Lyceum Society December 2022 Meeting

Social Time and Announcements: 11:30 am to 11:45 am

Initial Presentation: 11:45 am to 12:30 pm

Speaker: Clif Hotvedt

Topic: Nobel Prize in Physiology or Medicine 2022

The 2022 Nobel Prize in Physiology or Medicine was awarded to Svante Pääbo for his discoveries concerning the genomes of extinct hominins and human evolution. The relationship between Homo sapiens and extinct hominins has long been a topic of great interest. Modern DNA technology provides opportunities to investigate our ancient past with more precision. However, due to extreme technical challenges resulting from degradation of DNA over tens of thousands of years and contamination from both micro-organisms and contemporary humans, it was questionable whether the analysis of archaic DNA from extinct hominin forms would be possible. Through extensive technological developments, Pääbo set new rigorous standards in this challenging area and succeeded in obtaining the genome sequence of our closest extinct relative, the Neanderthal. This was followed by his sensational discovery of another extinct hominin, the Denisova, entirely from genome data retrieved from a small finger bone specimen. Pääbo’s work further established that Homo sapiens had mixed with Neanderthals and Denisovans during periods of co-existence, resulting in incorporation of archaic DNA in present-day humans. Through his groundbreaking discoveries, Pääbo opened a new window to our evolutionary past, revealing an unexpected complexity in the evolution and admixture of ancient hominins, as well as providing the basis for an improved understanding of genetic features that make us uniquely human. This brief talk will review Pääbo's discovery and its potential implications and applications.

Clif Hotvedt's diverse scientific background reflects his experience in the pharmaceutical industry, as a medical writer in the regulatory and clinical affairs departments of Ives Laboratories and at leading public relations firms including Robert Marston & Associates, Manning Selvage & Lee and Ketchum, where he served as vice president and global director of medical & scientific affairs. For 46 years, he has counseled companies on over 100 small molecule drugs, biologicals and devices for indications including cardiovascular disease, rheumatology, metabolic disease, dermatology, central nervous system disease, vaccines, infectious disease and cancer.

A New Mexico State University graduate in secondary education and journalism, Clif continues to use his teaching background to develop and present courses on the FDA approval process, pharmacokinetics, pharmacodynamics and biostatistics among other topics for coworkers and clients. Clif is a member of the Lyceum Society and has been a frequent presenter at our meetings. His previous topics have included: “The FDA Drug Approval Process”(November 2015); “How the new PCSK9 Cholesterol-Lowering Drugs work” (May 2016); “How to read a Drug Label” (April 2017); “Biosimilars: the New ‘Generics’?(June 2018); “The Human Microbiome” (May 2019); . "Drug Pricing" (June 2020); “Artificial Intelligence (AI) and Health Care” (October 2020)” and "Drug Pricing Revisited" (November 2020).

Main Presentation: 12:30 pm to 2:15pm

Speaker: Andrew M. Blakely, M.D.

Topic: Rationale for Intraperitoneal Delivery of Chemotherapy

Peritoneal metastasis is uniformly lethal, characterized by a relentlessly aggressive clinical course leading to significant morbidity. Peritoneal carcinomatosis is largely a result of regional spread of ovarian (50-60%) or gastrointestinal (GI) cancers (30-40%) or may develop from the peritoneum itself (mesothelioma). Management is primarily palliative, involving systemic chemotherapy and/or cytoreductive surgery (CRS) with the goal of locoregional disease control. However, survival outcomes with systemic chemotherapy or CRS alone have remained dismal (median survival: 24 months).

The rationale for administration of intraperitoneal chemotherapy is based on its regional treatment effect. The peritoneal surface has been characterized as similar to a dialysis membrane in its activity in drug transport between the peritoneal cavity and plasma, resembling a two compartment model. Peritoneal implants are thought to be less well-vascularized than metastatic deposits in the liver or lung, decreasing their relative susceptibility to systemic chemotherapy. Intraperitoneal administration of the same chemotherapeutic agent can achieve significantly higher peritoneal cavity drug concentrations than systemic administration. In this way, therapeutic doses of chemotherapy agents may be used, with less systemic uptake and resultant toxicity.

Dr. Blakely completed a Bachelor of Science in Biomedical Engineering followed by medical school at Drexel University. He went on to general surgery residency at Brown University. During residency, he spent two years of dedicated research time at the Center for Biomedical Engineering developing a device for tissue engineering applications. That work then led to a National Science Foundation grant and a patent. Dr. Blakely then completed his fellowship in Complex General Surgical Oncology at City of Hope National Medical Center. He is currently an Assistant Research Physician within the Surgical Oncology Program at the National Cancer Institute, National Institutes of Health.