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.
Nine experts break down the biggest biotech and health breakthroughs that didn't get the attention they deserved in 2022.
New drug targets for Alzheimer’s disease
Professor Julie Williams, Director, Dementia Research Institute, Cardiff University
Genetics has changed our view of Alzheimer’s disease in the last five to six years. The beta amyloid hypothesis has dominated Alzheimer’s research for a long time, but there are multiple components to this complex disease, of which getting rid of amyloid plaques is one, but it is not the whole story. In April 2022, Nature published a paper which is the culmination of a decade’s worth of work - groups all over the world working together to identify 75 genes associated with risk of developing Alzheimer’s. This provides us with a roadmap for understanding the disease mechanisms.
For example, it is showing that there is something different about the immune systems of people who develop Alzheimer’s disease. There is something different about the way they process lipids in the brain, and very specific processes of how things travel through cells called endocytosis. When it comes to immunity, it indicates that the complement system is affecting whether synapses, which are the connections between neurons, get eliminated or not. In Alzheimer’s this process is more severe, so patients are losing more synapses, and this is correlated with cognition.
The genetics also implicates very specific tissues like microglia, which are the housekeepers in the brain. One of their functions is to clear away beta amyloid, but they also prune and nibble away at parts of the brain that are indicated to be diseased. If you have these risk genes, it seems that you are likely to prune more tissue, which may be part of the cell death and neurodegeneration that we observe in Alzheimer’s patients.
Genetics is telling us that we need to be looking at multiple causes of this complex disease, and we are doing that now. It is showing us that there are a number of different processes which combine to push patients into a disease state which results in the death of connections between nerve cells. These findings around the complement system and other immune-related mechanisms are very interesting as there are already drugs which are available for other diseases which could be repurposed in clinical trials. So it is really a turning point for us in the Alzheimer’s disease field.
Preventing Pandemics with Organ-Tissue Equivalents
Anthony Atala, Director of the Wake Forest Institute for Regenerative Medicine
COVID-19 has shown us that we need to be better prepared ahead of future pandemics and have systems in place where we can quickly catalogue a new virus and have an idea of which treatment agents would work best against it.
At Wake Forest Institute, our scientists have developed what we call organ-tissue equivalents. These are miniature tissues and organs, created using the same regenerative medicine technologies which we have been using to create tissues for patients. For example, if we are making a miniature liver, we will recreate this structure using the six different cell types you find in the liver, in the right proportions, and then the right extracellular matrix which holds the structure together. You're trying to replicate all the characteristics of the liver, but just in a miniature format.
We can now put these organ-tissue equivalents in a chip-like device, where we can expose them to different types of viral infections, and start to get a realistic idea of how the human body reacts to these viruses. We can use artificial intelligence and machine learning to map the pathways of the body’s response. This will allow us to catalogue known viruses far more effectively, and begin storing information on them.
Powering Deep Brain Stimulators with Breath
Islam Mosa, Co-Founder and CTO of VoltXon
Deep brain stimulation (DBS) devices are becoming increasingly common with 150,000 new devices being implanted every year for people with Parkinson’s disease, but also psychiatric conditions such as treatment-resistant depression and obsessive-compulsive disorders. But one of the biggest limitations is the power source – I call DBS devices energy monsters. While cardiac pacemakers use similar technology, their batteries last seven to ten years, but DBS batteries need changing every two to three years. This is because they are generating between 60-180 pulses per second.
Replacing the batteries requires surgery which costs a lot of money, and with every repeat operation comes a risk of infection, plus there is a lot of anxiety on behalf of the patient that the battery is running out.
My colleagues at the University of Connecticut and I, have developed a new way of charging these devices using the person’s own breathing movements, which would mean that the batteries never need to be changed. As the patient breathes in and out, their chest wall presses on a thin electric generator, which converts that movement into static electricity, charging a supercapacitor. This discharges the electricity required to power the DBS device and send the necessary pulses to the brain.
So far it has only been tested in a simulated pig, using a pig lung connected to a pump, but there are plans now to test it in a real animal, and then progress to clinical trials.
