It seems like a simple question: how many chromosomes do human beings have? But for various reasons, getting an accurate count proved surprisingly hard for much of the last century. In fact, virtually every textbook once cited an incorrect number, until 1956 when a fiery Indonesian scientist finally determined the true count—and had to battle his boss over who would receive credit for this legacy-making discovery.

About The Disappearing Spoon

Hosted by New York Times best-selling author Sam Kean, The Disappearing Spoon tells little-known stories from our scientific past—from the shocking way the smallpox vaccine was transported around the world to why we don’t have a birth control pill for men. These topsy-turvy science tales, some of which have never made it into history books, are surprisingly powerful and insightful.

Credits

Host: Sam Kean
Senior Producer: Mariel Carr
Producer: Rigoberto Hernandez
Associate Producer: Sarah Kaplan
Audio Engineer: Rowhome Productions

Transcript

Biologist Joe Hin Tjio stormed into his boss’s office one day in 1956, waving a copy of a paper they’d recently written.

It certainly wasn’t the worst day of Tjio’s life. He’d spent three years in a concentration camp being tortured during World War II. It’s hard to get worse than that.

But Tjio was still furious. The paper concerned human chromosomes. Tjio thrust the paper in his boss’s face, shaking with rage.

“Why are you first author, and not me?,” he demanded.

His boss, Albert Levan, tried explaining. But Tjio wouldn’t back down. And things escalated quickly. Chio threatened that if Levan didn’t make him first author he would destroy their lab’s research.  He’d trash all the cells they used, all the slides, everything.

Levan sat there stunned. Was Tjio serious?

He was. Tjio was tired of being pushed around. And if he couldn’t be first author on this paper, he was absolutely willing to go nuclear.

To understand what made Joe Tjio so angry, we have to go back to the work of another, older biologist named Theophilus Painter. 

Painter lived and worked in Texas. At the lab bench, he was known as a tinkerer. He once said that every good scientist should be able to take apart a Model T and repair it with nothing but pliers and some wire.

In the early 1920s, Painter determined that mammals use the X and Y chromosomes to determine sex—a major discovery. But he’s primarily known today for a highly embarrassing mistake.

In 1923, Painter began investigating a deceptively simple question: how many chromosomes do human beings have?

Chromosomes are bundles of DNA in our cells. All animals have a different number, and that number can vary widely. Some ants have one chromosome. Koalas have 16. Cats have 38, dogs 78. The atlas blue butterfly has around 450. There’s a fern with 1440 chromosomes. 

But for decades, biologists didn’t know how many chromosomes humans had. Guesses ranged from 8 to 64. Now, you might be thinking, “Wait. How hard can this be? Just get a cell, find the chromosomes, and start counting.”

If only it were that easy. 

First of all, chromosomes are tiny—visible only under microscopes. They’re also the same color as the rest of the cell. You have to dye them to make them stand out, and even then, they’re hard to see.

Worst of all, chromosomes in cells are normally long and skinny. They’re like spaghetti noodles, only millions of times longer. They squiggle and overlap and twist all around each other. It’s hard to know where one stops and another begins. Imagine being handed a bowl of spaghetti and having to guess how many noodles were in it. Would you even get close? That’s essentially what biologists faced when counting chromosomes.

But there was one trick. As you might know, cells divide sometimes. You might remember pictures from high school biology. A cell copies its chromosomes. Then all the chromosomes line up in the middle of the cell and get pulled opposite directions.

The key point is that during this stage of division, chromosomes are far more compact. They cinch together, they tighten up. Not completely. There’s still some spaghetti overlap. But it is easier to count than before. 

So that’s what Theophilus Painter decided to do—find human cells that were dividing, then inject wax into them to gum things up and freeze them. Then he could try counting chromosomes.

The only problem was that adult cells don’t divide very often. They mostly just sit there. In fact, the only real exception to this rule is the cells in the testicles that produce sperm cells. 

Men produce a lot of sperm. Millions per week. And the sperm precursor cells in the testes are constantly dividing like crazy. So if Painter wanted to catch cells mid-division, testicles cells were his best bet. 

But this only introduced other problems. Those testicle cells had to be fresh. After death, chromosomes clump together, which again makes it hard to count them. So Painter needed very fresh cells, harvested right after someone died.

To compound the problem, people just didn’t donate their bodies to science in the early 1900s. Dissection was considered taboo, which made securing human tissue nearly impossible.

To get around this taboo, biologists did scandalous things. Some actually lurked near the gallows when criminals got hanged, and harvested their testicles. 

