It’s great to talk to Irv Weissman.
It has been a week to think about mentors and I posted somewhat autobiographically on how to find and be a good mentor a few days ago.
Also along these lines, I asked one of the great mentors of all time, Irv Weissman, about his early career and who were the mentors that made the difference to him.
Irv was kind enough to take time out of his schedule to answer me.
I found his response quite intriguing.
Thanks, Irv, for sharing this autobiographical piece!
Here is what I wrote to Irv:
Dear Irv,
I am writing a piece for my blog about mentoring and when I think about mentoring, you come to mind as someone who has mentored an astounding array of great scientists.
I wanted to make the point in part of my piece that great mentors were of course relatively new scientists at some point in their careers and they had mentors of their own that were important.
I wanted to ask you– who were the most important and influential mentors in your career?
How did they help you evolve as a scientist?
Any other thoughts or advice about mentoring?
Thanks!
Paul
And here is what he said in response:
What was amazingly lucky for me is that I had role models, but in fact no one overseeing my research after high school. I began research as a junior in high school with a pathologist who was tired of academia and moved to run a path lab practice at Montana Deaconess Hospital in Great Falls Montana. His name was Ernst Eichwald, and he had just discovered the HY antigen by showing in an inbred strain of mice [C57BL] that females always rejected male skin. By telling me that in an inbred strain of mice 25% of skin grafts were rejected, and that it was genetic, he allowed me to ‘rediscover’ the finding. I began with him to see if the HY was on all normal and cancer cells from males [it was], but on my own I wondered if transplantation tolerance could be induced to this antigen, much like Billingham, Brent and Medawar had just shown [1953,1956]; whether the HY was the same in all mouse strains; and why did some strains not reject male skin grafts? By the end of my senior year in high school I was mainly doing my own project. I continued in summers during my 3 years of college. By then I had published with EE that the unresponsive strains lacked immune reactivity genes [1957], that by grafting F1 males of reciprocal parentage crosses the HY was the same in all strains[1959], and [unpublished] that unresponsiveness was not caused by sharing a gestation with male fetuses [remembering ray owen and the freemartin cattle experiments]. When I entered Stanford Med School, I met Henry Kaplan who was a remarkable man; he was chief of all Radiology, had published on leading edge papers in immunology, leukemia, radiation targets, and even the primary establishment of high dose linear accelerators to deliver radiotherapy for cancers inside the body instead of in the skin. He had also just made Hodgkin’s Disease an 85% curable disease instead of 0%, and had even written a diagnostic radiology of the heart text. He gave me a lab, a part time technician, and allowed me to recruit other med students into the lab. We all had entered Stanford MD when it was 5 years required, spacing the first years of basic science over 3 years instead of 2, creating a half day every day for those 3 years plus summers to do research of our choosing. I chose to continue my exploration of immune tolerance to try to understand the development of the immune system, including the role of the thymus. I also set up a personal tutorial with Kaplan where I took his lab notebooks and reconstructed his mouse discoveries, meeting with him every other week or so to discuss the old experiments. I also read every paper he wrote. Those experiences taught me what it took to translate discoveries into potential therapies. Kaplan also sponsored me to spend the 4th’5th year 9 month interval with Gowans in Oxford, where I developed intrathymic and intra bone marrow radioactive nucleoside labeling of cells to determine their lineage potential and migration potential. Gowans left on sabbatical when I was 3 months into it, but I used the time to do research, and again, to read every paper he wrote. When I returned to finish Med School [1965 MD], I decided to keep doing research, and again Kaplan kept open a lab for me until I became an assistant professor in late 1968/early 1969. I will attach much of my remembrance of those days in a few articles I have written, but what should be obvious is that I had fantastic role models, but none of them oversaw much of my research. So I was free to learn the problems and possibilities of discovery on my own. The experiments on immune tolerance led to the lineage tracing technique I developed and from their to the bone marrow origins of all immune cells, and from there to stem cells.
To me several things stand out in what Irv wrote. First, Irv had at a very unusually early age an extraordinary passion for science, an extraordinary ability to process information on a very high level, and great vision for how to test ideas. These are things that no one, not even the best mentor in the world, can teach someone.
