JOURNAL OF BACTERIOLOGY, Apr. 2002, p. 2065–2071 Vol. 184, No. 80021-9193/02/$04.00�0 DOI: 10.1128/JB.184.8.2065–2071.2002Copyright © 2002, American Society for Microbiology. All Rights Reserved.

MINIREVIEW

Thanks, CharleyMichael D. Manson*

Department of Biology, Texas A&M University, College Station, Texas 77843-3258

Charley bloomed again this September. Phaleonopsis Char-ley Yanofsky (Fig. 1, left) is a persistent bloomer, a fittingrepresentative of its namesake (Fig. 1, right). Charley sits in alab window that gets afternoon sun. Twice annually since 1995Charley has sprouted stalks that bear corsage-perfect blos-soms. Now, in late October, there are three unimposing leaves.But next spring Charley will flower again, as surely as theswallows will return to the Stanford quad.

How many molecular biologists have orchids named forthem? How many have influenced three generations of scienceas Charley has? How often, in any discipline, can you mentiona first name and have everyone know whom you mean? Andhow many names are synonymous with a molecule? Charleyequals tryptophan.

Eric Selker remembers his early days as a graduate student.“I told Charley I was interested in eukaryotic gene regulation.Charley said that was fine, as long as my project had to do withtrp. I read whatever I could on trp regulation in yeast, peas,Neurospora, etc.” Eric decided on Neurospora. One wonderswhat would have happened had Eric chosen peas.

Charley was not a late bloomer. Paul Berg recalls, “Charleyhad already acquired giant status when I was a postdoc. Hislecture at a symposium in Detroit in 1955 or 1956 (Charley wasthen at Case Western) was the clearest evidence I knew thatsupported the direct gene-enzyme coding relationship impliedby Beadle and Tatum’s one gene-one enzyme model proposed10 years earlier. It was especially gratifying when he stopped atWashington University and stayed at my house on the way tobe interviewed for Ed Tatum’s position in Stanford’s BiologyDepartment. He knew that Arthur Kornberg and the entireDepartment of Microbiology had agreed to create a new De-partment of Biochemistry at Stanford. Persuaded by that,Charley accepted Stanford’s offer in spite of the less-than-adequate lab facilities that would be available to him at thetime.”

Those antiquated facilities in the old Jordan Hall did notquench the lab’s esprit. Milton Taylor, one of Charley’s firstgraduate students at Stanford, recalls “I arrived in 1961. I wasin the oldest Yanofsky lab, in the basement. It was verycrowded. Journal club was the highlight of the week. We metin the seminar room. After the session we went to Charley’shouse for coffee, cake, and ice cream, provided by Carol, whowas a gracious hostess. Wives were included. We played cro-quet after dessert. These �scientific-social’ events cemented the

lab. We functioned as a team. When I set up my lab, I orga-nized a journal club along the same lines, substituting bowlingfor croquet.”

Charley has a knack for making your life easier if you lethim. I was reminded of this gift after I offered to write thispiece. Without knowing what I was planning, Charley sent mea reprint of his scientific autobiography, “Advancing OurKnowledge in Biochemistry, Genetics, and Microbiologythrough Studies on Tryptophan Metabolism” (8). The title istypically Charley—to the point rather than cute or zippy. Thetext makes fascinating reading for anyone interested in learn-ing how Charley views the most significant and influentialevents in his professional life. The major discoveries are allthere: colinearity of gene and protein, translational suppres-sion, transcription attenuation, the basis of trp operator DNA/Trp repressor interaction, and control of conidiation in Neu-rospora. (1–7, 9). This happy coincidence leaves me free toelaborate on what Charley would not—the profound and en-during effect he has had on students, colleagues, collaborators,and friends—admirers all.

Charley is aware of this legacy. The abstract of his reviewstates, “I was fortunate to practice science during the last halfof the previous century, when many basic biological and bio-chemical concepts could be experimentally addressed for thefirst time. . .Throughout my career I enjoyed the excitement ofsolving basic scientific problems. Most rewarding, however,was the feeling that I was helping young scientists experiencethe pleasure of performing creative research.” What followsare the recollections of those scientists, all young when we firstmet Charley, some of us not so young anymore.

