Scientists are working on eye transplants for vision loss. Who will sign up?
Awash in a fluid finely calibrated to keep it alive, a human eye rests inside a transparent cubic device. This ECaBox, or Eyes in a Care Box, is a one-of-a-kind system built by scientists at Barcelona’s Centre for Genomic Regulation (CRG). Their goal is to preserve human eyes for transplantation and related research.
In recent years, scientists have learned to transplant delicate organs such as the liver, lungs or pancreas, but eyes are another story. Even when preserved at the average transplant temperature of 4 Centigrade, they last for 48 hours max. That's one explanation for why transplanting the whole eye isn’t possible—only the cornea, the dome-shaped, outer layer of the eye, can withstand the procedure. The retina, the layer at the back of the eyeball that turns light into electrical signals, which the brain converts into images, is extremely difficult to transplant because it's packed with nerve tissue and blood vessels.
These challenges also make it tough to research transplantation. “This greatly limits their use for experiments, particularly when it comes to the effectiveness of new drugs and treatments,” said Maria Pia Cosma, a biologist at Barcelona’s Centre for Genomic Regulation (CRG), whose team is working on the ECaBox.
Eye transplants are desperately needed, but they're nowhere in sight. About 12.7 million people worldwide need a corneal transplant, which means that only one in 70 people who require them, get them. The gaps are international. Eye banks in the United Kingdom are around 20 percent below the level needed to supply hospitals, while Indian eye banks, which need at least 250,000 corneas per year, collect only around 45 to 50 thousand donor corneas (and of those 60 to 70 percent are successfully transplanted).
As for retinas, it's impossible currently to put one into the eye of another person. Artificial devices can be implanted to restore the sight of patients suffering from severe retinal diseases, but the number of people around the world with such “bionic eyes” is less than 600, while in America alone 11 million people have some type of retinal disease leading to severe vision loss. Add to this an increasingly aging population, commonly facing various vision impairments, and you have a recipe for heavy burdens on individuals, the economy and society. In the U.S. alone, the total annual economic impact of vision problems was $51.4 billion in 2017.
Even if you try growing tissues in the petri dish route into organoids mimicking the function of the human eye, you will not get the physiological complexity of the structure and metabolism of the real thing, according to Cosma. She is a member of a scientific consortium that includes researchers from major institutions from Spain, the U.K., Portugal, Italy and Israel. The consortium has received about $3.8 million from the European Union to pursue innovative eye research. Her team’s goal is to give hope to at least 2.2 billion people across the world afflicted with a vision impairment and 33 million who go through life with avoidable blindness.
Their method? Resuscitating cadaveric eyes for at least a month.
If we succeed, it will be the first intact human model of the eye capable of exploring and analyzing regenerative processes ex vivo. -- Maria Pia Cosma.
“We proposed to resuscitate eyes, that is to restore the global physiology and function of human explanted tissues,” Cosma said, referring to living tissues extracted from the eye and placed in a medium for culture. Their ECaBox is an ex vivo biological system, in which eyes taken from dead donors are placed in an artificial environment, designed to preserve the eye’s temperature and pH levels, deter blood clots, and remove the metabolic waste and toxins that would otherwise spell their demise.
Scientists work on resuscitating eyes in the lab of Maria Pia Cosma.
Courtesy of Maria Pia Cosma.
“One of the great challenges is the passage of the blood in the capillary branches of the eye, what we call long-term perfusion,” Cosma said. Capillaries are an intricate network of very thin blood vessels that transport blood, nutrients and oxygen to cells in the body’s organs and systems. To maintain the garland-shaped structure of this network, sufficient amounts of oxygen and nutrients must be provided through the eye circulation and microcirculation. “Our ambition is to combine perfusion of the vessels with artificial blood," along with using a synthetic form of vitreous, or the gel-like fluid that lets in light and supports the the eye's round shape, Cosma said.
The scientists use this novel setup with the eye submersed in its medium to keep the organ viable, so they can test retinal function. “If we succeed, we will ensure full functionality of a human organ ex vivo. It will be the first intact human model of the eye capable of exploring and analyzing regenerative processes ex vivo,” Cosma added.
A rapidly developing field of regenerative medicine aims to stimulate the body's natural healing processes and restore or replace damaged tissues and organs. But for people with retinal diseases, regenerative medicine progress has been painfully slow. “Experiments on rodents show progress, but the risks for humans are unacceptable,” Cosma said.
