ROB:    This is Rob Hassett for btobmagazine.com.  Today I'm going to be interviewing Professor Niren Murthy at the Georgia Institute of Technology where he is a professor in biomedical engineering.  Niren, it's a pleasure having you on today.

NIREN:    Yes, it's great to be here.

ROB:    I am impressed by the kind of things you are doing there.  Now biomedical engineering, is that about the hardest degree that you could get at Tech as an undergrad?

NIREN:    You know, I wouldn't actually say that.  I think all the engineering sciences and many of the degrees here are very challenging.  I think there are some unique aspects of biomedical engineering that can be challenging to students.  The big one is that a degree in biomedical engineering forces the students to have a very solid grasp of engineering and mathematical concepts, but also to have a very sound understanding of biology and physiology.  And the way of studying those two subjects is very different, so usually some students can grasp the mathematical concepts much faster than they do the biological concepts, or vice versa.  So forcing the students to sort of understand both areas simultaneously does pose some unique challenges.

ROB:        What about chemistry?  Is that a major part of the program?

NIREN:    I think the biomedical engineer ...  There's a pre-med track, so there are biomedical engineering students who are interested in going on to medical school, and they would be required to take a year of organic chemistry.  Now there is also an area of biomedical engineering called biomaterials which does involve a certain amount of chemistry.  And the amount of chemistry in the area of biomaterials is rapidly increasing.  So I would say right now, there isn't a whole lot of chemistry in biomedical engineering, but that's going to change soon or is changing.

ROB:        Now this program is a joint program with Emory University, right?

NIREN:    That's correct.

ROB:        And you are a professor both at Tech and at Emory?

NIREN:    That's correct.

ROB:    Do you teach any classes?  I know you teach classes at Georgia Tech.  You teach two classes, right?

NIREN:    That's correct.

ROB:        And they're both in biomedical engineering, various aspects, right?

NIREN:    Yeah.

ROB:        What about at Emory?  Do you teach anything there?

NIREN:    No, I do not teach anything at Emory.

ROB:        Is it only a graduate level program at Emory?

NIREN:    That's right.  It's only graduate courses at Emory.

ROB:    You started off in a way that's a little unusual for a biomedical engineer.  You were an undergraduate political science major, right?

NIREN:    Yes, that's right.

ROB:    And then you got your Ph.D. in biomedical engineering at the University of Washington.

NIREN:    Yes.

ROB:        And then you worked as a post-doctorate fellow at Berkley, right?

NIREN:    That's correct.  Yes.

ROB:        And you've been at Georgia Tech for about six years?

NIREN:    Yes.

ROB:    And there is a program ...  There's some great research going on over there as I understand it.

NIREN:    Yeah, there's a lot of interesting research at Georgia Tech and Emory right now.

ROB:    And there's one program that you're heading up.  Grad students are working on the project with you, right?

NIREN:    Yes.  We have a project on the polyketals, which is a new family of biomaterials for drug delivery.  One of my graduate students, Michael Heffernan, initiated that project.  He's now a post-doc at the NIH.

ROB:        And basically when you say bioketal ...  Is that what you---?

NIREN:    It's a polyketal.

ROB:    Polyketal, I'm sorry.  A polyketal is just a way to transmit whatever drug it is to the right part of the body.

NIREN:    Yeah, that's basically it.  We're right now using polyketals ...  we're investigating their ability to improve the treatment of a variety of diseases, and this is all done in collaboration with many wonderful collaborators at Emory University mainly.  So, for example, with Michael Davis, who is also a professor in the Georgia Tech - Emory Biomedical Engineering Department, we've investigated the ability of polyketals to improve the treatment of myocardial infarctions or heart attacks.   In this case, the therapeutic aspect of polyketals is to simply directly inject them in to the heart tissue after a heart attack with the idea being that the polyketals can stay in the heart tissue for a long period of time and slowly release therapeutics.  We're also collaborating with other researchers on using polyketals for vaccine developments, such as Bali Pulendran at Emory, and also using polyketals to treat a variety of inflammatory liver diseases.

