Show Notes
Microbiologist Phillip Furman is the inventor of AZT, an anti-HIV drug, and other antiviral drugs for Herpes and Hepatitis B and C. He talks about his breakthrough moments, the difficulties of taking “miracle” drugs to market, and the culture shock of moving from New York to Florida as a teenager. Furman’s interest in science was fueled at age 8 with the gifts of a microscope from an uncle and a chemistry set from his parents. His advice to researchers: “Follow the data. Negative results give you as much information as positive results." *This episode was originally released on October 23, 2019.*
TRANSCRIPT:
Intro: 0:01
Inventors and their inventions. Welcome to Radio Cade a podcast from the Cade Museum for Creativity and Invention in Gainesville, Florida. The museum is named after James Robert Cade, who invented Gatorade in 1965. My name is Richard Miles. We'll introduce you to inventors and the things that motivate them, we'll learn about their personal stories, how their inventions work, and how their ideas get from the laboratory to the marketplace.
Richard Miles: 0:36
Treating viral diseases is hard, but not as hard as it used to be, thanks to the development of antiviral drugs. Welcome to Radio Cade, I'm your host, Richard Miles and today my guest is Phillip Furman, a microbiologist and the holder of 20 U.S. Patents. The inventor of AZT an anti-HIV drug, and a 2018 inductee into the Florida inventors hall of fame. Welcome to show Phillip and congratulations.
Phillip Furman: 1:00
Thank you very much, Richard.
Richard Miles: 1:01
So, the problem with interviewing super inventors like you is trying to focus on just one thing, but you have 20 patents, you've done a lot of things and you've developed antiviral drugs for herpes, HIV, hepatitis B and C. And we could talk about each one of those probably for a long time, but then we'd have to order in lunch, dinner, and probably sleeping bags for this session. So let's start though with a basic definition of viruses for listeners who may not be microbiologists , how viruses act in the body and how they can be treated.
Phillip Furman: 1:33
Well, viruses, some people think are very simple. They are an intracellular parasite. They have to infect a cell in order to be able to reproduce themselves and their basic components are there genetic information, a virus capsid, which surrounds them. It's a protein coat that protects them once they get into the cell. And some of them have a membrane, which they pick up when they are released from the cell, but viruses aren't quite that simple.
Richard Miles: 2:07
Spoiler alert, it's not that simple.
Phillip Furman: 2:08
They, a lot of them contain or code for proteins or enzymes, which function in the replication of the virus. Everybody thinks that well, once the virus gets into the cell, it requires the cell to produce enzymes and proteins that are essential for virus replication. And the buyer system takes that over and doesn't have any of its own proteins or enzymes to replicate itself, but indeed they do.
Richard Miles: 2:34
So you've been working on this for quite a long time. Right? You got your undergraduate degree in microbiology?
Phillip Furman: 2:40
In microbiology. Yes.
Richard Miles: 2:42
What was your big breakthrough? Which one of the antiviral drugs came first?
Phillip Furman: 2:46
Acyclovir was the first one I worked on.
Richard Miles: 2:49
And that's treatment for herpes viruses?
Phillip Furman: 2:52
Yes.
Richard Miles: 2:52
Do you remember the path, the conceptual path that got you there. What was the first thing that you noticed or discovered that made that possible?
Phillip Furman: 3:00
Well, the compound at the time was already discovered and patented. That happened in 1974 and I was a postdoc at Duke University and the department had at Burroughs Wellcome, Dr. Trudy Elion, who became a Nobel Laureate, was looking for a virologist to establish a virology laboratory within the company. And so I was hired to do that. My job was to work on the drug to try to find out how it worked, how it inhibited the virus.
Richard Miles: 3:32
So describe for us how long that takes. I mean, I think there's a popular conception out there with a lot of inventions, including miracle drugs that you have a brilliant researcher has an insight developmental breakthrough. And few months, years later, we've got a wonder drug, but I'm guessing it's not that simple.
Phillip Furman: 3:51
Are you referring to time of discovery to time of marketing?
