How Was Astatine Discovered? From Prediction to Synthesis

Astatine was first synthesized in 1940 by three scientists at the University of California, Berkeley, who bombarded bismuth with alpha particles in a cyclotron, but the path to that moment stretched back more than seven decades. Dmitri Mendeleev’s periodic table had predicted the element’s existence in the 1870s, and at least four groups of researchers claimed to have found it in nature before the Berkeley team finally produced it in the lab. The story of element 85 is less a single eureka moment and more a decades-long collision between theoretical confidence, experimental frustration, and the brute reality that this element barely exists in nature at all.

The Empty Box in Mendeleev’s Table

When Mendeleev published his periodic table in 1869 and refined it in the years that followed, one of the gaps sat directly below iodine. The logic of the table demanded that a heavier halogen should exist, one that would share chemical family traits with fluorine, chlorine, bromine, and iodine but would be heavier and likely more metallic in character. Mendeleev called this hypothetical substance “eka-iodine” and predicted some of its basic properties: it should be the heaviest halogen, it should form compounds analogous to those of iodine, and it should sit at roughly atomic number 85 once that concept was formalized decades later.

This prediction was not unusual for Mendeleev. He had successfully predicted several missing elements, and those predictions had been vindicated when gallium, scandium, and germanium were discovered in the following decades. Eka-iodine, however, proved far more stubborn. The reason, which nobody could have understood in the 1870s, was that element 85 has no stable isotopes. Every form of it is radioactive, and every form decays quickly. That fundamental instability made it almost invisible to the experimental techniques available for most of the next century.

Decades of False Alarms

Between the 1930s and the early 1940s, multiple research groups announced that they had detected element 85. These claims generated excitement each time and skepticism soon after. In 1931, the American chemist Fred Allison reported finding element 85 using a magneto-optical technique he had developed, and the proposed element was briefly given the name “alabamine” after his home state of Alabama. The technique, however, turned out to be unreliable, and other laboratories could not reproduce the results. The name was quietly shelved.

A Romanian physicist, Horia Hulubei, and a French chemist, Yvette Cauchois, claimed in 1936 to have detected element 85 in mineral samples using X-ray spectroscopy. They proposed the name “dor,” a Romanian word meaning longing. Their measurements were also contested. The X-ray lines they reported could be explained by nearby elements, and the scientific community remained unconvinced. Around the same time, the Indian physicist Rajendralal De similarly reported finding the element in monazite minerals. None of these claims held up under scrutiny.

A separate line of investigation came from researchers studying natural radioactive decay. In 1942, Berta Karlik and Traude Bernert in Vienna published work arguing that element 85 should appear as a short-lived intermediate in the natural decay of thorium and other heavy elements. Earlier, a team working with radiothorium had also attempted to separate element 85 from decay products, reasoning that certain isotopes in the thorium decay chain should undergo the type of radioactive decay that would briefly create atoms of element 85.¹ These natural-occurrence studies turned out to be correct in principle: astatine isotopes do appear fleetingly in uranium and thorium decay chains. But the amounts are so vanishingly small that the element could not be isolated, characterized, or studied through natural samples alone.

The Berkeley Breakthrough of 1940

The discovery that stuck came from a completely different approach: instead of looking for element 85 in nature, three researchers decided to make it. In 1940, Dale R. Corson, Kenneth Ross MacKenzie, and Emilio Segrè at the University of California prepared isotope 211 of element 85 by bombarding bismuth with alpha particles accelerated in the 60-inch cyclotron of the Radiation Laboratory.² Segrè was already famous for co-discovering technetium, the first artificially produced element, in 1937. The team at Berkeley applied the same philosophy: if nature would not hand you an element in usable quantities, you could create it with a particle accelerator.

Bismuth was chosen as the target for a straightforward reason. Bismuth has an atomic number of 83, and alpha particles (helium nuclei) carry an atomic number of 2. Smashing them together at sufficient energy can fuse the two nuclei and, after the new nucleus ejects a couple of neutrons to stabilize itself, you end up with an atom of element 85. The specific nuclear reaction produces astatine-211, an isotope with a half-life of about 7.2 hours. That half-life was long enough for the Berkeley team to confirm the new element’s existence and begin characterizing some of its chemical behavior before it decayed away.

The team did not formally name the element until 1947, when they published a more detailed account of its properties. They chose “astatine” from the Greek word astatos, meaning unstable, a fitting name for an element that refuses to stick around.

