Last night one of my mentors passed away. Dr. Joseph Meek was a lot of things to a lot of people. To me, he was the Dean of the School of Medicine at the University of Kansas in Wichita when I started school there, then an attending endocrinologist who wrote me a letter of recommendation for fellowship, and later in life a friend.
After he left the medical school to ride out the last few years of his career in private practice we lost touch for a year or two. But then in 2015 I became interested in his role in discovering the autoimmune cause of Graves’ disease.
I started visiting him every week, and every week I seemed to get a better story. So I asked if I could start recording them, and he consented. Dr. Meek told the stories with remarkable enthusiasm. He was a gifted storyteller, even the times he was speaking through a forehead bandage and a crusted upper lip from a recent fall. (note: I’ve not fact-checked these. I’m not a journalist. If anyone finds an error, please let me know so I can note and correct it.):
He had a lot to say about the discovery of thyroid-stimulating immunoglobulin:
Meek: ...at that time, the cause of Graves disease was entirely unknown. And since such luminaries as--I haven’t thought of his name--Sydney Warner felt it was due to a pituitary factor, and the TSH was involved.
Moore: So they thought some over-secretion of TSH was involved?
Meek: Yeah. And about that time a guy by the name of Brown-Dobbins discovered what he regarded as the exophthalmic factor. And so the hyperthyroidism was explained by an oversecretion of TSH and the exophthalmos of Graves disease was explained by the exopthalmic factor, “ES.”
Meek: And so that was where it stood to 1964. Well, McKenzie had developed a TSH assay, bioassay, that involved the preparation of mice. You injected radioactivity into the mice and it was recorded as an uptake. And then the mice were bled and two hours after the injection of TSH or Graves disease patients [ed: I assume he means the plasma/serum of Graves patients] they were bled--the mice were bled--and there was observed a rise in the radioactivity level of the mice.
Moore: That’s interesting. Okay.
Meek: Yeah. And the mice had to be prepared in a special way, and ruled out that it was a stimulation versus an infectious agent that caused the destruction of the TSH. The mice were initially prepared that stimulation was proven and the mice did stimulate and discharge radioactivity.
Moore: And the source of the stimulation was either the TSH or some other stimulation factor in the serum that had been injected?
Moore: Yeah. Yeah.
Meek: And in Graves disease patients there was evidence of a long-acting stimulator, LATS.
Moore: Yeah, yeah. Uh-huh.
Meek: Yeah. And the mice would stimulate sort of at 2 hours, and there was increased activity in the blood 7-24 hours afterwards. And Van der Laan [ed: 4th author on the paper above] came up with the idea (that’s my mentor)...
Moore: Was that in San Diego?
Meek: Yes. At the Scripps Clinic and Research Foundation in La Jolla. ...that it would be explained by an antibody. That was a unique observation, although it was copied by a Maxwell McKenzie and, oh gosh...well, this was a race.
Moore: Yeah. I bet.
Meek: Yeah. And the work that I did was to prove that it was an antibody, that it was a 7-S-gamma globulin that was present in the serum of mice and the serum really came from patients with Graves disease. And the stimulator was an antibody. Well, the man’s name was--from San Francisco, and he’s dead now--he came out with a publication about the same time that I did, and he is given credit for this work that he did, and it was published in the Journal of Clinical Endocrinology and Metabolism [ed: I think it was this paper]. But I beat him by a month through the National Academy of Sciences.
Moore: That was the journal that you published in?
Moore: A better journal! You got it into a better journal. (laughs)
Meek: And it was not peer-reviewed to the extent that it was in the Journal of Clinical Endocrinology.
Moore: It wasn’t? That’s interesting.
Meek: And it was introduced by Dr. Astwood, who was a member of the National Academy of Sciences, and so there was a race on, which fell in my favor due to circumstances beyond my control by senior men Van der Laan and Astwood. And they had known each other through their collaboration prior. The competitor just won’t come to me… And it culminated in review in Atlantic City. And that was when Atlantic City was meaningful as the senior moment of the Central Society for Clinical Research. They would hold their annual meeting in Atlantic City, NJ, and I was invited back in May of 1964 to give a paper. And so I did. And I remember an anecdote that before I left Scripps I was rehearsed by Dr. Van der Laan and Igray Diamond, who knew me from, because of, medical school days. And he was back in Kansas at that time as chairman of the Department of Internal Medicine.
