Regrowing human limbs and organs... the stuff of science fiction, is on the horizon.
The most extraordinary work in this field is coming from Tufts University scientist and entrepreneur Michael Levin, PhD. One of the world’s foremost experts in regenerative medicine and a leader in the growing field of “bioelectricity,” Levin has been developing the use of the bioelectric controls in the body to induce regeneration of tissues, limbs, and organs.
Most recently, Levin has teamed up with brilliant serial entrepreneur Jess Mah to found Astonishing Labs, a venture that aims to commercialize much of this groundbreaking research in regenerative medicine. When I think of key technologies that will enable extended healthspan, there is little question that Levin’s technology will be a critical element to replace worn and broken parts.
In today’s blog, which is based in part on my discussion with Levin atmy Longevity Platinum Tripin September 2023 and a recent interview he did onThe Templeton Ideas podcast, I’ll summarize Levin's revolutionary approach to regenerative medicine and share a few examples of his research.
Let’s dive in…
The Limitations of Genome Editing & The Promise of Bioelectricity
When we think about altering and manipulating life at its most fundamental level, our minds often jump straight to genome editing and CRISPR. After all, isn’t it DNA that represents the blueprint of life?
But what if there's more to the story beyond genetics?
This is the intriguing question posed by Levin.
"Why can't we just do it with DNA?" Levin asks, challenging the status quo.
He points out the crucial limitation of genetics: "With the exception of low-hanging fruit like single gene diseases, where you know exactly what gene you need to twist, most things that we care about, we have absolutely no idea which genes you would change to get them to happen."
Levin's insight here is profound... Genes code for proteins, not traits, and the traits we wish to alter in biomedicine are large, system-level characteristics, often with opaque genetic underpinnings. How do we cause biological systems to spark the regrowth of organs or limbs? For Levin, this capability is possible through the promise of bioelectricity.
In Levin's lab, his creation of a hybrid creature he calls the "frogolotl" illustrates this conundrum beautifully.
The frogolotl is a merger of frog and salamander cells, and when it was first created it raised a perplexing question: Will this new creature have legs or not? “Despite having both frog and axolotl genomes at our disposal, we can't predict the outcome to that question” says Levin.
This example underscores Levin's point that while we understand the genetic “hardware,” we're still grasping at the “software”—the algorithms that guide cellular collectives in making such decisions.
So, what's the alternative?
Enter the promising realm of bioelectricity. Levin describes it as the "cognitive glue" that binds cellular collectives to a common purpose. It's about the electrical networks within cells, the very same networks that operate in our brains. "It's the ability to form electrical networks and to process information in those networks," Levin explains. By understanding and manipulating these bioelectric patterns, we can potentially rewrite them for various purposes, much like adjusting a thermostat without needing to rewire the entire system.
Levin's vision is a paradigm shift, moving beyond the genetic code to the electric code. In his words, "What you need to understand is how it encodes the setting and then ask: How do I go about changing it?"
This approach could revolutionize regenerative medicine, allowing us to harness the body's innate abilities in ways we've only just begun to imagine.
Answering His Own Fundamental Question
At the heart of regenerative medicine is a pivotal question that Levin has raised: “How do we convince a group of cells to produce a nice, healthy organ?”
This fundamental question is not just theoretical for Levin; it's a real puzzle he's piecing together in his laboratory.
Levin believes that a key part of the answer lies in the environment surrounding the cells. Here’s how he articulates this perspective:
“...There’s going to be an environment that needs to be produced for these cells that convinces them that regeneration is going to be possible. It’s protected, it makes sense to put energy into doing it."
Levin's insight draws upon the evolutionary history of mammals. He speculates that early mammals, under constant threat in their environments, evolved to rapidly scar wounds rather than regrow limbs, as immediate healing was crucial for survival.
Levin’s approach extends beyond mere speculation. In his lab, he's working on creating a conducive environment for regeneration. This involves the use of what he calls “wearable bioreactors,” or “biodomes.”
These devices are designed to create an almost amniotic-like environment around a wound, signaling to the cells that conditions are favorable for regeneration rather than scarring. The aim is to concoct the right mixture of ion channel and other drugs within these biodomes to set the stage for regeneration.
By reimagining the cellular environment, Levin and his team are paving the way for innovations that could one day make the regeneration of healthy organs a reality.
The Future of Regenerative Medicine: Envisioning the Anatomical Compiler
So, what is the end game for regenerative medicine?
During my 2023 Longevity Platinum Trip, Levin shared his ambitious vision for the future of this transformative field, a concept he dubs “the Anatomical Compiler.”
Here’s how he explains it: "You will be able to sit down in front of a computer and you will draw the plant, animal, or organ that you want—whatever it is. This Anatomical Compiler would then compile that anatomical description, not at the level of molecules or genes or anything like that, but literally, what do you want? You want an organ. OK. You want a new biological robot, sure."
The essence of the Anatomical Compiler is to translate a desired anatomical outcome into a set of instructions, a set of stimuli that cells would follow to construct exactly what you envision.
Levin elaborates: "The reason this is interesting and why I think this is what we should all be shooting for is that if you think about all the needs of medicine—birth defects, traumatic injury, cancer, aging, degenerative disease, and so on—they all have one major thing in common, which is: Can we tell a collection of cells what we want them to build?"
Imagine the possibilities if we could direct cells to construct specific structures or repair damaged tissues. In this scenario, numerous medical challenges, from congenital defects to degenerative diseases, could potentially be addressed, leaving mainly infectious diseases as the primary health concern not covered by this technology.
Crucially, the Anatomical Compiler isn’t akin to a 3D printer. It's not about placing cells in precise locations to manually construct complex organs. Instead, as Levin describes it:
"The Anatomical Compiler is a translator. It will translate from your anatomical goals or needs to the set point that these cells are going to try to build.”
Levin’s Anatomical Compiler is a beacon of hope, a glimpse into a future where regenerative medicine is not just about healing or replacing but about creating and transforming. In this future, we're not just fixing what's broken—we're reimagining and rebuilding, using the body's own cellular language.
Why This Matters
In aninterviewwith The Tufts Daily last year, Levin discussed the critical need for a new approach in biomedicine:
“All of the biomedicine today is very focused on the molecular hardware, so genome editing, CRISPR pathway rewiring, protein engineering, single molecule, single cell approaches … We need to move beyond the focus of molecular hardware and really take advantage of the software of life.”
There are millions of people who suffer from birth defects, lost limbs, traumatic injuries, degenerative diseases, and other illnesses. And for Levin, much of this suffering is ultimately preventable. “This technology is a vital path for humanity forward. That’s what I want people to focus on.”
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