A Conversation with Dr. Andrew Lyon 
by Andrew Kerr
July 2007

Dr. Andrew Lyon of the School of Chemistry and Biochemistry has been enjoying a lot of media attention for his research into cancer treatment (to thwart tumors) and the detection of dangerous chemicals (to thwart would-be terrorists). We sat down with him at the end of June to discuss all this thwarting and other research his lab is conducting.

Q - Were you always interested in science and math?

A - I've been interested in lots of different things, but I've got a brother who is a chemist who is about 15 years older than me. Since he went to Rutgers for his Ph.D, he used to drag me into the lab and show me some cool stuff. That got me jazzed-up!

Q - What were some of the cool things he showed you?

A - The coolest thing I remember seeing the first day I walked into the lab was something that seems pretty pedestrian now: a magnetic stir plate. It seems to magically stir solutions by having a magnet underneath a hot plate which stirs a magnetic bar inside of a glass container.

Inorganic chemistry, which was what he did, made a lot of things change colors; you would do a lot of reactions [that made things turn] from red to pink to blue.

Q - Considering both you and your brother went into chemistry, did your parents work in science fields as well?

A - Not at all. My mother is a fine artist, she's a painter. My dad worked for a power company; he climbed electrical poles for a living.

Q - Did your mother's fine arts background surface in your own approach to science?

A - I'm very visual in the way I think about science. I was a philosophy minor in college. I definitely have a liberal arts side of me that comes into how I do research and how I run my research group. I think I drive my graduate students crazy talking about philosophy of science (instead of how bonds are made and broken) sometimes!

Q - Ethics is a hot-button issue in political discussions about science. Is that something that interests you as well?

A - Ethics is a huge part of philosophy of science. All the graduate students who work with me get an informal training [in ethics].

We talk about how research should be done, the presentation of your results, and ethical themes such as what sorts of things are correct and not correct to do. Young students always step out of line just because of ignorance of what is expected of a compassionate scientist.

Q - What are common ethical errors that young scientists make?

A - Probably the most common error is not making proper attribution to the work of others. Sometimes, that's done in a very innocent way. For example, you'd be talking about a reaction that somebody else has done in another research group in another university and simply not refer to that person being the originator of that research. Other times, it's done a bit more egregiously, where you might be writing a manuscript and not appropriately referencing something that you learned from literature. It hasn't happened in my own research group, but people actually actively borrow the work of others with the intent of making it seem like they did it. Of course, that is very serious.

Q - What do you think of popular accusations that Rosalind Franklin was railroaded by Watson and Crick in their pursuit of fame regarding unlocking the structure of DNA?

A - Oh, I think there's real substance to that. That was certainly the product of the old boy network, how science was done those days.

Q - You went to Rutgers, and then you went to Northwestern [University]. I can see why you went to Rutgers, having had a brother there, but what about Northwestern?

A - It's very common when you're coming out of an undergraduate education to go and visit graduate schools. I had visited a bunch, but there was always something about each one that turned me off.

Northwestern was my top choice because there was a wide range of scientists there that I really wanted to work with. It was a very dynamic place and had the research that I was interested in.

[After I had applied], they lost some of my GRE scores. So I called them up, probably a week before the typical deadline for making decisions, and they said that they hadn't decided on the application status because they didn't have my scores! So, over the phone I told them what my scores were. The secretary put me on hold and came back in five minutes and said, "You're accepted"!

Q - Is [Northwestern] in downtown Chicago?

A - It's in Evanston, which is a northern suburb in Chicago. It's a moderately urban environment. It's a beautiful area. It's around Lake Michigan, so it's a very nice and relaxing place to do a high and intense education. Then you can always hop on the train to go to Chicago for a good time. It's not too dissimilar to Georgia Tech from the standpoint that the Georgia Tech campus is centrally located, it has a lot of green space, it doesn't really feel like a city campus, but at the same time you can walk two blocks to the center of Atlanta.

Q - We have something vaguely in common. I went to the College of William and Mary. "Daily Show" anchor Jon Stewart graduated from there. And I know that the "Colbert Report"'s Stephen Colbert went to Northwestern.

A - So did [supermodel] Cindy Crawford!

Q - Cindy Crawford went to Northwestern?

A - That's right. She started off as a chemistry student.

Q - Wow. So what did you do after graduating from Northwestern?

A - In 1997 and '98 I was doing a postdoctoral fellowship at Penn State. Once you get a Ph.D. in the sciences, if you want to go on into academia it's common to do a [postdoctoral fellowship] in another research lab, learn some different techniques, learn some different science, and learn different things in terms of running a research group. It seasons you nicely before going into academia.

