs.
The demand for transplantable organs dwarfs their availability. There are currently over 100,000 people on the transplant waiting list in the U.S., compared to 40,000 transplants completed in 2021. But even this doesn’t reflect the number of people in dire straits who don’t qualify for a transplant because of things like frailty, smoking status and their low odds of surviving the surgery.
My journey to becoming a cyborg came about because of a lifelong medical condition characterized by pathologically low motility of the digestive system, called gastroparesis. Ever since I was in my teens, I’ve had chronic problems with severe nausea. Flareups can be totally incapacitating and last anywhere from hours to months, interspersed with periods of relief. The cycle is totally unpredictable, and for decades my condition went both un- and misdiagnosed by doctors who were not even aware that the condition existed. Over the years I was labeled with whatever fashionable but totally inappropriate medical label existed at the time, and not infrequently, hypochondria.
Living with the gastric pacer is easy. In fact, most of the time, I don’t even know it’s there.
One of the biggest turning points in my life came when a surgeon at the George Washington University Hospital, Dr. Frederick Brody, ordered a gastric emptying test that revealed gastroparesis. This was in 2009, and an implantable device, called a gastric pacer, had been approved by the FDA for compassionate use, meaning that no other treatments were available. The small device is like a pacemaker that’s implanted beneath the skin of the abdomen and is attached to the stomach through electrodes that carry electrical pulses that stimulate the stomach, making it contract as it’s supposed to.
Dr. Brody implanted the electrical wires and the device, and, once my stomach started to respond to the pulses, I got the most significant nausea relief I’d had in decades of futile treatments. It sounds cliché to say that my debt to Dr. Brody is immeasurable, but the pacer has given me more years of relative normalcy than I previously could have dreamed of.
I should emphasize that the pacer is not a cure. I still take a lot of medicine and have to maintain a soft, primarily vegetarian diet, and the condition has progressed with age. I have ups and downs, and can still have periods of severe illness, but there’s no doubt I would be far worse off without the electrical stimulation provided by the pacer.
Living with the gastric pacer is easy. In fact, most of the time, I don’t even know it’s there. It entails periodic visits with a surgeon who can adjust the strength of the electrical pulses using a wireless device, so when symptoms are worse, he or she can amp up the juice. If the pulses are too strong, they can cause annoying contractions in the abdominal muscles, but this is easily fixed with a simple wireless adjustment. The battery runs down after a few years, and when this happens the whole device has to be replaced in what is considered minor surgery.
Such devices could fill gaps in treating other organ failures. By far most of the people on transplant waiting lists are waiting for kidneys. Despite the fact that live donations are possible, there’s still a dire shortage of organs. A bright spot on the horizon is The Kidney Project, a program spearheaded by bioengineer Shuvo Roy at the University of California, San Francisco, which is developing a fully implantable artificial kidney. The device combines living cells with artificial materials and relies not on a battery, but on the patient’s own blood pressure to keep it functioning.
Several years into this project, a prototype of the kidney, about the size of a smart phone, has been successfully tested in pigs. The device seems to provide many of the functions of a biological kidney (unlike dialysis, which replaces only one main function) and reliably produces urine. One of its most critical components is a special artificial membrane, called a hemofilter, that filters out toxins and waste products from the blood without leaking important molecules like albumin. Since it allows for total mobility, the artificial kidney will provide patients with a higher quality of life than those on dialysis, and is in some important ways, even better than a biological transplant.
The beauty of the device is that, even though it contains kidney cells sourced, as of now, from cadavers or pigs, the cells are treated so that they can’t be rejected and the device doesn’t require the highly problematic immunosuppressant drugs a biological organ requires. “Anti-rejection drugs,” says Roy, “make you susceptible to all kinds of infections and damage the transplanted organ, causing steady deterioration. Eventually they kill the kidney. A biological transplant has about a 10-year limit,” after which the kidney fails and the body rejects it.
Eventually, says Roy, the cells used in the artificial kidney will be sourced from the patient himself, the ultimate genetic match. The patient’s adult stem cells can be used to produce some or all of the 25 to 30 specialized cells of a biological kidney that provide all the functions of a natural organ. People formerly on dialysis could drastically improve their functionality and quality of life without being tethered to a machine for hours at a time, three days a week.
As exciting as this project is, it suffers from a common theme in early biomedical research—keeping a steady stream of funding that will move the project from the lab, into human clinical trials and eventually to the bedside. “It’s the issue,” says Roy. “Potential investors want to see more data indicating that it works, but you need funding to create data. It’s a Catch-22 that puts you in a kind of no-man’s land of funding.” The constant pursuit of funding introduces a variable that makes it hard to predict when the kidney will make it to market, despite the enormous need for such a technology.