COMPETITOR AND SPORTSMAN

As I watched Stanford beat previously undefeated UCLA 38to 28, I wondered if Charley was in the stands. He would bepleased. Charley loves sports. After group meetings at hishouse, we repaired to the kitchen for dessert and to the den forPing-Pong or to the backyard for croquet, weather depending.(Hillard Berger, a postdoc with Charley in whose lab I didundergraduate research, warned me that those proving inept atcroquet were reassigned to shuffleboard.)

Charley played to win. These contests were legendary evenbeyond the Yanofsky lab. Fred Alt, a student with BobSchimke at the time, was good at table tennis. In a dream, Fredfound himself at the Yanofsky’s for the first time. After thepresentations, everyone migrated to the kitchen for cake andcookies, as Fred had heard. Charley came up to Fred with a

* Mailing address: Department of Biology, Texas A&M University,College Station, TX 77843-3258. Phone: (979) 845-5158. Fax: (979)845-2891. E-mail: mike@mail.bio.tamu.edu.

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welcoming smile, put his hand on Fred’s shoulder, and ges-tured toward the den. “A little Ping-Pong, Fred?”

I also remember a basketball game between the Yanofskyand Schimke labs. We graduate students and postdocs con-fined ourselves to outside shots. It was dangerous inside, whereBob and Charley jockeyed for rebounding position. This no-holds-barred approach to hoops extended to pickup games inthe Yanofsky driveway involving Charley, his three sons, andtheir friends. Matt Bonner recalls, “I spent many summers attheir house playing basketball and baseball (well, let’s face it,every sport invented) and swimming. I remember one basket-ball game when Charley was determined not to let the kids win.He twisted his ankle making a run at the basket over any kid inthe way. However, it was all in good fun, and never personal.”

Sunday-morning tennis consisted of matches among Char-ley, Paul Berg, another Stanford faculty member or two, andsometimes a decidedly nervous postdoc or graduate student.Charley mentions these contests in his Annual Review of Bio-chemistry memoirs (8), and Paul Berg also looks back on themfondly. “Having settled on the Stanford campus just down thestreet from Charley’s house, our two families became one, andwe soon discovered that our passions for science were matchedby our intensely competitive drives on the tennis court. Whatbetter way to spend Sunday mornings than facing each otheracross the net, determined to do each other in, and then endingup with an in-depth retelling of what went on in our respectivelabs during the previous week. Ideas flowed freely, often cul-minating in experiments to test them. It was in that setting thatour one collaboration—proving that missense suppression re-sults from mutant tRNAs—originated. It was then that I firstbegan to appreciate and use the power of microbial genetics.”

When I worked with Charley (1969 to1975) it was not obvi-ous that he competed against anyone but himself in science.He seemed unconcerned about getting scooped. I once askedCharley where he was going on sabbatical. He replied that he

would stay in his lab at Stanford because that was where themost exciting stuff was going on. This attitude was reassuringfor graduate students and postdocs. It provided security andtime to develop at our pace in the best place in the world. Italso kept us in science. We were shielded from the unpleasantaspects of the business. If Charley ever sweated a grant dead-line, it did not show.

Cathy Squires, who came with her husband Craig as a post-doc in the early 70s, remembers, “Charley gets more high-quality work from anyone than any scientist I have met. Hisweekly meetings with each person were the epitome of encour-agement. You went away filled with ideas to pursue and ex-citement about what you were doing. He never made you feelyou had let him or the project down—you just had to try morethings! Charley clearly didn’t concern himself with what youdid from minute to minute, but he expected some progresseach week, and that’s what he got.” Well, sometimes.

ATTENTION TO DETAIL

One thing that has contributed to Charley’s success is hisability to notice details that might seem insignificant and beglossed over by others. Matt Springer tells a story that capturesthis talent. “I was a grad student in Charley’s lab in the late 80s.I took his Gene Action class, which he taught every other year.We were required to present an example of gene regulation. Ichose the activation of a set of genes in Neurospora and endedmy presentation by showing a complex Rube Goldbergscheme. It relied on a long cascade of events—popping bal-loons, swinging knives, fish tanks filling up with water, etc.—toallow a biochemical signal to stimulate transcription. One ofthe steps involved a sketch of a housewife with her broom,taken from the comic strip Bloom County. The woman wasscared by the previous event, and her scream broke a glass,which led to the subsequent event. After taking several min-

FIG. 1. (Left) Phaleonopsis Charley Yanofsky in flower. (Right) Charley arriving at Asilomar for Gene Action ’95, his 70th birthday cele-bration.

