A Surprising Breakthrough Will Allow Tiny Implants to Fix—and Even Upgrade—Your Body
Imagine it's the year 2040 and you're due for your regular health checkup. Time to schedule your next colonoscopy, Pap smear if you're a woman, and prostate screen if you're a man.
"The evolution of the biological ion transistor technology is a game changer."
But wait, you no longer need any of those, since you recently got one of the new biomed implants – a device that integrates seamlessly with body tissues, because of a watershed breakthrough that happened in the early 2020s. It's an improved biological transistor driven by electrically charged particles that move in and out of your own cells. Like insulin pumps and cardiac pacemakers, the medical implants of the future will go where they are needed, on or inside the body.
But unlike current implants, biological transistors will have a remarkable range of applications. Currently small enough to fit between a patient's hair follicles, the devices could one day enable correction of problems ranging from damaged heart muscle to failing retinas to deficiencies of hormones and enzymes.
Their usefulness raises the prospect of overcorrection to the point of human enhancement, as in the bionic parts that were imagined on the ABC television series The Six Million Dollar Man, which aired in the 1970s.
"The evolution of the biological ion transistor technology is a game changer," says Zoltan Istvan, who ran as a U.S. Presidential candidate in 2016 for the Transhumanist Party and later ran for California governor. Istvan envisions humans becoming faster, stronger, and increasingly more capable by way of technological innovations, especially in the biotechnology realm. "It's a big step forward on how we can improve and upgrade the human body."
How It Works
The new transistors are more like the soft, organic machines that biology has evolved than like traditional transistors built of semiconductors and metal, according to electric engineering expert Dion Khodagholy, one of the leaders of the team at Columbia University that developed the technology.
The key to the advance, notes Khodagholy, is that the transistors will interface seamlessly with tissue, because the electricity will be of the biological type -- transmitted via the flow of ions through liquid, rather than electrons through metal. This will boost the sensitivity of detection and decoding of biological change.
Naturally, such a paradigm change in the world of medical devices raises potential societal and ethical dilemmas.
Known as an ion-gated transistor (IGT), the new class of technology effectively melds electronics with molecules of human skin. That's the current prototype, but ultimately, biological devices will be able to go anywhere in the body. "IGT-based devices hold great promise for development of fully implantable bioelectronic devices that can address key clinical issues for patients with neuropsychiatric disease," says Khodagholy, based on the expectation that future devices could fuse with, measure, and modulate cells of the human nervous system.
Naturally, such a paradigm change in the world of medical devices raises potential societal and ethical dilemmas, starting with who receives the new technology and who pays for it. But, according clinical ethicist and health care attorney David Hoffman, we can gain insight from past experience, such as how society reacted to the invention of kidney dialysis in the mid 20th century.
"Kidney dialysis has been federally funded for all these decades, largely because the who-gets-the-technology question was an issue when the technology entered clinical medicine," says Hoffman, who teaches bioethics at Columbia's College of Physicians and Surgeons as well as at the law school and medical school of Yeshiva University. Just as dialysis became a necessity for many patients, he suggests that the emerging bio-transistors may also become critical life-sustaining devices, prompting discussions about federal coverage.
But unlike dialysis, biological transistors could allow some users to become "better than well," making it more similar to medication for ADHD (attention deficit hyperactivity disorder): People who don't require it can still use it to improve their baseline normal functioning. This raises the classic question: Should society draw a line between treatment and enhancement? And who gets to decide the answer?
If it's strictly a medical use of the technology, should everyone who needs it get to use it, regardless of ability to pay, relying on federal or private insurance coverage? On the other hand, if it's used voluntarily for enhancement, should that option also be available to everyone -- but at an upfront cost?
From a transhumanist viewpoint, getting wrapped up with concerns about the evolution of devices from therapy to enhancement is not worth the trouble.
It seems safe to say that some lively debates and growing pains are on the horizon.
"Even if [the biological ion transistor] is developed only for medical devices that compensate for losses and deficiencies similar to that of a cardiac pacemaker, it will be hard to stop its eventual evolution from compensation to enhancement," says Istvan. "If you use it in a bionic eye to restore vision to the blind, how do you draw the line between replacement of normal function and provision of enhanced function? Do you pass a law placing limits on visual capabilities of a synthetic eye? Transhumanists would oppose such laws, and any restrictions in one country or another would allow another country to gain an advantage by creating their own real-life super human cyborg citizens."
