I
was born in New York City in 1918 into a family that had a number of artistic
people among its members. My father's brother and a sister's husband were probably
the best known. The latter, Ivan Olinsky, taught for many years at the Art Students'
League in New York City. I have been told that my paternal grandfather professionally
made artistic decorations in peoples' homes. The propensity for artistic endeavors
extended to my generation and beyond.

My mother was an excellent pianist and organist and it was one of her hopes
that I would become a professional pianist. As a youth I was entered into "Music
Week" competitions in New York City. I had some modest success, but found at
an early age that I had no taste for public performance. On the other hand,
I was strongly attracted to science as a lifelong career at an early age.

I had the privilege of attending schools in the New York City public school
system. Their standards of education, character building and discipline were
very high and I, most certainly, benefited from them. They separated out the
more advanced students and permitted them to progress at their own pace. In
my case, this occasionally led to some curious circumstances. In my senior year
in high school (Abraham Lincoln), the girls would join the boys to practice
dancing. I was 14 years old at the time and the girls were the usual 17-18 years
old. The physical discrepancy between this 14 year old boy and 17-18 year old
girls was considerable. Their first reaction was incredulity but after a while
they got used to my presence and even danced with me. I took the chemistry and
physics courses that were available, both taught by the same man. He recognized
my interests and was very encouraging to me.

I enjoyed a number of sports that I participated in at every opportunity, swimming
in the ocean nearby, a game called single-wall handball, played with a little
hard black ball and well-known mainly in some metropolitan areas, touch football
whose rules eliminate the bruises from tackling and ice-skating that was facilitated
by the flooding of a huge parking lot by the local fire department.

I entered the City College of New York in 1933 and, at first, found it to be
a bit of a struggle. Their academic standards were very high and they had a
concentration of the best students in New York City. In addition, I spent three
hours a day traveling on the subway system to and from home. This marked the
end of piano practicing. City College had no tuition fee. The only financial
requirement was one dollar per year for a library card. At the College, there
were broad course requirements for all students that ranged through mathematics,
the physical sciences, the social sciences and literature. There were even two
years of compulsory public speaking courses. I studied, in addition to the requirements,
some additional mathematics, some physics, and much chemistry and biology. The
year after graduation from City College was spent at Harvard University in the
study of biology, for which I received a master's degree, M.A., in 1938.

After a brief hiatus, I went to work with the New York State Health Department
in Albany. While there, I had the opportunity to spend some time again at the
piano. At the time I was in Albany, the fluoridation of drinking water was getting
underway. I developed a procedure for determining the amount of fluorine in
water supplies that became a standard method. This was my first modest contribution
to science.

It was my intention to save enough money while at the Health Department to return
to graduate school. This I did, and I entered the Chemistry Department of the
University of Michigan in 1940 where I met my wife, Isabella Lugoski, whom I
married in 1942, at an adjoining laboratory desk the first day that I went to
physical chemistry class. We were both attracted to physical chemistry and took
our degrees with Professor Lawrence O. Brockway whose speciality was the investigation
of gas-phase molecular structure by means of electron diffraction. Although
my Ph.D. degree was awarded in 1944, I had completed all my work for it during
the summer of 1943 and went off to work on the Manhattan Project at the University
of Chicago. Isabella joined me on this project a few months later.

In 1944, we returned to the University of Michigan, I went to work on a project
of the Naval Research Laboratory and Isabella as an instructor in the Chemistry
Department. While at the University of Michigan, I performed some experiments
on the structure of monolayers of long-chain hydrocarbon films involved in the
boundary lubrication of metallic surfaces. I also derived a theory that explained
the electron diffraction patterns obtained from the oriented monolayers.

In 1946 we both went to work permanently in Washington for the Naval Research
Laboratory. Our interest continued in developing the quantitative aspects of
gas electron diffraction analysis. The solution of a key problem that arose
in such analyses had evident implications for crystal structure analysis and,
in fact, other areas of structure determination. At about the time that these
matters were developing, Herbert Hauptman joined us at the Naval Research Laboratory
and we decided to pursue the implications for crystal structures. This eventually
led to the development of the direct methods for crystal structure analysis
with the major part of the mathematical foundations and procedural insights
established in the early 1950's.

While all this was going on and with hardly missing a step from her research
activities, Isabella mothered three children, Louise in 1946, Jean in 1950,
and Madeleine in 1955. Louise is a theoretical chemist, Jean an organic chemist
and Madeleine is a museum specialist trained in geology.

The initial applications of the procedure for structure determination for centrosymmetric
crystals involving probability measures and formulas derived from the joint
probability distribution were performed in the middle 1950's in collaboration
with colleagues at the U.S. Geological Survey. Then, in the second half of the
1950's, through the efforts of Isabella Karle, an experimental X-ray diffraction
facility was established in our own laboratory.

During the 1960's, there was an intensive program in my laboratory to develop
a procedure for crystal structure determination of broad applicability that
would encompass noncentrosymmetric as well as centrosymmetric crystals. Largely
through the efforts of Isabella Karle, such a procedure was developed and called
the symbolic addition procedure. This procedure had its origins in the theoretical
work and the experience in practical application of the 1950's, but it also
required some new procedural insights and some additional theoretical work to
make it efficient and broadly applicable and avoid the pitfalls that easily
arise when optimal pathways through a procedure must be chosen on the basis
of probability measures. The first application of the symbolic addition procedure
was published in 1963 and the first essentially equal atom noncentrosymmetric
crystal structure to be solved by direct phase determination was published in
1964. This was followed by a number of exciting applications and toward the
end of the 1960's many laboratories started to become interested in the potential
of the direct method for structure determination.

