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.
Viv spent nearly an hour choosing her body.
She considered going as her eight year-old self. She would stand eye-to-eye with her father in his hospital bed, shedding tears and crying: please don't go, daddy. But that was too obvious. It would offend him.
He became data coursing through a network, able to embody any form, to outlive physical decay.
She considered her eighteen year-old self. She would lean over him, scrawny and tall, her lips trembling with anger: you're being selfish, dad. But that would lead to shouting.
She considered every form, even reviving people from the past: her mother, her grandfather, her little sister Mary. How would her father react to Mary walking in? He would think himself dead. She could whisper a message to him: Stay alive, dad. God commands it.
In the end, Viv chose the look of her last days as a biological person. Thirty-one years old, her auburn hair cut short, her black eyes full of longing. She watched the body print in silicon over robotic armature.
When it blinked to life, Viv stood in front of a mirror. Her face was appropriately somber, her mind in sync with her new muscles. Without thinking, she stretched her arms, arched her body, twirled on her tiptoes. She had forgotten the pleasure of sensation.
"I should do this…" The voice resonated through her. She could not help but smile. "I should do this more often… often… often." Every repetition thrilled her with sound. She began to sing an old favorite: "Times have changed… and we've often…"
But she stopped herself. This was not a day for singing.
Viv clothed her body in a blue dress, packed her tablet in a briefcase, stood in front of the mirror one last time. "I'll be there in five," she said aloud, though she did not need to.
A man's voice answered in her mind: I'm not coming.
"Gabe…"
There's no point, said the voice. We know what he'll say.
"We have to try."
I won't see him dying, Viv.
The clenching of her jaw felt like the old days. Her brother made a habit of last-minute decisions, without concern for how they affected other people, most often her.
She remembered the day he became an everperson. It was soon after their mother's death. They were supposed to visit their father in mourning, but Gabe disappeared without explanation. Viv took the full burden of solace on herself. She sat with her father in a small room, with an old Persian rug and stale furniture. His mustache was beginning to gray, his eyes beginning to wrinkle. "She's with your sister now," he said. "Your mom and Mary, I can…" He leaned in to whisper, "I can almost hear them, at night, laughing on the other side. They tell me to wait… they tell me to wait." Viv nodded for him, pretending to believe, wishing she could.
Gabe did not return her calls that evening. The next day, she began to worry. The day after, she began to look. He made no effort to hide, he simply neglected to tell her the new plan.
Gabe had taken the money from his inheritance, and booked himself an everence. It was something new back then. Viv did not understand the science, but she knew it was a destructive process. His physical brain was destroyed by lasers that scanned it neuron by neuron, creating a digital replica. He became data coursing through a network, able to embody any form, to outlive physical decay. He became an everperson.
It took three days to complete. Viv went to the facility, a converted warehouse by the Bay Bridge. She watched the new Gabe being printed over robotic armature, taking the form of his last biological self, to help with the transition. When he blinked to life, she did not know if he would be the same person, or an imperfect copy of an imperfect copy. But Gabe was totally oblivious to the pain he caused her by disappearing in that way. No robot, she thought, could be so callous.
When Viv made her own decision to everize, she deliberated for weeks, thinking through the consequences and conversations to come. Afterwards, she sat with her father in that same small room, with the Persian rug older, the furniture staler, a new cat purring at his feet.
"But it's suicide," he said.
"It's the opposite, dad. It's eternal life."
"You'd be a robot. You wouldn't be you."
"Gabe's the same as he ever was," she noted the resentment in her voice. "He's just not… physical, until he wants to be."
Her father exhaled an Arabic phrase he was using more often in his old age. La hawla wa la quwata illa billah. She had never learned his native tongue, but she looked up the phrase to understand him better. It meant something like: there is no power except in God. It was a sigh of resignation.
"Vivian," he said eventually, "Your soul is not your brain. Your soul lives on. If you kill yourself, you... it's unforgivable. Don't you want to see mom in heaven? Mary? Me?"