The ECaBox could boost progress with regenerative medicine for people with retinal diseases, which has been painfully slow because human experiments involving their eyes are too risky. “We will test emerging treatments while reducing animal research, and greatly accelerate the discovery and preclinical research phase of new possible treatments for vision loss at significantly reduced costs,” Cosma explained. Much less time and money would be wasted during the drug discovery process. Their work may even make it possible to transplant the entire eyeball for those who need it.
“It is a very exciting project,” said Sanjay Sharma, a professor of ophthalmology and epidemiology at Queen's University, in Kingston, Canada. “The ability to explore and monitor regenerative interventions will increasingly be of importance as we develop therapies that can regenerate ocular tissues, including the retina.”
Seemingly, there's no sacred religious text or a holy book prohibiting the practice of eye donation.
But is the world ready for eye transplants? “People are a bit weird or very emotional about donating their eyes as compared to other organs,” Cosma said. And much can be said about the problem of eye donor shortage. Concerns include disfigurement and healthcare professionals’ fear that the conversation about eye donation will upset the departed person’s relatives because of cultural or religious considerations. As just one example, Sharma noted the paucity of eye donations in his home country, Canada.
Yet, experts like Sharma stress the importance of these donations for both the recipients and their family members. “It allows them some psychological benefit in a very difficult time,” he said. So why are global eye banks suffering? Is it because the eyes are the windows to the soul?
Seemingly, there's no sacred religious text or a holy book prohibiting the practice of eye donation. In fact, most major religions of the world permit and support organ transplantation and donation, and by extension eye donation, because they unequivocally see it as an “act of neighborly love and charity.” In Hinduism, the concept of eye donation aligns with the Hindu principle of daan or selfless giving, where individuals donate their organs or body after death to benefit others and contribute to society. In Islam, eye donation is a form of sadaqah jariyah, a perpetual charity, as it can continue to benefit others even after the donor's death.
Meanwhile, Buddhist masters teach that donating an organ gives another person the chance to live longer and practice dharma, the universal law and order, more meaningfully; they also dismiss misunderstandings of the type “if you donate an eye, you’ll be born without an eye in the next birth.” And Christian teachings emphasize the values of love, compassion, and selflessness, all compatible with organ donation, eye donation notwithstanding; besides, those that will have a house in heaven, will get a whole new body without imperfections and limitations.
The explanation for people’s resistance may lie in what Deepak Sarma, a professor of Indian religions and philosophy at Case Western Reserve University in Cleveland, calls “street interpretation” of religious or spiritual dogmas. Consider the mechanism of karma, which is about the causal relation between previous and current actions. “Maybe some Hindus believe there is karma in the eyes and, if the eye gets transplanted into another person, they will have to have that karmic card from now on,” Sarma said. “Even if there is peculiar karma due to an untimely death–which might be interpreted by some as bad karma–then you have the karma of the recipient, which is tremendously good karma, because they have access to these body parts, a tremendous gift,” Sarma said. The overall accumulation is that of good karma: “It’s a beautiful kind of balance,” Sarma said.
For the Jews, Christians, and Muslims who believe in the physical resurrection of the body that will be made new in an afterlife, the already existing body is sacred since it will be the basis of a new refashioned body in an afterlife.---Omar Sultan Haque.
With that said, Sarma believes it is a fallacy to personify or anthropomorphize the eye, which doesn’t have a soul, and stresses that the karma attaches itself to the soul and not the body parts. But for scholars like Omar Sultan Haque—a psychiatrist and social scientist at Harvard Medical School, investigating questions across global health, anthropology, social psychology, and bioethics—the hierarchy of sacredness of body parts is entrenched in human psychology. You cannot equate the pinky toe with the face, he explained.
“The eyes are the window to the soul,” Haque said. “People have a hierarchy of body parts that are considered more sacred or essential to the self or soul, such as the eyes, face, and brain.” In his view, the techno-utopian transhumanist communities (especially those in Silicon Valley) have reduced the totality of a person to a mere material object, a “wet robot” that knows no sacredness or hierarchy of human body parts. “But for the Jews, Christians, and Muslims who believe in the physical resurrection of the body that will be made new in an afterlife, the [already existing] body is sacred since it will be the basis of a new refashioned body in an afterlife,” Haque said. “You cannot treat the body like any old material artifact, or old chair or ragged cloth, just because materialistic, secular ideologies want so,” he continued.
For Cosma and her peers, however, the very definition of what is alive or not is a bit semantic. “As soon as we die, the electrophysiological activity in the eye stops,” she said. “The goal of the project is to restore this activity as soon as possible before the highly complex tissue of the eye starts degrading.” Cosma’s group doesn’t yet know when they will be able to keep the eyes alive and well in the ECaBox, but the consensus is that the sooner the better. Hopefully, the taboos and fears around the eye donations will dissipate around the same time.
