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11 epic mysteries scientists totally can’t solve

What is the universe made out of? When did the anus evolve? Can humans live to 150 years old? And more!

Brian Resnick is Vox’s science and health editor, and is the co-creator of Unexplainable, Vox's podcast about unanswered questions in science. Previously, Brian was a reporter at Vox and at National Journal.

To investigate some of the biggest mysteries in science, you have to venture to some pretty far-out places: the bottom of the oceans, inside the human brain, the tops of mountains, and even the end of time.

That’s what we’ve done on Unexplainable, a science podcast that Vox launched in March to explore the most important, interesting, and awe-inspiring unanswered questions in science. We set out to ask big questions that inspire scientists to do their work — questions that fill them with wonder or a sense of purpose, or remind them that the universe is still an enormous place with untapped potential.

In exploring these stories, we’ve learned some of the surprising reasons why major scientific mysteries can go unsolved for years or even decades: Some are due to the limits of technology, others are because of human failings. Regardless, working on Unexplainable has reminded us there’s hope in a question. Why ask one if you don’t believe an answer is possible?

Here, we rounded up 11 questions that astounded us the most.

For more mysteries, subscribe to Unexplainable wherever you listen to podcasts.

What is most of the universe made out of?

It’s a simple question that’s also bafflingly unanswered: What makes up the universe? It turns out all the stars in all the galaxies in all the universe barely even begin to account for all the stuff out there. Most of the matter in the universe is actually unseeable, untouchable, and, to this day, undiscovered. It’s called dark matter, and despite searching for it for decades, scientists still have no idea what it is.

Further reading: Dark Matter, unexplained

What lives in the ocean’s “twilight zone”?

As you dive deeper into the ocean, less and less sunlight shines through, and about 200 meters beneath the surface, you reach an area called the “twilight zone.” Sunlight fades almost completely out of view, and our knowledge about these dark depths fades too.

“It’s almost easier to define it by what we don’t know than what we do know,” Andone Lavery, an acoustician at the Woods Hole Oceanographic Institution, told Vox’s Byrd Pinkerton.

Yet this region of the ocean is extremely important. It’s possible — but not certain — that there are more fish living in the twilight zone than the rest of the ocean combined, and creatures of the dark ocean play a large role in regulating the climate.

Further reading: “It’s deep. It’s dark. It’s elusive.” The ocean’s twilight zone is full of wonders.

What killed Venus?

“Hellscape” is the most appropriate word to describe the surface of Venus, the second planet from the sun. At 900 degrees Fahrenheit, it’s the hottest planet in the solar system, thanks in part to an atmosphere of almost entirely carbon dioxide. Clouds of highly corrosive sulfuric acid are draped over a volcanic landscape of razor-sharp lava flows. Most crushingly, the pressure on the surface of Venus is about 92 times the pressure you’d feel at sea level on Earth.

Yet some scientists suspect Venus was once much like Earth, with a liquid water ocean like the ones that support life on our planet. This prompts an existential question for life on Earth. “It really is a question about why are we here,” says Robin George Andrews, volcanologist and author of Super Volcanoes: What They Reveal about Earth and the Worlds Beyond.

“Venus and Earth are planetary siblings,” Andrews says. “They were made at the same time and made of the same stuff, yet Venus is apocalyptic and awful in every possible way. Earth is a paradise. So why do we have a paradise next to a paradise lost?”

There are two leading hypotheses. One is that the sun cooked Venus to death. The other is that volcanoes did.

Further reading: Venus could have been a paradise but turned into a hellscape. Earthlings, pay attention.

What will animals look like in the future?

It’s impossible to completely predict how evolution will play out in the future, but that doesn’t mean we can’t try. Reporter Mandy Nguyen asked biologists and other experts to weigh in: What could animals look like a million years from now?

The experts took the question seriously. “I do think it’s a really useful and important exercise,” Liz Alter, professor of evolutionary biology at California State University Monterey Bay, told Nguyen. In thinking about the forces that will shape the future of life on Earth, we need to think about how humans are changing environments right now.

Further reading: The animals that may exist in a million years, imagined by biologists

What causes Alzheimer’s?

There is no cure for Alzheimer’s, a neurodegenerative disease that causes dementia, and no highly effective treatments, despite decades of research. Why? For one thing, scientists don’t have a complete understanding of what causes the disease.

For years, the prevailing theory has been that Alzheimer’s is caused by pile-ups of proteins called amyloids, which effectively create plaques in the brain. But drugs that help clear amyloids from the brain don’t seem to work very well in combating the disease.

Some scientists think Alzheimer’s researchers have been too focused on this one theory, at the expense of studying other potential causes, like viral infections.

