“I’m Coming to Your Lab and I’ll Be Your Guinea Pig: I Want My Foot Back”

By sheer coincidence, I read a New Yorker article about cell regeneration shortly after watching the documentary “My Octopus Teacher.” Those of you who’ve been with me for a while may recall my fascination with octopuses.

After several people reminded me that the Oscar-winning documentary was worth viewing, I finally saw it last week. It did not disappoint.

Spoiler alert: If you plan to watch the film, you may want to skip this portion of the post.

The disillusioned film-maker scuba diver gains a renewed vigor for life when he develops a hands-on (truly) relationship with an octopus in the seas near his South African home.

At one point, the wily octopus cannot outwit a tiger shark. She pulls herself away, but the shark swims off with one of her tentacles.

The film maker fears that will be the end of her, and her health does seem to be deteriorating. But she rallies, and in time a tiny tentacle begins to grow out of the wound. Eventually, it becomes full size; it has completely regenerated.

End of spoiler alert.

The New Yorker’s lede states: “Deer can regrow their antlers, and humans can replace their liver. What else might be possible?”

Written by Matthew Hutson, the article centers on a developmental biologist named Michael Levin, who is a Distinguished Professor and Director of the Allen Discovery Center at Tufts University, as well as the Director of the Tufts Center for Regenerative and Developmental Biology.

Levin has numerous publications in peer-reviewed journals and textbooks.

And he collaborates with computer scientists, philosophers, biologists, and others.

I tell you all this because his work may seem slightly “out there,” certainly on the cutting edge. Literally.

He’s made a number of discoveries based on the planarian flatworm, which author Hutson says appears, under the microscope, “like a cartoon of a cross-eyed phallus.”

The feature of the planarian that Levin finds so captivating is that no matter how many times its head is cut off, it grows another. And the severed head part grows a tail.

Hutson writes:

“Researchers have discovered that no matter how many pieces you cut a planarian into—the record is two hundred and seventy-nine—you will get as many new worms. Somehow, each part knows what’s missing and builds it anew.”

How does this happen?

While a great deal of contemporary research centers on genes and their associated proteins, Levin doesn’t do anything to the planarian’s genome. He actually changes the electrical signals that emanate from the animal’s cells:

“by altering this electric patterning, he’d revised the organism’s ‘memory’ of what it was supposed to look like.”

He was, in fact, reprogramming the worm.

This story, then, is yet another chapter in the quest to reveal the secrets of life—and to bend them to our will.

Levin’s focus is on a bioelectric code that he believes the body possesses. As artificial intelligence has become increasingly woven into research on humans, Hutson points out, the brain has been viewed as the computer that makes it all work.

Writes Hutson:

“Levin’s work involves a conceptual shift. The computers in our heads are often contrasted with the rest of the body; most of us don’t think of muscles and bones as making calculations.

“But how do our wounds ‘know’ how to heal? How do the tissues of our unborn bodies differentiate and take shape without direction from a brain?

“When a caterpillar becomes a moth, most of its brain liquefies and is rebuilt—and yet researchers have discovered that memories can be preserved across the metamorphosis. ‘What is that telling us?” Levin asked.

“Among other things, it suggests that limbs and tissues besides the brain might be able, at some primitive level, to remember, think, and act. Other researchers have discussed brainless intelligence in plants and bacterial communities, or studied bioelectricity as a mechanism in development.

“But Levin has spearheaded the notion that the two ideas can be unified: he argues that the cells in our bodies use bioelectricity to communicate and to make decisions among themselves about what they will become.”

Think how revolutionary this concept is. Since Watson and Crick discovered the double-helix structure of DNA in 1953, attention has been focused on the human genome.

We’ve been learning more and more about how to conquer diseases through identifying the genes involved and then finding the protein(s) they modify.

Most recently, the discovery of the Crispr technology’s ability to edit genes laid the foundation for the vaccines that are at last controlling the coronavirus pandemic.

Then here comes Levin, offering a totally different approach to molecular biology—one that could also have far-reaching impact.

In a speech before an artificial intelligence group, Levin had said:

“Regeneration is not just for so-called lower animals…You may or may not know that human children below the age of approximately seven to eleven are able to regenerate their fingertips.”

Hutson continues the line of Levin’s thinking:

“Why couldn’t human-growth programs be activated for other body parts—severed limbs, failed organs, even brain tissue damaged by stroke?”

To Levin, the key is using this biologic code to gain control over the body’s three-dimensional shape.

“If you think about it, everything other than infection could be handled if we controlled shape. So birth defects, traumatic injury, aging, degenerative disease, cancer…If we could understand what three-dimensional shape really was, we could do almost anything.”

