Dr. David Aronson November 22 ,2002

PDF: Aronson, David oral history 2002.pdf

This is an interview with Dr. David Aronson in Bethesda, Maryland, on November 22,2002. The interviewer is Jessie Saul. 

Saul: We're talking today with Dr. David Aronson, and Dr. Aronson has been at the FDA and, previous to that, the Bureau of Biologic Standards.

Aronson: The Division of Biologic Standards.

Saul: The Division of Biologic Standards, for quite some time. And we're going to talk today about safety practices in blood banking and how the NIH has been involved in producing blood-supply safety policies and your experiences with NIH in general, which is quite a wealth of experience. If I could ask you first about, we've been talking a little bit about sort ofblood issues in general, and I wondered how you ended up at the NIH to begin with.

Aronson: Well, in those days, there was a doctor draft.

Saul: A doctor draft.

Aronson: This was in 1956. After I finished my internship, I became what became known as the yellow berets, a stint in the Public Health Service. For the first year, actually, I worked down with an epidemiology group downtown under Dr. Carol Palmer, one of the big gurus in tuberculosis epidemiology. But the laboratory work was more my interest, and I found a position out here in the old Division of Biologic Standards headed up by Dr. Roderick Murray. And life was good in Bethesda, and to get out of the Public Health involved filling out too many forms, so I stayed in for 30 years.

Saul: Because there were too many forms to fill out.

Aronson: Yeah. And then when the work involved too many forms to fill out, I resigned. Saul: Okay. (Laughs) What kinds of projects were you working on when you first got here?

Aronson: The plasma proteins in general. I sort of fished around for the first year or so, working mostly on plasma protein, coagulant prothrombin, and the biochemistry of that, which was just beginning to be understood.

There were very few regulatory issues in those days. The first regulatory products we had were the some of the very early fibrinolytics, including streptokinase, plasmin, and plasminogen, but things like purified factor 8 for treatment of hemophilia A were on the horizon. Fibrinogen was a little bit of an issue. That's not back that far. I think those were the things I remember off of the top of my head. There must have been a couple of others.

Saul: Sure. Getting into that kind of product-related research, what kinds of
safety factors were on the horizon at that point in time?

Aronson: The issues always were hepatitis at that time. Hepatitis had been described after blood transfusion in the early '40s.

Saul: Okay. You had mentioned before that we should go back to the '40s to really understand blood safety at the time.

Aronson: Yeah. And that goes back to the birth ofblood banking and transfusion. In the early '40s, during the Second World War, was when they started appreciating that this was an issue. People turned yellow. You did not have accurate and precise tests for hepatitis in those days. What you had was a measurement of serum bilirubin or the patient getting jaundice, which, when they turned yellow, that was, you had a case ofhepatitis. Anditwashepatitis,onething. Andthepattern wassortofsimilar,and most people got better. Occasionally you would have somebody who didn't get better, and this was usually in an older age group. But it was considered an acceptable risk. Saul: By who?

Aronson:

By the public health community. If you read the literature in the mid-'40s, blood transfusion was considered one of the great therapeutic advances of the century, which was young then. And things like people with bleeding ulcers could be saved, when they used to die.

Saul: Right.

Aronson: So that was an acceptable risk.

What they didn't know was the degree of the risk. When I arrived at NIH, the open-heart surgery was just starting, and another member of DBS at the time, Joe O'Malley, was interested in hepatitis.

Saul: Who was that?

Aronson: Joe O'Malley, Dr. Joe O'Malley, and was working on isolating the virus. And samples, and he talked to the surgeons at the Clinical Center, and they said, "We never see hepatitis." When finally they did this study — I think it's the late '60s; it must have been about the late '60s —they found something like 30 percentofthe patientswere getting hepatitis.

Saul: Now, who said they never see hepatitis?

Aronson: This was Dr. --1 think his name was Dr. Moore, the chest surgeon, who used to use a lot of blood. These were 20 units just to prime the pumps in those days.

Saul: Sure. This was who ended up doing the heart study in the post transfusion hepatitis study.

Aronson: 

Well, he may have been o it, but . . . And Paul Schmidt at the blood bank, they didn't get any feedback on it. Occasionally there was a, one patient who finally, I think, got them interested in this -- it may have been in the mid-'60s -- who ...     And they said, "We never see it," because the patients were removed from the hospital. The surgeons, of course, never saw that, and the patients were all from out of town, somewhere else. But there was one patient who did come in. He was a professor of

biochemistry, ifmy memory serves me right, at a small college in Ohio You can check those facts with John Finlayson over in Building 29. But anyway, and he died, again if my memory is correct.

But that stirred up a little bit of interest because now, as you were getting into more pooled blood products, and just the baseline hepatitis risk became apparent with the biochemical tests you had available. Instead of just, what was it, the . . . There was bilirubin and there was something called the -- the test depended on sort of abnormal precipitation of some protein, which were very imprecise. The Keilen [sp.] floculation test.

And these were the tests ...    Then in the mid-'S0s, you developed biochemical tests that measured very specific enzymes, which are still in the laboratory testing used today. But you had no way of chasing down the virus. The only model you had was using human volunteers.

Now, Dr. Murray did that for a while and used mostly volunteers in prison, which will get everybody upset these days. But it was well done and honestly done and with all ethical considerations taken care of by most. There weren't three-page written things and nobody knew what was going to happen.

Now, these were done during the war. You actually had people who didn't want to go in the army. There's a word for it.

Saul: Conscientious objectors.

Aronson: Conscientious objectors who would volunteer for this and other studies that were done, as well as prisoner volunteers. Dr. Murray did several very important studies on viral inactivation at that point, showing that if you heated plasma for 10 hours at 60 degrees or plasma fractions for 10 hours at 60 degrees, you did not get hepatitis.

Saul: Just to clarify, we switched from talking about blood to talking about plasmaandthedifferentstudiesthatweregoingon. The post-transfusion hepatitis studies with cardiac surgery patients —that was with whole blood.

Aronson: Yes.

Saul: Okay. Okay. And the plasma, there was a similar concern for plasma? 

Aronson: Yes.

Saul: And how, what...

Aronson: This, because of the known hepatitis risk in blood transfusion, it was assumed that that would transfer to plasma, that the infectious agent would be in plasma as well in the blood cells. In fact it was more in plasma than in the blood cells, probably. So when plasma fractionation began under Dr. Cohen during the war, this was immediately realized as an issue. They assumed that it would be an issue, but they didn't have any data, obviously.

