Memories of a two-decade journey with a SC addict

Abstract

How many presentations by consultants who applied to your company can you remember? A very outstanding one, which was given more than 20 years ago, I remember exceptionally well. But what was so special or unique about it? Was it the quality of the lecture, its content or the person who gave it? I think it was simply everything together. This consultant was Anthony Vincent Rawlings, better known everywhere as “Tony”, someone whom Albert Kligman described in his last publication entitled “Corneobiology and corneotherapy – a final chapter” in IJCS in 2011 as the “indefatigable Master of the Masters.” I, on the other hand, simply called Tony “Mr. SC” or “the walking library.”

Fortunately, our company decided to take a chance on working with Tony. As it turned out, this was a wise decision. The business relationship lasted from 2002 to 2022, but our friendship still exists. Below are some of my more or less chronologically summarized memories of our long journey together.

I often wondered why Tony and I hadn't met earlier and when we met for the first time. It was probably at the IFSCC Conference in Platja d'Aro in 1993, where we both gave podium presentations. But somehow, we didn't really notice each other back then. It would be another 9 years before fate brought us together. The reason why Tony did not attend the Stratum corneum III Congress, which our company organized in Basel in 2001 together with Ronnie Marks and Jean-Luc Lévêque, was that Unilever's R&D department was once again being reorganized and Tony no longer wanted to move back from England to the USA with his young family. That was the moment he decided to start his own company, AVR Consulting, in 2002.

What a great time this Unilever SC gang, consisting of Tony, Clive Harding, Allan Watkinson and Ian Scott, had from the late 80s to the late 90s of the last century. How much light these extraordinary scientists shed on the SC, how many secrets they uncovered and unanswered questions they approached. It's unbelievable what these guys achieved in our field back then. We all still benefit from this today and build on many of these findings. I was envious of this special era more than once and often wished I could have been part of this group.

When the co-operation between our company and Tony began in 2002, two persons with similar scientific interests slowly came a little closer together. The time finally seemed ripe for us. For me, it was the beginning of something unique and wonderful. Tony and I were obsessed with understanding more about the key pathways in SC maturation and desquamation and the differences between different skin types, particularly on the face. We soon have developed the “Corneocare” concept as an umbrella for these processes. In the first phase of our collaboration, we focused on the serine proteases in the SC. It was a very fortunate circumstance that my colleagues in the Blood Coagulation Diagnostics Department at the time were experts in serine proteases and their inhibitors. They synthesized specific fluorogenic substrates and later inhibitors for SC serine proteases for us, some of which were not yet commercially available.

It was an obvious approach to obtain and analyse the SC proteases using tape stripping. At that time, however, there was no suitable device on the market that could measure the amount of removed SC and other analytes on the same tape. Together with Jürgen Heiland from Heiland electronic, we developed the NIR densitometer “SquameScan 850A”, which enables a fast quantification of the amount of SC protein on tape strippings. We presented the result of our first joint project at the ISBS Meeting in Philadelphia in 2005, where it immediately met with great interest. More than 200 of these devices are now in use in laboratories around the world. The SquameScan has fortunately established itself as a standard in SC research; the device seemed to be a need not only for us. Our first joint publication appeared in Skin Research and Technology in 2007 and represents a cornerstone in our collaboration with Tony.