With regard to cancer, instead of cells communicating with one another, he sees that communication disrupted.

His team did a 2016 experiment in which they injected frog embryos with cancer-causing mRNA.

First the cells in the area lost their electrical polarity. Then “tumor-like growths” appeared. When the researchers intervened to stop the loss of polarity, that was the end of some of the tumors.

As Hutson writes:

”In Levin’s terms, the cancer cells had lost the thread of the wider conversation, and begun to reproduce aimlessly, without coöperating with their neighbors. Once communications had been restored, they were able to make good decisions again.”

His conceptions have been percolating since he was a child. Before he was ten, he was reading about cybernetics, the brainchild of Norbert Wiener, who was a computer pioneer.

“Control systems” such as thermostats that react to a room’s temperature and car cruise control devices operate through what Hutson calls “a kind of internal communication.”

Why not consider the human body, as it develops, the same way?

Levin’s father was a big influence on him. Together, they found a used book, The Body Electric: Electromagnetism and the Foundation of Life. The author, an orthopedic surgeon named Robert O. Becker, had been exploring electricity in the regeneration of the limbs of salamanders and other animals.

Levin said of this book: “It looked like everything I was thinking about.”

He learned from going through the bibliography that electricity had actually been the subject of medical interest for thousands of years—from a former slave of the emperor Tiberius who had found his gout relieved after he’d stepped on an electric fish on a beach—to the finding of Luigi Galvini that animal electricity was evident when a muscle contracted after receiving an electrical charge. Mary Shelley used the concept of Galvinism in Frankenstein.

As the 20th Century progressed, electricity’s involvement in the life of cells had become an accepted part of biologists’ understanding.

It’s worth noting that when Levin did all this formative reading, he was 17 years old.

He began in college as a computer science major, but soon added a biology major. He gained valuable mentors and earned a PhD from Harvard Medical School. After running a lab at Harvard, he returned to Tufts, his undergraduate home.

There, in 2016, he was awarded a $10 million grant by Microsoft cofounder Paul Allen to “crack the morphogenetic code—the system that ‘orchestrates how cells communicate to create and repair complex anatomical shapes.’”

Hutson observes, not surprisingly, that there’s disagreement among researchers about the role of bioelectricity in morphogenesis. One biologist told him there are still many unknowns, including “how the genetic program and the bioelectrical signals are intermingled.”

Levin’s former dissertation adviser and the genetics chair at Harvard Med, Clifford Tabin, says he’s “agnostic” about whether there’s the kind of bioelectrical code that Levin believes exists.

He cites the likelihood of a switch that turns things on, rather than a code that moves the process along.

But Levin stresses that changing a particular signal can have obvious ramifications. He has, after all, planaria with varied heads—some spiky, some tube-shaped or hat-shaped.

“You can hack the system to make the changes. Currently, there’s no competing technology that can do these things.”

Hutson points out the many differing variations for explaining bodily systems: “genetics, biophysics, biochemistry, bioelectricity, biomechanics, anatomy, psychology, and finer gradations in between, all these levels acting together, each playing an integral role.”

And he notes that Levin himself “doesn’t claim to understand the entire system, nor does he maintain that bioelectricity is the only important level…He likens revising an organism’s body through bioelectric stimulation to launching software applications. ‘When you want to switch from Photoshop to Microsoft Word, you don’t get out your soldering iron,’ he said.”

Levin has done some fairly odd investigations, and he’s apparently wary of being thought of as a Dr. Frankenstein. But Hutson says his work with animals isn’t very different from that done by many researchers.

Levin told Hutson:

“I get two types of e-mails and phone calls…Some of the people call and say, ‘How dare you do these things?’ for various reasons—animal rights, playing God, whatever. And then most call and they say, ‘What the f**k is taking you so long?’”

Sometimes, a hopeful volunteer calls him. There was the man who said: “I’m going to come down to your lab, and I’ll be your guinea pig. I want my foot back.”

And his imagination takes him in diverse directions. He has a federal grant from the Department of Defense to build machines made from animal cells that may at some point become tiny robots cleaning up toxic waste or even performing microsurgery.

He’s working with a computer scientist who designed the model for these futuristic ancelbots. (I made up the name.)

So The New Yorker article wasn’t just about cell regeneration after all, though that would have been broad enough. We seem to be heading toward a world of human-machine meld at a faster pace than I’d imagined.

I have an image of my then-preteenage daughter at the Toronto Science Museum, her hand touching a large sphere, her long curly hair suddenly standing straight on end.

It feels as though this bioelectricity may mean we’re in for a wild ride.

What do you think?

Annie