Aronson: This is 1940-1945. But, incidentally, they found a way to, in one case, to make the fraction albumen viral-free. This was not the intent. The intent was to produce a product, which, in the vernacular of the old protein laboratory in Boston, would be stable in a tank in Tobruk, Tobruk being a small city in the north of the Sahara desert and under very hot conditions, and they found that there was a stabilizer, caprillic acid, that could be added, and it made it stable to high temperatures, and they tested this for 10 hours at 60 degrees. And later studies of Dr. Murray and other people of protein showed that albumen heated at 60 degrees for 10 hours did not transmit hepatitis. This was important to point out. This was liquid plasma, not dried plasma. 

Saul: Why is it important to point out?

Aronson: Becauseviruses areinactivatedatlowertemperaturesinliquid statethan in dry state.

Saul: Oh, okay.

Aronson: So that worked. 

The other plasma fractions that were being produced, fibrinogen and human thrombin, which was considered useful for stopping hemorrhage, were quickly found out to cause hepatitis, and the thrombin problem was fixed by making a bovine product which was free of hepatitis and, at that time, any known transmissible disease.

The fibrinogen was considered an important product, although there is no clinical data to this date that shows that.

Saul: What was it considered to be important for?

Aronson: 

Again, for stopping bleeding.

And one of the more interesting things was that the immunoglobulins, the antibodies from the plasma in a separate fraction, rarely produced any infectious disease. The Protein Foundation in Boston tried various methods to inactivate viruses, including a chemical beta­ propriolactone and ultraviolet light, common. These were tried out, but you didn't have good clinical data, and eventually it was quite clear that the way they were being used was not sufficient to inactivate viruses. So they pretty much fell by the wayside in this country, although a company in_Germany used that up until, oh, maybe 15 years ago.

Saul: Do you know what company that was?

Aronson: I can't remember their name offhand.

Saul: It wasn't Immuno, was it?

Aronson: No, no. Now, that leaves ...       I mean, the real holding point here was, after Dr. Murray's experience, nobody wanted to give test products in humans.

Saul: Dr. Murray being ...

Aronson: Being Ron Murray, who was head of DBS, had done the early work with the Protein Foundation on injecting samples into volunteers, and when he had a volunteer die, he decided this was not something to do. So, in essence, there was no way of getting around this. You either had the product with a risk or you had no product. This became very clear in the case of the hemophilia.

Now, the first product for use in hemophilia A patients in this country was licensed, I believe, in 1962 or 1963. It was a product made in the same way as you made fibrinogen, and you knew that it contained hepatitis.

A colleague who worked with Dr. Brinkhouse [sp.] in those days down in Chapel Hill was the big guru in hemophilia -- we didn't even have the word guru in those days -- talked about a meeting they had in the late '50s with a young biochemist, Murray Seelin [sp.], who was working on the purification of factor 8, and the issue of hepatitis came up. And Dr. Brinkhouse [sp.] looked up and said, "Our patients are dying of hemophilia. They're not dying of hepatitis." Now, the options in those days were plasma for any patient with hemophilia A, or we didn't know the difference between hemophilia A and hemophilia B for most of that time. It was to be treated with plasma transfusion or to be treated with nothing.

Now, to treat a severe hemophilia A with plasma would take a minimum of 500 units a year, and this was pushing the envelope for how much you could give to a patient.

Saul: How big is a unit?

Aronson: A unit is about 210 mils. A patient who had -- severe hemophilics who bleed 25 times a year, you want to treat them, so you give them the most you can give over 24 hours might be four units, four or five units, I guess, in a young, healthy guy, and you could raise the level up to about 20 percent of normal. But that level only stayed raised for about half a day to a day. It was not satisfactory treatment. These patients were in the hospital for months at a time. At that point, with plasma therapy, median age at death had gone up to about 30 years. Before plasma therapy was available, it was said to be about 15 years. I don't know how solid that data is, but that's . . . So there was a big advantage to having a pooled plasma fraction for the treatment of the patient with hemophilia. Instead of infusing two liters of plasma, you could get the same effect withl00 to 200 mils of the concentrate, and you could get much more efficacious treatment of the hemorrhage. So you were between a rock and a hard place in terms of transmissible diseases.

Saul: Because, was it known that ...   Not all of the products were infected with hepatitis. Or were they?

Aronson: You began to get the feeling that in fact -- and looking back, it was clear that every lot was infected with hepatitis, 100 percent of them.

Saul: Okay.  And was that known before, when            ?

Aronson:  No, no. And this was not detectable. And in fact this wasn't detectable by any test. And you treated the patients, and you had no test for whether they had hepatitis B other than they turned yellow. I'm not kidding.  This is basically it. Now, most patients who got hepatitis didn't turn yellow.

How many? What is it? You can check with Harvey Alter. He'll know. Five percent get jaundice within six weeks to six months, depending on the dose and the type of hepatitis. So these kids who got it young were okay because the problem...

Well, let's see how to jump at it.

Let's stay with hepatitis right now. We're thinking of one virus, although J. Garrett Allen [sp.] at Stanford said, because there seemed to be two incubation periods, there seems to be one a little bit shorter, more like six to eight weeks, and another one more like three to six months, and that was the only data you had about the chance of a different hepatitis virus.

It was quickly realized that the blood-transfusion hepatitis was not the common hepatitis, what we now call hepatitis A, because different epidemiology, shorter incubation time, etc. So the ...

Now, what did I want to split? Hepatitis Band hepatitis C. Hepatitis B was associated with more of the acute death, or so they thought at the time. And, again, all this stuff on hepatitis, Harvey can give you the real answer. But hepatitis C, when it was first described in the early '70s -- I think the publications are about 1975 -- was considered almost benign. Yes, you had occasional rises and sporadic rises for a long period in people of certain liver enzymes associated with hepatitis, but in general they looked healthy. So this was -- the hemophilia treaters considered this, well, it's just a transaminitis. It really doesn't mean ...

Our patients are doing very well. Whereas, and hepatitis B is our big concern. So that was your big effort in terms of improving viral safety. I mean, it's presumptuous of me to speak on hepatitis B testing with Harvey coming in, so maybe I ...

