Dr. Charles Swanton’s days are busy, but the work is rewarding.
The Francis Crick Institute, where he works, tested doctors at the Royal Marsden Hospital who were discharged after showing symptoms of Covid-19.
Those who have been found free from the virus are now back to work.
Overcrowded hospitals are in desperate need of more testing facilities like this one to help medical personnel return to work.
The UK government has set a target of 100,000 tests per day by the end of April, but is struggling to get close to that number.
A test to see if someone has the coronavirus is a complicated process (various tests, which see if someone has already had the virus, are still waiting for approval).
The molecules of a swab are broken down into genetic code, using chemicals, liquid handling robots and a PCR (polymerase chain reaction) machine that can make billions of copies of strands d ‘DNA.
Private and academic laboratories across the UK have donated enough equipment for three huge test centers in Glasgow, Milton Keynes and Alderley Park in Cheshire.
But having the machines isn’t enough, they also need mixed cocktails of chemicals to work.
These secret recipes have been tested over time, verified by regulators and kept by the companies that sell them.
Like a cook with a ready-to-bake cake mix, scientists know all of the ingredients, but the exact proportions are specific to each company.
Companies that manufacture and sell them include Qiagen, Roche, Merck and Eurofins Genomics. Each has its own recipes, designed for specific models of PCR machines.
Dr. Swanton and his colleagues at the Crick Institute realized that most of the world would demand these kits. They also knew that the companies that made them would be overwhelmed.
So rather than waiting, they reverse engineered their own “home brewing” to test local medical staff in London as a voluntary service.
The Crick Institute is chaired by Nobel laureate scientist Sir Paul Nurse, but is not managed by health services.
It is a research laboratory created in partnership between Cancer Research UK and London hospitals which include Royal Marsden, Imperial College London, King’s College London and University College London.
Three weeks ago, when the virus spread across Europe, their labs were deemed non-essential and closed. They handed over a large part of their machines to the Ministry of Health and Social Affairs, which is leading the ramp-up of tests, outside of hospitals.
Dr. Swanton, at the time, worked as the chief clinician at Cancer Research UK, researching how cancer progresses.
“We were going to be sent home. I thought to myself, “Well, there are a lot of non-essential workers I know who might actually be quite essential to the coronavirus effort,” “he said.
He sent an email. A working group has been formed. At the same time, Mr. Nurse sent an email to his employees at the Crick Institute asking for possible volunteers for a laboratory.
He received 300 responses in 24 hours.
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Clinicians, including Dr. Swanton, many from University College London, and some in a private laboratory near St Pancras called HSL (Health Service Laboratories), worked together to find a new procedure for making chemical kits with the equipment that the government had left behind.
Dr. Swanton is now leading Covid-19 testing efforts at the Crick Institute.
“We have the staff here, the facilities, the resources, the reagents and the know-how to go on and just do it. And that’s what we chose to do, “says Dr. Swanton.
Their homemade chemical kit (an RNA extraction kit) has been approved through a rapid accreditation process and they have released their procedures.
How chemicals work
The Covid-19 test uses two stages of pre-packaged chemical kits to extract genetic material from mucus and cells found on a skin pad.
RNA extraction – around £ 350 for a pack of 50
In this part of the test, the genetic code of the virus, its RNA, or ribonucleic acid, is found, cleaned and separated.
Enzymes and other chemicals break down all the cells that are sent to the end of the swab.
Enzymes called proteases break down proteins in the sample. (Similar chemicals are added to the laundry detergent to reduce protein in food stains.)
Another set of chemicals sticks RNA to a membrane.
And the reaction takes place in a liquid called a buffer.
At this point, the RNA is still too small to be detected. That’s when the second chemical cocktail comes into play.
PCR Kit – Around £ 250 for a pack of 200
This chemical cocktail allows the virus RNA code in the PCR machine to reproduce.
Here, the RNA is converted to a form of DNA, coated with fluorescent chemicals and copies are made until there is enough to detect.
If enough bright spots appear, the test indicates that the virus was present in the sample.
The companies that are better known for manufacturing these chemical kits warn against reverse engineering under the current circumstances.
Dr Thomas Theuringer, spokesperson for Qiagen, a German chemical company that supplies reagents to the UK, said that replacing these reagent cocktails with homemade recipes was like “playing with fire”.
“We can only guarantee that our extractions will work if we do them in our production facilities where we have a controlled environment. Any mistake and you could get a false positive and create more harm than good, ”he says.
Several reagents produced by the Centers for Disease Control (CDC) in the United States have not produced conclusive results. The CDC later admitted that the kits had been “rushed”.
“We’re not talking about baking a cake – it’s about life and death,” says Dr. Theuringer.
The advantage of using commercial solutions, he says, is that Qiagen has been manufacturing them for a long time and that standard operating procedures in their laboratories have been verified by several international health organizations.
Roche, a company that also currently manufactures reagent kits for test sites in the UK, agrees.
“The main hurdles in another company or manufacturer that produces Roche test and reagents are time and expertise. Roche cannot guarantee safety and reliability if the reagents required for the test have been manufactured outside our production network, “a BBC spokesperson said in an email.
Stanford University professor Eric Kool said, “People have been using homemade infusions for a long time for RNA extraction, but for scaling up, testing has to be done in an automated way that you can process many samples. “
Professor Kool teaches chemistry at Stanford, owns his own RNA extraction kit business, and has offered to help the United States, but test centers have told him that his kits are not suitable for machines. that they had in place.
“Much like printer ink – you have to buy the right one for the printer,” he says.
“These kits are all business secrets,” he says, but adds that the automated kits have plug-ins that work best with the type of 24-hour test that needs to be done with Covid-19.
“Even while people are sleeping, robots can run samples,” he says.
This is the crux of the problem with large test sites, such as those built by the government.
The PCR machines they have collected from laboratories across the UK will work best with the rarest chemical kits.
The problem is global, everyone is trying to get the same automated RNA extraction kit.
To add to the complexity, the companies selling them have different ideas that buyers should take priority over.
This has been a difficult prospect for Qiagen, says its representative, Dr. Theuringer, because his company had to find a version of what a fair allowance might be.
“No single company can help meet demand,” he says.
It has gone from manufacturing 1.5 million kits per month to 20 million per month, hiring new staff and going from one day in three shifts to 24-hour work.
Despite this, they were unable to meet demand and even passed on buyers to their competitors.
Roche says it remains committed to its partnership with the British government.
But his spokesperson warns that “because of the high demand for reagents and consumables, the supply situation can be difficult in the short term in some cases.”
Dr. Swanton cannot say whether making their own test kits for local NHS staff was the right decision.
“Only time will tell,” he said, “but we really thought that doing nothing was not an option. “