NARRATOR: Leonardo da Vinci.

Legendary artist.

VINCENT DELIEUVIN: His genius is universal.

It speaks to everybody.

NARRATOR: He was also a scientist and inventor.

KARLY BAST: There was a reason for every decision and every line.

NARRATOR: How did he create the most famous painting on Earth?

FRANCESCA BORGO: You can perceive the beating of the pulse underneath her skin.

♪ NARRATOR: The answers have been as elusive as her smile.

Leonardo embraced mystery.

NARRATOR: Now researchers are peeling away the layers.

DELIEUVIN: Thanks to a new kind of scientific investigation, we are really able to get inside the painting.

NARRATOR: Can science unlock her secrets?

MARGARET LIVINGSTONE: She seems like she's alive, because she looks different depending on where you're looking.

NARRATOR: And decipher the genius behind her creator?

"Decoding da Vinci," right now, on "NOVA."

♪ ♪ NARRATOR: In the heart of Paris lies a former royal castle.

It is now the world's busiest art museum: the Louvre.

Filled with glorious galleries of antiquities, mummies, and Michelangelos.

♪ But one masterpiece is the biggest draw of all.

Today's reigning queen-- the "Mona Lisa," by Leonardo da Vinci.

WALTER ISAACSON: The "Mona Lisa" has become some grand thing in our imagination.

DELIEUVIN: Each time you see the "Mona Lisa," you have a different feeling about what she has in mind.

NARRATOR: Every year, millions visit her, drawn by her beauty or, perhaps, her fame.

BORGO: They've clocked the average amount the visitors spend looking at the "Mona Lisa," and that's roughly about 15 seconds.

You're more focused on getting a good picture for your Instagram feed than actually looking at the painting.

NARRATOR: So is the "Mona Lisa" just famous for being famous?

More icon than art?

Or does she deserve her place on the Louvre's throne as the most celebrated painting in the world?

DELIEUVIN: It's not just a portrait of a woman who was living 500 years ago.

It's a demonstration of how painting could show life.

NARRATOR: Now researchers are using new techniques to investigate the most famous painting on Earth like never before.

♪ MARTIN KEMP: The smile is crucial.

It's teasing you, saying, "I know something you don't know."

NARRATOR: Could the "Mona Lisa," with her enigmatic smile, be the key to decoding the man who made her-- Leonardo da Vinci?

No doubt he was a brilliant artist, but he was also a groundbreaking scientist.

He anticipated theories by both Galileo and Newton by at least a century.

And dreamed up remarkable inventions that seem to predict our modern age: armored tanks, flying machines, even something like a self-driving car.

But were his scientific explorations a distraction from his painting?

Or was science the secret to his artistic genius?

Was the "Mona Lisa," in fact, Leonardo's greatest invention?

ISAACSON: If you want to understand Leonardo da Vinci, you just have to look at the "Mona Lisa," because it's all there.

It's the culmination of a lifetime spent loving science and art.

♪ NARRATOR: In the back streets of Florence, Italy, Valter Conti and his daughter Elena prepare for their tribute to Leonardo and the "Mona Lisa"... Human statues handing out Leonardo quotes.

It's their way of marking the 500th anniversary of Leonardo's death, and just one of many celebrations that are in the works around the world.

From a fine art museum in Beijing to a multimedia extravaganza in Peru... And a blockbuster exhibition at the Louvre.

DELIEUVIN: For the Louvre museum, it's a really important moment.

Because Louvre is like Leonardo da Vinci.

We have the third of all his paintings.

NARRATOR: Vincent Delieuvin oversees the five Leonardo masterpieces that hang at the Louvre.

♪ That's the largest collection in the world.

While Leonardo may be the most famous painter of all time, he completed surprisingly few paintings.

Leonardo was really someone experimental.

He didn't want to paint a lot.

He wanted to paint a perfect painting.

♪ NARRATOR: So what did it take for Leonardo to make a perfect painting?

The answer may be lying right under Delieuvin's feet.

For the upcoming exhibition, he is working with a team of scientists housed downstairs from the Louvre, at the Center for Research and Restoration of Museums in France.

