Would Aexl Richard have a chance today:))# Biology - 生物学
v*c
1 楼
想去看star trek，但是之前的系列一部都没看过，需不需要先补看至少其中的某一部
？哪一部？
？哪一部？
S*u
2 楼
尼玛一本丫都掌控不好
n*k
3 楼
As you folks are discussing Cori, I happened to read his autobiography and
find it both interesting and enlightening:)))...BTW, it sounds Richard Axel
is a lot nicer than what I/we have heard...or in another word, his cruelty
is rooted in his obsession with science and indifference to humanity:))); As
well, it is pretty...he noted Cori but left his ex out...pretty human or
not human?
Autobiography
Richard AxelNew York City is my world. I was born in Brooklyn, the first
child of immigrant parents whose education was disrupted by the Nazi
invasion of Poland. Although not themselves learned, my parents shared a
deep respect for learning. I grew up in a home rich in warmth, but empty of
books, art or music. My early life and education were centered on the
streets of Brooklyn. Stickball, baseball with a pink ball and broom handle,
and schoolyard basketball were my culture. In stickball, a ball hit the
distance to one manhole cover was a single, and four manhole covers, a home
run, a Nobel Prize. My father was a tailor. My mother, although quick and
incisive, did not direct her mind to intellectual pursuits and I had not
even the remotest thought of a career in academia. I was happy on the courts
. In those days, we worked at a relatively young age. At eleven, I was a
messenger, delivering false teeth to dentists. At twelve, I was laying
carpets, and at thirteen, I was serving corned beef and pastrami in a local
delicatessen. Vladimir, the Russian chef, was the first to expose me to
Shakespeare which he recited as we sliced cabbage heads for coleslaw.
My local high school had the best basketball team in Brooklyn but the
Principal of my grade school had a vision different from my own and insisted
that I attend Stuyvesant High School, far away in Manhattan. Stuyvesant
High advertised itself as a school for intellectually gifted boys but had
the worst basketball team in the city. I was unhappy about the prospect of
attending for it seemed antithetical to my self-image. Shortly after I
entered, however, my world changed. I embraced the culture and aesthetics of
Manhattan. The world of art, books and music opened before me and I
devoured it. In school, I heard bits of an opera for the first time. I
remember it distinctly, the Letter Duet from Mozart's Marriage of Figaro.
The next night I attended Tannhäuser at the Metropolitan Opera and thus
began a love affair, bordering on an obsession, that has had no end. Twice
a week, I stood on line for standing room tickets at the Metropolitan Opera
where I was exposed to a cult of similarly obsessed but far more
knowledgeable afficionados who taught me the intricate nuances of this rich
genre. The great Italian tenor, Franco Corelli, would serve us coffee as we
waited and the diva, Joan Sutherland, would invite us backstage.
On other days, I would read in a most beautifully appointed place, the
Reading Room of the Central New York Public Library on 42nd Street. One
passes the pair of sculpted lions, ascends a flight of stairs into a huge
high-ceilinged room of impressive silence where I read incessantly without
direction but with a newfound fascination that made up for years of
illiteracy. I met a coterie of library dwellers, men and women of New York,
who spent all of their days in the Reading Room. I did not know who they
were or how they came to be there, but they had an insight and understanding
of literature that amazed and still perplexes me and they were my teachers.
This was New York for me, a city of the culturally obsessed that opened up
before me and framed my new world.
To support a seemingly extravagant life for a young high school student, I
worked. I used my skills as a waiter in a delicatessen in Brooklyn, to wait
tables in the cafes and nightspots of Greenwich Village. In the sixties, the
Village was the home of the beat generation that through music and poetry
and ultimately protest translated discord into meaningful changes in both
America and the world. Stuyvesant High School was on the fringe of Greenwich
Village and some of its teachers were artists, writers, performers who
fueled the politically-fired student body, many the sons of Marxist
immigrants. With this array of artistic faculty Stuyvesant nourished my new
and voracious appetite.
But old worlds die hard. I continued to play basketball in high school and
this led to a most memorable and humbling experience. I came onto the court
as the starting center, and the center on the opposing team from Power
Memorial High School lumbered out on the court, a lanky 7 foot 2 inch
sixteen year old. When I was first passed the ball, he put his hands in
front of my face, looked at me and asked, "What are you going to do,
Einstein?" I did rather little. He scored 54 points and I scored two. He was
the young Lew Alcindor, later known as Karim Abdul Jabar, who went on to be
among the greatest basketball legends and I became a neurobiologist.
My decision to remain in New York and attend Columbia College revealed the
provincial but endearing quality of my family. When I chose to accept a
gracious scholarship offered by Columbia, my father was disappointed. It was
a fact well known that the brightest children of Brooklyn immigrants
attended City College. My freshman year at Columbia, I lived with abandon.
The opera, the arts, the freedom, the protest left little time for study. In
the first semester, I met a student from Tennessee, Kevin Brownlee, who
remains a dear friend and is now a Professor of Medieval French at the
University of Pennsylvania. Brownlee urged me to redirect this intensity to
learning. The world of the arts will remain, but my time at Columbia
University was limited. Once again, a new world opened before me. With Kevin
as my guide, I became a dedicated, even obsessed, student. My life was
spent in a small room lined with volumes of Keats' poetry at the Columbia
Library and I immersed myself in my studies. The study of literature at
Columbia in the sixties was exciting in the presence of the poet, Kenneth
Koch, the critics, Lionel Trilling, Moses Hadas, and Jacques Barzun. It was
largely chance, however, that led me to biology.
