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Mass Spectrometry For Proteomics Analysis
John B. Fenn
Virginia Commonwealth University, Richmond, VA
BioTechniques, Vol. 40, No. 6, June 2006, pp. 780–781
Full Text (PDF)
Abstract

Special Section: Mass Spectrometry for Proteomics Analysis

The scope of techniques covered by BioTechniques is extensive, ranging from permutations of PCR through microarray analysis to imaging of molecules in living cells. New methods that have been developed and applied in diverse areas of life science research populate every issue. Periodically, the editors select a particular technology or area of research and explore it in greater depth than is possible in the regular monthly issue, informing both experienced users of the technology and interested non-users alike. In this issue we are pleased to present a special section, Mass Spectrometry for Proteomics Analysis. Analysis of proteins by mass spectrometry encompasses a variety of approaches for the detection, characterization, and quantification of proteins and peptides. Review articles in this issue discuss ion/ion chemistry—a developing technology for protein sequence analysis (Good and Coon, p. 783), analysis of posttranslational modifications by tandem mass spectrometry (Larsen et al., p. 790), and strategies for sampling and bioinformatic analysis in biomarker discovery (Conrads et al., p. 799). John Fenn, 2002 Nobel laureate in Chemistry for his contributions to the development of electrospray ionization, steps away from the topic of mass spectrometry per se to share his thoughts on graduate education in a personal Perspective on page 780. The special section commences on p. 779 with an Introduction by John Yates of The Scripps Research Institute, which highlights the major milestones in this field of research and provides a brief overview of the areas treated in the Reviews.

I began my “higher” education in the fall of 1934 as a Freshman at Berea College in Berea, Kentucky. Because I had enjoyed a chemistry course in high school, I enrolled in the Introductory Chemistry course taught by Professor Julian Capps, then the only full-time member of the Chemistry Faculty and probably the best teacher I have ever had. He had worked as a chemist in industry and was able to tell his students why and how what we were trying to learn and understand really was meaningful and useful in the “real” world of commerce we would encounter after college. By the end of the first term, I had been persuaded to make Chemistry my major. When I graduated from Berea in 1937, the country was still in the throes of the Great Depression, and jobs were hard to find. Meanwhile, Julian had further fanned the flames of my interest in the subject per se, so I had applied for graduate study at several universities and was lucky enough to be offered Teaching Assistantships at Yale and Northwestern University. It happened that the son of Berea's Treasurer had been accepted as a freshman at Yale, and his father was planning to drive him and all his gear from the middle of Kentucky to New Haven, Connecticut. He kindly offered me a free ride to New Haven. Thus in June of 1940,I received my Ph.D. in Chemistry from Yale instead of Northwestern!

I spent the next dozen years in industrial R&D at three successively smaller companies. A sequence of unplanned events then took me to Princeton University in 1952 as Director of Project Squid, a program of basic and applied research in “those fields of science relating to Jet Propulsion” that was administered by Princeton for the U.S. Office of Naval Research. In 1959, Princeton offered me a faculty position in its newly organized Department of Mechanical Engineering and Aerospace Sciences. Eight years later, I returned to Yale as Professor of Chemical Engineering. In 1987,I became subject to that university's mandatory retirement policy and was ordered to give up my laboratory space. Eager to continue my research, I pursued a delaying action against the bureaucracy until 1993, when I gave up and moved to my present position as Research Professor of Chemistry at Virginia Commonwealth University (VCU) in Richmond. Over the years, it has also been my good fortune to have had extended visits as a guest scientist at a variety of institutions in Italy, Japan, Germany, Israel, China, Australia, New Zealand, France, Belgium, Canada (and California!). I mention all this not impress the reader, but to let him or her know that what I will say from here on has roots in many sources.

I have forgotten the name and authors of the text book used in my freshman chemistry course, but I do remember that it had some 350 or so pages. The text book used here at VCU some 25 years ago had 800 plus pages. The one now in use has 1150 pages! The implications of this trend in the size of introductory textbooks were brought vividly to my attention in a two-page article in the journal Science, of August 9,1963, page 486, vol. 141, written by Henry G. Booker, then a Professor of Engineering and Applied Mathematics at Cornell University. This was before the days of photocopiers, but I was so impressed that I asked the Departmental Secretary to type the article on mimeograph stencils and run off 200 or so copies. For the next few years, I would periodically give copies to both faculty colleagues and visitors to remind them of their true obligations as teachers. By the time my supply of mimeograph copies ran out, photocopiers were everywhere. Thus, for the next few years I was distributing photocopies of the mimeograph copy I had retained! Then David Miller, a former colleague at Princeton (and now Vice Chancellor at the University of California, San Diego), was able to get a few reprints of the original article from Professor Booker who had retired to the San Diego area. Thus, I now distribute photocopies of the reprints to colleagues, friends, visitors, and even strangers in the educational community.

In my view, Booker puts his finger on a fundamental and prevailing fallacy in the educational community. He starts with the assumption that the primary purpose of a university experience is to develop the minds of students, to take the best brains from high school and make them work as well as possible. He then notes that a university is a collection of different departments. Each one is concerned with a particular branch of knowledge, but all of them share the common purpose of developing the students’ minds. The expertise in a particular branch of knowledge with which a department and its faculty members are concerned is simply the means of achieving mental development, not the purpose of that development. Unfortunately, as Booker points out, there are people in many departments who fail to distinguish clearly between the “means” and the “objectives” of the educational process. Thus, one all too often hears from a faculty member in a particular department: “Students should not graduate in such and such a subject from this university without knowing so and so.” Such an individual can usually be tagged as a person who has allowed a misguided loyalty to a particular discipline, in which he or she is an expert, to supersede his or her loyalty to the profession of education—a person who talks about the means available for the educational process as if those means were the objective of the educational process.

Another problem is the common, but too often unrecognized, assumption that because more is now known about a particular subject than was known 50 years ago, a student must now learn more than he or she would have had to learn 50 years ago. The fallacy of that assumption becomes clear when one realizes that the student's brain today is the same as it was 50 years ago! What this great increase in knowledge really does is simply to give the teacher more material from which to select in fulfilling his or her primary obligation, i.e., to develop students’ minds!

Booker goes on to distinguish between the purposes of undergraduate and graduate education. The former is characterized by a primary concern with what is already known. Its objective is to enable a person to understand what has already been understood. Thus, its focus is on the study of what is already known. However, in the real world, one also encounters problems that have not been previously solved. Consequently, one cannot simply look up the solutions to those problems in a library, no matter how big that library is. How does one deal with such problems? The answer is: by a process and activity known as “research.” Thus, the primary purpose of graduate education is to provide students with experience in solving problems that have not been previously solved (i.e., problems to which the answers are not yet known and, therefore, cannot be found in any book or library of books). The most effective way that a student can get this much needed kind of research experience is to become part of a group or team of students and scholars engaged in research in a particular field, under the direction of a leader with knowledge and experience in that field. Such groups can be found in many places, including businesses as well as universities and research foundations. The big advantage of a university is the continuous turnover of personnel (students) who don't have a vested interest in the status quo and, therefore, are willing and even eager to question its underlying assumptions, as indeed they should!




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