DELIEUVIN: Thanks to a new kind of scientific investigation, we are really able to get inside the painting and to understand how Leonardo was working to perfect the painting for a long, long time-- during five, ten, 20 years.

It's really something really specific to Leonardo.

NARRATOR: They are peering deep inside Leonardo's masterpieces, hoping to reveal the secrets of his technique that our eyes cannot see.

BRUNO MOTTIN: The eye sees something that it believes to be two-dimensional, but which is really three-dimensional, because there is depth in a painting.

(phone ringing) NARRATOR: For art historian Bruno Mottin, the first step is to understand the chemistry of Leonardo's paint, starting with the powdered minerals that were the source of his colors.

MOTTIN: You have green, which is made with the scratching of copper plates, you have vermillion, which is made with mercury, you have lead white, which is made with lead.

But these can't be applied directly on a painting-- it has to be mixed with something else.

NARRATOR: These colored pigments are mixed with a liquid, like oil.

That gets painted on in layers.

♪ In a cross-section of a painting, you have the base- which today is frequently canvas, but in Leonardo's time, they used planks of wood.

On that is a coat of white that can reflect light.

As the artist works, semi-translucent paint is built up layer by layer and then sealed with a coat of varnish.

In the end, our eyes see the interplay between the light reflected off different pigments suspended in the layers, creating depth and elusive subtleties.

MOTTIN: Oil is a translucent medium, which gives to the mixture a deepness.

You can see through all the layers.

You don't only see a flat surface.

You have the feeling of what is beneath the painting.

NARRATOR: Leonardo worked on the "Mona Lisa" for about 16 years.

Can these investigative techniques help reveal, ultimately, what he was doing all that time?

♪ The "Mona Lisa" began in Florence, Italy, in 1503 as a commission from a wealthy cloth merchant to paint his wife, Lisa Gherardini.

The word "mona" was a polite form of address, much like "madam," hence "Mona Lisa."

Over time, she became something much more.

BORGO: The "Mona Lisa" started off as a portrait for a merchant's wife and ended up as a sort of manifesto, if you want, of his ability as a, as a painter, of his conception of the world, even.

NARRATOR: So is this what the real Lisa looked like?

And how different does she appear today from what Leonardo painted 500 years ago?

(device whirring) To find out, scientists captured the "Mona Lisa" with an array of high-tech cameras.

These detect light in the electromagnetic spectrum that is not visible to our eyes.

♪ So just as some cameras can see wildlife in the dark, these cameras can help us see the "Mona Lisa" in a new light-- literally.

Each image provides clues about her past.

MOTTIN: So we have a lot of different images, which can tell us about the structure of the painting and the, the way it has been made.

NARRATOR: In the ultraviolet image, blotches of dark blue appear.

These reveal areas of paint which are not by Leonardo's hand.

They are modern restorations to repair damage to the painting, like this dangerous crack in the wood base.

And for Mottin, it reveals even more.

MOTTIN: It shows us that the painting is in fact colored by a greenish and yellowish varnish which changes the colors of the true painting.

NARRATOR: This thick varnish has yellowed and darkened over time, making it difficult to make out some of the details.

She looks rather like a plump lady, we should say, because we do not know where the arm stops.

NARRATOR: But this infrared image clearly shows this dark area was once translucent.

Lisa is wearing a veil that gracefully falls over her surprisingly slender shoulders.

♪ To penetrate the very deepest layers, the team turn to a tool more familiar to us from a doctor's office: X-rays.

These can reveal how the painting began.

Most artists at the time began with a drawing and then filled it in with thick paint.

So the X-ray looks like this, Raphael's "La Belle Jardinière."

The figures started out clearly defined-- and stayed that way.

♪ But when Leonardo's paintings are X-rayed, the figures often vanish.

♪ ELISABETH RAVAUD: Leonardo image are like phantom.

We don't understand at first sight what really is on the picture.

NARRATOR: In the X-ray of the "Mona Lisa," there is no clear outline.

Instead, the image evolved as Leonardo made continual adjustments.

This also suggests Lisa may not have looked exactly like this.

ISAACSON: He keeps it.

