Thursday, January 8, 2009

Molecular Biophysics and Biochemistry Laboratory work

People who were associated with Fred through the lab at Yale University are encouraged to add comments and stories. If you have pictures, you can email them to the blog moderator and I'll add them.


  1. I worked in Fred's lab from 1982 through 1988. Fred was the reason they invented the cartoon with the lightbulb overhead, he came up with brilliant, out of the box ideas and he instigated similar discoveries from those who worked with him. Although I found it very hard to work in the lab I learned more during that time than any other. It was not the specific science, although there was plenty, but the capacity to work independently, to be broad in approach and to look at problems in a somewhat unorthodox way that was most influential to me. Fred's insight was novel, clever and usually brilliant. Fred's guidance was caring, potent and often more revealing in what he chose not to say. His mentorship has been an influence throughout my career training and supervisoring staff and raising children.
    Stephen Kaminsky

  2. Posted for David M. LeMaster by Sarah

    Among my many fond memories from my years in Fred's lab, I think my favorite was when as a first year grad student I was excitedly explaining my most recent calculations to him. Fred sat back slightly in his chair with an almost puzzled look on his face and said "I have trouble with that". It was his tactful way of telling me that I'd made a stupid assumption in my analysis. His gracious demeanor and his desire to get on with attacking the problem at hand helped the moment of embarrassment to
    quickly pass. Ever since I have used that memory as a prod to more thoroughly check the ground before standing on a conclusion. Much of Fred's clarity of thought came from his desire to truly understand, precious in a
    world where marketing a pet idea or technique is the familiar road to success in science. The surest (and most fun) path for Fred always started with correctly framing the proper question.

    David LeMaster

  3. I was lucky enough to spend five years in Fred's lab, from 1985-1990, and they were in many ways the years I most cherish. I have had the opportunity to work with many fine scientists, including several "bigger names" than Fred. But he was the most original thinker, and the greatest man, I've run across. Fred had the courage to think about problems starting from a blank slate, without resorting to preconceived biases. Most of us are too blinded by our background, or too insecure in our intellect, or just too lazy to really give every problem fresh deep thought. That was Fred's biggest gift to science, and his greatest example to those of us who trained with him. There was always a joy in doing science with Fred. His group meetings were marvelous freewheeling affairs that often felt most like extended brainstorming sessions. Whenever a clever idea came along he would push his glasses back on top of his head and get that infectious ear-to-ear grin -- a look that I will never forget.

    My favorite Fred story is from the day we first discussed results from a computer program to repack protein side chains. He was sitting with me at my desk as I came to a heavily color-coded chart I'd been working on for days; my "big result". I'd never noticed the chart bore a truly eerie resemblance to the design on an over-sized coffee mug that always sat on my desk. Of course, not much ever slipped past Fred. He took one look at the chart, saw the mug, glanced back at the chart, and back to the mug. Then he gave me the Fred-grin and blurted out "My God, man! What have you done!". After that I decided that in the future I should pay more attention to what was right in front of my nose!

    The other thing I will never forget is Fred's generosity with his time, and his unfailing ability to "do the right thing" for the people in his group. Fred always knew just what to say, or what not to say, to draw the best out of his coworkers and colleagues. He was caring to a fault, and had a very perceptive feel for human nature that I saw on many occasions. To this day, whenever I hear someone described as exceedingly wise, the first picture that pops into my head is one of Fred. He is about the only scientist I have known who might have had even greater success as a judge or general!

    What a wonderful man, and what a wonderful life he led. He will be missed.

  4. Posted for Jim Warwicker:

    As for David LeMaster, I have a clear memory of a very gentle correcting by Fred of a very silly mistake on my part. I also recall the mix of work in Fred's lab at the time I was there, visualising proteins but also probing them with a variety of physical, chemical and computational methods. This approach and the thinking behind it was stimulating, and is just as relevant today as it was then. It was a privilege to be a part of Fred's lab.

    Jim Warwicker

  5. Posted for Kathy Borden:

    I have always thought I was particularly lucky to do my PhD in the Richards lab, particularly as I was the last student that Fred took on. Fred’s problem-based approach and attitude that you had to do/learn/make whatever it takes to answer your question were inspiring. His ability to pass that passion on was another great gift. Fred was also kind and patient, and when I think of him, I always see him with that big grin. In a world where so often good science seems to be based on “spinning,” Fred’s voice and ideology are truly a great loss.

    -Kathy Borden

  6. Fred Richards and the charge on gas phase protein ions
    Juan Fernandez de la Mora, January 10/2009

    I first met Fred Richards as an emeritus Professor at his small Gibbs office. It must have been 1999, when I knew very little about him. I had heard that he was an expert on proteins, and I had seen the strong support letter he wrote long before for John Fenn when, as an emeritus, the survival of his Yale lab was under question. I hope someone retrieves that brave letter and places it in Fred’s blog. Thanks to it, Fenn managed to earn a Nobel Prize for work done at Yale, and for papers published with a Yale affiliation.

