More than 350 years ago, William Harvey revolutionised medical science by describing for the first time how blood circulated around the body.
Now scientists are on the verge of another seismic development in their knowledge of blood - producing a synthetic substitute that mimics the lifegiving properties of the real thing but is guaranteed to be free of deadly infections such as HIV and vCJD.
Artificial blood has the potential to solve a huge range of problems: shortages caused by falling donations; the need to ensure that only blood of the same type as the patient is transfused; the difficulty of transporting and storing supplies; and the risk of infection transmission in countries with high rates of Aids. But it also brings with it ethical concerns about how it is made and tested - and sociological quandaries about whether the public will even accept "fake" transfusions.
It will be most beneficial for accident victims who have lost massive amounts of blood and need an instant transfusion at the scene - yet this means testing potential products on people who may be unconscious, in deep shock and unable to consent to being treated with an unlicensed product.
Doctors believe that if it is in the "best interests" of the patient, the non-consent is ethically acceptable, but it remains to be seen whether the public will agree.
William Harvey's 17th-century peers believed that transfusions could not only cure disease but also change personalities, and even experimented with replacing blood with milk and wine - with somewhat predictable results.
Blood transfusions are now routinely given when someone has lost 40 per cent of their own supply and their vital organs are at risk of not receiving adequate oxygen.
But while the process itself is now simple and safe, there are problems with the safety - and supply - of the blood used. More than 1,200 haemophiliacs in Britain were infected with HIV from contaminated blood during the 1980s; fewer than 400 of them are still alive. At least two people are also known to have contracted vCJD, the human form of mad cow disease, from transfusions, and other patients have also been infected with hepatitis.
The National Blood Service now has stringent testing and screening procedures, and says that the risk of being infected is now very low (one in 900,000 for hepatitis B, one in 30 million for hepatitis C and one in several million more for HIV). But the danger of vCJD infection is still there - the scale of the risk is still unknown and does concern both patients and doctors.
Then there is the problem of supply and demand. The National Blood Service says that 8,000 donations are collected every day and transported to hospitals up and down the country. The service does meet the demand but it takes careful managing and there is a continual quest to attract new volunteers - only five per cent of people in the UK are considered to be "active" donors.
An ageing population and the increase in both the number and complexity of surgical procedures are also contributing to the difficulties. Blood cannot be stored indefinitely; it needs to be used within 30 to 35 days and around 10 per cent of all donated supplies are not used.
It also needs to be refrigerated and is therefore difficult to use in life-or-death situations such as at the scene of a car crash or on a battlefield. Which is why the American military first started researching the possibility of developing a synthetic blood substitute during the Vietnam war.
While blood has a number of important functions, the biggest problem during surgery or after an injury is the fall in oxygen being carried to the organs. So the challenge was to create a substance that could mimic haemoglobin, the molecule that transports oxygen and gives red blood cells their colour. Early attempts at creating "fake blood" were unsuccessful and caused toxicity when tested during animal trials, but the researchers learnt by their mistakes and have made huge advances in the last five years.
Haemoglobin can be extracted from out-of-date donor blood, cow's blood and even plants and fungi. It is then modified to ensure it remains stable when injected into the body. Because it does not contain the cells that make blood into different types, the same haemoglobin substitute can be used on all patients. It could be kept indefinitely and could be stored at room temperature, making it easy to transport.
Professor Chris Cooper, of the Department of Biological Sciences at Essex University, says: "Ideally the product would be in a powder form for rehydration with a salt solution when desired. What we are looking for is the powdered milk equivalent for blood."
Professor Cooper is part of the Euro Blood Substitutes Project, which was set up two years ago to investigate the issues around artificial blood and which aims to develop its own product. Researchers from Britain, Denmark, France, Holland, Italy, Sweden and Hungary are involved in the project which is focused on haemoglobin mimickers.
An American firm, Biopure Corporation, has already developed a product, called Hemopure. It is being used in South Africa, which has one of the world's highest rates of HIV infection, but has not been granted a licence in America or Europe.
Hemopure uses haemoglobin from cow's blood - which may make it less acceptable in the US and Europe, where there are concerns about BSE infection. The public may also be resistant to the idea of being injected with blood products from an animal.
While European researchers are focused on haemoglobin-based products, the Americans are turning to another source for artificial blood - a Teflon-type group of synthetic liquids called perfluorocarbons (PFCs). PFCs are capable of dissolving large volumes of oxygen, are cheap and easy to make and are simple to store. But for them to work, patients need to also be breathing 70 to 100 per cent oxygen through a mask, meaning that their use outside a hospital environment is limited.
Some products are in the last phase of clinical trials, when they are tested on humans, but have been shown to produce flu-like symptoms in some patients. And unlike the real red stuff, both haemoglobin and PFC alternatives only work in the bloodstream for a few days, so they are only useful in the short term. However, they do offer real potential for reducing transmission of infection as well as offering a possible alternative to people who object to blood transfusions on religious grounds.
Several American companies are now in the final phases of testing their products in clinical trials and the first artificial blood could be licensed within the next two years.
The Euro Blood project has conducted research into the public's views and initial findings suggest that people favour a synthetic substitute, such as a PFC product, over something derived from cow's blood.
However, Professor Cooper believes that the haemoglobin products are likely to win out in the end. He says: "There are still some hurdles, including the sociological ones about whether people will accept artificial blood but it is very exciting both scientifically and intellectually. Sooner than you think, you are likely to be faced with the offer of a pint of the red stuff [haemoglobin] rather than good old blood donated from an altruistic citizen."
'How artificial blood saved my life'
The daughter of country music star Hank Williams is among the first people to have received artificial blood. Hillary Williams, 27 (right), was severely injured in a car crash in March. The crash site, 45 miles from Memphis, was remote. An air ambulance was dispatched and medics realised she was losing large amounts of blood. They believed that her only chance was to receive a transfusion of PolyHeme, a haemoglobin-based blood substitute that is in clinical trials but hasn't yet been submitted to the licensing authorities. With Hillary in deep shock, the emergency team could not ask for her consent but took the decision to give it to give it to her anyway.
One of the team, Cindy Parker, believes that decision saved Hillary's life. "If she had not received this I don't think she would be here today. I think she would have died before we got to the hospital."
Hillary is now recovering and fully backs the medics' decision. She told USA Today: "I think it's a great thing. God and PolyHeme basically saved my life."
A spokeswoman for the British Medical Association says: "Doctors may decide that it is in the patient's best interests to receive such treatment even if they cannot consent, and that is acceptable."Reuse content