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.

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