Douglas Richman Interview – August 4, 1997

  • Interviewee: Douglas Richman
  • Interviewer: Mark Jones, PhD
  • Date: August 4, 1997

JONES: How long have you been here at UCSD?

RICHMAN: Twenty-one years.

JONES: When did you meet Karl Hostetler and Dennis Carson?

RICHMAN: When I arrived, I became friends with them. Yeah, actually, one of the guys I did a fellowship with at the NIH was a very close friend of Dennis', so I’ve known them both since I got here.

JONES: And you’ve collaborated closely with them over the years?

RICHMAN: I’ve done research with them since the ‘70s, some collaborations, and we’re friends as well.

JONES: Were you working with Karl when he was working with calcitonin and putting it in lipid envelopes?

RICHMAN: He was doing some of that. We had worked with a amantidine, an anti-influenza compound. We’d done some research for that, and then he was doing his liposomal stuff and I was working on anti-virals. We decided to put it together. There was a request for proposals for drug discovery programs at the NIH. We responded to that, and my memory of it was that, although we both thought it was a good proposal, the review committee decided to change the review criteria from what the NIH requested proposal was, when they set up their criteria for evaluation. The review criteria specified brain delivery, which had nothing to do with the NIH request for proposals. So, we didn’t get funded, and we were both upset about that. Karl was so ticked off that he said, ‘Well, I’m going to get private money to support it,’ and that was the start of, or at least part of the impetus of starting Vical. If we had gotten the NIH grant, we might not have done it.

JONES: Were you planning to be part of this from the beginning, or was it just Karl’s idea for his stuff with calcitonin?

RICHMAN: No, what prompted the Vical stuff, I think, was primarily the anti-viral drug delivery. Calcitonin was sort of added on, I think, as part of the package. Karl was sort of the major driving force.

JONES: Do you recall how he got hooked up with Tim Wollaeger?

RICHMAN: I think he just started snooping around for venture capital, to start something. He can tell you more of how, in his snooping, he managed to.

JONES: Then how did you get involved once...

RICHMAN: Well, you know, we were scientific collaborators, and that’s been my role, basically. I’ve sort of kept away from the business end. I’ve never fancied myself as much of a businessman. I’m sort of a....

JONES: So, prior to this, you never had any notion of commercializing any of your research?


JONES: When did you start working with AZT?

RICHMAN: In the beginning, when it was actually the first...Sam Broder and I, we were interns and residents together, and close friends. He was at the NCI at the time. He subsequently became the director of the National Cancer Institute. But he was the one who evaluated the drug under code for Burroughs-Wellcome, to show that it worked against HIV. And he called me up to see the data, and discussed it with me before it actually became public. And then they did the phase I study at the NCI, and when it was clear that it had some activity, and that a large phase II study was needed, I was asked to be one of the people to design the multi-center phase II trial.

JONES: And when Vical was started, was the idea initially to develop something with AZT?

RICHMAN: Yeah, the delivery of necleosides in a more effective way was part of the concept, yeah.

JONES: Is this something that Vical was shopping before Burroughs-Wellcome?

RICHMAN: No, clearly Burroughs-Wellcome had AZT. That was not an issue. But we thought that we had a way that could potentially deliver it more effectively in a modified form. And in fact, I guess the first business partner that Vical had was Burroughs-Wellcome, to evaluate that.

JONES: And were you involved in setting that up, did you go and make presentations?

RICHMAN: Yeah, yeah, I sort of made the initial contacts, and we went to RTP [Research Triangle Park] and made presentations.

JONES: So you knew people at Burroughs-Wellcome through your AZT research?

RICHMAN: Well, even before that. David Barry who was head of Infectious Diseases, and subsequently became president of Burroughs-Wellcome, we were fellows together back at the NIH, and I’ve known him since the early ‘70s.

JONES: So, they gave you, the company, $5 million.

RICHMAN: I can’t remember the numbers.

JONES: And you made it work, right? That was the outcome?

RICHMAN: Well, basically, the ultimate development of that AZT derivative was dropped by Burroughs-Wellcome.

