Wednesday, October 7, 2009

Tom Steitz wins Nobel Prize 2009

Today Venkatraman Ramakrishnan, Thomas Steitz, and Ada Yonath won the Nobel Prize in Chemistry. I'm sorry only that Fred was not here to see this moment, he would have been so happy and proud of Tom, his colleague whom he had hired so many years ago.

The family and I are delighted to hear the news and wish Tom congratulations and continued success.

Thursday, April 23, 2009

A retrospective in ASBMB

The journal of the American Society for Biochemistry and Molecular Biology (April 2009) has published a retrospective of Fred on pages 16 and 17. Jim Staros wrote the first and then the editors worked on it and added some fabulous comments. It's a very nice piece - thank you to the ASBMB.

Monday, March 2, 2009

From José M. Delfino

I will always cherish the memories of my time with Fred Richards. As a graduate student, I became attracted by the scope and depth of his published work. By the end of my PhD thesis and following the advice of the late Gregorio Weber, a frequent visitor to our institute in Buenos Aires, I approached Fred by mail and was lucky to be accepted to join his lab (I still keep that early typewritten and handwritten correspondence).

Of my post-doc years at MB&B (1985-1990) I treasure the most the highly stimulating intellectual atmosphere of the place and the kind comradeship of so many people (including the unforgettable Thelma and Johnnie Mouning). One outstanding event in Fred’s lab was marked by the exhilarating exchange of ideas at group meetings. Here, Fred’s views punctuated the events, illustrating the crystal clear nature of his reasoning and his profound insight into every aspect of protein biophysics. I will always remember the electrifying feeling at sharing his enthusiasm upon some progress on the speaker’s project. In many respects –perhaps more than he had ever imagined- he bore a profound and enduring influence on my attitudes toward science and people. On the other hand, I always admired his superb organizational skills, his uncompromisingly high standards and his strict ethics.

In my work meetings with him I sometimes felt awkward at seeing him doze in front of me -not that this would not be justified by the merit of the material in my report, compounded perhaps to the language barrier- but all of a sudden at some point, he would jump from his seat, fix his eyes on me, progressively develop a wide smile and utter the most incisive question, cutting right into the core of the matter. He would then proceed to the point where he would squeeze from me all the details of the experiment. My heart would then pound strongly at his passionate outpourings.

In science, one should underscore his bold attempts into less-trodden paths, avoiding the pervading dogma, and exploring everything from sound principles. Among the many aspects of his personality deserving admiration was the wisdom of his counsel, the rightfulness of his statements (and his silences), his extraordinary ability to draw the best out of each one, and his attitude at letting each one of us to be the owners of our projects (the ‘lone wolf’ approach in the words of David Le Master), generously allowing us to pursue our own personal ventures. Noteworthy was his love and flair at designing home-built devices, a rare gift in these times of ready available kits (I treasure copies of his glass-blowing manual and electrical engineering companion booklet, which have been and will be useful in my lab, and even to my grown-up children at home).

From a number of anecdotes that illustrate his caring and generous nature let me evoke the following:

1. In late October 1985, I had just arrived in New Haven with my wife Raquel and two babies. After a few days spent in a Yale temporary housing, Fred came to check the place we had just rented in Prospect Gardens, not far from Kline Biology Tower. He immediately noticed that our place was unfurnished. Without word, he left and returned (so quickly to us) in his pick-up truck with a crib, a chest of drawers and other furniture, that Sally and Fred proceeded to download into our place (at first we naïvely thought that they lived nearby, but we later knew they had brought this present all the way from their own home in Guilford).

2. The expiration date of my US visa was approaching and I expressed to Fred my willingness to continue working on the project. In this circumstance, Fred immediately arranged for me a few months stay (paid from his grant) at the ETH-Zürich. This meant for me a bonus enriching scientific experience (and allowed me to have a brand new visa issued to return to Yale).

3. Right at the scheduled time for my return to Argentina, the country was suffering an economic turmoil that compromised my appointment. Upon telling Fred about this unexpected turn of events, he once again arranged for me overnight an extension of my stay at Yale until the time was fit for me to travel back home. Later I knew (Fred never said anything to me) that this was not so simple, because it meant for him borrowing funds for my salary from a different grant. By that time, Fred’s generosity at letting me grow and expand on derivations of his own projects, even donating to me equipment from his and others’ labs (always aided by the intercession of Johnnie Mouning) helped me to launch my own research.

In the years that followed, I always set as a priority to pay a visit to Fred (sometimes it happened that he was sailing, as he always did in the summers). On those occasions, I deeply enjoyed sharing with him the science, and his insightful comments and wise advice were always truly appreciated. On the family side, he always asked: ‘How is everybody at home? (or How is the crew doing?) How many children in the family now? At my answer stating that the family still kept the same size (my wife and six children), he felt reassured and drew his proverbial ear-to-ear grin.