Smartwatches for Disease Detection
Jessilyn Dunn, Assistant Professor in Duke Biomedical Engineering
A group of researchers recently showed that digital biomarkers of infection can reveal when someone is sick, often before they feel sick. The team, which included Duke biomedical engineers, used information from smartwatches to detect Covid-19 cases five to 10 days earlier than diagnostic tests. Smartwatch data included aspects of heart rate, sleep quality and physical activity. Based on this data, we developed an algorithm to decide which people have the most need to take the diagnostic tests. With this approach, the percent of tests that come back positive are about four- to six-times higher, depending on which factors we monitor through the watches.
Our study was one of several showing the value of digital biomarkers, rather than a single blockbuster paper. With so many new ideas and technologies coming out around Covid, it’s hard to be that signal through the noise. More studies are needed, but this line of research is important because, rather than treat everyone as equally likely to have an infectious disease, we can use prior knowledge from smartwatches. With monkeypox, for example, you've got many more people who need to be tested than you have tests available. Information from the smartwatches enables you to improve how you allocate those tests.
Smartwatch data could also be applied to chronic diseases. For viruses, we’re looking for information about anomalies – a big change point in people’s health. For chronic diseases, it’s more like a slow, steady change. Our research lays the groundwork for the signals coming from smartwatches to be useful in a health setting, and now it’s up to us to detect more of these chronic cases. We want to go from the idea that we have this single change point, like a heart attack or stroke, and focus on the part before that, to see if we can detect it.
A Vaccine For RSV
Norbert Pardi, Vaccines Group Lead, Penn Institute for RNA Innovation, University of Pennsylvania
Scientists have long been trying to develop a vaccine for respiratory syncytial virus (RSV), and it looks like Pfizer are closing in on this goal, based on the latest clinical trial data in newborns which they released in November. Pfizer have developed a protein-based vaccine against the F protein of RSV, which they are giving to pregnant women. It turns out that it induces a robust immune response after the administration of a single shot and it seems to be highly protective in newborns. The efficacy was over 80% after 90 days, so it protected very well against severe disease, and even though this dropped a little after six month, it was still pretty high.
I think this has been a very important breakthrough, and very timely at the moment with both COVID-19, influenza and RSV circulating, which just shows the importance of having a vaccine which works well in both the very young and the very old.
The road to an RSV vaccine has also illustrated the importance of teamwork in 21st century vaccine development. You need people with different backgrounds to solve these challenges – microbiologists, immunologists and structural biologists working together to understand how viruses work, and how our immune system induces protective responses against certain viruses. It has been this kind of teamwork which has yielded the findings that targeting the prefusion stabilized form of the F protein in RSV induces much stronger and highly protective immune responses.
Gene therapy shows its potential
Nicole Paulk, Assistant Professor of Gene Therapy at the University of California, San Francisco
The recent US Food and Drug Administration (FDA) approval of Hemgenix, a gene therapy for hemophilia B, is big for a lot of reasons. While hemophilia is absolutely a rare disease, it is astronomically more common than the first two approvals – Luxturna for RPE65-meidated inherited retinal dystrophy and Zolgensma for spinal muscular atrophy - so many more patients will be treated with this. In terms of numbers of patients, we are now starting to creep up into things that are much more common, which is a huge step in terms of our ability to scale the production of an adeno-associated virus (AAV) vector for gene therapy.
Hemophilia is also a really special patient population because this has been the darling indication for AAV gene therapy for the last 20 to 30 years. AAV trafficks to the liver so well, it’s really easy for us to target the tissues that we want. If you look at the numbers, there have been more gene therapy scientists working on hemophilia than any other condition. There have just been thousands and thousands of us working on gene therapy indications for the last 20 or 30 years, so to see the first of these approvals make it, feels really special.
I am sure it is even more special for the patients because now they have a choice – do I want to stay on my recombinant factor drug that I need to take every day for the rest of my life, or right now I could get a one-time infusion of this virus and possibly experience curative levels of expression for the rest of my life. And this is just the first one for hemophilia, there’s going to end up being a dozen gene therapies within the next five years, targeted towards different hemophilias.