Painter drew on another squeamish source. A former student of his worked at a local insane asylum. Doctors there sometimes castrated inmates—surgically removed their testicles. So Painter hit his former student up.

In 1923, the student castrated three men. In each case, he quickly diced up the testes, then dunked them in preservative fluid within thirty seconds of their removal. Afterward, he rushed them to Painter’s lab. Painter had no other way to get fresh material.

Of those three castrated men, two were Black, one was white. After injecting the cells with wax, Painter sliced them into thin microscope slides with a special knife he’d invented that consisted of stacked razor blades.

Unfortunately, if you’re trying to count something that’s already hard to count, it’s not a great idea to chop it up into pieces—as Painter discovered the hard way when he studied his slides. Things were still messy. Sometimes he counted 46 chromosomes, sometimes 48. He kept counting and recounting, making himself cross-eyed following the spaghetti strands—and he still couldn’t decide. 

He finally took a deep breath and made an educated guess. He published a paper declaring that humans have 48 chromosomes.

Biologists were happy to have the number resolved, even on what amounted to a coin-flip. And Painter’s paper did have one positive effect. It established that Black people and white people have the same number of chromosomes. That refuted a nasty theory going around that Black people had fewer and might therefore be a different species. Painter declared otherwise.

After that, 48 became enshrined as the standard number for humans, and Painter’s results began appearing in textbooks. And they would continue to appear year after year, decade after decade—until Joe Tjio got involved.

Tjio was born on the island of Java in 1919. He lived under Dutch colonial rule there, and he could speak French, German, English, Dutch, and a native Javan language. His father worked as a photographer, and Joe grew up helping out in the darkroom. But he gravitated more toward science, and by the 1940s, he was working as a research biologist, focused on breeding disease-resistant potatoes. 

That research stopped abruptly in 1942 when Japan invaded Java during World War II. As someone of Chinese ethnicity, Tjio was thrown into a concentration camp and tortured. Despite this brutal treatment, he spent his time comforting fellow inmates. He even knitted underwear and sweaters for them to replace their ragged clothes—an act of decency in a ghastly place.

After World War II ended, Tjio quit Java and took a Red Cross relief ship to Holland. After recovering his strength, he resumed doing scientific research, bouncing around to labs in Copenhagen, Spain, and Sweden. 

It was in Sweden where he met Albert Levan, at a university in Lund. He and Tijo began collaborating, with Levan as the senior scientist and Tjio the junior technician. Over the next decade, they published five papers, always with Levan as first author.

Levan had started his career on plants, breeding sugar beets and clover. By 1955, he was studying how certain chemicals damaged the roots of plants. Specifically, the chemicals damaged the root cells’ chromosomes. 

And something about that damage struck Levan. It looked identical to the damage seen in the chromosomes of cancer cells. This intrigued Levan. So he decided to study the links between chromosome damage and cancer. He asked Tjio to join him. 

Now, in 1955, the study of chromosomes had advanced a lot since Theophilus Painter’s day. Biologists had new dyes that made chromosomes easier to see inside cells.

Biologists had also invented a preparation technique called the squash. Instead of infusing cells with wax and slicing them, you smooshed them under a slide. This kept chromosomes whole and intact.

Levan had found a neat trick as well. The crocus plant produces a chemical called colchicine. Colchicine happened to arrest cells right when they started dividing. Just sprinkle a little in, and cells froze right when the chromosomes were the most compact and most easy to see. 

Perhaps most important of all, Tjio and Levan didn’t need to lurk near the gallows to get human tissue. Sweden was a rare country back then where abortion was legal, and Levan had access to fetal tissue. 

That was important. Again, beyond sperm cells, adult cells in humans don’t divide often. But fetal cells do. As the fetus grows, cells multiply like mad. So with fetal cells, Tjio and Levan had lots of chances to catch cells dividing. Then they could freeze them with colchicine.

Now, it’s not clear why Tjio began counting chromosomes in the fetal cells. Perhaps just as a warm-up exercise. You know, make sure everything looked right before they moved on to more important matters. 

But that’s not how things worked out. The warm-up exercise became the prize, the most important aspect of the entire project. And it would destroy the two men’s friendship in the process.

Joe Tjio was a night owl, often working straight through until dawn. He also worked through holidays. So there was nothing unusual about him firing up his microscope at 2am a few days before Christmas in 1955. 

He began examining slides of fetal lung cells. After working in his father’s darkroom as a child, he still loved photography, and he used a special camera to snap pictures of what he saw through the scope. Then he started the warm-up counts. How many chromosomes were there?