He doesn't deliver it to the merchant who commissioned it.

Because for him, it's no longer a portrait of Mona Lisa.

It is a universal painting.

♪ NARRATOR: In the upcoming exhibition, Delieuvin plans to hang some of these scientific masterpieces along with Leonardo's original paintings.

The scans prove an essential point about Leonardo's artistry-- he painted like no one else.

DELIEUVIN: Leonardo is one of the first artists to be really free.

He felt free to change his mind, not only during the drawing preparation, but also during the painting of his work.

This is incredibly not common.

He is the only one to give such liberty, free manner, in his execution.

♪ NARRATOR: Artists then were considered craftsmen, and needed to churn out paintings for patrons.

So how did Leonardo become such a free spirit?

From the beginning, Leonardo was an outsider.

♪ Born in 1452 to an unwed farm girl in the small Italian town of Vinci, he was named "Leonardo from Vinci."

Therefore, Leonardo da Vinci.

ISAACSON: Leonardo had the great good fortune to be born out of wedlock.

It meant he didn't have crammed into him the sort of old dusty scholastic wisdom of the Middle Ages.

Instead, he got to be self-taught.

It also meant he didn't have to be a notary like his father.

And so he has a fresh life, where he can be anything he wants.

♪ NARRATOR: At about 14, Leonardo's father sent him to learn a trade in Florence, the epicenter of commerce, learning, and beauty at the beginning of the Renaissance.

PAOLO GALLUZZI: Florence was one of the most advanced social organization of the planet.

Very wealthy city.

A city that was attracting the brightest guys around.

(bicycle bell rings) KEMP: Florence is just extraordinary at this time, to produce Donatello, Masaccio, Brunelleschi, Michelangelo, Raphael.

♪ NARRATOR: With no formal education, Leonardo started as an apprentice in one of the leading artist's studios of the day: the workshop of Andrea del Verrocchio.

Verrocchio was a sculptor above all, but also a painter, an architect.

He could play music.

♪ So the example of Verrocchio was very important to Leonardo.

Leonardo's training with Verrocchio is a real model of how an artist should evolve.

Technique is subordinate to the act of seeing.

It's about the eye, and it's Leonardo who first described that.

NARRATOR: It is believed the handsome model for this Verrocchio statue of David is his apprentice, a young Leonardo.

So, they think that Leonardo posed for his master.

It's a very elegant boy face framed by these beautiful curls.

NARRATOR: Despite the circumstances of his illegitimate birth, the workshop gave Leonardo a way to get ahead in life.

ISAACSON: He's a misfit.

He's illegitimate.

He's gay, he's left-handed, he's a vegetarian, he's distracted, and yet he's embraced by the people of Florence because it was a very tolerant city.

NARRATOR: One of the most challenging construction projects of the day was capping the dome of the breathtaking cathedral with a golden sphere.

The commission of the crowning of the cupola with a gilded sphere was a very important one.

And that's a commission that Verrocchio secured.

NARRATOR: Verrocchio's team, which included a young Leonardo, had to figure out not only the design, but also how to secure the one-and-a-half-ton ball on top of the nearly 370-foot high cathedral.

ISAACSON: Figuring out how to get the ball on top of the cathedral helps Leonardo become a great engineer.

It helps him become an artist, because he gets the perspective of the ball right.

That combination of science, engineering, and art becomes part of who Leonardo da Vinci is.

NARRATOR: In fact, in sheer quantity, Leonardo's scientific investigations far outweigh his output of paintings.

The proof of that lies in a remarkable collection of replicas of his notebooks.

GALLUZZI: We have very few records, in the whole history of science, similar to Leonardo's manuscripts.

These are not books.

You cannot compare that to a work of, by Galileo or by Newton, because they have solved the problems before writing their books.

NARRATOR: Paolo Galluzzi is the director of the Galileo Museum in Florence.

GALLUZZI: What we have in Leonardo is the direct expression of his internal dialogue.

NARRATOR: Leonardo's notebooks span his lifetime.

They even come pocket-sized.

BORGO: We're sure that those 6,000 pages that we have are by him.

And this is just one-fourth of what he actually penned.

