Sep 1, 2020 7:00 AM

The Oysters That Knew What Time It Was

Scientists were convinced that biological clocks are predominantly driven by internal rhythms. There was just one problem—involving some mollusks and the moon.

Photoillustration of moon in night sky blending into an analogue clock

This story is adapted from The Human Cosmos: Civilization and the Stars, by Jo Marchant.

In February 1954 , a US biologist named Frank Brown discovered something so remarkable, so inexplicable, that his peers essentially wrote it out of history. Brown had dredged a batch of Atlantic oysters from the seabed off New Haven, Connecticut, and shipped them hundreds of miles inland to Northwestern University in Evanston, Illinois. Then he put them into pans of brine inside a sealed darkroom, shielded from any changes in temperature, pressure, water currents, or light. Normally, these oysters feed with the tides. They open their shells to filter plankton and algae from the seawater, with rest periods in between when their shells are closed. Brown had already established that they are most active at high tide, which arrives roughly twice a day. He was interested in how the mollusks time this behavior, so he devised the experiment to test what they would do when kept far from the sea and deprived of any information about the tides. Would their normal feeding rhythm persist?

For the first two weeks, it did. Their feeding activity continued to peak 50 minutes later each day, in time with the tides on the oysters’ home beach in New Haven. That in itself was an impressive result, suggesting that the shellfish could keep accurate time. But then something unexpected happened, which changed Brown’s life forever.

The oysters gradually shifted their feeding times later and later. After two more weeks, a stable cycle reappeared, but it now lagged three hours behind the New Haven tides. Brown was mystified, until he checked an astronomical almanac. High tides occur each day when the moon is highest in the sky or lowest below the horizon. Brown realized that the oysters had corrected their activity according to the local state of the moon; they were feeding when Evanston—if it had been by the sea—would experience high tide. He had isolated these organisms from every obvious environmental cue. And yet, somehow, they were following the moon.

For a while, Brown’s experiment became infamous, one of the most controversial results in biology. Scientists were just starting to appreciate that living processes vary according to environmental cycles such as the time of day, but every other major figure in the field was convinced these rhythms are ultimately driven by internal clocks; Brown’s lone insistence that organisms are plugged into mysterious cosmic cues was widely dismissed. The disagreement reflected a deeper, philosophical split regarding the relationship that living creatures have with our planet and the wider cosmos. Are we autonomous, self-running machines, or is life in constant, subtle communication with the Earth, sun, moon, and even stars?

Brown’s critics never relented, and his decades of work were thrown out as flawed. Conventional scientific accounts barely mention him except as a cautionary tale: a warning about the dangers of straying too far from common sense. The field of “chronobiology” has since exploded, with researchers uncovering intricate networks of molecular cogs and gears that keep time inside our cells, allowing virtually all creatures on this planet to anticipate the daily and seasonal movements of the sun. But there’s still a fundamental mystery at the heart of biological clocks that has never been explained. And the stubborn trickle of evidence hinting that Brown might have been onto something is fast becoming a flood.

That life on Earth moves in harmony with the sun’s daily path through the sky has been known for thousands of years. We wake in the morning and sleep at night. Flowers open and close depending on the time of day. Birdsong heralds the dawn.

But these daily cycles were generally seen as passive responses to changing environmental signals such as temperature or light. It wasn’t until 1832 that a Swiss botanist named Augustin de Candolle first suggested that sleep-wake movements in plants such as Mimosa might result from an internal timer.

By the early 1950s, a handful of other scientists were taking an interest in biological rhythms. In Germany, eminent botanist Erwin Bünning recorded the “sleep movements” of bean-seedling leaves, while physiologist Jürgen Aschoff discovered a 24-hour rhythm in human body temperature by experimenting on himself. In the United States, the British-born biologist Colin Pittendrigh started investigating insect rhythms after noticing daily cycles in mosquito activity while tackling malaria in Trinidad, and Romanian-born Franz Halberg entered the field after his drug test results were ruined by daily fluctuations in the levels of white blood cells in mice.

