Though it might seem like the ultimate reductionist approach,
the sequencing of the human genome is in fact a major advance toward achieving
an integrated understanding of physiology. Contrary to the commonly used
metaphor, a genome is not a ladder with genes as rungs. There is complexity to
the structure and organization of the genome, just as there is complexity to
the developmental, metabolic, and other pathways that make up biologic systems.
Genomics, and its sibling proteomics, provide essential tools for moving beyond
the characterization of individual components of these complex systems and
beginning the task of understanding how they are put together to make cells,
tissues, organisms, and populations. In Essentials of Medical Genomics, Stuart
Brown provides a "philosophical definition" of genomics, calling it
"a holistic or systems approach to information flow within the cell."
Extreme claims, including both extravagant promises and dire warnings, have
been made about the potential medical applications of genomics. There are
already several molecular tests that are used routinely for diagnosis or risk
assessment. As genomic approaches continue to help unravel pathophysiological
mechanisms, new ways to diagnose and treat both rare and common disorders will
emerge. It is becoming increasingly important to train physicians in this new
discipline, in part to prepare them to use these new tools wisely and in part
to allow recognition of clinical-research opportunities. The time is right to
include genomics in the medical-education curriculum, and thus there is a need
for books that can help guide the way. Essentials of Medical Genomics is a
readable account of the underpinnings of genomics and its medical applications,
with an intensive focus on technology. About a century of research on genetics
and molecular biology is covered in the first chapter. Following that there is
a tour through approaches to gene cloning, bioinformatics, the nature of
genetic variation, pharmacogenetics, the use of microarrays, and proteomics.
The author describes himself as a molecular biologist specializing in
bioinformatics; he is not a physician. The two chapters that focus on medical
applications -- one on genetic testing (by Harry Ostrer) and one on gene
therapy (by John G. Hay) -- were contributed by physicians who are immersed in
those disciplines. The chapter on gene therapy is a particularly lucid account that
places the challenges and prospects of this difficult area into perspective.
The final chapter of the book is devoted to ethical issues raised by genomics
in medicine. The discussion is important, though parts of the chapter have a
sermonic tone. Brown's book is based on an elective course on this topic taught
by the author. As such, it may be understandable that some areas of importance
are given only brief coverage or are not covered at all. Presumably these
topics, such as patterns of inheritance and the molecular basis for dominant
and recessive traits, are covered in a separate genetics course. Likewise, the
principles of cancer genetics are not described, although related topics, such
as the use of microarrays to classify tumors, are covered. There is a
discussion of the use of genetic testing in presymptomatic diagnosis in persons
at risk for cancer, but not of the concepts of nonpenetrance or
tumor-suppressor genes. This narrow focus may be a handicap if the book is used
as a stand-alone resource in a comprehensive course on genetics and genomics.
This is a clearly written book that makes a complex discipline understandable.
The emphasis is on broad concepts, with relatively little technical detail to
distract the reader. The style is informal, even colloquial; for example, in
referring to the development of the polymerase chain reaction, Brown writes,
"A lot of scientists were slapping themselves on the forehead when Mullis
picked up the Nobel prize in 1993." There are many illustrations, although
most are of relatively simple design; little has changed from what were
probably lecture slides. How much will physicians need to know about the
technology of genomics in order to use this approach in their practice? Most
are accustomed to ordering magnetic resonance imaging scans, yet very few could
explain the physics involved. Probably not many physicians could explain how a
complete blood count is now obtained, although most are familiar with the
indications for obtaining it and its interpretations. The basic-science
curriculum in medical education is predicated on the belief that some working
knowledge of the underpinnings of a field is necessary for physicians to be
sophisticated users of technology-intensive tests. Medical genomics is a
nascent field, so it remains to be seen to what extent the technology will
become submerged, leaving physicians to deal with a more user-friendly
interface. Essentials of Medical Genomics provides an approachable introduction
to a discipline that is likely to remain an engine of progress in medical
science, at least through the coming generation.
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