Paul Rochmis M.D. RIP

Paul Rochmis M.D. Princeton ’60 good friend and classmate died of cardiac amyloidosis Friday 26 July ’24. In 10 to 20 years given the structural chemistry we have recently learned we’ll probably be able to cure it (or at least stop it in its tracks). People with protein biochemistry chops can find out why after the ****

Years ago in Montana, I took care of a fellow doc’s father who was a very tough old rancher out of Birney. His neurologic disease put him in a wheelchair and he hated it. He’d say “Dammit Robbie, a man should die with his boots on”.

Paul went out fully booted, with his intellectual guns blazing, sending out eMails the day before he died. Paul felt everyone was entitled to his opinion.

He was certainly tough intellectually, but it wasn’t until years after graduation that I found out just how tough Paul was mentally and morally.

Back when we were undergraduates, Freshmen ate in commons; upper classmen ate in the ‘eating clubs’ which are called fraternities everywhere else. Those were the only options all of us thought.

I’ll let Paul describe it. This captures his character and voice better than anything I could write. It’s from a podcast of an oral history project from the Princeton Alumni Weekly

“Rochmis: I didn’t have any understanding of what the bicker process was or that you needed to network with people. There was one other student from my high school. I was of an ethnic religious minority (LR he is Jewish). I didn’t really feel horribly comfortable about the whole concept of it. It was just a personal feeling. It wasn’t really some sort of intellectual difficulty with it. I just didn’t like that way of being judged superficially.

But I went along with it and not terribly successfully. I ended up with a bid to what was thought to be one of the lesser clubs. I just didn’t feel I wanted to commit. The bicker process back in those days was famous – or notorious – for what was called the 100% bicker, because basically the University provided no eating facilities at all for anybody above the sophomore level. They relied on the club system as sort of an unwritten understanding, as I perceived it, that the people who ran bicker who were upperclassmen, and the club groups, would agree that everyone got a bid and therefore relieve the University of their responsibility along these lines. 100% bicker was a goal, a target, a lodestar so to speak.

Bicker would end at midnight on a certain date, and early in the evening, when a Chinese-American classmate of mine was not going to get a bid I basically said, “Take my bid. I’m out of here. I don’t want any part of this.” I don’t know where I got the courage to do that. I wasn’t a particularly brave person at that time. I sort of watched it, and I felt a burden had been taken off my shoulders. I sort of watched the situation as an observer. About 10 o’clock, 10:30 at night, the person running bicker, Steven Rockefeller, realized that there were about 23 or some number like that of classmates, 1960 classmates, who had not received bids, and he needed to forge this 100% bicker. He called for a meeting of the people that had not received bids, and I tagged along because I knew some of these people.

There was one club that was just off Prospect Street called Prospect Club. It was a cooperative club. In the ranking of clubs, where Ivy or Cottage was No. 1, Prospect felt rightfully or wrongfully to be the worst club and maybe not a real club because it wasn’t on Prospect Street – it was just off Prospect Street on Washington Street, or Washington Road – and it was a cooperative club. It basically had a very high percentage of the Jewish class in there. Steven Rockefeller forged a deal with the people that ran Prospect Club – talked them into or coerced them, I don’t really know what happened – that they turned around and they offered bids to all of the unbid students, at which point Steven Rockefeller declared a 100 percent bicker and success, at which point I walked out disgusted by the whole process.

The episode would place a lasting stain on the eating clubs. More than half of the 23 students who had not received bids were Jewish, and the indication of anti-Semitism drew attention on campus and beyond. Myron Margolin ’58, then president of Prospect Club, told The Daily Princetonian that the bicker system “tolerates and probably engenders dishonesty, disloyalty and discrimination.”

Rochmis, in the end, declined his bid and became a rare “independent” student.

Rochmis: I felt kind of proud and kind of scared at the same time. As it turned out, it was much better for me financially. I didn’t have very much money to spend. I would go down to an African-American luncheonette down Witherspoon Street called Griggs and have the world’s best hamburgers for 35 cents – goes to show you how long ago that was. Every weekend I would have an invitation by one of my friends to a club, so I didn’t really miss much in the way of social life. I was so busy carrying about 30 hours a week with engineering and running the engineering magazine that I really didn’t have a lot of time for social life. I didn’t play bridge and waste my time with things like that.

