In the early years of the Cold War, U.S. scientists tried to create synthetic uranium in a laboratory, spurred by fears that our country lacked enough natural deposits of the highly reactive material to keep up in the escalating nuclear race.
The U.S., it turned out, had ample uranium reserves in New Mexico and Pennsylvania. And not only did the man-made variety produce too small a bang to make bombs, the material was too volatile to be safely handled.
Wrong turns sometimes yield surprising results. Atoms decay, and when they do, they give rise to new particles. In this case, the nuclear sludge excreted in the creation of uranium 233 gave birth to another isotope, or variant of an element, called thorium 229. And the thorium gave birth to something else: an isotope known as actinium 225.
More than half a century later, that very substance is being tested as a cancer-killing agent, a next-generation radiation treatment whose highly concentrated potency, researchers hope, will allow doctors to target diseased cells without damaging healthy tissue, the way existing radiation therapies do.
“What’s so extraordinary about actinium is that it’s worked in doses a thousand times lower than anything else,” Dr. David Scheinberg, who runs the experimental therapeutic center at Memorial Sloan-Kettering Cancer Center and led much of the research on actinium.
In the early 1980s, Dr. Scheinberg was a researcher at Johns Hopkins University, studying a method for binding antibodies to cancerous tissue. What if he were able to attach cancer-fighting agents to those antibodies?
Dr. Scheinberg hit on the idea of alpha-emitting particles, a type of atom that would deliver a short, concentrated blast, more powerful than existing radiation treatments and in a form that would do less damage to healthy tissue.
At the time, the idea was theoretical—neither Dr. Scheinberg nor his partners knew which atom could deliver the payload they sought, yet prove stable enough to work with and be safe for the patient.
“It was just a dream,” Dr. Scheinberg told us. “We spent a long time at first figuring out what atoms had the properties we were looking for.”
Dr. Scheinberg was still searching for the right agent when someone else had an idea. Maurits Geerlings, a Dutch scientist, had read Dr. Scheinberg’s papers, and sought out the young researcher to suggest that he look into a certain by-product of uranium 233.
“He was so excited about the idea, he came and met me in Truro, Massachusetts,” said Dr. Scheinberg. “He flew in from Europe, we met on the beach, and we decided it was a good idea.”
But how to get their hands on actinium?
In nature, actinium is only found in the scantest traces. While the Soviets are believed to have produced large quantities of the same synthetic uranium 233 that the Americans had abandoned, those supplies hadn’t surfaced. If Dr. Scheinberg was going to begin testing his theory, Oak Ridge National Laboratory, where the U.S. Department of Energy had produced tons of uranium 233, was the place to start.
In the mid-1990s, Oak Ridge had hired a scientist named Saed Mirzadeh to produce the medically promising substance at the Tennessee laboratory, passing the nuclear sludge through a column and stripping the actinium off of the parent, working from behind leaded glass to purify the material.
“There’s a reason they use it for killing cancer,” he told The Observer. “When you work on it, you have to keep in mind that this damn thing is toxic.”
At first, Dr. Scheinberg had focused his attentions on bismuth 213, a by-product of actinium, successfully binding the isotope to an antibody and firing the compound toward blood-borne cancers. Test results were promising, but with a catch: bismuth’s half-life was a mere 46 minutes, meaning it had to be administered shortly after the drug was produced.
The ability to target the cancer-killing agent with high precision was a breakthrough, but the short half-life meant that the treatment could only be administered near the laboratory where the drug was created, making it unfeasible for widespread distribution.
Dr. Scheinberg returned his attention to actinium itself, which had a half-life of 10 days, and offered an additional benefit. After the atom was delivered to a cancer cell, it would spawn daughter atoms, which would join the attack. The result was something called a called a “generator drug,” because it multiplied during delivery.
By that time, Dr. Scheinberg had moved to Memorial Sloan-Kettering Cancer Center, where he began testing the drug on lab mice. When he published his results in the journal Science in 2001, the treatment received widespread attention as “mini-atom bomb” for cancer.
The discovery of actinium’s cancer-fighting properties wasn’t the first time that a medicine was born of warfare. The first important breakthrough in the development of chemotherapy as a cancer treatment occurred during World War II. The U.S. Army had stockpiled 100 tons of mustard gas on a ship stationed in an Italian harbor. The ship was bombed and the stockpile exploded; Autopsies of the victims led scientists to suspect the compound’s potency as a cell-killing agent.
When asked to draw a parallel between mustard gas and actinium, Dr. Scheinberg pointed out that many of the most effective cancer treatments have lacked precision; doctors knew that certain chemicals killed cells, and directed the agents at the disease, with limited ability to moderate the effects on healthy tissue.
The chief benefit of actinium is that its short wavelength enables it to attack cancer cells without destroying surrounding tissue. The substance could have huge implications: in Poland and Germany, actinium is being used to treat brain cancer, and in Australia, for use on melanoma patients.
The drug’s development, though, has been complicated by a need for more actinium. While Oak Ridge still has a massive stash of uranium 233, there isn’t funding to extract the actinium.
Later this month, a company called Actinium Pharmaceuticals plans to lead an initial public offering to raise $20 million to complete ongoing human testing on a treatment for acute myeloid leukemia by the end of next year. Dr. Dragan Cicic, the company’s chief operating officer, told The Observer that for a time, API used a cyclotron to produce actinium, but until a drug goes into mass production, the technology is an unwieldy expense.
Aside from scarce actinium supply, another stumbling block has been the key step of binding the cancer-fighting substance to the antibodies, a long process of trial and error. “We’re using the antibodies as guiding missiles to deliver the isotope,” Dr. Cicic told us. “It’s not trivial at all to make a radioactive element peak through a cell.”
For his part, Dr. Scheinberg prefaced his comments by noting that, as the inventor of technologies behind the drug and as an employee of Sloan-Kettering, which owns the patents, he has an interest in seeing the drug find commercial success.
“Acute myeloid leukemia is very difficult to treat right now, so the drug could be very important, especially for adults,” he told us. “As a proof of concept, it could be very important to allow more work on this type of platform to go forward.”
On a recent morning, The Observer visited API’s spartan offices, across Fifth Avenue from the New York Public Library. We asked company CEO Jack Talley if he had any actinium on hand to show us. “A pharmaceutical company is the last place you’ll find that kind of substance,” he said.
Dr. Mirzadeh, the Oak Ridge scientist charged with milking actinium from its parent materials, said that the would-be miracle drug is invisible to the naked eye, though its radioactive properties produce a fluorescent effect that causes it to glow in the dark.
It’s a light of hope for some cancer patients.