Every single approval is momentous for the entire field because it gets investors excited, it gets companies and physicians excited, and that helps speed things up. Right now, it's still a challenge to produce enough for double digit patients. But with more interest comes the experiments and trials that allow us to pick up the knowledge to scale things up, so that we can go after bigger diseases like diabetes, congestive heart failure, cancer, all of these much bigger afflictions.
Treating Thickened Hearts
John Spertus, Professor in Metabolic and Vascular Disease Research, UMKC School of Medicine
Hypertrophic cardiomyopathy (HCM) is a disease that causes your heart muscle to enlarge, and the walls of your heart chambers thicken and reduce in size. Because of this, they cannot hold as much blood and may stiffen, causing some sufferers to experience progressive shortness of breath, fatigue and ultimately heart failure.
So far we have only had very crude ways of treating it, using beta blockers, calcium channel blockers or other medications which cause the heart to beat less strongly. This works for some patients but a lot of time it does not, which means you have to consider removing part of the wall of the heart with surgery.
Earlier this year, a trial of a drug called mavacamten, became the first study to show positive results in treating HCM. What is remarkable about mavacamten is that it is directed at trying to block the overly vigorous contractile proteins in the heart, so it is a highly targeted, focused way of addressing the key problem in these patients. The study demonstrated a really large improvement in patient quality of life where they were on the drug, and when they went off the drug, the quality of life went away.
Some specialists are now hypothesizing that it may work for other cardiovascular diseases where the heart either beats too strongly or it does not relax well enough, but just having a treatment for HCM is a really big deal. For years we have not been very aggressive in identifying and treating these patients because there have not been great treatments available, so this could lead to a new era.
Regenerating Organs
David Andrijevic, Associate Research Scientist in neuroscience at Yale School of Medicine
As soon as the heartbeat stops, a whole chain of biochemical processes resulting from ischemia – the lack of blood flow, oxygen and nutrients – begins to destroy the body’s cells and organs. My colleagues and I at Yale School of Medicine have been investigating whether we can recover organs after prolonged ischemia, with the main goal of expanding the organ donor pool.
Earlier this year we published a paper in which we showed that we could use technology to restore blood circulation, other cellular functions and even heart activity in pigs, one hour after their deaths. This was done using a perfusion technology to substitute heart, lung and kidney function, and deliver an experimental cell protective fluid to these organs which aimed to stop cell death and aid in the recovery.
One of the aims of this technology is that it can be used in future to lengthen the time window for recovering organs for donation after a person has been declared dead, a logistical hurdle which would allow us to substantially increase the donor pool. We might also be able to use this cell protective fluid in studies to see if it can help people who have suffered from strokes and myocardial infarction. In future, if we managed to achieve an adequate brain recovery – and the brain, out of all the organs, is the most susceptible to ischemia – this might also change some paradigms in resuscitation medicine.
Antibody-Drug Conjugates for Cancer
Yosi Shamay, Cancer Nanomedicine and Nanoinformatics researcher at the Technion Israel Institute of Technology
For the past four or five years, antibody-drug conjugates (ADCs) - a cancer drug where you have an antibody conjugated to a toxin - have been used only in patients with specific cancers that display high expression of a target protein, for example HER2-positive breast cancer. But in 2022, there have been clinical trials where ADCs have shown remarkable results in patients with low expression of HER2, which is something we never expected to see.
In July 2022, AstraZeneca published the results of a clinical trial, which showed that an ADC called trastuzumab deruxtecan can offer a very big survival benefit to breast cancer patients with very little expression of HER2, levels so low that they would be borderline undetectable for a pathologist. They got a strong survival signal for patients with very aggressive, metastatic disease.
I think this is very interesting and important because it means that it might pave the way to include more patients in clinical trials looking at ADCs for other cancers, for example lymphoma, colon cancer, lung cancers, even if they have low expression of the protein target. It also holds implications for CAR-T cells - where you genetically engineer a T cell to attack the cancer - because the concept is very similar. If we now know that an ADC can have a survival benefit, even in patients with very low target expression, the same might be true for T cells.
Look back further: Breakthroughs of 2021
https://leaps.org/6-biotech-breakthroughs-of-2021-that-missed-the-attention-they-deserved/