To support myself in college, I obtained a job washing glassware in the
laboratory of Bernard Weinstein, a Professor of Medicine at Columbia
University. Bernie was working on the universality of the genetic code. The
early sixties was a time shortly after the elucidation of the structure of
DNA and the realization that DNA is the repository of all information and
from which all information flows. The genetic code had just been deciphered
and the central dogma was complete. I was fascinated by the new molecular
biology with its enormous explanatory power. I was a terrible glassware
washer because I was far more interested in experiments than dirty flasks. I
was fired and was rehired as a Research Assistant and Bernie spent endless
hours patiently teaching this scientifically naïve, but intensely
interested young student. I was torn between literature and science. Dubious
about my literary ambitions and fascinated by molecular biology, I decided
to attend graduate school in genetics.
My plans were thwarted by an unfortunate war and to assure deferment from
the military, I found myself a misplaced medical student at Johns Hopkins
University School of Medicine. I entered medical school by default. I was a
terrible medical student, pained by constant exposure to the suffering of
the ill and thwarted in my desire to do experiments. My clinical
incompetence was immediately recognized by the faculty and deans. I could
rarely, if ever, hear a heart murmur, never saw the retina, my glasses fell
into an abdominal incision and finally, I sewed a surgeon's finger to a
patient upon suturing an incision. It was during this period of incompetence
and disinterest that I met another extremely close friend, Frederick Kass,
now a Professor of Psychiatry at Columbia University. Fred was an unusual
medical student, a Texan with a degree in art history from Harvard, who
remains a kindred spirit.
It was a difficult time, but I was both nurtured and protected by Howard
Dintzis, Victor McCusick, and Julie Krevins, three professors at Johns
Hopkins who somehow saw and respected my conflict. Without them, there is
little question that I would not have been tolerated but they urged the
deans to come up with a solution. I was allowed to graduate medical school
early with an M.D. if I promised never to practice medicine on live patients
. I returned to Columbia as an intern in Pathology where I kept this promise
by performing autopsies. After a year in Pathology, I was asked by Don King
, the Chairman of Pathology, never to practice on dead patients.
Finally, I was afforded the opportunity to pursue molecular biology in
earnest. I joined the laboratory of Sol Spiegelman in the Department of
Gentics at Columbia University. Spiegelman was a short, incisive, witty man
with a tongue as sharp as his mind. Spiegelman was the first to synthesize
infectious RNA in vitro and this led to a series of extremely interesting
and clever experiments revealing Darwinian selection at the level of
molecules in a test tube. Sol recognized the importance of the early RNA
world in the evolution of life and had recently turned his laboratory to a
study of RNA tumor viruses. An immediate bond formed between us and Sol
taught me how to think about science, to identify important problems, and
how to effect their solution.
Although I felt a growing confidence in my abilities in molecular biology, I
was naïve in other areas of biology, notably biophysics. Importantly,
I had a sense early in my career that my interest in biology was eclectic
and that I would need a concomitantly broad background to embrace the
different areas of biology without trepidation. I left to begin a second
postdoctoral fellowship at the National Institutes of Health, working with
Gary Felsenfeld on DNA and chromatin structure. Since I entered medical
school to avoid the draft, I had a military obligation that was fulfilled by
my years at the NIH and was endearingly termed a "yellow beret." Gary was
great, but the NIH was alien, a government reservation with a fixed workday.
As a night person, I found it strange and at some level difficult since I
arrived at noon after all the parking spaces were occupied, left at midnight
and accumulated an increasing number of parking tickets. In the midst of a
molecular hybridization reaction, I was arrested by two FBI agents (the NIH
is a federal reservation) for 100 summonses for parking violations.
As a fellow in Felsenfeld's lab studying how chromatin serves to regulate
gene expression, I formed close friendships that continue to the present. On
the beach at Cold Spring Harbor, I sat with Tom Maniatis and Harold
Weintraub and talked about chromosome replication and gene expression and
within a few hours a bond formed, a respect for one another and for one
another's thinking, that has lasted for thirty years. Hal, unfortunately,
died ten years ago of a brain tumor, but his warmth, his creativity persist.
Sol Spiegelman invited me to return to Columbia as an Assistant Professor in
1974 in the Institute of Cancer Research. I was ecstatic to occupy a lab
and office adjacent to his. Sol had many visitors in those years, and when
he felt bored in a meeting he would excuse himself and hide in my office
where we talked science until his visitors finally gave up and left. I was
studying the structure of genes in chromatin and had the good fortune of
participating in a revolution made possible by recombinant DNA technology. I
spent a great deal of time with Tom Maniatis, who pioneered many of the
techniques in recombinant DNA. Tom left Harvard for Cal Tech, because he was
restricted from performing recombinant DNA experiments in Cambridge,
Massachusetts. We learned how to cut and paste DNA, to isolate genes and to
analyze their anatomy down to the last detail. We recognized that to
understand gene control and gene function, however, required a functional
assay. Within months of establishing my own laboratory in 1974, Michael
Wigler, my first graduate student along with Sol Silverstein, a Professor at
Columbia, developed novel procedures that allowed DNA-mediated
transformation of mammalian cells. Michael, even at this very early stage in
his career, was conceptually and technically masterful and within a few
years he devised procedures that permitted the introduction of virtually any
gene into any cell in culture. He developed a system that not only allowed
for the isolation of genes, but also for detailed analysis of how they
worked. We now had a facile assay to study the sequences regulating gene
expression as well as gene function.
