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.
The news last November that a rogue Chinese scientist had genetically altered the embryos of a pair of Chinese twins shocked the world. But although this use of advanced technology to change the human gene pool was premature, it was a harbinger of how genetic science will alter our healthcare, the way we make babies, the nature of the babies we make, and, ultimately, our sense of who and what we are as a species.
The healthcare applications of the genetics revolution are merely stations along the way to the ultimate destination.
But while the genetics revolution has already begun, we aren't prepared to handle these Promethean technologies responsibly.
By identifying the structure of DNA in the 1950s, Watson, Crick, Wilkins, and Franklin showed that the book of life was written in the DNA double helix. When the human genome project was completed in 2003, we saw how this book of human life could be transcribed. Painstaking research paired with advanced computational algorithms then showed what increasing numbers of genes do and how the genetic book of life can be read.
Now, with the advent of precision gene editing tools like CRISPR, we are seeing that the book of life -- and all biology -- can be re-written. Biology is being recognized as another form of readable, writable, and hackable information technology with we humans as the coders.
The impact of this transformation is being first experienced in our healthcare. Gene therapies including those extracting, re-engineering, then reintroducing a person's own cells enhanced into cancer-fighting supercells are already performing miracles in clinical trials. Thousands of applications have already been submitted to regulators across the globe for trials using gene therapies to address a host of other diseases.
Recently, the first gene editing of cells inside a person's body was deployed to treat the genetically relatively simple metabolic disorder Hunter syndrome, with many more applications to come. These new approaches are only the very first steps in our shift from the current system of generalized medicine based on population averages to precision medicine based on each patient's individual biology to predictive medicine based on AI-generated estimations of a person's future health state.
Jamie Metzl's groundbreaking new book, Hacking Darwin: Genetic Engineering and the Future of Humanity, explores how the genetic revolution is transforming our healthcare, the way we make babies, and the nature of and babies we make, what this means for each of us, and what we must all do now to prepare for what's coming.
This shift in our healthcare will ensure that millions and then billions of people will have their genomes sequenced as the foundation of their treatment. Big data analytics will then be used to compare at scale people's genotypes (what their genes say) to their phenotypes (how those genes are expressed over the course of their lives).
These massive datasets of genetic and life information will then make it possible to go far beyond the simple genetic analysis of today and to understand far more complex human diseases and traits influenced by hundreds or thousands of genes. Our understanding of this complex genetic system within the vaster ecosystem of our bodies and the environment around us will transform healthcare for the better and help us cure terrible diseases that have plagued our ancestors for millennia.
But as revolutionary as this challenge will be for medicine, the healthcare applications of the genetics revolution are merely stations along the way to the ultimate destination – a deep and fundamental transformation of our evolutionary trajectory as a species.
A first inkling of where we are heading can be seen in the direct-to-consumer genetic testing industry. Many people around the world have now sent their cheek swabs to companies like 23andMe for analysis. The information that comes back can tell people a lot about relatively simple genetic traits like carrier status for single gene mutation diseases, eye color, or whether they hate the taste of cilantro, but the information about complex traits like athletic predisposition, intelligence, or personality style today being shared by some of these companies is wildly misleading.
This will not always be the case. As the genetic and health data pools grow, analysis of large numbers of sequenced genomes will make it possible to apply big data analytics to predict some very complex genetic disease risks and the genetic components of traits like height, IQ, temperament, and personality style with increasing accuracy. This process, called "polygenic scoring," is already being offered in beta stage by a few companies and will become an ever bigger part of our lives going forward.
The most profound application of all this will be in our baby-making. Before making a decision about which of the fertilized eggs to implant, women undergoing in vitro fertilization can today elect to have a small number of cells extracted from their pre-implanted embryos and sequenced. With current technology, this can be used to screen for single-gene mutation diseases and other relatively simple disorders. Polygenic scoring, however, will soon make it possible to screen these early stage pre-implanted embryos to assess their risk of complex genetic diseases and even to make predictions about the heritable parts of complex human traits. The most intimate elements of being human will start feeling like high-pressure choices needing to be made by parents.
The limit of our imagination will become the most significant barrier to our recasting biology.
Adult stem cell technologies will then likely make it possible to generate hundreds or thousands of a woman's own eggs from her blood sample or skin graft. This would blow open the doors of reproductive possibility and allow parents to choose embryos with exceptional potential capabilities from a much larger set of options.
