July 21, 1971

Dr, Ntinos C. Myrianthopoulos —

Section on Epidemiology and Genetics

Perinatal Research Branch

National Institute of Neurological Diseases & Stroke
Bethesda, Maryland 20014

Dear Dino,

Thank you for the material on the sickle proposal and for the
other background on the collaborate study.

I was glad to see that you were two steps ahead of me in
thinking about this protocol, I have only a couple of rather minor
comments:

Skin color does not strike me as a reliable way of estimating
black ancestry in view of our dim understanding of the genetic
mechanisms. Besides, it also introduces a lot of confounding with
social factors because the phenotype is evident. One should at least
couple this with an examination of the bloods for other markers,
especially Duffy.

I hope birth weight is explicitly in mind within the heading
of weight at specific ages.

My most important point is one to which I know you are already
most sensitive, that is the desirability of getting the data out
as mich as possible for within kindred comparisona. When a sickler
child is identified one should seek to type the siblings so that
developmental comparisons can be made as between segregates within
a single family. Similarly whenever possible you should look for the
same as between sibling mothers, This will require more follow-up
at the collaborating institutions but a few families would be worth
much more than a great many scattered individual tests,

If this goes through conventional review procedures the application
probably should have considerably more detail about the protocols for
conducting specific comparisons and appropriate controls. It may seem
silly to ask that of a group like yourself but study sections are
notoriously unreliable in crediting good sense to their colleagues.
Believe it or not I would advocate that you make specific reference to
such obvious points as dividing the sickler children according to
which parent was the source of the gene. And sickler mothers according
to whether the offspring was or was not also positive. With such study
sections it, in my experience, is impossible to be toc meticulous in
explaining detail that perhaps should be accepted as a matter of common
sense, And of course, on the other side, we all know how often some
of our esteemed colleagues have themselves goofed!

over

 
Dr. N.C. Myrianthopoulos -2- 7/21/71

On page 7, question 14 is going to elicit some nit-picking.
About 55% of these children will be sicklers in either case,
inheriting the gene either from a heterozygotes mother or an
unselected father. It is not going to be easy to clear up all the
cases of umbilical sickle cell by retrospective examination; it
would of course be remarkable if this were manifest at birth when
there should be a prepomderance of hemoglobin F. As to question 13
are there really enough data in the records of the study to make
it likely that you can answer such a question?

Sincerely yours,

Joshua Lederkerg
Professor of Genetics

JL/rr