So we're talking about something he was obsessed by throughout his life.

NARRATOR: The brilliance and breadth of Leonardo's notebooks is astonishing.

His ideas seem to predict our modern age, making Leonardo much more than a Renaissance scientist for many.

His dreams of human flight include a helicopter-like machine and a parachute.

A fascination with water led to ambitious civil engineering proposals.

♪ And he conceived an intriguing self-propelled machine that seems part-automobile, part-early robot.

But could any of these inventive designs have actually worked?

JOHN OCHSENDORF: Leonardo is, of course, a great artist, but he's also a great scientist, and, I would argue, a great engineer.

The geometry is stunning... NARRATOR: One small sketch in Leonardo's notebooks has so intrigued M.I.T.

engineer John Ochsendorf that he asked his graduate student Karly Bast to bring 21st-century engineering rigor to see if Leonardo's 16th-century idea would in fact stand.

OCHSENDORF: There is a historical reason for this, because you see it in the drawing, right?

BAST: Yeah, these two aren't... NARRATOR: In 1502, the year before starting the "Mona Lisa," Leonardo proposed to the sultan of the Ottoman Empire a bridge in Constantinople five times longer than any other span at the time.

♪ His plan for this ambitious project, sketched upside-down in a small notebook, offers few details-- yet just enough for Bast to bring it to life.

Leonardo provided four measurements, but he provided two sketches.

At first, it seems like a rough sketch, but as I dug into it, I realized there was a reason for every decision and every line.

There was a lot of thought put into the force distribution, and it wasn't just aesthetic.

It was engineering.

NARRATOR: And to test that engineering, Bast and her colleagues have built a scale model of the bridge with a state-of-the-art 3-D printer.

MOHAMED ISMAIL: Before 3-D printing came along, we'd have to try to build that bridge as close as we could to the full scale, because you couldn't reliably get the geometry quite right.

NARRATOR: Leonardo's stone bridge would have been 500 times the size of this model, but the physics are exactly the same.

BAST: We have the bridge, and we have the mold that's holding it up.

The first piece should be easy to take off.

NARRATOR: Piece by piece, she removes the Styrofoam-- a modern day stand-in for the wooden scaffolding used in Leonardo's day.

OCHSENDORF: This is more like heart surgery than bridge construction.

NARRATOR: Finally, the last support is removed.

♪ And Leonardo's stone bridge stands.

OCHSENDORF: The geometry is aesthetically beautiful, and the fact that this is standing on its own tells us that it was feasible.

BAST: Absolutely.

OCHSENDORF: Wow.

NARRATOR: Leonardo's bridge even stays up when they simulate an earthquake.

Stop.

BAST: 1,500 pounds.

OCHSENDORF: Oh, my God.

It has moved by 30 feet, and the arch still stands.

NARRATOR: The bridge does eventually collapse, but only after being moved the equivalent of 50 feet.

Leonardo has the artistic ability, and he also has that scientific knowledge and that engineering capability where he can create things that are beautiful and structurally sound.

NARRATOR: Bast clearly had to fill in some details to get from this sketch to this model.

And we don't know if the bridge could have been built with the wooden scaffold of the day.

And he also shows... NARRATOR: But she has shown Leonardo got the basic physics right.

OCHSENDORF: What's extraordinary is the ideas that he was coming up with more than 500 years ago.

Yep.

OCHSENDORF: We're still trying to understand them.

♪ NARRATOR: As with this ambitious proposal to the sultan, Leonardo sought out wealthy patrons throughout his life to support not only his art, but his scientific explorations.

At 30, he moved to Milan to work for its duke.

17 years later, when the duke was deposed, Leonardo had to move once again, back to Florence, and later, Rome.

His accomplishments in science and art meant he had much to offer.

ISAACSON: Leonardo sells himself as an engineer, as well as an artist, because he knows he can make a better living.

But also, I think, Leonardo just loved the connection of the arts and sciences, and he didn't want to have to be siloed as just a painter.

NARRATOR: Leonardo's explorations in science can also be clearly seen in the details of his paintings.

He studied everything from botany to the physics of flowing water.

Even the curls of human hair.

