In 2009 in San Antonio, Texas, I (JSB) was attending the annual meeting
of American College of Clinical Pharmacology. My friend Bob Talbert (one of
the authors of the
Pharmacotherapy: A Pathophysiologic Approach
textbook) and his wife took me and my wife out for dinner and, after
sufficient Mexican food and drink, suggested that I edit a textbook on
Pharmacogenomics. Bob made the point that the publisher of the textbook that
he co-edits, McGraw-Hill, was very interested in this topic. The text would
be meant for students, trainees, and others who were interested in the
topic. This was a hard offer to turn down, a strong suggestion from an old
colleague and friend, with a well-known and successful publisher!
However, I did know that this textbook had to have a broad
editor and writer base. One of the jobs for the first editor is to beg (read
"twist their arms") his friends and colleagues to help him as editors. Their
job in turn is to convince their friends and colleagues to write chapters.
So, I started making calls. My criteria for editors were individuals
respected in the pharmacogenomic, clinical pharmacy, and clinical
pharmacology communities, who had done sufficient research with original
publications in the area of pharmacogenomics. These individuals also had to
have the ability to beg their friends and colleagues (read this as "twist
their arms") who also had done research and published in the area of
pharmacogenomics, to write chapters. I was fortunate to be able to convince
my four co-editors to contribute to this book. C. Lindsay DeVane, PharmD
(Medical University of South Carolina School of Medicine), was a fellow when
I was a student in Buffalo, NY, and had had an outstanding career in
psychopharmacology. Lindsay is the ultimate southern gentleman. Uwe Fuhr, MD
(University of Cologne, Faculty of Medicine), is a well-known and respected
clinical pharmacologist from Cologne, Germany (a beautiful city), who is an
editor for the European Journal of Clinical Pharmacology and has contributed
greatly to the science of drug metabolism. I knew that Uwe could put forward
a European perspective on this. Angela DM Kashuba, PharmD (University of
North Carolina School of Pharmacy), is a pharmacist and clinical
pharmacologist from Toronto, Canada (living in the USA for decades now), and
has made substantial contributions to the pharmacogenomics literature.
Additionally Angela works in the area of HIV eradication and prevention and
has an international reputation. Joseph D Ma, PharmD (University of
California at San Diego School of Pharmacy), is from Southern California.
His contributions to pharmacogenomics have spanned both the medical and
pharmacy literature and his passion for patient care, research, and teaching
is contagious. Joe is always either devising or attempting to validate
unique sampling methods to bring pharmacogenomics into the clinical setting.
All of these outstanding individuals are teachers, scientists, and
clinicians; thus, they discover, apply, and teach others pharmacogenomics. I
could not have recruited a better group. We worked together well and
complemented each other's knowledge.
The
criteria that we as editors agreed upon for chapter authors was that the
individuals must have contributed to original research in pharmacogenomics
and that the book must have an appropriate international perspective.
Chapter writers contribute to a textbook because of the pride of sharing
knowledge; there is virtually no monetary gain. Again, we were fortunate to
be able to recruit PharmD's, MDs, PhDs, and social scientists from 4
continents to contribute to this textbook. We are grateful to the
individuals who, despite being "in demand" people, contributed to this
textbook. The chapter authors are the experts in pharmacogenomics and we
appreciate their contributions.
Along the way,
when one puts a textbook together, things happen. We were fortunate in this
regard and, in fact, lucky. We lost only one writer due to over-commitment
(a gentleman who always apologizes profusely to this day but he did find a
superb replacement). One of our writers suffered from breast cancer but
successfully beat it (hooray!!), and another had a baby during the process
(both her chapter and a baby picture showed up in my email box). Others
changed jobs and moved on. But still, life goes on and they all came through
on time with great work.
