From Lamb-Grown To Lab-Grown: The History And Future Of Blood Transfusions

But it may not be for much longer. As societies across the world grow older, and their populations – and therefore the local donor pools – shrink, scientists have explored an alternative option: artificial blood.

So how did we get here?

A search in vein

Even for our most ancient ancestors, the fact that blood was somehow important to human health probably didn’t escape their notice. For a long time, though, we often figured the problem was too much, rather than not enough, of the red stuff – which is why physicians were using leeches to cure their patients some 3,000 years earlier than they were trying to perform blood transfusions.

That delay, though, probably saved countless lives. The first forays into blood-swapping weren’t what you’d call “successes” – or, for that matter, “sensible”.  To be honest, they were downright horrifying: “Although the exact date is disputed, it is believed that on either June 15 or 28, 1667 a Parisian physician and astrologer, Professor Jean-Baptiste Denis […] performed the first blood transfusion involving a human,” notes the Anesthesia History Association of the University of Wisconsin School of Medicine and Public Health. “The patient was a feverous young man on whom other doctors had employed leeches 20 times […] Denis transfused him with several ounces of either dog or lamb’s blood”.

It would be a while before people started thinking “hey, maybe humans should have human blood inside of them” – but even then, problems still remained. The first successful human-to-human transfusion – a last-ditch attempt to save a hemorrhaging mother using the blood of her husband – didn’t occur until 1818, at the hands of obstetrician James Blundell. His achievement made him something of a celebrity, and no wonder: in his subsequent transfusions, he was able to boast an astonishing success rate. A full 50 percent of his patients survived.

If that sounds low by modern standards, know this: Blundell was working with an advantage. “Blundell limited the use of his transfusion apparatus to women on the verge of death due to uterine haemorrhage, the heavy bleeding that can result from a difficult labor,” explains the UK’s Science Museum, and “a pregnant woman’s immune system is naturally lowered [which] means blood compatibility is not as much of a complication.”

Today, undergoing a blood transfusion is much, much safer – and that’s mostly thanks to one guy: Karl Landsteiner. It was he who, in 1901, figured out the ABO blood group system based on the presence of various antibodies on the surface of the red blood cells; it was also Landsteiner who, nearly 40 years later, helped identify the Rhesus factor that completes our modern blood type classifications.

At last, the stage was set for lifesaving blood transfusions. No more lambs’ or calves’ blood; no more transfusions from whoever happens to be in the room at the time – science now knew that humans had specific blood types, and only certain combinations could be successfully given and received. 

What could go wrong?

A bloody mess

The theory may have been sound – but it wouldn’t take long for the practical problems with blood transfusions to make themselves known. As injuries from two World Wars stretched blood reserves to their limit, health agencies took to splitting the blood into red cells, plasma, and platelets in an effort to ration them out further: “Division into components allowed donations to benefit three patients rather than one,” transfusion medicine specialist James Stubbs told Mayo Clinic in 2022. 

“Each patient would receive only the lacking blood portion, such as platelets,” Stubbs explained. “Since individual blood component volumes were lower, patients could get higher doses of the blood constituent needed in lower total volumes.”

It made the blood less effective overall – even if the ingredients are recombined, separating them out seems to sacrifice something along the way – but there were advantages past simple resource management. Component therapy, as the now-ubiquitous technique is known, means the availability of “universal” components for transfusion – a critical resource in emergency situations where a patient’s blood type is not immediately known. 

That’s not possible with whole blood transfusions – you really do need fully matching blood types for everything to go as well as possible. And here’s the problem: that’s completely unfeasible right now.

Why? Well, where to start: first of all, blood has an extremely short shelf life – the platelets, in particular, last just five days once donated, and even the best-preserved blood is much, much worse at its job than the stuff still inside your arteries. To continually have enough of every blood type, even the rarest of them, would be a logistical nightmare in terms of storage and turnover.

And that’s assuming such reserves could even be found. In many places, that’s not the case: in Japan, for example, donating blood is twice as popular as in the US – but the aging population is forcing the pool of eligible donors down. At the same time, the group of those who need that blood – primarily the elderly, who cannot donate – is growing. Increasingly, alternatives to the traditional methods are being sought out of not just curiosity, but necessity.

Elsewhere, other concerns are prompting the search for blood substitutes. In the US, for example, healthcare is notoriously price-dependent – and real blood, it seems, is too expensive. 

“The problem here is that there’s practically no reimbursement for prehospital blood by insurance and agencies,” renowned trauma surgeon John Holcomb told the New Yorker in February of this year. “And, in our system, if you don’t get reimbursed you don’t do it.”

The bleeding edge

So, with dwindling reserves, rising costs, and questions around efficiency, what could be the solution to our bloody woes?

The first blood substitute arrived, arguably, much earlier than you might have thought. So-called crystalloids – solutions of low-molecular-weight solutes dissolved in water, such as the currently-ubiquitous 0.9% saline solution – have been used to boost the volume of fluid, if not blood proper, within the body since 1831. 

But such products are not without dangers: “They were smart people back then, and they thought they were doing good,” Holcomb said. But crystalloid, he explained, does not heal the holes in the blood vessels that result from massive blood loss – “so now the fluid goes into the vessel and out into the tissue, and you get edema, and edema makes everything not work – the brain, lungs, kidneys, muscle, everything.”

Much better, then, would be a replacement that could somehow mimic real blood much more closely – and in very recent times, that’s precisely where the research has led. In the US, hopes are pinned on ErythroMer, a freeze-dried, entirely synthetic “blood”, designed to be universally compatible and stable at room temperatures (it reportedly looks like raspberry milkshake, and tastes… less than appealing).

Elsewhere, researchers have chased lab-grown blood – blood which, while artificial, is based on the real stuff. Japan has, only this year, begun clinical trials on a new potential: “blood” created by extracting hemoglobin from expired donor blood and encasing it in a new shell. The result, in theory at least, is an infusion of red blood cells with no blood type – the kind of thing that could make the difference between life and death in emergency situations.

It’s not the first clinical trial of artificial blood, either globally or even in Japan itself. Research into various options has been ongoing in the UK and Japan since 2020, with tentative success: a Japanese trial in 2022 found that up to 100 mL of a new artificial blood substitute could be tolerated in humans without severe adverse effects; in the UK, in the same year, the NHS RESTORE trial carried out its first in-human transfusions of lab-grown artificial blood, with no untoward side effects reported.

So far, these trials have only been small and preliminary. That’s partly for safety concerns – after all, would you be the first to accept an untested artificial blood transfusion, knowing what happened to Jean-Baptiste Denis’s patients? – but it’s also partly bureaucratic: the tech is simply so new that health agencies aren’t quite sure how to classify it, delaying its testing and rollout as governments try to figure out how it should be regulated.

Still, researchers are cautiously optimistic about the initial results. If a safe, effective, and user-friendly blood substitute could be developed, it could be a game-changer across the board: not only would it be invaluable in emergency situations where blood is needed urgently and blood types cannot be gauged, but it would also solve the problem of so-called “blood deserts” – areas, often rural and low-income, where more than 75 percent of patients in need of a blood transfusion cannot access it.

It’s a big goal to aim for. We may not have to wait all that long for it to appear, though: by some estimates, the new Japanese artificial blood cells should be available for practical use within five years. Until then, though, it seems there’s just no substitute for the real deal – and Dracula, we suppose, will just have to fight the Red Cross for access.