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.
A movie still from the 1966 film "Fantastic Voyage"
"Chemotherapy is delivered systemically," Bionaut-founder and CEO Michael Shpigelmacher says. "Often only a small percentage arrives at the location where it is actually needed."
But what if it was possible to send a tiny robot through the body to attack a tumor or deliver a drug at exactly the right location?
Several startups and academic institutes worldwide are working to develop such a solution but Bionaut Labs seems the furthest along in advancing its invention. "You can think of the Bionaut as a tiny screw that moves through the veins as if steered by an invisible screwdriver until it arrives at the tumor," Shpigelmacher explains. Via Zoom, he shares the screen of an X-ray machine in his Culver City lab to demonstrate how the half-transparent, yellowish device winds its way along the spine in the body. The nanobot contains a tiny but powerful magnet. The "invisible screwdriver" is an external magnetic field that rotates that magnet inside the device and gets it to move and change directions.
The current model has a diameter of less than a millimeter. Shpigelmacher's engineers could build the miniature vehicle even smaller but the current size has the advantage of being big enough to see with bare eyes. It can also deliver more medicine than a tinier version. In the Zoom demonstration, the micorobot is injected into the spine, not unlike an epidural, and pulled along the spine through an outside magnet until the Bionaut reaches the brainstem. Depending which organ it needs to reach, it could be inserted elsewhere, for instance through a catheter.
"The hope is that we can develop a vehicle to transport medication deep into the body," says Max Planck scientist Tian Qiu.
Imagine moving a screw through a steak with a magnet — that's essentially how the device works. But of course, the Bionaut is considerably different from an ordinary screw: "At the right location, we give a magnetic signal, and it unloads its medicine package," Shpigelmacher says.
To start, Bionaut Labs wants to use its device to treat Parkinson's disease and brain stem gliomas, a type of cancer that largely affects children and teenagers. About 300 to 400 young people a year are diagnosed with this type of tumor. Radiation and brain surgery risk damaging sensitive brain tissue, and chemotherapy often doesn't work. Most children with these tumors live less than 18 months. A nanobot delivering targeted chemotherapy could be a gamechanger. "These patients really don't have any other hope," Shpigelmacher says.
Of course, the main challenge of the developing such a device is guaranteeing that it's safe. Because tissue is so sensitive, any mistake could risk disastrous results. In recent years, Bionaut has tested its technology in dozens of healthy sheep and pigs with no major adverse effects. Sheep make a good stand-in for humans because their brains and spines are similar to ours.
The Bionaut device is about the size of a grain of rice.
Bionaut Labs
"As the Bionaut moves through brain tissue, it creates a transient track that heals within a few weeks," Shpigelmacher says. The company is hoping to be the first to test a nanobot in humans. In December 2022, it announced that a recent round of funding drew $43.2 million, for a total of 63.2 million, enabling more research and, if all goes smoothly, human clinical trials by early next year.
Once the technique has been perfected, further applications could include addressing other kinds of brain disorders that are considered incurable now, such as Alzheimer's or Huntington's disease. "Microrobots could serve as a bridgehead, opening the gateway to the brain and facilitating precise access of deep brain structure – either to deliver medication, take cell samples or stimulate specific brain regions," Shpigelmacher says.
Robot-assisted hybrid surgery with artificial intelligence is already used in state-of-the-art surgery centers, and many medical experts believe that nanorobotics will be the instrument of the future. In 2016, three scientists were awarded the Nobel Prize in Chemistry for their development of "the world's smallest machines," nano "elevators" and minuscule motors. Since then, the scientific experiments have progressed to the point where applicable devices are moving closer to actually being implemented.
Bionaut's technology was initially developed by a research team lead by Peer Fischer, head of the independent Micro Nano and Molecular Systems Lab at the Max Planck Institute for Intelligent Systems in Stuttgart, Germany. Fischer is considered a pioneer in the research of nano systems, which he began at Harvard University more than a decade ago. He and his team are advising Bionaut Labs and have licensed their technology to the company.
"The hope is that we can develop a vehicle to transport medication deep into the body," says Max Planck scientist Tian Qiu, who leads the cooperation with Bionaut Labs. He agrees with Shpigelmacher that the Bionaut's size is perfect for transporting medication loads and is researching potential applications for even smaller nanorobots, especially in the eye, where the tissue is extremely sensitive. "Nanorobots can sneak through very fine tissue without causing damage."