ROB:    So the bottom line is what you're developing is the way to get the medicine there, not the medicine itself.

NIREN:    That's correct.  That's exactly right.  Just to improve the efficacy of currently existing medicines.

ROB:    And were you the one that told me that with a heart attack, the biggest problem isn't the immediate aftermath of the heart attack; it's ... For those that survive, and most people do survive them, the inflammation is created when the heart tries to repair itself.

NIREN:    Yeah, that's exactly correct.  Many people will survive the initial heart attack, but that initial heart attack causes an inflammatory response that never goes away and persists.  And that chronic inflammation in the heart tissue essentially prevents the heart from regenerating properly and then causes essentially heart failure one to two years after the initial heart attack.

ROB:    So the polyketal that you inject is to get anti-inflammatory medicine directly in to the heart?

NIREN:    Yes.  It's to get the anti-inflammatory medicine in the heart, and then to keep it there for a period of months to years so that you can sort of bathe the heart tissue in this high concentration of the drug for a prolonged period of time.

ROB:        To leave it there?  You don't have to keep injecting it?

NIREN:    No, that's exactly right.  You just have to do one injection, and the rate at which the polyketals hydrolyze is slow enough to sort of allow the medicine to exist in the heart tissue for months.

ROB:        And you're also expecting to use this a lot to treat the liver, right?

NIREN:    Yes, that's correct.  In the heart example, we're using polyketals that are between ten to twenty microns in size.  One micron is one millionth of a meter.  For the heart project, we're using big particles.  For the liver project, we're using particles that are under one micron in size.  And the idea is that these particles are going to be injected intravenously, and because of their size, they get taken out by the liver and a particular cell type called a liver macrophage, also known as a Kupffer cell, these cells take up these particles extremely well because of their small size.

ROB:    And the bottom line trick here is that the macrophages generally attack bacteria right and grab bacteria and isolate them?

NIREN:    That's correct, yes.

ROB:    And here the polyketals are the same size as bacteria, and the macrophages are doing their job looking for bacteria without regard to the fact that it's not really bacteria that it's picking up here.  But it's polyketals with medicine in them.

NIREN:    That's exactly correct, yes.

ROB:        It sounds very clever.

NIREN:    Oh thank you.  Yeah.

ROB:        And nobody had thought of it before?

NIREN:    Well, no.  Some people have used micro particles for various procedures.  So the history here is interesting in the sense that people have wanted to do intravenous drug delivery for a long time, and there's a lot of publications on wanting to do intravenous drug delivery, but they're usually trying to avoid the macrophages because they're usually trying to deliver their drugs to some other part of the body, and it turns out that everything ends up in the macrophage.  And so there's not a lot of work on people delivering micro particles to macrophages for the purpose of treating macrophage-mediated diseases.  And some of the recent developments here is that the importance of macrophages in liver diseases has just recently been developed.  And many therapeutics that you would use such as siRNA have also been very recently developed.  But I should say people have tried to deliver therapeutics to macrophages using something similar to a micro particle which is a liposome.

ROB:        Which is also small and works the same way?

NIREN:    Yeah, basically.

ROB:    Now when we talk about microns or particles the size of bacteria, we're talking about nanotechnology in a very general sense, right?

NIREN:    Yes, that's correct.

ROB:    The specific definition of nanotechnology is that it specifically, in the technical sense, refers to particles that are much smaller than a micron, aren't they?

NIREN:    Yes.  The traditional notion of nanotechnology is something on the order of ten nanometers.

ROB:        And this is a hundred right?

NIREN:    It's actually a thousand.

ROB:        Bacteria are much larger than viruses or molecules?

NIREN:    That's correct.  Viruses are around a hundred to two hundred nanometers, bacteria about one micron.

ROB:        Now you've already done this with mice, and it works on mice, right?

NIREN:    That's correct.

ROB:    In fact, in the United States or maybe just generally in medicine, we have more ways to help mice than any other animal right?

NIREN:    Yes, that's correct.