When the hepatitis B tests came, they were implemented as soon as possible. We're going right through the whole, initially with the amino precipitation methods, counter electrophoresis. Ray Shulman [sp.] at the Arthritis Institute -- I think that's where the Hematology Branch -- had a complement fixation test.  As soon as he became available, they were used, and the big trial was done by. Martin Goldfield in New Jersey, which just blew your mind out. He got rid of essentially all fatalities from acute hepatitis, although there were still -- and 50 percent of people came down with clinical hepatitis, which we now realize is hepatitis C. But that was a breakthrough. Immediately, all the plasma fractionators started screening with and updated as the test came along. This was a no-brainer; there was simply no reason not to do it, and it was effective and everybody was happier.

This test really improved the blood-bank safety. The impact on the plasma products I think was significant. There was one study done by -- I think Hal Casper [sp.] was probably on that paper, and another, the Hemophilia Center at Los Angeles Children's Hospital, where they followed young patients who'd only been treated with factor 8 derived from screened plasma, and they found a low percentage of patients with antibodies to hepatitis B.

Now, what this indicated, it wasn't foolproof, but before you had that screening, it would have been 100 percent. There was -- you'd get one or two lots, and because of the pooled product, you didn't dilute enough to prevent disease. You ended up with, everybody had to be exposed.  So that was a great leap forward.

Now, you had a test for hepatitis B. Now you had people getting interested in developing other models, and development of the chimp hepatitis B model was -- a lot of that was done between sort of the triangular, between Harvey Alter, people in Building 29, Lou Barker [sp.], and Bob Purcell in Building 5, infectious disease. So you developed -- in the early '70s, you developed an animal model for hepatitis B using chimpanzees. You got their sensitivity, how long it lasted, how to test for it. You couldn't use -- turning yellow wasn't a good sign. They did have their drawbacks. There weren't that many of them. You had people who said that was not nice to use chimpanzees for that. In fact, it worked very well, and a tremendous amount of knowledge came out of that that allowed the development of the hepatitis B vaccine. So hepatitis B ...

Saul: Quick question. I'm sorry. The chimp colony here was —did that help get around the problem ofnot wantingto test in humans?

Aronson: Yes.

Saul: And that was for heated products, or was that .

Aronson: That was for both. First you developed the model ofhow sensitive they were. Then they were a primarytool in deciding whether inactivation methods were successful or not.

Saul: Okay.

Aronson: So they were a crude tool. A clinical trial of one chimp is not . . . But they really -- it was very important that this happened, because starting in 1975, we had a model to test viral inactivation. And there were a couple of things tried in Building 29, in Biologics, that didn't work, but at least we had the tools to test them.

Saul: What were those things?

Aronson: The chimps.

Saul: Yeah, but what was tested?

Aronson: Well, one was immune removal of hepatitis B by using a hepatitis B antibody column. We had good tests by 1975 for hepatitis B. Antibody you could get from donors with a high titer. One of them was me. And then you made, you bound this to a support and then you run your plasma through, and you then put the plasma that's been through that column into a chimp.

Did an experiment on that, and two out of three were fine, but the third experiment said there breakthrough. It would not be sufficiently good for therapeutic, but it was a start.

There were some other things tried.

Then -- I ought to get off. Well, I can't get off Harvey's subject.

In 19 ...    Okay. Once hepatitis C became known, the same progression went for hepatitis C. So by 1980, you had a chimp model for both hepatitis B and hepatitis C. And by ...

Okay. Now, that lays out the groundwork. Those were important steps. Those were very important steps. You'd identified hepatitis C and hepatitis B. You didn't have a hepatitis C blood test, though. That was more difficult. But you could get started on viral inactivation, and the manufacturers, most of the manufacturers, I think, started working on viral inactivation, even before that time.

Everybody           . Everybody had an idea what might work, and it always fell on its face, like the beta-propriolactone and the ultraviolet light. You had this problem of treating it, treating your plasma or plasma fraction or whole blood with some conditions that would selectively kill virus but leave the biological activity alive.

You still have that argument -- it's not an argument -- going on today with whole blood, because a lot of the crucial elements being used for treatment now are the cellular elements, and these you cannot treat the way you do the plasma protein, so there was a meeting on that several months ago. So our focus was on the easier part, the plasma proteins.

 
Saul: And the plasma proteins are easier because there wasn't the red cell...

Aronson: There weren't the cellular, and I don't know whether it's preferable to go through sort of a time sequence.

The first breakthrough -- and this . . . The particular aim here, at this point, had always been the hemophilia population. It really was -- this was the high-risk group. They're 100 percent; you don't get much higher than that. So you had some, you had a lot of characterization of hepatitis B, you had had a little characterization of hepatitis C, but you did have an animal model. And there were some ways you could say, okay, this is hepatitis C and not hepatitis B. Even though he has hepatitis B antibodies, this is probably caused by ...

The same other big thing coming out in 1980 was Harvey Alter's clinical report on follow-up of patients with hepatitis C, saying this is not a benign disease. A significant number of these patients after -- I think the follow-up at that time was 10 to 12 years -- have significant liver disease.

Okay. That's -- the viral inactivation is the next step you're interested in, I'll bet.

Saul: Right. And one thing to think about as well, and then we can go back to there. I'm also interested in the practices inside the laboratory that kept the laboratory technicians and technologists and the scientists safe and how those changed as well.

Aronson: You're young, you're beautiful, and you're immortal, and you accepted a risk, and hepatitis was not a lethal disease. It was annoying, it could make you sick. I think I may have gotten my hepatitis antibody pipetting with a mouthful of a peanut butter sandwich. But this is . . . You accepted, this was part of life. And, in fact, I developed hepatitis B antibodies as well. I had them as soon as the test became, any test became available. They started testing them, the people in the lab who wanted to be put on routine tests for the whole liver, every three months or six months. I did not see any reason for that. And over the years, Dr. Hoofnagle got his test results back and it said, "You have acute hepatitis," and he stayed home for a couple of days and said, "The hell with it. I'm bored. I'm going back to work.  I'll feel better at work than I do at home."   And then one of the veterinarians who dealt with blood products and the chimps came down with it, and he was a little sicker. How many people in the lab had antibodies to hepatitis, I don't know. But there were only two that had any clinical symptoms at all that I know of, and Jay wouldn't know what it was unless he'd gotten his liver test just done, and nobody turned yellow.  It was not an easy ...

I've got to admit, once the hepatitis C story started coming out, I got a little nervous, because I'd had a syringe full of a plasma product that was infected, and, you know, every time I went to stick a mouse, the mouse would move and I'd stick myself. I mean, I'd drop the syringe and it would go . . . I mean, right there every time.

