From: sidles@stein.u.washington.edu (John Sidles)
Newsgroups: sci.physics
Subject: Re: Compelling Mysteries (II)
Keywords: compelling, mysteries, partridges and pear trees
Date: 11 Nov 92 05:13:23 GMT
Article-I.D.: u.1992Nov11.051323.25125
Organization: University of Washington, Seattle

>|> |> >     Several people have complained lately about the subject matter
>|> |> >     around this neck of the woods, so I wonder if some of those people
>|> |> >     will oblige me by posting what they believe to be compelling
>|> |> >     mysteries or pressing problems in their particular field.

Dear "sci.physics" folks...

Here is a medical perspective on what constitutes a "pressing
problem" in physics.  It concludes with a challenge to the
collective theoretical, experimental, and inventive powers of
the sci.physics community.

I am an associate professor of orthopaedics.  In our clinic,
patients frequently present with problems that are beyond the
reach of present orthopaedic practice.  For example, two of
the most vexing problems we face in orthopaedics are aging
and HIV infection.  Neither is susceptible to surgical treatment.
But neither do we know very much about the molecular basis of
these disorders.

With regard to aging, one can't prepare pure samples of aged
collagen for x-ray or NMR structural analysis, because aged
collagens are heterogenous.  So at the molecular level, we
have limited understanding of the structural pathogenesis of,
for example, osteoarthritis.

In our clinical practice, we are limited to "cut and replace"
treatment of severely osteoarthritic joints, using plastic
and steel artificial joints.  It would be much better if we
knew how to prevent, and how to cure, osteoarthritic degeneration.
There is not much hope of achieving this until we learn more
about whatis going on at the molecular level.

Regarding HIV infection, the orthopaedic surgeons in our
department are committed to treating every patient who comes
in the door.  As a regional trauma center we treat many urban
trauma patients who have a high prevalence of HIV infection.
So our surgeons are at substantial risk for HIV exposure, and
minimizing this risk requires stringent precautionary measures.
This makes orthopaedic practice much more stressful... and
this is not a trivial concern, as it becomes difficult to
recruit surgeons willing to treat these patients.

Molecular biologists have acquired fairly complete knowledge
of the HIV genome, but not much structural information about
the proteins it encodes.  This makes rational design of
effective treatments very difficult and slow.  To the extent
that better instruments for obtaining molecular structure
information might speed medical research, everyone would
benefit.

Some non-biologists don't appreciate that presently there are
no good methods for nondestructive, single-copy molecular
structure determination.  Yet from a clinical perspective,
this lack severely impedes medical research.  It is as though
scientists had to study cell structure without using microscopy.
Instead, scientists would learn about cells by homogenizing,
filtering, and centrifuging them.  After much work, they might
determine that cells are surrounded by membranes, and contain
nuclei carrying genetic information, etc.  Biomedical researchers
would not feel handicapped by the lack of microscopy, rather
they would compete for access to the newest and most ingenious
filtering devices.  In this hypothetical world, it would not
be readily apparent that instrument technology was a crucial
medical/scientific issue.

Hopefully, the next generation of molecular biologists will
routinely, quickly, and easily obtain images showing the full
three-dimensional structure of the molecules they are studying,
in situ, with all their ligands, cross-links, and glycosylation
in place.  This would substantially accelerate the development
of effective treatments for presently intractable disorders.

The challenge posed to the collective theoretical, experimental,
and inventive powers of "sci.physics" is this: design a
molecular microscope with the above-named capabilities.

Three concluding comments...

(1) One stimulus for posting this note is Leo Kadanov's
too-downbeat editorial in this month's Physics Today...  you
young folks should keep in mind that there still remain many
"compelling mysteries and pressing problems" where physicists
can make contributions that are both aesthetically pleasing
and socially useful.

(2) If your ideas are good,then write them up and submit them
for publication.  If your ideas are too half-baked for
publication, then submit them to the net.  But please don't
send your ideas to me... I won't read them.  Everyone is better
off if you take the trouble to write things up clearly,
referencing the relevant literature, and submit for publication.

(3) To avoid being disingenuous, I have to state that my
colleagues and I have published in this area, most recently
in Rev. Sci. Instrum. 63(8) 3881-3899 (1992).  But my strong
recommendation is to think about the problem independently...
surely physicists can come up with better ideas than an
orthopaedist can!

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John Sidles, Ph.D.                  email: sidles@u.washington.edu
Associate Professor                 phone: (206) 543-3690
Department of Orthopaedics RK-10    FAX:   (206) 685-3139
School of Medicine
University of Washington
Seattle WA 98195
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