Tomas Ganz talks with
ScienceWatch.com and answers a few questions about
this month's Fast Moving Front in the field of
Article: Defensins: Antimicrobial peptides of
Journal: NAT REV IMMUNOL, 3 (9): 710-720 SEP 2003
Addresses: Univ Calif Los Angeles, Dept Med, David Geffen
Sch Med, Los Angeles, CA 90095 USA.
Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Los
Angeles, CA 90095 USA.
Univ Calif Los Angeles, Dept Pathol, David Geffen Sch Med,
Los Angeles, CA 90095 USA.
Why do you think your paper is highly
The study of antimicrobial peptides and their role in innate immunity
generated a lot of excitement because it focused on how microbes are killed
or prevented from multiplying. When the review was written, immunology was
still focused predominantly on antigenic recognition, which is only a small
part of host defense, and is lacking in invertebrates altogether. The
review summarized a lot of ideas that were brewing in the antimicrobial
peptide field at the time. I tried to assess objectively and sometimes
critically where the field was going, and this may have contributed to the
success of this review.
Does it describe a new discovery, methodology, or
synthesis of knowledge?
The review is a synthesis of work done by many investigators in the field.
Would you summarize the significance of your paper in
Humans, animals, and plants resist infections by making substances that
directly kill germs. These antimicrobials function in many respects like
antibiotics and disinfectants sold in a drugstore. This review summarized
what was known about one kind of such microbe-killing substances.
How did you become involved in this research and were
there any particular problems encountered along the way?
I was lucky to work in the laboratory of Prof. Robert Lehrer, who was a
pioneer in the field of antimicrobial peptides. Michael Selsted and I were
post-docs there together. I learned biology from Bob Lehrer and peptide
technology and chemistry from Mike Selsted. We worked first synergistically
and later independently. Our main problem was that it took a few years to
convince the immunology community of the importance of this area.
Where do you see your research leading in the
While studying urinary defensins, my lab discovered hepcidin, an important
peptide that turned out to be the long-sought iron-regulatory hormone.
Hepcidin controls the dietary absorption of iron, and regulates its storage
and distribution to tissues. Although hepcidin is also involved in innate
immunity, we think that it acts predominantly by starving bacteria of iron.
I have greatly enjoyed starting from scratch in a new area of biomedicine.
Do you foresee any social or political implications for
Microbes are becoming resistant to existing antibiotics, but the
pharmaceutical pipeline for new antibiotics may not be keeping up. I hope
that some of the ideas developed through the study of defensins and other
antimicrobial peptides will lead to new antibiotics for the treatment of
resistant infections or to ways of stimulating natural host defenses to
Tomas Ganz, Ph.D., M.D.
Professor of Medicine and Pathology
Department of Medicine
David Geffen School of Medicine at UCLA
Los Angeles, CA, USA
Keywords: antimicrobial peptides, innate immunity, antigenic
recognition, host defense, antimicrobials, microbe-killing substances,
urinary defensins, hepcidin, pharmaceutical pipeline.