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Francis Crick Institute
Hundreds of employees at the Francis Crick Institute volunteered to work on coronavirus testing
The days of Dr. Charles Swanton are busy, but the work is rewarding.
The Francis Crick Institute, where he works, has been evaluating doctors at the Royal Marsden Hospital who were sent home after showing symptoms of Covid-19.
Those who are virus free are now back on the job.
Overloaded hospitals have been desperate for more testing facilities like this to help medical personnel return to work.
The UK government set a target of 100,000 tests per day by the end of April, but has struggled to get close to that number.
A test to see if someone has the coronavirus is a complicated process (different tests, which see if someone has had the virus are still awaiting approval).
The molecules on a swab are broken down into genetic code, using chemicals, liquid-handling robots, and a PCR machine (polymerase chain reaction) that can produce billions of copies of DNA strands.
Private and university laboratories across the UK have donated enough equipment for three large test centers in Glasgow, Milton Keynes and Alderley Park in Cheshire.
But having the machines is not enough, they also need mixed cocktails of chemicals to function.
These secret recipes have been tested over time, verified by regulators, and watched by the companies that sell them.
Like a cook with a ready-to-bake cake mix, scientists know all the ingredients, but the exact proportions are company-specific.
The companies that manufacture and sell them are Qiagen, Roche, Merck and Eurofins Genomics. Each has its own recipes, designed for specific models of the PCR machines.
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Francis Crick Institute
Dr. Charles Swanton and his team created their own test kits.
Dr. Swanton and his colleagues at the Crick Institute realized that most of the world would be clamoring for these kits. They also knew that the companies that manufactured them would be flooded.
So instead of waiting, they reverse-engineered their own “homebrew” to evaluate local London medical staff as a volunteer service.
The Crick Institute is chaired by Nobel Prize-winning scientist Sir Paul Nurse, but is not run by the health services.
It is a research laboratory formed from a partnership between Cancer Research UK and London hospitals that include Royal Marsden, Imperial College London, King’s College London and University College London.
Three weeks ago, when the virus swept across Europe, its labs were deemed nonessential and closed. They delivered much of their machinery to the Department of Health and Social Assistance, which is leading the intensification of the tests, outside of hospitals.
Dr. Swanton, at the time, was working as clinical head of Cancer Research UK, investigating how cancer progresses.
“They were going to send us home. I thought, ‘Well, there are a lot of nonessential workers that I know of that could be really essential to the coronavirus effort,'” he says.
Sent a round of email. A working group was 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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Doctors, including Dr. Swanton, many from University College London, and some at a nearby private laboratory in St Pancras called HSL (Health Service Laboratories), worked together to find a new procedure for making the chemical kits with equipment that the government had left. behind.
Dr. Swanton now leads the Covid-19 testing efforts at the Crick Institute.
“We have the staff here, the facilities, the resources, the reagents and the knowledge to go ahead and just do it. And that’s what we choose to do,” says Dr. Swanton.
Their homemade chemical kit (an RNA extraction kit) has been approved through a rapid accreditation process and their operating procedure has been released.
How chemicals work
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The Covid-19 test uses two stages of prepackaged chemical kits to remove the genetic material from the mucus and the cells found on a skin swab.
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 shipped at the tip of the swab.
Enzymes called proteases break down proteins in the sample. (Chemicals similar to laundry detergent are added to cut protein from food stains.)
Another set of chemicals binds 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. This is when the second chemical cocktail comes into play.
PCR kit: around £ 250 for a pack of 200
This chemical cocktail allows the RNA code of the virus in the PCR machine to reproduce itself.
Here RNA is converted to a form of DNA, covered in fluorescent chemicals, and copies are made until there is enough to detect.
If enough bright spots are shown, the test indicates that the virus was present in the sample.
Companies that are best known for making these chemical kits warn against reverse engineering in today’s circumstances.
Dr. Thomas Theuringer, a spokesman for Qiagen, a German chemical company that supplies reagents to the UK, says that replacing these reagent cocktails with homemade recipes is “playing with fire.”
“We can only guarantee that our extractions will work if we perform them in our production facilities where we have a controlled environment. Any mistake and it could get a false positive and create more harm than good,” he says.
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Qiagen
Qiagen is one of the companies that makes virus test kits.
Several reagents produced by the Centers for Disease Control (CDC) in the United States did not produce conclusive results. The CDC later admitted that the kits had been “rushed”.
“We are not talking about baking a cake, it is about life and death,” says Dr. Theuringer.
The benefit of using commercial solutions, he says, is that Qiagen has been manufacturing them for a long time and that the standard operating procedures in its laboratories have been verified by various international health organizations.
Roche, a company that currently also makes reagent kits for test sites in the UK, agrees.
“The main hurdles at another company or manufacturer that produces any Roche test and reagents are time and experience. Roche cannot guarantee safety and reliability if the reagents required for the test were manufactured outside of our production network,” A spokesman told the BBC in an email.
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Eric Cool
US authorities told Professor Kool that his test kits were not the correct type
Stanford University professor Eric Kool says: “People have used homemade beers for RNA extraction for a long time, but to extend the tests it must be done in an automated way so that they can process many samples.”
Professor Kool teaches chemistry at Stanford, runs his own RNA extraction kit business, and offered to help with the effort in the United States, but testing centers there told him his kits weren’t the right type for the machines. that they had installed.
“Something like printer ink: You have to buy the right one for the printer,” he says.
“These kits are all corporate secrets,” he says, but adds that the automated kits have plugins that work best with the kind of 24-hour trial that should be done with Covid-19.
“Even while people sleep, 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 chemical kits in the shortest supply.
The problem is worldwide, everyone is trying to get the same automated RNA extraction kit.
To increase complexity, the companies that sell them have different ideas on which buyers should have priority.
This has been a difficult prospect for Qiagen, says his representative, Dr. Theuringer, because his company has had to find a version of what a fair allowance could be.
“No single company can help meet demand,” he says.
He went from manufacturing 1.5 million kits per month to 20 million per month, hired new staff, and went from a three-shift day to 24-hour work.
Still, they have been unable to keep up with demand and have even passed buyers on to their competitors.
Roche says it remains committed to its partnership with the UK government.
But his spokesman warns that “due to 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 his own test kits for local NHS personnel was the right decision.
“Only time will tell,” he says, “but we thought doing nothing was not an option, really.”