Whereas Brown was captivated by the influence of the moon, his rivals focused on 24-hour cycles. Whatever species they studied, they too found that in constant conditions, the rhythms continued. But in their experiments, the speed of the rhythms changed slightly in the absence of external cues, so that the peaks and troughs gradually drifted with respect to the solar day.

Different individuals ended up with varying cycle lengths—each close to, but not exactly, 24 hours. The researchers concluded that the rhythms must be driven by private, internal timers within the organism’s cells. Under normal conditions, the cycles were nudged by environmental cues such as light and temperature. But they were perfectly capable of running on their own.

At first, Brown thought this too. But he started to doubt it was possible. In his lab, crabs’ lunar and solar cycles persisted accurately for months, even when apparently isolated from the surrounding environment; he couldn’t imagine how an independent, internal clock could keep such good time. And then, in 1954, came the experiment with the time-shifting oysters. Despite being in a sealed darkroom, they had adjusted their activity according to the local movements of the moon. Instead of relying on inner timers, he was convinced they were sensing signals from the sky.

Brown decided to investigate the most fundamental biological process he could think of: metabolism. He studied sprouting potatoes—in experiments that ran for years—as well as bean seeds, mealworm larvae, chick eggs, and hamsters, shielding them all from changes in temperature, pressure, and light. Although they were supposedly cut off from the outside world, he saw patterns in their metabolic rate that matched not just the movements of the sun and moon, but pressure and weather changes in the Earth’s atmosphere. Even the potatoes “knew” not just the hour but the season of the year. It was as if life were pulsing in time with the planet.

Brown concluded that the organisms were sensitive to external geophysical factors, perhaps minute fluctuations in gravity, or even subtle forces that hadn’t yet been discovered. In his rivals’ experiments, supposedly proving the existence of independent clocks, Brown argued that the subjects weren’t cut off from the environment after all. They were bathed in—and influenced by—subtle, rhythmic fields that varied as the Earth turned.

Such ideas were viewed as threatening by his peers. Several of them had fought to have their own work on daily cycles taken seriously by other scientists. Their professional respectability hinged on using rigorous, reproducible methods, and basing their theories on impeccable physical principles of cause and effect; Brown’s claims of mysterious forces were dangerous nonsense that jeopardized the field. His measurements weren’t accurate enough, they insisted, or he was seeing patterns in his highly complex data that simply weren’t there. Yet Brown was charismatic and articulate, and he was swaying public opinion.

Something had to be done.

The first major blow came in 1957, with an extraordinary paper in the leading US scientific journal, Science, in which a respected ecologist named LaMont Cole claimed that by juggling random numbers, he had “discovered the exogenous rhythm of the unicorn.” The satire was aimed at Brown and his team, and its message was clear: Their results were as imaginary as the unicorn itself. It was an unprecedented, personal attack and it “hit us very hard,” Brown recalled later. “We were everywhere encountering innuendos from this article.” In 1959, Halberg followed up by coining the term that now defines the field: “circadian.”

It’s often said to refer to 24-hour cycles, but that isn’t quite right. It comes from the Latin meaning “about a day,” and Halberg chose it precisely to emphasize the key flaw in Brown’s theory: that most free-running daily rhythms are not exactly 24 hours long. Tensions came to a head in June 1960, at a prestigious conference on biological clocks held at Cold Spring Harbor, near New York City.

This event is now seen as chronobiology’s defining moment, at which Pittendrigh and the others set out their vision of circadian rhythms as internal and self-sustaining, controlled by oscillating biochemical mechanisms analogous to the cogs and gears of a clock. Everything was looking good for the young field, with its new terminology and a robust theoretical framework. There was just one problem: Brown. He wasn’t invited at first, but he went anyway, the only speaker to argue for a core pacemaker driven instead by cosmic cues. He faced a largely hostile audience.