I would call it the “right stuff” for science and Irv sure has it. Note that Irv was born on October 21, 1939 so literally as a teenager (age 19) he already was publishing great science.
Also it nonetheless is clear that mentors and role models such as Eichwald and Kaplan made a big difference for Irv as a young scientist, and I find it so admirable that Irv continues that tradition of mentoring and being a role model to many great young scientists.
Perhaps I should not be surprised, but Irv was also kind enough to include a bibliography (below) as well!
2. Eichwald, E.J., C.R. Silmser, and I. Weissman, Sex-linked rejection of normal and neoplastic tissue. I. Distribution and specificity. J Natl Cancer Inst, 1958. 20(3): p. 563-75. PMID: 13539607.
3. Eichwald, E.J., E.C. Lustgraaf, I. Weissman, and M. Strainer, Attempts to demonstrate sex-linked histocompatibility genes. Transplant Bull, 1958. 5(4): p. 387-8. PMID: 13592896.
5. Weissman, I.L. and E.C. Lustgraaf, Antibody formation and repressor systems. Transplant Bull, 1961. 28: p. 134-5. PMID: 14005927.
8. Weissman, I.L., Specific “conditioning” of the host, in Tissue Transplantation, E.J. Eichwald, Editor. 1963, Academic Press, Inc: New York. p. 160-177.
11. Weissman, I.L., Studies on the mechanism of split tolerance in mice. Transplantation, 1966. 4(5): p. 565-71. PMID: 5339404.
13. Weissman, I.L., Thymus cell migration. J Exp Med, 1967. 126(2): p. 291-304. PMID: 6028489
15. Weissman, I.L., The role of the thymus and extrathymic factors in the development of immune competence, in Developmental Aspects of Antibody Formation and Structure, Vol. I. Symposium. 474p. Illus. Academic Press: New York, N.Y., U.S.a.; London, England. 1970. 55-67., J. Sterzl and R. I, Editors. 1970.
19. Gutman, G.A. and I.L. Weissman, The bone marrow origin of lymphoid primary follicle small lymphocytes, in Morphological and Functional Aspects of Immunity, Lindahl-Kiessling, Alm, and Hanna, Editors. 1971, Plenum Publishing Corporation: New York. p. 595-602.
22. Weissman, I.L., Tumor immunology. Calif Med, 1971. 114(3): p. 76-8. PMID: 5544693
25. Gutman, G.A. and I.L. Weissman, Lymphoid tissue architecture. Experimental analysis of the origin and distribution of T-cells and B-cells. Immunology, 1972. 23(4): p. 465-79. PMID: 4563475.
29. Weissman, I.L., Transfer of tolerance. Transplantation, 1973. 15(3): p. 265-9. PMID: 4123075.
30. Weissman, I.L., Thymus cell maturation. Studies on the origin of cortisone-resistant thymic lymphocytes. J Exp Med, 1973. 137(2): p. 504-10. PMID: 4539848.
32. Weissman, I.L., Tumor immunity in vivo: evidence that immune destruction of tumor leaves “bystander” cells intact. J Natl Cancer Inst, 1973. 51(2): p. 443-8. PMID: 4765368.
33. Weissman, I.L., Failure to demonstrate postnatal testicular dependent expression of the male-specific transplantation antigen in mice. Transplantation, 1973. 16(2): p. 122-5. PMID: 4125965.
34. Gutman, G.A. and I.L. Weissman, Homing properties of thymus-independent follicular lymphocytes. Transplantation, 1973. 16(6): p. 621-9. PMID: 4585386.
49. Weissman, I.L., Development and distribution of immunoglobulin-bearing cells in mice. Transplant Rev, 1975. 24: p. 159-76. PMID: 1096381
59. Weissman, I.L., S. Baird, R.L. Gardner, V.E. Papaioannou, and W. Raschke. Normal and neoplastic maturation of T-lineage lymphocytes. in Cold Spring Harb Symp Quant Biol. 1977: Cold Spring Harbor Laboratory Press.
64. Weissman, I.L., The demise of the five-year plan. Stanford Med, 1977. 16: p. 6-13. PMID:
66. Weissman, I.L., R. Warnke, E.C. Butcher, R. Rouse, and R. Levy, The lymphoid system. Its normal architecture and the potential for understanding the system through the study of lymphoproliferative diseases. Hum Pathol, 1978. 9(1): p. 25-45. PMID: 344190.
