What did I actually work with at The Wistar Institute?

Thought I'd describe what I did in science in a way that a layperson could appreciate.

I began scientific work along side with my medical studies already in the third semester at the Department of Medical Biochemistry of The University of Göteborg. Professor Karl-Anders Karlsson had a very interesting program where his group studied a type of compound, a glycolipid, carbohydrate and fat, that was present in the cell membranes of cells at specific locations, such as the inner functional lining of the large and small bowel. Human blood group antigens A, B and O are examples of such compounds. There is also a lot of them in the brain where they are called gangliosides. The function is still unknown for glycolipids. The objective was to elucidate their function by structurally characterizing them.

My project, which I did under the supervision of Prof. Gunnar C. Hansson, was to compare the expression of glycolipids in normal rat large intestine with that of experimentally induced large intestinal tumors, a collaboration with Prof Hans-Olof Sjögren at the University of Lund who worked as an immunologist on a rat large intestinal tumor model.

Somewhat earlier Milstein and Köhler in Great Britain developed a metod to produce so called monoclonal antibodies that was adapted to the production of monclonal antibodies directed to cell surface molecules of human tumor cells by Hilary Koprowski and Carlo Croce at The Wistar Institute who actually patented this adaptation. Milstein and Köhler got the Nobel Prize 1984 for this methodology.

Antibodies are proteins that are produced by white blood cells of the B type that are directed to pathogens and help our body to cure disease from bacteria and viruses. A monoclonal antibody is produced by immunizing a mouse with an antigen, e.g., a viral protein. B lymphocytes are then taken from the spleen of the mouse and fused with a mouse tumor cell that immortalizes the hybrid which then can be used to produce large quantities of the monoclonal antibody. A rather pure protein that after purification could be used as a drug.

Such monoclonal antibodies directed to cell surface molecules of tumor cells were thought to be possible to use in the treatment of human tumors. One such monoclonal antibody called NS19-9 was discovered to be directed to bind to a ganglioside. I actually participated in a collaboration between Karl-Anders Karlsson and Hilary Koprowski, the Director of The Wistar Institute, defining the binding of NS19-9 with the ganglioside and the structural characterization of the ganglioside.

I got the job at Wistar in January 1984 because of an application for a so called National Institutes of Health Program Project Grant concerning Human Melanoma, a skin tumor originating in so called melanocytes, the cells giving us a sun tan. They had monoclonal antibodies directed to many cell surface molecules that needed to be identified and characterized that they got from immunizing mice with human melanoma cells. The Program Project was a collaboration between Koprowski and the group of Prof. Wallace Clark, a renown Dermatology/Pathologist at the University of Pennsylvania across the street. In addition to the therapeutic issue the grant also importantly dealt with the study of melanoma tumor progression, i.e., how the normal melanocytes became tumorous. I actually discovered that a special type of ganglioside was induced at the stage when cells develop from the so called radial cell growth phase to the vertical growth phase, i.e., when they turn malignant. My wife could later use this result to develop her NIH grant application. Dr. Meenhard Herlyn produced the cells used in the study.

A group meeting once a week for a seminar of results or other information was held by The Human Tumor Antigen Group led by Dr. Koprowski. This group was about 30 people at my arrival. The work went well and the Program Project was received once more with Dr. Meenhard Herlyn as the PI after five years, when I was only a consultant and did mostly other things. The objective of being able to treat human melanoma was met partly. About ten percent of patients responded with one of the monoclonal antibodies that I characterized the ganglioside antigen for, i.e., the ME361. I'm on the patent of this antibody. It is very interesting scientifically that this happened, and as far as I know it how this happened is still unknown, but it was unfortunately not enough for enticing physcians for clinical use of the monoclonal.

The Wistar Institute relied to 75% on money from NIH grants and from 25% of money from patents and licensings. The Institute was second after Stanford in the US on bringing in money on patents per capita. There was not teaching but full time research. The easiest way to describe my work at the Institute is therefore to follow the money. I should also mention that my wife Magalena Blaszczyk-Thurin came to the Institute right after did and we came to collaborate in many ways. She had been at the Institute earlier. We married at the time I became Assistant Professor in the summer of 1985. She was a staff scientist at the time. We specialized a little in the direction of carbohydrate antigen work for me and the biosynthesis of carbohydrate antigens via so called glycosyltransferases for her. Blaszczyk-Thurin eventually generated a NIH grant for the study of large intestinal tumor carbohydrate antigen biosynthesis and its possible involvment in the development of the tumor and also became Assistant Professor.

First I should mention a very interesting and pleasant project involving the structural characterization of the NS19-9 ganglioside saccharide which had been synthetized by a Canadian company Chembiomed Inc. As a graduate group member at the Department of Biochemistry and Biophysics, I had a Ph.D. student in Biophysics, Bethany Bechtel, in collaboration with a Biophysicist Dr. Joshua Wand.

I came to generate two NIH grants in the direction of AIDS research. One was the testing of a hypothesis I believe I was the first one to have suggested namely that the very heavy glycosylation seen on the main viral HIV protein was increasing the virulens of the virus, i.e., making it more harmful. Viral proteins are recognized by the immune system via the recognition of a series of amino acids called epitope. A protein is in fact a series of amino acids linked in a chain. The many carbohydrate chains attached so such epitopes could potentially inhibit the immune response to the virus and thus cause the disease. This project gave rise to a local research grant that I was the PI on and that Dr. Laszlo Ötvös, also at Wistar, and I successfully worked into a more structurally oriented NIH grant where Dr. Ötvös was Principal Investigator and I was Co-Principal Investigator. Dr. Ötvös became Assistant Professor with this grant.

At the time a large effort was taking place at the NIH where people tried to use so called immunological adjuvant to create a vaccine againt the AIDS virus. It should be remembered that there is still no vaccine for this disease. Prof. Bror Morein at the BMC in Uppsala worked on a very promising adjuvant system, the so called ISCOM system. Dr. Koprowski knew him from his Rabies vaccine work and introduced me to him at the Wistar. I was able to help Dr. Morein with the purification and characterization of this adjuvant preparation, actually derived from the bark of a South American tree. The compounds, so called saponins were of course glycolipids. I got an NIH grant, as one of many of the NIH adjuvant group, with Dr. Morein as a consultant for the purification and charactrization of these compounds. I am on Dr. Moreins patent of the ISCOM system.

The problem here was that there was seemingly fierce competition between American and European companies on projects involving these adjuvants and I had to quit this grant before finishing for diffculties of collaborative nature. There was also a "coup" at The Wistar where Dr. Koprowski, the person that built the Institute up from scratch since 1955, lost out and was demoted as director. This led to large changes in the Institute and the new director Dr. Giovanni Rovera made it into a Molecular Biology oriented Institute rather than the Virology and Cancer place it had been under Dr. Koprowski.

For reason still unkown to me a rather severe harassment against me was initiated around 1991. They used TTDE against me although I was of course without a chance not knowing about it. I really had a tough time. Among other things I was vomited once driving my car with my son in the back seat. I woulld like to say that it is not really possible to make progressive science without knowing about TTDE. It is such an insight that I don't understand why I was not informed by representatives at the Institute. After considering many career moves, I finally settled for the MD path to oncology in Sweden in August 1993. I could not do this in the US because of lacking the internship in Sweden.