Richard Miles: 3:55
Well, yeah, something like that or at what point are you certain of your results? How long did that take for instance, the herpes antiviral drug? Was it a matter of months or a matter of years? How much followup research and testing before you kind of knew this?
Phillip Furman: 4:07
Well, it really is a matter of years. I mean from time of discovery to getting it to the market takes roughly 12 to 18 years.
Richard Miles: 4:15
Wow.
Phillip Furman: 4:16
Now you really don't know how effective a drug is going to be until you test it in humans for the very first time. And that can take from time of discovery to actually, first in humans, maybe five years.
Richard Miles: 4:31
Cause you start out with animals first. Right?
Phillip Furman: 4:34
Well, if you're looking at efficacy, it depends on whether or not there is an animal model available to test its efficacy . If not, well, then you've got to, and of course you do any way to get a drug approved, show primarily that it is safe. That is the main criteria that the FDA is looking for, that the drug is safe. And there's a lot of tests that go on between the discovery and putting it into humans to show that it's safe, both in vitro or in cell culture essays to show that it's not toxic to cells all the way to animals and doing in vivo toxicology studies.
Richard Miles: 5:16
So after you've completed animal trials, of course, the next big thing is to start conducting human trials, which I understand is one, very expensive, right?
Phillip Furman: 5:24
It is.
Richard Miles: 5:25
And then two, fairly lengthy because you have to have, I presume a big enough sample size, which requires drawing in appropriate humans to do the study, make sure that you're demographically balanced, et cetera, et cetera. And then of course there's a safety angle, right? It's not going to let you do this and start experimenting in humans with experimental drug, unless you've given them some assurances that this is not going to kill people, right?
Phillip Furman: 5:48
That's correct. The first studies in humans are a short trial with a small population of volunteers.
Richard Miles: 5:54
And how small roughly are we talking about maybe?
Phillip Furman: 5:57
Um, 50 to 100. And what they do is they agree to take the drug for a certain amount of time and then are followed by physicians to look for any adverse reaction to the drug. And that's called the phase one study.
Richard Miles: 6:13
And that can take a couple years?
Phillip Furman: 6:15
No, that can take a year. Now the phase one study is primarily to show safety.
Richard Miles: 6:23
Okay. No negative effects. So you're not even looking to see does the drug work, does it not harm people?
Phillip Furman: 6:30
Now, that has changed a little bit in that the human volunteers can also be people who are infected with the virus. And that's what was done with AZT. That's what was done with drugs for hepatitis B and hepatitis C. The investigators were able to do these short term studies to show safety, but they were able to do them in volunteers who were infected with the virus. So they got a quick handle on whether or not there was any efficacy for the drug.
Richard Miles: 7:01
I see. So it's beneficial, I guess, from both sides, right? Because from the investigator side, you now get to jump to, I'm actually treating someone who has this condition. And from the patient side, they're getting access to potentially a lifesaving drug, presumably a lot earlier than they might.
Phillip Furman: 7:18
Not really, no. You still have to follow the protocol that the FDA requires. And that is to do the phase one study, which is primarily a safety study. Then if you show safety, you can go to phase two, which is where the bigger population of patients. And those are generally patients who are infected by the virus. So that's really your first real look at efficacy. The phase one study that's done in human volunteers shows you some efficacy. It helps you to determine what dose you might want to use in your next studies
Richard Miles: 7:57
In phase two studies. How many people does that involve?
Phillip Furman: 8:01
Oh geez, that's several hundred.
Richard Miles: 8:03
Several hundred. Okay . And they have to be presumably recruited and screened so that, you know, you're going to get some pretty representative results .
Phillip Furman: 8:11
That's right, that's right.
Richard Miles: 8:12
Those take several years or how long did this take?
Phillip Furman: 8:15
The study probably will go on six months to a year. A lot of it depends upon what the FDA is going to require. After the phase one study, you meet with the FDA with a proposal for phase two and they can have you adjust your study , uh , according to what they want to see.
Richard Miles: 8:33
Let's talk about efficacy. How does the world look different now for someone with HIV or hepatitis B or C with the development of these antiviral drugs? What was it before in terms of quality of life, life expectancy, that sort of thing. And what does it look like now?