During the 1960's, I collaborated with Isabella in some of her investigations
and derived with her a variance formula that was the basis for applying probability
measures to procedures for analyzing noncentrosymmetric crystals. In addition,
I also carried out a number of theoretical investigations. Perhaps, the most
useful one concerned a procedure for developing a fragment of a structure into
a complete one by use of the so-called tangent formula for phase determination.

During the 1950's and 1960's, I maintained an interest in gas electron diffraction
and made some experimental and theoretical studies of internal rotation and
coherent diffraction associated with excitation processes. The latter was especially
interesting, but required extensive experimental development that the resources
available to me did not permit.

In the 1970's, I continued theoretical work in crystal structure analysis that
included the derivation of a "tangent formula" for phase determination that
was based on the more restrictive higher and higher order determinants from
the determinantal inequalities. I showed how joint probability distributions
relevant to crystallographic quantities could be put into an exponential form
and thereby decrease considerably problems with asymptotic convergence. I also
derived heuristic joint probability distributions based on the determinants
involved in the determinantal inequalities and obtained from them formulas for
evaluating triplet phase invariants and, later on, formulas for the expected
values of phase invariants and embedded semi-invariants of any order, triplet,
quartet, quintet, etc. The utility of phase invariants of high order in phase
determination has so far been rather limited, except perhaps collectively in
the high order determinants where they have been useful for refining the values
of approximately determined phase values.

I participated with Wayne Hendrickson of my laboratory in some refinements of
macromolecular structure with the use of the tangent formula and also had some
early participation with John Konnert and Wayne Hendrickson in the constrained
refinement technique for macromolecules. In collaboration with John Konnert
and Peter D'Antonio, procedures were developed for determining atomic arrangements
in amorphous materials based on criteria similar to those applied to molecular
vapors. Collaborations on structural problems also included Judith Flippen-Anderson,
Clifford George, Richard Gilardi and Alfred Lowrey.

At the end of the 1970's Wayne Hendrickson made some valuable advances in the
application of anomalous dispersion to the determination of macromolecular structure
that rekindled an interest that I formerly had in this subject. I developed
an exact, linear algebraic theory that includes any number and type of anomalous
scatterer and any number of wavelengths. It can also incorporate information
from isomorphous replacement measurements. Exact data give exact values for
the unknown quantities that include phase differences. I have also been investigating
the evaluation of triplet phase invariants to see what their potential usefulness
may be. This activity continues to the present and is greatly facilitated by
Stephen Brenner who has performed my programming and computing for me since
the early 1960's.

In addition to participating in the development of new analytical methods and
their applications, I have taught from time to time, mathematics and physics
in the University College of the University of Maryland, I have taken an active
role in the affairs of crystallography over the years as, for example, President
of the International Union of Crystallography (1981-1984) and have enjoyed having
a laboratory that investigates a broad variety of subjects ranging over gaseous
molecules, amorphous solids, fibers, crystals and crystalline macromolecules.

During my entire married life I have had the strong support of my wife, both
technical and spiritual. I also deeply appreciate the supportive atmosphere
provided by the Naval Research Laboratory. This was especially helpful during
the early 1950's when a large number of fellow-scientists did not believe a
word we said.

From *Les Prix Nobel. The Nobel
Prizes 1985*, Editor Wilhelm Odelberg, [Nobel Foundation], Stockholm, 1986

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. To cite this document, always state the source as shown above.

**Added in 1992**

Since this biography was written in 1985, advances have been made in macromolecular
structure analysis by applications of the linear algebraic theory for the multiwavelength
anomalous dispersion technique that I published in 1980. A number of such applications
have been made by Wayne Hendrickson and colleagues who, along with the applications,
developed suitable techniques for the use of synchrotron radiation and relatively
weak anomalous scatterers. In recent years, I have been concerned with additional
developments in the anomalous dispersion technique and have become interested
in some aspects of the solution of nonlinear simultaneous equations, the determination
of electron densities in crystals and some new approaches to phase determination
in crystal structure problems.

Receipt of the Nobel Prize has given me the opportunity to have contact to an
unprecedented degree with young people who look forward to careers in science
and other intellectual and artistic pursuits. I have also had many contacts
with organizations whose purpose is to improve the quality of life on this planet
in a variety of contexts. These contacts have not changed my earlier views,
but, in many instances, have perhaps given some of them a sharper focus. I would
like to share a few.

Societies must provide a framework of encouragement in which its children can
develop their skills fully and an educational system open to all in which this
can be achieved. In many societies with which I am familiar, this would require
a major change of priorities. Encouragement within the family structure is also
very important.

This world has enormous social, economic and political problems, not the least
of which concern the environment and natural resources. The degradation of the
environment must be brought under control if there is to be a worthwhile and
sustainable quality of life for most people. This too will require a reordering
of priorities. It is very likely that continued population growth will defeat
any attempts to halt environmental degradation and the unconscionable destruction
of resources. Everyone has a responsibility in this regard.

Respect for the dignity of all human beings, if widespread, would go very far
toward relieving numerous social stresses that much too often lead to societal
deterioration and violence.

Our world has a long way to go.

Peace.