95. Butcher, E.C., R.G. Scollay, and I.L. Weissman, Organ specificity of lymphocyte migration: mediation by highly selective lymphocyte interaction with organ-specific determinants on high endothelial venules. Eur J Immunol, 1980. 10(7): p. 556-61. PMID: 6157544.
106. Lepault, F. and I.L. Weissman, An in vivo assay for thymus-homing bone marrow cells. Nature, 1981. 293(5828): p. 151-4. PMID: 6115320.
108. Coffman, R.L. and I.L. Weissman, A monoclonal antibody that recognizes B cells and B cell precursors in mice. J Exp Med, 1981. 153(2): p. 269-79. PMID: 6787164.
123. Butcher, E.C., R.A. Reichert, R.L. Coffman, C. Nottenburg, and I.L. Weissman, Surface phenotype and migratory capability of Peyer’s patch germinal center cells. Adv Exp Med Biol, 1982. 149: p. 765-72. PMID: 6983239
154. Ezine, S., I.L. Weissman, and R.V. Rouse, Bone marrow cells give rise to distinct cell clones within the thymus. Nature, 1984. 309(5969): p. 629-31. PMID: 6374470.
156. Weissman, I.L., L. Jerabek, and S. Greenspan, Tolerance and the H-Y antigen: Requirement for male T cells, but not B cells, to induce tolerance in neonatal female mice. Transplantation, 1984. 37(1): p. 3-6. PMID: 6364485.
180. Muller-Sieburg, C.E., C.A. Whitlock, and I.L. Weissman, Isolation of two early B lymphocyte progenitors from mouse marrow: a committed pre-pre-B cell and a clonogenic Thy-1-lo hematopoietic stem cell. Cell, 1986. 44(4): p. 653-62. PMID: 2868799.
184. Gallatin, M., T.P. St John, M. Siegelman, R. Reichert, E.C. Butcher, and I.L. Weissman, Lymphocyte homing receptors. Cell, 1986. 44(5): p. 673-80. PMID: 3004743.
186. Gershenfeld, H.K. and I.L. Weissman, Cloning of a cDNA for a T cell-specific serine protease from a cytotoxic T lymphocyte. Science, 1986. 232(4752): p. 854-8. PMID: 2422755.
199. Whitlock, C.A., G.F. Tidmarsh, C. Muller-Sieburg, and I.L. Weissman, Bone marrow stromal cell lines with lymphopoietic activity express high levels of a pre-B neoplasia-associated molecule. Cell, 1987. 48(6): p. 1009-21. PMID: 3493849.
204. Ezine, S., L. Jerabek, and I. Weissman, The phenotype of thymocytes derived from a single clonogenic precursor. J Immunol, 1987. 139(7): p. 2195-9. PMID: 2888822
216. Weissman, I.L., Approaches to an understanding of pathogenetic mechanisms in AIDS. Rev Infect Dis, 1988. 10(2): p. 385-98. PMID: 3287566.
222. Spangrude, G.J., S. Heimfeld, and I.L. Weissman, Purification and characterization of mouse hematopoietic stem cells. Science, 1988. 241(4861): p. 58-62. PMID: 2898810.
228. McCune, J.M., R. Namikawa, H. Kaneshima, L.D. Shultz, M. Lieberman, and I.L. Weissman, The SCID-hu mouse: murine model for the analysis of human hematolymphoid differentiation and function. Science, 1988. 241(4873): p. 1632-9. PMID: 2971269
233. Namikawa, R., H. Kaneshima, M. Lieberman, I.L. Weissman, and J.M. McCune, Infection of the SCID-hu mouse by HIV-1. Science, 1988. 242(4886): p. 1684-6. PMID: 3201256.
242. Siegelman, M.H., M. van de Rijn, and I.L. Weissman, Mouse lymph node homing receptor cDNA clone encodes a glycoprotein revealing tandem interaction domains. Science, 1989. 243(4895): p. 1165-72. PMID: 2646713.