DELIEUVIN: To paint something absolutely perfect, he had to understand how nature was done.

To paint a mountain, to paint rocks, he had to understand why the rocks were of that kind.

He was obsessed with that.

And that was what he called the science of painting.

NARRATOR: The science of painting was all-encompassing for Leonardo.

But how could he capture the beauty he observed in nature with paint?

♪ Back at the Louvre, art restorers and researchers are uncovering new clues in an elegant intensive care unit for priceless works of art.

♪ To prepare for the upcoming exhibit, Delieuvin and the team of scientists are restoring a painting long shrouded by controversy.

For centuries, this portrait of Bacchus was considered one of the few paintings by Leonardo's hand.

But now, experts aren't so sure.

(speaking French) DELIEUVIN: For centuries, that painting was attributed to Leonardo.

But during the 20th century, some historians said, "Well, it looks like difference compared to the other paintings."

NARRATOR: Cinzia Pasquali has been brought in to restore the painting.

Can Leonardo's unique scientific techniques provide the clue she needs to finally solve the mystery: did Leonardo in fact paint this?

(speaking French): PASQUALI: (both speaking French) NARRATOR: Restoration work is not for the faint of heart.

This painting may be in bad shape, but Pasquali is still taking her scalpel to an irreplaceable masterpiece.

She scrapes away the yellow darkened varnish, revealing a vibrant color beneath.

(speaking quietly) NARRATOR: But other parts of the painting appear more damaged.

So Pasquali must rely on her training not only in art history, but also chemistry.

♪ The colors of pigment in paint can change or fade over time.

But the chemistry of the pigments themselves can still be detected.

Pasquali orders a special scan for the element copper, often used in green paint.

The scan reveals this dark area of the painting was once a lush garden, until the copper in the paint darkened.

PASQUALI: So we can see a lot of vegetable and leaves and plants and flower, and when you look on the surface of the work, they are not.

NARRATOR: While the beauty of these plants may suggest Leonardo's meticulous attention to detail, that's not enough to say for sure he painted it himself.

So the investigation turns to his brushwork.

One of the most characteristic fingerprints of a Leonardo are remarkably thin layers of paint, which can only be seen with a powerful microscope.

[speaking French] NARRATOR: Some Leonardos have been found to have as many as 30 layers of paint-- many more than most painters.

As she continues her restoration, Pasquali is looking for evidence of this unusual technique.

But what was Leonardo trying to achieve with all those thin layers?

Just ask a living painter.

FLORENT FARGES: Da Vinci was always looking for beauty.

He's not just painting or drawing a tree.

He wants to paint the perfect expression of what a tree is.

This aspiration to beauty is, to me, very inspiring as an artist.

(birds chirping) NARRATOR: Florent Farges is a painter in Dijon, France.

In the tradition of the Renaissance, Farges runs an artist's workshop, but with a twist.

FARGES: Hello, everyone, and welcome to a new video.

NARRATOR: His is a virtual one.

FARGES: This one is going to guide you through the entire process of classical figure painting.

NARRATOR: Most Italian painters at the time mixed their pigments into an egg base, using real egg.

But egg tempera doesn't allow as much light to pass through it, so there is less depth in the painting.

Instead, Leonardo decided to use an oil, like linseed or walnut.

DELIEUVIN: Leonardo was using oil.

Because oil helps to reproduce in the best way the transition between light and shadow.

NARRATOR: Gradually, Farges' portrait comes to life.

♪ For the finishing touches, Farges demonstrates how oil paint can be applied very thinly to create a subtle shading of light falling across the human body.

FARGES: If I want, I can come back later and put another layer on top of that, to make this transition very soft.

NARRATOR: Leonardo's techniques are still being taught today in his hometown of Florence.

To make their paintings come alive, artists strive to capture human flesh and the way light reveals its shape.

CECIL: Leonardo speaks about the smoky transition of light to shade.

That's how we perceive in nature.

The problem often with photographic images we see is that there's so much detail, we don't get the broader effect.

We see life very much out of focus-- we glance.

NARRATOR: Other artists of the day, like Sandro Botticelli, painted figures with hard outlines.