Another critical variable is if and when insurance companies will decide to cover transplants with the artificial kidney, so that it becomes affordable for the average person. But Roy thinks that this hurdle, too, will be crossed. Insurance companies stand to save a great deal of money compared to what they ordinarily spend on transplant patients. The cost of yearly maintenance will be a fraction of that associated with the tens of thousands of dollars for immunosuppressant drugs and the attendant complications associated with a biological transplant.
One estimate that the multidisciplinary team of researchers involved with The Kidney Project are still trying to establish is how long the artificial kidney will last once transplanted into the body. Animal trials so far have been looking at how the kidney works for 30 days, and will soon extend that study to 90 days. Additional studies will extend much farther into the future, but first the kidneys have to be implanted into people who can be followed over many years to answer this question. But unlike the gastric pacer and other implants, there won’t be a need for periodic surgeries to replace a depleted battery, and the stark improvements in quality of life compared to dialysis add a special dimension to the value of whatever time the kidney lasts.
Another life-saving implant could address a major scourge of the modern world—heart disease. Despite significant advances in recent decades, including the cardiac implants mentioned above, cardiovascular disease still causes one in three deaths across the world. One of the most promising developments in recent years is the Total Artificial Heart, a pneumatically driven device that can be used in patients with biventricular heart failure, affecting both sides of the heart, when a biological organ is not available.
The TAH is implanted in the chest cavity and has two tubes that snake down the body, come out through the abdomen and attach to a 13.5-pound external driver that the patient carries around in a backpack. It was first developed as a bridge to transplant, a temporary alternative while the patient waited for a biological heart to replace it. However, SynCardia Systems, LLC, the Tucson-based company that makes it, is now investigating whether the heart can be used on a long-term basis.
There’s good reason to think that this will be the case. I spoke with Daniel Teo, one of the board members of SynCardia, who said that so far, one patient lived with the TAH for six years and nine months, before he died of other causes. Another patient, still alive, has lived with the device for over five years and another one has lived with it for over four years. About 2,000 of these transplants have been done in patients waiting for biological hearts so far, and most have lived mobile, even active lives. One TAH recipient hiked for 600 miles, and another ran the 4.2-mile Pat Tillman Run, both while on the artificial heart. This is a far cry from their activities before surgery, while living with advanced heart failure.
Randy Shepard, a recipient of the Total Artificial Heart, teaches archery to his son.
Randy Shepard
If removing and replacing one’s biological heart with a synthetic device sounds scary, it is. But then so is replacing one’s heart with biological one. “The TAH is very emotionally loaded for most people,” says Teo. “People sometimes hold back because of philosophical, existential questions and other nonmedical reasons.” He also cites cultural reasons why some people could be hesitant to accept an artificial heart, saying that some religions could frown upon it, just as they forbid other medical interventions.
The first TAHs that were approved were 70 cubic centimeters in size and fit into the chest cavities of men and larger women, but there’s now a smaller, 50 cc size meant for women and adolescents. The FDA first cleared the 70 cc heart as a bridge to transplant in 2004, and the 50 cc model received approval in 2014. SynCardia’s focus now is on seeking FDA approval to use the heart on a long-term basis. There are other improvements in the works.
One issue being refined deals with the external driver that holds the pneumatic device for moving the blood through a patient’s body. The two tubes connecting the driver to the heart entail openings in the skin that could get infected, and carrying the backpack is less than ideal. The driver also makes an audible sound that some people find disturbing. The next generation TAH will be quieter and involve wearing a smaller, lighter device on a belt rather than carrying the backpack. SynCardia is also working toward a fully implantable heart that wouldn’t require any external components and would contain an energy source that can be recharged wirelessly.
Teo says the jury is out as to whether artificial hearts will ever obviate the need for biological organs, but the world’s number one killer isn’t going away any time soon. “The heart is one of the strongest organs,” he says, “but it’s not made to last forever. If you live long enough, the heart will eventually fail, and heart failure leads to the failure of other organs like the kidney, the lungs and the liver.” As long as this remains the case and as long as the current direction of research continues, artificial organs are likely to play an ever larger part of our everyday lives.
Oh, wait. Maybe we cyborgs will take over the world after all.
Artificial Intelligence is already helping to grow some of the food we eat.
The chef-farmers choose from among 45 types of herb and leafy-greens seeds, plop them into grow trays, and a few weeks later they pick and serve. While success is predicated on at least a small amount of these humans’ care, the systems are autonomously surveilled round-the-clock from Babylon’s base of operations. And artificial intelligence is helping to run the show.
Babylon piloted the use of specialized cameras that take pictures in different spectrums to gather some less-obvious visual data about plants’ wellbeing and alert people if something seems off.
