Stephen Withers, a professor in the University of British Columbia’s Department of Chemistry, has long been intrigued by mechanisms of enzymatic reactions. More specifically, he has developed an expertise in reactions that involve a sugar, which includes how sugars might be removed from or added to larger molecular arrays. As it turns out, this skill set is perfectly suited to exploring some major medical challenges, such as the degradation of starches associated with diabetes or inhibiting influenza by removing a key sugar that allows the virus to spread.
Among the most ambitious of these undertakings has been Withers’ work on blood types, which are distinguished by the presence of particular sugars on a red blood cell’s surface.
“We have a Centre for Blood Research campus and I saw this as an area where we could provide some input,” he says, recalling how he got into this field about six years ago. Now he and his colleagues are on the hunt for enzymes that would transform blood from any donor into the same chemical format as what is known as type O, a “universal” version that can be given directly to any recipient, regardless of what their particular blood type might be.
Biochemist Stephen Withers, University of British Columbia
That accomplishment would be a milestone in and of itself, but it becomes even more remarkable in the context of how our attitude toward blood has evolved over the last two decades, along with the organizations that have become responsible for this unique product. As chemical concoctions go, few are more complex than blood and fewer still are more directly critical to the well-being of practically any animal on the planet. Our appreciation of its importance undoubtedly reaches into the mists of pre-history, since the effects of blood loss would have been obvious to anyone with experience of a significant wound. However, a genuinely scientific appreciation only goes back as far as the 17th century, when the pioneering anatomist William Harvey concluded that the body contains just a finite amount of blood that circulates continuously. Like the equally fundamental assertion that the earth goes around the sun, this observation might seem obvious to modern students who have been taught nothing else, yet each was a seminal insight. In the case of blood, that insight further augmented its value, confirming that this was nothing less than an extraordinary substance.
Today we know that blood serves as the backdrop for biochemical functions that range from the transport of oxygen throughout the body to providing a home for the immune system cells that fend off disease. We have also made a major enterprise out of transfusion, a life-saving practice that was honed at the beginning of the 20th century with the discovery of the various blood groups, so that an exchange of blood between donor and recipient could be conducted safely and successfully. By the time World War I was under way, further insights into the storage of blood had enabled the creation of blood banks that were necessary to treat the massive number of battlefield casualties. Later it was understood that extracted plasma could be substituted for whole blood during a transfusion, so that during World War II techniques for drying plasma made it possible to export blood from the United States to Britain.
An even greater challenge was overcome in the 1960s, when it became possible to isolate specific blood products that would allow haemophiliacs to live normal lives with the injection of missing components that would allow their blood to clot and save them from potentially fatal injuries. But while such decade-by-decade progress reinforced public confidence in our ever-increasing understanding of blood and its crucial role in medical treatment, that confidence was shattered in the 1980s as this same population of haemophiliacs became high-profile victims of a new and unknown epidemic. Thousands of Canadian patients receiving these blood products acquired the formerly unknown human immunodeficiency virus (HIV), an incurable ailment that could devastate the immune system and leave individuals vulnerable to death from simple infections.
It took years for researchers and health authorities to figure out how to cope with HIV, which still ranks as a major threat in many parts of the world. What was immediately apparent in Canada, however, was the inability of institutions handling blood products to deal with the appearance of deadly pathogens carried by the donors who were being recruited to shore up the blood supply for various medical procedures. Besides the 2,000 recipients in Canada who contracted HIV from blood transfusions, another 30,000 became infected with Hepatitis C. Around a quarter of all these people subsequently died, leading to a major criminal investigation and upward of $10 billion in legal claims.
This notorious “tainted blood crisis” also spawned a Commission of Inquiry led by Mr. Justice Horace Krever, which spent four years reviewing the underlying causes of the problem and recommending fundamental changes aimed at preventing any repeat of this tragedy. The most prominent result was the creation of Canadian Blood Services, an entirely new body at arm’s length from government, which took over the duties of blood bank management that had been handled by the Canadian Red Cross Society for decades, as well as establishing an entirely new interface between medical practitioners who require blood for their patients and members of the research community like Withers, for whom blood represents a lynchpin of scientific study.