Rightfully or wrongfully, I like to think of myself now – maybe I’m flattering myself too much – as the person that broke bicker. Subsequently, the University realized that this was an untenable situation and developed the alternative that I’m sitting in right now, Wilson College. Except at that point Wilson College was a lunchroom and commons which would serve a number of people that dropped out of the club system after me, not immediately after me but subsequently during the year for various reasons. The University had professors come and eat dinner with the Wilson members. I was happy being an independent so I didn’t join Wilson. I guess I was just an ornery guy, probably still am. The whole experience was bittersweet, but in retrospect I realize that it helped me develop strengths which were very useful later in life and showed me that I probably had more courage than I gave myself credit for.”

I’d see him around campus and in various classes as we were both preMeds, but I had no idea that he was cooking on a hot plate in his room for most of the time. To do that took incredible strength of character.

Princeton continues its proud tradition of antiSemitism, the only difference is that the participants now wrap themselves in holiness displaying their virtuous love for the Palestinians where before they were just bigoted scum.

Well that’s the hate part of the love-hate relationship Jews matriculating at Princeton in the late 50’s have.

Now for the love part. Princeton offered a fabulous education to everyone there regardless of origin, religion, social class. So I’ll use the wonderful education Princeton gave me to talk about why cardiac amyloidosis is likely to be a treatable and possibly curable disease in the near future. Beware: a technical biochemical background would really help, but give it a shot. Hopefully some of it will be comprehensible.

****

What follows it intellectually fascinating to any chemist but it’s not just intellectual diddle. Someday, probably within the next 20 years, it will help people like Paul.

Back 10 years or so when Paul told me he had cardiac amyloidosis despite having an unmutated transthyretin protein I was shock, as most amyloid was due to mutations in it (over 120 mutations were known back then). It was used to ferry fat soluble (but not water soluble) compounds such as thyroid hormone around in the blood. Transthyretin is a tetramer of a 127 amino acid protein.

Each transthyretin monomer is mostly made of beta strands which are linear essentially 1 dimensional stretches of the protein backbone. This is why transthyretin so readily forms amyloid. Basically, in amyloid some of the protein backbone flattens out so it lies in a single plane, and thousands of the planes stack on top of each other producing the amyloid fiber.

Well time has moved on and we know lots more about amyloid. Just as any brain can have a seizure if treated the right way, any protein can flatten out and form amyloid, some spontaneously, others with a lot of help. Examples include alpha-Synuclein which is the dominant amyloid former in the Lewy body of Parkinsonism, and the aBeta peptide which forms the amyloid of the senile plaque of Alzheimer’s disease.

Tau protein which forms the neurofibrillary tangle in Alzheimer’s give rise to at least 25 clinically distinct neurological diseases called tauopathies (3 more are chronic traumatic encephalopathy, corticobasal degeneration, and Pick’s disease). In each of the these four diseases, a different conformation of tau is seen.

Then Nature [ vol. 598, pp. 359 – 363 ’21] blows the field wide open, finding 19 different conformations of tau in clinically distinct diseases. Each clinical disease appears to be associated with a distinct polymorphism. This is also true for the polymorphisms of alpha-synuclein, with distinct conformations being seen in each of Parkinsonism, multiple system atrophy and Lewy body dementia.

In none of the above diseases is there a mutation (change in amino acid sequence) in the tau protein, so the conditions of formation of the amyloid must vary. All of this was unknown 10 or so years ago when Paul first told me of his illness

In the distant future people will be able to study the structure of Paul’s particular form of amyloid and throw stuff at it to see if they can break it up. This is not a new idea [ PNAS vol. 95 pp. 12956 – 12960 ’98 ] but we had no way to determine the microscopic structure of amyloid at the atomic level back then and see what effect the molecules we were throwing at it actually have.