In the same breath though, Istvan admits that biotechnology on a bionic scale is bound to complicate a range of international phenomena, from economic growth and military confrontations to sporting events like the Olympic Games.
The technology is already here, and it's just a matter of time before we see clinically viable, implantable devices. As for how society will react, it seems safe to say that some lively debates and growing pains are on the horizon.
Meet Dr. Renee Wegrzyn, the first Director of President Biden's new health agency, ARPA-H
In today’s podcast episode, I talk with Renee Wegrzyn, appointed by President Biden as the first director of a federal agency created last year called the Advanced Research Projects Agency for Health, or ARPA-H. It’s inspired by DARPA, the agency that develops innovations for the Defense department and has been credited with hatching world changing technologies such as ARPANET, which became the internet.
Time will tell if ARPA-H will lead to similar achievements in the realm of health. That’s what President Biden and Congress expect in return for funding ARPA-H at 2.5 billion dollars over three years.
Listen on Apple | Listen on Spotify | Listen on Stitcher | Listen on Amazon | Listen on Google
How will the agency figure out which projects to take on, especially with so many patient advocates for different diseases demanding moonshot funding for rapid progress.
I talked with Dr. Wegrzyn about the opportunities and challenges, what lessons ARPA-H is borrowing from Operation Warp Speed, how she decided on the first ARPA-H project which was just announced recently, why a separate agency was needed instead of trying to reform HHS and the National Institutes of Health to be better at innovation, and how ARPA-H will make progress on disease prevention in addition to treatments for cancer, Alzheimer’s and diabetes, among many other health priorities.
Dr. Wegrzyn’s resume is filled with experience for her important role. She was a program manager at DARPA where she focused on applying gene editing and synthetic biology to the goal of improving biosecurity. For her work there, she was given the Superior Public Service Medal and, just in case that wasn’t enough ARPA experience, she also worked at another ARPA that leads advanced projects in intelligence, called I-ARPA. Before that, she was in charge of technical teams in the private sector working on gene therapies and disease diagnostics, among other areas. She has been a vice president of business development at Gingko Bioworks and headed innovation at Concentric by Gingko. Her training and education includes a PhD and undergraduate degree in applied biology from the Georgia Institute of Technology and she did her postdoc as an Alexander von Humboldt Fellow in Heidelberg, Germany.
As Dr. Wegrzyn told me, she’s “in the hot seat” - the pressure is on for ARPA-H especially after the need and potential for health innovation was spot lit by the pandemic and the unprecedented speed of vaccine development. We'll soon find out if ARPA-H can produce something in health that’s equivalent to DARPA’s creation of the internet.
ARPA-H - https://arpa-h.gov/
Dr. Wegrzyn profile - https://arpa-h.gov/people/renee-wegrzyn/
Dr. Wegrzyn Twitter - https://twitter.com/rwegrzyn?lang=en
President Biden Announces Dr. Wegrzyn's appointment - https://www.whitehouse.gov/briefing-room/statement...
Leaps.org coverage of ARPA-H - https://leaps.org/arpa/
ARPA-H program for joints to heal themselves - https://arpa-h.gov/news/nitro/ -
ARPA-H virtual talent search - https://arpa-h.gov/news/aco-talent-search/
Matt Fuchs is the editor-in-chief of Leaps.org and Making Sense of Science. He is also a contributing reporter to the Washington Post and has written for the New York Times, Time Magazine, WIRED and the Washington Post Magazine, among other outlets. Follow him @fuchswriter.
Tiny, tough “water bears” may help bring new vaccines and medicines to sub-Saharan Africa
Microscopic tardigrades, widely considered to be some of the toughest animals on earth, can survive for decades without oxygen or water and are thought to have lived through a crash-landing on the moon. Also known as water bears, they survive by fully dehydrating and later rehydrating themselves – a feat only a few animals can accomplish. Now scientists are harnessing tardigrades’ talents to make medicines that can be dried and stored at ambient temperatures and later rehydrated for use—instead of being kept refrigerated or frozen.
