What is an isotope?

In 1922, British scientists Frederick Soddy and Francis William Aston were awarded Nobel Prize medals in chemistry for their groundbreaking work in discovering isotopes.

Now, a century later, Michigan State University is helping launch the next chapter in isotope history. The Facility for Rare Isotope Beams, or FRIB, a U.S. Department of Energy Office of Science user facility and the most powerful isotope-making accelerator on the planet, opens on MSU’s campus this spring.

So what makes isotopes deserving of historic awards, a new boundary-pushing facility and 100 years of research and innovation in between? The answer is that isotopes help to advance health care, promote understanding of Earth and expand the boundaries of celestial discovery.

Isotopes 101

When it comes to nuclear science, simple questions don’t always have simple answers. So it helps that MSU’s Artemis Spyrou is a nuclear astrophysicist with a knack for down-to-earth explanations.

“I have a Greek background and ‘isotope’ comes from a Greek word, ‘isotopo,’ which translates to ‘same place,’” says Spyrou, a professor of physics at FRIB and in MSU’s College of Natural Science. “It connects to the periodic table of the elements. Each box on the periodic table of the elements has one element, but isotopes are different variations of that same element.”

Think of elements as large, big box chain stores. A Walmart is different from a Target and both are different from a Costco. They may have things in common, but each are recognizably distinct to the shopper.

Isotopes are more like different locations of the same store. The nearest Walmart might be indistinguishable from the one a few towns over were it not for important differences like their business hours and where they keep their snacks.

Elements on the periodic table are grouped by how they behave and interact with the world around them in discernable ways. For example, hydrogen gas is extremely flammable. Its neighbor on the periodic table, helium, is safe for filling balloons at a child’s birthday party.

Isotopes of the same element share many of those outwardly recognizable features, but they also have important differences.

“Because isotopes are different versions of a particular element, isotopes will have the same chemical properties,” Spyrou says. “But they have very different properties from the nuclear physics point of view.”

To understand the differences, consider the core of an atom, which is called the nucleus. The nucleus is home to protons — subatomic particles with positive electric charge — and neutrons, which have no charge. If you change the number of protons in a nucleus, you change the element. If you change the number of neutrons, you change the isotope.

All hydrogen atoms have one proton, for example. But hydrogen also has three isotopes found in nature: one with no neutrons, one with one neutron and one with two. These different isotopes have different properties. The different number of neutrons gives them different masses, for example, which can make them useful for different applications.

The hydrogen without neutrons accounts for more than 99.9% of the hydrogen on the planet. It’s the dominant form of hydrogen in the water found in our bodies and Earth’s oceans, lakes and rivers. But the heavier, neutron-bearing isotopes can still make water that’s particularly useful for building nuclear power reactors and performing important, sensitive analyses for biology, chemistry and environmental sciences.

And those are just the naturally occurring isotopes of one element. There are 118 elements on the periodic table. There are more than 3,000 known isotopes and likely thousands more waiting to be discovered.

Using particle accelerators like the one at FRIB, scientists can create more isotopes of more elements to study more exotic nuclei. Doing so helps them explore the fundamental rules of physics governing all atoms while, at the same time, making isotopes that can go to work in the real world.

“Imagine taking a box on the periodic table and sort of stretching it out. All of a sudden you might have 20 different variations of that element, but each with slightly different nuclear properties,” Spyrou says. “You can choose the one you want for a specific application.”

Marvels of modern medicine

Out of those thousands of known isotopes, there are about 250 that are stable. That means that most are unstable, and thus radioactive.

Scientists first discovered radioactive materials near the end of the 19th century. Since then, researchers have learned much about how to safely harness the power of radioactive isotopes, or radioisotopes, to enable new scientific discoveries and new technologies that improve lives, notably in medicine.

MSU has been part of that history, with a legacy in discovery science and life-saving applications. In 2011, for example, Michigan State partnered with Cardinal Health to create mid-Michigan’s first radiopharmacy, a facility where researchers can safely and efficiently incorporate isotopes into pharmaceuticals.

Today, that radiopharmacy is producing more than 37,000 doses of a compound known as fluorodeoxyglucose, or FDG, every year. This compound has become a stalwart of medical imaging, used to detect and monitor cancer, since it was first made in the Czech Republic in the late 1960s.

FDG, which uses a radioisotope of fluorine, naturally accumulates in tumors. The fluorine isotope releases radiation that can be detected for what’s known as positron emission tomography, or PET, scans.