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utes to outline my scheme I held my breath, wondering ifCharley would be annoyed, exasperated, or simply tolerate mysense of humor. His response? �What’s the broom for?’ heasked, referring to the one object on the page that had notplayed a role in my pathway. Now THAT is attention to de-tail!”

Cathy Squires learned that you reject Charley’s advice atyour peril. “When I started, I was sure I knew far more thanCharley about the in vitro system I was setting up. So, I listenedto his suggestions politely and ignored them! After six months,I realized that some of his suggestions would have led to farquicker success if I had followed them. I mended my ways.”

Sometimes what Charley noticed were details that were notquite in place. My own vivid memory comes from a conversa-tion we had about the third manuscript in my dissertation. Wesubmitted the other two to the Journal of Bacteriology, andCharley asked where I wanted to send the third one. It wasobvious that he did not intend to be an author. I asked whatwas wrong. He could not put his finger on it, but somehow mydata did not convince him. (Subsequent work by Irv Crawfordand Ray Mosteller showed that Charley’s instinct was correct.)Although he did not speak disparagingly, I was peeved. I askedwhy he thought I would submit a paper that was not goodenough for him. The only answer I remember was a wry smile.I vowed then and there never to submit a paper that did notdeserve to have Charley Yanofsky on it. I have not lived up tothat standard, but it remains a fine one.

EFFICIENCY

Everyone marvels at Charley’s organization. Part of his se-cret, I am convinced, is that he adheres to an invariant sched-ule. Monday through Friday, come to work by 8:30 and leave at5:30. In the evening, dinner followed by paperwork in thestudy, maybe with a break for the evening news. On Saturday,it was work until noon, then to Harry’s Hofbrau for lunch.Charley loved Harry’s corned beef sandwiches and kosher dills.Saturday and Sunday afternoons and evenings were for familyor more paperwork; Sunday morning was for tennis.

Eric Selker expresses his wonder at Charley’s efficiency.“Back in the days before e-mail, prominent scientists likeCharley received a great deal of mail. Every morning, Charleywalked through the grad lab (my guess is that he designed thelab with this path in mind) with a huge load of mail, weighingperhaps 10 pounds. He would then start answering the mail,scanning the journals, etc., which would take most of us thewhole day, but within an hour he was done.”

Many of us benefited from Charley’s promptness in correct-ing manuscripts. Matt Sachs notes, “One thing that comes tomind immediately is the awesome way that Charley handlesdrafts of manuscripts (overnight when I was in the lab) and thethorough way he criticizes them.” Eric Selker adds, “The mostremarkable example that I recall concerns a set of papers onattenuation that took up half of one issue of the Journal ofMolecular Biology. Charley edited all the manuscripts in oneevening, despite his having been somewhat under the weatherthat day.” Jack Rose shares similar thoughts. “When studentsor postdocs wrote papers, Charley would have extensive com-ments and revisions back the next day. He taught sciencewriting just as vigorously as he taught science.”

Vigorous is right. I decided to inject literary flair into thefirst manuscript I submitted to Charley. The next day it was onmy desk with a terse note. “Nobody wants to read all thisgarbage. Try again.” My prose may still be “wordy” and “long-winded,” but not on purpose.

My 5-year postdoc was followed by 4 years as a researchscientist in Germany. I finally realized that it was “now ornever” if I wanted a faculty position in the United States. Iwrote Charley in some trepidation to ask if he could provide apositive recommendation. His reply began, “The letters I writeare fair.” I did not need to read further. If I deserved a job,Charley’s letter would help me, warts and all, to get it.