And a couple years ago I got a little nervous about this and I got, I sneaked in under the wire and got a test for hepatitis C, and I didn't have it.

And I should have been a prime candidate. But, no, I don't think anybody... This is not a big issue in the lab, really.

Saul: It's not now, or it has ...

Aronson: It was not at that time. Laboratory infections were very rare and usually benign.
Now, having said that, I have to say I got my middle name from a man who got a laboratory yellow fever infection and died of it just before I was born. So, my fatherworked with tuberculosis his whole life. I grew upontuberculosis. Iwastakentohis labasakid. Imean,infectious diseases were a part of life.
Saul: Didyouconsideritabadgeofhonortohavebeeninfected? Aronson: No. Itwas —youhad50to 100everyyearinhighschool,atleast,andthis wasavery smallhighschool. Atleastoneortwopeoplewouldget polio.
Thiswasjustlife. Iknow severalofmyclassmateshadsiblingswhodied ofbacterialdiseases asinfants. Andpoliowas partoflife,risk waspartof life, and you went on with it.
But the lab knew that -there were, I think, over in the virology group,Idon'tthink-withthevirusestheywereworkingwith,I don't thinkany,Idon'trememberanybodycomingdown... Amanwho'd worked there for a while and then went to a university did get a monkey virusthatgavehimabadencephalitis, wasnotagoodoutcome. But, yeah, this happened.
But we were the greatest generation and tough, I guess. We did not
fear exposure to things and knew that a little exposure gave good
antibodies. But we didn't know about hepatitis C or HIV. Okay. I'm going to get into the viral. The laboratory safety wasn't an issue. When they built —is it
building, not Building 5. Which building is the Infectious Disease
Institute? Eight? No. Ten, 11? Just up the hill from eight. And they
built that in about 1950 or '51 and they had, they had put in separate
ventilating units for each room or something so that the bacteria wouldn't
go from one placeto another.
There was a man by the name of Herman Debree [sp.] there, and I don't believe there's any... And he tested it. I think that maybe even the day he contaminated one room with spores from a benign bacteria and then tested the other labs, and they all -they found this going through all the labs.
Saul: Oh, he did? He found it?
Aronson: Yeah. Well,one oftheproblemswas-andthiswasnottheonlytimethat was... Thearchitectshadputthe airintakesrightnexttothe airoutput, orcloseenoughbythat... Ithinkthe samethinghappenedoveratWalter
Reed.
Anyway, viral inactivation; you're interested in viral inactivation.
Saul: Sure.
Aronson: Okay. The problem is to kill the virus and keep alive the proteins you're
interested in, and I'm going to focus on the proteins because I don't deal
with cells.
Everything was tried. Beta-propriolactone and the UV hadn't worked at doses. It was obvious from other reasons that ionizing radiation like cobalt or x-ray or things like that would not work because you killed the protein before you killed the virus. Nobody had a good idea. You were balking at sort of... You knew that at 60 degrees at 10 hours, you could get rid ofhepatitis B in solution. But the plasma preparations used for the treatment of hemophilia couldn't stand 10 hours at 60 degrees. They turned into jello in about half an hour or something.
And the initial breakthrough that was interesting in the sense —this was Boehring [sp.] in Germany. They were trying to further purify the factor8. Bytheway,I'musing factor8forwhatIusuallycallanti hemophilic factor human in the American parlance, but that's the more international. And that's the partthat's deficient in the patients with hemophiliaA. SoBoehring[sp.]wasinterestedinmakingmorepurified factor8. Mostoftheproteininthe factor8preparationswasfibrinogen. Fibrinogen isheat-sensitive, sothey decided maybewecanheat­precipitate the fibrinogen and still get out the, have the factor 8 be in solution. Whentheydidthis,they found,afterseveralyears,thatifthey putinalotof sugar, thatthey couldheatthepreparationenoughtokill,
Saul: Aronson:
Saul: Aronson:
precipitate the fibrinogen and at the same time maintain anti-hemophilic­factor activity. And so that was good. In, you know, a half an hour, and theygotrid ofthis,theygotatenfold morepurification. Thisisgood.
And then they got to thinking —now we're getting towards the late 70s —they started thinking —mid-to late 70s —"Well, maybe we can extend this heating period now that we've stabilized it. Maybe we can extend it enough so that we can pasteurize and kill hepatitis." I didn't know this whole story until I came across a court deposition, because I wanted ... But in 79, they presented the data at a meeting in London, and they didn't give out... [recorder cut off] They prepared it, but, "Look, we'vegota preparation. Wecangiveittochimpanzees,andtheydon'tget hepatitis." That was the first step.
Itturnedout severalothercompanieswere working atthattime, butnobodyreallyhadagoodidea. CutterLabsinCaliforniawasworking, actually, onasimilarmethodtothisandhavingalot oftrouble.
The problem with the Boehring [sp.] material was that you, the recovery was extremely bad.
Outofoneliterofplasma, youwouldget80units ofAHF, an8percent recovery, andyouwouldneed about five to 10 literstotreatasinglebleed. Right. Anyway, Boehring [sp.] had it, and that, to me, was a stimulus, and it can
be done. So other companies were working on it. We tried several other little piddling things that didn't work. And ... Saul: Was there a big push for this at the time? Whose motivation was it to take that viral-inactivated product?
Aronson: Well, you start going to the people in Blood and Blood Products over in Building 29, all blood. That was a big issue. That was probably the top, the holy grail to us.
Saul: Okay, to get heat-activated ... Aronson: Yeah. Tothemanufacturers,to someofthem,this wasveryimportant ifit could be done, but they didn't see any way to get it done. I... TAPE 1, SIDE B
Aronson: ...guesstherewereotherswithsmallerresearchdepartmentsthatdidn't think about it too much. But it was quite obvious by 1982 that most companieshadsomesortofwork. Mostcommercialcompanies, interestingly, hadviral-inactivation projects underway. This is in contrast to the national blood centers in Europe. Neither England nor France or any, Sweden, Denmark, had anyviral-inactivation procedures under investigation. Theseare muchsmaller groups anddidn'thavethe resources that somebody like Boehring [sp.] or Cutter or Immuno. Now, I don't know when immuno started on their viral inactivation. Okay. So
that was the state.
By, okay, 1982, things got a little bit exciting. One ofthe