Michael went off to the Cold Spring Harbor Laboratories and simultaneous
with Bob Weinberg at MIT identified the mutant ras gene as the gene
responsible for malignant transformation in many cancer cells. My laboratory
went off in many directions, first identifying the regulatory sequences
responsible for control of specific gene expression. At the same time, a
fellow, Dan Littman, now a Professor at NYU, joined the lab interested in
two molecules that characterize the major classes of T cells. Dan, along
with a student, Paul Maddon, succeeded in exploiting the gene transfer to
isolate these two molecules. As often in science, serendipity heightened the
interest in these molecules: we demonstrated that one of these receptors,
CD4, was the high affinity receptor for HIV, allowing attachment and
infection of immune cells.
This early work on recombinant DNA was a period of enormous excitement, for
it led to a revolution in both thinking and technology in biology. It
provided a new tool for the study of fundamental problems and spurred a new
and valuable industry, biotechnology. We, who were involved at its inception
, were perhaps a bit haughty, aggressive and proud, and were accused by many
of playing "God." As evidence, the press noted that "I baptized my first
child, Adam."
Recombinant DNA aroused a good deal of passion and hostility. The notion of
tinkering with life was thought to endanger life and this cry became one of
the major indictments of modern biology. These experiments raised endless
debate because the idea that genes can be taken out of one organism and
introduced into the chromosome of another is by itself upsetting. The very
notion of the performance of recombinant DNA was linked with the mysterious
and supernatural. This conjured up myths that elicited intense anxiety.
Recombinant DNA, it was feared, would permit biologists to alter individual
species as well as the evolution of species. This controversy emphasized the
fact that advances in science may indeed bring harm as well as benefit. In
the case of recombinant DNA, as François Jacob said, "Apocalypse was
predicted but nothing happened." In fact, with recombinant DNA, only good
things happened. At a practical level, the ability to construct bacteria
replicating eucaryotic genes has allowed for the production of an
increasingly large number of clinically important proteins. At a conceptual
level, gene cloning has permitted a detailed look at the molecular anatomy
of individual genes and from a precise analysis of these genes we have
deduced the informational potential of the gene and the way in which it
dictates the properties of an organism.
At a personal level, the emergence of a new discipline, biotechnology,
introduced me to a world outside of academia. This important excursion
showed me that brilliance is not limited to universities. I met and remain
very close to two dynamic leaders of technology development, Fred Adler and
Joe Pagano. Despite disparate histories, we remain very close and they
continue to fascinate me with lives quite different from that of a
university professor.
In 1982, I began to think about the potential impact of the new molecular
biology and recombinant DNA technology on problems in neuroscience.
Molecular biology was invented to solve fundamental problems in genetics at
a molecular level. With the demystification of the brain, with the
realization that the mind emerges from the brain and that the cells of the
brain often use the very same principles of organization and function as a
humble bacterium or a liver cell, perhaps molecular biology and genetics
could now interface with neuroscience to approach the tenuous relationship
between genes and behavior, cognition, memory, emotion, and perception. This
thinking was the result of a faculty meeting at which Eric Kandel and I
overcame our boredom with administration by talking science. Eric was
characteristically exuberant about his recent data that revealed a
correlation between a simple form of memory in the marine snail, Aplysia and
cellular memory at the level of a specific synapse. Molecular biologists
had encountered cellular memory before in the self-perpetuating control of
gene expression. This led to the realization that this was the moment to
begin to apply the techniques of molecular biology to brain function and I
would attempt to recruit Eric Kandel as my teacher.
A courageous new postdoctoral fellow in my laboratory, Richard Scheller, now
Director of Research for Genentech, was excited about embarking on an
initial effort in molecular neurobiology in a laboratory with absolutely no
expertise in neuroscience. Together with Richard and Eric, we set out to
isolate the genes responsible for the generation of stereotyped patterns of
innate behaviors. All organisms exhibit innate behaviors that are shaped by
evolution and inherited by successive generations that are largely
unmodified by experience or learning. It seemed reasonable to assume that
this innate behavior was dictated by genes that might be accessible to
molecular cloning. It was an exciting and amusing time with myself
unfamiliar with action potentials and Kandel uncomfortable with central
dogma. Richard Scheller exploited the techniques of recombinant DNA to
identify a family of genes encoding a set of related neuropeptides whose
coordinated release is likely to govern the fixed action pattern of
behaviors associated with egg laying. A single gene, the ELH gene, specifies
a polyprotein that is cut into small biologically active peptides such that
individual components of the behavioral array may be mediated by peptides
encoded by one gene.
