During the 1990s, Hamilton became interested in the controversial[[OPV argumentAIDS hypothesis|now-discredited hypothesis]] that the origin of [[HIV virus|HIV]] lay in [[Hilary Koprowski]]'s oral [[polio vaccine]] trials in Africa during the 1950s. Hamilton's letter on the topic to ''[[Science (journal)|Science]]'' journal was rejected in 1996. Despite this, he spoke to the BBC supporting [[OPV AIDS hypothesis|the hypothesis]],<ref>{{cite web |url=http://news.bbc.co.uk/2/hi/health/431167.stm |title='Scientists started Aids epidemic' |date=1 September 1999 |website=BBC News |access-date=1 September 2020}}</ref> and wrote the foreword of Edward Hooper's 1999 book ''The River''. To look for evidence of the hypothesis, Hamilton went on a 2000 field trip to the [[Democratic Republic of the Congo]] to assess natural levels of [[simian immunodeficiency virus]] in primates.<ref name=pol>{{cite journal |url=https://documents.uow.edu.au/~bmartin/pubs/05pls.html |title=The Politics of a Scientific Meeting: the Origin-of-AIDS Debate at the Royal Society |journal=[[Politics and the Life Sciences]] |volume=20 |issue=20 |date=September 2001 |access-date=1 September 2020}}</ref><ref name="the-star">{{cite news |last1=Allen |first1=Kate |title=He nearly died pursuing HIV's origins. Then this Canadian scientist set his sights on the COVID lab leak theory. Here's what he found |url=https://www.thestar.com/news/canada/he-nearly-died-pursuing-hiv-s-origins-then-this-canadian-scientist-set-his-sights-on/article_62ff5dd2-12b3-5db9-a912-0724bd2669ee.html |access-date=15 September 2023 |work=[[Toronto Star]] |date=29 April 2023}}</ref> None of the over 60 urine and faecal samples contained detectable [[Simian immunodeficiency virus|SIV virus]].<ref name="Horton 2000">{{cite journal |last=Horton |first=Richard |title=New data challenge OPV theory of AIDS origin | journal=The Lancet |volume=356 |issue=9234 |date=2000 |doi=10.1016/S0140-6736(00)02698-2 |page=1005}}</ref>
