Ann
 

4
}
a
5
t
#
3

ARTERIOSCLEROSIS RESEARCH LABORATORY

St. BARNABAS HospITAL RESEARCH FOUNDATION AND THE
UNIversiry OF MINNESOTA SCHOOL OF MEDICINE

601 Tenth Avenue South
Minneapolis 4, Minnesota

December 16, 1964

Dr. Michael De Bakey

. Department of Surgery

Baylor University School of Medicine
Houston 25, Texas

Dear Dr. De Bakey:

I hesitate to add to your burden in the collection of data as Head
of the Presidential Commission on Heart Disease, Cancer, and the Stroke. I
will therefore discuss only briefly that which, in my judgement, is the most
important and yet a neglected area in the nations effort to reduce the death
toll from heart. disease and the stroke. This area is our_inability to
accurately evaluate the individual with regard to a biochemical index of the
activity level of atherogenic factors. From this statement it becomes evident
that the problem revolves around learning the cause of arteriosclerosis. It is
in this area where the scientific community has become bogged down by individuals
and groups fighting for the financial support of their own important but limited
research project; the consequence thereof being unjust criticism of pertinent

variables in someone elses laboratory and hence prejudice and confusion with
little forward movement.

 

However, at this time there are a significant number of enzymatic
activities and specific protein and non-protein factors which have been stat-
istically correlated with arteriosclerosis. For just one example, in my labor-
atory we have found that the turnover rate of fibrinogen increases 45.4 %, as
a function of age, in the 53 yr old subject. If subjects of this age group incur
an infarct, the turnover rate will increase by 79.2 % above the young normal
subject. Both increases above the young normal subject are significant at P<
0.001, The increase of the arteriosclerotic subject with respect to the age
matched normal is significant at P < 0.04. These increases are not a function
of anticoagulant therapy or the stress or trauma of the myocardial infarct.

Although, we have at this time a number of biochemical indices of
atherogenesis, the problem is that no_one has the physical facility and staff
which would permit an adequate evaluation of the degree of correlat
activity or concentration levels of these factors and the degree of arteri
sclerosis in the living and deceased subject. I believe that such a broadly
conceived study is not-only feasible at this time but is an integral part of the
fight against vascular disease and thus will be essential sooner or later. It
is possible that an adequate statistical study of the known factors which change
as a function of arteriosclerosis would allow a regional center to take any
individual and by measuring these biochemical activities be able to predict an
infarct within a matter of a few weeks or days. While this may be of limited

 

   
value, the more important development would be the availability of facilities
and staff for determining the effect of therapy on the change in these bio-
chemical indices and on the physical indices of the progress or regression of
arteriosclerosis. With respect to therapy, facilities and staff would be
available for basic studies of intracellular and extracellular control mech-~
anisms which may change as a function of vascular disease, changes which may
be located at such fundamental levels as the transcription of DNA, translation
of the RNA message, and protein and enzyme synthesis.

Suifice it to say that this is a very rough and incomplete outline of
probably the most pressing problem in the area of heart disease and the stroke.
It is evident that the answers must come from the biochemical or molecular or
enzymatic level. The Framingham Heart Study might be considered as a guide of’
that which needs to be done at the molecular level and of that which needs to
be done at a greatly increased level of sensitivity and specificity.

LI find it doubtful that such a study emanating from one group, such
as my own, could secure adequate support through the NIH Study Section System.
However, an approach through direct financing by NIH, such as their recent
muiti-million dollar program on viruses, would appear workable. Or an approach
or proposal emanating from 5 or 6 regional principle investigators and their
co-workers might be able to receive approval through the Study Section System.

I am most interested in pursuing further this line of thought and
wish to learn your thoughts, your recommendations, and whether any action on

this matter might be facilitated by or forthcoming via the efforts of your
commission,

With my kindest regards, I am,

Sincerely yours,

2 Oh
Laurence 0, Pilgeram, Ph. D.

Director

via air mail
LOP: cz