After You Die, Your Digital Self Could Live on as a Chatbot
My wife and I visited a will-and-trust lawyer after our first son was born. Everything seemed simple and clear until the lawyer asked, without missing a beat, "So, what about your social media management?" My wife looked at me and, even though I'm more tech savvy, I felt as confused as a Luddite.
One can imagine chatbots becoming the next generation of care management alongside funeral services, and will and testaments.
"Social media management?" I laughed, making a joke about my wife spending more time on Facebook than I do. But the lawyer's question was serious, as were the legal documents asking for our profile page links, passwords, and related information.
What do you want to happen to your Facebook, Twitter, and other social media platforms after you die? Your grandfather may have wanted his cremated ashes poured into the Ganges, or a burial in a prepaid plot. But unlike earlier generations, whose personas ended with their last breath, your bits and bytes could live on across multiple servers, holding a space for you online like a digital obelisk. Or, if you desire, your relatives can do the equivalent of a DNR: Delete account.
"It is the future of 'Get your affairs in order,'" says John Havens, Executive Director of the IEEE Global Initiative on Ethics of Autonomous and Intelligent Systems. He remembers being pulled aside when his father was being put into the ICU and realizing that his dad wasn't going to come back.
Havens says if we are lucky enough to know that we are wrapping up our time, then we have the opportunity not just to bow out of the digital world gracefully, but to have our digital persona carry on beyond us. This persona could go beyond today's static memorial pages on Facebook and Instagram; it could be an interactive computer program designed from your specific speech patterns, memories, and personality – a chatbot.
"I could have an algorithm trained to hear what I say and how I say it," Havens told me. "You can say, 'I'm Damon and I'm going to pass in the next few months, but, you know, over the past six months, I've created a chatbot to continue our conversations. In the upcoming months, my partner or loved ones will let you know when the chatbot will take over and be involved.'"
The chatbot could become an extension of you on platforms like Messenger or WhatsApp, for example. One can imagine this becoming the next generation of care management alongside funeral services, and will and testaments. You can see the future in Eugenia Kuyda, an entrepreneur who successfully created an interactive chatbot of her late friend, Roman Mazurenko, just based on his text messages. Her new program, Replika, may eventually give us the same technology so we, too, can all potentially do the same with our loved ones. Expect other tech companies to follow suit.
There is now no real separation between IRL and online – just as there may be an increasingly blurred line between our personas before and after death.
Chatbots offer us an irresistible decision: They are artificial intelligence programs built to have conversations with people, usually within a service capacity like canceling a shipping order or getting to the right help desk. You can view it as a modern-day helpline and, no doubt, you've interacted with chatbots when you've made purchases online. Chatbots are now becoming verbal, too, managing phone calls you make to your credit card company, local utilities, and other daily operations.
We witnessed our future this spring when Google showed off Google Duplex. It is a voice-driven system that will call people on your behalf with the intention, Google says, to manage your life. At the Google I/O conference, Google CEO Sundar Pichai showed Duplex calling a hair salon and interacting with the human receptionist – with nearly all the pauses, mmm-hmms, and colloquialisms as its female counterpart. "The amazing part is the assistant can actually understand the nuances of conversation," Pichai said to the rapt tech audience.
Recode's Kurt Wagner explained the immediate problem with the Google Duplex demo, which is the same problem technologists so often overlook: What if someone uses your technology in ways you didn't intend? "The major concern with that demo was that Google Assistant never said it was a robot or told the salon that the call was being recorded. When pressed by members of the media in the days after the demo, Google declined to comment, leading some to believe the company had simply overlooked this privacy element altogether."
"This is why disclosure will be so huge," Havens says. "When people call, they will begin with, 'Hello. I am a human.'"
This conflict between the physical and the digital is now coming to a head, though it isn't the clichéd man against machine Skynet conspiracy theories, but rather us against us. Today, it is as if we are split into two or, perhaps more accurately, two personas – our "real-life" persona and our online persona – and we're now experiencing fatigue trying to hold center.
It is a new phenomenon reflective of our social media: Media forerunners like MySpace and Friendster as well as classic websites like LiveJournal and Tumblr allowed us to explore the online world – and, in a sense, the physical world beyond our physical reach – using avatars as close to or as far from our real selves as we desired. On the Internet, nobody knows you're a dog.