In January 2008 Raquel and I (with two of our now grown-up children Santiago and Cecilia) were very fortunate to visit Sally and Fred at their home in Guilford. We had then the last chance of enjoying his enthusiastic chat on science –say, his concern for the energy conservation policies and his anger at the useless waste of natural resources. He then shared with us his latest progress on his wood-carving activity. On bidding him farewell he uttered his characteristic ‘Listen!’ to let us know his offer of lodge for my family and me on a future occasion.

It was an enormous privilege for me to have been a member of Fred’s lab. For sure, his example of life has set an imprint on those of us who had the fortune of sharing part of his life. May all these shared recollections serve as a tribute to the memory of the marvelous scientist and human being, whom I will always remember for his towering example and compassionate nature.

Giving his contagious curiosity and the breadth of his interests, he has most likely set sail again to a brave new realm. Thank you for everything, Fred!


Sunday, February 22, 2009

Memorial Service Program for download

If you missed the service or need another program you can download the Program from his Memorial service. It is a large file. It's a bit different than the one distributed, because there are a few links related to the music performed.

Monday, February 16, 2009

Memorial service slideshow

Here is the slide show of pictures of Fred from the memorial service reception. Thanks to Sally B. Richards for putting this together. The pictures can be browsed and downloaded here. People are encouraged to add comments with descriptions and thoughts on the pictures.

Friday, February 6, 2009

From Melody Lane

This is how I remember Fred – sitting at his desk in KBT, white shirt, sleeves rolled up, ready to work. I was Fred’s secretary from 1971-1981. I was just out of college and he basically trained me to be a scientific secretary. My greatest skill was that I could type fast which was key with Fred as that was the only way to keep up with him. He was in the middle of his chairmanship of the MB&B department. It was then that I learned what a good leader should be. He did this through his charm, wit, cajoling, and even anger. He had no problem yelling at the faculty or staff or administration when he felt it was warranted. He had tremendous energy and enthusiasm for science. During those ten years with him he started the Program-Project Grant with the WERMS groups (Wyckoff, Engelman, Richards, Moore and Steitz) which is still being funded. He started the Research Reports for the department. He was on the Board of the Woods Hole Oceanographic Institute, the Whitney Marine Laboratory, the Advisory Board of Purdue University’s Magnetic Resonance Laboratory, and on the Board of Trustees of Cold Spring Harbor. In 1971 he became a member of the National Academy of Sciences, served on the Council of the International Union of Pure and Applied Biophysics, was President of the American Society of Biochemistry and Molecular Biology, and President of the Biophysical Society, as well as being on the Editorial Boards of the Journal of Molecular Biology and Advances in Protein Chemistry. He carried a full teaching load in an introductory biochemistry course, whose lectures are still taught by other faculty. He carried on a vast correspondence it seemed with everyone in biochemistry, biophysics, the government, and the Hinckley Boatyard. He was on a first-name basis with the University officers. He published extensively and served on many University committees, among which was to chair a committee to establish the Office of Cooperative Research. And he was the Director of the Jane Coffin Childs Fund for Medical Research. And he played hockey at noon! This was all within a ten year span – more than most accomplish in a lifetime. He was incredibly focused and clear in all he did, a very deep thinker. He would dictate correspondence without asking for rough drafts – they were almost always so well thought out that they needed only minor editing; the same for his manuscripts, and grant applications. I found out later how unique that was. His group called him The Chief. I called him Dr. Richards. He had a great team: Johnnie Mouning, Gerry Johnson, Paul Pepin, Art Perlo, all technicians who made the Core work. Fred made it fun to work with him.

Fred had a way of using phrases that I called Fredisms: Get (so-and-so) on the blower for me. Stop grousing and do it. Don’t get into a swivet. I have an appointment with the croaker. He also had a great way of filing which I believe his father taught him. If the pile on your desk gets too big, just take the bottom half and throw it away, because if you haven’t looked for it you don’t need it. Every few months I would hear a big THUMP from his office. It took me a while to catch on to the fact that we were engaged in what I called paper wars. He would spend the morning dictating and then bring out a big stack of papers with the tapes. He’d put them all on my desk with a gleeful smile. The game was on. It was now up to me to get it all done before I left for the day and put it back on HIS desk, so now his desk was cluttered and mine was clean. This is just an example of the challenges he presented in a playful manner. I put a cartoon on his door of a boss speaking to his employee that said “If I wanted it tomorrow, Smedley, I would have given it to you tomorrow.” He loved that.

He was a great communicator. He summed up his packing theory to me by saying, “Put a bunch of stones of different sizes into a bag and leave it – eventually the small stones will go to the bottom and the larger stones will be on top.” Early on we had a brief discussion about who is more creative, an artist or a scientist. His arguments made me aware of just how creative science is and I gained a greater understanding and respect for it. He called it thinking outside the box, which he was known for.

