Snowden-Warfield
  Family Stories · 20th & 21st Century Physician, Scientist, Inventor, Author and Entrepreneur
   
 

20th & 21st Century Physician, Scientist, Inventor, Author And Entrepreneur

   
 

Dr. Scheele is the fourth great-grandson of Dr. Charles Alexander Warfield, the 18th century patriot who is the Hero of "The Burning of the Peggy Stewart", which occurred on October 19, 1774 in the Annapolis Harbor. Dr. Scheele is the founder and author of the Snowden-Warfield family history website.

Dr. Scheele received an A.B. degree in Biology from Princeton University and an M.D. degree from Johns Hopkins Medical School. Following internship and residency in Medicine at Johns Hopkins Hospital and postdoctoral training at the Rockefeller University, he achieved professorships at Yale University School of Medicine (1974), the Rockefeller University (1974-88) and Harvard Medical School (1988-1995).

Dr. Scheele, a two-time Nobel Associate, is an internationally recognized authority on the cellular and molecular aspects of (i) protein sorting and trafficking, (ii) translocation of proteins across the RER membrane, (iii) processing of proteins in the regulated secretory pathway, (iii) regulation of gene expression in pancreatic adaptation, (iv) synthesis of full-length genes (cDNAs) and (v) potential treatments for Cystic Fibrosis and other pulmonary diseases.

NOBEL ASSOCIATE:

During his time at the Rockefeller University Dr. Scheele worked with two scientific teams, whose work was later honored in the Nobel Prizes in Medicine in 1974 and 1999.

  • The first team conducted seminal works that defined the intracellular secretory pathway, honored in the 1974 Nobel Prize in Medicine awarded to George E. Palade.
  • The second team conducted seminal works that helped establish the "signal peptide hypothesis" in the translocation of secretory proteins across the RER membrane, honored in the 1999 Nobel Prize in Medicine awarded to Gunter Blobel. This work established canine pancreatic microsomal membranes as the standard in vitro model for protein targeting and translocation and determined the structure of the first signal peptide believed to direct the translocation of secretory proteins across the RER membrane in the pancreas. Dr. Scheele played major roles in both discoveries.

On the day following announcement of the 1999 Nobel Prize in Medicine, Dr. Scheele wrote the following summary of the work to his family, friends and scientific associates:

"The Scientific work that I performed at the Rockefeller University between 1970 and 1983, together with that of others, won the Nobel Prize in Medicine yesterday. The recipient of the prize is Dr. Gunter Blobel, senior member of the research team. The prize awarded by the Nobel Committee of the Royal Swedish Academy of Science in Stockholm, was announced in the October 12 issue of the New York Times.

The work established the existence of peptide signals that direct the transport of subgroups of proteins into specific cellular compartments, e.g. those that are destined to be secreted from the cell. Secretory proteins perform valuable functions as digestive enzymes in the gastrointestinal tract, as hormones in intercellular communication and as binding proteins in the transport of solutes through the blood circulation.

The prize honors, in part, the studies that initially defined the N-terminal signal peptide responsible for targeting proteins to the secretory pathway of the cell. The first signal peptide to be discovered was that for pancreatic trypsin, a digestive enzyme responsible for the breakdown of protein in the diet.

The average human cell contains one billion proteins involved in a myriad of diverse processes including cell division, energy metabolism and protein secretion. The role of signal peptides in directing the traffic of proteins to their correct locations (addresses) within cells became the central tenet of the "signal hypothesis".

In the period from 1975 through 1983 my laboratory published a series of papers reporting on the underlying biochemical processes that helped to establish the signal hypothesis.

The seminal nature of the work performed at the Rockefeller University in the 70s and early 80s helped to launch the fields of protein trafficking and Molecular cellular biology, which have emerged on an international scale."

George A. Scheele, M.D.
October 12, 1999

PHYSICIAN:

Following undergraduate education in the Ivy League, Dr. Scheele attended Medical School at Johns Hopkins in Baltimore and received an MD degree in 1965. He served an internship in Internal Medicine on the prestigious Osler Medical Service from 7/65 through 6/66.

During 1967-69 Dr. Scheele served in the Public Health Service as a Fellow at the National Institutes of Health in Bethesda, MD. During that period he served as Director of Extramural Programs in Gastroenterology and supervised the administration of NIH research grants totaling $17 million per year.

Dr. Scheele then served a Residency in Internal Medicine on the Osler Medical Service from 7/68 through 6/69 and served a senior residency in Internal Medicine at the University of California, San Francisco Medical Center, from 7/69 to 6/70.

With excellent training under A. McGehee Harvey, Chairman of Medicine, at Johns Hopkins and Holly Smith, Chairman of Medicine, at the UCSF Medical Center, Dr. Scheele continued to practice medicine through the following careers:

  • Academic Medicine and basic research in the areas of cellular and molecular biology applied to the exocrine pancreas and the impact of this research on Human nutrition and pancreatic disease. These efforts led to professorships at the Rockefeller University, Yale School of Medicine and Harvard Medical School.
  • Biotechnology and Health Care through the founding and managing of several companies in the areas of genomics (AlphaGene, Inc.), health care through OTC products (NovaLife, Inc.), anti-viral drug development (Viral Shield Pharmaceuticals, Inc.) and development of inhalation therapies for Cystic Fibrosis (PH Pharmaceuticals, Inc.)

For futher details see Dr. Scheele's career website.

