In 2015, about a year before he was diagnosed with terminal lung cancer, John Vlahos posed for a picture with his son, James.
In 2016, when my family found out that my father was dying from cancer, I did something that at the time felt completely obvious: I started building a chatbot replica of him.
I simply wanted to create an interactive way to share key parts of his life story.
I was not under any delusion that the Dadbot, as I soon began calling it, would be a true avatar of him. From my research about the voice computing revolution—Siri, Alexa, the Google Assistant—I knew that fully humanlike AIs, like you see in the movies, were a vast ways from technological reality. Replicating my dad in any real sense was never the goal, anyway; that notion gave me the creeps.
Instead, I simply wanted to create an interactive way to share key parts of his life story: facts about his ancestors in Greece. Memories from growing up. Stories about his hobbies, family life, and career. And I wanted the Dadbot, which sent text messages and audio clips over Facebook Messenger, to remind me of his personality—warm, erudite, and funny. So I programmed it to use his distinctive phrasings; to tell a few of his signature jokes and sing his favorite songs.
While creating the Dadbot, a laborious undertaking that sprawled into 2017, I fixated on two things. The first was getting the programming right, which I did using a conversational agent authoring platform called PullString. The second, far more wrenching concern was my father's health. Failing to improve after chemotherapy and immunotherapy, and steadily losing energy, weight, and the animating sparkle of life, he died on February 9.
John Vlahos at a family reunion in the summer of 2016, a few months after his cancer diagnosis.
(Courtesy James Vlahos)
After a magazine article that I wrote about the Dadbot came out in the summer of 2017, messages poured in from readers. While most people simply expressed sympathy, some conveyed a more urgent message: They wanted their own memorializing chatbots. One man implored me to make a bot for him; he had been diagnosed with cancer and wanted his six-month-old daughter to have a way to remember him. A technology entrepreneur needed advice on replicating what I did for her father, who had stage IV cancer. And a teacher in India asked me to engineer a conversational replica of her son, who had recently been struck and killed by a bus.
Journalists from around the world also got in touch for interviews, and they inevitably came around to the same question. Will virtual immortality, they asked, ever become a business?
The prospect of this happening had never crossed my mind. I was consumed by my father's struggle and my own grief. But the notion has since become head-slappingly obvious. I am not the only person to confront the loss of a loved one; the experience is universal. And I am not alone in craving a way to keep memories alive. Of course people like the ones who wrote me will get Dadbots, Mombots, and Childbots of their own. If a moonlighting writer like me can create a minimum viable product, then a company employing actual computer scientists could do much more.
But this prospect raises unanswered and unsettling questions. For businesses, profit, and not some deeply personal mission, will be the motivation. This shift will raise issues that I didn't have to confront. To make money, a virtual immortality company could follow the lucrative but controversial business model that has worked so well for Google and Facebook. To wit, a company could provide the memorializing chatbot for free and then find ways to monetize the attention and data of whoever communicated with it. Given the copious amount of personal information flowing back and forth in conversations with replica bots, this would be a data gold mine for the company—and a massive privacy risk for users.
Virtual immortality as commercial product will doubtless become more sophisticated.
Alternately, a company could charge for memorializing avatars, perhaps with an annual subscription fee. This would put the business in a powerful position. Imagine the fee getting hiked each year. A customer like me would find himself facing a terrible decision—grit my teeth and keep paying, or be forced to pull the plug on the best, closest reminder of a loved one that I have. The same person would effectively wind up dying twice.
Another way that a beloved digital avatar could die is if the company that creates it ceases to exist. This is no mere academic concern for me: Earlier this year, PullString was swallowed up by Apple. I'm still able to access the Dadbot on my own computer, fortunately, but the acquisition means that other friends and family members can no longer chat with him remotely.
Startups like PullString, of course, are characterized by impermanence; they tend to get snapped up by bigger companies or run out of venture capital and fold. But even if big players like, say, Facebook or Google get into the virtual immortality game, we can't count on them existing even a few decades from now, which means that the avatars enabled by their technology would die, too.
The permanence problem is the biggest hurdle faced by the fledgling enterprise of virtual immortality. So some entrepreneurs are attempting to enable avatars whose existence isn't reliant upon any one company or set of computer servers. "By leveraging the power of blockchain and decentralized software to replicate information, we help users create avatars that live on forever," says Alex Roy, the founder and CEO of the startup Everlife.ai. But until this type of solution exists, give props to conventional technology for preserving memories: printed photos and words on paper can last for centuries.