interesting shifts there was, in 1982 was when the hepatitis B vaccine was licensed. All ofa sudden hepatitis B was much less of an issue than it had been in the past. But we did have procedures being worked on because we had the model system for hepatitis B, which was a little bit better, I think,
or better at that time than the hepatitis C.
And there was enough interest in 1982 that I put together a meeting. I wanted to have it in the spring of '82 but couldn't get the peopletogetheruntil,itturnedouttobeSeptember5th. Ithinkitwas September5th~whydoIsayadate? Itwasthefirstweekorsoin September—to discusswhatBiologieswantedinterms ofdata fora virally inactivated product.
There was much discussion about one chimp experiment. How much could you use what are now called surrogate viruses, viruses that are related, seem to be very tough viruses? If you kill so many viruses of X virusthatyoucanusequantitativelyinthe lab, doesthisgiveyou importantknowledge,andisthatausefulprocedure forlicensingaviral? And the basic overview at that time from Biologies was that, to be able to label yourstuffas viral inactivated, you'd betterhavedata saying you substantially removed, significantly removed a virus of importance to the patient. Well,there were onlytwoatthattime,hepatitis B and, well,HIV hadjustcomeuponthe radarscreen. That'sanewterm sinceIwasakid,
23
too.
So HIV, we didn't know anything at that time. You didn't know what it was, but you'd had the first report from CDC ofthe six —I think six, no, three —three hemophilics. I always enjoyed that first ~ I think it was the first line in that MMWR: Three hemophilics with no chronic disease. Anyways ...
Saul: Notwithstanding the fact that hemophilia is a chronic disease.
Aronson: Yeah.
So, anyways ... Saul: ThismeetingaboutBiologiesandwhattheywantedforviralinactivation, that was with manufacturers who would be presenting ?
Aronson: That was -1 got into trouble for that one. Maybe I shouldn't put this on the record. At that time, all meetings at FDA were supposed to be public andmust have,bepublishedinthe Federal Register. Well, this was an important working meeting, andthere's no way you wanted 53 or 100 peoplewhodidn't knowthe viral,thedetails oftheviral and viral-inactivated... Youwanted,youwantedmostlythecompanieswho were directlyinvolved. Ialsodidnotinviteanyofthecompanieswhowerenot licensed in the United States. This was our issue, and we had decided. It was, I think, a helpful meeting, and ...
Saul: Extra people wouldjustasktoomanyquestions ornot understand? What
was the concern?
Aronson: Well, you're in a class of 30 people or 100 people. Where do things go
better? You have a committee meeting with 10 people or 40 people. Which goes ... This was a very hard-working committee meeting with a lot ofdifferent, the views ofpeople very knowledgeable. I mean, among the manufacturers, we had, Harvey Alter was there, Bob Purcell. Was Lou Barker still... Yeah. Lou Barker was still there. So we had a lot of knowledge there. If you used virus, which ones were good? Bob Purcell discussed the heat-inactivation differences between the duck hepatitis and the opossum hepatitis or whatever they are, and, I mean, it was that kind of meeting.
But we came away saying, okay, the one-chimp model or a three­chimpmodeliswhatwe're goingtohaveto have. Idon'tthinkwedecided the numbers. Then we got into a problem with chimps in short supply. Some ofthe manufacturers seemed to have some. I tried to ... Well, that meeting atleastgotussetina frame ofmind, weknewwhatwewanted, at least at that time. And that came up again at an advisory committee meeting I think in November or early December. It must have been early December. And we laid down the law and said, "You need hepatitis B inactivation studies in chimps." Basically, the next day we sort of changed that. Ithinkitwasafterthatmeetingthatwesort ofchangedit. Sendus the data before your...
Thechimpstudytakesalongtime. It'ssixmonthsminimum,six
months and all the laboratorytesting, so you're talking nine months. So
sendus thedata,andwe'll startreviewing it evenifitdoesn't have chimp
data.
Saul: Okay.
Aronson: But the other point that was coming up was, with the hepatitis B vaccine, was the hepatitis C story, so we sort of dropped our primary goals being hepatitis B inactivation and said hepatitis C. And the results from the first studies looked very good for hepatitis C, or reasonably good. You were screeningout alot ofbaddonorsforotherreasonsbythistime. Itlooked okay, and the heat inactivation looked good. We had no idea about hepatitis C biology at this point. So we licensed between '82 — our first license for a viral-inactivated product was for the Baxter, and that was licensed in March of 1983. It was either February or March. Dennis Dunning [sp.], who was thenthedirectoroftheLaboratoryof,thedirectorofBlood andBlood Products, apologized to me. I'd signed off on the license, I think, December 11thorsomethingaroundthere,andDennisapologizedtomeat theend ofJanuary. Hesays,"WithalltheseAIDSmeetings,Ihaven't beenabletogettothatlicense application yousigned off,"which,in retrospect, I think was ironic.
Well, immediately after that was licensed, the Italians set up a trial withpeoplewho'dnotbeentreated previously, atermthat's nowknownin
the trade as PUPs, previously untreated patients. The PUPs were treated
byeitherthe heat-inactivated stuffofBaxteroranotherproduct, andthey
were followed for hepatitis. And guess what? They all came down with
hepatitis. Well, this is over a course of a year. This is an important year.
He started that probably in late '83 and had results in late '84.
Saul: Okay.
Aronson: And by late '84, well, all the patients, heated or unheated, came down with hepatitis. But by '84, you had tests. You'd identified the virus and you had antibody tests for it.
Saul: For?
Aronson: For... Sorry. By the mid-and end of '84, you had tests for HIV, what we now... We didn't have that same name for it. I forget what we called it then. You had tests for HIV virus that was doable and could be done, and youtestedthose patients, and Dr. Menucci's [sp.] trial for HIV,theones whogotthe heated stuffdidnotgetHIVandtheoneswhogotthe
unheated stuff did. Male: changethe tape?
Aronson: Yeah.
Male: Take a break?
Saul: Wouldyoulikea glassofwateroranything?
Aronson: What I'd really like to do is go to the smoking room, but you don't have
those anymore.
Saul: Unfortunately, no.
Aronson:
Saul: Male: Aronson: Male: Aronson:
I'm glad you said unfortunately. See, we took all sorts of risks.
As a kid, my father and I would put asbestos in the pipes in the basement. We were upper-middle —we were middle class. We had asbestos on the pipes, we had lead paint, high-class lead paint in the house.