Moore: And you had gone to medical school at KU, correct?
Meek: Yeah. And he was the speaker at Alpha Omega Alpha (AOA) when I was President of the AOA. And I introduced him as saying that--it was a brash statement on my part--as the erstwhile, but seldom seen, member of the faculty because he was gone so much of the time. (laughs). And he got up and said after that introduction that he had secured a spot for his residency in my favor and he was considerate of my position and he gave me the position as resident in Internal Medicine right on the spot. And so he knew me and said that my slides had not been acceptable because they were all on blue. At that time I couldn’t do anything about it.
Meek: Yeah. He went on and on in remorse, it caused remorse in me, because he said that was not acceptable. They should be in black and white. Yeah. And I came to give the talk in Atlantic City and found out that blue was more or less the outstanding color.
Moore: The industry standard.
Moore: Good. It was really hard to change slides back then I’m sure. You had to go back to the photography place.
Meek: The plates were in evidence and I couldn’t--I had to board the airplane to Atlantic City the next day and there was no way I could get the slides done. Well, that’s an anecdote. The work of mine was justified in my way of thinking because I had done some biochemistry and proved that it was a 7-S-gamma globulin.
Moore: That the stimulator was a gamma globulin?
Meek: Yes. That LATS, as defined by the mouse response, was due to an antibody in patients with Graves disease. And so from that point on the, and subsequent work, and I did a a little of this, was to see if you could convert TSH to a long-acting thyroid stimulator, and conversely, you could modify the 7-S-Gamma globulin by fragmentation and show that it was an antibody on that basis and convert short-acting thyroid stimulator by modifying the gamma globulin.
Meek: Well, then I went back to Kansas and did some clinical work and that was my highlight. And I am proud of the fact that I contributed something to the medical world.
Moore: A pretty big thing, I think.
Moore: Did they--I assume it was pretty well established by this point that antibodies were responsible for other autoimmune diseases, like Rheumatoid arthritis and whatnot?
Meek: Yes. Rheumatoid arthritis. Although they never--RF factor, which is an antibody in rheumatoid arthritis, was never injected into a patient and produced the joint destruction. And I, for long time, believed that the uniqueness of Graves disease was due to two factors: one, it was proven to be an antibody, and two, that it was a 7-S-gamma globulin antibody that was unique to, based on the fact that it stimulated the thyroid gland.
Moore: So you could actually reproduce the disease by introducing the antibody?
Meek: Yeah. And that sort of is where it was in 1964.
Moore: You know, the fact that it was a race, as a lot of these things are, interests me. Nowadays when you submit a paper to a pretty high-end journal like the Proceedings of the National Academy of Sciences, you have a response back in hours to days, at least an initial response.
Moore: So you can go from a completed paper to having something submitted for publication in the course of a few weeks. If you’re lucky. I assume that back then there was a huge element of faith involved. You had to send off a manuscript that got distributed out and it might take months to get edits back. Is that how it was?
Meek: Yes. The editorial that the edited version of the paper came out in the Proceedings of the National Academy of Sciences pretty much on--I think it was accepted for publication in May of 1964, and published in July issue. Whereas Kriss! Joseph Kriss! That was the author that did the companion. He did the work about the same time that I did, but he went through the channels of the JCEM, and got his published in September (laughs) [ed: it was October]
Moore: Somebody held up the editing process, somebody didn’t get their edits back in time. That’s the way it always goes.
Meek: Yes. Well, Chris is subsequently referred to--what’s the word? Referred to as the contributor to that just as frequently as I am. And to this day it’s still holding up. It’s an antibody, and the locus is sort of where TSH is, and it stimulates the patient to develop hyperthyroidism, and it, based on the TSI (thyroid stimulating immunoglobulin), it’s pathognomonic for Graves disease. So it’s still valuable information.