The science of
pharmacogenomics has been described since the 10
th century. It
was then when the Pythagoreans (pupils of Pythagorus) were banned by him
from eating fava beans (a staple at that time, still eaten today for its
flavor and nutritional value) because of his observation of the development
of hemolytic anemia in individuals with G6PD deficiency. These individuals
endured endless societal criticism because they followed the life-saving
directive of Pythagorus, as it was unheard of for such a basic food to be so
deadly to a human being. This restriction, and its rationale, was discussed
over the centuries, even by the philosopher Aristotle. But, most likely this
restriction of the eating of fava beans saved the lives of many individuals
with G6PD deficiency. This is the first known historical description of
pharmacogenomics. Skip ahead to the 19
th and 20
th
centuries with two very important developments in the field of genetics. The
first was the description of inherited traits by Dr. Gregory Mendel and the
second, a little recognized manuscript (at the time) published by Dr.
Archbald Garrot on chemical individuality (sounds like one dose isn't
right for everyone).
In the post-WWII world, an
interesting discovery was made by a young physician-scientist from the
University of Toronto. This physician-scientist, Dr. Werner Kalow, was a
prisoner of war held in Arizona after he was "drafted" by the Nazi regime to
be a German ship surgeon. The ship he was assigned to was captured in the
Pacific by Allied Forces and prisoners were taken. In WWII America, Dr.
Kalow served his time as the prisoner-of-war camp physician and would ride
along with the prison ambulance until the end of the war. As Dr. Kalow
stated "The Americans were smart, they knew that not all Germans in the
military were supportive of the Nazi cause and it seemed that they easily
picked out those of us that were not supportive, separated us and sent us to
camps in the USA that allowed much more freedom." After WWII, Dr. Kalow
returned to Berlin, and then moved to the University of Tornoto. In 1957,
he, along with Dr. Natalie Staron, described prolonged skeletal muscle
paralysis due to
succinylcholine in a patient with cholinesterase
deficiency. Kalow went on to describe the genetics of this finding by
genotyping 135 patients and dividing them into extensive, intermediate, and
poor metabolizers based on allele identification. Dr. Kalow went on to write
the first textbook on "Pharmacogenetics," which was published in 1962. He
worked until his passing at age 91 in 2008.
The
science continued to evolve slowly until the 1980s with the availability of
better analytical techniques to determine parent and metabolite drug
concentrations more efficiently and cheaply. Additionally genetic
advancements made finding genetic polymorphisms easier. These developments
were followed by the Human Genome Project, which has provided some very
valuable information that can be easily applied to pharmacogenomics. Many
have contributed to the advancement of pharmacogenomics. Thus, the reader
can get a sense of the volume of information that has been generated over 10
centuries.
This first edition of the book is meant
to be a basic introduction to the topic of pharmacogenomics. The textbook
has been written for students, trainees, scientists, and clinicians in
pharmacy, medicine, nursing and other allied health professions. We did not
intend this to be a comprehensive textbook covering all aspects of
pharmacogenomics, but to give the user a general overview of the topic.
The textbook is divided into two sections. The first
section covers more general aspects of pharmacogenomics. In these sections
we attempted to cover areas such as ethics, regulatory science, and
pharmacoeconomics among others. In particular, Chapters 2 and 3 provide a
"mini" course in molecular genetics and testing. The second section reviews
the role of pharmacogenomics in areas such as cardiovascular medicine and
immunology. The book presents learning objectives for each chapter. The
chapters in the second section also have cases for the reader to appreciate
the clinical application of pharmacogenomics. We hope that the readers of
this book understand that drug therapy must be individualized based on
genetics and environmental factors. Rather than suggesting the same drug,
biologic or vaccine dose for everyone, there are many instances where dosage
individualization is essential.
The editors hope
that you find this textbook informative. We always welcome suggestions to
improve the textbook. Please email us if you have suggestions or comments.
Joseph S. Bertino Jr., PharmD, FCP, FCCP
C. Lindsay
DeVane, PharmD
Uwe Fuhr, MD
Angela D. M. Kashuba, BScPhm, PharmD,
DABCP
Joseph D. Ma, PharmD