But Leonardo used his fine layers to create soft transitions, obscuring the lines.

This is his signature look, called "sfumato," from the Italian "fumo," or smoke.

Unquestionably, the most famous example of Leonardo's sfumato is that enigmatic smile of the "Mona Lisa."

DELIEUVIN: Just look at the mouth.

Look at the eyes.

You can't see lines.

You just see the movement of the light.

That's incredible, and there is no comparison with other artists at that time.

KEMP: There's no edge there at all.

It's all very uncertain.

This plays a psychological role, of course, because she is present but somehow not tangible.

She is idealized.

NARRATOR: For Leonardo, sfumato captured in two dimensions what he observed in the three-dimensional world.

But in order to get the skin just right, he had to go deeper-- to the muscles and tendons below.

Hold it like that.

NARRATOR: Trudy Van Houten has taught anatomy for 30 years.

Perfect.

VAN HOUTEN: Leonardo da Vinci constantly inspires me.

NARRATOR: She says the science of anatomy is beautiful.

SYLVAIN: Would you like me to cut that?

VAN HOUTEN: Yes, please.

NARRATOR: Though the process often is not.

VAN HOUTEN: Nice.

You've beautifully preserved that tiny little vessel.

NARRATOR: Leonardo dissected 30 bodies.

And with no refrigeration, it would have been especially unpleasant.

The intestines would've been a particular problem because they contain a lot of bacteria.

And even after death, the intestines become inflated, and larger and larger.

That's where things were going to go bad quickest, and smell the worst.

It's a very messy business.

NARRATOR: Many of the drawings from Leonardo's messy dissections today live on in the most refined of places: Windsor Castle, just outside of London.

Steps away from where Prince Harry and Meghan Markle posed for their wedding photos, more than 200 Leonardo drawings are secured in the Print Room.

Martin Clayton is the curator of those drawings.

CLAYTON: He couldn't help himself making a beautiful drawing.

But what most interested Leonardo was the structure, the machinery of the body.

And this particular drawing is one of the finest examples of Leonardo trying to understand how the shoulder works purely in mechanical terms.

There's no mystery of the body.

The body is a machine that can be looked at and analyzed in purely objective terms.

NARRATOR: The beauty of Leonardo's drawings is undeniable.

But in light of all that we've learned with the help of tools like the MRI, did he get it right?

VAN HOUTEN: If I were asked to grade his anatomical drawings, they would go from A to F. His drawing of the muscles, of things that he was directly observing and giving functional sense to, those I would give an A-plus.

In terms of some of the organs, I could not do so.

NARRATOR: One of Leonardo's most ambitious anatomical drawings is called the "Great Lady."

It is considered a masterpiece, but for Van Houten, it's a bit of a mess.

VAN HOUTEN: The feature I went to right away are strange structures flying out from the sides of the uterus.

They reminded me of carrots with tops.

CLAYTON: These strange sort of horn-like structures are ligaments observed by Leonardo in a cow.

Leonardo assumed that all mammals have the same structures.

He's sort of feeling his way into a field that had never been illustrated before.

NARRATOR: Leonardo's ground-breaking dissections certainly informed his art.

♪ He returned to this painting, "Saint Jerome," after 20 years, revising the neck to accurately portray the muscle beneath.

He did not revisit one of his earliest paintings, "Ginevra de' Benci," and it shows in what has been called the flatness of her face.

But by the time of the "Mona Lisa," Leonardo's knowledge of anatomy is beautifully convincing.

One intriguing page of Leonardo's notebooks shows several illustrations of human lips in exaggerated expressions, done from dissections.

ISAACSON: And it shows how each muscle and each nerve affects the lips, and at the very top is this tiny faint sketch, and you see the first sketch of what will be the smile of the "Mona Lisa."

NARRATOR: Anatomy and his painting technique explain in part how Leonardo infused the "Mona Lisa" with a lifelike quality.

But to complete the illusion, he needed to explore another area of science: how humans see.

GALLUZZI: Among the many aspects in which Leonardo was using his knowledge as a scientist to become a better painter is optics.

And optics is called by Leonardo "perspectiva"-- perspective.