249. Holzmann, B., B.W. McIntyre, and I.L. Weissman, Identification of a murine Peyer’s patch–specific lymphocyte homing receptor as an integrin molecule with an alpha chain homologous to human VLA-4 alpha. Cell, 1989. 56(1): p. 37-46. PMID: 2463092.
251. Weissman, I.L., Developing ethical human models for experimental medicine. Stanford Med, 1989(Winter): p. 17–32. PMID:
252. Siegelman, M.H. and I.L. Weissman, Human homologue of mouse lymph node homing receptor: evolutionary conservation at tandem cell interaction domains. Proc Natl Acad Sci U S A, 1989. 86(14): p. 5562-6. PMID: 2664786.
255. Jerabek, L., S. Greenspan, C. Okada, and I.L. Weissman, Tolerance, the thymus, and H-Y, in Realm of Tolerance. 1989, Springer-Verlag: New York. p. 50-59.
265. Weissman, I.L., Some observation on the life history of lymphocytes. Harvey Lect, 1989. 85: p. 43-69. PMID: 2519150.
288. Mueller, C., J. Shelby, I.L. Weissman, T. Perinat-Frey, and E.J. Eichwald, Expression of the protease gene HF as a marker in rejecting allogeneic murine heart transplants. Transplantation, 1991. 51(2): p. 514-7. PMID: 1994548.
314. Hu, M.C., M.H. Siegelman, B. Holzmann, D.T. Crowe, and I.L. Weissman, Lymphocyte homing receptors. Cold Spring Harb Symp Quant Biol, 1992. 57: p. 291-308. PMID: 1339666.
335. Vaux, D.L., I.L. Weissman, and S.K. Kim, Prevention of programmed cell death in Caenorhabditis elegans by human bcl-2. Science, 1992. 258(5090): p. 1955-7. PMID: 1470921.
319. Baum, C.M., I.L. Weissman, A.S. Tsukamoto, A.M. Buckle, and B. Peault, Isolation of a candidate human hematopoietic stem-cell population. Proc Natl Acad Sci U S A, 1992. 89(7): p. 2804-8. PMID: 1372992.
363. Weissman, I.L., Developmental switches in the immune system. Cell, 1994. 76(2): p. 207-18. PMID: 8293459.
375. Morrison, S.J. and I.L. Weissman, The long-term repopulating subset of hematopoietic stem cells is deterministic and isolatable by phenotype. Immunity, 1994. 1(8): p. 661-73. PMID: 7541305.
377. Weissman, I.L., Stem cells, clonal progenitors, and commitment to the three lymphocyte lineages: T, B, and NK cells. Immunity, 1994. 1(7): p. 529-31. PMID: 7600281
397. Shizuru, J.A., L. Jerabek, C.T. Edwards, and I.L. Weissman, Transplantation of purified hematopoietic stem cells: requirements for overcoming the barriers of allogeneic engraftment. Biol Blood Marrow Transplant, 1996. 2(1): p. 3-14. PMID: 9078349.
411. Weissman, I.L., From thymic lineages back to hematopoietic stem cells, sometimes using homing receptors. J Immunol, 1996. 156(6): p. 2019-25. PMID: 8690888.
426. Kondo, M., I.L. Weissman, and K. Akashi, Identification of clonogenic common lymphoid progenitors in mouse bone marrow. Cell, 1997. 91(5): p. 661-72. PMID: 9393859.
430. Gandy, K.L. and I.L. Weissman, Tolerance of allogeneic heart grafts in mice simultaneously reconstituted with purified allogeneic hematopoietic stem cells. Transplantation, 1998. 65(3): p. 295-304. PMID: 9484743.
441. Traver, D., K. Akashi, I.L. Weissman, and E. Lagasse, Mice defective in two apoptosis pathways in the myeloid lineage develop acute myeloblastic leukemia. Immunity, 1998. 9(1): p. 47-57. PMID: 9697835
449. Shizuru, J.A. and I.L. Weissman, Isolation and characterization of hematopoietic progenitor and stem cells, in Hematopoietic Cell Transplantation, E.D. Thomas, K.G. Blume, and S.J. Forman, Editors. 1999, Blackwell Sciences. p. 63–78.
462. Weissman, I.L., Stem cells: units of development, units of regeneration, and units in evolution. Cell, 2000. 100(1): p. 157-68. PMID: 10647940.
