The scientists who made a ‘home-brew’ coronavirus test
The scientists who made a ‘home-brew’ coronavirus test
Hundreds of Francis Crick Institute employees volunteered to work on coronavirus tests
The days of dr. Charles Swanton are busy, but the job is rewarding.
The Francis Crick Institute, where he works, tested doctors in London who were sent home after showing symptoms of Covid-19.
Those found free of the virus are back to work.
Overworked hospitals have been desperate for more test facilities like this to help medical staff get back to work.
The British government set a target of 100,000 tests per day by the end of April, but has struggled to get closer to that number.
A test to see if anyone has coronavirus is a complicated process (several tests, which see if anyone has ever 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 (polymerase chain reaction) machine that can make billions of copies of DNA strands.
Private and university labs across the UK have donated enough equipment to three huge test centers in Glasgow, Milton Keynes and Alderley Park in Cheshire.
But having the machines is not enough, they also need cocktails mixed with chemicals to work.
These secret recipes have been tested over time, verified by regulators and supervised by the companies that sell them.
Like a cook with a mix of pre-baked cakes, scientists know all the ingredients, but the exact proportions are specific to each company.
The 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 Charles Swanton and his team created their own test kits
Dr Swanton and his colleagues at the Crick Institute have understood that most of the world would have clamored for these kits. They also knew that the companies that made them would be submerged.
So rather than waiting, they reversed their “home brew” to test local medical staff in London as a voluntary service.
The Crick Institute is led by the Nobel Prize winning scientist, Sir Paul Nurse, but is not managed by the health services.
It is a research laboratory formed by a 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 crept into Europe, their labs were considered non-essential and closed. They have delivered much of their machinery to the Department of Health and Social Care, which is conducting the testing phase, outside of hospitals.
Dr Swanton, at the time, worked as the UK’s leading cancer research clinic, researching how cancer progresses.
“We would have been sent home. I thought to myself: ‘Well, there are many non-essential workers I know who may actually be quite essential to the coronavirus effort,” he says.
He sent a circular email. A working group has been formed. At the same time, Mr. Nurse sent an email to his Crick Institute employees asking for possible volunteers for a laboratory.
He received 300 replies in 24 hours.
Doctors 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 equipment. that the government had left behind.
Dr Swanton now leads the Covid-19 tests at the Crick Institute.
“We have the staff here, the facilities, the resources, the reagents and the know-how to go ahead and just do it. And that’s what we chose to do,” says Dr. Swanton.
Their homemade chemical kit (an RNA extraction kit) was approved through a rapid accreditation process and they did their public operating procedure.
How chemicals work
The Covid-19 test uses two stages of pre-packaged chemical kits to extract the genetic material from the mucus and cells present on a skin swab.
RNA extraction – about £ 350 for a 50 pack
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 destroy all cells that are sent to the tip of the swab.
Enzymes called proteases break proteins in the sample. (Similar chemicals are added to the laundry detergent to cut proteins in food stains.)
Another series of chemicals attaches 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 – Approximately £ 250 for a 200 pack
This chemical cocktail allows the virus RNA code in the PCR machine to reproduce.
Here the RNA is converted into a form of DNA, coated with fluorescent chemicals and copies are made until they are sufficient to detect.
If enough bright spots appear, the test indicates that the virus was present in the sample.
The companies best known for making these chemical kits warn against reverse engineering in current circumstances.
Dr Thomas Theuringer, a spokesman for Qiagen, a German chemical company that supplies reagents in the UK, says that replacing these reagent cocktails with homemade recipes is “playing with fire”.
“We can only ensure that our extractions work if we make them in our production facilities where we have a controlled environment. Any mistakes 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 failed to 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 implementing them for a long time and that the standard operating procedures in their laboratories have been verified by several international health organizations.
Roche, a company that currently also manufactures reagent kits for UK test sites, agrees.
“The main obstacles in another company or manufacturer producing Roche tests and reagents are time and competence. Roche cannot guarantee safety and reliability if the reagents required for the test were produced outside our production network” , a spokesman for the BBC said in an email.
Eric Kool, a Stanford University professor, says: “People have been using homemade beer for RNA extraction for a long time, but to increase the size of the tests they have to be done automatically so they can process many “samples.
Professor Kool teaches chemistry at Stanford, has his RNA extraction kit business and has offered to help the effort in the United States, but the test centers there told him that his kits were not the right type for machines they had in place.
“A bit 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 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 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 that are 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 over which buyers should have priority.
This was a difficult prospect for Qiagen, says his representative, Dr. Theuringer, because his company had to find a version of what could be a fair allocation.
“No company alone can help meet the demand,” he says.
He went from producing 1.5 million kits a month to 20 million a month, hired new staff, and went from one day to three shifts working all day.
However, they were unable to meet demand and even passed buyers on to their competitors.
Roche claims to remain committed to its partnership with the UK government.
But his spokesman warned that “due to the high demand for reagents and consumables, in some cases the supply situation could be difficult in the short term”.
Dr Swanton cannot say whether the right choice was to make his own test kits for NHS staff.
“Only time will tell,” he says, “But we thought that doing nothing wasn’t an option, really.”