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A flatworm grew an eye on its tail. A frog regrew a leg it never should have. No gene was edited — so what's really running the show?
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00:00What if you could grow a new organ without touching a single gene?
00:03Genes are supposed to be the blueprint of life.
00:06Every instruction for how your body grows, and what shape it takes, is written in that
00:10double helix.
00:11But if that is really true, how did one scientist make a flatworm grow a working eye on its
00:15tail?
00:16Give a tadpole two heads?
00:18Or make a fully grown frog regrow a leg it was never supposed to grow again?
00:22His name is Michael Levin.
00:23Over the past 30 years, his experiments have peeled back layer after layer of something
00:27hidden behind the genes.
00:29Something that is not inside the DNA, yet may be closer to the real answer of how a
00:33body knows what to build.
00:34Let us begin with the first experiment.
00:37Very early in the development of planarian flatworms, Levin's team completely scrambled their facial
00:41structure.
00:42Eyes drifted to the side.
00:44Mouths ended up on top of the head.
00:46The whole face looked like it had been painted by a madman.
00:49So they gave them a name, the Picasso Worms.
00:52And what truly stunned Levin was not that they recovered.
00:55It was how they recovered.
00:57Every single organ took a completely new route, one that had never existed before, to reach
01:01the place it was supposed to be, and then it stopped.
01:04It was as if these cells carried a perfect picture of the finished frog face inside them.
01:08No matter how badly you scrambled the starting point, they would find a way to assemble that
01:12target image again.
01:13Which raises the first big question.
01:16Where does that picture actually exist?
01:18There is no drawing of a frog face written in the genes.
01:22So how do the cells know the target?
01:24The thing Levin studies is called electricity.
01:26Every cell in your body maintains a tiny voltage across its membrane, created by charged ions moving in and out
01:32through miniature gates called ion channels.
01:34Levin had already found that manipulating these channels, and changing a cell's electrical state,
01:39could steer how an animal develops.
01:40For example, it could decide which side of the body the heart grows on.
01:44And again, without touching a single gene.
01:47But were these electrical signals just a byproduct of development?
01:50Or were they actually telling cells what to build?
01:53To settle this, he placed embryos in a fluorescent dye, letting him see differences in electrical
01:58state directly.
01:58Early in development, long before eyes appear, the exact spots where eyes will later grow
02:03already light up with two distinct electrical signals.
02:06Then he split the embryos into two groups.
02:08One developed normally.
02:10In the other, he changed the electrical state of those cells.
02:13The normal group grew normal eyes.
02:16The modified group had eyes that were severely deformed, or missing entirely.
02:20Same genes.
02:22Only the electrical signal was changed.
02:24Levin pushed further.
02:26If that electrical pattern really is an instruction that says, build an eye here,
02:30then what happens if you copy that instruction somewhere else on the body?
02:33He injected the embryos with a special messenger RNA, causing some cells to produce new ion channels,
02:38replicating the same electrical pattern found in the eye region, all over the body.
02:42The result, eyes started appearing everywhere.
02:45Some on the head.
02:46Some on the sides.
02:48Some even on the tail.
02:49And in a few of the flatworms, those cells assembled a complete eye, with a lens, a retina,
02:54and light-sensing cells, nearly identical to a normal eye.
02:57You might think growing one is already absurd enough.
03:00But here is the stranger part.
03:02These eyes, grown on the tail, could actually see.
03:06Levin's team built an automated training device and found these worms could learn to
03:09respond to visual signals.
03:11And the optic nerve from that tail eye did not connect to the brain.
03:14Some reached other tissues.
03:16Some connected to nothing at all.
03:18Yet they could still see.
03:20Stop and think about that.
03:22An eye grew on a tail.
03:24Its optic nerve hooked into a body part that had never processed vision.
03:27And the animal simply saw normally.
03:30So electrical signals can build a correct organ in the wrong place.
03:33But if the electrical signal really is the body's blueprint,
03:36could it build something far more complex than an eye?
03:39Something like an entire head.
03:41Levin turned to a creature called the planarian.
03:43Its regenerative powers are astonishing.
03:46Cut it in two, and each half grows into a complete worm.
03:49Cut it into more than 200 pieces, and every piece knows how to rebuild a full planarian.
03:54But textbooks rarely mention this, cut the worm exactly down the middle,
03:58and the cells on the left and right were, one second earlier, identical.
04:01Yet after the cut, one side knows to grow a head, and the other knows to grow a tail.
04:06Levin guessed that the cells must have some kind of collective mechanism,
04:09passing signals across the cut through structures called gap junctions,
04:12helping them figure out what each end should become.
04:14So what if you cut that communication?
04:17He soaked the worms in a drug that temporarily blocked the gap junctions,
04:20then cut off the head and tail.
04:22He waited a few days.
04:24When he returned to the lab, he saw something that looked almost alien.
04:28Some worms had grown a complete new head at both ends.
04:31Two heads.
04:32Two brains, trying to control the same body at once,
04:35their behavior contradicting itself again and again.
04:37These two-headed worms were genetically completely normal.
04:41Nothing had changed.
04:42So if you cut off the extra head, it should return to normal, right?
04:46After all, the genes are right there.
04:49For over a hundred years, nobody had bothered to test this assumption.
04:53Levin tested it anyway.
04:54He cut the two-headed worms in half again and put them in ordinary clean water,
04:58with no drugs at all.
04:59The result, both ends grew two heads again.
05:02Even stranger, when he went back and cut the worms from the first experiment that had only grown one head,
05:06about a quarter of them also grew two heads this time.
05:09If you look at these worms from the outside, one head and one tail, perfectly normal.
05:14Their molecular markers are perfectly normal too.