Further reading: The new Alzheimer’s drug that could break Medicare

How is a brainless yellow goo known as “slime mold” so smart?

Slime mold is an extremely simple organism that is also extraordinarily complex.

Technically, they are single-celled organisms. But many individual slime mold cells can fuse themselves together into a huge mass, capable of, well ... thinking.

Slime mold can solve mazes and seems to be able to make risk-benefit decisions. There’s even evidence that slime mold can keep track of time. They do this all without a brain or even a single brain cell. Whatever mechanism allows slime mold to solve these problems, it’s evolved in a manner different from humans. How exactly do they do this? And what can it teach us about the nature of intelligence?

Further reading: Hampshire College promoted a brainless slime mold to its faculty. And it’s working on border policy.

What’s the oldest possible age a human can reach?

Is the first human to live to 150 years old alive today? We don’t know. On average, the human lifespan has risen over the decades in most of the world, but it’s unclear if there’s a ceiling. Could a human live into their second century? The technology and medicine that could make that possible may already be in development. But if it works, there will be unsettling questions for societies to answer.

Further reading: Science reporter Ferris Jabr’s piece “How Long Can We Live?” for the New York Times Magazine inspired this episode.

Are long-haul symptoms unique to Covid-19?

Millions of people around the world have dealt with long-term symptoms of Covid-19 for weeks or months after their initial infection has cleared. Some scientists say these “long-haul” symptoms are not unique to Covid. Instead, they argue that many types of viral infections can leave people with long-term symptoms, which often can go under-recognized in medicine. The question is: What connects all of these long-haul symptoms?

“It has always been [and] is the case that patients who get sick experience high levels of symptoms like those described by long-Covid patients,” Megan Hosey, assistant professor at the Johns Hopkins Department of Physical Medicine and Rehabilitation, told Vox’s Julia Belluz. “We have just done a terrible job of acknowledging [and] treating them.”

Further reading: The nagging symptoms long-haulers experience reveal a frustrating blind spot in medicine.

Why don’t doctors know more about endometriosis?

In people with endometriosis, tissue similar to what grows inside the uterus grows elsewhere in the body. It’s a chronic condition that can be debilitatingly painful. Yet doctors don’t fully understand what causes it, and treatment options are limited.

Worse, many people with endometriosis find that doctors can be dismissive of their concerns. It can take years to get an accurate diagnosis, and research into the condition has been poorly funded.

Vox reporter Byrd Pinkerton highlighted how frustrating it can be to suffer from an often-ignored, chronic condition. “It’s just so, so, so soul-crushing to just live in this body day in and day out,” one patient told Pinkerton.

Further reading: People with endometriosis experience terrible pain. There’s finally a new treatment.

Why do we have anuses — or butts, for that matter?

This is a question we never even knew we wanted to answer — until we heard the Atlantic’s Katherine Wu explain that “the appearance of the anus was momentous in animal evolution.” Before the appearance of the anus, animals had to eat and excrete through the same hole. The anus allowed for a more efficient system, and allowed animal life on Earth to grow bigger and take on new shapes and forms.

But scientists don’t have a complete picture of the evolutionary history here; they don’t know which creature developed the anus first, and when. “It’s so hard to study something that must be millions and millions of years old and doesn’t fossilize,” Wu says.

And then there’s a whole other question: Why is the human butt so big, compared with other mammals?

Further reading: Katherine Wu’s “The Body’s Most Embarrassing Organ Is an Evolutionary Marvel,” at the Atlantic.

What the heck is ball lightning?

For millennia, people have been telling stories about mysterious spheres of light that glow, crackle, and hover eerily during thunderstorms. They’ve been spotted in homes, in rural areas, in cities, on airplanes, and even passing through windows.

They seem out of this world, but scientists believe they are very much of this world. These apparitions are called ball lightning, and they remain one of the most mysterious weather phenomena on Earth.

Ball lightning usually only lasts for a few moments, and it’s impossible to predict where and when it’ll show up. You can’t hunt ball lightning and reliably find it. Ball lightning finds you.

It’s rare, but many people have seen it. Scientists don’t know exactly where it comes from, but that hasn’t stopped them from trying to make it themselves, in their labs.

Further reading: Ball lightning is real, and very rare. This is what it’s like to experience it.

And so many more...

Those are just 11 of the mysteries we’ve explored in Unexplainable. There are so many more! They include questions like: Can we predict when tornadoes will form? Where does all the plastic go in the ocean? Why do some people think they can talk to the dead? What’s the deal with “Havana syndrome”? How will the universe end? How tall is Mount Everest? Why does the placebo effect work? Find all the episodes here.

If you have ideas for topics for future shows, send us an email at

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