TWO LIVES AND THE DOUBLE HELIX:
Okazaki Tsuneko (1933—), Molecular Biologist
by Miwae Yamazaki
Working in the United States and Japan as part of a
husband-wife research team, Tsuneko Okazaki helped discover the "Okazaki
fragments" that enable DNA to replicate. On the heels of this triumph,
however, came the ultimate tragedy of losing her partner in work and in
life. How she overcame this loss and numerous other obstacles to make her
mark on the world of molecular biology is one of science's truly inspiring
All living organisms require a kind of blueprint consisting
of genetic information. The human body is made up of about 60 trillion
cells, and each one of these cells contains within it the genetic blueprint
that makes us human—the human genome. The aim of my research over the
years has been to determine how that information is replicated.
In Search of Unchanging Truths
I was born on June 7, 1933, in Nagoya. I grew up surrounded
by my mother, father (a surgeon), older sister, and two younger brothers.
World War II broke out in East Asia when I was in second grade. By the time
I was in fifth and sixth grade, it was almost impossible to concentrate on
one's studies. Japanese cities were being bombed to ashes, and there was a
serious shortage of both food and labor. As a result, many children were
busy working in the fields or performing other chores.
In the summer of 1945, when I was in sixth grade, the war
came to an end. I will never forget seeing the textbooks we had been using
heavily censored with black ink, as ordered by the administrative
headquarters of the Allied Occupation forces. We were told that much of what
we had been taught up until then was untrue, and our faith in the state
seemed to collapse overnight.
As a junior high school student, I was fond of science and
mathematics. When I was in high school, my father let me look through a
microscope and watch in amazement as an antibiotic prevented bacteria from
multiplying. My father himself was deeply impressed to see the effects of
the antibiotics that began to be imported soon after the war ended; cholera
and tuberculosis patients who until then would most likely have died were
recovering before his eyes. That was what first stimulated my interest in
In 1952, I enrolled in the Nagoya University School of
Science. As a result of the educational reforms carried out after the war,
junior high school and high school had been made coeducational, and the
national universities, including Nagoya's, had opened their gates to women.
It seems to me that the confusion and insecurity that seized me when I
sensed all our values being overturned led me to search for unchanging
truths. And in those days, when even school buildings were in short supply,
I felt fortunate just to be able to study in peace.
The Code of Life
As I studied, I found myself particularly drawn by
developmental biology, or embryology, which focuses on the chemical,
physiological, and morphological processes between the fertilization of an
egg and the birth of an individual organism. I wanted to understand what
sort of substances controlled the formation of tissues and organs to create
an individual organism, and how the genetic information on which this
process is based is passed from parents to offspring. At that time, however,
Japanese universities were ill-equipped to teach anything beyond Gregor
Mendel's work on the inherited traits of pea plants.
All genetic information needed for the development of each
individual organism is contained in the molecules of deoxyribonucleic
acid—commonly known as DNA—which are chemical codes for the
creation of various proteins. DNA contains four chemical components referred
to as bases—adenine (A), guanine (G), thymine (T), and cytosine (C)
—which, lined up in various combinations, create the codes for the 20
different amino acids. These amino acids, in turn, link together in chains
of anywhere from several dozen to several hundred to make proteins.
Depending on how the four bases of the DNA molecule are arranged, the
combination of amino acids changes, resulting in different proteins with
different properties and functions. The information thus encoded in the
genome even includes instructions on faithfully and reliably passing that
information (the whole genome) to the cells and individuals of the next
generation. The study of life and its underlying mechanisms at the level of
molecules is called molecular biology, and when I was a student the field
was still very new.
In 1953, James Watson and Francis Crick discovered that the
four bases that form the two chains of the DNA molecule link together in
pairs—A with T, and G with C—forming a beautiful structure called
a double helix. It was this discovery that marked the true beginning of
molecular biology as a field in its own right. I continued on to graduate
school at Nagoya University, hoping to learn more about how DNA
Solving the Puzzle of DNA Replication
Each of us receives two complete genomes, or sets of
chromosomes, from our parents, one from our mother and one from our father.