Moore: Yeah. I agree. Someone at the time must have thought that it was important to have solicited an editorial to accompany the paper. That doesn’t happen every day.
Meek: No. And subsequently the EPS, the Brown Dobyns work, has faded from the scene. I know that his assay was an Atlantic minnow, and the Atlantic minnow developed exophthalmos (laughter). The lateral displacement of the minnow’s eyes was measured with a micrometer.
Moore: That’s amazing.
Moore: Would they just put the stimulator in the water?
Meek: They injected it into the animal. The Atlantic minnow.
Moore: Very interesting.
Meek: Yeah. I never did that assay. But I remember hearing about it.
Here’s one about the Mercury Program:
Meek: Yes, and I was found to be acceptable, and so Diamond wrote down to Captain Greybill, that was a Navy Captain, and he was in space medicine at Pensacola. And accepted me to avoid the draft and I went into the Navy and was assigned to Pensacola dispensary or flight aviation for two years. Well, Greybill was into flight disorientation.
Meek: Now, it was kind of ironic that my trouble--current trouble [ed: at this point, Dr. Meek was suffering from frequent falls and dizziness]--preceded that. And his claim to fame was disorientation about space sickness, which was brought about by circular rotation of the spaceship to create artificial gravity so the astronauts would have an up-down location/knowledge base.
Moore: So they were thinking of designing spacecraft that rotated to generate centrifugal force so that an astronaut would have some artificial gravity as it were?
Moore: OK. I’m following.
Meek: So the work really was brought to a head for NASA’s standpoint by the space race which we were engaged in in 1962. We participated in that because we in the Army and Navy were the only ones doing disorientation. So I was appointed as a research assistant, a typical post-doctoral fellowship.
Moore: You were out of residency at this point?
Meek: Uh-huh. Although just out of residency. And it was before I had seen Van der Laan [ed: 4th author on the above paper] and before I arranged for my endocrine fellowship at Scripps Clinic and Research Institute. Well, I thought that was a pretty good deal to be established in the Navy stateside for the following reason: captain Greybill had an understanding with the United States Navy that he would never be transferred from Pensacola.
Moore: That seems remarkable.
Meek: Yeah. And they were willing to do that because he was a student of Paul Dudley White, and White was Mr. Harvard Medicine at that time. And they wanted somebody to head up their space program, so many of the astronauts were navy recruits or marine recruits, including Scott Carpenter and John Glenn. So we did some preliminary data on the original seven Mercury astronauts, and, so, NASA was in a race with the Russian cosmonauts, and the cosmonaut fell into space at that time, certainly in the capsule…
Meek: Yeah, Yuri Gagarin. That name is familiar to me only because the space race was going on in full intensity at that time, and NASA had not considered it until Gagarin became violently ill in space because of the tumbling.
Moore: Did the Soviets admit that he’d been ill, or was it just intelligence? Somebody on the inside who’d passed along the information?
Meek: That’s how it all happened. So NASA said, “Where is our counterpart to this space station to be?” And the answer was Ashton Greybill.
Moore: He was the guy to solve this problem?
Moore: got it.
Meek: And so I was assigned to the recovery of Scott Carpenter on the space flight. I went for seven days on special assignment to sea. And I was assigned to the recovery ship the Intrepid.
Moore: Very famous ship.
Meek: Yes. The Gray Lady. Had a colorful history of being sunk but not being sunk, and being towed into Australia and refitted, and went out to sea. She is parked in the--because of her history--she is parked in NYC, and I went aboard her some years after I got out of the Navy. Well, there is a little anecdote around that which I will refer to at a later date. So the recovery mission of Scott Carpenter ended up 40 miles off range. 40 miles.
Moore: 40 miles away from the intended spot of impact, or whatever?