ROB:    So our next step ...  The next steps would be to use pigs because they are closer biologically to humans, right?

NIREN:    Yes, we are planning to do some pig studies with polyketals for improving the treatment of myocardial infarctions.

ROB:        And you've applied for a grant?

NIREN:    That's correct.  We formed a company in collaboration with Mike Davis and Lori Downy.  We formed a company together on polyketals.   One of the first experiments that this company plans to do is pig studies.

ROB:    The grants won't be enough to do the study, right?  You're going to have to raise capital too?

NIREN:    The initial pig study probably could be done.  I would say a small pig study could be done through just grants.  A much larger pig study may also be done through grants, but it's questionable.  At some point, we will have to raise outside capital.

ROB:    And you had mentioned to me that there is a silver lining in the recent recession conditions we have right now, the bad economy, for research in colleges.  And what was that?

NIREN:    It's very specific to the NIH or for people who apply to the NIH for funding in the sense that the Stimulus Package did give a certain amount ...  increase the amount of funding that the NIH got, so there were certain ...  I'm not sure what the exact number was, but the NIH did get extra additional funds, and those additional funds are being used to increase the amount of research activity that goes on in universities.

ROB:    Yeah, I mean that could really pay off in the long run.  It's sort of like the .com bust got us all the infrastructure for the internet.

NIREN:    That's absolutely right, yeah.

ROB:    Are there any other experiments going on at Tech that you can mention that are in biology or medicine that are interesting?

NIREN:    Yes.  So I think one of the very strong parts of Georgia Tech and Emory is their expanse in the areas of reactive oxygen species. So Emory is certainly one of the leading universities in the world on studying the biology of reactive oxygen species and understanding the role of reactive oxygen species in various different inflammatory diseases such as Atherosclerosis or various neurodegenerative diseases and cancer also.

ROB:        What is that?  Can you explain what that is?

NIREN:    A reactive oxygen species?

ROB:        Yes.

NIREN:    Yeah.  So a reactive oxygen species is essentially any molecule that contains oxygen, but has something called an unpaired electron.  And so these are also called free radicals basically.  And so you know how people always say you take antioxidants because those are good for you, so antioxidants are just Vitamin C, essentially scavenge these free radicals or reactive oxygen species.  And so a lot of the basic biology of how these reactive oxygen species are produced and why they cause disease, it turns out, was discovered at Emory University.  And my lab has benefited from this enormously because our lab has now developed a lot of ways of imaging reactive oxygen species, and so that works out really well with collaborators at Emory.

ROB:        And when you say species, what sense of the term are you---

NIREN:    Species just means that there are many different types of reactive oxygen molecules.  So to give you an example, one of the most common ones would be something called Superoxide.  And so Superoxide is a molecule that's produced essentially from oxygen, so your cells they need oxygen to make energy.  But in the process of converting oxygen into energy, it turns out that a small fraction of the oxygen gets converted into a reactive oxygen species called Superoxide.  And so basically if you add a few electrons to oxygen, you get Superoxide.

ROB:        And that's damaging?

NIREN:    That's very damaging because it will do a reaction called an oxidation to a variety of other molecules inside of cells, and then it also gets converted into another reactive oxygen species called Hydrogen Peroxide, and that also causes a bunch of bad things that lead to a variety of diseases such as Atherosclerosis and cancer.

ROB:    In the body we end up with Hydrogen Peroxide in our body without drinking any of it?

NIREN:    That's correct.

ROB:    Oh good grief!  Niren, if anyone wants to get in touch with you about the work you're doing or the school you're teaching in, what would be the best way for them to reach you?

NIREN:    E-mail would be the best way.  My e-mail is niren.murthy@bme.gatech.edu.

ROB:    Very good, thanks.  And I do want to thank Steve Nagler who was formally the chief surgeon at Northside Hospital for helping me to understand this and to meet with me and Niren to discuss some of these different issues and help with questions.  Niren, this was fascinating.

NIREN:    Thank you very much.

ROB:        And I really appreciate you're being on.

NIREN:    It was a pleasure being here.