MENTOR, FATHER FIGURE, AND ROLE MODEL

Mentor, father figure, and role model appear often in theresponses I received. Matt Bonner has such memories fromoutside of science. “Charley was a graduate student under myfather at Yale. When my father died he left my mother Miriamwith two small children. I can now imagine the fear and un-certainty she must have felt. Charley offered her a job as atechnician. She accepted and stayed until her retirement. Thiswas a generous and kind thing to do. I have always beengrateful. Charley and Carol’s house was an open, welcoming,and fun place to be.”

Eric Selker wrote, “People quickly recognize that Charley isknowledgeable, imaginative, and kind. It soon also becomesobvious that he is extremely gifted in the lab, that his instinctsare fantastic, and that his efficiency is unparalleled. Every mo-tion and every word count. Charley was a father figure; theGerman ‘Doktorvater’ seems to fit perfectly. A father’s mostimportant function is to set a good example. Charley was, andcontinues to be, a great model. I have found it impossible tocome close to his example in most areas, but it continues toprovide guidance.”

Terry Platt summarizes his feelings thus. “I fondly rememberthe golden years of the mid-1970s as a postdoc in Charley’s lab(1972 to 1975). The literature documents the elucidation of themechanism of attenuation. I was also fascinated by the wayCharley ran a successful lab and what I could learn to help melater as a faculty member. His group felt like a large family, fullof mutual affection and sibling rivalry. Charley, as patriarch,spurred us on with curiosity and enthusiasm, rarely expressingimpatience. He embraced all genuine effort, an approach thatI try to emulate in my own laboratory. There was also a re-markable convergence of multiple lines of inquiry to under-stand attenuation. The philosophy was that a laboratory shouldwork on an overall problem—tryptophan metabolism in Char-ley’s case—rather than addressing disparate questions. Every-one could talk with everyone and share a common interestdespite the apparent unrelatedness of specific projects. Whenthose projects pointed in the same direction, the realization wewere part of a team added energy to the thrill of discovery.Finally, over the past three decades Charley has continued tofollow and encourage my efforts to carve a research niche ofmy own. I will always cherish having Charley as mentor andfriend over this time.”

Charley was always excited when he learned new things fromstudents. Paul Babitzke, a postdoc from 1991 to 1994, looksback on such a moment. “I was studying the trp/TRAP system

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in Bacillus subtilis. I was testing the attenuation model pro-posed by Charley and Mitzi Kuroda. Charley and I designed anin vitro filter-binding experiment to determine if RNA second-ary structure occluded TRAP from one of two 10-nucleotidesites in the leader. My data made no sense.

“I had to give group meeting the next morning, so I wastrying to figure out how to explain the data. I examined the trpleader sequence, but I was constantly interrupted by labmateswho wanted to chat, Charley included. As a result, I kept losingmy place. Finally, I realized I kept getting lost because therewere 11 GAG and UAG repeats within the leader sequence,separated by two or three nucleotides. These repeats over-lapped the TRAP-binding sequences that Mitzi and Charleyhad identified. The more repeats, the tighter the binding. ThetrpG transcript had nine GAG repeats overlapping the Shine-Dalgarno sequence. I was convinced I had the answer.”

“I prepared an overhead and confidently presented it at thegroup meeting. I was reading off ‘GAG, space, space, GAG,space, space, UAG, etc.’ when Charley suddenly said ‘That’senough, sit down!’ I was stunned, my confidence visibly shaken.On the way back to the lab, someone joked that Charley hadinvoked the ‘GAG’ rule. Ten minutes later Charley burst intomy office. ‘Do you think this is right? Here’s what we need todo.’ Charley had not interrupted because he was annoyed. Hewanted to get back to his office to check the leader sequences.This day was, perhaps, the most exciting in my career. I, of allpeople, had taught Charley something.”

Charley expressed his view on mentoring to me in a 1998letter. Some of it was personal and brought a smile. Charleydid understand me! His more general comments illustrate whatCharley means to those who work with him. “I didn’t knowwhat to make of your letter—are you retiring? Kidding aside,from my perspective it is nice to know that at least one of yourstudents appreciated you! Handling students is much like deal-ing with your own children. Are you more helpful when you aretolerant and patient, or when you are critical—who knows?Each of us is different. It is probably a mistake to assume thatthere is only one correct approach. In your case. . .You alsomade a wonderful choice in picking Lily [my wife, Lily Bar-toszek, assistant to Journal of Bacteriology editors SusanGolden and Ry Young]. She is delightful and must be a greatcompanion.”

