StemCell Therapy

In this episode, were all about regeneration. We talk with a Tufts biologist about the ways some animals regrow lost body parts, and the real possibility of science helping humans do the same one day. An ecologist explains how forests have the capacity to recover from even the most devastating wildfiresan ability theyve honed over thousands of years.

We hear how some species have come back from near extinction with a little attention from their human counterparts, and some enthusiastic farmers show that even something as basic as dirt can come alive with the right care. We share one experts vision for growing a better, greener economy in the wake of the pandemic, before taking a detour for the tale of some long-lost paintings given a second chance for appreciation.

Finally, we talk with an alumna who suffered a great physical loss, but went on to build a new career and a new outlook for herself. As she says, Theres always an opportunity for renewal.

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Read More About Regenerative Medicine

Michael Levin, A92, is the director of the Allen Discovery Center at Tufts University and the Tufts Center for Regenerative and Developmental Biology. He is also Vannevar Bush Professor and Distinguished Professor of Biology. Read about frogs starting to regrow limbs, tadpoles prompted to grow extra eyes, and some other recent research from his lab on Tufts Now.

Michael Reed, professor of biology, studies avian ecology and conservation biology. He looks at how habitat loss and fragmentation affect extinction risk and population viability, as well as the role of animal behavior in extinction risk and conservation.To get a feel for why species regeneration is so urgent, read about the UN report on species extinction rates, the report on species population size decline, and the 3 billion North American birds that have vanished since 1970.

Erica Smithwick, J95, majored in geology and environmental studies at Tufts. She is now a professor of geography at Penn State, where she is director of the Ecology Institute. A landscape and ecosystem ecologist, she is involved in understanding how a wide range of disturbances, especially fire, affect ecosystem function.

Rachel Kyte is the dean of The Fletcher School. A 2002 graduate ofFletchers Global Master of Arts program, Kyte served as special representative of the UN secretary-general and chief executive officer ofSustainable Energy for All. Previously, she was the World Bank Group vice president and special envoy for climate change. Read more about her call for a green recovery in the New York Times.

Meghan Powers and Elliot Rossow started their cultivation careers through a course with the New Entry Sustainable Farming Project at the Friedman School of Nutrition Science and Policy, later applying for a plot of land through NESFPs incubator program. They now run Kona Farms as a living laboratory for environmental stewardship. Reach them at konafarmsma@gmail.com or on Instagram.

Christina Maranci is chair of the department of history of art and architecture in the School of Arts and Sciences. She is also the Arthur H. Dadian and Ara Oztemel Professor of Armenian Art and Architecture. Maranci's research is mainly onmedieval Armenian history and the relationship with the Sasanian, Byzantine, and Islamic empires. See some of her photos of the art of Ani Cathedral on Tufts Now.

Maggie Baumer, A04, studied clinical psychology at Tufts before graduating from law school. She manages the Springfield, Mass., location of Hanger Clinic, the nations largest provider of state-of-the-art prostheses. She is also a certified peer visitor for theAMPOWER program, a peer-to-peer network designed to empower and strengthen those affected by amputation or limb difference.

Transcript

JULIE FLAHERTY: 2020 has been a really rough year, which is why everyone is hoping that a new year will bring brighter times.

ANNA MILLER: And that got us thinkingabout renewal, about starting over, about rising from the ashes. This is Tell Me More, the Tufts University podcast. Im Anna Miller.

FLAHERTY: And Im Julie Flaherty. In this episode, were all about regeneration. Were talking forests that bounce back after massive wildfires, animals that regrow lost limbs, and people who manage to rebuild their lives after calamity.

MILLER: They are just the kind of inspiring stories we need right now.

FLAHERTY: If you want to be encouraged about the possibility of regeneration, just talk to Michael Levin. Levin is the director of the Allen Discovery Center at Tufts and the Tufts Center for Regenerative and Developmental Biology. I asked him about the most impressive examples of regeneration he knows.