Phillip Furman: 8:47
Well, for any of these chronic infections, we won't talk about herpes because that's really, although it's a chronic infection wasn't necessarily life threatening, but with HIV, it progressed dramatically from AZT to other drugs and combinations of drugs with AZT, there was some efficacy involved, but it wasn't perfect. It wasn't the best. And we knew that from the start, that AZT would be well, if you will, the breakthrough to show that you can treat HIV much, like you treat heart conditions, diabetes, cancer, as a chronic disease, it wouldn't be a cure, but you could hopefully extend the life expectancy of the patients. There was some positive effects with AZT , but as I said, it wasn't the best, but it opened the door to other pharmaceutical companies to come in and develop other drugs. And some of these drugs were put into combination with AZT. And now the life expectancy with the new drugs that have come out, people can live a normal life.
Richard Miles: 9:53
Wow. That's stunning. Really. I mean, if you think about HIV/AIDS was I guess, first discovered in the eighties, right?
Phillip Furman: 9:59
Yes.
Richard Miles: 9:59
And at that time effectively was a death sentence, right?
Phillip Furman: 10:02
Yeah, it was.
Richard Miles: 10:02
It was basically some matter of time. And now, like you said, it's in the same category as having heart disease or kidney disease or something that it's a serious condition, but yet it can be managed effectively. In combination with these drugs.
Phillip Furman: 10:16
Now hepatitis C on the other hand is totally different. It is a chronic disease, but it's curable. And the work that we did at Pharmaset, the discovery is Sofosbuvir showed that you can cure hepatitis C patients up to 99% of them, as opposed to the combination of Interferon and Ribavirin, which was able to cure maybe at the most 50% of the patients that were treated. A lot of them failed. A lot of them quit because the Interferon / Ribavirin in combination was actually like having the flu for as long as you were on the combination, people were just miserable.
Richard Miles: 10:58
Right, right. And taking it, it's a bit of a double edged sword when you have these incredible breakthroughs, like with HIV and AZT, do people begin to think that this is an easier process than it actually is because on hand, people say, well, look, once we throw enough money at this, then boom, we come up with a pretty good solution or does it spur maybe more funding, more research, more resources devoted to other diseases? Sometimes success is more problematic than failure, right? It brings new problems that you didn't even think of before has that also to some extent happened in the drug discovery world?
Phillip Furman: 11:33
Oh absolutely, I will refer back to Acyclovir. Prior to the discovery of Acyclovir, there was very little work going on in antivirals. The focus of antiviral drug discovery from 1960s forward to Acyclovir was minimal. Few companies were dabbling in. It all focused on herpes viruses and the drugs that they were coming up with all came from anticancer programs. So they were very toxic and could not be used systemically, but Acyclovir was really the game changer because, it was found to be not only specific for herpes virus, but very selective in that it was relatively nontoxic. And so it was consequently the first approved antiviral for herpes or antiviral drug that could be used systemically.
Richard Miles: 12:27
Wow.
Phillip Furman: 12:27
The others were all used topically.
Richard Miles: 12:28
So Phillip, you're uniquely, I think qualified to sort of look at the whole drug discovery process from the beginning to a successful conclusion. And this is something that constantly has the attention of politicians and society at large healthcare , particularly diseases. Are there things that from a policy perspective, say the government or even private foundations when they make their decisions about how to spend money, are there changes in that process? Again, starting out with the researcher, the investigator through to getting the drug or the treatment on market that government should be doing, whether it's national state local, or that foundations that support research should be doing that would make this process easier, that isn't getting attention? Only easy questions on this show Phillip, we don't go for hard ones. Or if you want to focus on any one segment of that, is there a policy change that would make some of this a little bit easier and faster?
