Twenty-five years of clinical flow cytometry: AIDS accelerated global instrument distribution.

Abstract

As a cell biologist, one experiences some ambivalencewith an enigmatic sensation on the occasion of the silverjubilee of Clinical Cytometry. This significant milestone iscelebrated with ominous feelings because of the remark-able symbiosis that was forged between the birth of a newclinical diagnostic tool and the emergence of one of themost devastating infectious diseases of the 20th century. Itis less then 25 years ago that the first reports surfacedabout clusters of aggressive opportunistic infections ap-pearing mysteriously in young gay men in some metropol-itan areas in the United States (1,2). The causative agent ofthe epidemic was unknown, yet the disease was wellcharacterized within a very short time span as the ac-quired immunodeficiency syndrome (AIDS). The initialCDC definition of AIDS incorporated leukocyte subsetnumbers from peripheral blood. AIDS’ defining conditionincluded CD4 T-cell counts of 200 or less (3,4). Initially, inmost immunology laboratories, immunophenotyping wasperformed with fluorescent microcopy. But quickly, thechoice of assay method shifted to flow cytometry. As theworld-wide apocalyptic devastation began, cellular immu-nologists engaged in research had at their disposal anarsenal of reagents and instruments just waiting for anopportunity for qualitative assessment of immunodefi-ciency. Therefore, in a very short time, instruments thatcould count T-helper cells were in great demand. Theepidemic had profound impact throughout the Westernworld, but those initial human losses paled in comparisonwith the carnage AIDS delivered and still is delivering inresource-poor regions of the globe. It is estimated that in2003, over 40 million individuals live with AIDS; about10% of this population lives in South Africa.Most of the time, significant scientific progress occursin dull obscurity, but occasionally human curiosity pre-vails and the odd science story proceeds with significantfanfare. The discoverers of the structure of DNA did re-ceive immediate accolades. However, in most instances oftechnical breakthroughs in diagnostics, the assessment ofthe day falls short of appropriate recognition. Invariablythe press selects trivia to report as newsworthy science.For example, the postmortem analysis of the space shuttledisaster received phenomenal coverage. Polemical reportswere bombarding us about how scientists were able todemonstrate that a piece of the foam debris at a certainvelocity could have or could not have damaged criticalceramic tiles attached to the wing on that doomed andmost unfortunate space vehicle. At the same time, thispast July, a subcommittee of the International Union ofPure and Applied Chemists identified the 110th element.The new chart recognizes darmstadtium (Ds) as a uniqueelement. It was formally added to the Periodic Chart. Thislatter event received virtually no publicity, while the sig-nificance of the finding is relatively easy to convey to thepublic, as we all learned about the elements while takinghigh school chemistry. The low profile coverage that isoften associated with our discipline was altered forever 25years ago. Events in cytology during the early 1980s weregoing to unfold in a most uneventful fashion. However,with a newly discovered incredibly devastating lethal dis-ease on the horizon, the role of the underrated flowcytometer changed forever. Because reliable diagnosing ofimmunodeficiency was an essential requirement, clinicalcytometry was born. With flow, rapid diagnosis of AIDSwas possible as early as 1981 (1). Clinical immunopheno-typing was possible just a few years after the discovery ofthe hybridoma technology. It opened the possibility forthe production of mAbs with high affinity and avidity.Between 1978 and 1981, Milstein, Reinhertz, Schlossman,Goldstein, Janossy, and many others were diligently crank-ing out antibody-producing murine clones and were de-fining and assigning function-specific roles to markers onhuman T- and B-cells. Flow cytometry, a laser-based tech-nology, was photogenic and there were no serologicaltests available to feature. Therefore, flow cytometry prof-ited from seemingly spontaneous and persistent presscoverage. The virtuosity and veracity of the investigators’productivity a quarter-century ago expedited research ca-pacity in immunology beyond any expectations. Unfortu-nately, to date the regulatory role of various T-cell subsetshas not been fully resolved. The scholarly struggle to gainmore knowledge in this area, including oncology, hasadvanced, but it is far from over.Thereisalwaysasilverliningtoanyhumancatastrophe.The story of the AIDS pandemic is no exception. In thiscase, 25 years ago we had instrumentation to analyzeperipheral blood cells, but there was no apparent wide-scale clinical application beyond differentiating various