Facebook truly eliminated the powerful choice of anonymity, as its extensive verification process required people to give up anonymity to participate in the biggest social network in the world. This was a willful, purposeful decision by Facebook: Founder Mark Zuckerberg has been an advocate of being yourself online, and the former Director of Market Development Randi Zuckerberg infamously said, "I think anonymity on the Internet has to go away… People behave a lot better when they have their real names down."
This was Facebook's intention and, whether or not its theory of people behaving better is true, especially in light of the 2016 U.S. Presidential election, the effects on us are real. Sex workers and other high-risk, anonymity-driven entrepreneurs are being outed via social media. The parallel rise in online addiction clinics isn't a coincidence, as the blur between the physical self and the digital self has never been hazier. There is now no real separation between IRL and online – just as there may be an increasingly blurred line between our personas before and after death.
Chatbots represent a tempting form of convenience: A way to remove our cognitive load to an assistant that will manage our relationships.
We have Carrie Fisher starring in the next Star Wars movie, potentially winning the first truly post-humous Oscar thanks to technology that can help transition older footage into live-recorded footage. Similar, more subtle turns occurred with Paul Walker in the Fast and the Furious 7, which used a combination of CGI and stand-ins. But a key difference is that we actually know they are dead before the movie is even released. As not-famous individuals, we have the ethical choice (duty?) to disclose that information to our social media followers after we die.
While we're still alive, though, chatbots represent a tempting form of convenience: A way to remove our cognitive load to an assistant that will manage our relationships. The rub is that our online relationships are our personal relationships, so we're not just potentially automating, say, our social media feed or our online postings, but our responsibilities in the real-life relationships that we've built. There is no line.
"It's naïve to think that the Google Duplex that was designed to make your hair appointments won't be used to do more difficult things like break up with a girlfriend," Havens says. "Record 50 words, use different inflections, and put in phrases like 'It's not you, it's me.' Why wouldn't people do that?"
Well, it really depends on the person. My wife and I ended up leaving the social media management section of our will blank for now. I even took a long social media sabbatical to connect with people more in person. If my online relationships and my in-person relationships are all becoming the same, then maybe it's OK to let them die – just like I will.
One Day, There Might Be a Drug for a Broken Heart
For Tony Y., 37, healing from heartbreak is slow and incomplete. Each of several exes is associated with a cluster of sore memories. Although he loves the Blue Ridge Mountains, he can't visit because they remind him of a romantic holiday years ago.
If a new drug made rejections less painful, one expert argues, it could relieve or even prevent major depression.
Like some 30 to 40 percent of depressed patients, Tony hasn't had success with current anti-depressants. One day, psychiatrists may be able to offer him a new kind of opioid, an anti-depressant for people suffering from the cruel pain of rejection.
A Surprising Discovery
As we move through life, rejections -- bullying in school, romantic breakups, and divorces -- are powerful triggers to depressive episodes, observes David Hsu, a neuroscientist at Stony Brook University School of Medicine in Long Island, New York. If a new drug made them less painful, he argues, it could relieve or even prevent major depression.
Our bodies naturally produce opioids to soothe physical pain, and opioid drugs like morphine and oxycodone work by plugging into the same receptors in our brains. The same natural opioids may also respond to emotional hurts, and painkillers can dramatically affect mood. Today's epidemic of opioid abuse raises the question: How many lives might have been saved if we had a safe, non-addictive option for medicating emotional pain?
Already one anti-depressant, tianeptine, locks into the mu opioid receptor, the target of morphine and oxycodone. Scientists knew that tianeptine, prescribed in some countries in Europe, Asia, and Latin America, acted differently than the most common anti-depressants in use today, which affect the levels of other brain chemicals, serotonin and norepinephrine. But the discovery in 2014 that tianeptine tapped the mu receptor was a "huge surprise," says co-author Jonathan Javitch, chief of the Division of Molecular Therapeutics at Columbia University.
The news arrived when scientists' basic understanding of depression is in flux; viewed biologically, it may cover several disorders. One of them could hinge on opioids. It's possible that some people release fewer opioids naturally or that the receptors for it are less effective.
Javitch has launched a startup, Kures, to make tianeptine more effective and convenient and to find other opioid-modulators. That may seem quixotic in the midst of an opioid epidemic, but tianeptine doesn't create dependency in low, prescription doses and has been used safely around the world for decades. To identify likely patients, cofounder Andrew Kruegel is looking for ways to "segment the depressed population by measures that have to do with opioid release," he says.
Is Emotional Pain Actually "Pain"?
No one imagines that the pain from rejection or loss is the same as pain from a broken leg. Physical pain is two perceptions—a sensory perception and an "affective" one, which makes pain unpleasant.