Being married to Carol and, after Carol succumbed to can-cer in 1990, Edna, widow of Charley’s close friend and scien-tific colleague Irv Crawford, has given Charley rich experiencewith wonderful companions. He has also been blessed withloyal and talented assistants: Miriam Bonner and Ginny Vaniaas technicians and Susan Lacoste as secretary. Aside from theirawesome professional skills, they always listened to students’problems and gave sensible advice, whether about science,Charley, or the travails of life in general. The women in his lifehelped keep Charley human. We loved them for it, and forthemselves.

FRIDAY MEETING

Mentoring was most intense during Friday meetings. Eachgraduate student and postdoc had an hour with Charley everyweek. I often found myself cringing at Charley’s “So?” when Ientered his office. What I had to say seldom seemed adequate.

I was not alone in my insecurity or in my later appreciation ofthese conferences. Mitzi Kuroda urged me to include them. “Ihope you will mention the value of the Friday meeting. I oftendreaded my meetings because of lack of progress, but some-thing interesting and insightful almost always came out ofthem. In retrospect, it was an amazing luxury to get Charley’sundivided attention! I carry on the tradition of the Fridaymeeting in my own lab.” So do many Yanofsky alumni.

Roberto Kolter, postdoc in the early 1980s, also retainsmemories of Friday meetings. “I was always excited to talk toCharley on Friday. A few times I had results to discuss, but itdid not matter. The beauty of going into Charley’s office wasthat, for those minutes, I had the undivided attention of one ofthe world’s brightest geneticists/biochemists. Brainstormingwith Charley was the best intellectual experience of my Stan-ford years. We would dream up genetic selections, new tech-niques, and new ways of looking at results. The vast majority ofthese ideas never were put to the test. However, the excitementwe felt was, for me at least, reward enough.”

Jack Rose also focused on the plus side. “Charley madehimself available in daily visits to the bench and scheduledweekly office visits for the standard inquiry, ‘What’s new?’ Icannot imagine a better atmosphere for a graduate student.”Terry Platt adds, “Charley taught me to hold weekly confer-ences with students and postdocs, always on Friday. No matterhow frustrating the week had been, Charley generated a set ofincisive questions and encouraging possibilities to reenergizeus for the next week. Some people came in over the weekendto start the next round of experimental troubleshooting togenerate preliminary answers by Monday.”

CHARLEY AS COLLEAGUE

Charley has been equally influential with his colleagues atStanford. Phil Hanawalt writes, “Charley Yanofsky has beenmy role model for how a professor should be professional.Although he is an intellectual giant in his field and has mademany seminal contributions in science, he has always main-tained a careful check on his ego. He is disarmingly humbleabout his accomplishments. Charley has always exhibited awarm generosity with his students and associates at all levels.Charley provided good advice and was most supportive duringmy stint as Department Chair in Biological Sciences. He al-most made it a joy to serve. It is a pleasure to have theopportunity to acknowledge his collegial friendship and thegreat respect I have held for him over the past half century.”

Allan Campbell noted Charley’s preference for no frills.“This is kind of a nonresponse. One time, long ago, Charleyintroduced me for a seminar. He remarked that he had con-sidered including some personal anecdotes but had then re-flected that some day I might be introducing him. Suffice it tosay I have a tremendous admiration and affection for Charley.”Allan’s story reminds me of when I hosted Charley at TexasA&M a few years ago. Since it was a sponsored guest lecture-ship, complete with a commemorative plaque, and becauseuniversity reporters and photographers were on hand, I hadprepared a rather long list of Charley’s awards, honors, andaccomplishments. I had barely launched into my introductionwhen Charley, in the first row, said in a stage whisper “If youkeep on like this, I won’t have time to talk.” That stopped me

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cold. I tried to cover my chagrin with a segue to, “And so,without further ado, here’s Charley!” You will not find a list ofawards and honors here. They are a matter of public record.