MICHAEL LEVIN: Many people know about things like the axolotl, which is a salamander that will regenerate almost any organ. So they regenerate their eyes, their jaws, their limbs, their ovaries, portions of their brain and heart. But some other cool ones are, for example, deer. So deer are a large adult mammal, and every year they regenerate their antlers. And antlers have bone and skin and vasculature and nerve, and they will regenerate those antlers at a rate of about a centimeter and a half per day. So think about that. Every day, that thing adds a centimeter and a half of new bone.

FLAHERTY: But even more impressive might be a creature Levin uses in a lot of his worka little guy called the flatworm.

LEVIN: Well, the planaria, the flatworms are an amazing model system. They combine most of the interesting problems of biology are found in this animal. Its just remarkable. First of all, they regenerate from any piece of the body. The record, I think is something like 275 pieces. You can cut the worm in any way you want. Every piece knows exactly what a correct worm looks like, and it will build exactly whats needed, no more, no less, to give you a tiny, perfect little worm. So they hold the secret to regeneration. So thats the first thing.

The second thing is theyre also immortal. They have no lifespan limits. So theres no such thing as an old planarian. They live forever, and thats telling us that in fact aging is not an inescapable part of life. These animals have been with us for probably 400 million years. And these are the exact same worms. They just do not age. So thats telling us that immortality is possible for a complex creature.

FLAHERTY: Thats all very well for the worms. But what about people?

LEVIN: The other thing a lot of people may not know is that even human children can regenerate their fingertips. So somewhere between the age of 7 and 11, most of us lose this. There used to be more of this back in the 70s, when fans werent covered with the metal grates and everything. But a clean amputation of a digit for a small child usually just grows back perfectly.

FLAHERTY: No one knows for sure why we lose the ability to regenerate as we get older. But Levin says that all of the information for how to do it is still inside us. We just need to figure out how to turn it back on. And Levin thinks it has something to do with bioelectricity, the flow of ions between cells in the body. Thats how cells communicate with each other.

Levin, who studied both biology and computer science as an undergrad at Tufts, likens it to software. If we can find the code that the cells use to communicate about regeneration, we can run that program, and get the cells to do the work of building a new finger or what have you.

LEVIN: So all of those kinds of computations, when the cells join together to say, what should we be building? Are we done yet? Is there a finger missing? How many fingers should there be? That kind of thing. All of that is mediated electrically.

So if we understood how that worked, we could artificially inject electrical information to get the cells to do whatever we wanted them to do. And so this means kickstart a normal regenerative cascade, or reprogram a tumor into normal tissues, or build a completely new anatomical structure thats never been seen before, some sort of synthetic living device. All of that is possible if we understand how cells cooperate towards these kinds of outcomes.

What weve developed are some of the first tools to listen in on, and then modify, the natural electrical conversations that cells are having with each other. We basically go in and we open and close the ion channels that are in those cells, to modify how they talk to each other.

FLAHERTY: Levins lab has conducted many groundbreaking experiments over the years. They have coaxed a mature frog, which typically does not have the ability to regenerate its limbs, to begin to grow a new leg. Another experiment involved convincing a tadpole to grow an eye. But they didnt want the eye in the usual place.

LEVIN: We observed that there was a special electrical pattern that was present in the embryo where the eye was going to form. So what we simply did was reproduce that same pattern somewhere else. What we found is that, sure enough, the cells know that that pattern means make an eye here. And if you make that electrical distribution in the gut, then you will have an eye in the gut, and if you make it in the tail, you will have an eye in the tail.

FLAHERTY: Yes, a tadpole with eyes on its tail is weird, but it showed something important. To use that software analogy again, it showed that cells can be reprogrammed. You dont have to rewire the hardware to make an eye.

LEVIN: We dont know how to make an eye ourselves. The eye has many different cell types, arranged in a really exquisite pattern. We cant reproduce any of that by hand. Its way too complex. But we found that with a very simple trigger, the whole eye is formed. So that told us that theres a path towards regenerative medicine where you dont need to try to micromanage the whole process. You need to find the logic of the natural software thats being used, and you can take advantage of it.

