Often called the window to the soul, the eyes are more sacred than other body parts, at least for some.
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.
Biomedical engineer Kevin Zhao has a sensor in his arm and his chest that monitors his oxygen level in those tissues in real time.
Last month, at a conference celebrating DARPA, the research arm of the Defense Department, FBI Special Agent Edward You declared, "The 21st century will be the revolution of the life sciences."
Biomedical engineer Kevin Zhao has a sensor in his arm and chest that monitors his oxygen level in real time.
Indeed, four years ago, the agency dedicated a new office solely to advancing biotechnology. Its primary goal is to combat bioterrorism, protect U.S. forces, and promote warfighter readiness. But its research could also carry over to improve health care for the general public.
With an annual budget of about $3 billion, DARPA's employees oversee about 250 research and development programs, working with contractors from corporations, universities, and government labs to bring new technologies to life.
Check out these three current programs:
1) IMPLANTABLE SENSORS TO MEASURE OXYGEN, LACTATE, AND GLUCOSE LEVELS IN REAL TIME
Biomedical engineer Kevin Zhao has a sensor in his arm and his chest that monitors his oxygen level in those tissues in real time. With funding from DARPA for the program "In Vivo Nanoplatforms," he developed soft, flexible hydrogels that are injected just beneath the skin to perform the monitoring and that sync to a smartphone app to give the user immediate health insights.
A first-in-man trial for the glucose sensor is now underway in Europe for monitoring diabetics, according to Zhao. Volunteers eat sugary food to spike their glucose levels and prompt the monitor to register the changes.
"If this pans out, with approval from FDA, then consumers could get the sensors implanted in their core to measure their levels of glucose, oxygen, and lactate," Zhao said.
Lactate, especially, interests DARPA because it's a first responder molecule to the onset of trauma, sepsis, and potentially infection.
"The sensor could potentially detect rise of these [body chemistry numbers] and alert the user to prevent onset of dangerous illness."
2) NEAR INSTANTANEOUS VACCINE PROTECTION DURING A PANDEMIC
Traditional vaccines can take months or years to develop, then weeks to become effective once you get it. But when an unknown virus emerges, there's no time to waste.
This program, called P3, envisions a much more ambitious approach to stop a pandemic in its tracks.
"We want to confer near instantaneous protection by doing it a different way – enlist the body as a bioreactor to produce therapeutics," said Col. Matthew Hepburn, the program manager.
So how would it work?
To fight a pandemic, we will need 20,000 doses of a vaccine in 60 days.
If you have antibodies against a certain infection, you'll be protected against that infection. This idea is to discover the genetic code for the antibody to a specific pathogen, manufacture those pieces of DNA and RNA, and then inject the code into a person's arm so the muscle cells will begin producing the required antibodies.
"The amazing thing is that it actually works, at least in animal models," said Hepburn. "The mouse muscles made enough protective antibodies so that the mice were protected."
The next step is to test the approach in humans, which the program will do over the next two years.
But the hard part is actually not discovering the genetic code for highly potent antibodies, according to Hepburn. In fact, researchers already have been able to do so in two to four weeks' time.
"The hard part is once I have an antibody, a large pharma company will say in 2 years, I can make 100-200 doses. Give us 4 years to get to 20,000 doses. That's not good enough," Hepburn said.
To fight a pandemic, we will need 20,000 doses of a vaccine in 60 days.
"We have to fundamentally change the idea that it takes a billion dollars and ten years to make a drug," he concluded. "We're going to do something radically different."
3) RAPID DIAGNOSING OF PATHOGEN EXPOSURE THROUGH EPIGENETICS
Imagine that you come down with a mysterious illness. It could be caused by a virus, bacteria, or in the most extreme catastrophe, a biological agent from a weapon of mass destruction.
What if a portable device existed that could identify--within 30 minutes—which pathogen you have been exposed to and when? It would be pretty remarkable for soldiers in the field, but also for civilians seeking medical treatment.
This is the lofty ambition of a DARPA program called Epigenetic Characterization and Observation, or ECHO.
Its success depends on a biological phenomenon known as the epigenome. While your DNA is relatively immutable, your environment can modify how your DNA is expressed, leaving marks of exposure that register within seconds to minutes; these marks can persist for decades. It's thanks to the epigenome that identical twins – who share identical DNA – can differ in health, temperament, and appearance.
These three mice are genetically identical. Epigenetic differences, however, result in vastly different observed characteristics.
Reading your epigenetic marks could theoretically reveal a time-stamped history of your body's environmental exposures.
Researchers in the ECHO program plan to create a database of signatures for exposure events, so that their envisioned device will be able to quickly scan someone's epigenome and refer to the database to sort out a diagnosis.
"One difficult part is to put a timestamp on this result, in addition to the sign of which exposure it was -- to tell us when this exposure happened," says Thomas Thomou, a contract scientist who is providing technical assistance to the ECHO program manager.
Other questions that remain up in the air for now: Do all humans have the same epigenetic response to the same exposure events? Is it possible to distinguish viral from bacterial exposures? Does dose and duration of exposure affect the signature of epigenome modification?
The program will kick off in January 2019 and is planned to last four years, as long as certain milestones of development are reached along the way. The desired prototype would be a simple device that any untrained person could operate by taking a swab or a fingerprick.
"In an outbreak," says Dr. Thomou, "it will help everyone on the ground immediately to have a rapidly deployable machine that will give you very quick answers to issues that could have far-reaching ramifications for public health safety."