Growing Human Organs Inside Pigs Could Save Lives, But the U.S. Won't Fund the Research
The shortage of organs is a public health menace. Approximately 120,000 people in the U.S. need a lifesaving organ transplant. Of those, approximately 75,000 patients are on the active waiting list. Every day, nearly 20 individuals die from the shortage of organs in the United States.
Ethical concerns about human-animal chimera research might be dramatically overblown.
Scientists worldwide are developing new methods with potential to save countless patients in need of organs. Such approaches have tremendous potential, if only ethical and regulatory challenges could be overcome first.
One way that scientists are proposing to increase the number of transplantable organs is to produce organs from patient stem cells. Owed to their ability to grow limitlessly in the lab and form all tissue types, pluripotent stem cells from patients, in principle, could supply an infinite amount of cells that could potentially be transplanted back into patients. Unfortunately, all efforts to generate organs that can be transplanted into patients from stem cells to date have been unsuccessful.
A different encouraging approach is to generate patient organs inside livestock species, such as pigs. In the latest methods, interspecies chimeras – animals containing cells from both humans and animals – are generated by introducing human stem cells into early-stage animal embryos. Key genes essential for organ formation are disabled, allowing the introduced human stem cells to fill the empty space. In theory, this strategy will produce a human organ inside pigs or sheep.
Creating chimeras is not new in biology. Chimeras, or animals comprised of tissues from two different individuals, have already been deployed in research. Mouse chimeras are routinely used to create genetically engineered mice to study genes. The concept of generating human organs inside pigs or sheep comes from previous studies involving interspecies chimeras generated between mice and rats. Past experiments have demonstrated that it is possible to generate a rat pancreas inside a mouse.
Scientific and Ethical Obstacles
Unfortunately, chimera research has faced hurdles that have impeded progress. Of note, attempts to generate interspecies chimeras by several groups have failed. The results of these studies indicate that human cells appear unable to grow inside mouse embryos. The levels of human chimerism – the number of human cells inside the host animal embryo – appear too low to support any human organ generation.
Another obstacle is that chimera generation is ethically controversial. Some question the moral status of an animal that is comprised of human and animal cells. The most concerning question is whether human cells will contribute to the host animal's brain, potentially altering the cognition of the animal. These issues have prompted scientists to proceed very cautiously with chimera experiments. However, such concerns might be dramatically overblown. This is because the levels of human chimerism are too low to cause any significant change in animal brain function.
The ethical controversy has affected research policy in the United States. In the United States, the National Institutes of Health (NIH), the major funding body of biomedical research, blocked funding for chimera research while ethical questions were considered. Later, it was proposed that a new review process would be instated for chimera research. However, no change in policy has actually happened. The restrictive NIH policy is a major barrier to chimera research progress because laboratories around the United States cannot obtain funding for it. Lifting the restrictions on NIH funding for chimera research would dramatically accelerate chimera research.
Nonetheless, despite the past and current hurdles that chimera research has faced, new advances are changing the landscape of chimera research.
It is time to lift restrictions on chimera research so that its promise can be fully realized.
Progress on the Horizon
Scientists are developing improved strategies to increase the numbers of cells in animal embryos to the point where it might be possible to generate a human organ in an animal. For example, it has been suggested that the human stem cells researchers have been using cannot grow in animals. Scientists have made advances in generating new types of human stem cells that might have an improved ability to form chimeras.
Additionally, scientists have identified some barriers responsible for the failure to generate chimeras. For example, preventing cell death and enhancing the ability of stem cells to compete with host animal tissues also improves the numbers of human cells to the point where human organs can be generated inside an animal.
Finally, a relaxation of regulatory hurdles in other countries has created a more permissive environment for human-animal interspecies chimera research. In March, the Japanese government approved the first such experiments that could comprise a new way of generating organs from patients for transplantation.
Additionally, in spite of the somewhat negative attention that chimera generation has received, the International Society for Stem Cell Research (ISSCR) supports the new Japanese policies allowing chimera experiments. The ISSCR maintains that research involving the generation of chimeras should be permitted, as long as rigorous oversight and ethics review occur.