I left the department for about 10 years and came back in 1991, back working for the chairman, a job that Fred had trained me to do years ago. I called him Fred now and he called me Mel and it’s been that way since. Once you work for Fred, you always work for Fred. And it’s been 28 years all told. But we all did it with love and great respect for him. He taught us all so much mostly by example. He even had an uncanny knack for bowing out at the right time – he had no problem handing the controls over to others to let it grow. Even his gruffness was fun because he loved the banter. I think he did it to keep everyone on their toes and keep pushing for excellence. Once he was going on about something and I said he was becoming a curmudgeon – he just smiled broadly, like I finally got it.

Fred was a great leader of the department, even though he had not been chair since 1973. He was always available for advice. You could count on him to really think about an issue and come up with just the right answer. You could trust that he was right. The only thing I can remember that didn’t work for him was his tire jetty project in Little Harbor. I think he would have made it work eventually if not for the neighbors.

One of the last acts as leader was last year when he called a meeting of some of us to put together a scholarship fund for Johnnie Mouning. He was very clear about what he wanted but we were all there as part of his team again to make it all happen. Again, he had an incredible grasp of knowing the right thing to do.

When he had done something he was really proud of, he would call it a thing of beauty and a joy forever. That’s how I remember Fred – a joy forever.

Thursday, February 5, 2009

Obituary Nature Structural & Molecular Biology

Frederic M. Richards, 1925-2009
Wendell A. Lim

Frederic Middlebrook Richards, Sterling Professor Emeritus of Molecular Biophysics and Biochemistry at Yale University, died on January 11, 2009 at the age of 83 (Figure 1). A founding father of the modern field of structural biology and a member of the U.S. National Academy of Sciences, Richards grappled for decades with understanding how proteins fold, and in the process broadly influenced how we determine, analyze and interpret molecular structures today. A master of seeing the forest from the trees, Fred's steady hand helped steer the nascent field forward with logic, common sense, creativity, and a preternatural clarity of vision.

Inspired by a chemist older sister, the young Richards was quickly drawn to the blossoming world of mid-20th century protein chemistry. After obtaining his undergraduate degree in chemistry at MIT in 1948, he entered graduate school in EJ Cohn's Department of Physical Chemistry at Harvard Medical School, where he studied the density and solvent content of protein crystals during his thesis with Barbara Low. In 1954, Richards set off for a short post-doctoral stint with Linderstrom-Lang at the Carlsberg Labs in Denmark, where he was to initiate his classic work on the enzyme ribonuclease.

At that time, bovine pancreatic ribonuclease A (RNase A) was the system of choice for protein chemists, since the Armour Meat Packing company had purified a whopping 1 kg of the protein and offered samples to scientists. At the Carlsberg Labs, Richards experimented with treating RNase A with limiting amounts of the protease subtilisin. He discovered that he could covalently cleave the protein to create a new form, called RNase S, which still retained enzymatic activity. When Richards returned to the U.S., now as a faculty member at Yale, he showed in 1957 that RNaseS could be chromatographically separated into two fragments (referred to as S-protein and S-peptide) each of which lacked any enzymatic activity. But, to the surprise of the protein chemistry community, Richards observed that when he remixed aliquots of the two fragments, complete ribonuclease activity was instantly restored (1, 2). This demonstration that the information encoding the protein's structure and function was robust enough to defy covalent cleavage and physical separation was a landmark finding in the young field of protein folding, and helped set the stage for Anfinsen’s classic experiments demonstrating that RNaseA could spontaneously refold to its native state even after chemical denaturation and scrambling of its disulfide linkages. Richard’s RNaseS work also illustrated the remarkable specificity of protein-protein interactions and how they can regulate protein activity, concepts central to modern cell biology.

Desperately curious to know what these protein structures looked like, Richards played an important role in the beginning days of protein crystallography. In 1967, he and Hal Wykoff solved the structure of RNaseS (3), which was the third protein structure determined (Harker and colleagues also determined the structure of RNase A that year). While on sabbatical in David Phillip's Lab at Oxford, Richards also devised a crucial new method to fit atomic models into electron density maps (4). Prior to this point, Kendrew had used colored clips, placed on a forest of metal rods, to represent electron density. The brass atomic models of the protein were then built within the forest of rods, although this cumbersome setup severely limited the ability to see and to adjust the atomic model. Never one to sit around when presented with an important challenge, Fred set about devising a solution that was typically ingenious in its simplicity. His invention -- the optical comparator (a.k.a. the Richard's Box or "Fred's Folly") -- used a half-silvered mirror placed in the right location relative to a stack of electron density contours and an atomic model (Figure 2). By viewing the device from the proper angle, the user could simultaneously see both the model and the electron density map, and could easily build and adjust the brass atomic pieces so that they fit the density. The Richard's box remained an indispensable tool used by crystallography labs around the world for about 10 years, when it was finally replaced by computer graphics systems. The earliest computer systems were referred to as "electronic Richard's Boxes," and today's programs still use the same basic superposition of electron density maps and atomic models for structure building.