FLAHERTY: Levin believes that one day, humans are going to be able to regrow eyes, limbs, hearts, and other useful things.

And you think youre going to see this happen in your lifetime?

LEVIN: I hope I not only to see it happen, I hope I help make it happen. Were working very hard towards this now. Im optimistic. I think were going to see amazing things out of regenerative medicine in the next decade or two.

MILLER: So some animals are pretty good at regenerating body parts. But what happens when a whole group of animals is threatened with extinction? Is there any way to regrow a species? We put that question to someone who studies animal populations.

MICHAEL REED: My name is Michael Reed, Im a professor in the biology department at Tufts University.

MILLER: There is an urgency behind this question. Right now, were in an environmental crisis. And a lot of animals are disappearing.

REED: Were now moving into a sixth mass extinction thats, if continued, would build to be similar to one of the mass extinctions during geologic time, the last of which was the disappearance of most of the dinosaurs.

MILLER: This time, theres no meteor. Instead, its us. Simply put, our actions are killing animals around the globe in shocking numbers. Since the 1970s, 68 percent of all animal populations have been wiped out.

REED: If you were paying attention to the news a year ago, you would have seen around the world headline news of 3 billion birds lost in North America.

MILLER: A report delivered by the United Nations estimates that within the next 30 years, anywhere from a third to half of all species on the planet might go extinct. So what are humans doing to cause this? Its climate change, its wildlife trafficking, its use of pesticidesbut the biggest killer, says Reed, these animals have run out of places to live.

REED: The number one problem globally is habitat loss, habitat fragmentation, and degradation of habitat. If you take away a species habitat, the species doesnt exist anymore.

MILLER: So can we even turn this around? I asked Reed if he knows of a species that people have successfully brought back from the brink of extinction.

REED: Yeah. Fortunately there are examples, otherwise I think people would give up in despair.

We kept bison from going extinct in the U.S. Theyre not anywhere near the numbers they were at one time. There used to be hundreds of millions of them and their range actually extended into the middle of New York state. In Pennsylvania you could see bison. Their numbers are extremely low compared to that. But since we were down to dozens, I think the tens of thousands we have now is pretty good. So at that stage, it depends on exactly how youre defining success.

MILLER: When we stopped using the pesticide DDT, which turned out to be damaging to eggs, some bird species bounced back.

REED: The bald eagle has moved off of the endangered species list. The peregrine falcon has moved off the endangered species list. Osprey are returning to many of their haunts on the East Coast of the U.S. and Northern Europe with the cessation of the use of DDT.

Ironically, the one large group of birds thats doing really well, and their numbers are going up instead of down, is waterfowl. And we hunt them. Animals were going out and shooting, harvesting, their numbers are going up, while the animals that were not harvesting are going down. The big difference is for harvested animals, people are putting their money where their mouth is and says, Id like more of them. Lets spend millions of dollars recreating habitat, bolstering populations.

Frankly, any of you who go to national wildlife refuges, those were paid for by duck hunters. Thats why we have these refuges. It demonstrates that with interest and money, we can turn these around really well, even for harvested things. Looking at examples like that gives me a lot of hope.

MILLER: There are simple things people can do to boost wildlife populations.

REED: So if youre cutting down lots of habitat and the species are disappearing, quit wrecking so much habitat, or find ways to leave patches behind that are sufficient for species or corridors that connect one reserve to another reserve. Or in your yard, instead of having a bunch of grass, let some wildflowers grow and bring back native pollinators.

We have proven that we have the capacity to make a difference and to turn things around and that it just requires some awareness and some thoughtfulness.

FLAHERTY: We humans can take all the blame for habitat loss. But sometimes destruction and regeneration are just part of the natural cycle.

Erica Smithwick has made a career studying how ecosystems recover from traumas like insect infestations and wildfires. Smithwick, who graduated from Tufts in 1995 and is now a professor of geography at Penn State, has extensively studied the 1988 wildfires in Yellowstone National Park. More than 40 percent of the park was burned, and news accounts at the time made it seem like the park might not survive.

NEWS ANCHOR: Our oldest National Park is under siege tonight...

