Tears of the cheetah : the genetic secrets of our animal ancestors

246 Pages·2005·1.16 MB·English

by  O'Brien

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Table of Contents
About the Author
Copyright Page

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To my teachers Ross MacIntyre, Bruce Wallace, and James
Edwards, who introduced me to the wonder of genetic thinking,
experimentation, and interpretation.
Foreword
There is no better way to introduce a beginner into the achievements of
molecular biology than Stephen J. O’Brien’s Tears of the Cheetah. Some early
biochemists loudly proclaimed that molecular biology would exterminate the
rest of biology. “There is only one biology,” one of them said, and “This is
molecular biology.” Nothing could have been more wrong. Instead, the study of
molecules has enormously enriched organismic biology and led to astonishing
discoveries in just about all branches of biology. O’Brien, in fourteen chapters,
shows in case study after case study how the molecular discoveries of genomes
have shed unexpected light on such problems as the loss of genetic variation in
the cheetah, the Florida panther, and the Asian lion; how we can find the degree
of genetic difference among populations of whales, of Indonesian orangutans,
and of many species of uncertain taxonomic rank; why the unique mating system
of lions is not in conflict with kin selection; how AIDS originated, and why it is
so resistant to all medical effort. Immune genes tell us about historical epidemics
hundreds or thousands of years ago. These fascinating scenarios are told by
O’Brien with such literary mastery that one can hardly lay his book down.
In chapter 10 the extraordinary similarities of the genomes of different
mammals (including the human) are presented, and it is pointed out to what great
extent the solution of human medical problems is helped by comparative studies
of the genomes of other mammalian families—for instance, cats. Though often
dealing with highly technical matters, O’Brien has succeeded in presenting his
stories in a simple language that can be understood even by the nonexpert. And
he also persuades us how important the findings made on animals often are for
human medicine. There is no other book I have read in recent years from which I
have learned more, and which I have more enjoyed, than this one. And so will
every reader.
—Ernst Mayr,
Alexander Agassiz Professor of Zoology, Emeritus, Harvard University
Prologue
The book you have opened contains a collection of stories. They are adventures,
they are science mysteries, they are medical enigmas, and they are detective
stories. Most draw their theme around an inimitable threatened animal species
and scientific advances that unveil past and present dangers. The chronicles are
all true and in different ways illustrate the power of new genomic technologies
to uncover hidden secrets in the history of wildlife species, of companion
animals, and of ourselves.
At first glimpse these tales describe the peril of beloved endangered species
—cheetahs, humpback whales, giant pandas, and others. What we discovered
beneath the surface of the fragile wildlife species reveals the rationale and
context for their successes, for their survival, and for their vulnerability. The
new perspectives derive from reading genetic codes of living species, only
recently available for inspection. The spectacular developments in genetic
technology and gene identification can be applied to any species with surprising
and sometimes disturbing results. From the viewpoint of evolutionary hindsight,
a thousand fables are slowly emerging through the lens of modern genomic
enquiries. What began as a quest for reversing species extinction opened my
eyes to as rich a history of magnificent creatures as anyone could have imagined.
The genetic thread that strings these stories together is the indisputable unity of
all living things. We are all intricately joined by a vast, weblike genealogical
network to our most ancient ancestors.
The genomes of modern mammals, the sum total of an individual’s genetic
instructions, contain an extraordinary cache of information. In their genetic
endowments of three billion nucleotide letters reside thirty-five thousand to fifty
thousand genes that specify each creature’s development. But they also retain the
script of historic brushes with extinction, adaptation, and survival. Every day
nature’s dutiful field experiments test new gene variants across individuals in
populations, among species, and across geographical space. All these trials have
been neatly catalogued in the genetic sequence of the survivors, the plants and
animals alive today. Scientists are only beginning to interpret the genetic
“pawprints” of ancient events. We are learning as we go how to discern the
message and lessons in DNA. Though progress may seem slow, the early views
on this genetic safari have galvanized our thinking and optimism for solving
countless mysteries about how living things came to be.
The genomics era appears to have unprecedented promise and potential for
nearly every aspect of biology. It is as if the printing press were just invented
and we anticipate the wide dissemination of the thoughts, ideas, feelings, and
experiences of a whole generation. The difference is that our collective genomes
encode the lessons of not one but tens of thousands of writers, multiplied across
every evolutionary lineage while also possessing their own unique and defining
experience. As the periodic table empowered chemical design and the silicon
chip changed all things computational forever, so will our cracking the genome
be remembered as a turning point in the underpinning of biological happenings
—past, present, and future.
An underlying theme of the science mysteries is the unusual insight that
animal studies bring to human medicine. Wild species have no hospital
emergency rooms, no HMOs or pharmacies to treat their ills. Still they are
regularly assaulted with scourges nearly identical to those that afflict humans—
cancers, deadly infectious diseases like AIDS and hepatitis, degenerative
diseases such as multiple sclerosis, Alzheimer’s, and arthritis. Many victims
succumb and die; indeed, well over 99.9% of all mammalian species that have
walked the earth have gone extinct. But others have escaped, and those lucky
species survive quietly today, carrying the evolved secrets to their success in
their genetic endowment. Can medical science learn from natural solutions to
hereditary, infectious, and neoplastic diseases acquired by free-living
orangutans, lions, cougars, and barn mice? I believe we can, and I will illustrate
how by the examples in the coming chapters.
These stories offer a window into twenty-first-century science, where
undoubtedly countless biomedical advances will come from mining the genome.
These are parables of hope and lessons of survival. They also navigate through
the torturous but exhilarating process of scientific discovery, interpretation, and
policy development.
Each chapter tells its own special narrative with twists and turns no novelist
would have imagined. I selected them because I have been personally involved
with each and with the lead characters I describe. The cast of players are
scientists, graduate students, postdoctoral fellows, physicians, veterinarians, field
ecologists, and many others who play into the mix of research advancement. I
have had the privilege of joining these adventures as a government scientist,
employed as a geneticist for thirty years at the U.S. National Institutes of Health
(NIH).
In 1971 I arrived as a rather naïve Drosophila (fruit fly) geneticist,
wondering if my chosen discipline might provide any benefit to medical
research. I now serve as a laboratory chief in NIH’s intramural research
program, overseeing the research projects of students, fellows, and senior staff.
We strive to use the genetic technologies and advances to chip away at the
causes, diagnostics, and treatments for cancer and infectious disease. The stories
I tell come from the challenge and exhilaration of exploring into the deepest
mysteries of biology—why some species have survived while others have not.
In the end, we have been fortunate to uncover animal and human genomic
secrets. Some discoveries, like solving the inscrutable origins of giant pandas,
resolved dusty old academic conundrums. Others, like the fragility of the
cheetah and Florida panther, informed the workings of conservation plans. Still
others, like the AIDS plague in lions and in humankind, opened new avenues for
clinical therapy for today’s most devastating infectious disease killer.
This collection offers a brief peek at the brilliant landscape that the post-
genomics era will display, a fascinating view of biological fits and starts that
preview finely tuned advances in conservation, forensics, and medicine. My
hope is to render the process understandable to the interested reader with little
background in the jargon and mystery of genomic thinking. In the process, I
have used some tricks, analogies, and literary license to make principles
understandable. Throughout, the technical terms are kept to a minimum. The
glossary at the back explains some of the basic terminology. I hope the reader
will enjoy the learning and share in the wonder of amazing science that is
opening our eyes for discovery and application across all the disciplines of
modern life sciences.