Watching the story unfold, observing the interface of molecular biology and
neuroscience provided great pleasure. More importantly, this collaboration
formed the basis of a continuing relationship with Eric Kandel, with his
incisive mind, inimitable laugh and boundless energy. In 1986, neuroscience
for me was made even richer when Tom Jessell came along. Tom joined the
faculty at Columbia and was to occupy a lab adjacent to my own. Not
surprisingly, the lab was not ready and I had the great pleasure of hosting
Tom in my own laboratory and this forged a long-lasting scientific and
personal relationship. Jessell, the understated British scientist with a wry
wit and piercing mind, joined a fellow in my laboratory, David Julius, now
at the University of California at San Francisco, and together they devised
a clever assay for the isolation of genes encoding the neurotransmitter
receptors. These experiments, which might have been the last performed by
the hands of Jessell, led to the isolation of genes encoding the seven
transmembrane domain serotonin receptor, 5HT1C, and more generally provided
an expression system that permitted the identification of functional genes
that encode receptors in the absence of any information on the nature of the
protein sequence. With Kandel one floor above, and Jessell next door, there
was no departure from neuroscience. I was surrounded and I did not want to
escape. I was beginning to feel that neuroscience was indeed an appropriate
occupation for a molecular biologist. To quote Woody Allen, a fellow New
Yorker, "The brain is my second favorite organ."
In the late 1980's I became fascinated in the problem of perception: how the
brain represents the external world. I was struck by observations from
animal behavior that what an organism detects in its environment is only
part of what is around it and that part can differ in different organisms.
The brain functions then not by recording an exact image of the world but by
creating its own selective picture. Biological reality will therefore
reflect the particular representation of the external world that a brain is
able to build and a brain builds with genes. If genes are indeed the
arbiters of what we perceive from the outside world then it follows that an
understanding of the function of these genes could provide insight into how
the external world is represented in the brain. Together with Linda Buck, a
creative fellow in the lab, we began to consider how the chemosensory world
is represented in the brain. The problem of olfaction was a perfect
intellectual target for a molecular biologist. How we recognize the vast
diversity of odorous molecules posed a fascinating problem. We assumed that
the solution would involve a large family of genes and Linda Buck devised a
creative approach that indeed identified the genes encoding the receptors
that recognize the vast array of odorants in the environment. Linda came to
me with the experimental data late one night, exuberant, and I fell
uncharacteristically silent. There were 1,000 odorant receptor genes in the
rat genome, the largest family of genes in the chromosome and this provided
the solution to the problem of the diversity of odor recognition. More
importantly, the identification of these 10,000 genes and their expression
revealed an early and unanticipated logic of olfaction. Indeed, the
subsequent use of these genes to manipulate the genome of mice has afforded
a view of how the olfactory world could be represented in the brain, how
genes shape our perception of the sensory environment. From that late night
moment to the present, it has been a joy to watch this story unfold.
It is this work for which Linda Buck and I share the profound honor and good
fortune of having been awarded the Nobel Prize in Physiology or Medicine.
But there are deeper, more human joys, two sons, Adam and Jonathan, my
sister, Linda, a very close coterie of friends, and a new love. Watching,
contributing to the growth of my children is not only moving but humbling
and puts my intense life in science in perspective. Often this intensity,
bordering on obsession, distracted me from fathering and this is a regret.
But my sons have emerged from a frenetic teenage into very human college
students, extremely unlikely to pursue a career in science. My sister
remains a close and dedicated member of an increasingly small family. A new
love, Cori Bargmann, a behavioral geneticist now at Rockefeller University,
has entered my world. Her intensity for science hides a knowledge and
passion for books, music, and art. I have learned much from her but most
importantly, Cori has shown me how to combine intellectual intensity with
humanity and warmth.
Finally, the Nobel Prize was awarded to me not as a man, but for my work, a
work of science that derives from the efforts of many brilliant students as
well as from the incisive teachings of devoted colleagues. I take equal
pride in the science that has been accomplished in the laboratory as in the
scientists that have trained with me and are now independently contributing
to our understanding of biology. I therefore feel that I can only accept the
Nobel Prize in trust, as a representative of a culture of science in my
laboratory and at Columbia University. I am deeply grateful for this culture.
From Les Prix Nobel. The Nobel Prizes 2004, Editor Tore Frängsmyr, [
Nobel Foundation], Stockholm, 2005
This autobiography/biography was written at the time of the award and later
published in the book series Les Prix Nobel/Nobel Lectures. The information
is sometimes updated with an addendum submitted by the Laureate.
find it both interesting and enlightening:)))...BTW, it sounds Richard Axel
is a lot nicer than what I/we have heard...or in another word, his cruelty
is rooted in his obsession with science and indifference to humanity:))); As
well, it is pretty...he noted Cori but left his ex out...pretty human or
not human?