NEWS ANCHOR #2: The president to declare Yellowstone National Park a national disaster area...

ERICA SMITHWICK: The media coverage at the time was really alarmist. It was talking about the destruction and all these D words, death, destruction, disaster. It really was portrayed in that way. And actually what the science showed us was completely the opposite. And its one of the lessons we learned from studying the Yellowstone landscape over decades, frankly, is that the system recovered, it had the potential to recover.

And if you go to Yellowstone today, you probably wouldnt know that it once was a blackened landscape because its completely green, you see all of the trees coming back, a carpet of trees really just covering the whole landscape. And you have to dig deeper to understand that a lot of that regeneration was because the trees have the capacity to recover from severe fire.

FLAHERTY: In fact, the trees depend on fire to reproduce. They need the heat of a large fire to melt the resin in their pinecones and release seeds of new plants.

SMITHWICK: And it turns out that the lodgepole pine trees that are dominating a lot of the Yellowstone landscapes have this trait because they have adapted to severe fires over the past 10,000 years, the entire quaternary period. Theres memory in the system of these large wildfires. And the fires that occurred in 1988 were basically on cue.

It was about time for one of these large fires. Now, they dont come often, they come every 150 to 300 years. Thats why it wasnt part of our social memory of what the park should be experiencing. But within the context of what we can tell by paleo records of ash and pollen, this was fitting right in with a normal fire cycle of the park.

FLAHERTY: Almost as soon as the fires ended, seedling began to appear. Within a decade, trees rose up, and became what you see now as large mature trees. The recovery was also picturesque, as wildflowers took advantage of newfound sunlight.

SMITHWICK: Fireweed is a particular plant that is very beautiful. Its this purple-pink color and it just is covering the entire understory of the forest. And along with that comes the understory plants that bring nitrogen to the soil. This is a very impoverished nutrient poor ecosystem. And these understory plants bring a lot of nutrients back into the soil.

FLAHERTY Smithwicks research has shown that the fire itself brought a pulse of nitrogen to the soil, in part by breaking down organic matter on the forest floor, making nutrients for the next forest. And as Yellowstone came back, it came back different. Like aspen trees that sprang up where they hadnt been any before. In fact, fires are known for creating biodiversity.

SMITHWICK: Well, this is the thing about disturbances generally in forest city ecosystems is that they do create surprises. They create opportunities for new organisms to persist and even get reintroduced into a certain area.

There are a lot of birds that really enjoy post-fire landscapes or burned landscapes. So black-backed woodpecker would be one Kirtlands warbler in other parts of the U.S. A number of these birds will come into burned environments because the burned ecosystem has lots of cavity in the trees for nesting. And it also has a lot of bugs and beetles. The insects in that forest are actually just presenting a smorgasbord to sunbirds. The sunbirds, they depend on these burned ecosystems for survival, and will seek them out.

FLAHERTY: So forests can recover from massive wildfires. They just need time to do it. And its the lack of time that worries Smithwick right now. These big fires that usually happen hundreds of years apart are now happening every 15 or 30 years.

SMITHWICK: When we see fires like we have in the West, 8.6 million acres burned this year in 2020, and actually five times that amount in the Australian fires, just enormous areas burning. This is out of the realm of what we would expect to be normal. Thats concerning in terms of the ability of those forests to be able to recover.

We want an ecosystem that constantly is renewing itself. We have to learn to live with fire. And we all also have to learn to give our systems time to recover, because they have the capacity to do so.

There is nothing more important right now than fixing the climate situation. And so buying time to do that. And frankly, a lot of the climate work suggests that we do have the potential, if we make the right decisions now, to move the needle and that the earth system, the climate system, will actually respond very quickly.

MILLER: So forests can literally rise from the ashes, and often come back differentmaybe even better. Rachel Kyte, dean of The Fletcher School, thinks that the same is true for economies. Right now, in the midst of the pandemic, economies worldwide are hanging by a string. But Kyte is already thinking about the recovery, and the opportunity it presents to do something for the climate situation Smithwick was just talking about.

