42 Scientific American, March 2022next batch, spending long, exhausting nights on the road. As the
pandemic intensified, they couldn’t keep up. Truckers awaiting
their test results were stalled at the border for days, in part because
the sample analysis in Kampala would sometimes take up to 72
hours to return a result. A queue of trucks formed, stretching for
kilometers, holding up the import of everything from home appli-
ances to construction materials to replacement parts for cars. Mak-
ing matters worse, authorities had closed the airport.
The government was desperate to alleviate the backlog. Ssen-
gooba considered the 265 machines he had set up throughout
Uganda over the years to test for tuberculosis. He realized he could
repurpose some of those small PCR machines to test for the coro-
navirus by using a different sample-processing cartridge. He relo-
cated that equipment directly to the border entry points and engi-
neered some basic infrastructure (electrical power; benchtop safety
spaces) to support their use. Unlike the lab setup in Kampala,
which requires multiple machines spread across different rooms
and experienced technicians to prepare and process the samples,
these so-called GeneXpert modules were automated and about the
size of a printer. They still used PCR technology but could return
results on the spot in around half an hour.
By May the first COVID testing systems were working at the
crossing point in the Kenya-Uganda border town of Malaba, reduc-
ing the waiting time for truck drivers from days to around half an
hour. Within a week the equipment was set up at two other major
border points. Many countries, even wealthy ones, struggled to get
COVID screenings off the ground in the early months of the pan-
demic. But Ssengooba understood how to balance the needs of pub-
lic health and the economy. By cobbling together testing infrastruc-
ture where it was most needed, he was preventing disease while
keeping critical goods flowing into the country.
Ssengooba’s creative repurposing of Uganda’s limited testing
resources was “tremendous,” says Wilber Sabiiti, an expert at the
University of St. Andrews in Scotland in the development of diag-
nostics tests. After Ssengooba had worked tirelessly for years to try
to make PCR testing more accessible for tuberculosis, his efforts
finally seemed to be getting validated. The pandemic, he says, has
clarified the urgency of deploying PCR technology more widely for
all kinds of infectious diseases, especially to politicians, who are
now allocating more money to the technology. “The SARS-CoV-2
outbreak has been like a blessing in disguise for the scale-up of
molecular assays,” he says.
Ssengooba is hardly alone in his thinking. Alex Greninger, assis-
tant director of the clinical virology labs at the University of Wash-
ington Medical Center, says that in the past, the facility where he
works typically ran 50,000 PCR tests a year for diseases such as
influenza and HIV. Between early 2020 and the end of 2021, it had
done four million PCR tests, mainly for COVID. Unlike in the past,
however, the results have been vital to informing immediate behav-
iors: those who test positive self-isolate or are kept in a special ward
of a hospital. This has created a massive new reliance on testing to
guide such decisions. “We [did] 81 years’ worth of molecular test-
ing in the virology lab in the first 22 months” of the pandemic,
Greninger says. He expects the demand for PCR testing to stick
around even after COVID ebbs. The general public is much more
aware of virology now, he says, and as rapid antigen tests become
a more routine part of living amid COVID and its potential future
surges, people will seek out PCR tests to confirm positive results.
COVID has not just increased the scale of disease testing and
created demand from pretty much everyone; it has also spurred
the adoption of more advanced versions of the tests themselves.
Hospital systems have begun purchasing PCR machines that are
small enough to install at a doctor’s office so that samples do not
have to be sent offsite to a huge, centralized lab. That means
patients can get a diagnosis on the spot and isolate immediately, if
needed—and take whatever antiviral or antibiotic is most appro-
priate. Companies and university researchers around the globe
who are working on PCR technologies say there is escalating inter-
est in their innovations, such as handheld versions that would
make testing anywhere—from supermarket parking lots to remote
villages—more feasible.
All of this may benefit more than just individual patients. As the
emergence of the quick-spreading Omicron variant demonstrated
in late 2021, ramping up testing at the population level is crucial to
keep tabs on how COVID might morph and push hospital systems
(among other sectors of society) to a breaking point. The sweeping
uptake of PCR for COVID could also pave the way for stronger pub-
lic health surveillance systems that can spot future pandemics by
scanning for dozens of pathogens at once. According to Jeffrey
Townsend, a biostatistician at the Yale School of Public Health, PCR
is a powerful tool to use for disease surveillance, and “there’s a lot
of people who say we need to be doing it even more.”A STRANGE TRIP
in 1983 Kary MUlliS WaS driving up to his cabin on the northern coast
of California with his girlfriend, a chemist at the biotechnology
company where they had been hired to synthesize genetic frag-
ments. Mullis had spent earlier years completing a Ph.D. at the
University of California, Berkeley, where he would trip on LSD
while making new chemicals. His girlfriend had fallen asleep, and
as he drove he had a vision of molecules dancing on the mountain
road. It was then that the idea for polymerase chain reaction came
to him. He pulled over the car and scribbled down his thoughts. It
won him a Nobel Prize a decade later.
At its heart, PCR is a method of making copies of genetic
sequences. There are now many dozens of different kinds of PCR,
but the most basic form that Mullis devised started with a tiny bit
of DNA and then used various cycles of heating and cooling to rep-
licate it. First, the process would heat the DNA to break its double
helix structure into two strands. Next, it would cycle to a cooler
temperature that would allow specially tailored primers to bind to
specific target sequences within the strands. The samples would
be warmed up again, and enzymes would get to work building off
those primers to finish replicating the complementary DNA
sequences. The cycle would then repeat. Ultimately it yielded a lot
of copies of the target strands. Special fluorescent tags were later
added to the process to flag the presence of those amplified short
sequences of interest.
It became possible to use this method to detect the presence or
absence of pathogens: if a virus was present in a person’s blood
sample, for example, the PCR machine would make a lot of copies
of its sequence, and the fluorescent tags would shine brightly. If
there was no virus, there would be only darkness.
The incorporation of fluorescent tags meant that the PCR
machines could also indicate how much virus was in a person’s sys-
tem. If the fluorescent light shined more strongly and sooner in
the replication cycling, it meant more virus was present. A PCR
could not only detect DNA, it could also detect genetic material