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Biomineralization. Progress in Biology Molecular Biology and Application

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Progress in Biology,
Molecular Biology
and Application.
Edited by Edmund
Buerlein. WileyVCH, Weinheim
2004. 337 pp.,
E 159.00.—ISBN
Mineral formation by organisms—biomineralization—is a widespread process
that takes place in organisms as diverse
as bacteria and vertebrates. The mineralized products range from single crystals that are no different from those
formed inorganically to complexshaped composite materials. Much of
the “action” occurs at the interface
between the mineral and the biological
macromolecules that constitute the
microenvironment in which the mineral
forms. Thus, the subject is inherently
interdisciplinary, spanning the inorganic
and biological worlds, with no clear-cut
division between them. The field of biomineralization attracts researchers from
molecular biology, biochemistry, cell
biology, genetics, medicine, and materials science. Biomineralization is also
important to the historical sciences
such as evolution, paleontology, archaeology, and paleoclimatology, as it is the
mineralized tissues that are most frequently preserved in the fossil record.
It is thus easy to see that all this interest
from such diverse disciplines can result
in a “Tower of Babel” syndrome, in
which everybody is talking or writing
on the same subject, but there is limited
communication between them.
Angew. Chem. Int. Ed. 2005, 44, 4833 – 4835
This revised second edition of a
multi-authored book on biomineralization does not overcome the communication problem, and therefore it is not an
easy read for the casual outsider, or for
the newcomer to this field. Indeed, for
the most part, there is very little effort
on the part of the authors to minimize
jargon and facilitate communication.
There is also no attempt to cover the
waterfront of this vast subject. Paradoxically, herein lies the book&s greatest
value, as some subjects are treated comprehensively. Several chapters are
devoted to silicification, and no less
than seven of the 18 chapters focus on
biologically formed iron minerals.
Thus, the book comprises overlapping
reviews of some subjects, interspersed
with single chapters devoted to a range
of other topics. So this is really a book
for the professionals in the field—in
fact, I would say it is almost a “must
have” on the shelf. In reading through
this book, I have learned a lot. Here
are some of my highlights.
The three chapters on the silicification of diatoms constitute an invaluable
package. Reading about the present
state of the art, it is difficult to believe
that, just about ten years ago, we knew
almost nothing about this subject, at
least at the molecular level. Kr-ger
and Sumper are among the pioneers of
this subfield, and their chapter on the
molecules and mechanisms involved in
diatom silicification is a gem. It is well
complemented by Hildebrand&s review
on silica acid transport, and by the chapter by Wetherbee, Crawford, and Mulvaney, which emphasizes the manner in
which biological control manipulates
the basic chemical properties of inorganic silica. In this context, it is interesting to note that the colloidal structure of
the gem precious opal is remarkably
ordered, despite the fact that it is
thought to be the product of an inorganic process.
The first of the seven chapters on
iron mineral formation is a comprehensive and thoughtful review by Bazylinski
and Frankel of the mainstream issues of
magnetite and greigite formation in bacteria. The other chapters cover topics
such as molecular taxonomy of magnetotactic bacteria (Amann et al.), the
all-important structure of the magnetosome itself where mineral formation
occurs (Sch4ler), the involvement of
enzymes (Fukumori), and even the technological applications of biogenic magnetite particles (Matsunaga et al.). I particularly enjoyed reading the review by
Winklhofer on geomagnetic perception
in animals. I also discovered a few facts
that really surprised me. The magnetosome contains silk fibroin-like proteins
and acidic proteins, both of which are
prominent components of the organic
matrix of mollusk shells (convergent or
divergent evolution?). Some magnetosomes contain both magnetite and greigite. It is rare in biology to find two different minerals in one structure.
I praise the editor&s choice of including two chapters on zebrafish. One of
these chapters (S-llner and Nicolson)
describes some of the most exciting
new insights we have into protein control over mineralization, in this case in
the calcitic otoliths of the fish. The
other is an encyclopedic review of zebrafish mutants that affect the skeleton
(Jun Du and Haga). The zebrafish is rapidly, and justifiably, becoming recognized as an important vertebrate model
for studying basic biomineralization
processes and mechanisms, and this
chapter is an exceptionally good
resource. Hopefully, these chapters will
encourage some investigators to make
a concerted effort to better characterize
the ultrastructure of wild-type bone and
teeth in zebrafish, as without this information we will not be able to fully
appreciate the significance of the mutations. Dentinogenesis is another wellestablished model for biomineralization,
and the chapter by Reichenmiller and
Klein draws attention to this.
An important theme in many of the
reviews is that the mineralization process involves much more than just the
formation of the mineralized structure
itself. For this to happen, the ions need
to be sequestered from the environment, transported, sometimes temporarily stored, and only then deposited.
The chapter by Jahnen-Dechent is a
well-illustrated and comprehensive
description of how complicated and
finely balanced the transport process
can be, particularly for the vertebrate
skeleton that utilizes a highly insoluble
mineral, carbonated apatite. Being so
insoluble, it can easily form in the
wrong location and not in the skeleton
/ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
itself, with tragic consequences. This
chapter, cutely entitled “Lot&s Wife&s
Problem Revisited”, presents fascinating insights into strategies used by the
organism to prevent that happening.