One of Brown’s arguments came down to temperature. Everyone agreed that the timing of the biological rhythms was surprisingly resistant to even quite dramatic temperature changes. Crabs switch color and flies emerge from their pupae at the correct time, regardless of how hot or cold they are. Dried seeds stored in constant conditions still showed an annual rhythm in their capacity to germinate, whether kept at 20 degrees below freezing or 50 degrees above. Yet the speeds of biochemical reactions vary hugely with temperature, Brown pointed out; as a general rule, rates double with every 10 degree C rise. His rivals could provide no explanation of how any biochemical mechanism could create a clock that was immune to such influences, whereas external, unvarying cues driven by the sun and moon would explain this property perfectly. By insisting that an internal timer existed, he warned, they risked “chasing a ghost.” Pittendrigh retorted that it was Brown, with his mysterious, subtle influences, who was chasing ghosts.

After the meeting, Brown noticed that his papers were increasingly rejected, and that others in the field now no longer cited his research at all. According to Brown, Halberg eventually admitted that at around this time, his rivals privately agreed to block, ignore, or discredit him for the sake of the field’s development. Whether or not that’s correct, they certainly stepped back from engaging with Brown and his ideas; from then on it was almost as if he didn’t exist.

Brown and his cosmic cues were cast out, and the study of biological rhythms became the study of circadian clocks. The resulting field has since transformed our understanding of how life works. Aschoff, for example, embarked on a pioneering series of experiments to investigate what happens when people are cut off from the sun. After conducting pilot studies in an old World War II bunker, he built a dedicated isolation facility into a Bavarian hillside in 1964. Working with a physicist colleague named Rütger Wever, he shut students inside it for weeks at a time, tracking them with a battery of instruments including motion sensors and a rectal probe. The soundproof chamber was comfortable, with a sitting room, shower, and small kitchen, but all clues to the time of day—such as a clocks, radio, or telephone—were banished.

Aschoff himself was the first volunteer, observed by Wever. At the end of his 10-day stay, he was “highly surprised” to discover on release that his last waking time was 3 pm. After that, more than 300 volunteers “went underground” for three to four weeks each.

Just as in other species, Aschoff found that the volunteers’ daily rhythms continued even in constant conditions, showing that humans have innate circadian clocks too. When deprived of information from the outside world, the sleep-wake cycle usually lagged slightly slower than the solar day, with a period averaging around 25 hours.

Over the years, he and Wever showed that the cycles could be trained to follow signals such as bright light, temperature, and social cues. For a few of the volunteers, sleep patterns varied wildly, with day lengths reaching up to 50 hours, even though they didn’t realize it. But their physiology—such as body temperature or excretion of metabolites—almost always continued to oscillate within a narrow band of 24 to 26 hours. This meant that their sleep-wake patterns fell out of step with their physiology, a phenomenon that Aschoff called “desynchronization.” It was one of his most important discoveries—the first hint that there are multiple clocks in the body, which drive different functions, and that without appropriate external cues, they can become uncoupled. Volunteers reported feeling less well when this happened, leading Aschoff to warn that cutting ties with the sun, for example with regular shift work, might have damaging consequences for health.

The first clue to how the clocks actually work came across the Atlantic in 1971, from a Californian graduate student studying daily rhythms in fruit flies. Ronald Konopka isolated three mutant fly strains that lost the ability to keep time: one with a slowed-down rhythm of 29 hours, one with a too-short period of 19 hours, and one with no cycles at all. All three, it turned out, had different errors in the same gene, which was subsequently identified by other researchers in 1984. They named the gene “period,” and found that the protein it encodes rises and falls in abundance every 24 hours. At last, they had a glimpse of the machinery inside the biological clock. Chronobiologists had found their ghost.