Autobiography
Richard AxelNew York City is my world. I was born in Brooklyn, the first
child of immigrant parents whose education was disrupted by the Nazi
invasion of Poland. Although not themselves learned, my parents shared a
deep respect for learning. I grew up in a home rich in warmth, but empty of
books, art or music. My early life and education were centered on the
streets of Brooklyn. Stickball, baseball with a pink ball and broom handle,
and schoolyard basketball were my culture. In stickball, a ball hit the
distance to one manhole cover was a single, and four manhole covers, a home
run, a Nobel Prize. My father was a tailor. My mother, although quick and
incisive, did not direct her mind to intellectual pursuits and I had not
even the remotest thought of a career in academia. I was happy on the courts
. In those days, we worked at a relatively young age. At eleven, I was a
messenger, delivering false teeth to dentists. At twelve, I was laying
carpets, and at thirteen, I was serving corned beef and pastrami in a local
delicatessen. Vladimir, the Russian chef, was the first to expose me to
Shakespeare which he recited as we sliced cabbage heads for coleslaw.
My local high school had the best basketball team in Brooklyn but the
Principal of my grade school had a vision different from my own and insisted
that I attend Stuyvesant High School, far away in Manhattan. Stuyvesant
High advertised itself as a school for intellectually gifted boys but had
the worst basketball team in the city. I was unhappy about the prospect of
attending for it seemed antithetical to my self-image. Shortly after I
entered, however, my world changed. I embraced the culture and aesthetics of
Manhattan. The world of art, books and music opened before me and I
devoured it. In school, I heard bits of an opera for the first time. I
remember it distinctly, the Letter Duet from Mozart's Marriage of Figaro.
The next night I attended Tannhäuser at the Metropolitan Opera and thus
began a love affair, bordering on an obsession, that has had no end. Twice
a week, I stood on line for standing room tickets at the Metropolitan Opera
where I was exposed to a cult of similarly obsessed but far more
knowledgeable afficionados who taught me the intricate nuances of this rich
genre. The great Italian tenor, Franco Corelli, would serve us coffee as we
waited and the diva, Joan Sutherland, would invite us backstage.
On other days, I would read in a most beautifully appointed place, the
Reading Room of the Central New York Public Library on 42nd Street. One
passes the pair of sculpted lions, ascends a flight of stairs into a huge
high-ceilinged room of impressive silence where I read incessantly without
direction but with a newfound fascination that made up for years of
illiteracy. I met a coterie of library dwellers, men and women of New York,
who spent all of their days in the Reading Room. I did not know who they
were or how they came to be there, but they had an insight and understanding
of literature that amazed and still perplexes me and they were my teachers.
This was New York for me, a city of the culturally obsessed that opened up
before me and framed my new world.
To support a seemingly extravagant life for a young high school student, I
worked. I used my skills as a waiter in a delicatessen in Brooklyn, to wait
tables in the cafes and nightspots of Greenwich Village. In the sixties, the
Village was the home of the beat generation that through music and poetry
and ultimately protest translated discord into meaningful changes in both
America and the world. Stuyvesant High School was on the fringe of Greenwich
Village and some of its teachers were artists, writers, performers who
fueled the politically-fired student body, many the sons of Marxist
immigrants. With this array of artistic faculty Stuyvesant nourished my new
and voracious appetite.
But old worlds die hard. I continued to play basketball in high school and
this led to a most memorable and humbling experience. I came onto the court
as the starting center, and the center on the opposing team from Power
Memorial High School lumbered out on the court, a lanky 7 foot 2 inch
sixteen year old. When I was first passed the ball, he put his hands in
front of my face, looked at me and asked, "What are you going to do,
Einstein?" I did rather little. He scored 54 points and I scored two. He was
the young Lew Alcindor, later known as Karim Abdul Jabar, who went on to be
among the greatest basketball legends and I became a neurobiologist.
My decision to remain in New York and attend Columbia College revealed the
provincial but endearing quality of my family. When I chose to accept a
gracious scholarship offered by Columbia, my father was disappointed. It was
a fact well known that the brightest children of Brooklyn immigrants
attended City College. My freshman year at Columbia, I lived with abandon.
The opera, the arts, the freedom, the protest left little time for study. In
the first semester, I met a student from Tennessee, Kevin Brownlee, who
remains a dear friend and is now a Professor of Medieval French at the
University of Pennsylvania. Brownlee urged me to redirect this intensity to
learning. The world of the arts will remain, but my time at Columbia
University was limited. Once again, a new world opened before me. With Kevin
as my guide, I became a dedicated, even obsessed, student. My life was
spent in a small room lined with volumes of Keats' poetry at the Columbia
Library and I immersed myself in my studies. The study of literature at
Columbia in the sixties was exciting in the presence of the poet, Kenneth
Koch, the critics, Lionel Trilling, Moses Hadas, and Jacques Barzun. It was
largely chance, however, that led me to biology.
To support myself in college, I obtained a job washing glassware in the
laboratory of Bernard Weinstein, a Professor of Medicine at Columbia
University. Bernie was working on the universality of the genetic code. The
early sixties was a time shortly after the elucidation of the structure of
DNA and the realization that DNA is the repository of all information and
from which all information flows. The genetic code had just been deciphered
and the central dogma was complete. I was fascinated by the new molecular
biology with its enormous explanatory power. I was a terrible glassware
washer because I was far more interested in experiments than dirty flasks. I
was fired and was rehired as a Research Assistant and Bernie spent endless
hours patiently teaching this scientifically naïve, but intensely
interested young student. I was torn between literature and science. Dubious
about my literary ambitions and fascinated by molecular biology, I decided
to attend graduate school in genetics.