    I visited Fred a few times to consult on the problem of the charge carried by gas phase protein ions produced by electrospraying their neutral aqueous solutions. I had a model that seemed to fit the data, but I did not know enough about the density of proteins to be sure the picture made sense. All these visits to Fred were wonderful. I discovered a truly charming man, who taught me what I needed to make things fit, and who even seemed to enjoy my intrusions. The matter connected to Fred’s early work on the density of protein crystals, whose value for gas phase ions was (and remains) largely unknown. The result of this interaction was a short paper [1] published in a collective Journal issue put together by John Fenn. It gave me little work and a lot of pleasure, and turned out to be among the three most cited among those I have written. The high point was all at Fred’s office.

    My second debt of gratitude with Fred was that, when he moved his lab to his home, he offered me the option to inherit his electrospray mass spectrometer. I had just obtained an almost identical one (with turbo rather than diffusion pumps, but which never worked), so I missed the chance to keep Fred's museum piece. Mark Johnson still stores it in his Yale lab.

    Dear Fred, our interaction was almost nil in perspective of your long and fruitful life. But I will always cherish it, and wish and wish it was not over. I pray that we may meet again, where the kind and the just go after this life. Amen

    [1] Electrospray ionization of large multiply charged species proceeds via Dole's charged residue mechanism. Analytica Chimica Acta, 406 (1) 93, 2000

  7. By Tony North, Leeds, UK

    Although I had known him before, I got to know Fred well when he was on sabbatical in David Phillips's lab in Oxford in about 1968, having sailed across the Atlantic with Sally, who then had to fly back to collect George.
    The molecular models for the first protein molecules to be solved by that time had been built in a cumbersome fashion; the calculated electron-density maps were drawn on transparent sheets stacked on top of each other and models were built with metal components in a framework alongside the stack. The builders had to estimate the positions of the atoms, adjust the models accordingly and go back and forth between maps and models until they agreed, measuring the positions of the atoms with the aid of a plumb-line. Fred hit upon the idea of using a half-silvered mirror so that the map could be seen through the mirror and simultaneously the model by reflection in it. Both map stack and model measured over 1 metre in each dimension, so Fred's device proved to be a rather large contraption. He acquired considerable quantities of timber which he cut up in the lab in order to provide the framework to support it all. I remember going with him to a glass merchant in order to arrange for the half-silvered mirror - he was actually quite impressed that we managed to find a place that would do it. Not surprisingly, the apparently vast construction (accompanied by piles of sawdust) acquired the name 'Fred's Folly'; however, it, and copies, were used successfully in a number of places until computer graphics became the standard method for interpreting protein maps. David Phillips and I always referred to the device as 'the folly', but elsewhere it was known by the much more proper name of 'the Richards optical comparator'.
    At later dates, I met Fred from time to time on both sides of the Atlantic, including Gordon Conferences and a visit to Yale, when I stayed with Fred & Sally. Always cheerful and with enormous energy, he enlivened all occasions. He'll be much missed.

  8. Posted for Peggy Geiger:

    I felt very saddened when I heard the news of Fred's death. Fred's lab was a great place to work. I came to MB & B from a chemistry department where there were very few women students or post-docs; at times, the environment was not very friendly. In contrast, I immediately felt very comfortable in Fred's lab with several other women in the lab or working close by in other WERMS labs. During my two years at Yale, I thought much about the direction of my career, especially since my research project did not go well. I decided that I wanted to pursue a teaching career. During my second year, Fred gave me the okay to teach a few hours a week as an organic chemistry TA. He gave me the freedom to make my own decisions about my career and helped me in many ways, never pressuring me to continue along the research path. When I started as an assistant chemistry professor at a 4 year college, he loaned me a UV-VIS spectrophotometer to use in my undergraduate research program. After a few years, the college started to pressure me about publication and I worked another summer in Fred's lab to help me get some research done. Fred helped me along my chosen path and I am very grateful.

    Peggy Geiger

  9. Posted for Howard Steinman

    I was a grad student in the Richards lab from about 1965 until I received my PhD in 1970. This was a time of incredible transition departmentally and scientifically. As Chair of Molecular Biophysics, Fred was active in the merger leading to the current MB&B department. Hal Wyckoff had recently moved to Yale to solve the RNase S crystal structure. As others noted, the problem of how to visualize and think about proteins in three dimensions was in its early stages of analysis, both intellectually and experimentally. Both these challenges were pursued by Fred as he assembled a diverse group of scientists in his lab. There were the protein chemists, Bill Benisek and Richard Perham, the resident crystallographers and those who visited from other institutions to learn the new craft of protein crystallography and there were the nascent bioinformaticians, like BK Lee, who develop novel methods of structural analysis. I remember Sanford Moore visiting the lab to see “Fred’s Folly”, aka “The Richards Box” of the RNase S structure. And of course I remember Johnnie Mouning.