The fidelity of avatars—just how lifelike they are—also raises serious concerns. Before I started creating the Dadbot, I worried that the tech might be just good enough to remind my family of the man it emulated, but so far off from my real father that it gave us all the creeps. But because the Dadbot was a simple chatbot and not some all-knowing AI, and because the interface was a messaging app, there was no danger of him encroaching on the reality of my actual dad.
But virtual immortality as commercial product will doubtless become more sophisticated. Avatars will have brains built by teams of computer scientists employing the latest techniques in conversational AI. The replicas will not just text but also speak, using synthetic voices that emulate the ones of the people being memorialized. They may even come to life as animated clones on computer screens or in 3D with the help of virtual reality headsets.
What fascinates me is how technology can help to preserve the past—genuine facts and memories from peoples' lives.
These are all lines that I don't personally want to cross; replicating my dad was never the goal. I also never aspired to have some synthetic version of him that continued to exist in the present, capable of acquiring knowledge about the world or my life and of reacting to it in real time.
Instead, what fascinates me is how technology can help to preserve the past—genuine facts and memories from people's lives—and their actual voices so that their stories can be shared interactively after they have gone. I'm working on ideas for doing this via voice computing platforms like Alexa and Assistant, and while I don't have all of the answers yet, I'm excited to figure out what might be possible.
[Adapted from Talk to Me: How Voice Computing Will Transform the Way We Live, Work, and Think (Houghton Mifflin Harcourt, March 26, 2019).]
Recent advancements in engineering mean that the first preclinical trials for an artificial kidney could happen soon.
Still, the devices aren’t ready for testing in humans—yet. But recent advancements in engineering mean that the first preclinical trials for an artificial kidney could happen soon, according to Jonathan Himmelfarb, a nephrologist at the University of Washington.
“It would liberate people with kidney failure,” Himmelfarb says.
An engineering marvel
Compared to the heart or the brain, the kidney doesn’t get as much respect from the medical profession, but its job is far more complex. “It does hundreds of different things,” says UCLA’s Ira Kurtz.
Kurtz would know. He’s worked as a nephrologist for 37 years, devoting his career to helping those with kidney disease. While his colleagues in cardiology and endocrinology have seen major advances in the development of artificial hearts and insulin pumps, little has changed for patients on hemodialysis. The machines remain bulky and require large volumes of a liquid called dialysate to remove toxins from a patient’s blood, along with gallons of purified water. A kidney transplant is the next best thing to someone’s own, functioning organ, but with over 600,000 Americans on dialysis and only about 100,000 kidney transplants each year, most of those in kidney failure are stuck on dialysis.
Part of the lack of progress in artificial kidney design is the sheer complexity of the kidney’s job. Each of the 45 different cell types in the kidney do something different.
Part of the lack of progress in artificial kidney design is the sheer complexity of the kidney’s job. To build an artificial heart, Kurtz says, you basically need to engineer a pump. An artificial pancreas needs to balance blood sugar levels with insulin secretion. While neither of these tasks is simple, they are fairly straightforward. The kidney, on the other hand, does more than get rid of waste products like urea and other toxins. Each of the 45 different cell types in the kidney do something different, helping to regulate electrolytes like sodium, potassium, and phosphorous; maintaining blood pressure and water balance; guiding the body’s hormonal and inflammatory responses; and aiding in the formation of red blood cells.
There's been little progress for patients during Ira Kurtz's 37 years as a nephrologist. Artificial kidneys would change that.
UCLA
Dialysis primarily filters waste, and does so well enough to keep someone alive, but it isn’t a true artificial kidney because it doesn’t perform the kidney’s other jobs, according to Kurtz, such as sensing levels of toxins, wastes, and electrolytes in the blood. Due to the size and water requirements of existing dialysis machines, the equipment isn’t portable. Physicians write a prescription for a certain duration of dialysis and assess how well it’s working with semi-regular blood tests. The process of dialysis itself, however, is conducted blind. Doctors can’t tell how much dialysis a patient needs based on kidney values at the time of treatment, says Meera Harhay, a nephrologist at Drexel University in Philadelphia.
But it’s the impact of dialysis on their day-to-day lives that creates the most problems for patients. Only one-quarter of those on dialysis are able to remain employed (compared to 85% of similar-aged adults), and many report a low quality of life. Having more flexibility in life would make a major different to her patients, Harhay says.
“Almost half their week is taken up by the burden of their treatment. It really eats away at their freedom and their ability to do things that add value to their life,” she says.
