Megan Hall: What if you could create any material, or invent a new one, by building particles one at a time? Chad Markin not only makes this possible, but also… I have spent my career exploring how these tiny creations can transform research, medicine, and technology.
This year, he won the Kavli Prize in Nanoscience for Bottom-Up Building Materials, along with Robert Langer and Paul Alivisatos.
Scientific American Custom Media, in partnership with the Kavli Prize, interviewed Chad to learn about his journey as a scientist and the future of this research.
Megan Hall: Chad Merkin likes to say that he was a natural born chemist.
Chad Merkin: You go to college. You’re young. You don’t really know what you want to do. Your mother says go out and become a rich doctor, or a rich lawyer, or a businesswoman. No one is telling you to become a scientist, right? At least not in my family. So I went to school thinking, oh, I’m going to be a doctor.
Megan Hall: When I attended the surgery, he was well on his way to using his chemistry degree to prepare for medical school.
Chad Merkin: And I thought it was the most boring, most unpleasant thing I’d ever seen. And I had a crisis. I said, “I can’t do that.” There’s no way I could do something like this in my life.
Megan Hall: Chad Mirkin quickly pivoted to a career in research and never looked back. He studied chemistry at Dickinson College and received his doctorate from Pennsylvania State University. Later, as a postdoc at MIT, he collaborated with chemist Mark Wroten, who was studying the effects of miniaturization.
Chad Mirkin: He was thinking about what happens when you use chemical systems to make electronic devices. And what happens when we reduce them to the microscale instead of the nanoscale?
Megan Hall: Nanoscience was in its infancy at the time, but when Chad came to Northwestern University as a young professor, it began to blossom. And Chad was hooked.
Chad Mirkin: This is a whole new sandbox. That’s wonderful. I tell people I have never worked a day in my life. You can come to work and have fun.
Megan Hall: Chad says there are two main principles when it comes to nanoscience. One is that everything behaves differently when you scale it down to the miniature level.
Chad Mirkin: Gold is a great example of that. Shrink money. Wedding rings are no longer gold. The color can be red. It doesn’t matter if it’s blue. Depending on the size and shape of the final particles, they may be green in color.
Megan Hall: And two, once you understand these differences, you know what to do with them.
So, to summarize what you’re doing, is it accurate to say, scale things down, see what happens when they’re smaller, and come up with something interesting with that?
Chad Markin: That’s right. And I would like to add one caveat. We will also try to understand why such characteristics occur when downscaling.
Megan Hall: Chad Merkin has been doing this type of work at Northwestern for over 30 years. He won the Kavli Prize for his innovation, which is constructed by attaching small pieces of DNA or RNA to the surface of tiny spheres called nanoparticles.
Chad Mirkin: It’s structured like a kouche ball. Think of the little hairs sticking out of the Koosh ball as DNA strands.
Megan Hall: When Chad’s team first built these globular nucleic acids, they started by making nanoparticles coated with single strands of DNA that didn’t recognize each other. They then added another complementary piece of DNA to form a bridge, or glue, to connect those particles to each other.
Chad Merkin: And now it’s like chemical-specific Velcro. Throw them into the solution. If they are designed to react with each other, they will react and form these beautiful lattices.
Megan Hall: The new nanostructure also did something unexpected.
Chad Merkin: I was in the office. A young graduate student, Bobby Music, ran up to me and said, “Chad, you should see this!”
Megan Hall: When Mucic mixed two types of nanoparticles, the solution changed.
Chad Merkin: The color of the solution went from a very dark ruby red to a deep blue.
Megan Hall: When his graduate students heated the solution, breaking the bonds between the DNA strands, the solution turned red again. Then he cooled it down, allowed the bonds to form again, and the solution turned blue.
Chad Merkin: And what he was observing at that time was the formation of a double helix and the disassembly of a double helix. And we almost unanimously said this is a new detection system for DNA.