We put mercury in our teeth. All kinds of stuff. This tape has one more hour. Do you think it's ? That's more than she can take. Okay. . Okay. Ihavethe Italianstory. Thisisanimportantstoryinallthehistory.
Sotheheatedpatients andtheuntreatedpatientscame down with hepatitis. The definition by that time —this was presumably almost all hepatitis C. But these patients who'd received the heated stuff did not come ~ in the interim, tests for HIV had been developed. The patients in the trial who received the heated stuff did not get HIV. And, boom, the world changed. This was the first time that hooked up the animal model.. . Well, it dissociated the animal model for hepatitis from the HIV. I'd gottenhellinthe '83-'84: You shouldn'thavelicensedthatheat-treated stuff;it'sjunk. You... AtaDBDRmeeting here,theadvisorycouncilto NHLBI on blood products, I was taken over the coals: You needed a clinical trial. Well, I felt better after that.
Saul: Aronson: Saul: Aronson:
And then out ofCDC came some very good data saying that HIV was a very sensitive agent, and, in fact, all the licensed products killed a lot of HIV, obviously some more than others. But that was a... But what is fascinating to me, if Dr. Menucci [sp.] had done that Italian trial a year earlier, look what would have happened. People would have said, "This is not a useful viral-inactivation technique. It shouldn't be on the market. Take it off. We won't use it," and we would not have, they would not have revisited that in the light of HIV. So that was the first trial? That was the first clinical trial. For the heat-treated... Yeah,yeah. AndthatcameoutjustaboutthetimedatafromCDCsaying that HIV was heat labile, more so than, obviously, than hepatitis B.
So that is interestingto me because people keep saying, "Well, why didn't you do this before? Why didn't you do this before?" Well, we didn't have animal models; we didn't have the models for either B or C until later on. When we had those, we developed the method, which did work on HIV but didn't work, even though the chimps liked it, it didn't...
Aweird sequenceofevents. Sometimesyou guessandyou'reright. Sol think our view was, even if it's not perfect, it's doing something. I think, again, the hepatitis inactivation had been a focus for really, inblood, formany years, andwe weremoreawareofitthaneitherthe
patients or the treaters.
Saul: More aware ofthe heat
Aronson: Ofthe issue. We wanted -that was a major issue to us, more so than the . .. Both the regulators and the manufacturers I think were more interested in this than the users, which is, you listen to the rhetoric now, it's quite different. I don't think that was true then. I know it wasn't; I know it wasn't.
Saul: There just wasn't a demand for it.
Aronson: No. Oh, until May of 1985, we allowed both heated and unheated on the market, and then enough ofthis stuff. But I received —there were abstracts. I received phone ... Ed Gompert [sp.], who was running the hemophilia center at Children's Hospital in L.A. at that time, called up and said,"My patients don'tthinkthattheheatedstuffworks aswell asthe unheated stuff." I don't know where that sense got built into this. Well, thiswasjustatthetimewhenwe weredeciding that... Isaid,"Don'tdo that trial, Ed, because we're going to stop it, all this unheated stuff." Saul: When did -well, did you ever actually outlaw unheated product? Aronson: Yes,asofMay29thor30thof1985. Wedidnothaveawithdraw. That becomes a big issue with lawyers. Saul: Right. Aronson: Did not have a withdraw because you wouldn't have had enough stuff on the market for at least six months.
Saul: So you would have been shortchanging the patients. They wouldn't have
had product at all.
Aronson: They wouldn't have had product. The second thing, the tragic thing to remember, is by June of 1985, essentially everybody who was going to be infected had been infected, except the newborns. But this becomes a big issue and a legal issue. Did youwithdrawthings? Andtheanswerwasno. As youimproved,you didn't withdraw. In March of 1983, changes in donor screening were mandated. Should we have withdrawn things that were, had withdrawn before? Well, thatwouldhavemadeasix-monthgapthere. Sixmonthslater,there were other changes. And this went on down the line for years. When a given lot, when a given donor was clearly implicated, then we would withdraw the lots where that donor was known to have ... But that was about all
that could be done.
The American Association of Blood Banks set up a meeting about sixyears ago askingthequestion,"Ifanothervirus likeHIV comes along, howcanwe anticipateit?" Now,(a)thevery goodvirologiststhere,we had no idea there was a virus like AIDS, like HTV. And after a day of discussion, Neal Nathanson [sp.], Bob Shope [sp.], Harvey Alter was there. We can't. Here's a virus which has a long incubation period and hasnovisible signs. Ialwayswonderedwhywe onlyfoundhepatitis.
Because people turned yellow.
And this comes up again because of the issue on West Nile. I had occasion somewhere in the '83 to call the CDC's expert on arboviruses. I forget his name. He was out in Fort Collins, Colorado, and I finally got him on the phone and said, "I'm not a virologist, but we're finding new things. Viruses other than those that turn you yellow are involved in transfusion issues, and should we be worried about arboviruses?" I mean, theseareacommon andvariedgroup. Andhealmostlaughed meoffthe phone;healmostlaughedme offthephone. Isaid,"Okay,sorrytobother you." AndsothenI readaboutWestNile,andthenexttestwe'vegotto have is a West Nile, a test for West Nile arbovirus. It's not the issue that HIVwasorhepatitisB. Butfunnythingshappen. ButIdon'tthinkWest Nile virus is a big issue, I've got to admit. Where do we stop? I just read an article by Michael Bush. You know the name?
Saul: Mm-hmm.
Aronson: Okay. Hewas speaking-1thinkitwaswrittenwith Harvey-onthe nucleicacidtesting,ifyoudidindividuals versuspooled,andthecost. I mean, there is a limit. Now, in the FDA, you didn't have to think ofthe economics except astaxpayersandhealthinsurancepayers. Butwe werefocusedonsafety. But even there, you had to -there's a risk-benefit. You inject something, the risk is not zero. The patients who think they should have zero risk, it
doesn't happen.
Saul: Doyouthinkthat'schanged,theexpectationforzero risk? Hasthat changed over the last 10,20 years? I mean...