SCIENTIST

Following training in Internal Medicine Dr. Scheele entered Academic Medicine to pursue basic research on secretory organs, particularly that of the exocrine pancreas. Initially joining the laboratory of George E. Palade at the Rockefeller University in NYC, he became fascinated by the interplay between methods development and scientific discoveries. Dr. Scheele states, "My abilities to develop or invent new methods with quantum potential allowed my laboratory to forge a number of breakthrough discoveries in biology and medicine."

Serving as Laboratory Director at the Rockefeller University for 18 years (1970-1988), Yale University School of Medicine for one year (1974) and Harvard Medical School for 7 years (1988-1995) and utilizing the disciplines of physiology, cell biology, electron microscopy, molecular biology and protein chemistry, Dr. Scheele and his coworkers were able to make the following seminal discoveries:

In addition to the work which was honored in two Nobel Prizes (see above), Dr. Scheele's scientific achievements include:

  • Characterization of the complete repertoire of pancreatic enzymes and isoenzymes in five mammalian species, including man.
  • Definition and characterization of a novel class of secretory stress proteins in the pancreas
  • Discovery of pathological mechanisms by which pancreatic enzymes are released into the blood circulation
  • Definition of the role of the redox potential and chaperones in the correct folding of proteins sequestered into the rough endoplasmic reticulum (RER).
  • Discovery of the novel GP2/THP gene family, involved in regulating endocytosis and recycling of secretory membranes at the apical plasma membrane (APM) of regulated secretory cells throughout the body.
  • Discovery of the role of pH and enzyme mechanisms in coupling endocytosis and exocytosis at the APM of pancreatic acinar cells.
  • Characterization of downstream molecular defects resulting from genetically defective CFTR isoforms leading to the discovery of the ultimate biochemical deficiency in Cystic Fibrosis.
  • Elucidation of mechanisms by which hormones and nutritional substrates regulate gene expression and therefore pancreatic adaptation to change in food composition in the diet. These studies elucidated the mechanisms and extended the observations of I. P. Pavlov on adaptation of pancreatic enzymes to changes in the diet.

For futher details see Dr. Scheele's career website.

INVENTOR:

During Dr. Scheele's early training in the laboratory of George E. Palade, he became convinced that the development or invention of new technologies provided the opportunity to make quantum leaps in scientific discovery. As a result of this belief Dr. Scheele devoted substantial time to the invention of new techniques and strategies, which allowed his laboratory to make a number of seminal discoveries in the fields of protein sorting and trafficking, regulated secretion, regulation of gene expression, synthesis of full-length genes, prevention and early treatment of envelop viral infections and treatment of pulmonary diseases including Cystic Fibrosis.

Dr. Scheele's Inventions included (i) development of Pancreatic Lobules for the in vitro study of pancreatic function, (ii) development of 2D gel electrophoresis, which separates proteins by both charge and size, (iii) the first membrane models for studying the translocation of secretory enzymes across the RER membrane, (iv) improvement of in-vitro translation systems through the addition of purified RNase inhibitor, (v) development of the first procedure to significantly increase the full-length character of cDNA libraries (FLEXT technology), (vi) bicarbonate treatment for Cystic Fibrosis and (vii) topical beta-cyclodextrin treatments for prevention and early treatment of viral infections.

For futher details see Dr. Scheele's career website.

AUTHOR:

As Dr. Scheele's several careers unfolded he became fascinated by the power of the written word, phrase or text in communicating current information and new ideas in strong, powerful ways. These interests have resulted in a professional lifetime dedicated to publishing books (3), book chapters (26), original scientific papers (84) and patent applications (7).

Dr. Scheele organized and co-edited the first two editions of the leading textbook in the field, entitled "The Pancreas, Biology, Pathobiology and Diseases" (V.L. Go, J.D. Gardner, F.P. Brooks, E. Lebenthal, E.P. DiMagno, G.A. Scheele, eds.) Raven Press, New York, NY., 1986; first edition, 1986. Five chapters in this book were written by Dr. Scheele:

For futher details see Dr. Scheele's career website.

ENTREPRENEUR:

In order to bridge the gap between medical discoveries in basic research and drug development that impacts on individuals suffering from disease, Dr. Scheele founded five commercial companies and one nonprofit Institute in the health-care field. Explains Dr. Scheele, "Each of these companies is strategically positioned to attack major unmet needs in the health-care industry."

Dr. Scheele is the Founder of PH Pharmaceuticals, Inc., which is currently developing inhalation therapies for Cystic Fibrosis, and Founder, Chairman and CEO of Viral Shield Pharmaceuticals, Inc., which has developed topical products, which provide prevention and early treatment against a broad spectrum of envelope viruses, including HIV, HTLV, Herpes, Hepatitis B & C, Influenza and Pox viruses. He is the Founder and Chairman of Nova-Life, Inc., an E-commerce business, which markets anti-aging skin-care products and weight control products. He is President of La Jolla Biosciences, LLC, an in-licensing and out-licensing intellectual property firm specializing in global solutions in health care. He also serves as President of the Institute of Genomic Medicine, Inc., a non-commercial corporation whose mission is to elucidate the genetic causes of chronic degenerative disease in humans. He is the founder and former Chairman, President and CEO of AlphaGene, Inc., a genomics company that has introduced "AlphaGenomics", the first disease-based, full-length genomics technology platform, to the bio/pharmaceutical industry.

For futher details see Dr. Scheele's career website.

   
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©2005 George A. Scheele MD