Since then, many other clock genes have been identified. They encode proteins that regulate each other in a complex network of feedback loops, ultimately creating what Brown had thought impossible: a steady cycle that pulses roughly once each day, in time with the sun. Similar systems are found not just in fruit flies but in every type of life from bacteria to people. These sun clocks tell animals when to feed, when to run, when to sleep, and when to digest. They allow plants to ration their starch reserves through the night, and to get their photosynthesis machinery up and running for dawn. They tell fungi when to form spores; insects when to emerge from their pupae; and signal thousands of species of ocean plankton to sink before dawn and rise to the surface each night—the largest movement of biomass on the planet. By tracking the shifting times of sunrise and sunset, the clocks can also drive seasonal changes, telling organisms precisely when to migrate, molt, or reproduce.

Meanwhile, in humans, the study of circadian rhythms has become one of the hottest areas in medicine. Inner clocks regulate our sleep patterns, as well as body functions such as digestion, blood pressure, temperature, blood sugar levels, immune responses, and even cell division. As Aschoff warned, we ignore these rhythms at our peril. In the two centuries since the first artificial lights switched on, our lifestyles have become increasingly detached from the 24-hour cycle of sunrise and sunset. Many of us stay up late, work varying shifts, hop between time zones. We work in gloomy offices during the day and are exposed to light from computers, TVs, and smartphones at night. That is a problem, because although our body clocks can run independently, if they aren’t reinforced by external cues they can veer wildly off course.

In 2017, the field of chronobiology received the ultimate scientific recognition: a Nobel Prize, for the researchers who identified the period gene. “We on this planet are slaves to the sun,” commented the prominent biologist Paul Nurse. “The circadian clock is embedded in our mechanisms of working, our metabolism, it’s embedded everywhere.”

What, then, was the mysterious force that allowed Brown’s oysters to track the heavens? Scientists are increasingly recognizing the importance of the moon, too, as a synchronizing force in nature, through varying patterns of moonlight and its influence on ocean tides. But in this experiment, the oysters were shielded from these cues. Brown knew his rivals wouldn’t take him seriously unless he could suggest a mechanism. So he spent the summer of 1959 carefully monitoring the creepings of 34,000 snails, collected from the mud flats of the New England coast. He was astounded to find that the snails could distinguish between different compass directions.

Not only that, their preferred orientation varied over time, following both the solar and lunar day. He could influence or disrupt this behavior using magnets. Finally, he believed he could explain how animals might detect local time even in a sealed lab: They were sensing daily changes in Earth’s magnetic field.

This field is mostly generated by molten iron that circulates within Earth’s outer core. Overall, it’s shaped as if the planet contains a huge bar magnet, with north at one pole and south at the other. But it is also influenced by external factors such as weather and magnetic storms—as well as the movements of the sun and moon. Radiation from the sun ionizes atoms in the upper atmosphere, producing free electrons. Meanwhile the sun’s heat causes atmospheric tidal winds that move these charged particles across the Earth’s field lines. The resulting electric current creates its own magnetism: a 24-hour ripple superimposed on the larger magnetic field of the Earth. A similar, smaller ripple occurs every lunar day due to the gravity of the moon. These effects interact with each other, creating peaks and troughs during spring and neap tides. They’re also dependent on the amount of sunlight falling on the upper atmosphere, so they vary with latitude and with the seasons.

The Earth’s geomagnetic field is extremely weak, around a hundred times smaller than that of a standard fridge magnet, and the solar and lunar tides are even tinier. Brown was one of the very first researchers to suggest that animals might have a magnetic sense, and he had no idea how his snails might detect such subtle changes.

But he knew it could be clinching evidence for his theory of external cosmic cues. He excitedly presented his results at the biological clocks symposium in 1960, telling the audience that living things are fantastically sensitive to very weak magnetic fields. Although we can’t see it, we’re all immersed in an electromagnetic ocean, he insisted, with waves, tides, and ripples that shift according to the relative positions of the Earth, sun, and moon, keeping organisms in constant touch with the state of the solar system and the time of day.