FARGES: It's basic geometry, because when you have an object with parallel lines, they will seem to vanish into a point, which is called the vanishing point.

NARRATOR: Leonardo was fascinated by many aspects of how we perceive our world.

He even studied the composition of air to determine how atmosphere affects the appearance of objects in the distance.

Leonardo is trying to capture the complexity of the world.

But how can you paint something that you cannot see, like the transparency of air?

ISAACSON: Leonardo not only looked at mathematical perspective, but he looked at how colors change as you get further away, how the sharpness of something changes as you get further away from it.

NARRATOR: And did Leonardo also discover tricks of perception to pull off the greatest illusion of all: that elusive smile?

She's looking out, and her smile is a reaction triggered by the arrival of somebody.

This is the fiction that the painting tries to establish.

The great artists know how to draw you in, but not to tell you what to think.

They offer the tease.

NARRATOR: The ambiguity of Mona Lisa's smile is indeed part of her allure.

How did Leonardo pull that effect off?

That is a question that intrigued neurophysiologist Margaret Livingstone.

She studies the human visual system: how our eyes and brain operate together to make sense of the world.

LIVINGSTONE: As a neurophysiologist, I actually learn a lot from artists, because they study how we see.

I study how we see.

A lot of good art takes advantage of the computations your brain makes by exaggerating things that your visual system finds important.

NARRATOR: Human vision is among the best in the animal kingdom.

The center of our retina is packed with special photoreceptors that enable us to see details, or sharpness.

But away from the center-- toward the periphery-- there are fewer of those types of receptors.

We can see movement, but not detail.

LIVINGSTONE: Okay, now I want you to close your eyes.

I'm going to put up two version of the "Mona Lisa," one accurate and one distorted.

NARRATOR: To illustrate, Livingstone enlists her colleague Peter to see if he can spot a fake "Mona Lisa" using just his peripheral vision.

Okay, briefly open your eyes and look at the yellow spot, then close them right away.

And point to which is the accurate reproduction.

Open your eyes and see whether you chose the correct one.

♪ ♪ (chuckles) LIVINGSTONE: Point at the real version.

(laughs) Can I keep that?

(laughs) NARRATOR: Peter got only one of four "Mona Lisas" right, and Livingstone says that's not unusual.

LIVINGSTONE: Most people don't know how bad peripheral vision is, because as soon as something happens in their peripheral vision, they look at it, and then they bring the high-resolution part of their visual system onto it.

NARRATOR: In fact, our eyes are constantly moving-- three times a second, filling in the details.

The effect got Livingstone thinking: could this explain why the "Mona Lisa" sometimes seems to be smiling, and sometimes not?

Using a photo app, she blurs the image, like in our peripheral vision.

LIVINGSTONE: So I filtered the image in such a way that it would look like what you would see to your peripheral vision, knowing what I know about processing.

NARRATOR: The result?

LIVINGSTONE: She's grinning from ear to ear.

NARRATOR: As you look at the "Mona Lisa," your eye moves around the painting.

When you look away from her mouth, it enters your peripheral vision, and Mona Lisa appears to smile.

But look directly at the mouth, and the smile vanishes.

LIVINGSTONE: She seems like she's alive, because she looks different depending on where you're looking.

ISAACSON: Leonardo's paintings come alive because he understands human emotion, and because he has a good feel for the underlying science.

That combination comes together year after year as he's doing the "Mona Lisa" to make it such an interactive painting.

(people talking in background) (speaking French) NARRATOR: Back at the Louvre, Cinzia Pasquali has removed the old yellowed varnish from "Bacchus," uncovering the brilliant original colors.

It reveals an atmospheric perspective that suggests Leonardo's touch.

DELIEUVIN: Taking off these layers of darkened and yellowed varnish, we were able to rediscover the original forms, the quality of the blue.

It's a wonderful blue.

And see how the painter represent these cities with that effect of humidity, of what Leonardo called the atmospheric perspective.

NARRATOR: But Pasquali's investigation has also uncovered details like the harsh shading in the face, that don't show the characteristic sfumato fingerprint of Leonardo.

I can't see Leonardo's touch.

This is a little mechanical.

