As mentioned, early studies of CQ resistance in P. falciparum showed resistance was associated with decreased drug accumulation that was reversed by the ion-channel blocker VPL [33, 61] . Similar phenomena had been seen in MDR tumor cells. Thus, Wirth and colleagues screened P. falciparum for hsmdr1 homologs and identified pfmdr1 and pfmdr2 [38] . While both encode proteins expressed in drug-sensitive P. falciparum, a MQR strain showed elevated pfmdr1 [54] . MQ is chemically similar to CQ, so at the time resistance pathways were expected to overlap. In support of this, another group found pfmdr1 to be upregulated in some CQR P. falciparum [39] . However, subsequent experiments showed that pfmdr1 overexpression did not correlate with CQ resistance [62] . This was not surprising since Wellems et al. had earlier shown that CQ resistance did not segregate with the pfmdr1 chromosome 5 locus in progeny from a CQS × CQR genetic cross [46] . Proposals arguing against a dominant role for HsMDR1 protein in tumor resistance were also being made during this period, as ion transporters were found to be alternatively expressed in some MDR tumor cells well before overexpression of HsMDR1 [42] .