The bombshell didn’t convince his rivals, though; in fact it hardened them against him. Just as they were setting out rigorous principles for the study of biochemical internal clocks, the notion of a subtle magnetic sense was beyond the pale. And yet, though they shunned Brown in public, they didn’t completely ignore his idea: quite the reverse.

Aschoff didn’t mention the shielding experiment or the apparent role of electromagnetic fields in any of his own papers on desynchronization.

What’s rarely mentioned today about Aschoff and Wever’s famous bunker, built just a few years later, is that it contained not just one underground apartment, but two. The parallel units were almost identical, with matching beds, kitchens, and record players. But there was a very important difference: One of them was completely enclosed within a hefty capsule of cork, coiled wire, glass wool, and steel, through which no electromagnetic radiation could pass; anyone living inside was completely cut off from the Earth’s magnetic field. The aim was to show that the shielding made no difference to the volunteers’ biological clocks, and prove, once and for all, that Brown was wrong.

Between 1964 and 1970, more than 80 volunteers stayed in the two units. As Aschoff predicted, their circadian rhythms did continue. But there was a problem; the results in the two groups were not the same. In the unshielded bunker, isolated from clocks and sunlight but still exposed to magnetic fields, people’s sleep and waking patterns departed from the solar day, reaching an average period of 24.8 hours.

But when magnetic fields were also blocked, the volunteers’ circadian cycles deteriorated further. Their day length slipped even longer. There was significantly more variation between individuals. And their different rhythms were much more likely to become uncoupled. As mentioned earlier, Aschoff championed desynchronization as one of his key discoveries. Yet over those six years, it only ever occurred in the shielded bunker, cut off from the Earth’s magnetic field. Wever found that if he exposed the volunteers to a similar artificial field, all of these effects were reversed.

The results proved that we do have an inner clock that runs independently, regardless of any electromagnetic information from the outside world. And yet, that clearly wasn’t the whole story. Even though the volunteers couldn’t consciously perceive the Earth’s vanishingly weak magnetism, the results suggested that their bodies could somehow sense it, and that this had a profound impact on the workings of their biological clocks. Wever published the data in a series of now-obscure papers in the 1970s; it was a “remarkable” result, he said, the first scientific evidence that humans are influenced by natural magnetic fields. But Aschoff didn’t put his name to them, and he didn’t mention the shielding experiment or the apparent role of electromagnetic fields in any of his own papers on desynchronization.

The existence of the second chamber was largely forgotten, and circadian rhythm research continued as if the magnetism experiment never happened.

Just as these researchers were ignoring any links to magnetic fields, however, other biologists were being forced to address their effects, despite the dubious connotations. These scientists were studying the impressive ability of many animals to navigate across the planet, from turtles and salamanders to birds and bees. How did millions of monarch butterflies each year find their way thousands of miles from North America to a particular patch of fir groves in central Mexico?

How did female loggerhead turtles, after growing up in the open ocean, return to lay their eggs at the very same beach where they hatched more than 10 years earlier? How did racing pigeons fly straight home from distant places they had never previously visited?

Since the 1950s, biologists had been realizing that many species are expert in deciphering celestial signals. Butterflies track the sun; moths follow the moon. Starlings orient north from the celestial pole around which the stars turn. Dung beetles roll their dung balls in straight lines by orienting against the glowing streak of the Milky Way. Animals often combine these visual cues with information from their circadian clocks, allowing them to compensate for the time of day. They are clued in to their place in the wider cosmos, using the circling heavens not just to tell the time, but to navigate around the globe.

But this wasn’t enough to explain the behavior of many species, some of which could still find their way even when the sky was overcast. It turned out that some detect patterns in the polarized light of sunlight and even moonlight, allowing them to pinpoint the sun or moon’s position even through clouds. Then in 1972, a German graduate student named Wolfgang Wiltschko showed that artificial magnetic fields, similar in strength to Earth’s, could disrupt or alter the direction in which robins tried to migrate. It was the start of a flood of evidence that animals, from pigeons and sparrows to lobsters and newts, are sensitive to the magnetic field lines generated as the Earth spins in space. Wood mice and mole rats use them when siting their nests; cattle and deer orient their bodies along them while grazing; dogs—for unknown reasons—prefer to point themselves north or south when they wee or poo. Other species, such as turtles, even appeared to have a magnetic map sense, telling them not just direction but position. Life, it seems, really is plugged into the invisible, electromagnetic world.