Q - All these places you went to, they are around the same latitude. Now you're down here in Atlanta's 100 degree temperatures. Why Georgia Tech? And was it a shock adjusting to the environment?

A - The heat doesn't shock me, because Chicago, Jersey and even Pennsylvania can get very hot in the summer. The lack of winter, on the other hand, is shocking. Georgia Tech's chemistry and biochemistry department was really up and coming at the time. Now it's maintained an upper-level reputation. It's been an interesting place to build a nice program.

I liked the idea of a state institution: a little bit small, a little bit specialized in terms of its educational focus, but also that it drew nationally. So there's a nice and diverse student population to interact with.

Q - Most articles I read about you on the web focused on two areas of your research. One was the work you did with cancer. The other was your work in chemical detectors that could potentially be applied to homeland security issues. Are these still your primary areas of research, or have you moved on to other things?

A - We still have projects using nanoparticles in cancer tumor targeting, and we still have efforts in biosensors. We also have efforts on making coatings for implants such as drug delivery devices and pacemaker leads and glucose sensors. Every time you put a foreign object into the human body, some bad things can happen in terms of rejection, inflammation and infection. We're focusing on how to make polymeric coatings on those types of devices that will allow the body to be more tolerant to those types of implantations.

Q - How do you trick the body into accepting [foreign objects]?

A - There's a short term trick, and that is to make the object invisible. It's what we call a "stealth mode", where you put something on the material that is chemically very similar to the surrounding tissue in a way that the body doesn't recognize it as a foreign invader. The stealth mode works for a period of time and has been moderately successful.

However, if you've got something that is to be implanted for a long time, for example, a pacemaker or birth control implants; those types of things get into a long term wound healing process. So the skin tissue around that eventually has to heal completely. If the implantation is just stealth, then the body doesn't ever heal or completely integrate the object. The long term implantation is not addressed by the stealth mode. You have to be more dynamic. The approach is trying to get the material to actively talk to the body, so you use biochemical cues, such as the molecules your body secrete naturally, to try to heal tissue, and you implant those in the materials that you're putting on the device. If those are released in a controlled fashion, you're basically tricking the body into thinking that it is an active healing process. We integrate those natural mechanisms into the synthetic materials that we make. This makes a partially stealth, partially active dynamic interface that looks like human tissue.

Q - The stealth method seems to be the idea behind cancer targeting. I presume its killing tumors is a short-lived event, so that you don't need to worry about those long term issues.

A - Cancer targeting is what we call a partially stealth, partially "Trojan horse" approach. The idea is that when you inject something into the body you want it to be invisible to the body's natural defense mechanisms so that is will circulate in the blood until it finds the tumor.

Once it gets there, you want to trick the cancer into thinking that this is something it can use for productive growth. In our case, we load the particles with folic acid. All cells need folic acid to grow because it a necessary nutrient for making DNA. Rapidly dividing cells (cancer cells) need a lot.

The receptors on the cell's surface bind to the folic acid and pull the particles into the cell. There are a lot more of those [receptors] on the surface of the cancer cells than there are on the normal cells. When you inject that formulation in the blood, the hope is that the normal cells won't take much of the drug loaded nanoparticles because they don't really require a huge amount of folic acid because they are dividing slowly. The tumors are out of control, they're growing rapidly, sucking up all the nutrients they can, so they'll suck up much more of those killer nanoparticles. Hopefully that will allow a greater differentiation between killing tumor cells and killing normal cells. (Killing normal cells is the typical [negative] side effect of traditional chemotherapy.)

Q - I read so much about amazing new breakthroughs in cancer treatment, but when will these methods will actually make it into hospitals?

A - There are a number of things in clinical trials right now, and there are portions of those technologies already out there. A common drug called Doxorubicin is being sold in a formulation, where the Doxorubicin is encapsulated inside of nanoparticles. This allows for longer circulation, and for a little bit of a decrease in side effects.

There are targeting approach drugs out there, drugs that are meant to specifically bind to the cells. One of them is called Herceptin, which is good for certain types of breast cancer. It's a protein that binds specifically to markers or proteins that are expressed on the surface of breast cancer cells. An interesting thing about that is that it's the targeting molecules that do all the work for you. There are no drugs attached to them. The molecule IS the drug. It's been very effective and it increases the survivability of breast cancer patients. I think we're looking at a couple of years for the research that's currently in medical trials to go on the market, where you combine nanoparticle delivery method with targeting.