My plans were thwarted by an unfortunate war and to assure deferment from
the military, I found myself a misplaced medical student at Johns Hopkins
University School of Medicine. I entered medical school by default. I was a
terrible medical student, pained by constant exposure to the suffering of
the ill and thwarted in my desire to do experiments. My clinical
incompetence was immediately recognized by the faculty and deans. I could
rarely, if ever, hear a heart murmur, never saw the retina, my glasses fell
into an abdominal incision and finally, I sewed a surgeon's finger to a
patient upon suturing an incision. It was during this period of incompetence
and disinterest that I met another extremely close friend, Frederick Kass,
now a Professor of Psychiatry at Columbia University. Fred was an unusual
medical student, a Texan with a degree in art history from Harvard, who
remains a kindred spirit.
It was a difficult time, but I was both nurtured and protected by Howard
Dintzis, Victor McCusick, and Julie Krevins, three professors at Johns
Hopkins who somehow saw and respected my conflict. Without them, there is
little question that I would not have been tolerated but they urged the
deans to come up with a solution. I was allowed to graduate medical school
early with an M.D. if I promised never to practice medicine on live patients
. I returned to Columbia as an intern in Pathology where I kept this promise
by performing autopsies. After a year in Pathology, I was asked by Don King
, the Chairman of Pathology, never to practice on dead patients.
Finally, I was afforded the opportunity to pursue molecular biology in
earnest. I joined the laboratory of Sol Spiegelman in the Department of
Gentics at Columbia University. Spiegelman was a short, incisive, witty man
with a tongue as sharp as his mind. Spiegelman was the first to synthesize
infectious RNA in vitro and this led to a series of extremely interesting
and clever experiments revealing Darwinian selection at the level of
molecules in a test tube. Sol recognized the importance of the early RNA
world in the evolution of life and had recently turned his laboratory to a
study of RNA tumor viruses. An immediate bond formed between us and Sol
taught me how to think about science, to identify important problems, and
how to effect their solution.
Although I felt a growing confidence in my abilities in molecular biology, I
was naïve in other areas of biology, notably biophysics. Importantly,
I had a sense early in my career that my interest in biology was eclectic
and that I would need a concomitantly broad background to embrace the
different areas of biology without trepidation. I left to begin a second
postdoctoral fellowship at the National Institutes of Health, working with
Gary Felsenfeld on DNA and chromatin structure. Since I entered medical
school to avoid the draft, I had a military obligation that was fulfilled by
my years at the NIH and was endearingly termed a "yellow beret." Gary was
great, but the NIH was alien, a government reservation with a fixed workday.
As a night person, I found it strange and at some level difficult since I
arrived at noon after all the parking spaces were occupied, left at midnight
and accumulated an increasing number of parking tickets. In the midst of a
molecular hybridization reaction, I was arrested by two FBI agents (the NIH
is a federal reservation) for 100 summonses for parking violations.
As a fellow in Felsenfeld's lab studying how chromatin serves to regulate
gene expression, I formed close friendships that continue to the present. On
the beach at Cold Spring Harbor, I sat with Tom Maniatis and Harold
Weintraub and talked about chromosome replication and gene expression and
within a few hours a bond formed, a respect for one another and for one
another's thinking, that has lasted for thirty years. Hal, unfortunately,
died ten years ago of a brain tumor, but his warmth, his creativity persist.
Sol Spiegelman invited me to return to Columbia as an Assistant Professor in
1974 in the Institute of Cancer Research. I was ecstatic to occupy a lab
and office adjacent to his. Sol had many visitors in those years, and when
he felt bored in a meeting he would excuse himself and hide in my office
where we talked science until his visitors finally gave up and left. I was
studying the structure of genes in chromatin and had the good fortune of
participating in a revolution made possible by recombinant DNA technology. I
spent a great deal of time with Tom Maniatis, who pioneered many of the
techniques in recombinant DNA. Tom left Harvard for Cal Tech, because he was
restricted from performing recombinant DNA experiments in Cambridge,
Massachusetts. We learned how to cut and paste DNA, to isolate genes and to
analyze their anatomy down to the last detail. We recognized that to
understand gene control and gene function, however, required a functional
assay. Within months of establishing my own laboratory in 1974, Michael
Wigler, my first graduate student along with Sol Silverstein, a Professor at
Columbia, developed novel procedures that allowed DNA-mediated
transformation of mammalian cells. Michael, even at this very early stage in
his career, was conceptually and technically masterful and within a few
years he devised procedures that permitted the introduction of virtually any
gene into any cell in culture. He developed a system that not only allowed
for the isolation of genes, but also for detailed analysis of how they
worked. We now had a facile assay to study the sequences regulating gene
expression as well as gene function.
Michael went off to the Cold Spring Harbor Laboratories and simultaneous
with Bob Weinberg at MIT identified the mutant ras gene as the gene
responsible for malignant transformation in many cancer cells. My laboratory
went off in many directions, first identifying the regulatory sequences
responsible for control of specific gene expression. At the same time, a
fellow, Dan Littman, now a Professor at NYU, joined the lab interested in
two molecules that characterize the major classes of T cells. Dan, along
with a student, Paul Maddon, succeeded in exploiting the gene transfer to
isolate these two molecules. As often in science, serendipity heightened the
interest in these molecules: we demonstrated that one of these receptors,
CD4, was the high affinity receptor for HIV, allowing attachment and
infection of immune cells.