How the Synthesis Works

The nuclear reaction at the heart of astatine production is still the standard method today. Natural bismuth, which conveniently exists as a single stable isotope (bismuth-209), serves as the target. Alpha particles are accelerated to energies of roughly 28 to 29 MeV and directed at the bismuth target.³ When an alpha particle hits a bismuth nucleus with enough energy, the two merge briefly, and the resulting compound nucleus promptly spits out two neutrons, leaving behind astatine-211.

The reaction can be performed in reasonable yield using straightforward methods, and bismuth is cheap and abundant.⁴ The bottleneck is the cyclotron itself. Most medical and research cyclotrons produce protons or deuterons for making common medical isotopes, but generating alpha particles at the required energy demands a larger, more specialized machine. Only a limited number of cyclotrons worldwide are capable of accelerating alpha particles above 28 MeV with the beam intensity needed for useful quantities of astatine-211.⁵ This equipment limitation is the single biggest reason astatine remains difficult to work with more than 80 years after its discovery.

Energy tuning matters, too. If the beam energy is too high, the reaction produces astatine-210 as a contaminant, which is undesirable for medical applications because it decays into polonium-210, a notoriously toxic alpha emitter. Research has shown that keeping the beam energy just below about 29 MeV provides a large increase in useful yield while maintaining sufficient purity of the astatine-211 produced.³

Astatine in Nature

Although the Berkeley synthesis is considered the official discovery, astatine does exist in nature in spectacularly small amounts. Several of its isotopes appear as fleeting intermediates in the natural decay chains of uranium and thorium. When radium-219 or radium-223 undergoes alpha decay, for example, the daughter products can include short-lived astatine isotopes like astatine-215, astatine-217, and astatine-218. These isotopes have half-lives measured in fractions of a second to a few seconds, so they exist only as momentary blips in an ongoing cascade of nuclear transformations.

Estimates of how much astatine exists on Earth at any given instant vary, but the commonly cited figure is around 25 grams across the entire planet’s crust. That would make it the rarest naturally occurring element. To put that in perspective, if you gathered every atom of natural astatine on Earth into one spot, you would have a speck too small to see. This extreme scarcity is why the pre-1940 detection attempts were so difficult and why synthesis remains the only practical way to obtain astatine for study.

An Element That Defies Its Own Family

Mendeleev predicted eka-iodine would behave like a heavier version of iodine, and in some respects that is true. Astatine sits in the halogen group and can form halide-like compounds. But the more scientists have studied it, the more they have found that astatine breaks the rules expected of a halogen in surprising ways.

One of the most striking predictions from computational chemistry is that if you could somehow gather enough astatine atoms to form a condensed solid, it would be a metal, not a molecular solid like iodine. Calculations suggest that condensed astatine would be monatomic, meaning it would not form the diatomic molecules that define every other halogen. It might even be a superconductor.⁶ Of course, nobody has ever assembled enough astatine to test this experimentally. Every sample decays long before it could reach a visible, let alone testable, quantity. The prediction rests on theoretical calculations that account for the strong relativistic effects acting on astatine’s electrons. Because astatine’s nucleus has 85 protons, its inner electrons move at a significant fraction of the speed of light, which warps the electron cloud in ways that change the element’s bonding behavior and make it more metallic than a simple extrapolation from lighter halogens would suggest.

In solution chemistry, astatine’s behavior is similarly unexpected. When researchers compared how astatide (the negatively charged astatine ion) reacts in certain substitution reactions, they found it was more reactive than iodide, with a meaningfully lower activation energy. Quantum chemical calculations supported the idea that astatine forms reaction intermediates structurally distinct from those formed by iodine, rather than simply following the halogen trend.⁷ This unpredictability is both scientifically fascinating and practically important, because anyone trying to attach astatine to a molecule for medical use needs to understand how it actually bonds rather than assuming it will behave like a bigger iodine.

The Fragile Carbon-Astatine Bond

One of the persistent challenges in astatine chemistry is keeping it attached to organic molecules. For medical applications, astatine-211 typically needs to be bonded to a carbon-containing targeting molecule that carries it to the right cells in the body. The problem is that carbon-astatine bonds are weaker than carbon-iodine bonds and more vulnerable to breaking under biological conditions.

