Racing to make coronavirus tests

Disclaimer: The author of this article is married to an employee of one of the companies featured in this article. For the sake of impartiality, the company in question will not be named.

When explaining how countries could control the spread of COVID-19, the Director-General of the World Health Organization was blunt. Dr. Adhanom Ghebreyesus said that countries “must isolate, test, treat and trace” if they wanted to suppress the pandemic’s growth. But that approach requires nations to have the necessary infrastructure to identify and test those with the infection. The UK has struggled, with tests being rationed and only used in hospitals or other healthcare settings. The UK purchased 3.5 million finger-prick tests in the hope of harnessing them as part of a wide testing scheme. But researchers, when attempting to validate the products, found they don’t actually work.

The situation is little better in the US, with testing numbers falling far short of what experts say is needed. BBC News reported that a retired doctor, Claudia Bahorik, believed she had symptoms, but despite requesting a test on March 9th, she was still waiting for results on the 23rd — the CDC said her profile did not qualify her, at the time, for one of the rationed tests. Her plight illustrates the US failure to follow the “test, treat and trace” strategy. And The New Yorker reported that in South Dakota, there is just one public health laboratory conducting COVID-19 tests for the entire state of close to 900,000 people.

The New York Times found that the UK government lacked the means to test every suspected case. Reporters even identified a rogue private doctor who bought up tests to sell at a high markup to private clients. Public Health England, the nation’s public health body, has advised against using these tests, which are yet to be proven accurate. But in desperation, people are turning to these kits as the country struggles to implement a holistic nationwide testing regime. And it’s not clear where the solution is coming from.

A small private DNA and drug testing company sits in a secure unit on the site of a decommissioned Air Force base in Norfolk, in the east of the UK. It normally supplies DNA relationship testing for court cases relating to immigration and family disputes. It also offers “peace of mind” tests, a home DNA-testing kit sold in major retailers, that enable people to check their family relationships. The company decided to use its expertise to help out as the coronavirus crisis began to become apparent.

“We’d all seen the news about a need for testing,” said Dr. Thomas Haizel, the lab’s managing director, “and decided that we could do it.” The company believed it could quickly and easily use some of its capacity to bolster the testing facilities at the nearby hospital. Not only did it have the raw materials to produce tests, but it has a number of automated Polymerase Chain Reaction (PCR) machines, each one costing up to £100,000 ($122,000). And thanks to the Chinese scientists who successfully sequenced the genome for SARS-CoV-2 back in January, the blueprint for the test is known.

The company emptied out a pair of labs, turning them into a virology suite that would be suitable for COVID-19 testing.

In the UK, labs are graded on their Containment Level (CL), which determines what organisms they can handle. Public Health England said that researchers that propagate, culture or do any form of “deliberate work on SARS-CoV-2” must be a CL3 lab. But standard tests for the virus, run on commercially available auto-analyzers, only require CL2. The only requirement that Haizel’s lab couldn’t immediately meet was having a specific form of Microbiological Safety Cabinet, or MSC.

It certainly had several MSCs already, but these were hard-wired into the DNA-testing facilities and so couldn’t be moved. Unfortunately, in the early stages of a pandemic, it’s not a piece of kit that’s particularly easy to get. And so began a frantic race to call every lab supplier in the country in the hunt for a spare cabinet. The company found one, 200 miles away, but it couldn’t make a delivery for several weeks due to high demand. Rather than wait, one employee -- armed with his own truck -- drove to collect it the following day.

With the MSC delivered, the team planned to have a working test facility up and running by March 23rd. And then the power ran out. “The day before we were due to have [the MSC] commissioned, a local power transformer went down, and we lost power to the site,” said Dr. Haizel. The company quickly found and set up a generator, and after a short delay, technicians got the system going. The lab now has the ability and capacity to offer COVID-19 tests — it’s just waiting for approval from official bodies.

How does a PCR Test work?

Polymerase Chain Reaction testing involves the application of oligonucleotides to strands of Deoxyribonucleic and Ribonucleic Acid…

Okay, how does a PCR test work, and please explain to me like I’m five.

A strand of DNA is usually represented as a ladder, with two uprights and a series of rungs that connect them. Normally, this ladder is curled, like a spiral staircase, but it’s easier to imagine a ladder propped up against a wall. RNA (Ribonucleic Acid), by comparison, looks as if someone just sliced a ladder from top to bottom, with one upright and shorter rungs sticking out of the side. We’re talking about RNA, by the way, because SARS-CoV-2 is a virus with RNA rather than DNA.