Many biologics—pharmaceutical products made by using living cells or synthesized from biological sources—require refrigeration, which isn’t always available in many remote locales or places with unreliable electricity. These products include mRNA and other vaccines, monoclonal antibodies and immuno-therapies for cancer, rheumatoid arthritis and other conditions. Cooling is also needed for medicines for blood clotting disorders like hemophilia and for trauma patients.
Formulating biologics to withstand drying and hot temperatures has been the holy grail for pharmaceutical researchers for decades. It’s a hard feat to manage. “Biologic pharmaceuticals are highly efficacious, but many are inherently unstable,” says Thomas Boothby, assistant professor of molecular biology at University of Wyoming. Therefore, during storage and shipping, they must be refrigerated at 2 to 8 degrees Celsius (35 to 46 degrees Fahrenheit). Some must be frozen, typically at -20 degrees Celsius, but sometimes as low -90 degrees Celsius as was the case with the Pfizer Covid vaccine.
For Covid, fewer than 73 percent of the global population received even one dose. The need for refrigerated or frozen handling was partially to blame.
The costly cold chain
The logistics network that ensures those temperature requirements are met from production to administration is called the cold chain. This cold chain network is often unreliable or entirely lacking in remote, rural areas in developing nations that have malfunctioning electrical grids. “Almost all routine vaccines require a cold chain,” says Christopher Fox, senior vice president of formulations at the Access to Advanced Health Institute. But when the power goes out, so does refrigeration, putting refrigerated or frozen medical products at risk. Consequently, the mRNA vaccines developed for Covid-19 and other conditions, as well as more traditional vaccines for cholera, tetanus and other diseases, often can’t be delivered to the most remote parts of the world.
To understand the scope of the challenge, consider this: In the U.S., more than 984 million doses of Covid-19 vaccine have been distributed so far. Each one needed refrigeration that, even in the U.S., proved challenging. Now extrapolate to all vaccines and the entire world. For Covid, fewer than 73 percent of the global population received even one dose. The need for refrigerated or frozen handling was partially to blame.
Globally, the cold chain packaging market is valued at over $15 billion and is expected to exceed $60 billion by 2033.
Freeze-drying, also called lyophilization, which is common for many vaccines, isn’t always an option. Many freeze-dried vaccines still need refrigeration, and even medicines approved for storage at ambient temperatures break down in the heat of sub-Saharan Africa. “Even in a freeze-dried state, biologics often will undergo partial rehydration and dehydration, which can be extremely damaging,” Boothby explains.
The cold chain is also very expensive to maintain. The global pharmaceutical cold chain packaging market is valued at more than $15 billion, and is expected to exceed $60 billion by 2033, according to a report by Future Market Insights. This cost is only expected to grow. According to the consulting company Accenture, the number of medicines that require the cold chain are expected to grow by 48 percent, compared to only 21 percent for non-cold-chain therapies.
Tardigrades to the rescue
Tardigrades are only about a millimeter long – with four legs and claws, and they lumber around like bears, thus their nickname – but could provide a big solution. “Tardigrades are unique in the animal kingdom, in that they’re able to survive a vast array of environmental insults,” says Boothby, the Wyoming professor. “They can be dried out, frozen, heated past the boiling point of water and irradiated at levels that are thousands of times more than you or I could survive.” So, his team is gradually unlocking tardigrades’ survival secrets and applying them to biologic pharmaceuticals to make them withstand both extreme heat and desiccation without losing efficacy.
Boothby’s team is focusing on blood clotting factor VIII, which, as the name implies, causes blood to clot. Currently, Boothby is concentrating on the so-called cytoplasmic abundant heat soluble (CAHS) protein family, which is found only in tardigrades, protecting them when they dry out. “We showed we can desiccate a biologic (blood clotting factor VIII, a key clotting component) in the presence of tardigrade proteins,” he says—without losing any of its effectiveness.
The researchers mixed the tardigrade protein with the blood clotting factor and then dried and rehydrated that substance six times without damaging the latter. This suggests that biologics protected with tardigrade proteins can withstand real-world fluctuations in humidity.
