A Pore Poem

Morris Karnovsky, M.B.B.Ch, D.Sc.

The amazing John Pappenheimer,
(Whose name defies any rhymer!)
And many others, postulated small and large pores to be
The basis of capillary permeability
I, perhaps foolishly, ascribed small pore function
To the endothelial junction
Which I opined is incompletely tight
But I was told this is not right!
Suppose there are also rare gaps, sufficiently large
Thru which big macromolecules can barge
Others fervidly disagree,
And localize to Palade’s caveolae
Not only large, but small pores as well!
What is correct? Will time tell?
Will this 35 year old dispute
Be one day rendered mute?

      �

At the VB99 meeting, NAVBO proudly recognized Morris J. Karnovsky as the 1999 Earl P. Benditt Awardee.  At the awards ceremony, Dr. Karnovsky was presented with an engraved crystal jade award and gave the premiere Earl P. Benditt Award Lecture.

 Dr. Morris J. Karnovsky was recognized for his numerous fundamental discoveries on cell structural and functional relationships that have had far-reaching impact in pathology as well as cell biology and physiology.  Dr. Karnovsky was born in South Africa and received his medical education at the University of Witwaterstrand and after internships in medicine and surgery, he went to London where he received a postgraduate degree in clinical pathology.  He then moved to Boston to work as a Research Fellow in Pathology at Harvard Medical School.  Dr. Karnovsky remained at Harvard, advancing through the ranks, and today is the Shattuck Professor of Pathological Anatomy at Harvard Medical School.  From 1975 to 1989 he was the Chair of the Program in Cell and Developmental Biology at Harvard Medical School.

Two common threads link Morris’ research through the years -- the study of the structural components of cells and their function, and the analysis of how disease states change structure and function.  His research papers pioneered the invention and development of different technologies and are often an elegant weave of innovative techniques, creative experimental techniques and sophisticated models.

One of Morris’ most widely recognized contributions was the extension of the horseradish peroxidase (HRP) tracer method of Werner Straus to both the light and electron microscopic level, by introducing diaminobenzidine (DAB) as an electron donor. HRP oxidizes DAB in the presence of H₂O₂ and converts it to an insoluble primer which causes the reduction of added osmium tetroxide.  The reduced osmium forms an insoluble electron opaque precipitate, localized to the site of the HRP.  When HRP is injected into the bloodstream, its pathways can be followed by fixation of the tissue at various times following injection and then carrying out the DAB reaction.  The first paper to introduce this technique authored by Morris Karnovsky and Richard Graham traced the endocytotic uptake of HRP from the glomerular filtrate into cells of the proximal tubules.  This study is a citation classic, and is one of the most highly quoted studies in the biomedical literature.

With Thomas Reese, Morris used the HRP method to establish that the endothelial cells in the brain vasculature form the cellular correlate of the so-called blood brain barrier.  This endothelial barrier prevents macromolecules in the blood from reaching neurons.  Likewise, with Elio Raviola, Morris established the blood-thymus barrier, and with Eveline Schneeberger, the blood-air barrier of the lungs.  The small pore system of Pappenheimer was identified in muscle capillaries at the level of permeable intercellular junction, an observation that is still controversial today (see poem above).

Another innovation developed by Morris was the introduction of colloidal lanthanum as an electron opaque tracer.  Using this tracer, Morris and Jean-Paul Revel succeeded in revealing the fine structure of gap junctions, the structural correlate of electrophysiologically defined electrical synapses that were known to occur in cells of excitable tissues.  Morris advanced a number of other cytochemistry techniques including methods to detect mitochondrial cytochrome c oxidase, cholinesterases, and oxygen derived products of the oxygen burst.  With Richard Rodewald, he described the slit diaphragm of the glomerulus, and with Graeme Ryan, he demonstrated that the glomerular basement membrane serves as the barrier to endogenous albumin.

More recently, Morris, together with Alexander Clowes, discovered that heparin, a well known anticoagulant, also inhibits the proliferation of smooth muscle cells. The antiproliferative activity of heparin and related molecules is presently a major research focus of Morris’s laboratory, and was the subject of his Benditt Award Lecture.

In addition to his research contributions, Morris is an inspiring teacher and a prominent figure in the community of experimental pathology and cell biology.  He has served as the President of the American Society of Cell Biology (1984), and Co-President of the American Association of Pathologists (1978).  He has served on the editorial boards of The Journal of Cell Biology, and The American Journal of Pathology, among others.  Morris has received numerous honors and awards, among them: the Rous-Whipple Award of the American Association of Pathologists (1981); the E.B. Wilson Award of the American Society for Cell Biology (1990), the Gold-Headed Cane Award (1994) from the American Society for Investigative Pathology (formerly the American Association of Pathologists), and was the Maude Abbott Lecturer (1994) of the US and Canadian Academy of Pathology.  He is a member of the Institute of Medicine of the National Academy of Sciences, a fellow in the American Academy of Arts and Sciences, and Honorary Fellow of the Royal Microscopical Society, London, and a Distinguished Scientist Awardee of the Electron Microscope Society of America.

 Apart from indulging in the writing of light verse, Morris is an avid fly fisherman.  (Perhaps that was Morris you saw floating around in his waiters and the tube catching the big trout on the weekends?)

 Our congratulations to Dr. Karnovsky!