According to Dana Devine, who is Chief Medical and Scientific Officer for Canadian Blood Services in addition to being a professor in UBC’s Department of Pathology and Laboratory Medicine, Krever’s Commission fostered a revolution in the Canadian approach to blood. In fact it represents a rare example of health care consensus, one that is supported by the federal and provincial governments alike. At the heart of this administrative structure is not just a commitment to the handling of blood products so that the safety of recipients becomes a top priority, the CBS also maintains a research and development capacity to make sure this priority can be met with the latest scientific insights.
“We’re trying to build capacity in the country,” explains Devine, who represents a small cadre of research scientists within Canadian Blood Services who are based in Vancouver, Edmonton, Hamilton, Toronto, Ottawa, and Halifax.
“We have a presence in the universities in each of those locations as well,” she adds, noting that the organization has built links not just with the science, but with scientists themselves and above all their protégés.“We wanted to have some direct pipeline into trainees.”
Dana Devine, Chief Medical & Scientific Officer for Canadian Blood Services [Canadian Blood Services]
Devine points out that the overarching objective is not just a matter of being on the lookout for hazards in the blood supply, but an unprecedented ability to build new testing protocols should anything unexpected appear. Expected hazards, such as HIV and Hepatitis C, have all but disappeared, but if that record provides renewed assurance to a Canadian public that may once again be taking the safety of blood products for granted, Devine insists that Canadian Blood Services is not resting on its laurels. The organization is working with researchers to bring other technologies into mainstream practice, such as the identification and classification of cellular components.
“Each person who walks in the door of a blood clinic is a unique source of raw material,” she says, noting that the latest research attempts to match optimal donors with optimal products. “You can’t qualify that raw material the way you would qualify steel to build cars. Some people will make, say a blood platelet that just doesn’t like being kept in a plastic bag and being shaken around at room temperature for 7 days. The quality of those platelets is much worse than the average quality of everybody else’s platelets.”
An even more basic shift in attitude among doctors and surgeons affects whether they need to use blood at all.
“Blood operators are probably the only industry where we actively spend a lot of time and money trying to drive ourselves out of business,” Devine argues. “We’ve seen in the last 10 years or so a real change in how we think about blood transfusion, to the point where we’re basically saying the best transfusion is no transfusion.”
This outlook has been facilitated through innovative surgical techniques, such as minimally invasive procedures using laparoscopic instrumentation. Similarly, caregivers coach their patients so that they will be healthy enough to avoid needing blood during such procedures. The use of blood in all kinds of elective surgeries has consequently plummeted, with an associated shift in the proportion of various blood types being used. An increasing share of blood transfusion now occurs under emergency conditions, where there may be little time to sort out blood groups. Under these circumstances the preferred type is O, which removes any worry about compatibility problems.
“That means the demand for O blood has grown proportionally compared with what it was a decade ago,” says Devine. “From the blood operator’s side, we now see that our orders are shifting to be more disproportionate to the blood types of people who walk into clinics.”
This sets the stage for the work being conducted by Withers and his colleagues. If all of this donated blood can be turned into a single pool of type O, it will simplify life for everyone sorting out the donations and increase the supply available for emergencies.
Withers observes that the scientific genesis of his current work goes back to the 1980s, when the ability to manipulate enzymes was less sophisticated. His own lab has also refined its strategy, starting with “directed evolution” — a form of natural selection to identify the best enzymatic candidates for cleaving blood sugars — to the application of metagenomics, which transfers pre-selected DNA samples into bacteria as part of a high-throughput effort to find these candidates.
“The screening may be less time-consuming,” he acknowledges, “but what still really takes time is the biochemistry follow-up when you get a hit on a particular enzyme.”
While he searches for one of those hits, administrators at Canadian Blood Services stand ready to receive their own hits, in the form of something unusual that would threaten the blood supply. At the same time, the concept of “tainted blood” slowly recedes into little more than a memory — among the most bitter that the country has ever faced — given the number of known threats that are now being encountered.