In "Fantastic Voyage," Raquel Welch's adventures inside the body of a dissident scientist let her swim through his veins into his brain, but her shrunken miniature submarine is attacked by antibodies; she has to flee through the nerves into the scientist's eye where she escapes into freedom on a tear drop. In reality, the exit in the lab is much more mundane. The Bionaut simply leaves the body through the same port where it entered. But apart from the dramatization, the "Fantastic Voyage" was almost prophetic, or, as Shpigelmacher says, "Science fiction becomes science reality."
This article was first published by Leaps.org on April 12, 2021.
In 2013, the Human Brain Project set out to build a realistic computer model of the brain over ten years. Now, experts are reflecting on HBP's achievements with an eye toward the future.
Scholars have found that the project did help advance neuroscience more than some detractors initially expected, specifically in the area of brain simulations and virtual models. Using an interdisciplinary approach of combining technology, such as AI and digital simulations, with neuroscience, the HBP worked to gain a deeper understanding of the human brain’s complicated structure and functions, which in some cases led to novel treatments for brain disorders. Lastly, through online platforms, the HBP spearheaded a previously unmatched level of global neuroscience collaborations.
Simulating a human brain stirs up controversy
Right from the start, the project was plagued with controversy and condemnation. One of its prominent critics was Yves Fregnac, a professor in cognitive science at the Polytechnic Institute of Paris and research director at the French National Centre for Scientific Research. Fregnac argued in numerous articles that the HBP was overfunded based on proposals with unrealistic goals. “This new way of over-selling scientific targets, deeply aligned with what modern society expects from mega-sciences in the broad sense (big investment, big return), has been observed on several occasions in different scientific sub-fields,” he wrote in one of his articles, “before invading the field of brain sciences and neuromarketing.”
"A human brain model can simulate an experiment a million times for many different conditions, but the actual human experiment can be performed only once or a few times," said Viktor Jirsa, a professor at Aix-Marseille University.
Responding to such critiques, the HBP worked to restructure the effort in its early days with new leadership, organization, and goals that were more flexible and attainable. “The HBP got a more versatile, pluralistic approach,” said Viktor Jirsa, a professor at Aix-Marseille University and one of the HBP lead scientists. He believes that these changes fixed at least some of HBP’s issues. “The project has been on a very productive and scientifically fruitful course since then.”
After restructuring, the HBP became a European hub on brain research, with hundreds of scientists joining its growing network. The HBP created projects focused on various brain topics, from consciousness to neurodegenerative diseases. HBP scientists worked on complex subjects, such as mapping out the brain, combining neuroscience and robotics, and experimenting with neuromorphic computing, a computational technique inspired by the human brain structure and function—to name just a few.
Simulations advance knowledge and treatment options
In 2013, it seemed that bringing neuroscience into a digital age would be farfetched, but research within the HBP has made this achievable. The virtual maps and simulations various HBP teams create through brain imaging data make it easier for neuroscientists to understand brain developments and functions. The teams publish these models on the HBP’s EBRAINS online platform—one of the first to offer access to such data to neuroscientists worldwide via an open-source online site. “This digital infrastructure is backed by high-performance computers, with large datasets and various computational tools,” said Lucy Xiaolu Wang, an assistant professor in the Resource Economics Department at the University of Massachusetts Amherst, who studies the economics of the HBP. That means it can be used in place of many different types of human experimentation.
Jirsa’s team is one of many within the project that works on virtual brain models and brain simulations. Compiling patient data, Jirsa and his team can create digital simulations of different brain activities—and repeat these experiments many times, which isn’t often possible in surgeries on real brains. “A human brain model can simulate an experiment a million times for many different conditions,” Jirsa explained, “but the actual human experiment can be performed only once or a few times.” Using simulations also saves scientists and doctors time and money when looking at ways to diagnose and treat patients with brain disorders.
Compiling patient data, scientists can create digital simulations of different brain activities—and repeat these experiments many times.
The Human Brain Project
Simulations can help scientists get a full picture that otherwise is unattainable. “Another benefit is data completion,” added Jirsa, “in which incomplete data can be complemented by the model. In clinical settings, we can often measure only certain brain areas, but when linked to the brain model, we can enlarge the range of accessible brain regions and make better diagnostic predictions.”