Bob Fisher, who was with Charley from 1981 to 1983, pro-vides the perspective of someone who made the transitionfrom postdoc to colleague. “I stayed at Stanford since thattime, working with Sharon Long, so I have continued to seeCharley for the last 20 years. My strongest impression is themodel that he sets to this very day. He is still in the lab, doingexperiments. He calls me up occasionally to ask me to look ata column he has poured or to review the use of the Frenchpress. I have been tickled by this classic example of the masterasking the student for guidance. The man loves science and thediscovery of new information. He wants to be involved in theprocess, hands-on. He is also extremely generous with equip-ment, materials, and space, and our lab has benefited on nu-merous occasions. He’s the best.”

This is an opinion shared by Jim Spudich, who got his Ph.D.with Arthur Kornberg and then did a 1-year postdoc withCharley in 1968. Jim subsequently returned to Stanford as afaculty member in Biochemistry. “Charley is one of my fewheroes, not only as a scientist, but as a special human being. Ifeel deeply honored to have worked with him and to haveknown him all of these years. He has been a role model for me.They just don’t come any better than Charley.”

DREAMS AND DECOYS

Charley loomed larger than life. Although Charley toleratedeccentricity, he did not accept mediocrity. My fears of notmeasuring up coalesced in a dream. I was invited to lunch withCharley to find his home transformed into a Roman villa.Carol, in flowing robes, met me at the door and ushered me toan atrium, where toga-clad Charley reclined on a couch. Aftera horizontal repast by the marble fountain, Charley motionedtoward an alcove containing an engraved chessboard. Beforewe sat down he said offhandedly, “You know, Mike, I just don’tenjoy playing a mediocre opponent.” I reacted with a sudden,spastic move that swept chessmen onto the tile floor. Thedream ended with me kicking pieces into the fountain andshrubbery as Charley scrambled to recover the scatteredpawns, rooks, and bishops.

Charley’s visits to the bench could come too often when youwere goofing off. Ford Doolittle confesses after 30� years. “Iwas not one of Charley’s hardest working graduate students.When he popped into the lab, I often did not have much to sayin response to his interrogatory ‘So?’ After several embarrass-ments when I was caught snoozing with nothing new to report,I developed a foolproof stratagem. I kept a rack of tubescontaining the colorful indole assay in the drawer of my desk.When Charley exited his office, I bustled off to read them in theKlett, too busy for idle chatter. If the tube contents faded orevaporated, I’d replace them. Charley never said whether hefound this suspicious. Now, when I ask my students about theirprogress I hear Charley’s ‘So?’ and wonder if they have similartricks.”

Charley did not trigger these visions and subterfuges by whathe said or did. They occurred because Charley was Charley—amodel for excellence who could cope with anything. That

tended to get you down when you could not finish your smallpiece of the big Yanofsky pie.

CAREER COUNSELOR

The colorful indole assay could serve other functions, aspostdoc Manny Murgola discovered. “After a year and a half inthe lab, I had no positive results. Nothing was working, and Iwas depressed. How bad was it? It was so bad that I started todo the following. Before going home at night, I would set upL-broth cultures of three strains: a null tryptophanase mutant,a partial tryptophanase mutant, and wild type. Why? Because,when I arrived the next morning, I would add indole reagent toeach culture. The first turned bright yellow, the second pink,and the third deep fuchsia. That way, by the end of each day,something had worked!”

That was not a permanent solution, however, so Mannyfinally went to Charley “to discuss my future (or lack thereof)in science. He expressed confidence in my abilities, encouragedme to continue what I was trying to do, and supported mystaying for another year beyond the two for which I had afellowship. Except for his understanding, I might today beplaying saxophone (Fig. 2, right) on some street corner in SanFrancisco rather than doing the scientific research and teach-ing I so enjoy!”

Charley fostered the careers of many scientists. RobertoKolter came to “iron out the wrinkles of attenuation in gram-negative bacteria,” but his research interests wandered. “Char-ley never showed concern when I got involved in projectsthroughout the campus. I appreciated the freedom to grow as

FIG. 2. (Left) Terry Platt holds aloft the dreaded eye chart as awarning to long-winded orators at the beginning of Gene Action ’95.The eye chart was shown to the audience at Tryptophan Meetings toinduce applause when a speaker egregiously exceeded the allottedtime. (Right) Manny Murgola on soprano sax entertaining the crowdat Gene Action ’95. Manny still plays in a professional band in Hous-ton.