RACHEL KYTE: I think its really important to remember that before COVID hit, and I know that feels like a very long time ago, the economy wasnt working for everybody and it wasnt working for the planet.

When we think now about recovery, we have to recover, and through recovery, get ourselves on a trajectory for net-zero emissions by 2050. We have to recover clean and we have to recover in a way that we don't leave people behind. The good news is that thats entirely possible. They are not in opposition to each other.

MILLER: Kyte says that people are going to need jobs, and those jobs could easily be a part of building a greener economy.

KYTE: Whats been interesting through the pandemic is to see that we can agree, the economists worldwide, every international organization that we used to govern the global economy, that there are things that governments can do that will spur short-term income generation, short-term jobs, as well as mid-term growth and long-term emissions reduction.

For example, here in the Northeast of the United States, one of the most important things we could do is massively invest in programs to refurbish, deeply refurbish the built environment. Every time we make a building energy-efficient, those are good, local, skilled, and semi-skilled jobs, we reduce the emissions from this part of the United States, and we build our resilience to the next shocks.

We also know that investing in the infrastructure we need to drive electric cars and hydrogen fuel cells will be important. We also know that investing in the clean energy infrastructure that will allow us to use much more renewable energy will be important. These are good local jobs. Good, local jobs, well-paid put us on a better trajectory and put us on track for zero-net emissions.

MILLER: One way to help reduce carbon emissions is by fixing how we grow food. And thats where something called regenerative farming comes into play. Elliot Rossow is a soil microbiologist. And he cares so much about the earth, he can actually taste it.

ELLIOTROSSOW: Theres this entire classification system of soils and so I can grab some in my hand and put a little bit on my tongue and I can tell you, to a very specific content, how much sand, silt, and clay is in that soil. Which is awesome, its a great party trick.

MILLER:What does good soil taste like?

ROSSOW:Well, no soil really tastes good.

MILLER: Rossow and fellow soil-enthusiast Meghan Powers are incubator farmers with the New Entry Sustainable Farming Projectrun by the Friedman School of Nutrition Science and Policy.

They farm a small plot of land in Beverly, Massachusetts, where they groworganicvegetablesmost of which they donate to charity. But their real aim is figuring out how to bring life back to depleted soil.Heres Powers:

MEGHAN POWERS: So the main purpose of the farm is to test out new and really interesting sustainable management practices and sustainable inputs with the goal of regenerating the land and the soil itself.

MILLER: Why regenerate the land? Powers says the problem is that our agricultural system tends to treat soil like an inert thingput enough chemical fertilizers into it and plants will grow. But chemicals also break down the soil, degrading it. And over time, once you put in enough chemicals, the soil can become unusable.

POWERS:Its really important to start from this holistic perspective that we are working with the soil, and the soil is a living thing.

MILLER: Healthy soil is actually alive with active microbial communitiesmicrobes that help plants and make the soil more resilient. Rossow says you can actually see when dirt is thriving.

ROSSOW:You can definitely feel when soil is alive and intense, and if youve ever played in dirt, played in soil, you notice that it comes in different clumps. Theyre called aggregates, these big clods of dirt you see kids throwing at each other or people break it when they step on them.

But really, the more aggregates and the larger the aggregates means that theres more biological activity happening and flowing through that entire system. And so the more aggregates you have, and the healthier it is, you can see that they kind of grow in size. Whenever were soil sampling out there, and we find it, Oh, my gosh. Look at this one, its as big as my hand. Theyre massive.

MILLER: For the next three years, theyll be using their farm as a living laboratory, testing what works best to produce crops while still making the soil healthy. Because ultimately, healthy soil is a defense against climate change.

POWERS: And the great thing about soil is that you can regenerate it, you can build it back up, its not one and done, you can put carbon back in. And I think thats one of the few solutions that we have really for the climate problem is that we can put carbon in the soil, and we can recharge this system and doing that would take it out of the air and make itmore healthy.Soits really a win-win.

Excerpt from:
Seven Stories of Regeneration | Tufts Now - Tufts Now

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