Finally, we were able to address the questions that really interested us, the SquameScan was the door opener. We started with the investigation of serine protease gradients in the SC at different body sites. To our surprise, we found markedly increased protease activities of desquamatory kallikreins and inflammatory proteases of the plasminogen system in the face compared to the forearm. We hypothesized that the thickness of the SC and the relationship between stratum compactum and stratum disjunctum are key to understanding the treatment of different types of dry skin. In retention hyperkeratosis, which occurs mainly on the body, arms and legs, the thickness of the SC is increased due to hyperproliferation and decreased serine protease activity, leading to an accumulation of corneocytes on the skin surface. However, in skin conditions with premature desquamation, especially on the face, which is mainly due to erythematous photoaging, the thickness of the SC is reduced due to protease overactivity. The skin of this type exhibits inflammatory conditions that are often pre-inflammatory or subclinical. The barrier reserve on the face is therefore much weaker than on most other parts of the body. One of our publications on this topic was awarded the IJCS Publication Prize 2008. In this paper we demonstrated that plasmin activity in the SC correlates highly significantly with basal TEWL. A little later we found massively upregulated plasmin activity in the SC of acute eczematous atopic skin. The culmination of our work on plasmin in the SC and the application of a specific inhibitor was rewarded the IFSCC Award for Applied Research in 2016. Until recently, it was assumed that epidermal plasminogen originates from the bloodstream. However, due to the high plasmin activity we found in the SC, this transport route was questionable for us. In 2019, together with Marek Haftek from the University of Lyon, we were able to show for the first time ultrastructurally using immunogold labeling and transmission electron microscopy that plasmin is most likely localized in lamellar bodies and integrated into the corneocyte envelopes. This indicates that epidermal plaminogen is synthesized in the epidermis in non-pathogenic skin diseases.

In 2011 Tony became a Visiting Professor at the University College London (UCL). We were incredibly happy for him and proud to now be advised by a professor!

From 2003 to 2012, Tony was Editor in Chief of the IJCS and catapulted the quality, appearance and searchability of the journal to new heights. Tony's big aim was to register IJCS in PubMed. Few of us realize what a time- and energy-consuming undertaking this was. Tony was sometimes on the verge of throwing in the towel. At the moment when “Torture” became a PubMed cited journal and the IJCS once again did not, he made another vigorous attempt, which was finally crowned with success in 2008. A thousand thanks for that Mr. SC! The SCS awarded Tony the Silver Medal in 2013 for this achievement and his outstanding contributions to cosmetic science and he gave a legendary Medal Lecture at The Royal Society of Chemistry in London (Figure 1).

Tony's good relationships with universities heralded another creative and productive phase. With Majella Lane we supported two PhD theses in succession at UCL from 2012 to 2019, with Rachel Watson a post-doc at the University of Manchester from 2013 to 2017, with Reinhard Neubert two MS theses at the University of Halle from 2018 to 2019 and with Beverley Summers at Sefako Makgatho University in Pretoria we carried out several human studies from 2013 to 2018.

When considering analysing sun-damaged and sun-protected facial skin of different skin types, we came up with the idea of also investigating the SC of Albino Africans. The intention was to analyse their SC as an extreme model for pronounced photodamage in order to find important indications for the corresponding signalling pathways and signalling molecules. At the IFSCC Conference in Johannesburg in 2012, we were able to get Beverley Summers from Sefako Makgatho University in Pretoria on board for the project. Her good relationship with the local Albino Society was very valuable. The comparative biophysical and biochemical results of differently pigmented facial skin and the comprehensive “corneome” data generated with proteomics and ceramidomics were included in various publications and expanded our knowledge of the barrier, barrier repair and facial photodamage.

In parallel, we wanted to quickly investigate the unexpectedly large biophysical gradients in the face that we noticed during the measurements in the above-mentioned study. Our approach consisted of measuring skin hydration, TEWL and skin surface pH with conventional devices at 30 precisely defined facial sites. In order to make the flood of data manageable, we converted the measured values into colours and visualized them by projecting the gradients onto digital portraits. The aim was for the results to be quickly understandable for everyone. The ingenious mathematician Pierre Seroul from Newtone Technologies developed an algorithm for this purpose. Interestingly, there were major differences between the four ethnic groups, all of whose test subjects lived in the Pretoria region. The results were impressive, the complexity of facial SC far exceeded our expectations and ideas. There were remarkable gradients of skin hydration, TEWL, skin surface pH and sebum within short distances across the face and the gradients were distinctive among different ethnic groups. We called the approach “Facial Color Mapping” and published it for the first time in IJCS in 2015 (Figure 2). At the ISBS World Congress in 2016, our approach was honoured with the Johann Wilhelm Ritter Award for Innovative Skin Imaging. Further publications on this topic followed, our most recent one in IJCS in 2022 contained a comprehensive comparison of Corneometer and Skicon, each with 3750 measurements on the face.

