}
Yale University Department of Epidemiology

and Public Health

School of Medicine

60 College Street

P.O. Box 208034

New Haven, Connecticut 06520-8034

A Kaas
Ee oY

4 Jan 1995
‘Dear Dr. Lederberg,

Your approach to the threat of pandemic disease is much broader than that
which I followed in the enclosed papers. I chose to focus on the effect of
population homogeneity on adaptation by infectious agents, rather than adaptation
to the world's population as a whole.

The evidence is thin and I put this out as a hypothesis in the hope that more
evidence, pro or con, might be mustered. It has now been presented orally in a
number of forums, with no convincingly negative data elicited in rebuttle. The
hypothesis derived from the inverse relationship between polymorphism at the MHC
and susceptiblity to epidemic disease in New World and Old World populations.
The best hard evidence comes from the work of Garenne and Aaby on the dependence
of measles mortality on genetic relatedness between primary and secondary
patients (JID 161:1088,1990). A weakness here is that closely related people may
transfer larger innocula, but there is data indicating the effect of innoculum
size is minor. I also consider supportive that fact that EBV takes on a different
antigenic structure in a population (New Guinea lowlanders with high All freq.)
that is particularly responsive, immunologically, to the usual form (deCampos-
Lima et al Science 260:98,1993). The chief alternative explanation of high New
World mortality has been that these people are genetically more susceptible, but
we find almost no evidence of this in extensive studies with standard (vaccine)
infections that have no opportunity to adapt.

The idea that viruses might take on host HLA proteins and thus hide from new
hosts that carry the same alleles, opens up an alternative mechanism for
dependence of virulence on population homogeneity and I thank you for drawing it
to my attention. I gather this phenomenon is known only in HIV, but it would
seem possible with other enveloped viruses. I shall particularly bear it in mind
vis-a-vis HTLV-II which attains extraordinary prevalence rates in some of our
populations (AIDS Res Hum Retrov 10:1165,1994).

Thank you for your suggestions,

Francis L. Black

__

CLA Caskey vty”