Meek: Yes. Drop. And so we were on the flight deck of the Intrepid and craning our sights to the skies and seeing if we could see the ship come down. Only to learn later that she had--that Scott Carpenter had landed 40 miles downrange, 40 miles off the target area. And the plans were diverted on the spot to a destroyer picking up Scott Carpenter. Well, the Navy, in contrast to the marine corps, had Jet-assisted helicopters [ed: he pronounced “helicopter “heel-i-copter,” which is officially the most Kansan thing ever], and that was in the early days of jet-assisted helicopters, and Huey current breed of helicopter which followed that. And that had the range of 40 miles. But the Marines didn’t have that, so the Navy left the Intrepid the original plans were adhered to. Well, there was a big folderol and I was in my moment of glory, and I gave Scott Carpenter the original assessment to see if there were any remains of space sickness occurred. Including a ice water bath to induce nystagmus.
Moore: You mean irrigation into his ear canal?
Meek: yes. I only mention that because my hands were steady during the entire procedure and the intrepid was under full steam to make it to the islands, Grand Turk Islands, and the ship just yawed and strained and it was awfully difficult to hold a steady hand.
Moore: Well that’s a very difficult environment to evaluate someone’s balance, I’m sure.
Meek: Yeah! And Scott Carpenter was a wonderful guy, and he’s still alive--or just died [ed: he died October 10, 2013]--and he played it to the hilt. Now there was this about it: Scott Carpenter had been out on the Caribbean sea for a long time waiting for his recovery. So if he did show any deterioration in his baseline figures, including the threshold caloric test, it would have been seasickness rather than space sickness.
Moore: Because he’d been bobbing in the water forever waiting for someone to come pick him up?
Meek: Yeah. But we played it to the hilt and I received some notoriety about that. Because you can’t imagine how the people stateside were enamored with the space program.
Moore: Those guys were the rock stars of their day.
Meek: They were, and they handled their fame beautifully, as would be expected, as they had so much training to do prior to the selection for the space program, and even today the space station is not accommodated to generate artificial gravity. And that remains to be seen, whether NASA intends the space station to be constructed to generate artificial gravity or not. It doesn’t take much: 3-6 rotations per minute in weightlessness corrects artificial gravity to a point that, up and down, is reproduced artificially.
Moore: Was that at a specific radius?
Meek: Well, we did some preliminary space sickness, and we felt that everybody was subject to space sickness, although you adapted to it over the long haul.
Moore: How long did it take?
Meek: 72 hours, +/- their sensitivity, as determined by the threshold caloric test. And whether you had been a seasoned aviator or not, that helped.
Moore: Meaning experienced pilots got over it a little more quickly?
Meek: Yes. They were subject to less of it, although the seasoned aviators, including the astronauts, could always manifest space sickness by sweating. They couldn’t control that. But the nausea and vomiting that accompanied that--car sickness would be the closest we could come, land-locked selection, and not everybody was subject to car sickness, but everybody would, if they had normal semicircular function, was subject to nausea and vomiting.
Moore: Did you guys consider using anti-cholinergic medications?
Meek: Yes. Scopolamine. And that masked it, but it brought out some undesirable side effects from the scopolamine. And the patients were subjects in the slow rotation room environment, and then re-adapted to space sickness symptoms upon entering weightlessness. And there was a little readaptation. And I think it’s been proven enough of a problem that they don’t create an artificial environment because of that single effect. And they always give the astronauts time to re-adapt to weightlessness and following their return to earth. You aren’t aware of that, but they sit out on the space recovery mission after that, and they’re a little wobbly.
Moore: You mean after they launch they get some time to adapt before they’re assigned any tasks, and after they re-enter they get a little while to re-adapt before anyone asks them to do anything else? I see.
Moore: That seems cheaper than building a rotating spacecraft.
Meek: The human is--particularly the seasoned aviators--used to that through their flying
Moore: Was the idea with this slow rotation room, was that something they tried to do pre-launch to get them accustomed to it?
Moore: From what you’re telling me I assume it didn’t work very well.
Meek: No. Well, the history of the intrepid was such that its glory days were extended through the second World War, the Korean War, and other war duty.
Moore: All the way into Vietnam, right?