The two PhD students of Majella Lane at UCL, Nidhin Raj and Dilek Guneri, worked on enzymatic processes in the maturation of the SC, in particular on late stage filaggrinolysis and corneocyte lipid envelope maturation. The focus was on bleomycin, calpain 1, 12R-LOX, eLOX3 and transglutaminase 1. They developed new and improved assays to better describe and understand these pathways involved in the maturation of the corneocyte envelope and performed several human studies. Our publication on sensitive skin won us the IJCS Publication Prize for the second time in 2017. Some of these methods were well received by research groups from other universities and we were invited to participate in studies and publications.

The topic of Rachel Watson's postdoc at the University of Manchester, Victoria Newton was skin ageing at the dermal-epidermal junction (DEJ). Three-dimensional images generated with RCM and μCT illustrated the differences between sun-protected and sun-exposed skin in young and older subjects, but most importantly the spatial differences in the complex topography of the DEJ and highlighted for the first time the distinct morphology of the dermal papillae and the rete ridges (Figure 3). Pierre Seroul from Newtone Technologies and his new colleague Marie Cherel once again supported us in creating the 3D images. The ageing effects at the DEJ were also investigated using proteomics. We came to the conclusion that photoageing should not be regarded as accelerated intrinsic ageing, but as an independent physiological process.

Like Beethoven's 10th symphony, the co-operation with Reinhard Neubert at the University of Halle unfortunately became “the unfinished” due to external influences. Although the two Master's students, Angelica Avila and Christina Jochimsen, did excellent preliminary work on the isolation and structural characterization of the lipids covalently bound to the corneocyte envelope, the Covid-19 pandemic delayed the continuation and ultimately brought it to a standstill. This was like a pinprick in Tony's SC soul, one of the white spots on the SC map remained unexplored by him.

At the 2019 SCC's Annual Scientific Meeting in New York, Tony was honoured with the society's highest award, the Maison G. de Navarre Medal Award, for his services to the interests of the cosmetics and personal care industry (Figure 4).

In April 2022, Tony's consultancy contract with our company was terminated by mutual agreement due to his well-deserved retirement. Together with Tony we published 45 papers, 27 of them in IJCS.

You may now know a little more about Tony's achievements as an outstanding and multi-award-winning scientist. But who is this contemporary actually? I have always greatly appreciated his pragmatism as a scientist who never lost focus on the essentials and his brilliant and pragmatic approach to data analyses. As a consultant, he often delivered reliably more than was asked of him, sometimes providing extremely interesting information that was not even requested. His response time during the day was usually less than an hour. Tony was always on hand as quickly as possible when problems of any kind arose, and he showered us with pioneering ideas for new concepts and projects. Unfortunately, we were only able to devote ourselves to a small fraction of them. Nevertheless, his contributions led to numerous market launches. Tony was our engine, he became more and more a team member rather than just being a consultant. His style makes him undisputedly THE number one benchmark for consultants worldwide. As a teacher, I appreciated his calm manner and the excellent pedagogy and content of his presentations, which he gave internally at our company and to our customers, as well as at countless international conferences. He taught us all a lot about skin biology with incredible passion and even more patience. I soon got to know and appreciate Tony as a friend. We spent an endless amount of time debating together (also about topics other than SC), laughed a lot together, but also shared rare sad moments when tears flowed. I wouldn't want to miss a single second of it. Tony, the guy with the hard shell (like a corneocyte envelope), has an incredibly soft core. When it comes to family and friends, the SC has to take a back seat. Hard to believe, isn't it?

Well, there is actually something I've been able to teach Tony over the years that I am very proud of. He recently wrote me the following: “Thank you for having the patience to educate a dumb Englishman about good food and especially good wines.” There is now even a rumour that a photo of Tony wearing a chef's apron exists.

Remark:

“Company” stands for Pentapharm until the acquisition by DSM in 2007, as well as for DSM until 2022 and for DSM-Firmenich from 2023 after their merger.

RV was employee of DSM-Firmenich.