“The radioisotope essentially gets trapped in the tumor. Then we can image a patient from head to toe to detect cancer or see if it’s become metastatic,” says Kurt Zinn, chief of the Chemical Biology Division at MSU’s Institute for Quantitative Health Science and Engineering, or IQ. “PET imaging is very deep and very sensitive. It does things that no other imaging modality can do.”

Creating established medical isotopes, such as the fluorine in FDG, doesn’t require the power of a facility like FRIB, which means the technology is more accessible. In fact, many hospitals and universities have medical cyclotrons on-site to create radiopharmaceuticals as needed and deliver them to patients as quickly as possible.

Having a one-of-a-kind facility like FRIB, however, creates powerful new opportunities for medical applications and that's exciting for researchers like Zinn.

MSU hired Zinn as part of its Global Impact Initiative in 2017. He came here to develop new ways to diagnose and treat cancer with radioisotopes, but his career path was initially focused on nutrition.

As a graduate student at the University of Missouri, Zinn invented a way to make very pure samples of a copper isotope called copper-64 (it has 29 protons and 35 neutrons, which add up to 64). This isotope would help him and other scientists more closely examine how the human body uses copper, an essential mineral in our diets.  

It turns out that copper-64 could also be used in PET imaging, and researchers at nearby Washington University in St. Louis wanted to explore its potential. This was Zinn’s first academic connection to medicine, but his decision to pursue that over nutrition was also personal.

“I lost my first wife to cancer in 2006. She was also a scientist working in imaging and therapy,” Zinn says. “I realized, to go forward from that, I really needed to focus on being able to help relieve some of the pain and suffering from cancer.”

Zinn’s now been part of about a dozen phase-one clinical trials, which are crucial steps in testing the safety and efficacy of new treatments and diagnostics. He also had a hand, very literally, in building MSU’s new radiopharmacy.

Because MSU’s existing radiopharmacy is hard at work making FDG, MSU needed an additional facility where it could do cutting-edge, experimental work. Zinn and his colleague Jinda Fan — an expert in the chemistry used to make new products for PET imaging — had the know-how to help get that new facility up and running.

“There were Saturday runs to Home Depot where we’d pick up pipes and cement blocks,” Zinn says.

The pipes made the plumbing to carry isotope-rich liquids from a medical cyclotron into the radiopharmacy, where some crafty chemistry weaves radioactive atoms into compounds that can help save lives. The cement serves as a barrier to block the radiation from the cyclotron’s products and keep the researchers safe. In addition to the concrete, the radiopharmacy uses tens of thousands of pounds of lead to provide even more shielding.

“Safety is our utmost concern. That's why we have a radiopharmacy, to do things in the best possible way,” Zinn says. “That’s not only in how we manufacture the drugs but also in dosing to the patient to make sure everything is as safe as possible.”

Illustrating Zinn’s point, Fan, an assistant professor in the Department of Radiology and the Department of Chemistry, opens what looks to be a wall-mounted oven. It’s actually what’s known as a hot cell, a lead-encased chamber that allows researchers to safely work with the radioactive materials inside. Inside one of them, a pair of robotic arms called manipulators are used by researchers to safely move and handle radioactive samples inside.

Another hot cell is home to an array of small cylinders and tubes that perform chemical reactions that have been programmed by the researchers. The system takes raw starting ingredients and automatically transforms them into the desired products at exactly the right dosage without wasting reagents or time.

“When you’re working with radioisotopes, every minute counts,” Fan says. “We’re racing against the clock.”

Radioisotopes have a characteristic lifespan known as a half-life that describes how quickly they decay. The fluorine-18 in FDG, for example, has a half-life of 109 minutes. That means if you had a pound of fluorine-18, half of it would decay, transforming into oxygen-18, within two hours. Fan also works with the isotope carbon-11 that has a half-life of 20 minutes.

Having access to isotopes with a variety of half-lives helps researchers achieve different goals. Whereas one patient’s diagnosis would be improved by more frequent observations, another might benefit from a longer duration. The half-life becomes a dial researchers can tune for specific cases.

Beyond half-life, different isotopes also offer different types of radiation. Not all radioisotopes emit the radiation used in PET scans. There are several other types researchers can choose from based on the desired application. For instance, Zinn is helping develop new cancer treatments that attack cancer cells with what are known as alpha particles.

And none of these new diagnostics or treatments are developed in a vacuum. One of the most attractive parts about using isotopes in this field is their potential to dovetail with other modern medical innovations, such as nanomedicine, stem cell therapy and immunotherapy.

“We’re trying to integrate our therapies and imaging with other up-and-coming strategies,” Zinn says. “That’s what really gets me excited nowadays.”

