Experimental Hematology 2013;41:323–324

In memoriam: Christa Muller-Sieburg (1952–2013)

Hans Sieburg and Christa Muller-Sieburg

Christa Muller-Sieburg, a long-standing active member ofthe ISEH and a pioneer in stem cell research, died January2013 in San Diego, California.

Christa started her scientific life as an immunologist.She studied biology in Cologne, Germany, and between1978 and 1983 completed both her diploma thesis andher Ph.D. thesis in the laboratory of Klaus Rajewski atthe Institute of Genetics, one of the best molecular biologyinstitutes in Germany. Klaus Rajewski remembers, ‘‘Shestarted her work in the high times of Jerne’s idiotypicnetwork theory and addressed a key element of this theory,namely the control of antibody responses by anti-idiotypicantibodies (M€uller, C.E. and Rajewsky, K. 1983, 1984). Shewas an ambitious, highly motivated student, a friendly,supportive colleague and a dedicated scientist.’’

During this time, I was a first-year Ph.D. student atCologne University, where Christa and I were part ofa group of close friends. She taught me to generate mono-clonal antibodies and supervised my efforts with greatpatience and endless good advice. To this day, I rememberher telling me that one must never cut corners with exper-iments. Her seriousness was always mixed with humour.She made me laugh as she conjured up a hilarious pictureof my frustrated self, juggling hundreds of empty wells intissue culture plates for many weeks because of makinga mistake early in the experiment. Throughout her career,she never lost the talent for looking after younger scientistsand teaching them how to do good science.

After her Ph.D. studies, Christa obtained a fellowshipfrom the Deutsche Forschungsgemeinschaft and joined thelaboratory of Irv Weissman at Stanford University, where

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she purified the most elusive of blood cellsdthe hematopoi-etic stem cell (HSC). These cells had so far been functionallydefined only by their ability to reconstitute the hematopoi-etic system of lethally irradiated mice. Her paper was pub-lished in Cell (Muller-Sieburg et al., 1986) and for the firsttime showed that such cells could be purified prospectivelyusing defined molecular markers, a result with a huge impacton basic and medical science. Irv Weissman remembers, ‘‘Itmust have been 1984 when Christa was in the lab, designingassays for the earliest B cell progenitor. We were usinga cloned stromal line made by Cheryl Whitlock in the labfrom Whitlock-Witte cultures. Christa had isolated bonemarrow B220+ and B220– bone marrow cells, and addedthem at limit dilution to the stroma. When late-appearingcolonies with cobblestone appearance showed up in theB220–, but not the B220+ cultures, we realized we were nolonger studying B cell maturation, but were on the searchfor hematopoietic stem cells.’’

After leaving the Weissman laboratory, she continuedher work on refining HSC purification, first as a postdoctoralfellow in Jacques Chiller’s laboratory at the Lilly ResearchInstitute in La Jolla, CA, and from 1989 onward as anindependent group leader and Scholar of the AmericanLeukemia Society at the Medical Biology Institute, alsoin La Jolla.

Early on, Christa saw the need to propagate HSCs invitro while maintaining their multilineage and self-renewalpotential. A string of publications in the nineties establishedher as a pioneer of stromal-stem cell cocultures. During thistime, she also published a landmark study (Muller-Sieburget al., 1996) demonstrating for the first time that thefrequency of HSCs was under genetic control.

Her husband Hans Sieburg, a mathematician, had accom-panied her to the United States after her Ph.D. work, and thecouple increasingly worked together. During this time, theidea of mathematical modeling and computer simulation ofcellular behavior was only just beginning to emerge. Basedon her in vitro studies, and after moving to the SidneyKimmel Cancer Center in La Jolla, they started to study theautonomous regulation and programmed behaviors of adultlong-term repopulating HSCs in vivo. Christa’s lab demon-strated for the first time the biased differentiation behaviorof individual stem cell clones, a result that was difficult topublish but finally came out inBlood in 2002. They thenwenton to demonstrate that aging enhanced this bias, using theirtrademark interdisciplinary approach combining experi-ments and mathematics. Irv Weissman remembers, ‘‘When

gy and Stem Cells. Published by Elsevier Inc.

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Christa andHans toldme that HSCswere heterogeneous, andsome were myeloid-biased, I felt skeptical. Later, when werediscovered her findings, that in fact not only were HSCsborn different, some balanced, some biased one way, someanother, and the myeloid-biased HSC clones were rare inyoung but dominant in aged mice, it changed my thinking.I remember how gracious she was when I wrote her thatshe was right after all.’’

Christa and Hans continued towork together on modelingstem cell behavior. Their publications in 2012 summarizethis work. Interestingly, in a recent review, Christa went backto her roots as an immunologist by writing about the‘‘puzzling origins of lymphocytes’’ (Blood, 2012).

This success came with a price. Working on hematopoi-etic stem cell function is elaborate and difficult, with eachassay lasting many months. In particular, the studies onclonal heterogeneity of stem cells took years. Much ofChrista’s work was done with little support and sometimesonly the most basic of equipment. She was a champion of‘‘small, but smart’’ science. When she and Hans started towork at the Sanford-Burnham Institute, she jokingly wroteto me that for the first time ever somebody offered tocustomize her laboratory, asking her what equipment shewanted and finally allowing her to throw away those

decades-old centrifuges. In addition, during her pre-Burn-ham period, she was always dependent on someone else’scell sorter, regularly walking ‘‘over the hill’’ to Scripps ordriving to the Salk Institute with her cells. Her determina-tion, energy and commitment to science, doing the rightexperiments no matter what and how difficult, was exem-plary. She possessed an outstanding degree of scientificrigor and an absolutely fine mind.

Sadly, there was one battle Christa could not win; shefinally succumbed to illness this year. She was a wonderfuland generous friend to all of us whose private lives shetouched and an inspiration to her colleagues.

Christa will be terribly missed.

I would like to thank Irv Weissman, Klaus Rajewsky,Elaine Dzierzak and Kateri Moore for their kindcontribution to this obituary.

Constanze BoniferChair of Experimental Haematology

School of Cancer SciencesInstitute of Biomedical Research

College of Medical and Dental SciencesUniversity of Birmingham, Birmingham B15 2TT, UK