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).]
Many women want non-hormonal birth control. A 22-year-old's findings were used to launch a company that could, within the decade, bring a new kind of contraceptive to the marketplace.
Now a scientist with NextVivo, Shrestha is not directly involved in the development of the contraceptive that is based on her research. But, back in 2016 when she was going through her own problems with hormonal contraceptives, she “was very personally invested” in her research project, Shrestha says. She was coping with a long list of negative effects from an implanted hormonal IUD. According to the Mayo Clinic, those can include severe pelvic pain, headaches, acute acne, breast tenderness, irregular bleeding and mood swings. After a year, she had the IUD removed, but it took another full year before all the side effects finally subsided; she also watched her sister suffer the “same tribulations” after trying a hormonal IUD, she says.
For contraceptive use either daily or monthly, Shrestha says, “You want the antibody to be very potent and also cheap.” That was her goal when she launched her study.
Shrestha unshelved antibody research that had been sitting idle for decades. It was in the late 80s that scientists in Japan first tried to develop anti-sperm antibodies for contraceptive use. But, 35 years ago, “Antibody production had not been streamlined as it is now, so antibodies were very expensive,” Shrestha explains. So, they shifted away from birth control, opting to focus on developing antibodies for vaccines.
Over the course of the last three decades, different teams of researchers have been working to make the antibody more effective, bringing the cost down, though it’s still expensive, according to Shrestha. For contraceptive use either daily or monthly, she says, “You want the antibody to be very potent and also cheap.” That was her goal when she launched her study.
The problem
The problem with contraceptives for women, Shrestha says, is that all but a few of them are hormone-based or have other negative side effects. In fact, some studies and reports show that millions of women risk unintended pregnancy because of medical contraindications with hormone-based contraceptives or to avoid the risks and side effects. While there are about a dozen contraceptive choices for women, there are two for men: the condom, considered 98% effective if used correctly, and vasectomy, 99% effective. Neither of these choices are hormone-based.
On the non-hormonal side for women, there is the diaphragm which is considered only 87 percent effective. It works better with the addition of spermicides — Nonoxynol-9, or N-9 — however, they are detergents; they not only kill the sperm, they also erode the vaginal epithelium. And, there’s the non-hormonal IUD which is 99% effective. However, the IUD needs to be inserted by a medical professional, and it has a number of negative side effects, including painful cramping at a higher frequency and extremely heavy or “abnormal” and unpredictable menstrual flows.
The hormonal version of the IUD, also considered 99% effective, is the one Shrestha used which caused her two years of pain. Of course, there’s the pill, which needs to be taken daily, and the birth control ring which is worn 24/7. Both cause side effects similar to the other hormonal contraceptives on the market. The ring is considered 93% effective mostly because of user error; the pill is considered 99% effective if taken correctly.
“That’s where we saw this opening or gap for women. We want a safe, non-hormonal contraceptive,” Shrestha says. Compounding the lack of good choices, is poor access to quality sex education and family planning information, according to the non-profit Urban Institute. A focus group survey suggested that the sex education women received “often lacked substance, leaving them feeling unprepared to make smart decisions about their sexual health and safety,” wrote the authors of the Urban Institute report. In fact, nearly half (45%, or 2.8 million) of the pregnancies that occur each year in the US are unintended, reports the Guttmacher Institute. Globally the numbers are similar. According to a new report by the United Nations, each year there are 121 million unintended pregnancies, worldwide.
The science
The early work on antibodies as a contraceptive had been inspired by women with infertility. It turns out that 9 to 12 percent of women who are treated for infertility have antibodies that develop naturally and work against sperm. Shrestha was encouraged that the antibodies were specific to the target — sperm — and therefore “very safe to use in women.” She aimed to make the antibodies more stable, more effective and less expensive so they could be more easily manufactured.
Since antibodies tend to stick to things that you tell them to stick to, the idea was, basically, to engineer antibodies to stick to sperm so they would stop swimming. Shrestha and her colleagues took the binding arm of an antibody that they’d isolated from an infertile woman. Then, targeting a unique surface antigen present on human sperm, they engineered a panel of antibodies with as many as six to 10 binding arms — “almost like tongs with prongs on the tongs, that bind the sperm,” explains Shrestha. “We decided to add those grabbers on top of it, behind it. So it went from having two prongs to almost 10. And the whole goal was to have so many arms binding the sperm that it clumps it” into a “dollop,” explains Shrestha, who earned a patent on her research.
Suruchi Shrestha works in the lab with a colleague. In 2016, her research on antibodies for birth control was inspired by her own experience with side effects from an implanted hormonal IUD.
UNC - Chapel Hill
The sperm stays right where it met the antibody, never reaching the egg for fertilization. Eventually, and naturally, “Our vaginal system will just flush it out,” Shrestha explains.