Richards' contributions to protein crystallography also included early experiments that helped the young science weather the skepticism of biochemists who would frequently ask "Why should there be any relation between the structure of a protein in a crystal and in its biologically relevant form in solution?" (5). With Marilyn Doscher and Flo Quiocho, Richards performed decisive experiments demonstrating that enzymes are still active in their crystalline state, thus effectively silencing the nagging doubts and providing support for the crystallographer's leap of faith (6,7). Never tied down to one technique, Fred also made key contributions to the use of NMR and photoaffinity labels to probe molecular structure (8-10). In the later stages of his career, Fred helped shepherd the field as a leader in the movement to require public deposition of published structure coordinates.

Perhaps Richard's longest lasting impact has been on how we think about and interpret structures -- developing the concepts of solvent accessible surface area and internal packing (11). The earliest protein structures yielded complex, disorganized masses that defied the elegant and obvious functional logic of the DNA double helix. Cutting through this complexity, Richards saw the need for simple geometric ways to understand protein structure and function, and in 1971, with BK Lee, developed the concept of solvent accessible surface area -- the surface defined by rolling a sphere the size of solvent over the molecule (Figure 3) (12). This systematic way to determine and quantitate the properties of a protein's "inside" and "outside" as well as the stereochemical properties of the surface that it presents to other potential interaction partners, has played a central role in nearly all studies of protein folding, protein interactions, and the forces that underlie them. Because of the clarity with which molecular surfaces illustrate functional characteristics of a protein, nearly every structural paper today has a molecular surface depiction determined in this basic way.

Richards also quantitatively analyzed the packing within proteins and showed that their interiors were as densely packed as small molecule crystals (11). His thinking on how proteins fold in a manner that solves the puzzle-like problem of close packing their interiors (13) – allowing both maximal occlusion of hydrophobic surface area and optimization of van der Waals interactions -- is central to modern methods in structure prediction and protein design. Current drug design algorithms also trace their origins to ideas of optimizing surface complementarity.

Fred deeply influenced many scientists, beyond his own students and postdocs. At Yale, Fred was the rock upon which the Department of Molecular Biophysics and Biochemisty was built (he was the founding chair in 1967). This department went on to become one of the premier groups in modern structural biology, with seven of the faculty he hired later becoming members of the National Academy of Sciences. Fred, who was often referred to as “the Chief,” led the department with respect and dignity for all. A New England blueblood who could trace his lineage back to the pilgrims, Fred still spoke to everyone with the same square-jawed directness, respect and humor -- whether you were a Nobel laureate, a wide-eyed first year graduate student, or a loyal technician. Despite a sometimes curmudgeonly veneer, it never took long before Fred would break out his famous grin. His renown balanced thinking and sage advice led to his prominent role on diverse scientific advisory committees and as the president of several major scientific societies.

Fred's uncanny ability to home in on the heart of a problem was a key attribute that allowed him to make so many pioneering discoveries and inventions in diverse areas of structural biology. His keen abilities of perception were evident to the generations of Yale students who can recount similar stories: while attending a seminar on a distantly related topic, Fred seemingly dozes off mid-seminar, but awakens as the speaker concludes, only to ask a question that goes straight to the key issue in the field and outlines directions that the field should move in over the next ten years. Because of his clarity of thought, Fred was not often swayed by the distracting forces of dogma and intellectual fashion. Thus, his ideas and opinions always seemed remarkably modern and never outdated.

Perhaps what Fred would have wanted to be remembered for the most was the sheer joy he had for the practice of science. I recall Fred once telling me about how as a young boy, one of his greatest pleasures was convincing his mother to take him to the chemical shops of lower Manhattan, where he would delight in searching for chemicals that might cause pleasing explosions and such. During my postdoc with Fred in the mid 1990's, I witnessed this seventy year-old emeritus professor coming into work each day, giddy with excitement as he sweated at the hood trying to develop a new method to chemically footprint exposed surfaces on proteins (Figure 4) (14). The delight that he took in pursuing his latest creative endeavor was evident. After all of those decades, little had changed -- Fred Richards always knew how to have fun.

Wendell Lim is an HHMI Investigator in the Department of Cellular and Molecular Pharmacology, University of California San Francisco, 600 - 16th Street, San Francisco, CA 94158. email: He was a postdoctoral fellow in Fred Richards' lab from 1992-1996. Much of this material was adapted from an autobiographical review by Richards (4). The author wishes to thank the many admirers of Fred Richards who passed on stories and comments, with special thanks to David Eisenberg (from whom the descriptor "square-jawed directness" is taken), Bob Sauer, Tack Kuntz, Ron Raines, Gerry Olack, Karen Fleming, Melody Lane, and Raghavan Varadarajan. Thanks to Eric Martz for providing pictures of the original Richards optical comparator. References

1. Richards, FM. 1958. On the enzymic activity of subtilisin-modified ribonuclease. Proc. Natl. Acad. Sci USA 44:162-166.