This early work on recombinant DNA was a period of enormous excitement, for
it led to a revolution in both thinking and technology in biology. It
provided a new tool for the study of fundamental problems and spurred a new
and valuable industry, biotechnology. We, who were involved at its inception
, were perhaps a bit haughty, aggressive and proud, and were accused by many
of playing "God." As evidence, the press noted that "I baptized my first
child, Adam."
Recombinant DNA aroused a good deal of passion and hostility. The notion of
tinkering with life was thought to endanger life and this cry became one of
the major indictments of modern biology. These experiments raised endless
debate because the idea that genes can be taken out of one organism and
introduced into the chromosome of another is by itself upsetting. The very
notion of the performance of recombinant DNA was linked with the mysterious
and supernatural. This conjured up myths that elicited intense anxiety.
Recombinant DNA, it was feared, would permit biologists to alter individual
species as well as the evolution of species. This controversy emphasized the
fact that advances in science may indeed bring harm as well as benefit. In
the case of recombinant DNA, as François Jacob said, "Apocalypse was
predicted but nothing happened." In fact, with recombinant DNA, only good
things happened. At a practical level, the ability to construct bacteria
replicating eucaryotic genes has allowed for the production of an
increasingly large number of clinically important proteins. At a conceptual
level, gene cloning has permitted a detailed look at the molecular anatomy
of individual genes and from a precise analysis of these genes we have
deduced the informational potential of the gene and the way in which it
dictates the properties of an organism.
At a personal level, the emergence of a new discipline, biotechnology,
introduced me to a world outside of academia. This important excursion
showed me that brilliance is not limited to universities. I met and remain
very close to two dynamic leaders of technology development, Fred Adler and
Joe Pagano. Despite disparate histories, we remain very close and they
continue to fascinate me with lives quite different from that of a
university professor.
In 1982, I began to think about the potential impact of the new molecular
biology and recombinant DNA technology on problems in neuroscience.
Molecular biology was invented to solve fundamental problems in genetics at
a molecular level. With the demystification of the brain, with the
realization that the mind emerges from the brain and that the cells of the
brain often use the very same principles of organization and function as a
humble bacterium or a liver cell, perhaps molecular biology and genetics
could now interface with neuroscience to approach the tenuous relationship
between genes and behavior, cognition, memory, emotion, and perception. This
thinking was the result of a faculty meeting at which Eric Kandel and I
overcame our boredom with administration by talking science. Eric was
characteristically exuberant about his recent data that revealed a
correlation between a simple form of memory in the marine snail, Aplysia and
cellular memory at the level of a specific synapse. Molecular biologists
had encountered cellular memory before in the self-perpetuating control of
gene expression. This led to the realization that this was the moment to
begin to apply the techniques of molecular biology to brain function and I
would attempt to recruit Eric Kandel as my teacher.
A courageous new postdoctoral fellow in my laboratory, Richard Scheller, now
Director of Research for Genentech, was excited about embarking on an
initial effort in molecular neurobiology in a laboratory with absolutely no
expertise in neuroscience. Together with Richard and Eric, we set out to
isolate the genes responsible for the generation of stereotyped patterns of
innate behaviors. All organisms exhibit innate behaviors that are shaped by
evolution and inherited by successive generations that are largely
unmodified by experience or learning. It seemed reasonable to assume that
this innate behavior was dictated by genes that might be accessible to
molecular cloning. It was an exciting and amusing time with myself
unfamiliar with action potentials and Kandel uncomfortable with central
dogma. Richard Scheller exploited the techniques of recombinant DNA to
identify a family of genes encoding a set of related neuropeptides whose
coordinated release is likely to govern the fixed action pattern of
behaviors associated with egg laying. A single gene, the ELH gene, specifies
a polyprotein that is cut into small biologically active peptides such that
individual components of the behavioral array may be mediated by peptides
encoded by one gene.
Watching the story unfold, observing the interface of molecular biology and
neuroscience provided great pleasure. More importantly, this collaboration
formed the basis of a continuing relationship with Eric Kandel, with his
incisive mind, inimitable laugh and boundless energy. In 1986, neuroscience
for me was made even richer when Tom Jessell came along. Tom joined the
faculty at Columbia and was to occupy a lab adjacent to my own. Not
surprisingly, the lab was not ready and I had the great pleasure of hosting
Tom in my own laboratory and this forged a long-lasting scientific and
personal relationship. Jessell, the understated British scientist with a wry
wit and piercing mind, joined a fellow in my laboratory, David Julius, now
at the University of California at San Francisco, and together they devised
a clever assay for the isolation of genes encoding the neurotransmitter
receptors. These experiments, which might have been the last performed by
the hands of Jessell, led to the isolation of genes encoding the seven
transmembrane domain serotonin receptor, 5HT1C, and more generally provided
an expression system that permitted the identification of functional genes
that encode receptors in the absence of any information on the nature of the
protein sequence. With Kandel one floor above, and Jessell next door, there
was no departure from neuroscience. I was surrounded and I did not want to
escape. I was beginning to feel that neuroscience was indeed an appropriate
occupation for a molecular biologist. To quote Woody Allen, a fellow New
Yorker, "The brain is my second favorite organ."