Exploration of an overlap between physical and what research psychologists call "social pain" has heated up since the mid-2000s.
The sensory perception, processed by regions of the brain called the primary and secondary somatosensory cortices and the posterior insula, tells us whether the pain is in your arm or your leg, how strong it is and whether it is a sting, ache, or has some other quality. The affective perception, in another part of the brain called the dorsal anterior cingulate cortex and the anterior insula, tells us that we want the pain to stop, fast! When people with lesions in the latter areas experience a stimulus that ordinarily would be painful, they don't mind it.
Science now suggests that emotional pain arises in the affective brain circuits. Exploration of an overlap between physical and what research psychologists call "social pain" has heated up since the mid-2000s. Animal evidence goes back to the 1970s: babies separated from their mothers showed less distress when given morphine, and more if dosed with naloxone, the opioid antagonist.
Parents, of course, face the question of whether Baby feels alone or wet whenever she howls. And the answer is: both hurt. Being abandoned is the ultimate threat in our early life, and it makes sense that a brain system to monitor social threats would piggyback upon an existing system for pain. Piggybacking is a feature of evolution. An ancestor who felt "hurt" when threatened by rejection might learn adaptive behavior: to cooperate or run.
In 2010, a large multi-university team led by Nathan DeWall at the University of Kentucky, reported that acetaminophen (Tylenol) reduced social pain. Undergraduates took 500 mg of acetaminophen upon awakening and at bedtime every day for three weeks and reported nightly about their day using a previously-tested "Hurt Feelings Scale," rating how strongly they agreed with questions like, "Today, being teased hurt my feelings."
Over the weeks, their reports of hurt feelings steadily declined, while remaining flat in a control group that took placebos. In a second experiment, the research group showed that, compared to controls, people who had taken acetaminophen for three weeks showed less brain activity in the affective brain circuits while they experienced rejection during a virtual ball-tossing game. Later, Hsu's brain scan research supported the idea that rejection triggers the mu opioid receptor system, which normally provides pain-dampening opioids.
More evidence comes from nonhuman primates with lesions in the affective circuits: They cry less when separated from caregivers or social groups.
Heartbreak seems to lie in those regions: women with major depression are more hurt by romantic rejection than normal controls are and show more activity in those areas in brain scans, Hsu found. Also, factors that make us more vulnerable to rejection -- like low self-esteem -- are linked to more activity in the key areas, studies show.
The trait "high rejection sensitivity" increases your risk of depression more than "global neuroticism" does, Hsu observes, and predicts a poor recovery from depression. Pain sensitivity is another clue: People with a gene linked to it seem to be more hurt by social exclusion. Once you're depressed, you become more rejection-sensitive and prone to pain—a classic bad feedback loop.
"Ideally, we'd have biomarkers to distinguish when loss becomes complicated grief and then depression, and we might prevent the transition with a drug."
Helen Mayberg, a neurologist renowned for her study of brain circuits in depression, sees, as Hsu does, the possibility of preventing depressions. "Nobody would suggest we treat routine bad social pain with drugs. But it is true that in susceptible people, losing a partner, for example, can lead to a full-blown depression," says Mayberg, who is the founding director of The Center for Advanced Circuit Therapeutics at Mount Sinai's Icahn School of Medicine in New York City. "Ideally, we'd have biomarkers to distinguish when loss becomes complicated grief and then depression, and we might prevent the transition with a drug. It would be like taking medication when you feel the warning symptoms of a headache to prevent a full-blown migraine."
A Way Out of the Opioid Crisis?
The exploration of social pain should lead us to a deeper understanding of pain, beyond the sharp distinctions between "physical" and "psychological." Finding our way out of the current crisis may require that deeper understanding. About half of the people with opioid prescriptions have mental health disorders. "I expect there are a lot of people using street opioids—heroin or prescriptions purchased from others--to self-medicate psychological pain," Kreugel says.
What we may need, he suggests, is "a new paradigm for using opioids in psychiatry: low, sub-analgesic, sub-euphoric dosing." But so far it hasn't been easy. Investors don't flock to fund psychiatric drugs and in 2018, the word opioid is poison.
As for Tony Y., he's struggled for three years to recover from his most serious relationship. "Driving around highways looking at exit signs toward places we visited together sometimes fills me with unbearable anguish," he admits. "And because we used to do so much bird watching together, sometimes a mere glimpse of a random bird sets me off." He perks up at the idea of a heartbreak drug. "If the side effects didn't seem bad, I would consider it, absolutely."