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To help the wounded soldiers of the Second World War, a Canadian lab freeze-dried and mass-produced plasma through innovate methods Canada would later abandon. These scientists want to pick up where they left off

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At the trauma bay of St. Michael’s Hospital, Andrew Beckett and his team depend on fresh, clean blood products to treat severe injuries. Dr. Beckett set out to learn about the blood serum Canada made in the Second World War to see how it could improve transfusion medicine today.Sammy Kogan/The Globe and Mail

Andrew Beckett says he will never forget witnessing a Canadian soldier bleed to death during a United Nations peacekeeping mission in Croatia in 1994.

Dr. Beckett, who is director of trauma at St. Michael’s Hospital in Toronto, was a 24-year-old paramedic at the time. The solider he was attending to was a combat engineer, severely injured by a bouncing mine – a device that jumps up when triggered and explodes at waist height.

The soldier was evacuated for medical treatment and given an intravenous saline solution to maintain blood pressure and prevent shock. With no blood products on hand to replace what he was losing or to promote clotting, the soldier succumbed to his multiple wounds. “That always stuck with me,” Dr. Beckett said. “We were just giving him salt water.”

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Dr. Beckett served in Croatia in the summer of 1994, during the violent upheaval after the breakup of Yugoslavia.Supplied

Decades later, with another war in Europe under way and geopolitical tensions rising elsewhere, Dr. Beckett worries that Canadians troops could find themselves in similarly dire circumstances if they are involved in an armed conflict.

“The ability for us to get blood products overseas is going to be critical to supporting our casualties, if it comes to that,” he said.

As a lieutenant-colonel with the Royal Canadian Medical Service, Dr. Beckett has been drawing on his own experience and on Canada’s wartime medical history in his efforts to improve the country’s preparedness for treating the wounded in future combat situations.

It’s a career-long quest that unexpectedly led him to a museum exhibit sample of freeze-dried blood serum that Canada produced during the Second World War.

In an experiment he describes as “a combination of transfusion medicine and Indiana Jones,” the historic material was reconstituted and analyzed in a laboratory at St. Michael’s last year to test its long-term stability.

“Even after 80 years the sample still showed activity,“ said Kanwal Singh, a scientist with Defence Research and Development Canada, who collaborated with Dr. Beckett on the project.

The result, published earlier this year in the British Journal of Haematology, reveals the robustness of an emergency treatment that is no longer in use by the Canadian military, but which was a mainstay of battlefield medicine during the Second World War.

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Kanwal Singh from Defence Research and Development Canada helped Dr. Beckett take freeze-dried plasma from 1943, which this empty bottle once contained, and see how well it had held up over time.Sammy Kogan/The Globe and Mail

Connaught Laboratories made 400,000 bottles of blood serum during the Second World War. In 1941, staff test the production process at their Toronto facility, while in North Africa, wounded soldiers receive the serum at a casualty station. Sanofi Toronto Archives

Back then, at a time when the population of Canada numbered only 11.5 million, 2.5 million individual blood donations were made to the Canadian Red Cross in support of a public campaign dubbed “Blood for the Wounded.”

That blood became the basis for the production of 400,000 bottles of freeze-dried blood serum in Toronto under the supervision of insulin codiscoverer Charles Best. An additional 30,000 bottles was produced at the University of Montreal.

The product was made by putting whole blood through a centrifuge to separate out red blood cells, platelets and proteins known as clotting factors.

What remains is blood serum, a yellowish fluid containing additional proteins, such as albumin and other beneficial constituents. When the clotting factors are not removed, the result is blood plasma.

Both serum and plasma can be freeze-dried – or lyophilized – to remove its water content. This enables long-term storage and easy transportation.

“What you’re left with is a powder,” said Dr. Singh. “Essentially, it’s like whey protein.”

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Connaught's equipment could separate the red cells from donor blood, leaving serum and plasma that could be freeze-dried for later use.Sanofi Toronto Archives

According to Roderick Bailey, a medical historian and research fellow at the University of Oxford, about 109,000 of the bottles of the freeze-dried serum made it to Canadian and British forces on the front lines during the war, where they proved invaluable.

Unlike whole blood, which has a limited shelf-life and requires refrigeration, freeze-dried blood products – serum or plasma – can be stored at room temperature for longer periods of time and then reconstituted simply by adding water.

It was therefore ideal for forces without ready access to medical support, like those involved in the airborne and amphibious assaults that occurred during and after D-Day.

“You’ve got your bottle of distilled water and you’ve got your dried blood product. Neither needs to be in the fridge. So it’s easy. It’s quick,” Dr. Bailey said.

The method, used effectively during the Second World War, can help keep injured soldiers alive while they are transported away from danger to a place where there are supplies of whole blood or available donors.

In other words, said Dr. Singh, the freeze-dried blood product “bridges to whole blood and whole blood bridges to surgery.”

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Red Cross blood clinics got millions of Canadians to donate during the war years, but the spread of hepatitis raised concerns about how to protect recipients from tainted supply.Sanofi Toronto Archives

So why would a system that proved so successful 80 years ago no longer be in use by the Canadian military today?

A key part of the answer is the risk of contamination that comes with pooling donated blood, which was common at that time. Toward the end of the war it became increasingly apparent that some recipients were developing viral hepatitis. By the 1950s military use of freeze-dried serum had ceased in Canada.