With time, Jirsa’s team was able to move into patient-specific simulations. “We advanced from generic brain models to the ability to use a specific patient’s brain data, from measurements like MRI and others, to create individualized predictive models and simulations,” Jirsa explained. He and his team are working on this personalization technique to treat patients with epilepsy. According to the World Health Organization, about 50 million people worldwide suffer from epilepsy, a disorder that causes recurring seizures. While some epilepsy causes are known others remain an enigma, and many are hard to treat. For some patients whose epilepsy doesn’t respond to medications, removing part of the brain where seizures occur may be the only option. Understanding where in the patients’ brains seizures arise can give scientists a better idea of how to treat them and whether to use surgery versus medications.
“We apply such personalized models…to precisely identify where in a patient’s brain seizures emerge,” Jirsa explained. “This guides individual surgery decisions for patients for which surgery is the only treatment option.” He credits the HBP for the opportunity to develop this novel approach. “The personalization of our epilepsy models was only made possible by the Human Brain Project, in which all the necessary tools have been developed. Without the HBP, the technology would not be in clinical trials today.”
Personalized simulations can significantly advance treatments, predict the outcome of specific medical procedures and optimize them before actually treating patients. Jirsa is watching this happen firsthand in his ongoing research. “Our technology for creating personalized brain models is now used in a large clinical trial for epilepsy, funded by the French state, where we collaborate with clinicians in hospitals,” he explained. “We have also founded a spinoff company called VB Tech (Virtual Brain Technologies) to commercialize our personalized brain model technology and make it available to all patients.”
The Human Brain Project created a level of interconnectedness within the neuroscience research community that never existed before—a network not unlike the brain’s own.
Other experts believe it’s too soon to tell whether brain simulations could change epilepsy treatments. “The life cycle of developing treatments applicable to patients often runs over a decade,” Wang stated. “It is still too early to draw a clear link between HBP’s various project areas with patient care.” However, she admits that some studies built on the HBP-collected knowledge are already showing promise. “Researchers have used neuroscientific atlases and computational tools to develop activity-specific stimulation programs that enabled paraplegic patients to move again in a small-size clinical trial,” Wang said. Another intriguing study looked at simulations of Alzheimer’s in the brain to understand how it evolves over time.
Some challenges remain hard to overcome even with computer simulations. “The major challenge has always been the parameter explosion, which means that many different model parameters can lead to the same result,” Jirsa explained. An example of this parameter explosion could be two different types of neurodegenerative conditions, such as Parkinson’s and Huntington’s diseases. Both afflict the same area of the brain, the basal ganglia, which can affect movement, but are caused by two different underlying mechanisms. “We face the same situation in the living brain, in which a large range of diverse mechanisms can produce the same behavior,” Jirsa said. The simulations still have to overcome the same challenge.
Understanding where in the patients’ brains seizures arise can give scientists a better idea of how to treat them and whether to use surgery versus medications.
The Human Brain Project
A network not unlike the brain’s own
Though the HBP will be closing this year, its legacy continues in various studies, spin-off companies, and its online platform, EBRAINS. “The HBP is one of the earliest brain initiatives in the world, and the 10-year long-term goal has united many researchers to collaborate on brain sciences with advanced computational tools,” Wang said. “Beyond the many research articles and projects collaborated on during the HBP, the online neuroscience research infrastructure EBRAINS will be left as a legacy even after the project ends.”
Those who worked within the HBP see the end of this project as the next step in neuroscience research. “Neuroscience has come closer to very meaningful applications through the systematic link with new digital technologies and collaborative work,” Jirsa stated. “In that way, the project really had a pioneering role.” It also created a level of interconnectedness within the neuroscience research community that never existed before—a network not unlike the brain’s own. “Interconnectedness is an important advance and prerequisite for progress,” Jirsa said. “The neuroscience community has in the past been rather fragmented and this has dramatically changed in recent years thanks to the Human Brain Project.”
According to its website, by 2023 HBP’s network counted over 500 scientists from over 123 institutions and 16 different countries, creating one of the largest multi-national research groups in the world. Even though the project hasn’t produced the in-silico brain as Markram envisioned it, the HBP created a communal mind with immense potential. “It has challenged us to think beyond the boundaries of our own laboratories,” Jirsa said, “and enabled us to go much further together than we could have ever conceived going by ourselves.”