To the
Colonel:
In 1964 I was sitting at a balance in Gibbs; I was
weighing out platinum tetrachloride in preparation for
doing a heavy atom soak with carboxypeptidase when the
Colonel came up behind me and said, "I hope you won\92t
consider this immoral." I stopped and waited in great
anticipation for whatever statement was to follow that
one. The Colonel said that Christopher Longett Higgins.
a distinguished theoretical chemist and pianist. was
visiting Harvard from England and it was the Colonel\92s
plan to gather a few of his fellow musicians from the
Boston Symphony Orchestra at his house in order to play
chamber music. He was inviting a few friends over to
listen and wondered whether I would ask a first-year
graduate student. Joan Argetsinger, to accompany me to
this evening concert at his home. He and Joan had met
some years earlier in Minneapolis when he was in the
chemistry department at the University of Minnesota and
occasionally participated in playing chamber music at
the Unitarian Society, as did Joan. I, as it turned out,
was pleased to do this, and we went along to a very nice
evening of chamber music. I only learned many years
later that Joan had already had plans for that evening
but changed them, not in order to have a date with me,
but rather to be able to hear some good chamber music.
That was our first date and the rest, as they say. is
history.
I had originally come to Harvard thinking that I might
wish to do my graduate research in the laboratory of
Paul Dody, since I was very interested in the physical
chemistry of macromolecules. After waiting weeks on a
couple of occasions in order to talk to Dody, between
his many trips to Washington. I was frustrated and
disappointed at the disorganized conversations that I
had with him. In the spring of 1964 Max Perutz came to
Harvard Medical School to present three Dunham Lectures
on the crystal structures of myoglobin and hemoglobin. I
remember the enormous excitement in that packed,
extremely large lecture room when Perutz showed the
first stereo slide of a macromolecule that any of us had
ever seen and the loud "Oh" that simultaneously emanated
from the whole audience when it finally came into
three-dimensional view. I found these three lectures to
be extremely exciting and immediately recognized that
protein crystallography was the way to understand
protein structure and function at the atomic level. I
lamented to a graduate student of Lipscomb\92s, Peter
Boer, with whom I was playing tennis that it was too bad
that no one at Harvard did protein crystallography since
I strictly wished to enter this field. He pointed out to
me that Lipscomb had a group that had been working on
carboxypeptidase for a couple of years and suggested
that I go talk to him. I remember going excitedly to his
office hoping to make an appointment to see him at some
point in the future. I was surprised and pleased after
my experiences with Dody that he immediately invited me
into his office to talk about possible projects on
carboxypeptidase; we sealed the deal then and there.
I had a simply wonderful time in the Lipscomb
laboratory. I loved the carboxypeptidase project and
often daydreamed about what the active site of an enzyme
might actually look like. At that time, active sites
were represented by the crudest of cartoons with the
enzyme being represented by an indented rectangle
labeled E.
I delighted in the extreme diversity of the laboratory -
the vacuum line boron hydride chemists, the small
molecule X-ray crystallographers, the theoretical
chemists off in their separate room and the protein
crystallographers trying to do something none of them
had ever done before. I thought that the Colonel must be
extremely smart to be able to talk to all of these
people and be on top of what they were doing.
I learned a lot about how an outstanding research
laboratory is run during my time under his mentorship. I
do not think that it is an accident or simply good
fortune on his part that so many of his former students
and postdocs have been so successful in their careers
after leaving his laboratory. He got us excited and he
got us thinking, infecting us with his own boundless
enthusiasm when every evening he came bounding through
the lab to see what was new. He inspired us by positive
reinforcement of success not by badgering and tormenting
the unsuccessful. We were always made to feel that we
could do anything we wished if we tried hard enough and,
indeed, we did. I sometimes wonder ifI did not take some
of his principles too seriously. I remember his
recounting on several occasions the dictum he attributed
to Linus Pauling that any scientist who never made a
mistake was a scientist who never tried to do anything
important and creative. I suppose I cannot assume that
since I have put forward hypotheses that subsequently
proved to be not correct that, therefore, I have been
doing important and creative work. Nevertheless, we were
all encouraged, both by example and by suggestion, to
ask the big questions and think about the big picture
rather than get bogged down in detail.
When Joan and I decided to get married in 1966 and
invited the Colonel to come to our wedding he responded
by offering to not only come but invite two of his
friends from the Minneapolis Symphony to join him in
playing the Haydn London Trios at the wedding and the
reception afterwards. We both greatly appreciated this
wonderful and generous offer on his part and the
marvelous contribution that it made to the occasion at
that time. As I look back, being now as busy myself as
he was at that time. I appreciate even more what a
thoughtful and generous gift of his time that was.