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a scientist and an individual. It was vital to my development. Iarrived enamored with the miracles his lab had performed withbacteria. I left confident that I could explore whatever questionI dreamt of in bacteria because of the wonders that could bedone with them. Charley’s love for microorganisms provedcontagious, and I left more passionate about the microbialworld. My work over the 20 years since I left Charley’s lab hasnothing to do with tryptophan, but it bears the imprint of theintellectual impression Charley left in me.”

Naomi Franklin has known Charley longer than anyone.“Charley was already a driving wheel in the Bonner lab at Yalewhen I started graduate studies in 1950. The scientific fermentwas just what I hoped to find. The language seemed Chinesethose first 6 months, but with the help of Charley and others,I began to catch the lingo. Enhanced by camaraderie among awild assortment of personalities, the pleasure of science I ex-perienced then has lasted a rich lifetime.

“My interest in phage � proved valuable when I joinedCharley’s lab at Stanford in 1963. Phage �’s cousin �80 residesin the Escherichia coli chromosome next to the trp operon.Deletions fusing trp to a �/�80 hybrid prophage integrated atthis site, providing direct proof for Allan Campbell’s idea thatthe � prophage inserts linearly, with permuted gene order, intothe E. coli chromosome.

“The dependence of phage � on N protein involves over-coming intrinsic transcription terminators within the N operon.Polarity induced by nonsense mutations in the trp genes alsoproved to be due to transcription termination, reversible invivo by N protein. Charley’s lab discovered a related phenom-enon, attenuation in the trp operon, about this time (in 1973).The notion that mRNA structure can regulate gene expressionwas new in the early seventies and undoubtedly influenced mysubsequent thinking about the nature of N antitermination.

“Very early in this epic, Charley set me upon a course ofresearch autonomy by endorsing my application for an inde-pendent grant. NSF proved willing and supported the workover the next thirty-some years. Charley’s initiative set things inmotion. I also remain grateful for 16 years of haven in Char-ley’s stimulating circle: great science, lively colleagues, and thefriendship of Carol and the Yanofsky boys. Miriam Bonneralso found a productive haven with Charley, enhancing ourfamily circle. The big professional lesson that I took away fromthose years was the value of pursuing a scientific problem to itsdepths.”

Another former Yanofsky postdoc, Bob Landick, in hisnomination of Charley for an Abbott-ASM Lifetime Achieve-ment Award, emphasized the value of mining in-depth ratherthan on the surface. “He dissected the pathway and regulationof tryptophan biosynthesis with such insight and imaginationthat he revealed major principles of biology that will remainforever etched in the edifice of science. Some of us spend ourcareers moving from one perceived opportunity to another,trying to be the first to uncover and glimpse a new gem ofknowledge. Charles Yanofsky spent his working on a singlelarge and ever more luminous stone. Through his persever-ance, intellect, and creativity he polished it to reveal a jewel ofunequaled clarity, each facet offering more insight into thetruth of nature than dozens of more easily discovered gems. Hetruly is a giant of microbiology upon whose shoulders futuregenerations will stand.”

GENE ACTION ’95

I helped Mitzi Kuroda, Manny Murgola, and Terry Plattorganize Charley’s 70th birthday celebration on Passover/Eas-ter weekend of 1995. Charley was persuaded to go along underthe condition it would be staged as a scientific conference. Wesweetened the pot by holding it at the Asilomar ConferenceGrounds in Pacific Grove, Calif., a spot beloved by Charley andsite of the biennial Tryptophan Meeting. The most recogniz-able artifact of that meeting was on hand—the eye chart (Fig.2, left). The disguised party was dubbed Gene Action ’95 afterCharley’s famous course and the year he reached his seven-decade milestone. The slogan, which appeared on the com-memorative T-shirts and on the birthday cake frosting, was“Follow the Leader.” Arthur Kornberg helped by securingindustrial funding to underwrite expenses.