Imagine consistently perfect greens and tomatoes and strawberries, grown hyper-locally, using less water, without chemicals or environmental contaminants. This is the hefty promise of controlled environment agriculture (CEA) — basically, indoor farms that can be hydroponic, aeroponic (plant roots are suspended and fed through misting), or aquaponic (where fish play a role in fertilizing vegetables). But whether they grow 4,160 leafy-green servings per year, like one Babylon farm, or millions of servings, like some of the large, centralized facilities starting to supply supermarkets across the U.S., they seek to minimize failure as much as possible.
Babylon’s soilless hydroponic growing system
Courtesy Babylon Micro-Farms
Here, AI is starting to play a pivotal role. CEA growers use it to help “make sense of what’s happening” to the plants in their care, says Scott Lowman, vice president of applied research at the Institute for Advanced Learning and Research (IALR) in Virginia, a state that’s investing heavily in CEA companies. And although these companies say they’re not aiming for a future with zero human employees, AI is certainly poised to take a lot of human farming intervention out of the equation — for better and worse.
Most of these companies are compiling their own data sets to identify anything that might block the success of their systems. Babylon had already integrated sensor data into its farms to measure heat and humidity, the nutrient content of water, and the amount of light plants receive. Last year, they got a National Science Foundation grant that allowed them to pilot the use of specialized cameras that take pictures in different spectrums to gather some less-obvious visual data about plants’ wellbeing and alert people if something seems off. “Will this plant be healthy tomorrow? Are there things…that the human eye can't see that the plant starts expressing?” says Amandeep Ratte, the company’s head of data science. “If our system can say, Hey, this plant is unhealthy, we can reach out to [users] preemptively about what they’re doing wrong, or is there a disease at the farm?” Ratte says. The earlier the better, to avoid crop failures.
Natural light accounts for 70 percent of Greenswell Growers’ energy use on a sunny day.
Courtesy Greenswell Growers
IALR’s Lowman says that other CEA companies are developing their AI systems to account for the different crops they grow — lettuces come in all shapes and sizes, after all, and each has different growing needs than, for example, tomatoes. The ways they run their operations differs also. Babylon is unusual in its decentralized structure. But centralized growing systems with one main location have variabilities, too. AeroFarms, which recently declared bankruptcy but will continue to run its 140,000-square foot vertical operation in Danville, Virginia, is entirely enclosed and reliant on the intense violet glow of grow lights to produce microgreens.
Different companies have different data needs. What data is essential to AeroFarms isn’t quite the same as for Greenswell Growers located in Goochland County, Virginia. Raising four kinds of lettuce in a 77,000-square-foot automated hydroponic greenhouse, the vagaries of naturally available light, which accounts for 70 percent of Greenswell’s energy use on a sunny day, affect operations. Their tech needs to account for “outside weather impacts,” says president Carl Gupton. “What adjustments do we have to make inside of the greenhouse to offset what's going on outside environmentally, to give that plant optimal conditions? When it's 85 percent humidity outside, the system needs to do X, Y and Z to get the conditions that we want inside.”
AI will help identify diseases, as well as when a plant is thirsty or overly hydrated, when it needs more or less calcium, phosphorous, nitrogen.
Nevertheless, every CEA system has the same core needs — consistent yield of high quality crops to keep up year-round supply to customers. Additionally, “Everybody’s got the same set of problems,” Gupton says. Pests may come into a facility with seeds. A disease called pythium, one of the most common in CEA, can damage plant roots. “Then you have root disease pressures that can also come internally — a change in [growing] substrate can change the way the plant performs,” Gupton says.
AI will help identify diseases, as well as when a plant is thirsty or overly hydrated, when it needs more or less calcium, phosphorous, nitrogen. So, while companies amass their own hyper-specific data sets, Lowman foresees a time within the next decade “when there will be some type of [open-source] database that has the most common types of plant stress identified” that growers will be able to tap into. Such databases will “create a community and move the science forward,” says Lowman.
In fact, IALR is working on assembling images for just such a database now. On so-called “smart tables” inside an Institute lab, a team is growing greens and subjects them to various stressors. Then, they’re administering treatments while taking images of every plant every 15 minutes, says Lowman. Some experiments generate 80,000 images; the challenge lies in analyzing and annotating the vast trove of them, marking each one to reflect outcome—for example increasing the phosphate delivery and the plant’s response to it. Eventually, they’ll be fed into AI systems to help them learn.
For all the enthusiasm surrounding this technology, it’s not without downsides. Training just one AI system can emit over 250,000 pounds of carbon dioxide, according to MIT Technology Review. AI could also be used “to enhance environmental benefit for CEA and optimize [its] energy consumption,” says Rozita Dara, a computer science professor at the University of Guelph in Canada, specializing in AI and data governance, “but we first need to collect data to measure [it].”