Furthermore, Boothby’s team found that when the blood clotting factor was dried and stabilized with tardigrade proteins, it retained its efficacy at temperatures as high as 95 degrees Celsius. That’s over 200 degrees Fahrenheit, much hotter than the 58 degrees Celsius that the World Meteorological Organization lists as the hottest recorded air temperature on earth. In contrast, without the protein, the blood clotting factor degraded significantly. The team published their findings in the journal Nature in March.
Although tardigrades rarely live more than 2.5 years, they have survived in a desiccated state for up to two decades, according to Animal Diversity Web. This suggests that tardigrades’ CAHS protein can protect biologic pharmaceuticals nearly indefinitely without refrigeration or freezing, which makes it significantly easier to deliver them in locations where refrigeration is unreliable or doesn’t exist.
The tricks of the tardigrades
Besides the CAHS proteins, tardigrades rely on a type of sugar called trehalose and some other protectants. So, rather than drying up, their cells solidify into rigid, glass-like structures. As that happens, viscosity between cells increases, thereby slowing their biological functions so much that they all but stop.
Now Boothby is combining CAHS D, one of the proteins in the CAHS family, with trehalose. He found that CAHS D and trehalose each protected proteins through repeated drying and rehydrating cycles. They also work synergistically, which means that together they might stabilize biologics under a variety of dry storage conditions.
“We’re finding the protective effect is not just additive but actually is synergistic,” he says. “We’re keen to see if something like that also holds true with different protein combinations.” If so, combinations could possibly protect against a variety of conditions.
Before any stabilization technology for biologics can be commercialized, it first must be approved by the appropriate regulators. In the U.S., that’s the U.S. Food and Drug Administration. Developing a new formulation would require clinical testing and vast numbers of participants. So existing vaccines and biologics likely won’t be re-formulated for dry storage. “Many were developed decades ago,” says Fox. “They‘re not going to be reformulated into thermo-stable vaccines overnight,” if ever, he predicts.
Extending stability outside the cold chain, even for a few days, can have profound health, environmental and economic benefits.
Instead, this technology is most likely to be used for the new products and formulations that are just being created. New and improved vaccines will be the first to benefit. Good candidates include the plethora of mRNA vaccines, as well as biologic pharmaceuticals for neglected diseases that affect parts of the world where reliable cold chain is difficult to maintain, Boothby says. Some examples include new, more effective vaccines for malaria and for pathogenic Escherichia coli, which causes diarrhea.
Tallying up the benefits
Extending stability outside the cold chain, even for a few days, can have profound health, environmental and economic benefits. For instance, MenAfriVac, a meningitis vaccine (without tardigrade proteins) developed for sub-Saharan Africa, can be stored at up to 40 degrees Celsius for four days before administration. “If you have a few days where you don’t need to maintain the cold chain, it’s easier to transport vaccines to remote areas,” Fox says, where refrigeration does not exist or is not reliable.
Better health is an obvious benefit. MenAfriVac reduced suspected meningitis cases by 57 percent in the overall population and more than 99 percent among vaccinated individuals.
Lower healthcare costs are another benefit. One study done in Togo found that the cold chain-related costs increased the per dose vaccine price up to 11-fold. The ability to ship the vaccines using the usual cold chain, but transporting them at ambient temperatures for the final few days cut the cost in half.
There are environmental benefits, too, such as reducing fuel consumption and greenhouse gas emissions. Cold chain transports consume 20 percent more fuel than non-cold chain shipping, due to refrigeration equipment, according to the International Trade Administration.
A study by researchers at Johns Hopkins University compared the greenhouse gas emissions of the new, oral Vaxart COVID-19 vaccine (which doesn’t require refrigeration) with four intramuscular vaccines (which require refrigeration or freezing). While the Vaxart vaccine is still in clinical trials, the study found that “up to 82.25 million kilograms of CO2 could be averted by using oral vaccines in the U.S. alone.” That is akin to taking 17,700 vehicles out of service for one year.
Although tardigrades’ protective proteins won’t be a component of biologic pharmaceutics for several years, scientists are proving that this approach is viable. They are hopeful that a day will come when vaccines and biologics can be delivered anywhere in the world without needing refrigerators or freezers en route.