McLafferty Rearrangement

December 26, 2021 marked a sad day, as Professor Fred W. Mclafferty of Cornell University passed away at the age of 98.  Fred played a huge role in the lives of those who knew him, and even more so to those who had the honor of calling him a friend and mentor.  Of course, he is well known for enduring scientific achievements (The McLafferty Rearrangement!) and advancements in the field of mass spectrometry through the decades, as early as the 1950’s.  But even more than the significance of his science was the significance of the role he, and his wife Tibby, played in the lives of students, colleagues, and friends.

Fred maintained an extensive network of friends throughout his career, going back to his days as a Cornell graduate student in the department of Chemistry.  Fred earned his Ph.D. with the prominent Cornell organo-fluorine chemist, Professor William T. Miller.  The life-long relationships forged with fellow Cornell grads, including Walter C. McCrone, Robert Ehrenfeld, and William Gavlin, went on to shape his personal and professional life.  On his embarkation into an academic career, first at Purdue and then ultimately returning to Cornell, Fred’s approach to life, research, and running a group was deeply influenced by his experience of those past days. 

Fred gave his time to graduate and undergraduate students most freely.  He always had a robust group of students, both undergraduate and graduate, alongside more experienced post-doctoral associates.  Fred agreed to serve on my Ph.D. thesis committee most enthusiastically, even though I was a student in another (competitive) research group at Cornell.  He made me understand his door was always open, especially if there were any questions or problems that he might help with. Having Fred “on committee” was seen as something of a risk by fellow graduate students, as Fred had the department reputation of being exceptionally tough. This of course proved to be true.  His graduate level course on the mass spectral identification of organic compounds, was both thorough and exceptionally demanding.

Little did I know that having Fred serving on committee would lead to a “McLafferty Rearrangement” in my own life.

Some years later, at the conclusion of my Ph.D. thesis defense, Fred surprised me with his invitation to join his group as a post-doctoral research associate.  Not having conducted research in mass spectrometry, I was in a bit of shock at this. However, as he was willing and most enthusiastic to take a chance on me, I accepted his invitation on the spot.  Completely unaware of what the future would hold, I moved my desk to Fred’s historic lab in Baker Laboratory.  Step one of the McLafferty Rearrangement reaction had started.

Inspired by his life-long relationship with Walter McCrone, the leading scholar in the application of light microscopy to chemical analysis, Fred understood the great opportunities in the miniaturization of chemical analysis.  His firmly held belief was that mass spectrometry would rapidly develop to play a fundamental role in biological and life science; like that done many decades earlier by light microscopy.  

One surprise of joining Fred’s group was that with post-doctoral associates, he left much of the research direction up to the individual.  This was a time of simply fantastic improvements in the ESI-MS analysis of intact proteins.  Everyone in the group was dedicated to take risks, work hard, and accomplish what we could with the significant resources at hand, which at the time included the world’s best performing MS for intact protein analysis.   My own post-doctoral work culminated in a Science paper along with then graduate student Neil Kelleher. This work was also the technical basis behind a Cornell University patent supporting New Objective’s future PicoTip/SilicaTip/PicoFrit technologies. This work echoed Fred’s early career success, together with Roland Gohlke, on the invention of GC-MS.   Step two of the Rearrangement was at hand.

Near the end of my time as a post-doctoral associate, conversations with Fred turned toward next steps in career development, and how Fred would generously help in significant ways.  This is what Fred did for all his students and post-docs; he would put everything on the line in time and energy to help you develop your scientific career.  Your success after your time at Cornell was just as important to Fred as your success while in his lab.

During conversations with Fred about the pursuit of an assistant research professorship, my own personal McLafferty Rearrangement was reaching completion.  Through these (intense!) discussions, Fred helped me understand myself, and my goals better. The commercialization of nanospray technologies, and the starting of New Objective, resulted from these discussions.  Fred was thrilled that technology developed in his Cornell lab would directly propagate to the general scientific market.  His vision and dream that mass spectrometry “make a difference” in the world would be another step forward.  

Fred’s belief in what we, as individuals and collaborators, could do with the science of mass spectrometry was truly boundless.  That belief is what kept him motivated and highly relevant for all his decades in industrial and academic research.  My story is not isolated; it is certainly familiar and shared by many who worked with Fred.   We learned from his determination, energy, enthusiasm, and belief. Indeed many of us have our own personal version of the McLafferty Rearrangement.

As led by Mike Lee, Emily Ehrenfeld, and the talented New Objective team, I believe that the transition and growth of New Objective to a solutions-based company will continue to further enable the dream of Fred McLafferty, so that the science and technology of mass spectrometry does indeed “make a difference”.

-Gary A. Valaskovic, Ph.D.