It is a great honour for me to receive the Honoris Causa of the University of Santiago de Compostela. This award is not only the recognition of an individual’s achievements but also an acknowledgement of the hard work and contributions of all the collaborators who participated in my work. I am touched by the generosity of the rectorate and the University of Santiago de Compostela and I am humbled to be included among the giants who have received this recognition before.
My contributions to science over the past forty-seven years have been in the fields of biomaterials science, polymer science, drug delivery and biomedical engineering. I was born in Athens, Greece. My father was an economist and playwright, my mother a professor of French literature. I was brought up in a loving home in the suburbs of Athens and in the early days I was taught to read and admire the classics. I learned to love Greek and Latin history and literature, but also to appreciate European traditions and the work of German, French, British, Italian, Spanish and Russian authors. History, archaeology and Italian opera kept me busy as I was growing up in the 1960s, but the educational environment was fertile and eventually chemistry prevailed. Upon taking national examinations, as was the norm at that time, I entered the Chemical Engineering Department of the National Technical University of Athens, at that time the most prestigious department in Greece. There, I was fascinated by novel mathematical techniques, advanced transport phenomena and chemical reaction engineering.
For my Doctor of Science (ScD) degree, I arrived in Cambridge, Massachussetts, in August 1971 and I enrolled in chemical engineering at the Massachussetts Institute of Technology (MIT). At the MIT, I had the great fortune to be a student of this great pioneer of biomedical engineering, one of the fathers of the field, Edward Wilson Merrill, still with us at 96 years old. Doctor Merrill instilled upon all of us the idea that the principles of engineering and physiology could be applied to the solution of important medical problems. Those were the days when medical scientists from the Harvard Medical School and the main hospitals of Boston would cross Charles River to collaborate with MIT professors on medical problems requiring modeling, rheology, new materials and innovative technical solutions. I was fortunate to be in the same class and laboratories with other ambitious young men, notably Professor Robert Langer of the MIT, Michael Sefton, now of the University of Toronto, and a young undergraduate chemist, David Tirrell, now provost of CalTech.
Those were truly wonderful days for biomedical education. We worked on the development of new non-thrombogenic biomaterials for artificial organs, on valves for artificial hearts, on new membranes for artificial kidneys, on contact lenses, prostheses, but also on a fundamental understanding of the causes of diseases from thrombosis to arteriosclerosis. These were the wonderful days when funding from the National Institutes of Health (NIH) was plentiful. I will always be grateful to the United States for allowing a young European engineer and scientist like me to delve into important medical problems and make an impact in the medical and materials fields. At the MIT I had the opportunity to interact with Paul Flory (Nobel 1974) who had been invited by Ed Merrill to the MIT and was a visiting professor in chemical engineering at a time we were all doing our doctoral dissertations. You can imagine the impact he had to our thinking about biopolymers and crosslinked structures.
I became an independent researcher and faculty member at Purdue University in 1976. In my laboratories at Purdue University, I started working on hydrogels as biomaterials, first for artificial vocal cords, then for articular cartilage replacement, followed by work on contact and intraocular lenses, non-thrombogenic biomaterials, and new artificial kidney membranes. These were also the early days of drug delivery, a subject we started pursuing in 1977. In the beginning there were some obstacles but funding came early, first with Research Corporation and National Science Foundation (NSF) grants in 1977. In 1980 I had secured my first NIH R01 grant, one that I must admit with pride I continue having now, after 39 years.
By 1978 we had started addressing important new areas of drug targeting, drug delivery, parenteral and oral delivery, mucosal targeting, cell transport, and so on. My students and I became passionate on providing solutions to significant medical problems. We believed that the treatment of diabetes, osteoporosis, asthma, cardiac problems, and cancer should not be based only on conventional pharmaceutical formulations. Indeed, I believe that a key problem of biology and medicine this century has been to reduce the problems of disease to problems of molecular science. Many of the associated methodological advances in biomedical sciences are the result of earlier investments in the basic sciences.I believe that breakthroughs in molecular science have led new opportunities for curing disease. In the last few years, we have been promoting the idea of “convergence in biomedical sciences”. This is a paramount idea in bioengineering and has been a standard in my laboratory in the last 43 years. These interactions have led to collaboration with biologists, pharmacists, and practicing physicians.
In my years of research, I was fortunate to have many interactions with Europe, Japan, China and Singapore. It all started with my meeting with Robert Gurny of the University of Geneva at Purdue in 1977 where he was a postdoctoral fellow. We worked together and published the first two papers on drug delivery. I came to the University of Geneva for a wonderful sabbatical stay at “Pharmacie galenique”, in September 1982, wheer I worked also with Pierre Buri, Eric Doellker, Robert Gurny. While in Geneva, I was the Zyma Foundation Fellow for the Advancement of Medical and Biological Sciences. Through Zyma of Nyon, Switzerland, I met again Pierre Galletti who was visiting Lausanne and Martigny —where he grew up— from time to time. It was in Geneva where we started the work on bioadhesion and mucoadhesion. That’s where we perfected the “exponential equation”. That is where we got seriously into swelling-controlled release systems. My PhD student Richard Korsmeyer(now an National Academy of Engineering (NAE) member) spent six months in Geneva and did some of his pioneering work on swellable delivery, while my student Paula Hansen came to do her pioneering work on the rheological properties and drug diffusion in mucus.