“She showed in her early studies that [she] definitely got the sperm immotile, so they didn't move. And that was a really promising start,” says Jasmine Edelstein, a scientist with an expertise in antibody engineering who was not involved in this research. Shrestha’s team at UNC reproduced the effect in the sheep, notes Edelstein, who works at the startup Be Biopharma. In fact, Shrestha’s anti-sperm antibodies that caused the sperm to agglutinate, or clump together, were 99.9% effective when delivered topically to the sheep’s reproductive tracts.
The future
Going forward, Shrestha thinks the ideal approach would be delivering the antibodies through a vaginal ring. “We want to use it at the source of the spark,” Shrestha says, as opposed to less direct methods, such as taking a pill. The ring would dissolve after one month, she explains, “and then you get another one.”
Engineered to have a long shelf life, the anti-sperm antibody ring could be purchased without a prescription, and women could insert it themselves, without a doctor. “That's our hope, so that it is accessible,” Shrestha says. “Anybody can just go and grab it and not worry about pregnancy or unintended pregnancy.”
Her patented research has been licensed by several biotech companies for clinical trials. A number of Shrestha’s co-authors, including her lab advisor, Sam Lai, have launched a company, Mucommune, to continue developing the contraceptives based on these antibodies.
And, results from a small clinical trial run by researchers at Boston University Chobanian & Avedisian School of Medicine show that a dissolvable vaginal film with antibodies was safe when tested on healthy women of reproductive age. That same group of researchers last year received a $7.2 million grant from the National Institute of Health for further research on monoclonal antibody-based contraceptives, which have also been shown to block transmission of viruses, like HIV.
“As the costs come down, this becomes a more realistic option potentially for women,” says Edelstein. “The impact could be tremendous.”
This article was first published by Leaps.org in December, 2022. It has been lightly edited with updates for timeliness.
When all traditional therapeutic approaches fail for alcohol abuse disorder, a radical gene therapy might be something to try in the future.
In the U.S., more than 10 percent of people over the age of 12 are estimated to have AUD, and while medications, counseling, or sheer willpower can help some stop drinking, staying sober can be a huge struggle — an estimated 40-60 percent of people relapse at least once.
A team of U.S. researchers suspected that an in-development gene therapy for Parkinson’s disease might work as a dopamine-replenishing treatment for alcoholism, too.
According to the CDC, more than 140,000 Americans are dying each year from alcohol-related causes, and the rate of deaths has been rising for years, especially during the pandemic.
The idea: For occasional drinkers, alcohol causes the brain to release more dopamine, a chemical that makes you feel good. Chronic alcohol use, however, causes the brain to produce, and process, less dopamine, and this persistent dopamine deficit has been linked to alcohol relapse.
There is currently no way to reverse the changes in the brain brought about by AUD, but a team of U.S. researchers suspected that an in-development gene therapy for Parkinson’s disease might work as a dopamine-replenishing treatment for alcoholism, too.
To find out, they tested it in heavy-drinking monkeys — and the animals’ alcohol consumption dropped by 90% over the course of a year.
How it works: The treatment centers on the protein GDNF (“glial cell line-derived neurotrophic factor”), which supports the survival of certain neurons, including ones linked to dopamine.
For the new study, a harmless virus was used to deliver the gene that codes for GDNF into the brains of four monkeys that, when they had the option, drank heavily — the amount of ethanol-infused water they consumed would be equivalent to a person having nine drinks per day.
“We targeted the cell bodies that produce dopamine with this gene to increase dopamine synthesis, thereby replenishing or restoring what chronic drinking has taken away,” said co-lead researcher Kathleen Grant.
To serve as controls, another four heavy-drinking monkeys underwent the same procedure, but with a saline solution delivered instead of the gene therapy.
The results: All of the monkeys had their access to alcohol removed for two months following the surgery. When it was then reintroduced for four weeks, the heavy drinkers consumed 50 percent less compared to the control group.
When the researchers examined the monkeys’ brains at the end of the study, they were able to confirm that dopamine levels had been replenished in the treated animals, but remained low in the controls.
The researchers then took the alcohol away for another four weeks, before giving it back for four. They repeated this cycle for a year, and by the end of it, the treated monkeys’ consumption had fallen by more than 90 percent compared to the controls.
“Drinking went down to almost zero,” said Grant. “For months on end, these animals would choose to drink water and just avoid drinking alcohol altogether. They decreased their drinking to the point that it was so low we didn’t record a blood-alcohol level.”
When the researchers examined the monkeys’ brains at the end of the study, they were able to confirm that dopamine levels had been replenished in the treated animals, but remained low in the controls.
Looking ahead: Dopamine is involved in a lot more than addiction, so more research is needed to not only see if the results translate to people but whether the gene therapy leads to any unwanted changes to mood or behavior.
Because the therapy requires invasive brain surgery and is likely irreversible, it’s unlikely to ever become a common treatment for alcoholism — but it could one day be the only thing standing between people with severe AUD and death.
“[The treatment] would be most appropriate for people who have already shown that all our normal therapeutic approaches do not work for them,” said Grant. “They are likely to create severe harm or kill themselves or others due to their drinking.”
This article originally appeared on Freethink, home of the brightest minds and biggest ideas of all time.