The complexity of human biology will place some limits to the extent of possible gene edits that might be made to these embryos, but all of biology, including our own, is extremely flexible. How else could all the diversity of life have emerged from a single cell nearly four billion years ago? The limit of our imagination will become the most significant barrier to our recasting biology.
But while we humans are gaining the powers of the gods, we aren't at all ready to use them.
The same tools that will help cure our worst afflictions, save our children, help us live longer, healthier, more robust lives will also open the door to potential abuses. Prospective parents with the best of intentions or governments with lax regulatory structures or aggressive ideas of how population-wide genetic engineering might be used to enhance national competitiveness or achieve some other goal could propel us into a genetic arms race that could undermine our essential diversity, dangerously divide societies, lead to dangerous, destabilizing, and potentially even deadly conflicts between us, and threaten our very humanity.
But while the advance of genetic technologies is inevitable, how it plays out is anything but. If we don't want the genetic revolution to undermine our species or lead to grave conflicts between genetic haves and have nots or between societies opting in and those opting out, now is the time when we need to make smart decisions based on our individual and collective best values. Although the technology driving the genetic revolution is new, the value systems we will need to optimize the benefits and minimize the harms of this massive transformation are ones we have been developing for thousands of years.
And while some very smart and well-intentioned scientists have been meeting to explore what comes next, it won't be enough for a few of even our wisest prophets to make decisions about the future of our species that will impact everyone. We'll also need smart regulations on both the national and international levels.
Every country will need to have its own regulatory guidelines for human genetic engineering based on both international best practices and the country's unique traditions and values. Because we are all one species, however, we will also ultimately need to develop guidelines that can apply to all of us.
As a first step toward making this possible, we must urgently launch a global, species-wide education effort and inclusive dialogue on the future of human genetic engineering that can eventually inform global norms that will need to underpin international regulations. This process will not be easy, but the alternative of an unregulated genetic arms race would be far worse.
The overlapping genomics and AI revolutions may seem like distant science fiction but are closer than you think. Far sooner than most people recognize, the inherent benefits of these technologies and competition between us will spark rapid adoption. Before that spark ignites, we have a brief moment to come together as a species like we never have before to articulate and translate into action the future we jointly envision. The north star of our best shared values can help us navigate the almost unimaginable opportunities and very real challenges that lie ahead.
Here's something to chew on. Can a gulp of water help save the planet? If you're drinking *and* eating your water at the same time, the answer may be yes.
The tasteless packaging is made from brown seaweed that biodegrades naturally in four to six weeks.
The Lowdown
A start-up company called Skipping Rocks Lab has created a "water bubble" encased in an edible sachet that you can pop in your mouth whole. Or if you're not into swallowing it, you can tear off the edge, drink up, and toss the rest in a composter. The tasteless packaging is made from brown seaweed that biodegrades naturally in four to six weeks, whereas plastic water bottles can linger for hundreds of years.
The founders of the London-based company are determined to "make plastic packaging disappear." They had two foodie inspirations: molecular gastronomists and fruit. They tried to emulate the way chefs used edible membranes to encase bubbles of liquid to make things like fake caviar and fake egg yolks; and they also considered the peel of an orange or banana, which protects the tasty insides but can be composted.
The sachets can also contain other liquids that come in single-serve plastic containers -- think packets of condiments with takeout meals, specialty cocktails at parties, and especially single servings of water for sporting events. The London Marathon last month gave out the water bubble pods at a station along the route, using them to replace 200,000 plastic bottles that would have likely ended up first in the street, and ultimately in the ocean.
Next Up
The engineers and chemists at Skipping Rocks intend to lease their machines to others who can then manufacture their own sachets on-site to fill with whatever they desire. The new material, which is dubbed "Notpla" (not plastic), also has other applications beyond holding liquids. It can be used to replace the plastic lining in cardboard takeout boxes, for example. And the startup is working on additional materials to replace other types of ubiquitous plastic packaging, like the netting that encases garlic and onions, and the sachets that hold nails and screws.
Edible water bubbles may be the future of drinks at sporting events and festivals.
Open Questions
One hurdle is that the pods are not very hardy, so while they work fine to hand out along a marathon route, they wouldn't really be viable for a hiker to throw in her backpack. Another issue concerns the retail market: to be stable on a shelf, they'd have to be protected from all that handling, which brings us back to the problem the engineers tried to solve in the first place -- disposable packaging.
So while Skipping Rocks may not achieve their ultimate goal of ridding the world of plastic waste, a little progress can still go a long way. If edible water bubbles are the future of drinks at sporting events and festivals, the environment will certainly benefit from their presence -- and absence.