While in Geneva, I visited many other Universities in Switzerland, France, Belgium and Italy. I became friends for life, with many pharmaceutical scientists, including Dominique Duchêne, Patrick Couvreur, Francis Puisieux, Jean Pierre Benoit, Michel Traisnel, Alice Verain, Paolo Colombo, Aldo LaManna, Ubaldo Conte, Carla Caramella, Andrea Gazzaniga, and through them with many (then) students who later became the great generation of today’s great pharmaceutical scientists, including María José Alonso, Ruggero Bettini, Gaia Colombo , Lauretta Maggi, the late Didi Sangalli, Giovanni Caponetti , Patrizia Santi, Maria Teresa Peracchia, etc. Among them, my scientifc interactions and personal relation with professor Paolo Colombo has led to numerous contributions in the field.
My relation with Spain (and Portugal) has been very special. It dates back to a very first meeting at Paris-Sud with María José Alonso in 1986, when she was a postdoctoral fellow with Patrick Couvreur, and I was on my third sabbatical leave at Paris-Sud. That led to exceptional relations and interactions with professor María José Alonso, professor J. Vila Jato, Marcos García —who came to our labs for a year to work with us—, Neomi Csaba, Carmen Remuñán, and later with professors Dolores Torres, Carmen Álvarez Lorenzo and Ángel Concheiro.
Just a parenthesis to say that my first interactions with someone from Santiago were as early as 1971, when I first met this exceptional biomaterials scientist Miguel Refojo. His quiet style and good understanding of hydrogels will always remain in my memory. I am glad to shar this Honoris Causa with him, we were honored by you about 30 years ago.
Later, we started the Controlled Release Society (CRS) chapter and I met Rogerio Gaspar and Antonio Almeida. Antonio was the first to introduce me to the universities of Coimbra and Lisbon, plus the magnificent Lady Fátima. I also love the Camino de Santiago. Eventually I have come to Santiago de Compostela five times, to Spain about 20, the last one in 2017. I had a sabbatical leave in 2001 with professor Juan José Torrado at the Complutense University. There, I met Marta Gómez who did her PhD with me. And then Juan José Torrado had the idea to allow me to visit (every Friday) a different Spanish university and give a seminar. This led to visits to the universities of Sevilla, Córdoba, Alcalá, Toledo, Barcelona and many others. Visiting these universities, I learned to love Spanish culture and cities. I cherish my interactions with the wonderful student choruses, “Las Tunas de Farmacia y Medicina”. I have now numerous recordings with their music. A very special place in my heart was also the visit to the University of Barcelona, the works of Antoni Gaudí and la Sagrada Familia. There, I met professors Josep Domènech and Conchita Pereira who became good friends. Two of their students came to my lab as PhD or postdoctoral students. Laura Serra did her PhD with me while doctor Mar Creixell did her postdoc with me.
I loved Sevilla and Andalucía where I first met Matilde Durán Lobato, who worked with me before going to the Anderson/Langer lab and now María José Alonso’s lab. In Madrid while at the Complutense in 2001 I strengthened my relations with professors María Vallet Regí, Rocío Herrero of the Complutense, and Julio San Roman, and Carmen Mijangos Ugarte of the Instituto de Ciencia y Tecnología de Polímeros, with whom we shared a common PhD student Coro Echeverría Zabala, my first Basque student. And while in Barcelona for a meeting, I met this wonderful chemical engineer PhD student Edgar Pérez Herrero from the University of Salamanca, who came and worked with me before going to María Vicent’s and María José Alonso’s labs. He is now at the University of La Laguna in Tenerife with another friend professor Carmen Évora. I will be there next week (May 2019) to give a series of lectures on an industrial short course, as Robert Langer and I do at the MIT. A special mention must be made of doctor María Vicent of Valencia, whom I met in person only the last few years but who has become a very good friend. And I will never forget also another PhD student of mine, Ana María Fernández Olleros, who is now an associate professor at the Universidad Europea de Madrid. But how can I forget the late evenings in Madrid going up and down la Gran Vía. And the many visits to the Prado and the palaces? And the musical visits to buy any available and any possible zarzuela record? Why all this love for Spain? Why not? After all, El Greco was Cretan/Greec and la reina Sofia was a Greek princess!