Thomas A. Steitz
Steitz's Publications with Lipscomb
Lipscomb, W. N., Hartsuck, J. A., Reeke, G. N., Quiocho,
F. A., Bethge, P. H., Ludwig, M. L., Steitz, T. A.,
Muirhead, H., and Coppola, J. C., "The Structure of
Carboxypeptidase A. VII. The 2.0 A Resolution Studies of
the Enzyme and of its Complex with Glycyl-Tyrosine, and
Mechanistic Deductions,"
Brookhaven Symposia in Biology (June
3-5, 1968: 1968) 24.
Reeke, G. N., Hartsuck, I. A., Ludwig, M. L., Quiocho,
F. A., Steitz, T. A., and Lipscomb, W. N., "The
Structure of Carboxypeptidase A. V1. Some Results at 2.0
A Resolution and the Complex with Glycyl-Tyrosine at 2.8
A Resolution,"
Proc.
Natl. Acad. Sci. USA 58, 2220-2226 (1967).
Steitz, T. A., Wiley, D. C., and Lipscomb, W. N.,
\93The Structure of Aspartate Transcarbamylase. I. A
Molecular Two Fold Axis in the Complex with Cytidine
Triphosphate," Proc.
Natl. Acad. Sci. USA 58, 1859-1861
(1967).
Steitz, T. A., Ludwig, M. L., Quiocho, F. A., and
Lipscomb, W. N., "The Structure of . Carboxypeptidase
A. V. Studies of Enzyme-Substrate and Enzyme-Inhibitor
Complexes at 6 A Resolution," J. Biol. Chem. 242, 4662-4668
(1967).
Ludwig, M. L., Hartsuck, J. A., Steitz, T. A., Muirhead,
H., Coppola, J. C., Reeke, G. N., and Lipscomb, W. N.,
"Structure of Carboxypeptidase A, IV. Preliminary
Results at 2.8 A Resolution and a Substrate Complex at 6
A Resolution,\94
Proc.
Natl. Acad. Sci. USA 57, 511-514 (1967).
Lipscomb, W. N, Ludwig, M. L., Hartsuck, J. A., Steitz,
T. A., Muirhead, H., Coppola, J. C., Reeke, G. N., and
Quiocho, F. A., "Molecular Structure of Carboxypeptidase
A at 2.8 A Resolution and an Isomorphous
Enzyme-Substrate Complex at 6 A Resolution,"
Federation Proc.
26, 385 (1967).
Coppola, J. C., Hartsuck, J. A., Ludwig, M. L.,
Muirhead, H., Searl, J., Steitz, T. A., and Lipscomb, W.
N., "The Low Resolution Structure of Carboxypeptidase A,
"Acta Cryst.
21,
A160 (1966).
Ludwig, M. L., Coppola, J. C., Hartsuck, J. A.,
Muirhead, H., Searl, J., Steitz, T. A., and Lipscomb, W.
N., "Molecular Structure of Carboxypeptidase A at 6 A
Resolution,"
Federation
Proc.
25,
Part I, 346 (1966).
Lipscomb, W. N., Coppola, J. C., Hartsuck, J. A.,
Ludwig, M. L., Muirhead, H., Searl, J., and Steitz, T.
A., "The Structure of Carboxypeptidase A. III. Molecular
Structure at 6 A Resolution,"
J. Mol. Biol.
19, 423-441 (1966).
Steitz, T. A. and Lipscomb, W. N., "Molecular Structure
of Methyl Ethylene Phosphate,"
J. Am. Chem. Soc.
87, 2488 (1965).
Hartsuck, J. A., Ludwig, M. L., Muirhead, H., Steitz, T.
A., and Lipscomb, W. N., "Carboxypeptidase A. II. The
Three-dimensional Electron Density Map at 6 A
Resolution,"
Proc.
Natl. Acad. Sci. USA 53, 396-403 (1965).
More Information
Tom Steitz was awarded the Nobel Prize in Chemistry in
2009.
Some of the story above is
retold
by Tom Steitz and
retold
by Joan and Tom Steitz in the Rememberences
section of this website.
Wikepedia
page about Tom Steitz
Tom
Steitz at Yale
Warren's Publications with Lipscomb
Honzatko, R. B., Crawford, J. L., Monaco, H. L., Ladner,
J. E., Edwards, B. F. P., Evans, D. R., Warren, S. G.,
Wiley, D. C., Ladner, R. C., and Lipscomb, W. N.,
"Crystal and molecular structures of native and
CTP-liganded aspartate carbamoyltransferase from
Escherichia coli,"
J. Mol. Biol.
160, 219-263 (1983).
Lipscomb, W. N., Evans, D. R., Edwards, B. F. P.,
Warren, S. G., Pastra-Landis, S. C., and Wiley, D. C.,
"Three-Dimensional Structures at 5.5 A Resolution and
Regulatory Processes in Aspartate Transcarbamylase from
E. coli,"
J. Supramolecular
Structure 2,
82-99 (1974).