The chef-farmers can choose from 45 types of herb and leafy-greens seeds.
Courtesy Babylon Micro-Farms
Any system connected to the Internet of Things is also vulnerable to hacking; if CEA grows to the point where “there are many of these similar farms, and you're depending on feeding a population based on those, it would be quite scary,” Dara says. And there are privacy concerns, too, in systems where imaging is happening constantly. It’s partly for this reason, says Babylon’s Ratte, that the company’s in-farm cameras all “face down into the trays, so the only thing [visible] is pictures of plants.”
Tweaks to improve AI for CEA are happening all the time. Greenswell made its first harvest in 2022 and now has annual data points they can use to start making more intelligent choices about how to feed, water, and supply light to plants, says Gupton. Ratte says he’s confident Babylon’s system can already “get our customers reliable harvests. But in terms of how far we have to go, it's a different problem,” he says. For example, if AI could detect whether the farm is mostly empty—meaning the farm’s user hasn’t planted a new crop of greens—it can alert Babylon to check “what's going on with engagement with this user?” Ratte says. “Do they need more training? Did the main person responsible for the farm quit?”
Lowman says more automation is coming, offering greater ability for systems to identify problems and mitigate them on the spot. “We still have to develop datasets that are specific, so you can have a very clear control plan, [because] artificial intelligence is only as smart as what we tell it, and in plant science, there's so much variation,” he says. He believes AI’s next level will be “looking at those first early days of plant growth: when the seed germinates, how fast it germinates, what it looks like when it germinates.” Imaging all that and pairing it with AI, “can be a really powerful tool, for sure.”
Researchers from the University of Cambridge have laid the foundations for growing synthetic embryos that could develop a beating heart, gut and brain.
The organoid revolution
In 1981, scientists discovered how to keep stem cells alive. This was a significant breakthrough, as stem cells have notoriously rigorous demands. Nevertheless, stem cells remained a relatively niche research area, mainly because scientists didn’t know how to convince the cells to turn into other cells.
Then, in 1987, scientists embedded isolated stem cells in a gelatinous protein mixture called Matrigel, which simulated the three-dimensional environment of animal tissue. The cells thrived, but they also did something remarkable: they created breast tissue capable of producing milk proteins. This was the first organoid — a clump of cells that behave and function like a real organ. The organoid revolution had begun, and it all started with a boob in Jello.
For the next 20 years, it was rare to find a scientist who identified as an “organoid researcher,” but there were many “stem cell researchers” who wanted to figure out how to turn stem cells into other cells. Eventually, they discovered the signals (called growth factors) that stem cells require to differentiate into other types of cells.
For a human embryo (and its organs) to develop successfully, there needs to be a “dialogue” between these three types of stem cells.
By the end of the 2000s, researchers began combining stem cells, Matrigel, and the newly characterized growth factors to create dozens of organoids, from liver organoids capable of producing the bile salts necessary for digesting fat to brain organoids with components that resemble eyes, the spinal cord, and arguably, the beginnings of sentience.
Synthetic embryos
Organoids possess an intrinsic flaw: they are organ-like. They share some characteristics with real organs, making them powerful tools for research. However, no one has found a way to create an organoid with all the characteristics and functions of a real organ. But Magdalena Żernicka-Goetz, a developmental biologist, might have set the foundation for that discovery.
Żernicka-Goetz hypothesized that organoids fail to develop into fully functional organs because organs develop as a collective. Organoid research often uses embryonic stem cells, which are the cells from which the developing organism is created. However, there are two other types of stem cells in an early embryo: stem cells that become the placenta and those that become the yolk sac (where the embryo grows and gets its nutrients in early development). For a human embryo (and its organs) to develop successfully, there needs to be a “dialogue” between these three types of stem cells. In other words, Żernicka-Goetz suspected the best way to grow a functional organoid was to produce a synthetic embryoid.
As described in the aforementioned Nature paper, Żernicka-Goetz and her team mimicked the embryonic environment by mixing these three types of stem cells from mice. Amazingly, the stem cells self-organized into structures and progressed through the successive developmental stages until they had beating hearts and the foundations of the brain.
“Our mouse embryo model not only develops a brain, but also a beating heart [and] all the components that go on to make up the body,” said Żernicka-Goetz. “It’s just unbelievable that we’ve got this far. This has been the dream of our community for years and major focus of our work for a decade and finally we’ve done it.”
If the methods developed by Żernicka-Goetz’s team are successful with human stem cells, scientists someday could use them to guide the development of synthetic organs for patients awaiting transplants. It also opens the door to studying how embryos develop during pregnancy.
This article originally appeared on Big Think, home of the brightest minds and biggest ideas of all time.
