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.
Sarah Watts's son Henry was born with spina bifida and can't stand or walk without assistance.
When our son Henry, now six, was diagnosed with spina bifida at his 20-week ultrasound, my husband and I were in shock. It took us more than a few minutes to understand what the doctor was telling us.
When Henry was diagnosed in 2012, postnatal surgery was still the standard of care – but that was about to change.
Neither of us had any family history of birth defects. Our fifteen-month-old daughter, June, was in perfect health.
But more than that, spina bifida – a malformation of the neural tube that eventually becomes the baby's spine – is woefully complex. The defect, the doctor explained, was essentially a hole in Henry's lower spine from which his spinal nerves were protruding – and because they were exposed to my amniotic fluid, those nerves were already permanently damaged. After birth, doctors could push the nerves back into his body and sew up the hole, but he would likely experience some level of paralysis, bladder and bowel dysfunction, and a buildup of cerebrospinal fluid that would require a surgical implant called a shunt to correct. The damage was devastating – and irreversible.
We returned home with June and spent the next few days cycling between disbelief and total despair. But within a week, the maternal-fetal medicine specialist who diagnosed Henry called us up and gave us the first real optimism we had felt in days: There was a new, experimental surgery for spina bifida that was available in just a handful of hospitals around the country. Rather than waiting until birth to repair the baby's defect, some doctors were now trying out a prenatal repair, operating on the baby via c-section, closing the defect, and then keeping the mother on strict bedrest until it was time for the baby to be delivered, just before term.
This new surgery carried risks, he told us – but if it went well, there was a chance Henry wouldn't need a shunt. And because repairing the defect during my pregnancy meant the spinal nerves were exposed for a shorter amount of time, that meant we'd be preventing nerve damage – and less nerve damage meant that there was a chance he'd be able to walk.
Did we want in? the doctor asked.
Had I known more about spina bifida and the history of its treatment, this surgery would have seemed even more miraculous. Not too long ago, the standard of care for babies born with spina bifida was to simply let them die without medical treatment. In fact, it wasn't until the early 1950s that doctors even attempted to surgically repair the baby's defect at all, instead of opting to let the more severe cases die of meningitis from their open wound. (Babies who had closed spina bifida – a spinal defect covered by skin – sometimes survived past infancy, but rarely into adulthood).
But in the 1960s and 1970s, as more doctors started repairing defects and the shunting technology improved, patients with spina bifida began to survive past infancy. When catheterization was introduced, spina bifida patients who had urinary dysfunction, as is common, were able to preserve their renal function into adulthood, and they began living even longer. Within a few decades, spina bifida was no longer considered a death sentence; people were living fuller, happier lives.
When Henry was diagnosed in 2012, postnatal surgery was still the standard of care – but that was about to change. The first major clinical trial for prenatal surgery and spina bifida, called Management of Myelomeningocele (MOMS) had just concluded, and its objective was to see whether repairing the baby's defect in utero would be beneficial. In the trial, doctors assigned eligible women to undergo prenatal surgery in the second trimester of their pregnancies and then followed up with their children throughout the first 30 months of the child's life.
The results were groundbreaking: Not only did the children in the surgery group perform better on motor skills and cognitive tests than did patients in the control group, only 40 percent of patients ended up needing shunts compared to 80 percent of patients who had postnatal surgery. The results were so overwhelmingly positive that the trial was discontinued early (and is now, happily, the medical standard of care). Our doctor relayed this information to us over the phone, breathless, and left my husband and me to make our decision.
After a few days of consideration, and despite the benefits, my husband and I actually ended up opting for the postnatal surgery instead. Prenatal surgery, although miraculous, would have required extensive travel for us, as well as giving birth in a city thousands of miles from home with no one to watch our toddler while my husband worked and I recovered. But other parents I met online throughout our pregnancy did end up choosing prenatal surgery for their children – and the majority of them now walk with little assistance and only a few require shunting.
Even more amazing to me is that now – seven years after Henry's diagnosis, and not quite a decade since the landmark MOMS trial – the standard of care could be about to change yet again.
Regardless of whether they have postnatal or prenatal surgery, most kids with spina bifida still experience some level of paralysis and rely on wheelchairs and walkers to move around. Now, researchers at UC Davis want to augment the fetal surgery with a stem cell treatment, using human placenta-derived mesenchymal stromal cells (PMSCs) and affixing them to a cellular scaffold on the baby's defect, which not only protects the spinal cord from further damage but actually encourages cellular regeneration as well.
The hope is that this treatment will restore gross motor function after the baby is born – and so far, in animal trials, that's exactly what's happening. Fetal sheep, who were induced with spinal cord injuries in utero, were born with complete motor function after receiving prenatal surgery and PMSCs. In 2017, a pair of bulldogs born with spina bifida received the stem cell treatment a few weeks after birth – and two months after surgery, both dogs could run and play freely, whereas before they had dragged their hind legs on the ground behind them. UC Davis researchers hope to bring this treatment into human clinical trials within the next year.
A century ago, a diagnosis of spina bifida meant almost certain death. Today, most children with spina bifida live into adulthood, albeit with significant disabilities. But thanks to research and innovation, it's entirely possible that within my lifetime – and certainly within Henry's – for the first time in human history, the disabilities associated with spina bifida could be a thing of the past.