Theoretical calculations show that the carbon-astatine bond in oxidized aromatic compounds is roughly 25% less stable than the corresponding carbon-iodine bond, with bond dissociation energies of about 28 kcal/mol for the astatinated compound versus about 38 kcal/mol for the iodinated version.⁸ In the oxidizing environment inside a living body, this means astatine can detach from its carrier molecule before it reaches the target. Researchers have been exploring workarounds, including adding chemical groups near the bonding site that shield the astatine or make the molecule harder to oxidize. This kind of molecular engineering is an active and essential area of research for anyone hoping to turn astatine into a practical medicine.

Why Oncologists Care About an Element From 1940

The reason astatine has attracted so much modern interest comes down to one property: it emits alpha particles when it decays. Alpha particles are heavy, highly energetic, and travel only a very short distance in tissue, roughly a few cell diameters. That makes them devastating to individual cancer cells while leaving surrounding healthy tissue relatively unharmed, at least compared to the gamma rays and beta particles emitted by more commonly used medical isotopes. This approach, known as targeted alpha therapy, pairs an alpha emitter with a molecule designed to seek out and bind to cancer cells.

Astatine-211 is a particularly attractive alpha emitter for several reasons. Its 7.2-hour half-life is long enough to manufacture a drug, transport it to a hospital, and administer it to a patient, but short enough that it does not linger in the body for days or weeks. When it decays, it does not produce a long chain of dangerous radioactive daughter products, which simplifies dosimetry and safety. Researchers have described these as “clean decay characteristics.”⁹

Clinical trials are now underway testing astatine-211-labeled drugs against prostate cancer, one of the most common cancers worldwide. One Japanese group has developed a compound that targets PSMA, a protein found on the surface of prostate cancer cells, and labeled it with astatine-211. In a first-in-human trial involving nine patients with advanced, treatment-resistant prostate cancer, the drug showed high accumulation in tumor lesions.⁹ Separately, preclinical studies using astatine-211 attached to antibodies targeting a different prostate cancer marker, PSCA, demonstrated clear tumor growth inhibition in both soft-tissue tumors and bone microtumors in animal models.¹⁰ The bone result is particularly significant because prostate cancer commonly spreads to bone, where it is notoriously hard to treat.

The Supply Chain Problem

For all its therapeutic promise, astatine-211 faces a logistical challenge that no amount of clever chemistry can solve on its own. The number of cyclotrons worldwide capable of producing it is small. Most hospital-based cyclotrons are designed for lower-energy proton beams used to make fluorine-18 for PET scans. Producing astatine requires a machine that can accelerate alpha particles to at least 28 MeV with enough beam current to generate clinically useful amounts.⁵ These machines exist mainly at large research universities and national laboratories.

The 7.2-hour half-life compounds the difficulty. You cannot stockpile astatine-211. Every batch begins decaying the moment it is made, losing half its activity every seven hours or so. A dose produced at a university cyclotron in the morning needs to be purified, attached to the targeting molecule, quality-tested, and injected into a patient, all within the same day. Shipping it across the country is possible but tight. Shipping it across an ocean is essentially impractical unless production sites are established on both sides.

The number of production sites has been growing in recent years, driven by the expanding interest in targeted alpha therapy.⁹ Researchers have also explored an alternative production route using a radon-211 generator system, which could in theory allow astatine-211 to be produced at sites without their own cyclotron. The generator approach involves creating radon-211 at a central facility and shipping it to hospitals, where it decays into astatine-211 on site. This idea is promising but still in development.

Naming and Legacy

Astatine holds an odd place in the history of chemistry. It was one of the last gaps in the periodic table to be filled, and its discovery confirmed one of Mendeleev’s oldest predictions, yet hardly anyone outside chemistry has heard of it. Part of the reason is that astatine has no everyday industrial use. You cannot hold it, see it, or buy it. It exists in quantities so small that most of what scientists know about its chemistry comes from experiments conducted on a few billion atoms at a time, an amount too small to weigh on any balance.

The name the Berkeley team chose in 1947 has proven apt in ways they could not have fully anticipated. “Astatos,” unstable, describes not just the element’s radioactivity but its entire relationship with human knowledge. Its chemical behavior is harder to pin down than that of its lighter halogen relatives. Its bonds to organic molecules are fragile. Its supply is perpetually scarce. And yet the same instability that makes astatine so elusive is precisely what makes it valuable: those alpha particles it emits as it falls apart are now being aimed at cancer cells with increasing precision. Element 85 spent decades resisting discovery, and it has spent the decades since resisting easy characterization, but it may finally be on the verge of practical usefulness.