This line for the shadow is so hard, you know.

Leonardo don't do this.

NARRATOR: Pasquali and the team at the Louvre have solved a centuries-old mystery.

The "Bacchus" cannot be attributed to Leonardo.

♪ But that doesn't mean he wasn't involved.

Very often, his apprentices are actually painting the pictures, so he would conceive the general design of the work, and then the manual execution would be delegated to members of his workshop.

♪ NARRATOR: The restoration has succeeded in bringing much of the original beauty back to this painting.

But it also raises an intriguing question: should the same thing be done to the "Mona Lisa"?

DELIEUVIN: You have to imagine that under that varnish, you could see a wonderful blue sky.

Probably also the face or the hand are more pink, like natural skin.

ISAACSON: If we could just take that varnish off, we could see it the way Leonardo really did it.

But I think French governments have fallen for less cause than trying to take the "Mona Lisa" out of circulation and clean it.

NARRATOR: Perhaps there is another way.

Could she be given a digital makeover?

That is what Pascal Cotte is trying to do.

He has analyzed the "Mona Lisa" with a remarkably powerful camera and lights, which he demonstrates using a replica.

(device whirring) COTTE: We make the measurements in the basement of the Louvre, inside the laboratory.

It's very emotional, to have the painting in your hands without the frame.

You can look at this painting under this very intense light, that reveal everything that you cannot see usually.

♪ NARRATOR: Cotte's extremely detailed scan of the "Mona Lisa" and his analysis of the optics and chemistry of paint reveal how the colors may have changed over time.

It's not just the varnish that yellows and darkens, but the pigments and oil in the paint itself.

Cotte's challenge is to reverse-engineer the effects of that aging.

KEMP: This is not just photoshopping it and messing around with the colors, which you and I could do and get tolerable results, but this is based on pigment analysis.

NARRATOR: First, Cotte determines how much the varnish has darkened, and with his computer, peels it away.

(whirring) Next, he identifies what the color of each pigment would have looked like 500 years ago, and recreates them to see the colors just as Leonardo did.

COTTE: For example, we know that Leonardo make the sky with white lead and lapis lazuli.

So, we have software that remove the wrong colors to obtain the genuine color.

NARRATOR: Then, pixel by pixel, Cotte restores those colors.

Suddenly, a greenish sky becomes brilliantly blue, and a bit of flush comes back to Lisa's cheeks.

Finally, as the French say: voilà.

KEMP: Suddenly, she doesn't look like a submarine goddess.

She looks as if she's in the fresh air, which is just terrific.

NARRATOR: Cotte's restoration has brought Lisa back to life, at least digitally-- closer to the state that Leonardo saw her, allowing us all to see the painting's legendary beauty and the science it took: the geometry and optics of perspective; the anatomy behind her face; and the sfumato soft lines, capturing the mystery and movement of life.

But even with all the modern insights, the "Mona Lisa" is vastly more than the sum of her scientific parts.

Pinning down exactly why we are so drawn to her ultimately remains as elusive as her smile.

NARRATOR: Three years before his death, Leonardo was invited to France to live and work for the king.

He crossed the Alps by horse or mule, carrying three paintings.

Those paintings, including the "Mona Lisa," now hang at the Louvre, where the doors are about to open on the 500-year blockbuster Leonardo exhibition-- a celebration of a genius who fused together the worlds of art and science.

DELIEUVIN: Leonardo is an Italian Renaissance painter, but his genius is universal, and it speaks to everybody.

♪ BORGO: Leonardo wanted you to forget that you're looking at pigments on a piece of wood.

The idea is that you're looking at a real living, breathing being.

♪ ISAACSON: The key to Leonardo da Vinci is that he doesn't make a distinction between the beauty of nature that he studies in his science and the beauty of his art.

♪ He could have spent more time just being a painter.

But had he done that, he wouldn't have been Leonardo da Vinci, and he wouldn't have painted the "Mona Lisa."

♪ ♪ To order this program on DVD, visit ShopPBS or call 1-800-PLAY-PBS.

Episodes of "NOVA" are available with Passport.

"NOVA" is also available on Amazon Prime Video.

♪