There was huge skepticism at first, of course. Natural magnetic fields were thought to be far too weak to influence biological tissue, so how could the signal possibly be detected? Well, life finds a way. Or, as it turns out, several ways. Fish have an electrical solution: They use networks of jelly-filled canals to measure the flow of current as they swim through a field. Another method involves physical forces. In 1975, researchers discovered “magnetotactic” bacteria that use chains of tiny magnetic crystals as compass needles, to steer themselves down magnetic field lines.

In 1978, German biophysicist Klaus Schulten suggested a third possibility after studying a class of obscure chemical reactions influenced by quantum effects. Electrons have a quantum property that physicists call “spin,” and Schulten was investigating how light energy can trigger the formation of short-lived pairs of “radicals”—molecules with lone electrons, which can spin in either the same or opposite directions.

These two spin states are chemically different, and the amount of time the electrons spend in each state can be influenced by magnetic fields. So even if a field is too weak to influence a chemical reaction directly, light creates an excited state in which it can then nudge the outcome one way or another. Imagine a fly unable to move a stone block by flying into it. If you balance the block on its edge, a fly striking at just the right position and moment might be enough to tip it and create a much larger effect.

It was an example of what everyone had thought impossible: a mechanism by which an extremely weak magnetic field can produce chemical cues large enough to be detected by the nervous system. “I thought, well, maybe that’s the internal compass the biologists were looking for,” said Schulten.

But no receptors capable of forming radical pairs were known in living organisms, and when he submitted his theory to the prominent journal Science, it was swiftly rejected. “A less bold scientist,” said one reviewer, “would have designated this piece of work for the waste paper basket.”

Two decades later, biologists studying fruit flies discovered proteins called cryptochromes, which form radical pairs when exposed to blue light. Cryptochromes are now known to be common in organisms from plants to fish; they’re found in insect antennas, and the retinas of mammals and birds. And there’s good evidence in several species that cryptochromes are indeed involved in magnetosensing and navigation. Researchers have suggested that they enable birds to “see” magnetic field lines, perhaps by perceiving a brighter image if they are facing in a certain direction.

Humans have cryptochromes too. Until recently, most scientists agreed that people can’t sense magnetic fields. But in 2011, researchers put the human cryptochrome protein into fruit flies that lacked their own version, and found that it restored the flies’ magnetosensing ability perfectly. The finding hints that Wever was right: Even if we don’t consciously perceive it, our bodies are sensitive to magnetic fields. And here’s the really interesting thing: Cryptochromes are actually best known not as magnetosensors but for quite a different reason. They are also crucial components of biological clocks.

This discovery that biological clock machinery is sensitive to magnetism is still very new, and it’s not yet clear precisely if or how magnetic fields are influencing our sense of time. One theory is that at least some species tell the time using daily tidal variations in Earth’s field, just as Brown originally suggested. Others think the link may relate to how clocks resist temperature changes: a question posed by Brown and never fully answered. If you lose temperature compensation, you’d expect the body’s rhythms to continue but to become less stable, more variable, and to start uncoupling, just as Wever found in the bunker shielded from magnetic fields.

Perhaps it is an external cue after all—the Earth’s magnetic field, as influenced by the sun and moon—that enables biological clocks to run regardless of temperature: not necessarily driving behavior directly, but providing the fundamental “tick” of the clock.

From The Human Cosmos: Civilization and the Stars, by Jo Marchant, published by Dutton, an imprint of Penguin Publishing Group, a division of Penguin Random House, LLC. Copyright © 2020 by Jo Marchant