Megan Hall: Chad and his graduate students realized that they could design spherical nucleic acids that would only attach with Velcro if a particular form of DNA was present.
Chad Merkin: So what that means is that we can create particles that are designed to recognize every living thing, every living thing, every person, every genetic disease, every bacterial disease, every viral disease. . You can create particles to complement it.
Megan Hall: And if the particles are complementary to a form of DNA from a particular disease, for example, they will bind and the solution will change color. Chad quickly founded a company to leverage this discovery and develop technology for new diagnostic tools.
Chad Merkin: That technology still exists and is used in many hospitals around the world.
Megan Hall: But globular nucleic acids are more than just a useful diagnostic tool. Chad says placing DNA and RNA on nanoparticles provides exciting new functionality. For example, DNA itself cannot enter cells, but DNA as a globular nucleic acid can.
Chad Mirkin: We can now get large amounts of DNA and RNA into cells and use that to start manipulating what’s going on inside the cell.
Megan Hall: Moving DNA and RNA in this way can help address all kinds of medical problems, from cancer to cancer.
Chad Merkin: For example, there are cancer cells that produce too many proteins that cause problems. We can create globular nucleic acids and dock their protein production back to normal.
Megan Hall: …Psoriasis.
Chad Mirkin: If they’re producing too many inflammatory proteins, we can create structures that regulate their production and bring them back from an unhealthy psoriatic state to a healthier skin state.
Megan Hall: In addition, Chad says globular nucleic acids are helping to transform another important area of health care.
Chad Mirkin: We believe this will completely revolutionize the way vaccines are developed.
Megan Hall: Chad says all vaccines contain two key elements. adjuvants, which stimulate the immune system, and antigens, which train the immune system to attack infections and diseases.
Chad Mirkin: Typically, the way vaccines are developed is you take these ingredients, mix them together, inject them, and hope for the best.
Megan Hall: But what if instead of mixing them together, we could carefully place the adjuvant and antigen on a spherical nucleic acid-like structure? Would that make a difference in the effectiveness of the vaccine? To find out, Chad took the same elements and created four different vaccines.
Chad Mirkin: One is…based on what I call the blender approach, where you just mix the adjuvant antigen together, and then you mix the other three in the form of a globular nucleic acid.
Megan Hall: Next, his team injected these vaccines into mice infected with human papillomavirus (HPV).
Chad Mirkin: The blender approach has almost no effect, but different structure placements on the surface where we place the antigen, the training element, can lead to significant improvements and, in some cases or classes of structures, complete healing.
Megan Hall: He said this is an important point. – The structure of a vaccine is as important as its components. It will also help scientists design vaccines rationally and quickly by using AI to narrow down thousands of possible nanostructures to those most likely to be effective.
Chad Markin: So if we can use machine learning to take a subset of those and determine what is most productive, we can get the drug to us faster in the most optimized and effective form. Masu.
Megan Hall: This is just another way that globular nucleic acids are transforming the world of medicine.
In a way, it’s like you’re a doctor, right?
Chad Markin: Yeah. It’s kind of interesting. My interest, my curiosity, took me back to medicine in a big way. That’s kind of ironic. People give me awards for all these kinds of things that I ran away from early in life and came full circle.
Megan Hall: Chad is excited to spend the rest of his life in this work studying small structures while simultaneously transforming medicine.
Chad Mirkin is director of the International Institute for Nanotechnology at Northwestern University. This year he will share the Kavli Prize in nanoscience with Robert Langer and Paul Alivisatos. The Kavli Prize recognizes scientists whose breakthrough advances in astrophysics, nanoscience, and neuroscience have transformed our understanding of the big, the small, and the complex.
The Kavli Prize was established in partnership between the Norwegian Academy of Science and Letters, the Norwegian Ministry of Education and Research, and the US-based Kavli Foundation.
This study was produced by Scientific American Custom Media and made possible with support from the Kavli Award.
