Scientists create 'plastic' blood

The researchers said the artificial blood was easier to store Scientists have developed an artificial plastic blood which could act as a substitute in emergencies.

Researchers at Sheffield University said their creation could be a huge advantage in war zones.

They say that the artificial blood is light to carry, does not need to be kept cool and can be kept for longer.

The new blood is made up of plastic molecules that have an iron atom at their core, like haemoglobin, that can carry oxygen through the body.

The scientists said the artificial blood could be cheap to produce and they were looking for extra funding to develop a final prototype that would be suitable for biological testing.

'Very excited'

Dr Lance Twyman, of the university's Department of Chemistry, said: "We are very excited about the potential for this product and about the fact that this could save lives.

"Many people die from superficial wounds when they are trapped in an accident or are injured on the battlefield and can't get blood before they get to hospital.

"This product can be stored a lot more easily than blood, meaning large quantities could be carried easily by ambulances and the armed forces."

A sample of the artificial blood prototype will be on display at the Science Museum in London from 22 May as part of an exhibition about the history of plastics.

How plastic blood could move from test tube to battlefield

We're all familiar with the calls for blood donors. But donated blood, while valuable, also poses risks to the recipient, including diseases such as hepatitis C or HHIV, the virus that causes Aids.

Wouldn't an artificial form be better? It could be made completely sterile, and might even be manufactured in dehydrated form: just add water and you have a litre of O negative, the universally transfusible version, which could be easily transported to locations where it was needed, or stored against future need.

Lance Twyman is trying to do just that: with a PhD from the University of Kent, he's working to make usable plastic blood in his University of Sheffield laboratory.

Twyman has long been interested in creating molecules that mimic nature, including synthetic enzymes to catalyse novel reactions. Early in his career he came across porphyrins, hollow square-shaped molecules which combine readily with metals like iron. "The iron is in the centre of the molecule, just like haemoglobin," says Twyman.

Things are not quite the same in nature, of course. Although the oxygen-carrying protein haemoglobin in your red blood cells contains an iron-based porphyrin to bind oxygen reversibly (so it can grab oxygen from the air in the lungs, and then give it up at the tissues), porphyrin alone won't work. "It clumps together or ends up reacting with the oxygen rather than just binding it," says Twyman. "But if you combine porphyrin chemistry and polymer chemistry, you can make a molecule which mimics haemoglobin."

Oxygen binding

Making an artificial blood might not have occurred to Twyman were it not for a chance discussion with a cardiologist. Although perfect blood substitutes are a clinician's dream, creating something just to carry oxygen around the bloodstream seemed intriguingly feasible.

Developed over the past five years, Twyman has now done just that by combining a porphyrin with monomers that build together in a hyper-branching or tree-like structure. His molecule is remarkably similar to haemoglobin in size and shape, while providing exactly the right environment around the porphyrin core for iron to bind and release oxygen. And the polyethylene glycol (PEG), a water-soluble polymer used to assemble the branched structure is already used for medical applications.

So what does it look like? Twyman's plastic blood is a dark red water-soluble paste with the consistency of honey. As with real blood, the colour comes from the porphyrin.

Putting plastic blood into your body - even to save your life - sounds risky. But Twyman points out that porphyrins are natural. He also reckons that the polymer component would be ignored by the body's immune system; there is some reassurance from existing medical uses. So far, though, his experimentation is confined to the test tube.

"At the moment, we have no idea regarding the polymer's lifetime in the body. However, for its intended application, a short lifetime is an advantage," says Twyman. "One obvious application is the battlefield or site of a major incident where replacing blood loss quickly can save lives."

Unlike donated blood, it's easy to store and is stable at room temperature. A second-generation molecule is now being developed for more rigorous investigation and, if all goes well, human use may eventually follow.

Professor Adrian Newland, president of the Royal College of Pathologists, says that people have worked on artificial blood for many years. It remains the medical equivalent of the holy grail - mainly because small foreign molecules in blood substitutes are swiftly removed from the bloodstream by the kidneys. "The drive has been to develop a larger molecule that will stay in the circulation and carry oxygen to the tissues," Newland says.

The EU-funded Euro Blood Substitutes consortium is also undertaking such research and includes biochemist Professor Chris Cooper of the University of Essex. He says that there are two types of blood substitutes - haemoglobin-based substitutes, which use human or bovine haemoglobin, and the perfluorocarbons. "Many compounds have gone into clinical trials and there are currently two products licensed for use," Cooper says.

Twyman's work now offers a third possibility that doesn't depend on haemoglobin supplies. "It's an interesting bit of chemistry. What they have to do is prove that the molecule is stable for hours in the presence of oxygen," Cooper says. "The phrase 'plastic blood' is cute, but a bit of a red herring as all blood substitutes add PEGs [polyethylene gycols]."

Body's defences

Newland worries about using PEGs in the body in transfusion quantities, although small-scale medical use is well established in association with drug delivery. "The amount of PEG that you'd give with artificial blood is several times larger than the amount we give attached to a simple drug. There needs to be some idea of what happens to PEG if it's given in that volume," Newland says.

While Twyman cannot yet answer such concerns, he says his approach uses a branched PEG, not the simple linear PEGs found with haemoglobin-based blood substitutes. "Hb [haemoglobin] work uses Hb extracted from animal or human blood. This has to be protected from the body's defences, usually using linear PEGs. These do work, but they migrate into the fatty lining of veins, which causes toxic effects. They also cause high blood pressure and there are ethical/religious issues regarding their general use," Twyman says.

Newland says that modified haemoglobin doesn't stay in the blood circulation long and can cause allergic-type reactions. But once haemoglobin is removed from the body's red blood cells, no cross-matching is needed before use.

An oxygen-carrying molecule that mimics haemoglobin would have universal donor characteristics - although the immune response and clearance time from the bloodstream is as yet unknown.

"If you are giving artificial blood, you don't have to worry about the transmission of infection from blood from donors, shelf life and the lack of availability from donations," Newland says. "It's a very interesting concept."

While Twyman believes his work might find military use one day, the Ministry of Defence is unwilling to comment until more research has been done. Meanwhile, the plastic blood will be in "Plasticity - 100 years of making plastics" at London's Science Museum from May 22. Plastic blood may yet benefit people beyond laboratories.

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