2. Richards, FM , Vithayathil, PJ. 1959. The preparation of subtilisim-modified ribonuclease and the separation of the peptide and protein components. J. Biol. Chem. 234: 1459-1465.

3. Wykoff HW, Hardman KD, Allewell NM, Inagami T, Johnson LN, Richards FM. 1967. the structure of ribonuclease-S at 3.5 Å resolution. J. Biol. Chem. 242:3984-88.

4. Richards FM. 1968. The matching of physical models to three-dimensional electron-density maps: a simple optical device. J. Mol. Biol. 82:1-14.

5. Richards FM. 1997. Whatever happened to the fun? An autobiographical investigation. Annu. Rev. Biophys. Biomol. Struct. 26:1-25.

6. Doscher, MS, Richards FM. 1963. The activity of an enzyme in the crystalline state: Ribonuclease-S. J. Biol. Chem. 238: 2399-406.

7. Quiocho, FA, Richards, FM. 1964. Intermolecular cross-linking of a protein in the crystalline state: carboxypeptidase-A. Proc. Natl. Acad. Sci. USA. 52: 833-839.

8. Lemaster, DM, Richards, FM. 1985. 1H-15N Heteronuclear NMR studies of E. Coli thioredoxin in samples isotopically labeled by residue type. Biochemistry. 24: 7263-7268.

9. Wishart, DS, Sykes BD, Richards, FM. 1991. The relationship between NMR chemical shift and protein structure. J. Mol. Biol. 222: 311-333.

10. Staros, JV, Richards FM. 1974. Photochemical labeling of the surface proteins of human erythocytes. Biochemistry. 13:2720-2726.

11. Richards, FM. 1977 Areas, volume, packing, and protein structure. Ann. Rev. Biophys. Bioeng. 6: 151-176.

12. Lee, B, Richards, FM. 1971. The interpretation of protein structure: estimation of static accessibility. J. Mol. Biol. 55: 379-400.

13. Ponder, JW, Richards, FM. 1987. Tertiary template for proteins - use of packing criteria in the enumeration of allowed sequences for different structural classes. J. Mol. Biol. 193:775-791.

14. Richards, FM, Lamed, R. Wynn, R, Patel, D., Olack, G. 2000. Methylene as a possible universal footprinting reagent that will include hydrophobic surface areas: properties of diazirine as a precursor. Protein Sci. 9:2506-17.

Picture of Fred

Figure 1. Fred Richards with his wife Sally aboard their sailboat Hekla in 1994. A dedicated sailor since childhood, Fred almost always took a month off each summer to captain a major sailing excursion, returning to lab afterwards refreshed and ready to work. His sailing adventures included several transatlantic voyages. He was also an avid ice hockey player (photo by Frank Schley).

Figure 2. The Richards Box: an optical comparator for fitting atomic models to electron density maps. a. The original Richards Box, which was assembled in front of David Philips office at Oxford while Richards was on sabbatical there in 1967-68. The half-silvered mirror for viewing is in the upper left, the atomic model is below, and the electron density map (contours printed on acetates) are in the back (photo from Eric Martz). b. The superimposed image of model and map that the user would see when using the Richards Box (photo from Wendell Lim).

Figure 3. Analyzing protein structures. a. Richards (with BK Lee) developed the concept of solvent accessible surface area. These surfaces were defined by effectively rolling a sphere the size of a water molecule across the protein. This simple geometrical concept allowed a systematic and quantitative analysis of the properties of the "inside" and "outside" of protein structures (image from ref. 11).

b. Richards’ analysis of dense packing within the interior of proteins led to his comparison of protein folding to solving a three-dimensional puzzle (slide from Fred Richards).

Figure 4. Still having fun. a. While in high school at Philips Exeter Academy (1943), Richards and his roommate, John King, attempted to replicate the 1797 Cavendish experiment to measure the earth’s mass and gravitational constant, using a home built apparatus (photo courtesy Don Engelman and David Eisenberg).

b. Richards, still working at the bench in 2004 at the age of 79 (photo by Karen Fleming).

Sunday, January 25, 2009

A Toast To My Captain

Picture of Fred
Here’s to you, Fred. Your wisdom has been passed to thousands of students. A few of them might match your intellect, but I doubt any of us could measure up. You taught chemistry, biology, sailing, woodworking, engineering, metallurgy, machine shop, engine repair, boat building, epoxy impregnated fiberglass construction, celestial navigation… the list goes on. And all of that was just to me! How long a list would we create if all your students were polled? You taught me subjects which I was explaining to you. Your probing questions and insightful mind made me think deeply about my own field. Your curiosity was infectious. We are all better for having been your students.

What patience you had! To teach teenagers navigation on long sails. To insist we could not leave the dock until everyone could tie a bowline behind their back. To clean up the mess and fix the mistakes as we learned. I am still amazed that you would allow us to take the helm while you slept. Your trust and acceptance of our failures is the example I hold myself to as I teach others what I know. Oh, not that your growl was never heard! You were quick to correct. The snarl of the Captain kept us striving for perfection. But, after the growl came the gruff order to “try again, Laddie”. Your satisfaction when we got it right was the best reward.

