Blood

When the body loses a large amount of blood, or is unable to manufacture it quickly enough, the blood must be obtained from outside the body.

Blood transfusions are one method of obtaining blood, but there are many issues with this method. Some diseases can travel via the blood, some religious people refuse to accept the blood of other humans, and incorrectly cross-matched blood types can cause other issues.

And so we need generic prosthetic blood, more commonly called substitute blood.

The first blood substitutes date back to the 1600s, shortly after William Harvey discovered blood pathways in 1616. Replacing your blood with urine, plant resins, or beer (as was attempted!) is not going to work, because it misses the point of the blood - to transport oxygen and carbon dioxide through the body.

Even milk was put forward. In 1854, milk was injected into patients in an effort to increase white blood cells in order to fight Asiatic cholera. Enough patients seemed to improve that milk was seen by some as a successful blood substitute, but there was not enough evidence that this was true, so the more skeptical doctors did not pursue this.

In 1868, it was discovered that liquid containing red blood cells work as successful blood substitutes, which started the path towards modern substitutes.

Animal blood was attempted in 1871, but the technical challenges involved in removing toxic materials was too much for the technology of the time.

No real progress was made in blood substitutes for almost a century. During the major wars of the early twentieth century, the need for substitutes was met by donations from humans. Real blood, not substitutes.

In 1964, it was discovered that perfluorochemicals (PFCs) can be used as a temporary blood substitute. Experiments with mice showed that the mice could survive for hours when their blood was replaced with PFC, and recovered completely when the PFC was then replaced with their original blood. PFC was so good at absorbing oxygen that mice that were completely immersed in a bath of PFC could breath normally.

In the 1980s, the research into blood substitutes resulted in the creation of companies to market them, with products such as HemAssist (1985), Polyheme (in development since 1969, but only publically available in 1994), Hemopure (1998). Clinical research focussed on shelf life, effects on blood pressure, vasoconstrictive effects. All three of these popular products are produced from actual real blood that is scrubbed and conditioned to reduce adverse effects that might happen from pure transfusions. The third one, Hemopure, is made from cow blood.

But, because these blood substitutes are based on original biological blood, they do not solve the issues with disease transmission and the religious objections that some people have.

PFCs worked well in mice in the 1960s as a completely non-biological replacement for blood, but there were technical challenges that meant that they could not be used alongside existing blood in the circulation. Firstly, PFCs are not water soluble, so require fatty lipids to be injected alongside them, and secondly, PFCs do not absorb as much oxygen as haemoglobin.

It turns out that you can create haemoglobin completely artificially. A method was developed and tested in 2011 which uses E. coli bacteria which has been engineered to create haemoglobin.

In 2014, a refinement on this idea was developed. Haemoglobin can be toxic if it is not contained within the walls of red blood cells, and artificially created haemoglobin doesn't come packaged in red blood cells. A team in the UK (University of Essex) developed an artificial haemoglobin which was designed to self-destruct rather than become toxic, as it was exposed in the blood stream.