Art imitates life
The challenge for artificial kidney designers was how to compress the kidney’s natural functions into a portable, wearable, or implantable device that wouldn’t need constant access to gallons of purified and sterilized water. The other universal challenge they faced was ensuring that any part of the artificial kidney that would come in contact with blood was kept germ-free to prevent infection.
As part of the 2021 KidneyX Prize, a partnership between the U.S. Department of Health and Human Services and the American Society of Nephrology, inventors were challenged to create prototypes for artificial kidneys. Himmelfarb’s team at the University of Washington’s Center for Dialysis Innovation won the prize by focusing on miniaturizing existing technologies to create a portable dialysis machine. The backpack sized AKTIV device (Ambulatory Kidney to Increase Vitality) will recycle dialysate in a closed loop system that removes urea from blood and uses light-based chemical reactions to convert the urea to nitrogen and carbon dioxide, which allows the dialysate to be recirculated.
Himmelfarb says that the AKTIV can be used when at home, work, or traveling, which will give users more flexibility and freedom. “If you had a 30-pound device that you could put in the overhead bins when traveling, you could go visit your grandkids,” he says.
Kurtz’s team at UCLA partnered with the U.S. Kidney Research Corporation and Arkansas University to develop a dialysate-free desktop device (about the size of a small printer) as the first phase of a progression that will he hopes will lead to something small and implantable. Part of the reason for the artificial kidney’s size, Kurtz says, is the number of functions his team are cramming into it. Not only will it filter urea from blood, but it will also use electricity to help regulate electrolyte levels in a process called electrodeionization. Kurtz emphasizes that these additional functions are what makes his design a true artificial kidney instead of just a small dialysis machine.
One version of an artificial kidney.
UCLA
“It doesn't have just a static function. It has a bank of sensors that measure chemicals in the blood and feeds that information back to the device,” Kurtz says.
Other startups are getting in on the game. Nephria Bio, a spinout from the South Korean-based EOFlow, is working to develop a wearable dialysis device, akin to an insulin pump, that uses miniature cartridges with nanomaterial filters to clean blood (Harhay is a scientific advisor to Nephria). Ian Welsford, Nephria’s co-founder and CTO, says that the device’s design means that it can also be used to treat acute kidney injuries in resource-limited settings. These potentials have garnered interest and investment in artificial kidneys from the U.S. Department of Defense.
For his part, Burton is most interested in an implantable device, as that would give him the most freedom. Even having a regular outpatient procedure to change batteries or filters would be a minor inconvenience to him.
“Being plugged into a machine, that’s not mimicking life,” he says.
This article was first published by Leaps.org on May 5, 2022.
New research focuses on methods that could change medicine-making worldwide. The scientists propose bursting cells open, removing their DNA and using the cellular gears inside to make therapies.
Rao and his team of collaborators, which spans multiple research institutions, believe they have a better approach that may change medicine-making worldwide. They suggest forgoing the concept of using living cells as medicine-producers. Instead, they propose breaking the cells and using the remaining cellular gears for assembling the therapeutic compounds. Instead of inserting the DNA into living cells, the team burst them open, and removed their DNA altogether. Yet, the residual molecular machinery of ribosomes, polymerases and other cogwheels still functioned the way it would in a cell. “Now if you drop your DNA drug-making instructions into that soup, this machinery starts making what you need,” Rao explains. “And because you're no longer worrying about living cells, it becomes much simpler and more efficient.” The collaborators detail their cell-free protein synthesis or CFPS method in their recent paper published in preprint BioAxiv.
While CFPS does not use living cells, it still needs the basic building blocks to assemble proteins from—such as amino acids, nucleotides and certain types of enzymes. These are regularly added into this “soup” to keep the molecular factory chugging. “We just mix everything in as a batch and we let it integrate,” says James Robert Swartz, professor of chemical engineering and bioengineering at Stanford University and co-author of the paper. “And we make sure that we provide enough oxygen.” Rao likens the process to making milk from milk powder.
For a variety of reasons—from the field’s general inertia to regulatory approval hurdles—the method hasn’t become mainstream. The pandemic rekindled interest in medicines that can be made quickly and easily, so it drew more attention to the technology.
The idea of a cell-free protein synthesis is older than one might think. Swartz first experimented with it around 1997, when he was a chemical engineer at Genentech. While working on engineering bacteria to make pharmaceuticals, he discovered that there was a limit to what E. coli cells, the workhorse darling of pharma, could do. For example, it couldn’t grow and properly fold some complex proteins. “We tried many genetic engineering approaches, many fermentation, development, and environmental control approaches,” Swartz recalls—to no avail.