Phillip Furman: 13:22
Well, there was a policy change in the FDA that occurred because of the approval of AZT and what it allowed the FDA to do was to approve certain drugs for diseases that were serious diseases, basically like AZT where the outcome was obviously you are going to die, right? And the approval of AZT did help the speed up the approval process in that the FDA shortened, the approval process for drugs that met an unmet medical need. And that was for patients who were dying from a disease, that there was no drug available. And so they actually changed the regulations so that in situations where there is an unmet medical need and it was life threatening, that they would allow drugs to be approved more rapidly with less data.
Richard Miles: 14:22
Okay. So if you were to compare this, to say some new drug or procedure that aided in heart disease, the FDA could say, well, look, there are other available treatments for heart disease. So we need to go slower on this. Cause we're not sure if it's better, et cetera, et cetera. But in this case in HIV, there was no alternate treatment,
Phillip Furman: 14:38
That's absolutely right.
Richard Miles: 14:39
And people are dying l eft a nd right. So i n those cases, that's a pretty solid contribution I think, as a lay person, what I would hear and continue to hear to some extent i s t hat, well, gosh, if only the FDA, w e're not as slow, we're more efficient t han we'd have more of these drugs on the market. And it sounds like the development of A ZT in particular helped shorten that cycle for those cases, in which,
Phillip Furman: 15:00
There was an unmet medical need.
Richard Miles: 15:03
Right, there's no other option on the table. Phillip let's talk about you for a little bit. And like a lot of people in Florida, you're from New York. You're not from Florida lets put it that way, you came to Florida as a teenager to Tarpon Springs.
Phillip Furman: 15:16
That's correct.
Richard Miles: 15:17
So what was that like? Was that a bit of a culture shock?
Phillip Furman: 15:19
Oh it was.
Richard Miles: 15:20
To come down to Tarpon Springs, first of all, why did you move? Did your parents get a new job down here?
Phillip Furman: 15:25
My dad took a job that required him to travel. He worked for a refrigeration company and he was given the state of Florida, Georgia and,
Richard Miles: 15:36
Kind of as his territory?
Phillip Furman: 15:37
Yeah. It was his territory. And so felt that moving to Florida and centralizing in Florida would be the thing to do.
Richard Miles: 15:46
And so you were kind of drawn to science at an early age, right? I mean you fairly were a good student. Is there a particular teacher or class in particular where you thought this is great? I love this.
Phillip Furman: 15:56
Well, yes. I mean, when you said that I was drawn at an early age, I was, probably about eight years old. My uncle gave me a microscope. That was his, when he was a kid. And I was just absolutely fascinated with what you could see with a microscope.
Richard Miles: 16:12
Do you remember some of the first things that you would try putting in the ,
Phillip Furman: 16:15
Just water from, out in the driveway or leaves or onion skins? Oh , you know, a lot of the same things that most people would probably look at, but it opened a whole new world for me. And then, well then after that probably a year or two later, my folks gave me a chemistry set. One of those big Gilbert chemistry sets. If you ever seen one of those. And I would work in the garage in the summertime with that chemistry set, there was a bench out there and I'd have that set up in the winter when it was snowing, I would go down in the basement and there was a work bench there that I put it up .
Richard Miles: 16:51
Were your parents ever worried about the garage blowing up?
Phillip Furman: 16:53
No, no.
Richard Miles: 16:53
So between the microscope and the chemistry set,
Phillip Furman: 16:59
That got me.
Richard Miles: 17:00
That got you, kind of hooked.
Phillip Furman: 17:01
I think there was always interested in exploring. And I think that opened up the whole idea of wanting to discover things, because the next thing, when I was 12 years old, my dad came home. He was taking flying lessons at the airport up in New York. And he came home and said that some people found arrowheads down along the river bank there where they plowed the fields, plant corn right next to the airport. Oh boy, I want to do that. So I went down and I actually , uh , been interested in archeology ever since and have done site surveys for the state of North Carolina.
Richard Miles: 17:41
Oh wow, okay . This is more than just a hobby?
Phillip Furman: 17:43
I was living in North Carolina. Well, I thought about that as a career, but I enjoy this too much. This is too much like fun. This is my relaxation.
Richard Miles: 17:51
Ok right, you didn't want to make it, you didn't want to ruin it by making it work.