You taught me to be prepared. You always had the spare part or the material to make it. The clutter in your shop and garage was the result. In that clutter, you could find the exact piece you remembered saving five years ago. How did you do that? I believe there are enough spare parts on Hekla to rebuild her should she ever break on some remote shore. The boat yard may not understand, but all of us who saw you pull the proper fitting from the bilge learned a lesson.

From you I learned not to fight the storm. The storm will always win. Secure your lines, shorten your sails and wait. The storm will pass and the world will settle down. There is no reason to batter yourself and your boat trying to maintain speed. Have patience, Boyo. Just slow down. You taught it is not failure to heave to for awhile, it is wisdom. I still fight the impulse to push too hard, but when I do, I hear your voice.

Thank you, Fred. I can never repay all you gave me. I can only try to pass to others the lessons you taught. Your storms are behind you. I wish you clear skies, fair winds and deep water. I learn from you still.

Birthday Celebrations Onboard Hekla

Meg and I have been sailing with Fred and Sally on Hekla for many years. Frequently, the sail would span Fred’s birthday. We tried to come up with a gift that would elicit that famous smile. Picture of Fred
In this first picture, Fred was presented with his birthday pancakes in 1997.

Picture of Fred
Our young son Frank had a stuffed tiger. The parallels with Calvin and Hobbs were unmistakable. We loved the comic strips and found many similarities with life around our house. In 1991, we brought Fred a Calvin and Hobbs book. Fred spent the next hour in tears. I am sure it was sympathy for our situation and not remembrances of George’s (or Fred's) childhood behavior!

Picture of Fred
In 1997, the gift was a puzzle. This puzzle is created from wooden cubes. Each face of each cube has a different piece of a different picture. So, each piece has 6 sides and 28 possible positions yielding 6 different correct solutions. Fred has just finished calculating the number of possibilities!

Click on any of the pictures above to jump to my SmugMug account. You can see larger versions of the pictures and download any you would like to save. If you have any great pictures of Fred, send them to me and I will post them for his many fans. (To avoid spam, I am not using my normal email address and I am displaying it in a graphic.)

Frank's email

Thursday, January 22, 2009

Retrospective for ASBMB Today

The following was prepared for use in a Retrospective for ASBMB Today, the monthly magazine of the American Society for Biochemistry & Molecular Biology, and is reproduced here with the permission of Greg Petsko, the President of the ASBMB, and Nicole Kresge, Editor of ASBMB Today:


Frederic M. Richards (1925-2009)


Frederic M. Richards, former President of the ASBMB (when it was the American Society of Biological Chemists) and of the Biophysical Society passed away at his home in Guilford, Connecticut on January 11th.  He was 83.

Fred Richards was a towering figure in protein chemistry, having played a key role in moving the concept of proteins from amorphous colloids to discrete molecular structures.  His contributions to protein science ranged from his central role in founding what is now known as structural biology–both experimental and computational–to the design and application of new chemical reagents for probing protein structure and function.

Richards was born on August 19, 1925, in New York City, the youngest child of George H. Richards and Marianna Middlebrook Richards, both parents from old New England families.  After his graduation from Phillips Exeter Academy, he matriculated at MIT.  Military service toward the end of WWII intervened, but he returned to MIT after his discharge and received the B.S. degree in 1948.  For his graduate study, he moved to E.J. Cohn’s department at Harvard Medical School, where he worked with Barbara Low, receiving the Ph.D. in 1952.  He stayed at Harvard for a year as a Research Fellow with Cohn and then moved to the Carlsberg Laboratory in Denmark, where, with Kaj Linderstrøm-Lang and others, he began working with ribonuclease.  After a short stint at Cambridge as an NSF Postdoctoral Fellow, Richards joined the faculty of the Department of Biochemistry at Yale in 1955 as an Assistant Professor.  He rose rapidly through the ranks, becoming Professor in 1963.

In 1963, Richards was appointed Chairman of the Department of Molecular Biology and Biophysics at Yale, which entailed a move from the Medical School to the Yale College campus.  Following a sabbatical at Oxford in 1967-1968, for which Richards and his wife Sally sailed their own boat with a small crew across the Atlantic, Yale merged the Medical School Department of Biochemistry and the Yale College Department of Molecular Biology and Biophysics to form a new University-wide Department of Molecular Biophysics & Biochemistry (MB&B) with Richards as its founding chair (1969-1973).  There was considerable skepticism about the viability of a department with divided space on the two (Yale College and Medical School) campuses, not to mention faculty from the two distinct campus cultures.  However, due in good part to Richards’ strong leadership in the department’s early days, including a spectacular initial class of junior faculty hires that included at least two future chairs of the department (as well as a future chair of Chemistry), MB&B will celebrate its 40th anniversary later this year.