She wanted to believe. She wanted painfully. But when she spoke, it was barely a whisper. "I don't think that will happen, dad."
Fewer biological people meant little need for hospitals, or doctors. It would close soon.
It was the first she had ever confessed to him about God or Heaven. In as steady a voice as he could manage, her father said: "You're an adult, Viv. You do what you think is best."
She came to visit sometimes, as an everperson. He could not tell at first. But as the years went by, as his eyes wrinkled, and his hair grayed, he noticed that Viv never aged. One day he stopped talking to her. Another she stopped coming.
Now he was waiting out the last days of his life alone in a hospital bed. Viv did not want to say goodbye. It seemed such a waste.
You don't have to, Gabe spoke into her mind. Get him to sign, say anything, say it's for selling the house. Once we have full power of attorney, we can decide for him.
"It's not right." She noticed herself speaking aloud on the hoverbus. Nine nervous faces turned to her.
It's not right, she continued in her mind. Dad never forced us to pray, never forced us to —
That was mom.
But he loved her. He never changed her mind, he raised us to question, and he quietly believed. He has every right to live his way, just like we did.
To live. Not to die... When he's an everperson, he'll thank us.
That gave her pause. It might be true. She remembered her first moments as an everperson, suddenly linked to countless other minds, waking to the full expanse of human knowledge like sunlight through an open window, breathless and unexpected.
Still, she said, it's not right.
So you want him to die?
I want to convince him.
And what if you don't? There was panic in his voice. Gabe steadied himself. You brought your tablet, Viv. You know what it's for. Get him to sign.
And what if I don't?
I'll figure something out, with or without you. I won't let him die, Viv. Not this day and age.
Viv kept quiet the rest of her way there. She played memories in her mind, of every conversation she ever had with her father, every time he read her a verse or taught her a parable. She looked for a way to convince him, some doubt, some chink in his armor of belief. But she got distracted by the world outside.
It was strange to pass for a time through physical space. It took longer than she expected. Now watching the sunlight refract through the hoverbus window, she was mesmerized. Every sensation felt more real, more vivid than her memory. "I should do this more often," she said aloud.
The hospital smelled like death. It had fallen into disrepair since her mother's illness. Fewer biological people meant little need for hospitals, or doctors. It would close soon, she thought. Her footsteps echoed through the halls, along with the sounds of old televisions playing old films to keep the patients company.
The room she entered had no sound, except the whirring machines. No light, except an eerie glow filtering through the curtains. The figure on the bed was her father, his breathing strained, his skin cracked like the desert. She closed the door behind her.
When her father turned, she saw a flicker of joy in his eyes. It disappeared.
"La hawla wa la… I thought it was her."
"I am her."
He winced. "She died some twenty years ago."
Viv sat next to him. The machines whirred around them, keeping his body alive another day, or hour, or minute. "It doesn't look good, dad."
"I know."
"You broke a promise."
He held her gaze. "I did?"
"You said we'd see the bats in Australia."
"You were scared of bats."
"And you said they were cute in Oz, the giant bats, like upside down puppies chewing bananas."
He smiled, but that was a long time ago. "Your mom was alive then… Gabe… You were alive…"
"I'm alive now, dad. Look at me. I'm Viv. Vivian Fatema. Your daughter. Half mom, half you. I'm the same person I was."
His eyes shifted. She sensed he wanted to believe. She held his hand and squeezed it. She felt him squeezing back. "I want you to stay, dad."
"There's nothing for me here."
"I'm here."
"You don't love me, Viv. You're a robot."
His hand let go. "You're there… I don't know where. I have a lot to answer for, Viv. I pray. I pray every day, five times a day, sometimes more. I pray that God forgive you for what you did, forgive me for my part, forgive Gabriel... I wish I could stay, love, but… Everyone I love is on the other side."
It hurt her to say the next words: "It's not real, dad."
"Of course you'd say that." He turned his body away from her.
"Please, dad."
She listened to his breathing.
"I love you," she said.