JONES: But you had delivered something to them that could have been developed into a product.

RICHMAN: Yeah, and for various reasons, they chose not to do it.

JONES: So what was the fate of that technology?

RICHMAN: Well, this is something that has had its ups and downs because there were many other subsequent derivatives of this technology that have gone into a whole series of patents that Karl has been the prime mover on, with applications for hepatitis and HIV, and those patents were...when Vical sort of discovered the naked DNA technology, it was decided by the business leaders that they should keep the business plan clean and focused, and they sold off all of the drug delivery component to Nexstar, or whatever, it was a different name initially, and they were simply incompetent in developing and managing that opportunity. They ultimately dropped it and gave it back to Karl.

JONES: So he owns it now?


JONES: Is he trying to do something with it?


JONES: But not with AZT, right?

RICHMAN: Yeah, but actually Boehringer-Mannheim is doing something with AZT that, in fact, ended up being covered by one of these patents.

JONES: So they’re now licensing it?

RICHMAN: Well, I think they had to license it, yeah. Karl can tell you the details.

JONES: Well, after the drug delivery component was sold off, did that effectively end your participation in the company?

RICHMAN: No, when that was discovered, we had scientific advisory board meetings to discuss what to do. And I suggested that the best way to prove that this was effective was to show that you could immunize animals and protect them from dying. Prevention of death was the most convincing. And so I suggested that the influenza model would be the best way to do it. And actually I generated the reagents and the various constructs and viruses and models from various colleagues that I knew from when I was in influenza research, and assembled them, brought them to Vical, and designed the experiments that ultimately proved that the naked DNA protected mice. They sold that to Merck and in its various configurations, I was basically dropped from even the conception. You know, it was published without my name even being acknowledged, that Science paper that showed that it worked, and my comments to them about how they had performed and various other things probably led them to choose to drop me, as well as Dennis Carson, from the Scientific Advisory Board. So, my history as a co-founder, that was the end of it.

JONES: That was something that you decided not to challenge?

RICHMAN: I told them what I thought of them and just left. I have work to do. I’m an academic.

JONES: Early on, were you involved in recruiting people to Vical?

RICHMAN: Yeah, I was involved in evaluating people like Danny King and Wick Goodspeed, and various other people who were hired. I was involved in interviewing them and talking to them.

JONES: And scientific people as well?

RICHMAN: Yeah, Phil Felgner, for example, right. So, early on, I was sort of more involved. I was actually on the Board for the first several months or whatever, but as venture capital came in, the venture capitalists took board positions.

JONES: Have you been involved in other companies locally, or elsewhere?

RICHMAN: I’ve been a consultant on scientific advisory boards for a number of companies.

JONES: Nexstar?

RICHMAN: No. Initially, Viagene. I’m on the board of company up in the Bay Area, Virologics, and then I’m involved with Triangle, which Karl and Dennis founded.

JONES: What were the connections with Viagene?

RICHMAN: That’s sort of a gene therapy company, and they wanted to get into HIV, so they wanted somebody who knew something about HIV.

JONES: Who contacted you?

RICHMAN: Doug Jolly.

JONES: Did you know him when he was here?

RICHMAN: A little bit.

JONES: But mostly by reputation?

RICHMAN: Yeah, I guess so.

JONES: Are you involved with Dynavax?

RICHMAN: I’m on their SAB as well, because I’ve been working closely with Dennis and [?]. We have a paper in this month’s Nature Medicine.

JONES: What was your impression when Vical started, you were aware of Hybritech?

RICHMAN: Yeah, actually Ivor and Sam Broder and I were all interns and residents together at Stanford, twenty-seven, eight years ago, and his lab was right next to mine at the VA.

JONES: Did you ever collaborate with him?

RICHMAN: I never did any research collaboration, but I knew what they were doing, and I knew Howard Birndorf, his lab tech in the lab next door at the VA on the sixth floor.

JONES: What was your impression of the Hybritech people and what was going on?

RICHMAN: It struck me as more entrepreneurial than science, but, you know, that’s fine, I’ve got my work to do.