Summarizing Richards’ contributions to protein science is difficult, because of the breadth that he covered.  A few examples will have to suffice.  Much of the early work in Richards’ laboratory focused on bovine pancreatic ribonuclease, and in particular a preparation that he discovered while in Linderstrøm-Lang’s laboratory, dubbed ribonuclease-S (RNaseS) that had been treated with subtilisin, to cleave the peptide bond between Ala20 and Ser21.  Richards and coworkers purified and characterized RNaseS, separated it into S-peptide (residues 1-20) and S-protein (residues 21-124), both enzymatically inactive, and showed that S-peptide did not retain an ordered structure in solution but could be reconstituted with S-protein into enzymatically active RNaseS.  They crystallized RNaseS and showed that RNaseS was enzymatically active in the crystal, putting to rest the widely held view at that time that protein crystal structures were irrelevant to the conformation and behavior of enzymes in solution.  In collaboration with the late H.W. Wyckoff, they solved the structure to atomic resolution (a tie for the third protein structure ever solved to atomic resolution) with and without bound nucleoside monophosphate.   While on sabbatical at Oxford, Richards designed and built the Richards Optical Comparator, better known in the field as Fred’s Folly, or simply the Folly, which remained the method of choice for converting electron density maps to models until it was supplanted by computer graphics.

The availability of high resolution structures led to the first computational studies (at a time when computational studies required a main frame computer).  First were calculations of the accessibility of solvent to the surface of proteins, followed shortly thereafter by calculations of the packing of amino acyl side chains in the interior.   These were followed by calculations of the packing of α-helices in myoglobin.  Calculations of the interior packing of proteins led much later to calculations of sequences compatible with a particular main chain conformation and in silico protein evolution.

The Richards Lab always included a “wet” component, focused on the properties of proteins in solution and on the design and application of new chemical reagents for modifying proteins in ways that reported on the proteins’ structure and/or function.  Types of reagents pioneered in the Richards laboratory included hydrophilic and hydrophobic photoactive reagents for studying membrane protein topology, cleavable cross-linking reagents for studying protein quaternary structure, and reagents that exploited the remarkably strong binding between ferritin and avidin for use in localizing target proteins within cellular structures.

Richards received many honors for his scientific achievements, including the Pfizer-Paul Lewis Award in Enzyme Chemistry (1965), a Guggenheim Fellowship (1967-1968), election as Fellow of the American Academy of Arts and Sciences (1968), election to the National Academy of Sciences (1971), the Kai Linderstrøm-Lang Prize in Protein Chemistry (1978), ASBMB Merck Award (1988), the Stein and Moore Award of the Protein Society (1988), and the State of Connecticut Medal of Science (1995).

What should not be overlooked in reviewing Richards’ science is that the Richards Lab was a wonderful place to develop as a scientist, whether one’s experience there was as an undergraduate student, graduate student, postdoctoral fellow, or sabbatical visitor.



Quotes for use with the Retrospective on Frederic M. Richards


James V. Staros, who had been a graduate student with Fred Richards in the early 1970’s, and who is currently Professor of Biochemistry and Dean of the College of Arts & Sciences at the State University of New York at Stony Brook, remarked, “One of Fred’s outstanding characteristics was his penetrating, almost prescient vision, his ability to see far beyond the experiment at hand.  One example:  In a paper published in the JBC half a century ago (Richards & Vithayathil [1959] JBC 234: 1459-1465), in which were described the separation of ribonuclease S into enzymatically inactive S-protein and S-peptide and the reconstitution of enzyme activity by the re-association of S-protein and S-peptide, he observed ‘The strength of the interaction in this enzyme system appears to be of the order of magnitude that might be required to explain the initial effects of peptide hormones in the target organs.’  As someone who has spent much of his scientific career working on receptors for one class of polypeptide hormones, I find this remarkably visionary—and typical of Fred.”


Louise Johnson, who spent a postdoctoral year with Fred Richard in 1966 and was a member of the crystallographic team that solved the structure of RNaseS, and who is currently the Sir David Phillips Professor of Molecular Biophysics at Oxford University, offered the following remembrance: 

“Fred’s lab was a marvellous place to be. I had also come to learn some biochemistry. Fred was enormously encouraging and was prepared to support some way-out experiments. One such was our attempt to determine the binding site for the platinum heavy atom derivative, platinum diaminodichloride with RNAse, using neutron activation.  We travelled by a small plane to Brookhaven where our electrophoresis samples were irradiated. The samples came back red-hot from the sodium in the chromatography paper. Fortunately the activated sodium isotope decayed before the gold isotope of the activated platinum.

We all had tremendous admiration for Fred both for his scientific wisdom, expertise and creativity and also for his extra-science pursuits in ice-hockey and in sailing.