Aronson: Oh,yeah. Well, peoplewantzeroriskasopposedtotheviewbefore. Oh, hepatitis, we'll get it, and that's that. But it's a societal change now. It's a societal change. And, yes, a young child dying is a tragedy, but paying $100billion forsomebodynotto die... Whatwasit? Ithinkthe figure Mike Bush gave for saving one person from a hepatitis C infection was $20 million or $20 billion or one infected unit. It'snot politicaltodiscussthesethings. Butmybiggestriskinlife wasnot workinginthe lab. It'stowalktowork andcrossOld Georgetown Road. I'm not kidding. Three times I've been carried on hoodsofcars intothemiddle ofOldGeorgetownRoadasapedestrian. I've been lucky. Mostofus, 99.999999 percent of us are very lucky. Zero
risk I don't think comes.
Can you describe for me, the issue of zero risk for patients who receive
Saul:
these products is something that's come about more recently. What about
theissueofriskforpeoplewhoworkinlabs? That'sverydifferentnow thanitwaswhenyoufirststartedworking. Andcanyoutracewhomade thechangesinthat attitude shiftand sortofwhat...
Aronson: Ithasn'tbeenanattitudeshift,Ithink, ofmostofthepeoplewhoworkin labs. Ithink forthevocalgroups,ithasbeen. Imean,Iworkedina lab. I
worked in Building 29 from '58 to '87. I then moved downtown to George
Washington and worked in a lab there for 10 years. Now, by the time I left
... Now, when John Petriccani [sp.] gave me a tube of HIV, which had
just been described, with a dose of nominally 10" per mil, we didn't have
PI, 2 or 3 facilities. I did use it under a hood and I did wear gloves, and
maybe even wore a mask. I doubt that. No, I couldn't. I did not pipette it
by mouth. There were certainthings ... Most ofthe pipetting I did in
Building 30 was by mouth.
Saul: Through what time period?
Aronson: From 1958 to 1987. I was exposed. I was bathing in plasma. What it had, I was going to get. That didn't bother me. I rarely wore gloves. Occasionally ... With a known infectious sample, I would wear gloves. With a standard sample, no, because it was cumbersome, you couldn't... Sothenyou'dpickupapento writeandyou'vegot stuff... Imean,it didn't make sense to me. Now I'm over at the Clinical Center and I work inalabthere,andIlook around andmake surenobodyiswatchingandI pipettebymouthbecause I'musedtothis. Now, I don't think the people in the lab really care that much, but thespokesmenfeeltheyhaveto. Ifyouhaveacommitteemeeting,the mostconservativepersonwinsthe day. AndI don'tthinkthatthe people
are that worried.
Saul: The people working in the lab?
Aronson: We were wallowing in HIV before ... You know, HTV didn't start in '82;
it was probably around since 75 or even before that.
Lab risk, yeah. There are different kinds of labs. There are certain things I wouldn't work with or I'd work very carefully with. But with standard patient samples... The needle stick issue is, yeah, I didn't like to stick myselfwith aneedle,but most ofthe time it wasn't because I threwaway,Ireachedinthewasteand ... Itwas becauseIdroppedthe thing. When we disposed stuff, we tended to bend the needles to keep people from getting stuck. We autoclaved all our infectious material right in the lab and then threw it in the regular trash. There were chemical issues I think that were probablymore than the infectious-disease issues there. There were a couple steps we did that we didn't have a hood for and we did without a hood that probably would have been better under the hood. But did we worry about lab safety?
Well, there was one issue. Yeah. We had moved from Building 8 toBuilding29in Julyof1960,1thinkitwas. AndinBuilding8therewas a routine. You checked the laboratory showers, the hazardous-material showers,everycoupleofmonthsbecausethey'dget filledwithrust. And somebody will holda washbasin under the shower andwe'd pullthe shower and often we'd unscrew the head and dump out the rust.
Got over to Building 29, brand-new building. You know, after a year, you know, "Over in 8 we always had problems. Let's -we'd better
check the showers." Well, we had a big, tall, broad-boned girl from
Saul: Aronson:
Saul: Aronson:
Kansas, Genevieve. I had been trying to think ofthat name for a couple days. Genevieve Nash. "Genevieve, you're tall. Can you hold this under the shower, and I'll pull the chain?" She says, "Sure." I pulled the chain, the shower comes out, I let go ofthe chain, and it doesn't stop. And Genevieve what's happened. The water's rising in the room.
Oh no!
Finally it stopped. It was on a controlled -it had to release at least 50 gallons. Oh, my God! Thesenewfangled things. Sowewereconcernedthatthesafetyshowers, we were aware of where the fire extinguishers were in the lab. They were bythe door, butifwegottrapped inthebackofthe lab, wecouldn'treach them. Those I think were almost more of issues that... I don't remember anybody worrying about getting an infectious side effect. I think we were more at risk for the chemicals. Then they came out with you should wear gloves when you use acrylomide. Well, wedidn't wear gloves with acrylomide, and the only person who came down withacrylomide­associated illness, aguywhouseditalot and keptgloveson,butthe acrylomide got inunderhis glove andhewasexposedtoit all day long.
So it's a crap shoot. The laboratory? I don't see this as an issue at all.
Saul: What about the OSHA regulations for lab workers who deal with blood
and infectious materials?
Aronson: I remember going to a meeting where we heard spokespeople say, oh, we've got to do this and that, and mostly I thought it was nothing that was helpful or would improve safety. These were often union representatives. I don't know what OSHA lab regs are. A lot ofregs I don't know and most other people know. Does OSHA say I can't pipette by mouth?
Saul: Yes.
Aronson: Why does it say I can't pipette by mouth on benign buffers?
Saul: I don't know.
Aronson: I know more than OSHA about pipetting and do more than anybody who wrote those regulations. Yes, I've pipetted sodium hydroxide into my mouthandI'm awareofthedamagethere. AsIsay,thechemicalhazards are... But I don't see any... Yeah, you can make mistakes. But there arealot ofpoints. IpipettebetterandmoreefficientlybymouththanIdo with bulbs and things like that. Now, if I grew up with them, maybe it would be different. If somebody new came in the lab, I'd say, "Okay, do it this way, but here's the way we used to do it." Saul: Sure. What has been the relationship -I'm moving more into the policy issues here -what has been the relationship between the FDA and the NIH,thebloodbank particularly, sincetheywerethe onesdealingwith a lot ofthe blood ?
Aronson: Well, first off, originally the Clinical Center blood bank was under
Biologies. You knew that.
Saul: Yes.