Q - Regarding the biosensors, techniques that might allow law enforcement to detect certain particles in the air…how would such a device work?

A - Because my group is more of a materials group, we don't make many "gadgets". The biosensors we're studying right now are optical biosensors. They almost work like the elements in a fly's eye.

Most school kids have seen these graphical images of a fly's eye: all those microlenses clustered into a single eyeball. We make microlenses, which are actually smaller than the microlenses in a fly's eye. We make them so that they change their focal length, their ability to focus light to a point. When a molecule of interest binds to them they change their focal length. By looking at an image through them the image goes in and out of focus.

It's kind of neat from a visual standpoint. A student would be sitting there looking at these things, the specific molecule binds, and all of sudden an image comes crisp and clean into focus--an indicator that this cool thing has happened. Similar types of microlens technology is already used for document security or miniature scanners.

Q - What's the difference between this technique and the way chemical detection is done now?

A - There's a lot of ways to detect chemicals. A lot of us have gone to the airport and had someone from TSA [the Transportation Security Administration] open up your laptop and swab something on the keyboards to detect residues of explosives. That's done by mass detection. They know the mass of certain explosives or byproducts of explosives. The tool they use allows for detection of specific molecules of that mass.

Those are great tools, but the problem is that they are a little bit bulky. They are large; they are static. You'd have to have the samples come to you. Homeland security is looking for things where you can have a compact design to detect multiple things and being able to take that to the source without necessarily letting the source come to you.

Q - You said you don't make gadgets, but just for the amusement of it, I'm trying to imagine what this might look like: somebody walking around the airport with a Blackberry-sized detector that would display on its screen the nefarious chemicals that are in the air at any one time, and lead the user to the source.

A - People are definitely doing research in that area. There are companies based on "electronic noses" trying to mimic how mammals actually smell things. Professor Jiri Janata, whose office is right down the hall from mine, investigates "chemical plume tracking", which tries to understand how biological entities do what you just talked about: sensing a chemical trail and trying to figure out where the source of that trail is.

As I said before, we make materials, which is only one part of a sensing system. You need to have things that tell you when something is there, at the same time you need to be able to exclude all the background things that you don't care about. In addition, you need to be able to track the source, so you need have some kind of circuitry built that times the changing in signal. For example, you took one step in this direction, the signal got stronger, but how much stronger? Does it take you any closer to the source? All kinds of knowledge, from electrical engineering, to chemical engineering, to computer science and so on go into making chemical sensing devices that may one day be used in homeland security.

Q - I want to wrap up with your research into getting the body to accept implants for the long run. What are some common applications with that?

A - One typical application that is becoming more and more important is pacemakers. When you implant a pacemaker the wound needs to heal around that. As with any wound, scar tissue may form. A pacemaker is delivering an electrical signal and sensing feedback from the heart so that it knows how to pace the heart. A thick layer of scar tissue would change that electrical signal in the biological system. As more and more people, especially the younger population that is getting arrhythmia, are getting pacemakers, a problem called "fibrous capsule" becomes increasingly significant.

If you put a pacemaker in a 15 year-old, by the time he turns 25 it needs to be replaced, and by the time he's 35, it needs to be replaced again. This means that a person could need multiple surgeries in his lifetime just to replace the battery of his pacemaker because the wound that healed around the pacemaker lead was a very thick, ugly, fibrous capsule. By better integrating the lead with the cardiovascular tissue one could make pacemakers with severely extended lifetimes, so that the surgeries one person may have to go through to replace the battery of his pacemaker could be significantly reduced.

Q - Is there any advice you want to give to kids who are in middle school or high school right now thinking about going into a career in science?

A - Obviously, I love science; I think it's fascinating. I think one of the things that is really encouraging about opportunities in science is that it's no longer the case that people have to be biologists, or physicists, or chemists. Modern science, as it's currently practiced, is so interdisciplinary. My research group collaborates with at least four departments on campus in order to solve these problems.

People who go into science today have so many more opportunities than I did to interact with all kinds of different people who are looking at these tough problems. You no longer have to be compartmentalized. You no longer have to sit in chemistry class and say, "Gee, I really hate doing pKa calculations," or, "I really hate looking at solubility expressions," because even though that's a part of chemistry, it's not necessarily what chemistry is about anymore.

I look at science in terms of problems--what kinds of problems I want to solve--then bring in different kinds of tools from different disciplines to solve them!