Dr. Andrew Brooks of RUCDR Infinite Biologics holds up a saliva sample.
The patient tilts back her head and winces as the long swab stick pushes six inches up her nose. The tip twirls around uncomfortably before it's withdrawn.
"Our saliva test can detect the virus in asymptomatic and pre-symptomatic cases."
A gloved and gowned healthcare worker wearing a face shield and mask tells the patient that she will learn whether she is positive for COVID-19 as soon as the lab can process her test.
This is the typical unpleasant scenario for getting a coronavirus test. But times are rapidly changing: Today, for the first time, the U.S. Food and Drug Administration cleared one company to sell saliva collection kits for individuals to use at home.
Scientists at the startup venture, RUCDR Infinite Biologics at Rutgers University in New Jersey, say that saliva testing offers an easier, more useful alternative to the standard nasal swab.
"Our saliva test can detect the virus in asymptomatic and pre-symptomatic cases," said Dr. Andrew Brooks, chief operating officer at RUCDR.
Another venture, Darwin BioSciences in Colorado, has separately developed an innovative method of testing saliva for the coronavirus that causes COVID-19.
Saliva testing can allow earlier detection to identify people who may not know they are contagious, say scientists at both companies. In addition, because patients spit into a tube or cup, saliva testing is safer for healthcare workers than taking swabs. This frees up scarce personal protective equipment (PPE) for use elsewhere. Nasal swabs themselves have been in scarce supply.
Saliva testing, if it becomes widespread, potentially could mean opening society sooner. The more ubiquitous testing becomes across the population, experts say, the more feasible it becomes for public health officials to trace and isolate contacts, especially of asymptomatic cases. Testing early and often will be essential to containing emerging hot spots before a vast outbreak can take root.
Darwin Biosceiences is preparing to seek an FDA Emergency Use Authorization (EUA) this month for its patented "CoVScreen" testing system, which potentially could be available to labs nationally by mid-summer.
Meanwhile, Infinite Biologics will now begin selling kits to consumers for home collection, upon order by a physician. The FDA said that the company's saliva test was as accurate as the nasal swab method used by health care professionals. An FDA summary documenting the company's data reported: "There was 100% positive and negative agreement between the results obtained from testing of saliva and those obtained from nasopharyngeal and oropharyngeal swabs."
The greatest scientific advantage, said Dr. Brooks, is that nasal and oral swabs only collect the surface area where the swab goes, which may not be the place with most viral load. In contrast, the virus occurs throughout a saliva sample, so the test is more trustworthy.
The lab at Rutgers can process 20,000 tests a day, with a 48-hour turnaround. They have 75,000 tests ready to ship now.
The Leap: Detecting Sickness Before You Feel It
"We wanted to create a device that could detect infections before symptoms appeared," explained Nicholas Meyerson, co-founder and CEO of Darwin.
For more than 300 years, he said, "the thermometer was the gold standard for detecting disease because we thought the first sign of illness was a fever. This COVID-19 pandemic has proven that not all pathogens cause a fever. You can be highly contagious without knowing it."
"The question is whether we can scale up fast enough to meet the need. I believe saliva testing can help."
Therefore, Meyerson and co-founder Sara Sawyer from the University of Colorado began to identify RNA biomarkers that can sense when a pathogen first enters a molecule and "sets off alarms." They focused on the nucleic acids concentrated in saliva as the best and easiest place to collect samples for testing.
"The isothermal reaction in saliva takes place at body or room temperature," he said, "so there's no need for complicated testing machinery. The chemical reaction can be read out on a paper strip, like a pregnancy test -- two stripes if you're sick, and one stripe if you're okay."
Before the pandemic, limited but successful human trials were already underway at CU in Boulder and at the CU Anschutz Medical Campus east of Denver. "This was our proof of concept," he said.
Darwin was founded in March and has secured enough venture capital to concentrate protype development on detecting the virus causing COVID-19. So far, said Meyerson, "Everything works."
A small double-blind test of 30 samples at CU produced 100 percent accuracy. "I'm not sure if that will hold true as we go into clinical trials," he said, "but I'm confident we will satisfy all the requirements for at least 95 percent clinical validation."
The specific "CoVStick" test strips will roll out soon, he said: "We hope before the second wave of the pandemic hits."
The broader saliva test-strip product from Darwin, "SickStick," is still one to two years away from deployment by the military and introduction into the consumer drugstore market for home use, said Meyerson. It will affordably and quickly detect a range of viral and bacterial infections.
An illustration of the "CoVStick."
(Darwin Biosciences)
A Potential Game Changer
Society needs widespread testing daily, said George Church, founding core faculty of the Wyss Institute for Biologically Inspired Engineering at Harvard University. Speaking at an online SynBioBeta webinar in April, he urged developing stockpiles of testing kits for home use.
As for any potential of false positives, Church said a much bigger risk is not having enough tests.
"Saliva testing is going to speed up the timeline for opening society a lot," said Meyerson. "People need to self-collect samples at home. A lot more people are going to be willing to spit into a tube than to push a swab six inches up their own nose."
Brooks, of Rutgers, addressed the big picture. "It's critical that we open society as soon as possible to minimize the economic impact of the pandemic. Testing is the surest and safest path. The question is whether we can scale up fast enough to meet the need. I believe saliva testing can help."