Aronson: Oh, you know more than I do. I don't think there was ever any formal arrangement. Certainly, I mean, the triumvirate for the viral diseases was alwaysthere. Purcell,bloodbanks,andHarveyandourgroupwasalways there. Most of my contactwith the blood bank was to carry their plasma over to Building 29, which I wouldn't have been allowed to do without getting a material-transfer form. I can't get a little bit of plasma without... I mean, I think the world is not going better in some ways. Boy,we hadalotof intermsofpolicy. No. Imean,policy issuesarekindofeasy. Wewanttomakethings safer. Thatwas —Idon't think we ... I can't ever remember sitting down and discussing blood-bank issues, policy issues.
Saul: Whatabout,wheredidyouget-didyou bringinexpertadvice fromother places whenyouwould, for FDA regulations?
Aronson: Wehadaverygood... In1975,thefirsttimewe hadanadvisory committeethat was appointed, about75, it was reallythebestpeople in thecountry, andthatkeeps uptilltoday,justas DBDRhadtheirown advisory committee. Now, wewould sitinonthose meetings, too, and therewouldbemorepolicy issues comeup therethanIthinkinour day­to-day contact with the blood bank. But, yes, wehad an extremely good
initial group, really, with a consumer advocate, Lou Alladord [sp.]. And
there was always . It's grown a little bit and gotten a little too
politically correct, I think. But...
Saul: What do you mean by too politically correct?
Aronson: Well,you can't... Allbloodbankershaveaconflict ofinterest. Therefore,youcan'thavea bloodbankeronyouradvisoryboard. And MikeBish [sp.] wasonthereandtheyfired him,andtheyfiredalot of... Sothere'sveryfewpeoplewho knowthatmuchaboutthebloodbanking. Manymore consumerrepresentatives, someofthemwhomwere very helpful, and someofthemwerejustapaininthebutt. But the advisory committee, a very interesting phenomenon there. It'sareal socialphenomenon. Theadvisorycommitteemeetings were always openand announced aheadoftime, andyouwouldhaveafair number ofpeople come in. You might have, oh, 80people come into listen to the advisory committee. Most of these were manufacturers, but there'dbeotherissuesyou'dhave people come infor, tohearwhatwas going on. And there was a lot offree and open discussion between everybody in the room.
SinceI'veleft,it's becomemuchmoreformalized. Andbeforethe meeting, the FDA outlines its questions, and then you take a vote, whereas previouslyitwas moreofa consensusdevelopment and moreofa policy ratherthana regulationmeeting, anditwas veryuseful, atleastformeit
Saul: Aronson:
Saul: Aronson:
Saul: Aronson:
Saul: Aronson: Saul: Aronson:
was.
Why were they useful?
(A) you meet some very good people who have a lot of knowledge. It was useful —a different kind of knowledge than I ever had. These were people you could pick up the phone in those days and call them up and say, "Look, you said this at the meeting, and you know this. But we're having a problem here. What about that?" And now I gather you can't speak to your advisory committee before meetings or give them any briefings or even call them for advice, for technical advice.
Well, now you've got to separate it, the advisors. You can't be clubby with the members of your... ... the advisory board. Yes. What am I looking for. And money. The people who got in trouble last fall for keeping bad books.
Enron.
The bookkeepers. The accountants.
The accountants, yeah. The accountants andthe groupcan'tgettogether. There are bad sides ofthat, but there's some awfully good sides to that, andwe gotthegoodsidesto that. Itwas -wehadvery,verygoodpeople, no question, and knowledgeable people.
Saul: Sure.
Aronson: But the Blood Bank, I mean, I'm sure in almost all those advisory committees, there'd be somebody from the Blood Bank there speaking or just listening. There'd be all sorts of people in there. Then those meetings got huge, and I don't understand it. Yeah, I'm interested in it, but I don't know why the marketing people are interested, and you get 37 marketing people in there. It's become a less productive meeting. It's a very formal meeting. If you want to make any statement, you have to file with the secretary beforehand, and you can't just... When somebody starts something and I don't think that's true or we have some more extensive information on that. You don't have that kind of meeting anymore.
Saul: Doesitprovide goodinformation? Imean,doesitstilladviseon issues?
Aronson: Yeah,yeah,butitwasn't,itdoesn't adviseasbroadly. Yes,youhavemore "official"consumerrepresentation,butyoudon'thavethesame free and easydiscussions withthe audience, whoare seeingit from different sides, too, and it's not as much fun. Saul: Great. Onelastquestion,unlessyouhavesomethingelsethatwecantalk about in a little bit. InyourCV,itliststhat youhavereceivedthe PHS Meritorious Service Medal. I just wondered what that was for. Aronson: Idon'tknow. Ithinkthecitationhadsomethingaboutstandardization of
factor 8. I think there were other things involved there. I don't know what
that was for. Surviving. And I think I was involved with another award
there, too, something, a group award of some sort, but I don't think I ever
knew what it was.
Saul: AretherethingsI'mnotaskingaboutthatIshouldbethatwe didn'ttalk about that are important to this story?
Aronson: I mean, the thing that fascinates me is the whole time frame. You can't usehumansandyoudon'twantto usehumans,the development ofthe chimps, andthenyoumovedon,andthenyougetanew disease and you haven'tany ideaaboutit,andthechimpmodel fails youintheinactivate patient. Butif we'ddone-iftheclinicalexperimenthadbeendoneayear earlier, it would have sunk the whole ship. That would have been it. Saul: Very important timing. Aronson: Yeah. But isn't that weird?
Saul: Yeah.
I hadn't thought of that until I was talking to a lawyer. Geez, you know, if
Aronson:
that had happened a year before, it would have been a disaster. Saul: Mm-hmm. Becausealot ofthe youdon'tknow. Yeah. Andthatbecame,andrightfullyso,thebigissue. Butbythattime
Aronson:
we'dsolvedthebigissuebeforeweknew whatitwas. AndI thought,you tell thatto the lawyers, and they don't like it, but I think we did a pretty goodjob onthat, although our friends inFrance that gotojail; myfriend,
Mike Rodale [sp.], is going to be accused of manslaughter or something in Canada. We like our scapegoats. Saul: Yes, we do, and the legal issues are a whole 'nother story that I may ask to
talk to you about later.
Aronson: But I think these are social issues, not legal issues.
Saul: Oh, yeah. Oh, absolutely, absolutely. Well, thank you very much.
Aronson: I enjoyed every minute. I love to talk. I hate to listen. As a historian ofmedicine, did you go to hear Donald Kennedy the other day?
Saul: I did not. I've been out oftown for a couple days.
Aronson: Itwas agreattalk. Ifyougetachancetohearhim,it wasvery,very interesting. He's a very wise, knowledgeable, and thoughtful man, and what he did was draw a parallel in the biological investigation, biomedical investigation
END OF INTERVIEW