Teamwork is essential to making this all possible, which you might be able to guess from the breadth of Zinn’s appointments. He’s a professor in the Department of Radiology, the Department of Biomedical Engineering and the Department of Small Animal Clinical Sciences. Being able to work with so many experts in so many different fields — chemistry, radiology, veterinary medicine and more — is what attracted him to MSU. Having FRIB on campus didn’t hurt either.

“FRIB was one of the reasons I came to MSU because I knew it would make isotopes that weren’t commercially available, that were brand new,” he says. “FRIB will enable research to be done that can’t be done elsewhere.”

From the atomic to the cosmic

At this point, we hope you feel comfortable with the idea of an isotope. But what about a rare isotope? You might wonder where is that line between a common isotope and rare one. Not to worry. FRIB will be operating with the objective clarity that comes with being one of a kind: It’s going to produce isotopes humans have never observed before, an unassailable standard for “rare.”

“FRIB is a unique place for producing rare isotopes,” says Spyrou, the nuclear astrophysicist. “It's the most powerful heavy-ion accelerator in the world, so it has the ability to produce isotopes that no other facility can produce.”

Which means FRIB’s goal isn’t just about making isotopes for nuclear science research, medicine or any other specific use. It’s about affording the opportunity to make discoveries that create knowledge or change lives.

FRIB is taking us into the unknown, which is why scientists from around the world want to test their ideas here. With support from MSU, the state of Michigan and the DOE Office of Science, FRIB is opening new doors to discovery, expanding our knowledge of fundamental science while furthering our ability to put that knowledge to work in applications.

“History has shown that new facilities and new discoveries, they always lead to something useful for society,” Spyrou says. “This is also what we expect for FRIB.”

The isotopes that go to work in the real world will be made while a global community strives to create nuclei that have never been witnessed on this planet. And those never-before-seen isotopes will help answer some really big, fundamental questions.

For Spyrou, those questions center on how the universe makes its elements and isotopes. Science knows that these atoms are forged in the stars, but questions remain about the exact processes that create them.

“My own research focuses on rare isotopes that we don’t find on Earth naturally, they live for a very short time — less than a second,” Spyrou says. “But they are part of the stellar environment and they’re part of astrophysical processes.”

FRIB can’t perfectly replicate suns or supernovae, but it doesn’t need to. Rather, it will create the rare isotopes that are present in those celestial bodies and those isotopes will move with the same speeds and energies they’d have in the stars. Having new isotopes will thus help reveal the intimate details of atoms and nuclei as well as the grandeur of the heavens that created them. Spyrou’s work is just one example of that.

“It's not exactly like being inside the star, but we have the right conditions to study what's going on in the star,” Spyrou says. “And what FRIB can do, it can’t be done anywhere else on Earth.”

The facility will also help nuclear scientists better understand the forces that hold nuclei and all matter together. Researchers will be able to explore extremely unstable isotopes and unusual nuclear reactions, stress-testing what we think we know, attempting to explain what we don’t and discovering new questions to ask.

It’s this process of discovery that drew Spyrou to her work and FRIB.

“It’s just something that I love to do, working with people and figuring out the answers to problems,” she says.

“There’s a moment in experiments that I think experimentalists live for. You've been setting up your experiment for a month and you haven't slept for days and finally the data comes in and you look at it,” Spyrou says. “It's that realization for a second that no one has seen this ever before. No one knows what this is all about. That moment, for me, it’s irresistible.”

Big questions need big science. The physical scope is part of that. The facility consists of four buildings with more than 500,000 square feet of space. But the teams are also big and interdisciplinary.

FRIB was built not only to accommodate but also to encourage that teamwork. It’s the only such DOE Office of Science facility to exist on a university campus. That university also happens to be home to the top-ranked nuclear physics graduate program, with some of the world’s best faculty in both theory and experiment. FRIB is a nexus for a diverse network of bright minds and that network extends well beyond the building itself and the campus where it lives.

FRIB’s first call for proposals, completed last February, elicited responses from 597 scientists, representing 130 institutions in 30 countries.

“There are always new people and new information coming in. That really creates an exciting environment to work in. It helps science move forward and move forward faster,” Spyrou says. “This is the place to be. This is the future of rare isotope science.”

More than a century ago, Frederick Soddy coined the term “isotope” and claimed the 1921 Nobel Prize in chemistry. He did not, however, receive the prize until 1922, thanks to a seldom-used caveat in the will of Alfred Nobel that established the awards.

And perhaps that’s fitting.

After all, seeking out the rare and unusual has helped scientists learn more about isotopes and their potential over the past 100 years. And that drive for discovery is opening a new era in isotope research — an era that starts here and starts now.