It is definitely synthetic, a trimethyl-ammonium derivative of polystyrene.
The first to use it as a human medication seems to be Stanley S. Bergen, Jr. et al.
See Effect of an Ion Exchange Resin on Serum Cholesterol in Man Proceedings of the Society for Experimental Biology and Medicine, Volume 102, 1959, Pages 676–679:
It is well known that bile acids are a major
end product of cholesterol metabolism and
that cholesterol is probably the only precursor
of bile acids([references]1-3 ) . Rate of oxidation of cholesterol
to bile acids is believed to be regulated
by need for bile acids for digestive purposes,
cholesterol normally being oxidized at
a rate sufficient to replace the bile acid that
escapes reabsorption and is lost in the feces
([references] 4 - 5). If an agent could be found that would
sequester bile acids and thereby promote their
excretion in the feces, 2 consequences of clinical
interest might be anticipated: (1) increase
in rate of oxidative degradation of cholesterol.
and (2) decrease in serum cholesterol level.
Tennent ([reference] 6) described lowering of serum cholesterol
levels in animals fed the chloride salt
of a basic anion exchange resin. This material
(MK-135) has marked affinity for bile
acids in vitro and is believed to exert its serum
cholesterol-lowering effect by virtue of this
property( 6 ) . The present report summarizes
results obtained when MK 135 was administered
to 26 patients, many with elevated serum
Reference 6 is Tennent, D. M., Siegel, H., Zanetti, M. E., Kuron, C. W., Ott, W. H., Wolf, F. J., Circulation, 1959, v20, 996.
Even though Bergen's paper only uses the term "MK 135", according to the editor's note on the current online version, this paper is the first use of cholestyramine as a medication in humans.