465. Weissman, I.L., Translating stem and progenitor cell biology to the clinic: barriers and opportunities. Science, 2000. 287(5457): p. 1442-6. PMID: 10688785.
467. Akashi, K., D. Traver, T. Miyamoto, and I.L. Weissman, A clonogenic common myeloid progenitor that gives rise to all myeloid lineages. Nature, 2000. 404(6774): p. 193-7. PMID: 10724173.
471. Negrin, R.S., K. Atkinson, T. Leemhuis, E. Hanania, C. Juttner, K. Tierney, W.W. Hu, L.J. Johnston, J.A. Shizurn, K.E. Stockerl-Goldstein, K.G. Blume, I.L. Weissman, S. Bower, R. Baynes, R. Dansey, C. Karanes, W. Peters, and J. Klein, Transplantation of highly purified CD34+Thy-1+ hematopoietic stem cells in patients with metastatic breast cancer. Biol Blood Marrow Transplant, 2000. 6(3): p. 262-71. PMID: 10871151.
476. Kondo, M., D.C. Scherer, T. Miyamoto, A.G. King, K. Akashi, K. Sugamura, and I.L. Weissman, Cell-fate conversion of lymphoid-committed progenitors by instructive actions of cytokines. Nature, 2000. 407(6802): p. 383-6. PMID: 11014194.
481. Uchida, N., D.W. Buck, D. He, M.J. Reitsma, M. Masek, T.V. Phan, A.S. Tsukamoto, F.H. Gage, and I.L. Weissman, Direct isolation of human central nervous system stem cells. Proc Natl Acad Sci U S A, 2000. 97(26): p. 14720-5. PMID: 11121071.
505. Reya, T., S.J. Morrison, M.F. Clarke, and I.L. Weissman, Stem cells, cancer, and cancer stem cells. Nature, 2001. 414(6859): p. 105-11. PMID: 11689955.
513. Weissman, I.L., A.L. Beaudet, P.K. Donohoe, D.J. Gallas, B.L.M. Mogan, R.B. Jaffe, E.R.B. McCabe, A. McClaren, G.M. Rubin, M. Siegler, and J.G. Hall, Scientific and medical aspects of human reproductive cloning. 2002: National Academies Press. 296.
514. Weissman, I.L., Stem cells–scientific, medical, and political issues. N Engl J Med, 2002. 346(20): p. 1576-9. PMID: 11994551.
520. Weissman, I.L., The road ended up at stem cells. Immunol Rev, 2002. 185: p. 159-74. PMID: 12190929.
522. Wagers, A.J., R.I. Sherwood, J.L. Christensen, and I.L. Weissman, Little evidence for developmental plasticity of adult hematopoietic stem cells. Science, 2002. 297(5590): p. 2256-9. PMID: 12215650.
473. Miyamoto, T., I.L. Weissman, and K. Akashi, AML1/ETO-expressing nonleukemic stem cells in acute myelogenous leukemia with 8;21 chromosomal translocation. Proc Natl Acad Sci U S A, 2000. 97(13): p. 7521-6. PMID: 10861016.
534. Beilhack, G.F., Y.C. Scheffold, I.L. Weissman, C. Taylor, L. Jerabek, M.J. Burge, M.A. Masek, and J.A. Shizuru, Purified allogeneic hematopoietic stem cell transplantation blocks diabetes pathogenesis in NOD mice. Diabetes, 2003. 52(1): p. 59-68. PMID: 12502494.
571. Jamieson, C.H., L.E. Ailles, S.J. Dylla, M. Muijtjens, C. Jones, J.L. Zehnder, J. Gotlib, K. Li, M.G. Manz, A. Keating, C.L. Sawyers, and I.L. Weissman, Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML. N Engl J Med, 2004. 351(7): p. 657-67. PMID: 15306667.
579. Sherwood, R.I., J.L. Christensen, I.M. Conboy, M.J. Conboy, T.A. Rando, I.L. Weissman, and A.J. Wagers, Isolation of adult mouse myogenic progenitors: functional heterogeneity of cells within and engrafting skeletal muscle. Cell, 2004. 119(4): p. 543-54. PMID: 15537543.