Each rung of this half-ladder is one of four different nucleotides, which make up any organism’s genetic code. Because the genome for COVID-19, or more accurately SARS-CoV-2, has been sequenced, you can create a “primer,” essentially a chunk of genetic material that finds and joins on to the SARS-CoV-2 code. Add some more ingredients and you can make a section of DNA that sits on or beside the SARS-CoV-2 strand. But this strand, on its own, is too small to be spotted by an analysis machine.

So, to make it bigger and, therefore, readable, you heat the mixture to separate and essentially duplicate the strands, and then let it cool. The more times you do this, the more times the strands will separate and replicate until you’ve got enough of a sample to see. All you have to do then is add a dye or fluorescent marker to find this material, and you can see if the SARS-CoV-2 RNA is present. This is how Polymerase Chain Reaction, or PCR, tests work.

A number of laboratories in the UK are working to devote resources to help the effort against COVID-19. In a statement, King’s College London said it’s offering its staff to support King’s College Hospital. King’s also has a commercial DNA lab that offers paid-for relationship testing for court cases and private individuals. It said it would work to “free up laboratory space for COVID-19 testing” and offered an “inventory of all the PCR machines on site to amplify NHS resources.”

In the US, Quest Labs told NPR that it has a backlog of 115,000 tests that it has yet to process. And while the company has successfully managed to increase the number of tests it can process, it is still overwhelmed. The report added that Quest’s tests take between four and five days to process. This, coupled with failures with initial kits and supply shortages, has meant that testing is far behind where it needs to be.

By comparison, Germany’s labs are said to be processing tens of thousands of tests each day and began manufacturing test kits in January. Italy, which has been hit hard by the virus, has said it plans to begin nationwide testing in the hope of restarting its economy very soon. The picture is different in some African countries, with Science reporting that several (unnamed) nations on the continent have only one or two facilities capable of conducting the tests.

A number of large international biotech companies, like Bosch and bioMérieux, are developing rapid COVID-19 tests. Tech companies, including Verily, Google/Alphabet’s life sciences subsidiary, have joined the effort in various ways. A presidential announcement claimed that the company was building a tool to help screen for COVID-19, which, according to The Washington Post, prompted employees to scramble to make one. It has since launched a testing program, offering drive-thru swabs in California as part of the wider Baseline project.

Plenty of other big names in tech have pivoted to help in some way with the effort against the coronavirus. Razer has pledged to make surgical face masks that can be given to healthcare workers working with COVID-19 patients. Similarly, Tesla has offered to produce ventilators to cover the likely fall in supply when current resources become overwhelmed.

In the eyes of another lab owner, it’s going to be a long wait before the overwhelmed UK government can approve independent tests. “There’s no point going top-down at the moment on anything,” says Mike Fischer, the co-founder of Research Machines and Alamy. He has funneled his wealth into the Fischer Family Trust, which bankrolls bodies in education, research and conservation.

One of Fischer’s tentpole projects is Systems Biology Laboratory (SBL), an Oxfordshire lab that looks into improving healthcare outcomes. SBL specializes in things like DNA instability, cancer immunotherapy and examining the medical applications of vitamin D. It has deep ties with a number of general practitioners (GPs) in the region and offers help when asked.

“My chief scientist was approached by a practice asking if [we] could test a couple of their GPs,” said Fischer. The doctors in question were showing symptoms of COVID-19 and were concerned that they were putting their patients at risk. “We ordered the first testing kit on March 6th,” said Fischer, and SBL could see “how valuable it was to [doctors] both motivationally and practically.”

Since SBL was already involved in biological research, it was an easy process to set up its PCR machines to offer the test. Since then, the lab has reached out to a number of GP surgeries in South Oxfordshire, testing more than 200 medical staff twice a week. That is enabling doctors and nurses who are free of COVID-19 to return to work while carriers can isolate as soon as possible.

These small-scale tests have inspired Fischer to set up the COVID-19 Volunteer Testing Network, a body that helps private labs test healthcare workers. “Our big thing is a call to labs,” said Fischer, who has the knowledge, resources and equipment to help. Fischer has promised to fund “consumable costs” for these tests out of his own pocket and will offer additional monetary support where required.

This sort of private largesse shouldn’t be necessary, but unfortunately, it is now. In the UK and US, there may be the capability and capacity to offer COVID-19 tests to those that need them, but both countries have so far struggled. They’ve been unable to implement the WHO’s isolate, test, treat and trace strategy, and the consequences could be very, very, bad.