05:17You would not notice anything unusual.
05:19But if you look at their voltage distribution,
05:21you find that this worm's body is hiding an incorrect memory.
05:24It thinks it is supposed to have two heads.
05:27You just will not know it until you cut it open.
05:29It is like a programmable calculator.
05:32You rewrite the code, turn it off and on again, and it remembers the new pattern.
05:36Living tissue may work the same way.
05:38So far, Levin made cells build correct organs in the wrong places,
05:42made them build structures the body should not have,
05:44and even rewrote the body's memory of what it should look like.
05:47And at every step, he never touched the genes.
05:50Is that absurd enough?
05:51Well, the next question is more direct.
05:54Can any of this actually help people?
05:56If electrical signals control what the body builds,
05:59could you make an adult animal regrow a leg it could never grow back?
06:02Levin chose an adult frog called the African clawed frog.
06:05Once it grows up, its regenerative ability is basically gone.
06:09He amputated one leg from two groups.
06:11One group was left to heal naturally, as a control.
06:14On the other, he immediately fitted a wearable micro device over the wound,
06:18filled with a gel that promotes healing,
06:20while also altering the electrical state of the wound cells.
06:23And here is the critical detail.
06:25This device was worn for only 24 hours.
06:28Then it was removed.
06:29After that, there was no intervention at all.
06:32Over the next 18 months, he watched both groups.
06:35The control group grew a thin, spike-like stub.
06:38The device group grew a thicker, far more complex limb-like structure,
06:42with more blood vessels and denser nerves.
06:44Some even developed hints of toes.
06:47Later, Levin mixed five compounds,
06:49each proven effective at different stages of regeneration,
06:51into a single device.
06:53Again, worn for only 24 hours.
06:5618 months later, this group had grown an even larger and more complex limb,
07:00with more nerves and blood vessels.
07:02Some grew complete toes.
07:04Follow-up experiments found that these newly grown legs had feeling, and could move.
07:08Think about that.
07:10Something placed on the wound for 24 hours, then completely ignored.
07:13And the leg grew by itself for a year and a half.
07:16This was not 3D printing.
07:18Not a scaffold.
07:20Not manually directing stem cells where to go.
07:23Nobody knows how to manually build a frog leg.
07:26But you do not need to know.
07:28Because the cells already know how to build it.
07:30All you have to do is tell them one thing, do not scar, regenerate.
07:34If changing the signals of normal cells can make them build new organs,
07:37then could changing the signals of cancer cells stop them from being cancer?
07:41Cancer, at its core, is a group of cells that once belonged to a collective,
07:44suddenly deciding to work for themselves, multiplying wildly and out of control.
07:49Levin's team inserted a powerful cancer-causing gene into frog legs.
07:52Some cells began to develop tumors.
07:55Then they changed the electrical state of these cells,
07:58making them re-establish electrical connections with the surrounding cells.
08:01As a result, many tumors were suppressed, even while the cancer gene was still being expressed wildly.
08:06In 2016, he went further, inserting a human cancer gene into frog legs and letting the tumors grow to a
08:12mature stage before intervening.
08:14When they changed the electrical state of these cancer cells, many tumors shrank or returned to normal behavior.
08:19The cancer gene was still being expressed.
08:22But the tumors simply did not grow.
08:24Because what really drives cell behavior is not the gene itself,
08:27but the communication between the cell and the collective around it.
08:30Once these cells are reconnected to the collective's electrical network,
08:33they go back to doing their job, building skin, building muscle, building everything they should.
08:38Now come back to the first question.
08:40Why can the body grow new organs without changing genes?
08:44From the Picasso worms that fix their own faces, to the seeing eyes grown on tails,
08:48from the two-headed worms hiding a false memory, to a leg regenerated by 24 hours of intervention
08:52lasting a year and a half, all the way to silencing wildly active cancer genes.
08:57Levin's 30 years of experiments point to the same thing.
09:00We thought genes were the blueprint of life.
09:02But what truly decides how a body builds itself, what shape it takes, and how it repairs itself,
09:07may be something we have long ignored, the invisible electrical network between cells.
09:11Genes are the hardware, producing proteins and molecular parts.
09:15But how those parts get assembled, what shape they form, when to start, and when to stop,
09:19is controlled by electrical signals.
09:22The software
09:23In 2016, Levin was chosen as one of the first heads of the Allen Discovery Center,
09:27bringing together researchers in biology, engineering, and computer science.
09:31His team even later created living robots that can self-replicate.
09:35He imagines that one day, children will look back at the diseases and disabilities we simply accept today,
09:40the way we look back at earlier generations, and think it is unbelievable.
09:44Why could they not fix these things?
09:46And maybe in a sense, what Levin has been chasing all along is still that thing that fascinated him as
09:50a child.
09:51His father opened the back of a broken television set and showed him the dense nest of wires inside.
09:56Just a bunch of independent parts.
09:58As long as they were put in the right place, with the right signals, an image would appear.
10:03His father told him this was engineering.
10:05But what the young Levin heard was magic.
10:08Thirty years later, what he faces is no longer the wires inside a television,
10:11but the electrical signals between living cells.
10:14Yet the way he looks at them may have never changed.
10:30So what he looks at them now is now, what they are.
10:33The way he looks at them may have never changed.
10:34So what he looks at them may have never changed.
10:39Then he did the wire that night at his own home.
10:39He has a very light.
10:39He is still on the other side of the wall.
10:41As long as he's from being over,
10:43him can't see the area between the windows to be in the middle of the house.
10:44He can't see it.
10:44But the engine is no longer that he looks at,
10:46but the engine is no longer the bottom of the house to be in the middle of the house.

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