Chimera research has the potential to transform medicine. Of all the impediments, the NIH restrictions on funding remain the single most significant barrier. It is time to lift restrictions on chimera research so that its promise can be fully realized. One day, it might be possible to grow patient-specific organs inside of livestock animals such as pigs and sheep, saving thousands of human lives. But to change our current policy, the public, scientists, and bioethicists must first agree that this critical cause is worth fighting for.
Fast for Longevity, with Less Hunger, with Dr. Valter Longo
You’ve probably heard about intermittent fasting, where you don’t eat for about 16 hours each day and limit the window where you’re taking in food to the remaining eight hours.
But there’s another type of fasting, called a fasting-mimicking diet, with studies pointing to important benefits. For today’s podcast episode, I chatted with Dr. Valter Longo, a biogerontologist at the University of Southern California, about all kinds of fasting, and particularly the fasting-mimicking diet, which minimizes hunger as much as possible. Going without food for a period of time is an example of good stress: challenges that work at the cellular level to boost health and longevity.
Listen on Apple | Listen on Spotify | Listen on Stitcher | Listen on Amazon | Listen on Google
If you’ve ever spent more than a few minutes looking into fasting, you’ve almost certainly come upon Dr. Longo's name. He is the author of the bestselling book, The Longevity Diet, and the best known researcher of fasting-mimicking diets.
With intermittent fasting, your body might begin to switch up its fuel type. It's usually running on carbs you get from food, which gets turned into glucose, but without food, your liver starts making something called ketones, which are molecules that may benefit the body in a number of ways.
With the fasting-mimicking diet, you go for several days eating only types of food that, in a way, keep themselves secret from your body. So at the level of your cells, the body still thinks that it’s fasting. This is the best of both worlds – you’re not completely starving because you do take in some food, and you’re getting the boosts to health that come with letting a fast run longer than intermittent fasting. In this episode, Dr. Longo talks about the growing number of studies showing why this could be very advantageous for health, as long as you undertake the diet no more than a few times per year.
Dr. Longo is the director of the Longevity Institute at USC’s Leonard Davis School of Gerontology, and the director of the Longevity and Cancer program at the IFOM Institute of Molecular Oncology in Milan. In addition, he's the founder and president of the Create Cures Foundation in L.A., which focuses on nutrition for the prevention and treatment of major chronic illnesses. In 2016, he received the Glenn Award for Research on Aging for the discovery of genes and dietary interventions that regulate aging and prevent diseases. Dr. Longo received his PhD in biochemistry from UCLA and completed his postdoc in the neurobiology of aging and Alzheimer’s at USC.
Show links:
Create Cures Foundation, founded by Dr. Longo: www.createcures.org
Dr. Longo's Facebook: https://www.facebook.com/profvalterlongo/
Dr. Longo's Instagram: https://www.instagram.com/prof_valterlongo/
Dr. Longo's book: The Longevity Diet
The USC Longevity Institute: https://gero.usc.edu/longevity-institute/
Dr. Longo's research on nutrition, longevity and disease: https://pubmed.ncbi.nlm.nih.gov/35487190/
Dr. Longo's research on fasting mimicking diet and cancer: https://pubmed.ncbi.nlm.nih.gov/34707136/
Full list of Dr. Longo's studies: https://pubmed.ncbi.nlm.nih.gov/?term=Longo%2C+Valter%5BAuthor%5D&sort=date
Research on MCT oil and Alzheimer's: https://alz-journals.onlinelibrary.wiley.com/doi/f...
Keto Mojo device for measuring ketones
Silkworms with spider DNA spin silk stronger than Kevlar
Story by Freethink
The study and copying of nature’s models, systems, or elements to address complex human challenges is known as “biomimetics.” Five hundred years ago, an elderly Italian polymath spent months looking at the soaring flight of birds. The result was Leonardo da Vinci’s biomimetic Codex on the Flight of Birds, one of the foundational texts in the science of aerodynamics. It’s the science that elevated the Wright Brothers and has yet to peak.