Meek: Yes. They put a pictorial essay, pictures, up when we, just prior to when we went aboard the time it was tethered in NYC. And you could go aboard and see the Intrepid. The pictorial essay of space was pictorially depicted about the Intrepid’s life at sea. And the time aboard we took time aboard, they had just done the pictures--taken them down--and so we thought that it was all over, although we had no idea that they’d depicted the shot that showed me administering the Heath Rail balance problem to the astronaut, to Scott Carpenter.
Moore: So there was a photo in the exhibit showing you doing this with Scott Carpenter? How about that.
Meek: Yes. And it had been in Life magazine.
Meek: And the Life photographer, who was a neat guy, captured that when Scott Carpenter was interviewed after the tests were administered. And so sick bay was converted into the ability to do the threshold caloric test and the Heath Rail. So Scott Carpenter came in to pictures being taken, flashbulbs going off.
Moore: (laughs) More things to add to the validity of the testing.
Meek: Yes. And because the Navy wanted maximum publicity on this, the results were negative plus or minus three, the threshold caloric and the Heath Rail test was administered by me, and you had to stand up on the rails, which looked like a railroad yard, for so many seconds, and there’s Scott Carpenter with his arms folded and looking intently down on the Heath Rail and balancing. Now, that wasn’t the purpose of the picture, to get my picture in with Scott Carpenter, but it added to my luster. (laughs)
Moore: I would have put that in my application to fellowship, for sure.
Meek: Well, that was it. That was my claim to fame. Six days aboard the Intrepid, and subsequently the falderal and attention that I got as…
Moore: Were you allowed to publish any of the data you got out of this experience? It wasn’t classified then?
Meek: No. Although my publications were on the experience I had in the slow rotation room in Pensacola. That’s in Aerospace Medicine. [ed: paper regarding monkeys and slow rotation here: http://www.ncbi.nlm.nih.gov/pubmed/14472044] And that was one of the publications I got out of it in my quest to enter academic medicine.
Moore: How much time did you have in the Navy after this experience was over? Was this near the end, or was this...
Meek: This was right during the end. I got out in July of that year, ‘62, and went to my fellowship and discovered the antibody formation of LATS [ed: long-acting thyroid stimulator] that we have discussed prior to that. But even though the ENT work was instrumental in that period, it was never exposed beyond the publicity on that, although when we went to Pensacola some years thereafter, after I got out of the Navy, the slow rotation room was still in operation.
Moore: Is that right? Were they using it for just routine flight medicine stuff then, or was it still affiliated with NASA?
Meek: No, the building was semicircular, a full circle, and that was constructed because of the human centrifuge that had gone on prior to that. But Captain Greybill slowed the centrifuge down and found out that we could reproduce the symptoms at a very slow rotation. So he had done all that work prior to my entering the Navy. And I developed the threshold caloric test and Heath Rails that were part of the experience--part of the “package”--that astronauts were put through as well as the Navy recruits that came in.
Moore: I’m sure they cursed your name if they knew.
Meek: Yeah. (laughs) They did. They forced me to ride aboard the spacecraft, slow rotation room, and experience first hand the adaptation that occurred. And we had dials that you had to set up here and over here to bring out the case of space sickness. Because if you kept your head in the plane of rotation you could avoid the adaptation.
Moore: You had to move around?
Moore: That is so fascinating.
Meek: The experiments at that time were pretty crude, and they consisted of a water bath and temperature adjustments which were displayed on a human--I forget what we did to keep the water bath temperature and they syringing adjusted to threshold as determined by nystagmus.
It was so fantastically great hearing those stories and others. It was good even after he lost the ability to talk and we just watched baseball together for 30 minutes a week.
I’ll miss him. I’ll miss his excitement at nailing down a straightforward diagnosis of Graves disease. I’ll miss the enthusiasm with which he told the story of the time he discovered and successfully treated a case of thyroid lymphoma. I’ll miss the way he tried to hug everybody, including me, even though I hate hugging.
But I won’t forget him, and that’s all most of us can wish for.