Phillip Furman: 17:55
But getting back to the question of who, when I was in college, I took a microbiology course and became very interested in microbiology. And I happened to be myself and my suite mate. I happened to be very fortunate to have a very good relationship with the chairman of the department. And he kind of took us under our wing and under his wing, sorry, he kind of pushed me towards medical microbiology. I thought that's what I wanted to be. It was a medical microbiologist and working in the hospital laboratory and doing,
Richard Miles: 18:32
And that was here at University of South Florida, right?
Phillip Furman: 18:34
No, this was at Piedmont College. Yeah. Where I got my bachelor's , but then when I graduated, I thought, you know, I really probably need more education and I should probably get a master's . And so I applied to USF and got into the master's program and was very fortunate again, to have another tremendous mentor , uh , Dr. John Betts , who passed away a few years ago. And I did my dissertation research with him and it was amazing. I mean, I worked on a phenomenon called the auto plaque phenomenon. This particular type of bacteria kind of kills itself. And we tried to figure out why I did all sorts of experiments, played around with bacteria phage, which is a bacteria virus that infects bacteria and kills them and did a lot of work on electron microscope. And I thought , wow, this is terrific. And so when I finished up everything, I went and talked to him about what I ought to do for a career. Should I do anything more? And he said, you should go on and get your PhD. I said, well, I'd like to do the same things I'm doing with you. And he says , no, you ought to consider animal viruses their up and coming thing. And that was actually back in 1970. So animal viruses were beginning to become very popular to work with. And so I went on to Tulane and got my PhD in microbiology with an emphasis in virology.
Richard Miles: 20:07
That's a perfect segue into my next question, in which I imagine now roles are reversed in which you have graduate students coming to you, or you have other people maybe in the industry coming to you, seeking advice, if you could meet your 21 or 22 year old self, or maybe 21 or 22 year olds seek your advice, what sort of advice do you generally give them? And then I guess I'll tack on one question. What sort of questions do you normally get? Are they all sort of very specific? Do I go to this program or that program? Are they more general? Like what do I do as a career type of questions?
Phillip Furman: 20:38
I think it's more, what should I do for a career? Basically tell them to follow their heart. What did they love? And once they find what they're looking for to not just focus on that one specific thing. You know, don't focus in on virology, learn everything that you possibly can. If it includes other disciplines, learn that you're bound to find something in a totally different discipline that might be applied to what you are really interested in focusing on. And then I would probably tell them as Jim Valvano, the basketball coach that died of cancer, who was a coach at North Carolina State University, don't give up, don't ever give up. One last thing is with regard to their own personal research as to keep an open mind, follow the data, that negative results to give you as much information as a positive result. Well, that is all great advice. I think you need to write a book or something about something you said jumped out at me and something I've heard from a lot of inventors and that is while you're focused on one area, nevertheless, bring in insights from other disciplines or other areas because that's, I think truly where the invention part happens, right? Because if you're just staring at your data all day long, that's all you see. But if you're able to bring in other models, other paradigms from totally different fields or dissimilar fields, that's often where you're able to now look at the same data and just come away with different conclusions or insights . I've heard that from a lot of inventors. I'm guessing there's something there. I think there is.
Richard Miles: 22:18
I think there's something there. Thank you very much for being on this episode of Radio Cade, I neglected to mention we're recording this and the Palatial Studios of University of South Florida in Tampa with the assistance of the Ford Inventors Hall of Fame with whom the Cade Museum has a partnership. So we're very happy that USF and Ford Inventors Hall of fame connection and Phillip thank you very much for being on the show.
Phillip Furman: 22:38
Thank you.
Outro: 22:40
Radio Cade would like to thank the following people for their help and support Liz Gist of the Cade Museum for coordinating and vendor interviews. Bob McPeak of Heartwood Soundstage in downtown Gainesville, Florida for recording, editing and production of the podcasts and music theme, Tracy Collins for the composition and performance of the Radio Cade theme song, featuring violinist, Jacob Lawson and special thanks to the Cade Museum for Creativity and Invention located in Gainesville, Florida.
