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William S. Beck, M.D.
Professor of Medicine
Harvard Medical School
Massachusetts General Hospital
55 Fruit Street
Boston, MA 02114
I greatly appreciate your taking the time to meet with
me last week to discuss some of my future goals in
biomedical science. As we discussed, for a number of
professional and personal reasons, I am extremely keen to
return Harvard to continue my clinical education.
For professional reasons, the Harvard Medical School
and, in particular, the HST program is the ideal place for me
to grow and develop my research interests. It goes without
saying that the range and depth of the clinical faculty is
overwhelmingly outstanding and strongly committed to the
highest level of excellence in biomedical research. With my
training in structural biology as well as my commitment to
understanding underlying mechanisms, I bring a strong
background and enthusiasm to the solution of fundamental
clinical problems. When I chose my Ph.D. specialization in
1989, structural biology and x-ray crystallography were
considered relatively esoteric and certainly much too
fundamental for an MD/PhD to consider pursuing.
Nevertheless, I prevailed in this goal in the belief roughly
speaking, that \u201cphenotype\u201d would be the ultimate locus of
preventative and therapeutic intervention. The isolation of
specific disease-producing genes has given us great powers
of diagnosis and prognosis (indeed, Hippocrates hailed the
latter as the most important challenge facing the physician).
To proceed beyond that, however, our understanding needs
to be directed at the level at which diseases express
themselves andat the point in which our medicines act\ue000
We didn\u2019t get a chance to discuss research per se, so I
thought I would give synopsis of one of my recent results.
Last fall, I proposed to Prof. Wayne Hendrickson the idea of
usingkrypton as a multiwavelength anomalous diffraction
(MAD) phasing vehicle for the x-ray crystallographic
structural analyses of protein structures. The premise of that
idea was that individual krypton atoms serving as anomalous
scatterers would bind at nonpolar pockets (packing defects)
within the hydrophobic core of the protein. As it turns out,
the actual result was completely unexpected with the
krypton binding tightly and specifically to thesurface of the
protein. Although we are presently refining the site to
elucidate the details of the interaction, it is nevertheless
clear that the binding is mediated by electronic polarization
of the uncharged, spherically symmetric krypton atom as it
lies nestled between the charged side chains of a glutamate
and a lysine. The nature and existence of this unique binding
site has important implications for ligand-protein interactions
in general and for structure based drug-design in particular.
My return to Boston is also important for personal and
family reasons. First, is my mother\u2019s recent diagnosis of
diabetes mellitus\ue000 although, in my estimation, she had
clinical symptoms for as long as five years now. During
these past years while my parents were living in Cambrige, I
had insisted that she see a doctor, but the combination of
my physical distance as well as her fears in the face of her
uncle\u2019s death from the same condition, has resulted in the
active denial of her illness. The recent diagnosis, while being
a step forward in the improvement of her health, adds
additional urgency to my desire to spend more time with my
parents. Second, is my wife\u2019s unhappiness in New York. The
crime and stresses of ordinary living have cumulatively
compromised our family\u2019s well-being and ultimately our
productivity. Both of us love the Boston area and look
forward to living in circumstances that will allow us to work
to our full potential, in public health and biomedical science,
I hope that in these short pages, I\u2019ve been able to
present my reasons for returning to Harvard clearly and
convincingly. Once again, I appreciate all your interest and
advice. As you suggested, I\u2019ve spoken to Dr. H. Franklin
Bunn who was very encouraging and suggested that I write
Now bringing you back...
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