To his confusion, he found just 46. That puzzled him, so he grabbed a photograph of a different slide, and counted that one. 43, 44, 45 … and got 46 again. Huh.

So he grabbed another photo and another. He eventually counted over 250 slides. By the end of which, he was certain: Theophilus Painter and all the textbooks were wrong. Humans didn’t have 48 chromosomes. They have 46.

Just try to imagine the thrill here! Tjio had had a solid but unspectacular career before this, working under Levan’s shadow. Now, at age 36, he’d discovered something epochal. It’s what scientists call a “golden moment”—that heart-pounding instant when they know something that no one else in history ever has. 

And Tjio surely would have rushed to tell Levan this. Except Levan was on vacation at the time, nowhere near the lab. Tijo waited impatiently for the holiday break to end, then told him. Levan was thrilled as well, and they agreed to rush something into print.

For whatever reason, Levan took the lead writing the paper. And when he showed a draft to Tjio, Tjio was shocked to find that Levan had listed himself as first author.

Now, why was this such a big deal? Because credit for discoveries means prestige for scientists. It’s their currency. Scientists often work long hours for lousy pay. Credit for discoveries is the one thing they have—and here Levan was trying to usurp credit for Tjio’s discovery.

When Tjio asked what the hell, Levan got patronizing. He reminded him that that’s just the way things were done. Senior scientists always got top billing—as Levan had on their previous five papers. 

But this sixth time, Tjio put his foot down. He’d been toiling away at 2am all by himself while Levan was off drinking eggnog and singing Christmas carols. Tjio snapped and told Leven that if he wanted credit, he should have been in the damn lab himself.

Annoyed, Levan pushed back. He asserted his seniority again.

So Tjio decided to go scorched-earth. He threatened to destroy all the slides, all the cells—everything, if he didn’t get his name first.

Talk about a tantrum. But however indignant, Levan backed down. He let Tjio switch their names, and thereby secure his place in history.

But Levan’s capitulation couldn’t save their relationship. Tjio couldn’t trust Levan anymore. And Levan resented Tjio, especially after their paper’s publication made Tjio a scientific star. 

So Tjio skipped out to the United States, which had less hierarchy in its labs. Tjio ended working 37 years at the NIH in Maryland, mostly on cancer and genetics. Along the way, President John F. Kennedy gave him a medal for his work.

Looking back on Tjio’s discovery, it’s kind of shocking how long it took. Remember, it happened in 1956. Scientists by then had already discovered the famous double helix of DNA. But we still couldn’t do something as simple as count the number of chromosomes we have. If Tjio had not made the correct count, biologists could conceivably have gotten all the way to the Human Genome Project in 2001 without knowing.

And if that sounds far-fetched, remember: Authority casts a very strong spell on humans. It blinds us to what we can see. Tjio actually went back later and looked in old textbooks at pictures of human chromosomes. And with his eyes opened, he could clearly see just 46. But people before him couldn’t see what was right in front of them.

For his part, Theophilus Painter was mortified to know that he’d overcounted. The human chromosome count was supposed to be the seminal discovery of his life—what he was known for—and it was completely wrong. Talk about embarrassing.

Tjio’s work on human chromosome number eventually opened up several avenues of research. One involved cancer, since again, cancer cells often have abnormal chromosomes.

Another involved human evolution. Even though humans have 46 chromosomes, our closest ape relatives all have 48 chromosomes: chimpanzees, gorillas, orangutans. It’s a fundamental biological difference between humans and other apes.

And if you’re wondering how that’s possible—how you just lose two chromosomes—I’ve actually put together a bonus episode at patreon.com/disappearingspoon. It’s a fascinating glimpse into the emergence of humankind.

The bonus also details a bizarre case from China of a man who has only 44 chromosomes—two fewer than most people. And the kicker is, he’s perfectly healthy, a medical marvel. All that and more at patreon.com/disappearingspoon.

Tjio’s work on human chromosome number also opened research into genetic disorders that involve people having extra chromosomes. 

In fact, just three years after Tjio’s discovery, scientists in France built on his work to prove that Down syndrome results from an extra copy of chromosome 21. 

Unfortunately, that discovery also involved a senior scientist allegedly stealing credit from an underling. And this dispute got even more heated than Tjio and Levan’s. Even a half-century after the initial work, it was still raging—to the point that the underling’s opp onents sent law officers storming into a scientific meeting where she was speaking, using bullying and harassment that shut the meeting down and silence her.

These opponents were essentially using the law to censor science—something that smacks of the Inquisition. And indeed, the man behind all this is now in line to become an official Catholic saint. It’s a wild story. And we’ll hear all about it in next week’s episode.