doi:10.1016/S0092-8674(03)00520-8 Book Reviews 17 area it does not cover concerns the trickier questions into their schedule. Although there will be a tendency that young investigators face when submitting their first to feel like this is the last thing that a new investigator grant. For instance, many PIs do not know how to direct should spend time doing, the book is well worth the their grant to the appropriate study section or when they time. The book replaces that senior faculty mentor who should contact a program official for advice. However, is not around when a crisis strikes. Another advantage as pointed out in one of the quotes, there is nothing as to reading Academic Scientists at Work is that it forces useful as talking to senior colleagues: “Remember, your one to think about things ahead of time that might save colleagues are concerned about your getting funded, a lot of effort in the long run. For good reason, most and they realize the road may be bumpy. They will help junior PIs are very focused on the current major issues. if asked.” Why worry about a class that needs to be taught next The biggest hurdle other than obtaining funding for semester when a tech needs to be hired today? Although most young investigators is getting and supervising this is true, the great thing about the book is that it people. Managing personnel is difficult because unlike points out things that will need to be dealt with in the experiments, it will not work the same way every time. future so one is better prepared to handle them when Although it is critical that employees are treated consis- the time comes. I would encourage new investigators to tently, applying a single rule to everyone will probably read the book, and to read it earlier than later. Preventing backfire. The authors therefore outline the various rea- even one mistake will be a sufficient return on the time sons why each type of employee is valuable and provide invested. estimates about how much time a PI should expect to spend with them. In addition, there are good ideas about Sue Bigginshow to assign dissertation projects as well as various Fred Hutchinson Cancer Research Centertips for teaching students how to do experiments and 1100 Fairview Avenue N., A2-168write papers. Seattle, Washington 98109In addition to the topics of managing money, people, and science, the book also explains how to be a faculty citizen, mentor, and teacher throughout the first years. The authors describe how to say “no,” and how to get along with the chair and other colleagues. The issue of Chromosome Beauty picking and using mentors is also covered, a potentially valuable resource for new investigators. However, there is no discussion of issues that might face specific Chromosomes: Organization and Function groups of faculty members, such as women or minori- By Adrian Sumner ties. There is an excellent section that explains how to Malden, MA: Blackwell Publishers (2003). review and make decisions about manuscripts and grant 238 pp. $69.95 applications. In addition, the book offers strategies for preparing and submitting papers and learning how to respond to reviewer criticisms when resubmitting a Without question, the chromosome holds a special manuscript. The teaching chapter offers many organiza- place in the heart of many biologists. Many are capti- tional tips for running a course. vated by its aesthetic appeal and, for some, it has come The book ends the junior PI phase by discussing the to symbolize the most tangible and beautiful display of promotion process. It describes how to prepare a dos- our genetic substance. To add to their appeal, chromo-sier and the various expectations that may need to be somes can be shown to friends and visitors more or lessfulfilled to obtain tenure. Since it will be too late to sud- as they are in our cells, using an affordable microscope.denly obtain enough publications, it is a good reminder Indeed, I know of a few chromosomologists who havethat young investigators need to monitor their own prog- grown so fond of, or comfortable with, this subject thatress over the years. The strategies for assembling a they have become reluctant or even terrified to step outstrong packet are good. Finally, the book actually makes of what is quite literally the microscope stage, into thesuggestions for how to handle a negative promotion. submicroscopic and fast-moving world of DNA and itsThe greatest strength of the book is also the biggest companion molecules. In the end, though, when pitchedweakness—none of the topics are covered in detail. The against something of the enormity of the molecular tidaladvantage is that the reader gets a broad overview about wave, we have witnessed the inescapable withering ofall the key issues in starting a lab. However, the general- research of the sort that is based purely on microscopicizations mean that any unusual or difficult issues, such observations. In their place, we have seen the emer-as how to handle sexual harassment or maintain lab gence of many exciting studies that have elegantly em-enthusiasm, are not covered. Although some of the braced the new molecular tools to peer deeper into whatdeeper issues are not discussed, a similar book by Kathy lies beneath the chromosome.Barker called At the Helm, a Laboratory Navigator is So what have we learned about the chromosome?much more focused and thorough about complicated For one, we have sequenced many genomes and nowpersonnel issues. Since Barker’s book does not include know a great deal about the nucleotide sequence of theissues described in Academic Scientists at Work, such genes that are dotted from one end of a chromosomeas how to obtain funding or how to organize a class, to the other. We know about what types of DNA and,they are an excellent complementary set. to a much lesser extent, proteins cohabit the longitudinalAcademic Scientists at Work is an extremely fast and easy read, so junior PIs will have an easy time fitting it segments of a chromosome. We have become ruthlessly Cell 18 good at knocking these proteins about in cell culture or needed modern treatment with molecular tales. It is a text attempting to cover practically everything to do within whole model organisms to see what any disastrous consequences might tell us about their functions. We chromosomes and, generally speaking, has done a very fine job in that regard. Understandably, given that it ishave become obsessed with mechanistic insights, not to mention little choice if we want to woo the big journals a mere 238 pages, the book falls short on detail in many places for which individual books and major reviewsand granting bodies; thankfully, though, we have learned quite a few things about the mechanisms for many of can be and have been written, but through clever and liberal use of tables and figures, Chromosomes: Organi-the processes. And what remains to be learned about the chromo- zation and Function has managed to capture a large amount of information, with adequate referencing andsome? The answer is a definite “whole lot more.” To this end, we should be, and some already are, critical web linkages to extend its depth. The inclusion of an impressive number of real life micrographs and imagesthat the “reductionist approaches” that we have grown to depend so much on, allow us to look at only one or a of chromosomes doing various things