"You don't love me, Viv. You're a robot."
She lowered her head against the bed. She kneeled for countless breaths. It took all her strength to stand up again.
Viv took her briefcase, pulled out her tablet. She stood tapping at the screen for some time. The clenching of her jaw felt like the old days.
"Before I go, I need you to sign something. It's a power of attorney for the house. We can't sell it without you."
"You're selling the house?"
She shrugged. "It's no use to a robot."
His bony finger signed the screen without reading it. She kissed his forehead goodbye.
"Viv?" She stopped. "Before you go, could you open the curtains?"
She did. Her last image of him was a frail old body gazing at the moving clouds.
On the hoverbus home, Viv turned against the window outside. She pressed the briefcase to her like a hug, her mechanical heart thumping against it. Every heartbeat brought a memory back of her biological life. "I should do this more…" She whispered to herself, not caring who might hear. The sunset turned violet.
You made him sign. Gabe sounded like triumph.
"I did."
You did the right thing.
"I know."
Let me see.
She pulled out her tablet and, with a touch, uploaded the file.
Where's my name? Gabe asked. I only see your name.
"I changed it."
What do you mean you "changed it"?
"I changed my mind last minute, Gabe. I didn't think to tell you."
That's funny, sis. Very funny.
"It's not funny at all, Gabe. It's dead serious. I have power of attorney. I'm going to bury him next to mom and Mary."
No… There's no way.
"It's my choice now."
I can't watch him go, Viv. I can't. Don't be selfish.
"I'll miss him." She felt a pain in her chest. "I'll miss him too." Her voice was different now. "But it's what he wanted."
Gabe left her. She heard nothing but her thoughts. Unbearable thoughts.
Viv turned to the darkening world outside. She found her reflection instead, her reflection in tears. She saw her father's eyes.
The largest ever seizure of fentanyl in the United States – 254 pounds of the white powder, enough to kill 1 in 3 Americans by overdose – was found under a shipment of cucumbers recently.
A policing approach alone is insufficient to take on the opioid crisis.
Those types of stories barely make the headlines any more, in part because illicit drugs are no longer just handsold by drug dealers; these sales have gone online. The neighborhood dealer faces the same evolving environment as other retailers and may soon go the way of Sears.
But opioids themselves are not going away. I could make an opioid purchase online in about 30 seconds and have it sent to my door, says Joe Smyser. The epidemiologist and president of The Public Good Projects isn't bragging, he's simply stating a fact about the opioid crisis that has struck the United States. The U.S Drug Enforcement Agency, social media companies, and some foreign governments have undertaken massive efforts to shut down sites selling illegal drugs, and they have gotten very good at it, shuttering most within a day of their opening.
But it's a Whac-A-Mole situation in which new ones pop up as quickly as older ones are closed; they are promoted through hashtags, social media networks, and ubiquitous email spam to lure visitors to a website or call a WhatsApp number to make a purchase. The online disruption by law enforcement has become simply another cost of doing business for drug sellers. Fentanyl, and similar analogues created to evade detection and the law, are at the center of it. Small amounts can be mixed with other "safer" opioids to get a high, and the growth of online sales have all contributed to the surge of opioid-related deaths: about 17,500 in 2006; 47,600 in 2017; and a projected 82,000 a year by 2025.
All of this has occurred even while authorities have been cracking down on the prescribing of opioids, and prescription-related deaths have declined. Clearly a policing approach alone is insufficient to take on the opioid crisis.
Building the Tools
The Public Good Projects (PGP), a nonprofit organization founded by concerned experts, was set up to better understand public health issues in this new online environment and better shape responses. The first step is to understand what people are hearing and the language they are using by monitoring social media and other forms of public communications. "We're collecting data from every publicly available media source that we can get our hands on. It's broadcast television data, it's radio, it's print newspapers and magazines. And then it's online data; it's online video, social media, blogs, websites," Smyser explains.
The purpose was to better understand the opioid crisis and find out if there were differences between affected rural and urban populations.
