“The Sequenced Generation: From Your Inadequate Genome to your Dynamic
Microbiome”
Jonathan Lawson
Annotated Bibliography
Davies, Kevin. The $1,000 Genome: The Revolution in DNA Sequencing and the
New Era of Personalized Medicine, Free Press, 2010
Being the editor of the scientific journal, Nature Genetics, provides Kevin Davies
with a seat at the scientific table where the promises of science are met with the
reality of data. The accounts of technological developments to more rapidly
sequence DNA are intertwined with the challenges to translate this information into
usable knowledge. I appreciated the time spent on the fundamental question of the
rights and ownership of one’s genetic information. The book provides many
unfiltered accounts of the utopian or dystopian visions of the use of genetic data
while not taking a particular side. The quotes in this book are priceless in terms of
nailing the personalities of many of the scientists involved in this struggle to
translate information into knowledge. A primary criticism of this book is the
eclectic timeline, which can be difficult to follow, but with so many intertwining
stories a chronological account is not possible. An eye-opening fact after reading
this book, was the number of companies out of business after four years following
it’s publication. In fact only one of the direct-to-consumer genomic information
companies was still in business (23 and Me) and even it had been reduced to only
providing genealogical information. With this in mind while reading the book it
becomes even more clear that the hope of a few visionaries is still premature for
societies, still dealing with racial, religious and political persecution, that throwing
in genomic information was simply too much to soon. While genomic information is
starting to be integrated into medicine, it must follow the rigorous and slow path of
science. This book left me hopeful but saddened at the lack of the public and
political understanding to take advantage of this revolution.
Davies, Kevin. Cracking the Genome: Inside the Race to Unlock Human DNA,
Johns Hopkins University Press , 2002
This title was not included in my original bibliography, but found it to be a good
complement to my studies. Again, Kevin Davies shares his unique perspective on
one of the most storied races in biology since the elucidation of the structure of
DNA. What is highlighted in his accounts is the politics and personalities involved in
such a massive scientific project: from Craig Venter’s bravado or out-right cockiness,
James Watson’s hubris and lack of political filters, to Francis Collin’s optimism and
faith in the future value of the Human Genome Project (HGP). The book does an
excellent job of articulating and explaining the “rumblings” in the scientific
community during this period, and does so with personal accounts of meetings with
many of the principle players in the race. While a general audience will appreciate
the curtain being pulled back on the public face of this exciting race, I found many of
the quotes to be particularly entertaining only with a greater knowledge of the
individuals involved. What I found most enlightening is the extent of the “business
of patents”, that surrounded this race and how this influenced the speed and
direction of the public and private efforts to sequence the Human Genome. If
anything, this was an excellent book to set the stage of intense promise and hope of
the Human Genome and concludes long before the breath of challenges to translate
this knowledge is brought to bear on the scientific community.
Ewald, Paul. Plague Time: The New Germ Theory of Disease, Anchor, 2002
Every freshman biology student and science professor should be required to read
this book. Period. While I may be a bit biased here, I cannot understate how
powerful the ideas in this book are, not only in the insightful challenges to our ideas
of disease causation, but more importantly in how we objectively approach
problems in science. Paul Ewald late in his book describes the value, the necessity,
of prepared minds in science that I would willfully plagiarize as my manifesto as to
why I teach. Ewald takes his knowledge of microbiology, evolution, epidemiology,
and history to objectively look at diseases and challenge the engrained biases with
data and fantastic testable hypotheses. His ability to identify and spear assumptions
made daily by scientists and physicians was humbling to read. The history of the
infectious causation of peptic ulcer disease is used not only as a profound example,
but a warning to the medical and scientific community to be objective in
approaching problems, particularly problems to which we assume we have a wellestablished answer. His presentation on the infectious causation of atherosclerosis
and the role of genetic markers as markers of increased susceptibility to bacterial
infections leaves you with the impression that not only are these ideas plausible, but
probable. Moreover, these ideas marry many of the hypotheses at the intersection
of human genetics and microbiome research. This book is eye-opening, challenging,
and filled with a call to return to science and medicine as it should be conducted.
Carey, Nessa. The Epigenetics Revolution. Columbia University Press. 2012.
A tangent to the original arc of my study grant was the exploration of the field of
epigenetics. In exploring how genetic information could be used, it was clear that the
genome sequence alone was not dictatorial in its ability to predict and define diseases.
Epigenetics, or how the DNA script is performed (to use Carey’s analogy), is a
significant filter that is often ignored when interpreting genetic data. The author presents
this rapidly developing field in a readable way that communicates the ideas of the field
without the scientific jargon that turns people away from science. The history of this
field is well presented, and it was fascinating to read what is a lesser know parallel
history to the more popular field of genetics. Now epigenetics stands as an important
pillar in our understanding of how the genome is “executed”. Starting with playful
examples of epigenetics in cats, Carey does a wonderful job of explaining cellular
differentiation and how epigenetics plays a role in this process. Understanding
Epigenetics mechanisms have now lead to the development of pluripotent stem cells, and
our ability to define a number of diseases. Interwoven throughout the text is the
cautionary call that the genome sequence is only a part of the production of life, and the
idea that is pervasive in science that the sequence is not only the script, but the director, is
false.