is particularly pleasing, not only because of the illustrative utility ofvery limited number of components at a time, in isolation from most other possible players. They do not help us these pictures, but also for the vivid reminders they provide of the aesthetic appeal of the subject.to capture and interdigitize all the important in-between pieces that are still missing from the big picture. Take The first chapter provides some historical background and reminisces about the few fascinating but largelya couple of examples that have been covered in Adrian Sumner’s book, Chromosomes: Organization and Func- ignored years in the mid-to-late 1800s when four of the most commanding discoveries of modern biology hadtion. For the centromere: although we have now identi- fied a plethora of proteins on this structure, we still have their unparalleled beginnings in remarkably close suc- cession: the publication of the principles of genetics inlittle idea as to what many of them actually do, especially concerning how they interact physically or temporally, 1866 by Mendel, the isolation of an impure form of DNA in 1868 by Miescher, the description of mitotic chromo-and what other players are missing, to enable us to reconstruct the complete pathways for both the assem- somes in 1873 by Schneider, and the proposal of the theory of evolution by Darwin in the 1860s (althoughbly and proper workings of this important structure. Or take another example: although we have known for a that last is not mentioned in this book). In 2003, we commemorate 50 years of cracking the DNA structure,considerable time now about the basic components of a nucleosome and how the chromatin undergoes the but those early discoveries 130 or so years ago deserve every bit as much to come to the forefront of our mind.initial 40- to 50-fold packing (up to the solenoid stage), we struggle to demonstrate how it reaches its final Chapter two gives an overview of the events that occur at mitosis and meiosis and provides a useful back-10,000-fold state of condensation—never mind the even less understood process of decondensation. Further ground for subsequent chapters. The next few chapters take us from the DNA molecule through to its assemblymethodological and technological advancements such as those along the lines of proteomics (Tyers, M., and into chromatin, interphase chromosomes, and finally mi- totic and meiotic chromosomes. These chapters provideMann, M. [2003]. Nature 422, 193–197.), physical and temporal imaging, and mathematical and computational a good mix of tidbits of information—such as how many nucleotides and genes are found in various species,modeling (Chitnis, A.B., and Goodhill, G.J. [2001]. Cell 105, 328–329.), will clearly be necessary to address the and how long and how thick the DNA and its more compacted chromatin and chromosome relations are—big-picture tasks. The recent launch of a pilot Encyclo- pedia of DNA Elements (ENCODE) project by NIH, aimed and more substantial discussions of known mecha- nisms and individual protein involvements in processesat testing and comparing methods for the exhaustive identification and verification of functional elements in such as: mitotic start control, DNA replication, spindle checkpoint, sister cohesion and separation, meioticthe human genome, is a step in the right direction. The story so far is much like that of Frodo, setting out crossing over, chromatin assembly and modification, arrangement of interphase chromosomes, and how theon a journey through a massive and daunting labyrinth in order to deliver the ring of Mordor to the fires of Mount cell deals with different types of DNA damage. These accounts, while inevitably reflecting the incompletenessDoom. Frodo now has the unenviable task of learning everything he can about the labyrinth (primary and inter- of information in many areas, have quite unmistakably succeeded in portraying the impressive advances weacting pathways), what players (genetic and epigenetic) are interested in the journey, with whom he can form have made. The book then turns to specific features of the chro-partnerships (intermolecular complexing and networking), what he and his partners can do (functional understand- mosome, devoting a chapter each to euchromatin, het- erochromatin, sex chromosomes, imprinting, nucleolusing of each player), the loyalty and worth of his fellow travelers (some may have many and variable talents organizer regions, centromeres, telomeres, lampbrush chromosomes, and polytene chromosomes. These chap-or agendas, and others may be dispensable), and any obstacles confronting him (regulatory and inhibitory ters are full of useful information of both descriptive and mechanistic kinds. Several tables list large numbers ofmechanisms). For the sake of humankind, elves, dwarves, and hobbits alike, Frodo will, of course, gallantly and protein components involved in various processes. Al- though the lists in these tables are not exhaustive andpainstakingly inch his journey forward. Having access to useful and accurate intelligence will definitely help do not provide enough information to give the reader a real understanding of the roles of the individual compo-his journey, and here enters Sumner’s book. The book dwells heavily on many long-unresolved nents, they nonetheless serve to inform on the range of proteins that have been discovered. These chapters alsotopics relating to chromosomes and gives them a much- Book Reviews 19 contain a wealth of information that will help the reader to appreciate both the constancy and the diversity of chromosomal phenomena through the phylogeny. The last three chapters offer interesting reading on the role of the chromosome in evolution, disease, and genetic modification and therapy (through chromosome engineering). These pages provide a welcome reprieve from the hard facts of the earlier chapters, turning to the more speculative arena of evolution, as well as possible clinical and practical implications of chromosome biology. Overall, this is an excellent book, written in an easy- to-read style and packed with interesting and accurate information that both novices and learned scholars of Chromosome and Cell Biology will find useful. It takes on many fast-changing topics, but much of the carefully presented information in this book should endure the inevitable onslaught of new research findings. The book could have been strengthened in many areas—for exam- ple, by providing a more in-depth evaluation of weak or missing links, discussing the different chromosomal structures more interactively (such as the significance of common proteins or shared interphase arrangements), highlighting the role of epigenetic influences on and plasticity of some of the structures, indicating possible future research methodologies and directions, and per- haps offering some predictions as to what the field may hold in the years to come. But to insist on these would be to pick faults for their own sake, and to unfairly de- tract from a job that is already well done. Whether read from cover to cover or used as a handy reference, this is a book that will educate on the beauty and complexity of the chromosome. And finally, then, to those em- barking on the journey with Frodo—good luck! K.H. Andy Choo Murdoch Childrens Research Institute Royal Children’s Hospital Flemington Road Parkville 3052 Australia