“The organism had its own agenda,” he quips. “And because everything was happening within the organism, we just couldn't really change those conditions very easily. Some of them we couldn’t change at all—we didn’t have control.”
It was out of frustration with the defiant bacteria that a new idea took hold. Could the cells be opened instead, so that the protein-forming reactions could be influenced more easily? “Obviously, we’d lose the ability for them to reproduce,” Swartz says. But that also meant that they no longer needed to keep the cells alive and could focus on making the specific reactions happen. “We could take the catalysts, the enzymes, and the more complex catalysts and activate them, make them work together, much as they would in a living cell, but the way we wanted.”
In 1998, Swartz joined Stanford, and began perfecting the biochemistry of the cell-free method, identifying the reactions he wanted to foster and stopping those he didn’t want. He managed to make the idea work, but for a variety of reasons—from the field’s general inertia to regulatory approval hurdles—the method hasn’t become mainstream. The pandemic rekindled interest in medicines that can be made quickly and easily, so it drew more attention to the technology. For their BioArxiv paper, the team tested the method by growing a specific antiviral protein called griffithsin.
First identified by Barry O’Keefe at National Cancer Institute over a decade ago, griffithsin is an antiviral known to interfere with many viruses’ ability to enter cells—including HIV, SARS, SARS-CoV-2, MERS and others. Originally isolated from the red algae Griffithsia, it works differently from antibodies and antibody cocktails.
Most antiviral medicines tend to target the specific receptors that viruses use to gain entry to the cells they infect. For example, SARS-CoV-2 uses the infamous spike protein to latch onto the ACE2 receptor of mammalian cells. The antibodies or other antiviral molecules stick to the spike protein, shutting off its ability to cling onto the ACE2 receptors. Unfortunately, the spike proteins mutate very often, so the medicines lose their potency. On the contrary, griffithsin has the ability to cling to the different parts of viral shells called capsids—namely to the molecules of mannose, a type of sugar. That extra stuff, glued all around the capsid like dead weight, makes it impossible for the virus to squeeze into the cell.
“Every time we have a vaccine or an antibody against a specific SARS-CoV-2 strain, that strain then mutates and so you lose efficacy,” Rao explains. “But griffithsin molecules glom onto the viral capsid, so the capsid essentially becomes a sticky mess and can’t enter the cell.” Mannose molecules also don’t mutate as easily as viruses’ receptors, so griffithsin-based antivirals do not have to be constantly updated. And because mannose molecules are found on many viruses’ capsids, it makes griffithsin “a universal neutralizer,” Rao explains.
“When griffithsin was discovered, we recognized that it held a lot of promise as a potential antiviral agent,” O’Keefe says. In 2010, he published a paper about griffithsin efficacy in neutralizing viruses of the corona family—after the first SARS outbreak in the early 2000s, the scientific community was interested in such antivirals. Yet, griffithsin is still not available as an off-the-shelf product. So during the Covid pandemic, the team experimented with synthesizing griffithsin using the cell-free production method. They were able to generate potent griffithsin in less than 24 hours without having to grow living cells.
The antiviral protein isn't the only type of medicine that can be made cell-free. The proteins needed for vaccine production could also be made the same way. “Such portable, on-demand drug manufacturing platforms can produce antiviral proteins within hours, making them ideal for combating future pandemics,” Rao says. “We would be able to stop the pandemic before it spreads.”
Top: Describes the process used in the study. Bottom: Describes how the new medicines and vaccines could be made at the site of a future viral outbreak.
Image courtesy of Rao and team, sourced from An approach to rapid distributed manufacturing of broad spectrumanti-viral griffithsin using cell-free systems to mitigate pandemics.
Rao’s idea is to perfect the technology to the point that any hospital or pharmacy can load up the media containing molecular factories, mix up the required amino acids, nucleotides and enzymes, and harvest the meds within hours. That will allow making medicines onsite and on demand. “That would be a self-contained production unit, so that you could just ship the production wherever the pandemic is breaking out,” says Swartz.
These units and the meds they produce, will, of course, have to undergo rigorous testing. “The biggest hurdles will be validating these against conventional technology,” Rao says. The biotech industry is risk-averse and prefers the familiar methods. But if this approach works, it may go beyond emergency situations and revolutionize the medicine-making paradigm even outside hospitals and pharmacies. Rao hopes that someday the method might become so mainstream that people may be able to buy and operate such reactors at home. “You can imagine a diabetic patient making insulin that way, or some other drugs,” Rao says. It would work not unlike making baby formula from the mere white powder. Just add water—and some oxygen, too.