596. Weissman, I., Stem cell research: paths to cancer therapies and regenerative medicine. Jama, 2005. 294(11): p. 1359-66. PMID: 16174694.
603. Laird, D.J., A.W. De Tomaso, and I.L. Weissman, Stem cells are units of natural selection in a colonial ascidian. Cell, 2005. 123(7): p. 1351-60. PMID: 16377573.
608. Bhattacharya, D., D.J. Rossi, D. Bryder, and I.L. Weissman, Purified hematopoietic stem cell engraftment of rare niches corrects severe lymphoid deficiencies without host conditioning. J Exp Med, 2006. 203(1): p. 73-85. PMID: 16380511.
648. Czechowicz, A., D. Kraft, I.L. Weissman, and D. Bhattacharya, Efficient transplantation via antibody-based clearance of hematopoietic stem cell niches. Science, 2007. 318(5854): p. 1296-9. PMID: 18033883
653. Rossi, D.J., C.H. Jamieson, and I.L. Weissman, Stems cells and the pathways to aging and cancer. Cell, 2008. 132(4): p. 681-96. PMID: 18295583
666. Weissman, I.L. and J.A. Shizuru, The origins of the identification and isolation of hematopoietic stem cells, and their capability to induce donor-specific transplantation tolerance and treat autoimmune diseases. Blood, 2008. 112(9): p. 3543-53. PMID: 18948588.
675. Chan, C.K., C.C. Chen, C.A. Luppen, J.B. Kim, A.T. Deboer, K. Wei, J.A. Helms, C.J. Kuo, D.L. Kraft, and I.L. Weissman, Endochondral ossification is required for haematopoietic stem-cell niche formation. Nature, 2008. PMID: 19078959.
676. Ueno, H., B.B. Turnbull, and I.L. Weissman, Two-step oligoclonal development of male germ cells. Proc Natl Acad Sci U S A, 2009. 106(1): p. 175-80. PMID: 19098099.
688. Jaiswal, S., C.H. Jamieson, W.W. Pang, C.Y. Park, M.P. Chao, R. Majeti, D. Traver, N. van Rooijen, and I.L. Weissman, CD47 is upregulated on circulating hematopoietic stem cells and leukemia cells to avoid phagocytosis. Cell, 2009. 138(2): p. 271-85. PMID: 19632178.
689. Majeti, R., M.P. Chao, A.A. Alizadeh, W.W. Pang, S. Jaiswal, K.D. Gibbs, Jr., N. van Rooijen, and I.L. Weissman, CD47 is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells. Cell, 2009. 138(2): p. 286-99. PMID: 19632179.
691. Weissman, I., The ISSCR: who are we and where are we going? Cell Stem Cell, 2009. 5(2): p. 151-3. PMID: 19664988.
692. Chan, K.S., I. Espinosa, M. Chao, D. Wong, L. Ailles, M. Diehn, H. Gill, J. Presti, Jr., H.Y. Chang, M. van de Rijn, L. Shortliffe, and I.L. Weissman, Identification, molecular characterization, clinical prognosis, and therapeutic targeting of human bladder tumor-initiating cells. Proc Natl Acad Sci U S A, 2009. 106(33): p. 14016-21. PMID: 19666525.
724. Chao, M.P., S. Jaiswal, R. Weissman-Tsukamoto, A.A. Alizadeh, A.J. Gentles, J. Volkmer, K. Weiskopf, S.B. Willingham, T. Raveh, C.Y. Park, R. Majeti, and I.L. Weissman, Calreticulin Is the Dominant Pro-Phagocytic Signal on Multiple Human Cancers and Is Counterbalanced by CD47. Sci Transl Med 2010, 2(63):63ra94. PMID: 21178137.
728. Weissman, I.L., 50 Years Later: Remembering the Paper. Radiat Res. 2011, 175(2):143-144. PMID: 21268706.
Hello Paul,
Do you know any REAL specific cell surface marker for mesenchymal stem cells? There are a lot of known marker for these cells published (CD29, CD90, CD105….) but none is really specific, such as myosin heavy chain is specific for cardiomyocytes (dispite being intracellular, in this case).
Any sugestion?
best regards
Creise