Bearing in mind that surface seawater
is also saturated with respect to calcite
and aragonite, the problems exist for
many other marine organisms (see the
chapters on coccolith formation by
Marsh and Gonz<lez).
This is a serious and comprehensive
book for professionals in the field of biomineralization. Much of the credit is due
to the broad view that the editor takes of
the subject, as exemplified by his including a chapter by Epple on modern methods of investigation in biomineralization, and his own opening chapter on
peptides, prebiotic selection, and prebiotic vesicles.
Steve Weiner
Department of Structural Biology
Weizmann Institute of Science
Rehovot (Israel)
DOI: 10.1002/anie.200485303
The Merck Druggernaut
The Inside Story of
a Pharmaceutical
Giant. By Fran
Hawthorne. John
Wiley & Sons,
Hoboken 2003.
290 pp., hardcover
E 29.90.—ISBN
To give the verdict right at the start: this
is a highly informative and objective
description of one of the world&s most
important pharmaceutical companies,
and also of current practices in this
industry generally. It is of a kind that
is—unfortunately—rarely seen. As the
subtitle states, it is an “inside story”,
which the author, a prominent journalist
in the area of business and finance, has
based on about 175 interviews with
people who work in the Merck organization, formerly worked there, or are
involved in the same industry. This
book of 290 pages, with a carefully prepared index, makes easy and absorbing
reading. It contains a wealth of factual
information, not only about the company and the ups and downs of its historical development, but also about the
general problems and risks of developing new drugs, and the methods and
side-effects involved in the ethical pharmaceuticals business. The book is in no
way tendentious or negative in its portrayal, it is an objective description
that can be recommended for reading
by everyone concerned with the development, production, use, and marketing
of pharmaceuticals. I also hope that it
might be read by politicians responsible
for health legislation, so that their decisions might be better based on reality.
The author gives a short outline of
the history of the company, which grew
out of the firm E. Merck in Darmstadt.
In 1900, George Merck, a grandson of
the founder Emanuel Merck, acquired
a large site in Rahway, New Jersey, and
began to manufacture fine chemicals
and pharmaceuticals. During World
War 1, the originally German company,
like all German companies in the
USA, became Americanized. (This was
the time when orchestras in the USA
stopped playing Beethoven, and “Hamburgers” were renamed “Salisbury
steaks”.) However, after the war
George Merck bought the company
back—although it had to be operated
for ten years under a trusteeship of
Goldman Sachs & Co. and Lehman
Brothers. In 1915, George&s son,
George Wilhelm Merck, after finishing
his studies at Harvard University,
joined the company. He subsequently
headed it from 1925 until two years
before his death in 1957. The author
emphasizes the roles of George W.
Merck and P. Roy Vagelos as the “legendary leaders” of Merck. As early as the
1930s, George W. Merck began a program of research on pharmaceutical
compounds, and hired a number of
prominent academic researchers, including the outstanding and highly successful scientist Max Tishler from Harvard.
The research topics at that time were
vitamins, sulfonamides, antibiotics, steroids, and other hormones.
Following G. W. Merck, the company was led by John T. Connor (from
/ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1955), Henry W. Gadsden (from 1965),
John J. Horan (from 1976), the biochemist Roy P. Vagelos (from 1985), and
lastly Ray Gilmartin, a Harvard MBA
(from 1994). Under the leadership of
J. J. Horan&s chosen successor Roy
Vagelos, Merck experienced a remarkable upturn. Many innovative products
were developed by the highly motivated
and hand-picked research team, who
benefited from an outstandingly good
working environment; it is said that
Vagelos, as CEO, insisted on talking
with every scientist job applicant
before he or she could be appointed!
Until a few years ago, Merck was the
biggest and most successful pharmaceutical company in the world, held in high
esteem by employees, doctors, and
patients. In every one of the seven
years from 1987 to 1993, Merck was
named by Fortune magazine as the
year&s “most admired company”.
However, Merck, which was the brilliant star of Wall Street up to 2001, now
faces a mountain of problems. The company&s capital value has fallen drastically, and the exemplary shining image
that it used to have now shows deep
scratches. The author has tried to identify the causes of this “fall from grace”.
It began with the acquisition of the
“medical benefits manager” company
Medco in 1992, which was based on a
misreading of the prospects for success
of President Clinton&s over-ambitious
health reforms, which subsequently
failed. The reforms, if successful, would
have brought about great changes in
marketing operations. The acquisition
did not pay off for Merck. At the same
time, its competitors, especially Pfizer,
greatly increased the number of their
salespeople (reps) who visit doctors.
Several profitable blockbuster drugs of
Merck lost patent protection in the last
few years and fell victim to competition
from generic products. Not enough new
products with potential for success are
emerging from Merck&s R & D pipeline.
In 2002, some embarrassing accounting
irregularities in connection with
Medco&s activities came to light. Lastly,
in September 2004, Merck&s osteoarthritis drug Vioxx, with an annual turnover
of more than 2.5 billion dollars, had to
be withdrawn from the market worldwide because of serious side-effects.
Vioxx, a COX-2 inhibitor that had
Angew. Chem. Int. Ed. 2005, 44, 4833 – 4835
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progress, molecular, application, biomineralization, biologya
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