    Here are my legacies from the Fred Richards lab. Independence, the freedom to conceive an experimental plan, see it fall flat on its face, pick yourself up and find a new and more profitable direction to pursue. Interaction, the opportunity to seek help from colleagues, to stimulate their discussion and create a working scientific relationship. Ingenuity, the possibility of solving a scientific problem with your hands and your mind, of actually making things to make your experiments work.

    As the grandson of a carpenter and son of a onetime mechanical engineer, I find the legacy of ingenuity particularly long lasting. Ingenuity was there from the moment you entered the lab: the home made amino acid analyzer tended by Johnnie and The Richards Box. I remember Hal Wyckoff rummaging through drawers of metal and plastic hardware and spare parts in the X-ray lab. When I asked him what he was looking for, Hal said, “Ideas”.

    The passing of one’s PhD advisor is a shock. Many of us think our advisors will live forever. And actually, they do live forever—in their influences on our lives and the lives of our own mentees.

    Howard Steinman
    Professor of Biochemistry
    Asst Dean for Biomedical Science Education
    Albert Einstein College of Medicine
    Bronx, New York

  10. Wendell Lim sent me this:

    Dear Sally,

    I was a postdoctoral fellow in Fred's lab from 1992-1996. I was deeply saddened to hear of Fred's passing, and I offer you and your family my deepest sympathies. Fred was an important and influential figure in my life, and I have attached here, a tribute which I wrote for Fred, which will be published later this month in the journal Nature Structural and Molecular Biology. Please feel free to share it with others or to post it on the blog (I have already cleared this with the publisher). In researching this piece, I had many wonderful conversations with colleagues who had fond memories of Fred that they wanted to share. Clearly Fred touched many in the scientific community in an unusual and exceptional way.

    Aside from Fred's obvious scientific prowess and accomplishments, I greatly admired the man behind these accomplishments more. I was always amazed by the unadulterated joy he took in doing the things he loved, as well as with his integrity and straightforwardness with people. I continue to do my best to emulate him in this regard, as difficult as it can be. I always thought that Fred was remarkably kind and supportive to people, though he often seemed to do his best to hide it.
    It was an absolute delight to be in Fred's lab and an honor to have had the chance to work with him. I'll always be thankful for a wonderful pre-wedding BBQ that Fred and Sally hosted for us at their home in Guilford in 1996, and for the annual Little Harbor oyster harvesting parties that we would have, which were always fun, despite the inevitable stomachache that developed after gorging yourself on oysters.
    I regret that I will not be able to attend the memorial service next week, but my thoughts are with you.

  11. Posted for Jim Clifton

    I was one of Fred’s last graduate students, but the story I’d like to relate comes from before I arrived at Yale. When I was taking freshman Chemistry our instructor was called away for a week. As his substitute, David Eisenberg gave a series of lectures on protein diffraction. I was quite intrigued by the method and the results it offered. However, I remember asking him how they knew that the structure of a protein in a crystal had any relevance to the solution structure. He replied that it had been demonstrated that protein crystals could catalyze their normal reactions; I decided then that I wanted to study structural biology. I didn’t know it at the time, but he was referring, of course, to the work done by Fred and Marilynn Doscher on ribonuclease S. Asking critical questions and providing rigorous answers was the hallmark of Fred’s entire career, and it’s fitting that his work has served as an example of that to Chemistry and Biochemistry students.

    Jim Clifton

  12. Graduate students in Fred's lab learn independence, to think for yourself, do for yourself and speak for yourself. Although painful at the start, in hindsight there was no better lesson to be had. Although it may sound as if it was sink or swim, it was far from it. You knew that if you ran into a wall Fred was there for you. And most refreshing, if Fred didn't know the answer he was the first to admit it and had the connections (because everyone would take his call) to get just the right person on the blower.
    Fred also believed it was important to start from beginning principles, for my thesis the use of a well established mathematical formula for the propagation of sound in proteins solutions and the compressibility led to Fred rederiving it from scratch to convince himself (and me) that he completely understood the physics. 5 pages of math later we proceeded to the next chapter.
    Beginning principles meant that you needed to have Fred teach you to glass blow your apparatus yourself. Only after you gave it a real effort were you allowed to use the university's glass blower.
    There are many tales of the "Chief" and his magic (which was really top notch science) in the lab, in his office, at seminars and at home that bring back wonderful memories. There is many a time when I exeperience that wow for some revelation and it is quickly followed by the memory of Fred as a deja vu. When I work with my lab staff and students I find myself adhering to the same methods that were so helpful to me in my graduate studies with Fred. I value all he taught me, the way he did it, his friendship as well as that of the many people he chose to work with in his lab at Yale.


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