Edwards, B. F. P., Evans, D. R., Warren, S. G., Monaco,
H. L., Landfear, S. M., Eisele, G., Crawford, J. L.,
Wiley, D. C., and Lipscomb, W. N., "Complex of Aspartate
Transcarbamoylase from Escherichia coli with its
Allosteric Inhibitor, Cytidine Triphosphate: Electron
Density at 5.5 A Resolution,"
Proc. Natl. Acad. Sci. USA 71, 4437 (1974).
Warren, S. G., Edwards, B. F. P., Evans, D. R., Wiley,
D. C., and Lipscomb, W. N., "Aspartate Transcarbamoylase
from
E. coli.
Electron Density at 5.5 A Resolution,"
Proc. Nat. Acad. Sci. USA
70,
1117-1121 (1973).
Evans, D. R., Warren, S. G., Edwards, B. F. P.,
McMurray, C. H., Bethge, P. H., Wiley, D. C., and
Lipscomb, W. N., "The Aqueous Central Cavity in
Aspartate Transcarbamylase from E. coli,"
Science 179, 683 (1973).
Wiley, D. C., Evans, D. R., Warren, S. G., McMurray, C.
H., Edwards, B. F. P., Franks, W. A., and Lipscomb, W.
N., "The 5.5 A Resolution Structure of the Regulatory
Enzyme, Aspartate Transcarbamylase,"
Cold Spring Harbor
Symposium 36,
285-290 (1971).
More Information
Steve
Warren at the University of Washington
6.
Edward Wong. Explosion ignited by Tesla
coil. Bill directs thesis progress.
UNIVERSITY
OF NEW HAMPSHIRE
Department of Chemistry
College of Engineering and Physical Sciences
Parsons Hall
23 College Road
Durham, New Hampshire 03824-3598
(603) 862-1550
Fix; (603) 862-4278
March 31, 2000
As I look back on my graduate school experience under
the mentorship of the Colonel 25 years ago, I recall
discouraging and trying periods as well as
exhilarating and joyous moments. Together these
comprise my version of
"My Time with Colonel".
During my third year as a graduate student in the
Lipscomb Group, I foolishly tested a vacuum-line leak
by applying a Tesla Coil to a sample of C
sB
3H
8!
Needless to say, the resulting explosion shattered the
tube and chipped my glasses, cut my face, and singed
my hair, to say nothing of damaging my pride. When he
learned of this mishap, Colonel was quite concerned
about my well-being and showed me much kindness,
greatly aiding my recovery.
My thesis project of synthesizing B
8H
8,
however, was going nowhere. I still remember being
very discouraged and demoralized, even wondering
whether I should consider alternate careers. Despite
my lack of progress towards my degree, Colonel was
unfailingly positive and supportive through out this
unproductive period. After selecting an alternative
synthetic project late into my program, my thesis work
started to finally gather momentum, and the proverbial
light appeared at the end of the Ph.D. tunnel. Or so I
thought! I distinctly remember the day Colonel and I
discussed some results and his saying something to the
effect that, as a Lipscomb student, I should really
complete an X-ray diffraction study before finishing
up. I didn\92t expect this extra work but nonetheless
proceeded to go about growing crystals of a carborane
I\92ve made. Unfortunately, the one diffractometer we
had for small molecules at the time was an extremely
balky
Picker
instrument that relied on a single company technician,
Tom Harris, to keep limping along. Since Tom traveled
all over the world servicing similar instruments, I
remember saying many a prayer for his safe return from
trips overseas. Somehow, with a great deal of help
from Mrs. Chiu, things did work out and my thesis work
was completed.
The last summer months of 1974 in the Colonel\92s Group
was a heady time for me, waiting for final Orteps to
print out at MIT, typing up my thesis on a portable
typewriter, drafting a manuscript for
Inorganic Chemistry,
finalizing wedding plans for late August, plotting a
honeymoon drive across the country through Wyoming,
Montana, Alberta, and British Columbia before a
post-doc with Fred Hawthorne at UCLA in October.
On this occasion of Colonel\92s 80th birthday, I want to
express my recognition and gratitude for the indelible
and beneficial influence his mentorship has had on me
personally and professionally. Thanks, Colonel!
Edward H. Wong
Wong's Publications with Lipscomb
Wong, H. S. and Lipscomb, W. N., "Studies on the
Thermal Rearrangements of Chlorophosphacarboranes.
Molecular and Crystal Structure of
9,10-Dichloro-phosphacarborane,"
Inorg. Chem.
14, 1350-1357
(1975).
Tolpin, E. I., Wong, H. S., and Lipscomb, W. N.,
"Binding Studies of Boron Hydride Derivatives to
Proteins for Neutron Capture Therapy,"
J. Medicinal Chem.
17, 792
(1974).
Wong, H. S., Tolpin, E. I., and Lipscomb, W. N.,
"Boron Hydride Derivatives for Neutron Capture
Therapy: Antibody Approach," J. Medicinal Chem.
17, 785
(1974).
More Information
Edward
Wong at the University of New Hampshire
-- 2009, last updated Nov. 2018,
Home page
https://wlipscomb.tripod.com/