I was fortunate to have had some great doctoral students in all my years at Purdue and the University of Texas at Austin, 112 PhDs, 52 of them professors in the academia. Four of them were particularly instrumental in biomedical research in those days, and are members of the National Academy of Engineering and National Academy of Medicine now.Doctor Richard Korsmeyer, a senior fellow of Pfizer and internationally known leader in development of new pharmaceutical formulations, was a PhD student in my laboratory with whom we applied transport theory to understand drug transport in controlled release systems and in tissues. Those pioneering studies of 1979-1982 have led to an equation and a theory (Korsmeyer-Peppas theory) that is now the basis for the design of new drug delivery systems. Another former student is Antonios Mikos of Rice University, with whom we studied targeting to specific sites and developed advanced theories of bioadhesion in tissues. Doctor Mikos went on to become one of the brilliant engineers and scientists in tissue engineering and regenerative medicine. Doctor John Klier of the University of Massachusetts was the main force behind all the polyethylene glycol based formulations that eventually became the novel protein delivery systems. And doctor Robert Scott of Alcon (Novartis) became the originator of all our ocular biomaterials and delivery systems.
My career in the 1980s, and 1990s, and especially this past decade at the University of Texas at Austin has allowed me to design, study and utilize advanced biomaterials and advanced drug delivery formulations. These formulations do not simply release the drug, peptide or protein at some characteristic rate, but do so in a way that we design them to do. Consequently, pulsatile swelling/deswelling of a polymer carriers and the associated drug delivery are consequences of significant changes of the physiological environment. For example, in collaboration with my former PhD student Anthony Lowman, now Provost at Rowan University, we have developed new systems with which insulin may be delivered to diabetic patients only when the glucose concentration in the blood is above the normal level.Calcitonin may be directed to bypass the stomach and be delivered only in the upper small intestine of women suffering from osteoporosis, from where it will be finally absorbed and pass in the blood. Finally, large molecular weight, genetically engineered molecules can be delivered across tissues at acceptable rates. For example, we have exciting new results on oral delivery of interferon-beta–1a for treatment of multiple sclerosis.
These biomedical developments and inventions use intelligent, hydrophilic, biomedical polymers, often hydrogels or networks, as carriers. The structure of these materials plays a key role in their diffusional behavior and the molecular stability of the incorporated bioactive agents.In my scientific career we have also advanced fundamental aspects of materials science and polymer gel theory. Some of the major developments in the field of rapid photopolymerizations came from the PhD work of my former students Alec Scranton, now dean of engineering at the University of Iowa, and Christopher Bowman, member of the National Academy of Medicine and head of chemical engineering at the University of Colorado. Doctor Bowman and I had the fortune to meet and work together with a brilliant young student at different stages of her career. Kristi Anseth, a member of the National Academy of Sciences (NAS), the National Academy of Engineering (NAE) and the Institute of Medicine (IOM), has become a major contributor to the field of biomaterials and tissue engineering. Among other hydrogel-based formulations, we have also studied new polymers that can respond to changes of the physiological environment, especially changes of the pH, temperature, ionic strength and analyte concentration. The pioneer in this work was doctor Lisa Brannon-Peppas, with whom we developed not only some of the early pH-sensitive but also the associated theories for swelling behavior and diffusion through ionic networks. I thank her for being a wonderful and highly innovative scientist but also for having been a great partner in life.
As I close, I want to say that for me this Honoris Causa is not the end of a career. I was fortunate enough to have wonderful colleagues, great collaborators and brilliant, innovative graduate students and postdoctoral fellows who shared my vision to do research based on the principles of my field but also with an immediate application and a concern for patients. I am glad the medical and pharmaceutical industry used these ideas for important medical products. I share the feelings of my friend and colleague Bob Langer that “by the end of the next century disease as we know it today will no longer pose a major threat to human life and that highly effective methods to diagnose disease, prolong life, and relieve suffering will have been created.” I believe that the convergence in biomedical sciences, chemistry, biology and engineering will allow us to understand how diseases and genetic defects occur, develop new chemicals, biomaterials and drugs to treat these diseases, engineer delivery systems that will target drugs and genes to the correct tissues, cells or cell components, noninvasively diagnose diseases, and create new replacement tissues and organs.
I thank you for this great honor you have bestowed upon me today and I am grateful to all those who helped me pursue and achieve my dream to help our patients and use chemistry of crosslinked macromolecular structures and of polymer science to develop the next generation of medical systems that will improve the quality of life of our patients world wide. As André Gide, Nobel 1947, wote once ‘you cannot discover new lands without leaving the coast for a long time”. And as Constantine Kavafy, this wonderful Greek poet of the 1920s who wrote about the return of Odysseus (Ulysses) to Ithaca, said “As you set out for Ithaca hope your road is a long one, full of adventure, full of discovery.” We have set out for Ithaca but have not arrived yet, the trip continues and will continue for the benefit of science, of our patients and those who need our help and support.