In the late 1980's I became fascinated in the problem of perception: how the
brain represents the external world. I was struck by observations from
animal behavior that what an organism detects in its environment is only
part of what is around it and that part can differ in different organisms.
The brain functions then not by recording an exact image of the world but by
creating its own selective picture. Biological reality will therefore
reflect the particular representation of the external world that a brain is
able to build and a brain builds with genes. If genes are indeed the
arbiters of what we perceive from the outside world then it follows that an
understanding of the function of these genes could provide insight into how
the external world is represented in the brain. Together with Linda Buck, a
creative fellow in the lab, we began to consider how the chemosensory world
is represented in the brain. The problem of olfaction was a perfect
intellectual target for a molecular biologist. How we recognize the vast
diversity of odorous molecules posed a fascinating problem. We assumed that
the solution would involve a large family of genes and Linda Buck devised a
creative approach that indeed identified the genes encoding the receptors
that recognize the vast array of odorants in the environment. Linda came to
me with the experimental data late one night, exuberant, and I fell
uncharacteristically silent. There were 1,000 odorant receptor genes in the
rat genome, the largest family of genes in the chromosome and this provided
the solution to the problem of the diversity of odor recognition. More
importantly, the identification of these 10,000 genes and their expression
revealed an early and unanticipated logic of olfaction. Indeed, the
subsequent use of these genes to manipulate the genome of mice has afforded
a view of how the olfactory world could be represented in the brain, how
genes shape our perception of the sensory environment. From that late night
moment to the present, it has been a joy to watch this story unfold.
It is this work for which Linda Buck and I share the profound honor and good
fortune of having been awarded the Nobel Prize in Physiology or Medicine.
But there are deeper, more human joys, two sons, Adam and Jonathan, my
sister, Linda, a very close coterie of friends, and a new love. Watching,
contributing to the growth of my children is not only moving but humbling
and puts my intense life in science in perspective. Often this intensity,
bordering on obsession, distracted me from fathering and this is a regret.
But my sons have emerged from a frenetic teenage into very human college
students, extremely unlikely to pursue a career in science. My sister
remains a close and dedicated member of an increasingly small family. A new
love, Cori Bargmann, a behavioral geneticist now at Rockefeller University,
has entered my world. Her intensity for science hides a knowledge and
passion for books, music, and art. I have learned much from her but most
importantly, Cori has shown me how to combine intellectual intensity with
humanity and warmth.
Finally, the Nobel Prize was awarded to me not as a man, but for my work, a
work of science that derives from the efforts of many brilliant students as
well as from the incisive teachings of devoted colleagues. I take equal
pride in the science that has been accomplished in the laboratory as in the
scientists that have trained with me and are now independently contributing
to our understanding of biology. I therefore feel that I can only accept the
Nobel Prize in trust, as a representative of a culture of science in my
laboratory and at Columbia University. I am deeply grateful for this culture.
From Les Prix Nobel. The Nobel Prizes 2004, Editor Tore Frängsmyr, [
Nobel Foundation], Stockholm, 2005
This autobiography/biography was written at the time of the award and later
published in the book series Les Prix Nobel/Nobel Lectures. The information
is sometimes updated with an addendum submitted by the Laureate.
k*r
4 楼
就补看09年那部就行了，这是reboot的新系列，更老的不需要。当然你要是有时间都看
了的话这一部里的一些细节看了会明白是对老一代的致敬。
了的话这一部里的一些细节看了会明白是对老一代的致敬。
a*n
5 楼
代笔啊
D*D
6 楼
no,it is pretty much an independent story, you will have no problem to
understand the movie
【在 v**c 的大作中提到】
: 想去看star trek，但是之前的系列一部都没看过，需不需要先补看至少其中的某一部
: ？哪一部？
understand the movie
【在 v**c 的大作中提到】
: 想去看star trek，但是之前的系列一部都没看过，需不需要先补看至少其中的某一部
: ？哪一部？
f*g
7 楼
六迹是几个写手各写一个中篇之类的，妄语似乎也有一部，不算正经作品
【在 S**********u 的大作中提到】
: 尼玛一本丫都掌控不好
【在 S**********u 的大作中提到】
: 尼玛一本丫都掌控不好
D*S
8 楼
还是最好补看下2009年的,否则最起码不明白怎么能同时出现年轻/老年Spock.
【在 D******D 的大作中提到】
: no,it is pretty much an independent story, you will have no problem to
: understand the movie
【在 D******D 的大作中提到】
: no,it is pretty much an independent story, you will have no problem to
: understand the movie
s*r
9 楼
这两篇里，明显六迹写得不错啊。道缘浮图没看出啥亮点。
S*d
10 楼
Better know who Kahn is.
★ 发自iPhone App: ChineseWeb 7.8
【在 v**c 的大作中提到】
: 想去看star trek，但是之前的系列一部都没看过，需不需要先补看至少其中的某一部
: ？哪一部？
★ 发自iPhone App: ChineseWeb 7.8
【在 v**c 的大作中提到】
: 想去看star trek，但是之前的系列一部都没看过，需不需要先补看至少其中的某一部
: ？哪一部？
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