As we pondered over an appropriate present, Dale Oxender,who spent his sabbaticals with Charley, had the genial idea ofasking the McCallum Company, orchid breeders, to name oneof their creations “Charley.” They declined—not dignifiedenough. Thus, did Phaleonopsis Charley Yanofsky receive itsmore respectable name. Laughter erupted when we learnedthat Charley Yanofsky is a cross between “Mad Lips” and“Stop Sign.”

One of Charley’s blooms graces the poster Mitzi designed tocommemorate Gene Action ’95 (Fig. 3). After the poster pre-sentation, Prasanta Datta brought out the real McCallum andset it on the table occupied by Charley and Edna. This livingand lasting gift was possible because Dale knew that Edna andIrv’s passion for orchids had infected Charley.

The response to our invitation was overwhelming and inter-national. Charley’s scientific progeny have dispersed aroundthe globe. Former and current students, postdocs, technicians,colleagues, collaborators, friends, and relatives gathered (Fig.4). The respect, admiration, and love that poured forth werepalpable. Old comrades were reunited, new acquaintanceswere made, and good feelings permeated the conferencegrounds.

The 10-min presentations were spaced out over 3 days toaccommodate everyone who wanted to speak. Some talks wereresearch oriented. Others, defying Charley’s preference, ex-uded more humor and nostalgia than scientific insight. No one,however, summed up our thoughts and emotions more suc-

FIG. 3. Mitzi Kuroda presents Charley with the commemorativeposter for Gene Action ’95.

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cinctly than George Bennett, who was a postdoc with Charleyin the early seventies. He had found a “THANKS. . .CHAR-LEY” consensus sequence in the protein database. It has notryptophan, but neither does the focus of so much of Charley’swork: the tryptophan synthetase � subunit. You see, Charley, Ido remember something you taught me.

ACKNOWLEDGMENTS

I appreciate all who responded to my request for reminiscencesabout Charley with their own stories and thoughts or just by wishingme well. I owe a special debt to Matt Sachs, who chronicled the eventsof Gene Action �95. He helped select the photos used here and pre-pared them for publication. Finally, thanks to Charley, who after learn-ing what we had in mind, still gave this project his blessing.

REFERENCES

1. Babitzke, P., J. T. Stults, S. J. Shire, and C. Yanofsky. 1994. TRAP, the trpRNA-binding attenuation protein of Bacillus subtilis, is a dodecameric protein

that appears to recognize G/UAG repeats in the trpEDEFBA and trpG tran-scripts. J. Biol. Chem. 269:16597–16604.

2. Carbon, J., P. Berg, and C. Yanofsky. Missense suppression due to a genet-ically altered tRNA. Cold Spring Harbor Symp. Quant. Biol. 31: 487–497.

3. Kelly, R. L., and C. Yanofsky. 1985. Mutational studies with the trp repressorof E. coli support the helix-turn-helix model of repressor recognition ofoperator DNA. Proc. Natl. Acad. Sci. USA 82:483–487.

4. Madi, L., D. J. Ebbole, B. T. White, and C. Yanofsky. 1994. Mutants ofNeurospora crassa that alter gene expression and conidia development. Proc.Natl. Acad. Sci. USA 91:6226–6230.

5. Yanofsky, C. 1971. Tryptophan biosynthesis in Escherichia coli. Genetic de-termination of the proteins involved. JAMA 218:1026–1035.

6. Yanofsky, C. 1981. Attenuation in the control of expression of bacterialoperons. Nature 289:751–758.

7. Yanofsky, C. 1984. Comparison of regulatory and structural regions of genesof tryptophan metabolism. Mol. Biol. Evol. 1:143–161.

8. Yanofsky, C. 2001. Advancing our knowledge in biochemistry, genetics, andmicrobiology through studies on tryptophan metabolism. Annu. Rev. Bio-chem. 70:1–37.

9. Yanofsky, C., B. C. Carlton, J. R. Guest, D. R. Helsinki, and U. Henning. 1964.On the colinearity of gene structure and protein structure. Proc. Natl. Acad.Sci. USA 51:266–272.

FIG. 4. Easter morning portrait of the multitude assembled at Asilomar for Gene Action ’95. Many who attended the Saturday evening banquethad already left, including most of Charley’s Stanford colleagues.

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