Letter to the Editor: Distanced Inspiration from the Career of Stephen H. White

Dear Editors,

I am writing to add my voice to those making BLANCO-80 contributions to the Journal of Membrane Biology to celebrate the birthday of Professor Stephen H. White of the University of California-lrvine and his long career of discovery in membrane biophysics. Even before I had met Dr. White in person, work from his lab was critical in shaping my thinking about membranes, as summarized elsewhere (Sanders, 2019). Moreover, through attendance of the long-running FASEB Summer Conference on Membrane Biophysics, the Biophysical Society Annual Meeting, and the new Gordon Conference on Membrane Protein Folding, I have seen him on at least a yearly basis for most of the past 25+ years. Nevertheless, unlike some other BLANCO-80 contributors, I never had the pleasure of working directly with Dr. White. It must therefore be noted that the interpretation of certain aspects of his career accomplishments and profession demeanor presented herein reflect my own personal impressions from a distance. Here, I highlight three aspects of career that I find both inspiring and instructive.

The work of the White lab is surpassingly thorough and patient. His Ph.D. studies in the 1960s and later postdoctoral and early independent work led to a series of papers on the properties of what are often referred to as “black lipid membranes” or “planar bilayers”, where a single lipid bilayer seals the pinhole separating two aqueous compartments. He published roughly a dozen papers on this topic, most as the lone author (c.f. (White, 1970; 1972; White et al., 1976; White, 1978; 1980)). This work helps underpin what is now an entire sub-field of electrophysiology based on measuring electrical current across planar bilayers that contain ion channels, toxins, or other conductive molecules. I also note with delight a 1972 paper authored by US Army Captain Dr. Stephen White, based on results from the military lab he ran in the two years prior to his postdoctoral stint (White & O’Brien, 1972). It was shown in that paper that the plasma membrane of E. coli has a transmembrane potential of −26 mV, which is one of the most interesting little-known facts that I can imagine. In the early 1980s his lab shifted its focus to energetics and dynamic structural aspect of solute-bilayer interactions. Papers from this era included no less than 5 on alkane-bilayer interactions (White, 1980; White et al., 1981; Jacobs & White, 1984b; a; King et al., 1985). This period of his career culminated in the classic Weiner and White paper on the dynamics structure of lipid bilayers (Wiener & White, 1992). While his work is sometimes almost exhaustively thorough, Dr. White has also demonstrated the capacity to reinvent himself repeatedly over the years, taking his program in new directions. By the mid-1990s his lab had shifted its focus to exacting studies of polypeptide-bilayer interactions that illuminated the fundamental biophysics of both protein-bilayer interactions and membrane protein folding (c.f. (Wimley & White, 1996; Hristova et al., 1999; Ladokhin & White, 1999; White & Wimley, 1999; Wimley & White, 2000; Hristova et al., 2001; Jayasinghe et al., 2001; Ladokhin & White, 2001; White et al., 2001; Ladokhin & White, 2004; Fernandez-Vidal et al., 2007)). In the 2000s his lab took a cellular direction by joining forces with Gunnar von Heijne of Stockholm University to conduct groundbreaking quantitative measurements of the membrane position-dependent impact of each amino acid on the partitioning of helical segments between luminal and transmembrane destinations in cell-derived microsomes as a membrane protein is translated through the translocon (Hessa et al., 2005a; Hessa et al., 2007; White & von Heijne, 2008; Jaud et al., 2009). These studies included successful efforts to illuminate the evolutionary paradox in membrane protein design represented by the S4 transmembrane helix of voltage-gated ion channels, which must contain a pronounced net positive charge while at the same time maintaining a transmembrane placement (Freites et al., 2005; Hessa et al., 2005b; Krepkiy et al., 2009). During the 2010s White increasingly embraced the use of computational modeling methods to generate a robust dialog between experimental results and the vivid dynamics and atomic-level insight offered by simulations (c.f. (Bondar et al., 2010; Ulmschneider et al., 2011; Bondar & White, 2012; Schow et al., 2012; Andersson et al., 2013; Capponi et al., 2015; Ulmschneider et al., 2017; Capponi et al., 2019)). Nowadays it is increasingly clear that anyone who wants to sustain a career at the cutting edge of virtually any area of biology needs to be lithe and able to periodically reinvent themself in light of rapidly emerging new technologies and biological advances. Steve White’s career shows how this can be done without losing one’s scientific soul.

My understanding is that the size White lab has never been numerically large. And yet he has mentored a good many scientists who have gone on to highly successful careers, the ones I know being in academia. This includes the co-editors of this BLANCHO-80 series of papers. All of his trainees I am acquainted with—most of whom I consider to be friends— are creative, careful, collegial, reliable, and modest. It is very often the case that kids resemble their parents, especially when they come to adulthood, and I think this applies to the scientific world as well. The quality of his former trainees, both scientifically and personally, speaks volumes about Steve White as a person and mentor.

Finally, as far as I have ever been able to tell, Stephen White is fundamentally a devoted scholar who is driven by a thirst for knowledge and truth that is its own reward. While he has received accolades and honors over the years I often have wondered if his work remains somewhat underrecognized. However, nothing has come up in my interactions with him over the years to suggest he has given it any thought. I wish Dr. Stephen White good health and very much hope there will be yet another body of fantastic new work from his lab for us to review by the time #90 rolls around!

Sincerely and respectfully yours,