Today, biomimetics is everywhere. Shark-inspired swimming trunks, gecko-inspired adhesives, and lotus-inspired water-repellents are all taken from observing the natural world. After millions of years of evolution, nature has quite a few tricks up its sleeve. They are tricks we can learn from. And now, thanks to some spider DNA and clever genetic engineering, we have another one to add to the list.
The elusive spider silk
We’ve known for a long time that spider silk is remarkable, in ways that synthetic fibers can’t emulate. Nylon is incredibly strong (it can support a lot of force), and Kevlar is incredibly tough (it can absorb a lot of force). But neither is both strong and tough. In all artificial polymeric fibers, strength and toughness are mutually exclusive, and so we pick the material best for the job and make do.
Spider silk, a natural polymeric fiber, breaks this rule. It is somehow both strong and tough. No surprise, then, that spider silk is a source of much study.The problem, though, is that spiders are incredibly hard to cultivate — let alone farm. If you put them together, they will attack and kill each other until only one or a few survive. If you put 100 spiders in an enclosed space, they will go about an aggressive, arachnocidal Hunger Games. You need to give each its own space and boundaries, and a spider hotel is hard and costly. Silkworms, on the other hand, are peaceful and productive. They’ll hang around all day to make the silk that has been used in textiles for centuries. But silkworm silk is fragile. It has very limited use.
The elusive – and lucrative – trick, then, would be to genetically engineer a silkworm to produce spider-quality silk. So far, efforts have been fruitless. That is, until now.
We can have silkworms creating silk six times as tough as Kevlar and ten times as strong as nylon.
Spider-silkworms
Junpeng Mi and his colleagues working at Donghua University, China, used CRISPR gene-editing technology to recode the silk-creating properties of a silkworm. First, they took genes from Araneus ventricosus, an East Asian orb-weaving spider known for its strong silk. Then they placed these complex genes – genes that involve more than 100 amino acids – into silkworm egg cells. (This description fails to capture how time-consuming, technical, and laborious this was; it’s a procedure that requires hundreds of thousands of microinjections.)
This had all been done before, and this had failed before. Where Mi and his team succeeded was using a concept called “localization.” Localization involves narrowing in on a very specific location in a genome. For this experiment, the team from Donghua University developed a “minimal basic structure model” of silkworm silk, which guided the genetic modifications. They wanted to make sure they had the exactly right transgenic spider silk proteins. Mi said that combining localization with this basic structure model “represents a significant departure from previous research.” And, judging only from the results, he might be right. Their “fibers exhibited impressive tensile strength (1,299 MPa) and toughness (319 MJ/m3), surpassing Kevlar’s toughness 6-fold.”
A world of super-materials
Mi’s research represents the bursting of a barrier. It opens up hugely important avenues for future biomimetic materials. As Mi puts it, “This groundbreaking achievement effectively resolves the scientific, technical, and engineering challenges that have hindered the commercialization of spider silk, positioning it as a viable alternative to commercially synthesized fibers like nylon and contributing to the advancement of ecological civilization.”
Around 60 percent of our clothing is made from synthetic fibers like nylon, polyester, and acrylic. These plastics are useful, but often bad for the environment. They shed into our waterways and sometimes damage wildlife. The production of these fibers is a source of greenhouse gas emissions. Now, we have a “sustainable, eco-friendly high-strength and ultra-tough alternative.” We can have silkworms creating silk six times as tough as Kevlar and ten times as strong as nylon.
We shouldn’t get carried away. This isn’t going to transform the textiles industry overnight. Gene-edited silkworms are still only going to produce a comparatively small amount of silk – even if farmed in the millions. But, as Mi himself concedes, this is only the beginning. If Mi’s localization and structure-model techniques are as remarkable as they seem, then this opens up the door to a great many supermaterials.
Nature continues to inspire. We had the bird, the gecko, and the shark. Now we have the spider-silkworm. What new secrets will we unravel in the future? And in what exciting ways will it change the world?