Leonard Zwelling

         First name only needed. Everyone knew who you were talking about. He was like Madonna or Cher. No last name required and no name tag. Just Josh. Out of respect he became Dr. Fidler. Sometimes his name was half of a duo. Josh and Margaret. It was clear who you meant. He was, they were, that important. When the term “giant” is thrown around in biomedical science, few really measure up. Josh did. His passing last week leaves a vacuum that cannot be filled.

         I first heard Josh speak in 1981 at the AACR meeting in Washington, DC when he described his melanoma mouse model. The mice would be injected in the limb with the malignant cells. The cancer would quite predictably metastasize to the lungs and kill the animal. Using an immune-stimulant with a short intravascular half-life thus requiring its encapsulation in a protective lipid vesicle, Josh was able to prime the pulmonary macrophages to kill the micro-metastases and save the animals. These were animals that had demonstrable metastatic disease. It was successful immune-therapy before there was immune-therapy.

         I was sitting next to the BW (Beautiful Wife), aka, Dr. Kleinerman, at that meeting. She said, “that’s osteosarcoma and I’m going to use that therapy to cure kids with bone cancer.” To make a long story short—she did. I’ve met the teenagers she’s saved when conventional medicine had given up on them. Had she not gone to NCI-Frederick and collaborated with Josh to reproduce his mouse work in humans, she would have never migrated with him to Houston and, developed MTP-PE for the treatment of bone cancer. She would have never circled the globe teaching doctors from Kazakhstan to Israel how to use the drug and saving many lives along the way. Without Josh, no mouse model, no MTP-PE, no cures.  There are grown-up teenagers with children of their own now thanks to Josh and Genie. One survivor is a cancer surgeon himself.

         Eulogizing Josh at this point in time is most difficult. There have been many tributes while he was alive. He won many awards and many honors. He published hundreds of papers and made some of the most important observations in the history of cancer biology. Most critical was one with Margaret Kripke, his wife. That was the absolute proof of tumor heterogeneity and the fact that primary tumors contained cells with different propensities to metastasize. He also described the metastatic process in detail and the critical importance of the microenvironment to the establishment of metastatic cancer foci. His work proved the “seed soil hypothesis” of Paget and is the basis of our understanding of human cancer today.

         Josh was absolutely essential to my understanding of cancer in patients, its clinical behavior, its resistance to therapy, and the principles that guide clinical oncology and the treatment of human malignancy.

         On a personal note he was critical to my development as a physician, scientist and administrator. Josh always made you think. He made you want to be your best. He exemplified courage. He was outspoken and a champion of the people he recruited, hired and trained. And there were hundreds of these people from all over the world. He also had a huge heart and cared about what was right. He was as much of a father figure and mentor as I was likely to have in science and he was also my youngest son’s godfather.

         He was the most special person in the world and unique in every way. MD Anderson was less when he retired and we are all less now that he is gone. I shall miss him a great deal.

Leonard Zwelling