The need also diminished. After the Korean War, Canadian troops were less likely to find themselves wounded in combat without access to blood or the possibility of an airlift. In addition, freeze-dried blood plasma, now regarded as preferable to blood serum, can be purchased from international suppliers should the need arise.

But for years Dr. Beckett has advocated that Canada resume producing freeze-dried blood products as a secure supply for its armed forces, taking advantage of modern screening methods to avoid contamination. Starting in 2014, he began working with Canadian Blood Services on the development of a prototype product – a freeze-dried blood plasma rather than serum, in order to provide more clotting power to staunch wounds.

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The war in Ukraine has created high demand for products to treat wounded soldiers, like this one at a stabilization centre in Donetsk.ROMAN PILIPEY/AFP via Getty Images

Since then, reasons for moving ahead with the idea have only grown, he said.

One is the changing nature of the battlefield, as demonstrated by the war in Ukraine. That conflict features higher casualties and new threats such as drones, which were not a factor when Canadian soldiers were active in Afghanistan a decade ago.

Another reason became clear during the COVID-19 pandemic: At times of global crisis, countries who rely solely on international sources for their crucial medical supplies are vulnerable.

“Having a domestic product available would give us some buffer against the shocks that could come,” Dr. Beckett said.

Beyond the military, a made-in-Canada freeze-dried blood product could also be useful for emergency responders serving remote areas across the country, he added.

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Dr. Beckett's research focused on the Connaught lab's work under Charles Best, left, who co-discovered insulin with Frederick Banting, right.The Globe and Mail

It was Dr. Beckett’s interest in advancing this project that led him, a few years ago, to delve into the history of Canada’s wartime production of freeze-dried serum led by Charles Best.

The role was one that Best was well prepared to take on at the time by virtue of his previous experience.

“That’s essentially what he did for the first insulin factory, in 1923,” said Christopher Rutty, a Toronto-based public health historian. “He ran the show.”

As with insulin in its early days, Connaught Laboratories in Toronto became the production site for the freeze-dried serum. A public entity at that time, Connaught was later privatized in the 1980s and its scientific legacy now resides with the multinational pharmaceutical company Sanofi.

In the course of researching the story, Dr. Beckett came across a photo of a museum-style display cabinet located at Sanofi’s Toronto facility. Within the display, he could see what appeared to be a bottle of the original 1940s-era blood product. Here, he realized, was an opportunity to test something he had long been curious about: how long could freeze-dried serum hold up?

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Opening up this 80-year-old bottle from the Sanofi collection was 'like stepping back in time,' Dr. Beckett says.Supplied by Christopher Rutty

To explore the possibility, he tracked down Dr. Rutty, who serves as resident historian and manager of the Sanofi Toronto archives. Then the pandemic hit and the idea was temporarily shelved. Finally, last year, Dr. Beckett was able to get access to one of a few bottles of the freeze-dried serum that Sanofi has in its collection.

“It was like stepping back in time,” said Dr. Beckett, describing the moment when the 80-year-old bottle was cracked open in the laboratory. “We knew we would be able to use some of the product to illuminate Best’s, the Canadian Red Cross and Connaught Lab’s great contribution to transfusion and Canadian military efforts in World War II.”

For the test, he and Dr. Singh added sterile water to the freeze-dried serum, first produced and bottled in 1943. They also prepared fresh blood serum from the pooled, donated blood of 10 people to act as a control.

The 80-year-old serum produced a large amount of solid proteins that precipitated out of the solution and could be removed. What was left was a liquid that still contained most of the same constituents as fresh serum, though in lower quantities.

The sample was also found to contain small quantities of DNA of the Hepatitis B virus. This was a clear reminder of the original problem with using pooled blood in the 1940s. It’s not known if the serum would still cause an infection after so many years, Dr. Singh said, but the results do not rule out the possibility.

Nevertheless, the reconstituted serum “still retained its original purpose,” as a means of expanding volume in the blood stream during trauma while helping maintain the body’s response to injury, the researchers reported in their study.

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Canadian Blood Services is developing its own freeze-dried plasma, and Dr. Beckett's team had an old enough sample to see what would happen if it were reconstituted.Jeff McIntosh/The Canadian Press

In another part of the experiment, they also reconstituted a four-year-old sample of the prototype freeze-dried plasma under development by Canadian Blood Services. This proved comparable in performance to a fresh frozen plasma preparation.

The results indicate that the freeze-dried plasma, if produced in Canada, can be successfully stockpiled and deployed as needed by the military.

The Department of National Defence and Veterans Affairs Canada recently approved a new round of funding for Canadian Blood Services to continue working on freeze-dried plasma, with the goal of testing its product in a future clinical trial.

“It’s been a torturous journey, but I think we are moving in the right direction now and will be able to get a freeze-dried plasma product into the hands of Canadian clinicians to benefit all patients, whether military or civilian,” Dr. Beckett said.

The outcome may serve to revive another feature of Canada’s relationship to its military that was present during the Second World War, when the practice of donating blood carried emotional resonance beyond its medical importance.

“It’s the tie between the home front and the soldiers fighting,” Dr. Beckett said. “There’s tremendous psychological impact in being able to resuscitate casualties with blood.”

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