In the following year 1967, Fred and Sally came to Oxford for a Sabbatical year with David Phillips.  They made the unusual travel arrangements in sailing their own boat across the Atlantic. They also took the precaution of having an admiral’s son on board.  The Sabbatical in Oxford was a great success.  In those days the manual interpretation of electron density maps in protein crystallography was a time-consuming and inaccurate process. In Oxford Fred constructed with his own hands and with the help of the workshop staff the device that became known formerly as the Richards Box (or less formally in the lab as Fred’s Folly).  Using a half-silvered mirror it allowed a projection of the model onto the electron density map and greatly aided interpretation before the days of computer graphics.  I also recall in Oxford Fred was interested in chitinases and would cycle over to Wytham Woods (a University reservation about 5 miles from Oxford) to collect mushrooms as a source of enzyme.

I recall Fred with great affection.  He was a marvellous mentor (although I was always a little in awe of him), and great scientist with whom one could discuss a whole range of phenomena (for example diffusion of ligands into proteins and protein crystals), and most of all a person who made science and the life of science great fun.”

Monday, January 19, 2009


For those who knew Fred, he was wont to using amusing turns of phrase and odd use of words. If you remember any of these terms and can also describe their usage by him please add them to the comments here.

Friday, January 16, 2009

Obituaries: Yale Daily News, New Haven Register

Yale Daily News: Sterling Professor Richards, MB&B pioneer, passes away at 83

New Haven Daily Register:


Frederic M. Richards died of natural causes at his home in Guilford, CT on January 11, 2009, at the age of 83. He was a Sterling Professor Emeritus of Molecular Biophysics & Biochemistry at Yale University.

Fred was born in New York City in 1925. He graduated from Phillips Exeter Academy in 1944, received a BS in 1948 from the Massachusetts Institute of Technology, and a PhD in 1952 from Harvard University. After completing a postdoctoral program at the Carlsberg Lab in Denmark, he joined the Yale faculty in 1955 and remained there until his retirement in 1991.

During his scientific career, Fred was instrumental in determining the structure of the RNA molecule with Harold Wyckoff. He was the first chair of the Molecular Biophysics and Biochemistry Department at Yale University. He served as a leader in the National Academy of Sciences, and as the scientific director of the Jane Coffin Childs Foundation.

Besides science, Fred Richards had a passion for sailing. He was an active member of the Cruising Club of America, made two trans-Atlantic crossings to England, and many voyages from the coast of Florida to the northern latitudes off Cape Breton, Newfoundland and Labrador.

Fred and his wife, Sally, were active supporters of the Coast Guard Auxiliary, Guilford Land Conservation Trust and its West Woods Trails Committee, and participated in many Faulkner’s Island projects.

He is survived by his wife of 49 years, Sarah (Sally) Wheatland Richards. He also leaves three children: Sarah O. Richards of Coupeville, WA, Ruth G Richards of Cabot, VT, and George H. Richards of Fairfield, CT, and four grandchildren Benjamin H. Lillie of New York City, George H. Richards III, William S. Richards, and Kate E. Richards of Fairfield, CT.

A Memorial Service will be at Yale Battell Chapel on Feb. 12 at 2:00 p.m. with a reception following at New Haven Lawn Club. Memories may be added at any time to the website: In lieu of flowers, donations may be made to Guilford Land Conservation Trust, P.O. Box 200, Guilford, CT 06437 or Woods Hole Oceanographic Institute, Woods Hole, MA 02543.

Thursday, January 15, 2009

Memorial Service

The Memorial Service is scheduled for Feb. 12 at 2:00 pm at the Battell Chapel at Yale University. A reception will be immediately following at the New Haven Lawn Club.

Thursday, January 8, 2009


Fred made his home in Guilford, Connecticut. He was active in that community in so many ways - West Woods Trails, Lighthouse work, shoreline projects, ice skating, Coast Guard Auxilliary.... You know more stories.... please add them.

Family & Friends

Fred has three children that were born to him, lots of cousins, nieces, nephews, grandchildren, students... The people who consider him a father figure go way beyond blood lines. Please add your stories here.


Many people sailed with Fred and Sally over the years. He made two trans-Atlantic crossings, and made many other trips over the years. If you have sailing stories you'd like to share, please comment here.

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.

From Rags with pictures

I worked with Fred as a postdoctoral fellow during the years 1988-1992. He has had an abiding influence on everything I do. Fred was an outstanding scientist whose contributions have deeply influenced the way people think about protein structure and folding. More importantly, he was an exceptional person, warm, cheerful and solid as a rock. One trait that I particularly admired was his ability to continue doing his own science, whether it was banging out programs down in C-10 or working on his pet photolabeling project for experimental accessibility measurements. Both activities were occasionally punctuated by a variety of juicy, muttered phrases when things were not going smoothly. I have attached a few photographs, which more than anything I can say, capture a few of the many memorable and happy moments spent around him.

Raghavan Varadarajan aka Rags

Link to photos:

Monday, January 5, 2009

Welcome to FMR's Commemoration Blog

You are invited to join in commemorating Frederic Middlebrook Richards. This blog has been created by his children to allow family, friends, and colleagues to share their memories and wishes of this hardworking and beloved man.