Francis, Richard. Epigenetics: The Ultimate Mystery of Inheritance. W.W. Norton
& Company. 2011.
The environment’s influence on organisms has reached a new level in the field of
epigenetics. How the environment can physically alter the genome was an idea that was
thought to be dead with Darwinian evolution’s triumph over Lamarckian ideas.
However, the field of epigenetics has given Lamarckian genetics a new birth. The core
idea that the sequence of your genome dictates how it interacts with the environment,
independent of the environmental history of not only you, but your parents and
grandparents is cracked with descriptions of fascinating studies of families subjected to
what is referred to as the Dutch Hunger Winter towards the end of World War II. The
author does a good job of presenting these data and translating the scientific discoveries
that are being made as a result. While Francis’s account of the field of epigenetics is less
readable than Carey’s it does a more thorough job of describing the science behind this
increasingly important field of genetics. The translation of this knowledge has profound
implications for stem cells and cancer treatments, and is rapidly rising as a fringe group
of geneticist to an essential aspect of understanding human genetics.
Cowan, Ruth Schwartz. Heredity and Hope: The Case for Genetic Screening.
Harvard University Press. 2008.
This text was not on my original reading list, but turned out to be my favorite text on
the subject of genetic testing. The author does a masterful job of objectively
approaching the question of how genetic testing should be used. Ethics are often
defined by a history of experiences, but genomic technology has advanced at a pace
that we assume precludes the use of historical experiences to guide its use.
However, the history of genetics is much richer than I thought and can provide a
strong framework for decision-making moving forward. The great challenge of
genetic information is the separation of genetic testing from the fear of eugenics.
Cowan strips away her subjective opinions and objectively looks at the history of
genetics and genetic testing. She masterfully deconstructs the false marriage of
genetic testing and eugenics by exploring the history of both. I particularly enjoyed
the history of many of the techniques used in early genetic testing and found her
description of the wonderfully serendipitous path of the development of
amniocentesis enlightening. Her description of the development of, and application
of, testing for blood disorders like Tay-Sachs, PKU, and Beta-thalassemia and what
made these programs work in contrast to efforts to test for Sickle-cell anemia and
why this program failed, an eye-opening description of a path for the application of
the new technologies. A society’s motivation to reduce suffering, when wed to
sound science can bear tremendous fruit.
Gillham, Nicholas Wright. Genes, Chromosomes, and Disease: From Simple
Traits, to Complex Traits, to Personalized Medicine, FT Press, 2011
This book is an excellent exploration of the history of genetics and genetic testing,
but falls short in its translation to personalized medicine. While I enjoyed the
history of science presented in this book, it seemed to lack the social implications
and applications that were so well presented in Ruth Cowan’s book. The early
history of genetics was very well written and described in greater detail and
completeness than in other books I read, but this came at the cost of readability that
would turn off many non-science oriented readers. The crescendo leading to the
application genetic information to personalized medicine falls short, and becomes a
dry description of a few examples of statistically challenged genome-wide
association studies. I think Gillham’s presentation of the early debates in genetics
and the misapplication to eugenics is well done, but one could conclude the book
4/5ths of the way in and not be cheated in their reading experience.
Relman, David. Microbiology: Learning about who we are. Nature 486, 194195, June 14 2012.
In this relatively short commentary by David Relman, he does an excellent job of
summarizing the insights and challenges revealed by the two major microbiome
sequencing projects (the Human Microbiome Project and the MetaHIT project). I
have my students read this paper, because it is a readable “30,000 foot view” of the
American and European microbiome sequencing projects. My favorite quote from
this commentary is not only insightful, but and understatement, “Studying the
human microbiome has so far been a lesson in humility.” Despite the obtuseness of
the initial reports reviewed in this commentary, Relman highlights the success and
frames some of the questions and challenges ahead in this field. In his final
paragraph Relman posses four questions that could consume many a career, and I
hope that I am around when these questions are answered.
The Human Microbiome Project Consortium. Structure, function and diversity
of the healthy human microbiome. Nature, 486, 207-214. June 14, 2012.
This paper represents one of the seminal publications of the Human Microbiome Project
Consortium. The data represented in any of its figures stands as a scientific tour de force
of DNA sequencing and data analysis. What I particularly love about this paper is how,
in an attempt to define the “normal” healthy human microbiome, they highlighted the
tremendous diversity found among healthy individuals. The release of this paper, along
with many others in June of 2012, redefined the challenge of understanding the human
microbiome. The traditional, and still pursued, idea that a collection of specific microbial
species is the key to answering questions related to the interactions microbes and human
health was dealt a fantastic blow with the data presented in this report. However, in the
data is the idea that within the microbial community, it is not the “who”, but rather what
functions are present that may provide the fruitful insights. This paper stands as a great
example of how the application of a new technology, high-throughput sequencing in this
case, can be applied to an area of unexplored science that, as it often does, provides many
more questions than answers.