Science: NEW BLOOD? IT'S IN THE BAG

With HIV and CJD undermining faith in blood for transfusions, progress is being made in finding alternatives. Roger Dobson reports on the fakes

ARTHUR COGA was either very brave, very foolhardy, or, just possibly, very intoxicated.

After volunteering to have a bottle or two of sheep's blood infused into him, he was laid on a wooden table in a London hospital and then, by all accounts, joked with doctors as rudimentary metal pumps and needles were wheeled into position.

A few anxious moments later, Coga got his blood. He survived the experience, for which he was paid 20 shillings, and the pioneering procedure, carried out by two physicians in 1667 helped lay the foundations for the modern blood transfusion. A series of setbacks which followed - including several people dying either from viral infections in the animal blood or because they were given the wrong type of blood - delayed the growth in transfusions, which did not take off until the start of the 20th century. Currently, 17 million pints of blood are donated each year across Europe, 13 million in the US and 7 million in Japan.

But after a century of almost unqualified success, there have been mounting concerns about blood transfusions. These include blood shortages, rising incidences of blood-born diseases like HIV and hepatitis, increasing fears that Creutzfeldt-Jakob disease (CJD) has infected blood stocks, and the logistical problems of handling blood in a hi-tech world. Although blood shortages can and are addressed by public campaigns for donors, the popular perception that blood stocks may be infected is growing. As a consequence of concerns like these, the hunt is now on for blood substitutes and even totally synthetic alternatives.

The latest fear to emerge, that CJD may have got into blood supplies given by donors unaware they are incubating the disease, is likely to give further impetus to research. Professor John Pattison, chairman of the Spongiform Encephalopathy Advisory Board, believes that the Government should revise safety procedures on blood. He and others also say it may well be safer for patients to donate their own blood prior to surgery.

As a result of similar fears about viral contamination in the US, there is a growing demand for facilities where people can store their own blood in advance of an operation for which they might need a transfusion. There has also been an explosion in "bloodless" operations, where spilt blood from the patient is cleaned and recycled rather than being sluiced away.

There are also logistical problems in the handling of blood. It must be kept refrigerated and can be stored for no more than six weeks. It cannot be stockpiled for use in disaster relief or for combat-casualty care; nor can it be carried easily on-board ambulances.

The need for typing and cross-matching of patient's blood also means blood transfusions can rarely be given at the optimum time, during the first so-called golden hour immediately following a trauma event.

These concerns have now prompted a dozen biotech companies to work on trials of substitutes and artificial blood. US-based Baxter Healthcare is about to complete work on the world's biggest blood-making factory, a 100,000 square foot production centre in Switzerland, and is expecting to produce its first blood some time next year.

The new substitute products, so far used in trials on more than 1,000 patients, have the potential to change radically the way casualty and other acute patients are treated, and the worldwide market for the successful products is estimated at in excess of pounds 3bn.

For decades, scientists have been looking for a good, usable blood substitute which is free of viral infections and which can be given to patients without fear of side effects. According to Mary Thomas of Baxter Healthcare in Illinois, it was the experiences in the Vietnam war and increasing public concerns about contamination in the 1980s and 1990s, which speeded up research.

The new generation of temporary blood substitutes are oxygen-carrying solutions designed to be an effective short-term alternative to blood transfusions for the treatment of trauma and surgical blood-loss.

One of the main functions of natural blood is to carry oxygen to all parts of the body, and haemoglobin is the natural iron-containing, oxygen- carrying protein in red blood cells. In trauma cases, synthetic blood has the advantage in that it can be administered immediately without losing precious time blood-typing and cross-matching and, unlike real blood, the new materials on trial can be stored for six months to a year and stockpiled for disaster relief. It also reduces the risks of viral transmissions.

Different biotech researchers have a range of strategies for their blood substitutes and differing sources for their haemoglobin. Several, like Baxter Healthcare's HemAssist, use human haemoglobin from outdated human blood to make chemically stabilised haemoglobin solutions.

Because the haemoglobin splits in half when removed from the protective red blood cell membrane, Baxter's researchers have developed a method to stabilise the molecule using an aspirin-based drug. The stabilisation process allows the solution to be put through various anti-viral processes that are not possible with real blood.

Some companies are using bovine haemoglobin, and two such products have so far entered clinical trials. The big attraction of using haemoglobin from cows, which is similar to the human type, is that there is an almost limitless supply, and it is cheap. The down side is that not so much is known about cow's blood.

Research teams are also looking at ways of genetically engineering blood substitutes using micro- organisms and transgenic animals as alternative sources of haemoglobin.

In the micro-organism approach, a product based on a mutant human haemoglobin produced in E. coli bacteria, is now in clinical trials. It involves taking a gene coded for human haemoglobin, inserting it in a parent bacteria cell of E. coli and allowing it to multiply thus producing additional haemoglobin.

In the animal approach, pigs have also been genetically engineered to produce human haemoglobin inside their red blood cells which can then be harvested.

In yet another area, HemaGen in Missouri is looking at using a totally synthetic chemical solution made from perfluro-carbons (PFCs) to deliver oxygen to tissue. PFCs absorb oxygen very readily and, when mixed with certain detergents, form an emulsion that can be administered intravenously and used to deliver oxygen to tissue.

Like most of these first-generation blood replacements, it is a short- term substitute, and does not have the other crucial characteristics of blood that are essential for clotting and the immune system.

But researchers are already working on the next generation of substitutes and the holy grail of scientists is to find a long-term, truly artificial blood. The next stages of research leading towards this goal involve liposome-encapsulated haemoglobin and other oxygen-carrying artificial red cells.

Latest predictions are that there will be a long term artificial blood substitute in use within 25 years. And there are hopes that such a breakthrough will not only radically reduce the need for blood transfusions, but also remove the risks of acquiring infections such as Aids and CJD.

Next week Norman Miller investigates the growing trade in artificial tissues

BLOOD - THE BEST-CELLER

OUR BODIES contain around one gallon of blood. A drop of blood the size of a pinhead contains some 5 million cells, and each cell takes one minute to circumnavigate the body and return to the heart. Approximately once every second the muscular walls of the heart contract and pump the blood out into the arteries.

Natural blood, produced in the bone marrow, carries out a number of functions, including the transport of oxygen around the body to the cells. Haemoglobin, the iron-containing protein that gives blood its red colour, picks up the oxygen and nutrients at the lungs and circulates around the body serving vital organs and tissue.

Blood also contains white cells, which protect the body against illness and fight infection, and platelets, the smallest type of the three blood cells, which help the process of blood clotting.