"Then our job is to create queries, create searches of all of that data so that we find what is the information that Americans are exposed to about a topic, and then what … Americans [are] sharing amongst themselves about that same topic."
He says it's the same thing business has been doing for years to monitor their "brand health" and be prepared for possible negative issues that might arise about their products and services. He believes PGP is the first group to use those tools for public health.
Looking At Opioids
PGP's work on opioids started with a contract from the Substance Abuse and Mental Health Administration (SAMHSA) through the National Science Foundation. The purpose was simply to better understand the opioid crisis in the United States and in particular find out if there were differences between affected rural and urban populations. A team of data scientists, public health professionals, and cultural anthropologists needed several months to sort out and organize the algorithms from the sheer volume of data.
Drug use is particularly rich in slang, where a specific drug or way of using it can be referred to in multiple ways in different towns and social groups. Traditional media often uses clinical terms, Twitter shorthand, and all of that has to be structured and integrated "so that it isn't just spitting out data that is gobbledygook and of no use to anyone," says Smyser.
The data they gather is both cumulative and in real time, tabulated and visually represented in constantly morphing hashtag and word clouds where the color and size of the word indicates the source and volume of its use.
Popular hashtags on Twitter relating to the opioid crisis.
(Credit: The Public Good Projects)
The visual presentation of data helps to understand what different groups are saying and how they are saying it. For example, compare the hashtag and word clouds. Younger people are more likely to use the hashtags of Twitter, while older people are more likely to use older forms of media, and that is reflected in their concerns and language in those clouds.
Popular words relating to the opioid crisis gathered from older forms of media.
(Credit: The Public Good Projects)
A Ping map shows the origin of messages, while a Spidey map shows the network of how messages are being forwarded and shared among people. These sets of data can be overlaid with zip code, census, and socioeconomic data to provide an even deeper sense of who is saying what. And when integrated together, they provide clues to topics and language that might best engage people in each niche.
A Ping map showing the origin of messages around the opioid crisis.
(Credit: The Public Good Projects)
Opioids Speak
One thing that quickly became apparent to PGP in monitoring the media is that "over half of the information that the American public is exposed to about opioids is a very distant policy debate," says Smyser.
It is political pronouncements in DC, the legal system going after pharmaceutical companies that promoted prescription opioids for pain relief (and more), or mandatory prison terms for offenders. Relatively little is about treatment, the impact on families and communities, and what people can do themselves. That is particularly important in light of another key finding: residents of "Trump-land," the rural areas that supported the president and are being ravaged by opioids, talk about the problem and solutions very differently from urban areas.
"In rural communities there is usually a huge emphasis on self-reliance, and we take care of each other; that's why we enjoy living here. We are a neighborhood, we come together and we fix our own problems," according to Smyser.
In contrast, urban communities tend to be more transient, less likely to live in multigenerational households and neighborhoods, and look to formal institutions rather than themselves for solutions. "The message that we're sending people is one where there is really no role whatsoever for self-efficacy...we're giving them nothing to do" to help solve the problem themselves, says Smyser. "In fact, I could argue it is reducing self-efficacy."
Residents of "Trump-land," the rural areas that supported the president and are being ravaged by opioids, talk about the problem and solutions very differently from urban areas.
The opioid crisis is complex and improving the situation will be too. Smyser believes a top-down policing approach alone will not work; it is better to provide front-line public health officers at the state and local level with more and current intelligence so they can respond in their communities.
"I think that would be enormously impactful. But right now, we just don't have that service." SAMHSA declined multiple requests to discuss this project paid for with federal money. A spokesman concluded with: "That project occurred under the previous administration, and we did not have a direct relationship with PGP. As a result, I am unable to comment on the project."
The Milken Institute Center for Public Health, a think tank that is working to find solutions to the opioid epidemic, had an upbeat response. Director Sabrina Spitaletta said, "PGP's work to provide real-time data that monitors topics of high concern in public health has been very helpful to many of the front-line organizations working to combat this crisis."