In the case of human beings, it takes 60 trillion cell divisions for the
fertilized egg to develop into a fully formed organism, and each time, the
two genomes are copied with perfect accuracy. This copying process is
carried out very quickly and accurately within each tiny cell. In the 1950s,
the mechanism of the process was still a riddle.
In 1956, I married Reiji Okazaki, who was three years my
senior at the university. That was also the year that the American scientist
Arthur Kornberg succeeded in extracting from the bacterium Escherichia
coli an enzyme that synthesizes a new DNA molecule from the old. It was
a major discovery for which he was later awarded the Nobel Prize in
physiology and medicine.
My husband Reiji submitted an application to do research at
Stanford University under Dr. Kornberg, the world's leading expert in DNA
synthesis. Fortunately, I was also admitted to Stanford. Beginning in late
1961, the two of us spent a very productive year and three months carrying
out research under Dr. Kornberg.`
There was a problem when it came to explaining DNA synthesis
with the enzyme Kornberg had discovered, DNA polymerase. The DNA molecule
consists of two complementary, oppositely oriented chains, or strands, which
are joined to make a kind of ladder—the double helix. When DNA
replicates, the two strands of the double helix begin to separate, or
"unzip," and as they do, a new complementary "daughter strand" grows along
each original "parental strand." This yields two DNA molecules, each
containing a parental strand and a daughter strand, and each identical to
the original molecule (referred to as the template). But with Kornberg's
enzyme, it was clear that new strands only grew in one chemical direction.
This worked fine for one of the parental strands; growth of the
complementary daughter strand would proceed from one end of the unzipping
DNA molecule in the direction of the "replication fork" until the entire
molecule was unzipped and a new molecule synthesized. But since the other
parental strand had the opposite chemical orientation, how could a new chain
grow along it to synthesize the second DNA molecule? Some scientists
suspected that a different enzyme, as yet undiscovered, synthesized the
second new strand. After my husband and I returned to Japan in 1963, we
concentrated on unraveling this mystery.
Because the natural process of DNA replication takes place in
an instant, we struggled to develop techniques that would allow us to
analyze the process in a test tube. Meanwhile, the birth of our first child
not long after our return to Japan obliged me to juggle research and child
rearing. Eventually, however, we discovered that in the earliest stage of
replication, small fragments of DNA are formed. This led us to hypothesize
that the problematical daughter strand was synthesized through a repeated
process in which small fragments grew, one after another, and were later
joined. This is how it works: As the template DNA unzips and exposes a
segment of the parental strand, a complementary segment is synthesized,
growing in the opposite direction from the replication fork. As more of the
template unzips, another segment is formed, and so forth, until the entire
template is unzipped. In this way, a daughter strand is synthesized on each
of the two parental strands with the help of just the one DNAsynthesizing
enzyme, creating two DNA molecules. This was hailed as a major finding. The
small DNA fragments were given the name "Okazaki fragments," which is how
they appear in biochemistry textbooks around the world today.
On My Own
After this important discovery, we decided to try to isolate
the "primer" that triggers the synthesis of the Okazaki fragments. Because
the substance breaks down quickly, and the small fragments of DNA link up
neatly leaving no clues behind, analysis was extremely difficult.
Then in 1975, in the midst of this research, tragedy struck.
My husband Reiji became ill and died. Our son was 12 years old, and our
daughter was only two and a half. I had lost my research partner of 20
years, and I doubted whether I had the courage to continue on my own.
In the midst of my grief, I received a letter from Dr.
Kornberg. He urged me not to give up what I did best and reminded me that
through my research I could support myself and my children while staying
connected with the rest of the scientific community. I resolved to continue,
and three years later, to my great joy, I finally succeeded in separating
and analyzing the substance that triggers the formation of the Okazaki
As a woman scientist, I faced serious obstacles, but with the
help and support of many people, including the graduate students who worked
with me, I was able to continue the research we began with my husband. I
also owe a great deal to those who looked after my children over the years.
Were it not for all these people, I would never have been able to continue
my research these many years. And had I not continued my research, I would
never have met all the wonderful people who have helped me along the
The Committee for the Encouragement of Future Scientists. Blazing a Path: Japanese Women’s Contributions to Modern Science. Tokyo: 2001. include("../includes/resfooter.php") ?>