November 1996
Volume 60 |
Number 11
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| Letters to the
Editor |
Molecular Biology:
The Virtue of Our Motives
The August issue of the ASA NEWSLETTER, "Molecular
Biology and Anesthesiology," opened for discussion the inroads
molecular biology has made in our practice. I believe a few comments
may be in order to set the broader genetic and historical picture.
The entire human genome consists of roughly 3 billion base pairs
of DNA, of which 98 percent does not code for proteins and has
no known role at present. There are about 100,000 genes encoding
specific regulatory or structural peptides in bits spanning the
genome. Virtually all of the medicine we practice today rests
on knowledge of about 6,000 proteins, each consuming the careers
of numerous investigators. Within the next five years and with
no additional conceptual or technical advances, the remaining
95 percent of the human genome will be sequenced in full, enabling
discovery of the total complement of proteins required to construct
a human being. The consequences for anesthesiology, for medicine
and for society are hardly imaginable.
As I write, perhaps 500 human genes have been described in their
entirety; the coding sequence and each of the boundaries between
coding and noncoding regions have been resolved. The coding sequence
alone is known for around 5,000 additional genes, but boundaries
remain to be identified. Partial sequence (expressed sequence
tags, or ESTs) for 50,000 additional human genes can be found
in a variety of databases. Five thousand ESTs are added per week,
and more no doubt may reside behind proprietary protection. The
code for transcribing and translating DNA to protein sequence
is invariant; hence, it is elementary to predict the amino acid
sequence of novel proteins and to begin dissection of their function
in the cell with traditional biochemical tools.
There are three reasons for going to the bother of completing
the Human Genome Project. Diagnosis of inherited diseases by DNA
analysis is the most publicized but, in the end, may be the least
consequential spin-off. Human populations are conspicuously outbred,
and most traits, including diseases, are genetically heterogeneous.
Assigning traits to stretches of DNA too easily falls into the
same traps as assigning proclivities to lumps on the head. Accounting
for the complexity of the underlying system and for the influences
of environment and life experiences of the individual is imperative
and daunting. It will not be quick or cheap to establish grounds
for genetic causality for each newly identified mutation.
The second justification for sequencing the human genome is to
disclose the fundamental mechanisms of human growth, development,
disease, senescence and death. Sequence, the essential feature
of DNA, is linear and conservative, changing slowly over decades
and millennia. Contemporary tools for revealing DNA sequence are
sharp and robust. The crucial attributes of protein are shape
and the capacity to change shape from millisecond to millisecond.
Instruments available to investigate protein shape are crude at
present, yet DNA-based technologies allow us to ensnare proteins,
give them names and learn their roles. Biologists will still be
characterizing protein-protein interactions years from now, but
they will look back on the coming decade in wonder and envy as
the time when our science first stood from a crawl.
Finally, the human genome will be our ultimate artifact. Many
thousands of years ago, we imposed our intent on stones, shaping
tools that in turn shaped us by altering our DNA. Barely 6,000
years ago, the discovery of controlled breeding enabled us to
impose our intent on the DNA of plants and animals, creating civilization.
Inevitably, we will not be content only to read DNA but will rewrite
sequences to suit our own purposes. It is too early to tell whether
compassion and the relief of pain and suffering, or more sinister
intentions, will predominate in the long run.
As in the past, those of us on the preceding edge of a technical
singularity will regard changes of this magnitude as detrimental.
Our descendants will question the relevance of our judgment. By
familiarizing themselves with the promise and perils of molecular
medicine, anesthesiologists can help to ensure that they will
not doubt the virtue our motives.
Kirk Hogan, M.D.
Madison, Wisconsin
Variation on Preceptorship Theme
A topic of much discussion of late in regard to apparent waning
interest in the specialty of anesthesiology has been resurrection
of preceptorships in which medical students devote a month or
two of their medical school training to the specialty.
A variant of the theme may also warrant reconsideration. In the
mid-1950s, Stuart C. Cullen, M.D., developed a program at the
University of Iowa in which two to three medical students each
year were selected to rotate in-house night call with the anesthesiology
residents and participate in any anesthesia-related activity that
presented itself. The medical students were actually paid a small
stipend for their services.
This program, termed a "board job," was perpetuated
by William Hamilton, M.D., when he replaced Dr. Cullen as Chair
of the department, and he is of the opinion that the program was
instrumental in attracting a number of individuals into the specialty.
The program indeed played a significant role in my developing
interest in anesthesia.
Thomas H. Cromwell, M.D.
ASA District Director, District 22 - California
San Francisco, California
The views and opinions expressed
in the "Letters to the Editor" are those of the authors
and do not necessarily reflect the views of ASA or the NEWSLETTER
Editorial Board. The Editor has the authority to accept or reject
any letter submitted for publication. Letters must be signed (although
name may be withheld on request) and are subject to editing and
abridgment.
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