Maintaining a Balance Topic 13: Artificial Blood and its Importance Biology in Focus, HSC Course Glenda Childrawi, Margaret Robson and Stephanie Hollis

DOT POINT Analyse and present information from secondary sources to report on progress in the production of artificial blood and use available evidence to propose reasons why such research is needed.

In The Past In 1616 when William Harvey first described the circulation of blood, scientists started thinking about whether blood could be replaced by other liquids to cure diseases. This included wine and milk! sciencephoto.com

In The Past Attempts to treat massive bleeding in soldiers during WWI and II often failed and this spurred on modern efforts to produce artificial blood in the hope that this could prove more effective in replacing blood. med-dept.com

In The Past Severe bleeding is a life- threating condition because of the loss of two main functions to blood: Transport of oxygen and its delivery to the cells Maintenance of fluid volume, water and salt concentration and blood pressure in the internal environment en.wikibooks.org

In The Past Although these functions could be served by transfusing donated blood or blood products into patients, blood transfusions bring with them their own problems as we know. granthammatters.co.uk

In The Past The need for artificial blood was at first identified to overcome early setbacks associated with transfused blood, such as: Cross matching blood types The short storage life (only a few weeks) before donated blood and products must be discarded The difficulty transporting blood into battle zones armedforces-int.com

In The Past There was a resurgence in military- driven efforts in research for a blood substitute in the 1960’s, in response to difficulties in supplying blood to soldiers in the hot jungle conditions during the Vietnam war. (American and Australian soldiers were there between 1962 and 1972). The search was on for an oxygen-carrying solution that could expand the blood volume and also deliver (release) the oxygen to tissues where it was required. en.wikipedia.org

Progress It was during this era that a breakthrough was made by Dr. Leland Clark, who began experimenting in the mid-1960’s with oxygen carrying compounds known as perfluorocarbons. pinterest.com

Progress Research into artificial blood continued slowly and with poor results until the late 1980’s, when active and urgent research began in response to sudden appearance of HIV in patients who had been given blood transfusions. This brought with it concerns of the transmission of other infectious diseases such as Hepatitis C. avert.org

Progress The ideal characteristics expected in an artificial replacement for blood have become more complex and include characteristics that were identified in the past as well as some new requirements. For example: Can be stored for long periods and easily transported Does not need to be cross-matched for different blood types Can be produced in large quantities at low cost Is completely safe (has no toxic effects on the body and is free from disease) Does not trigger an immune response Continues to circulate (does not settle out) and, once the patient’s own blood is restored, may be safely excreted.

Areas of Research The main area of current research, however, targets the transport of oxygen so that it is easily picked up and, more importantly, efficiently released where it is required. Three main types of oxygen carriers are being developed: perfluorocarbons (PFCs), haemoglobin-based oxygen carriers (BHOCs) and artificial red cells called microcapsules. clevelandleader.com

Areas of Research perfluorocarbons (PFCs) carry oxygen in a dissolved form. They can carry up to 50 times more dissolved oxygen than plasma, enough to supply sufficient oxygen to tissues in the absence of red blood cells. biomed.brown.edu

Areas of Research The main difficulty with these products is in enabling them to mix with the bloodstream – they must be combined with lipids to form an emulsion. The lipid tested was approved by the Food and Drug Administration in the USA, but has not been successful because it cannot be given large enough quantities to produce a significant result. Future research includes improved versions of perfluorocarbon emulsions for easier combination with blood. en.wikipedia.org

Areas of Research Haemoglobin-based oxygen carriers (HBOCs) involve extracting haemoglobin from out-dated donated human blood and modifying it to a form in which it can be used in artificial blood. Raw haemoglobin cannot be used, as it exists in an unstable form that is potentially toxic and can damage surrounding tissues and the kidneys. dujs.dartmouth.edu

Areas of Research Current research for the development and use of HBOCs in artificial blood involves the cross-linking of the haemoglobin to enzymes found naturally in blood, to create a more stable ‘second generation’ HBOC that will not break down. tdgnews.it

Areas of Research Second generation HBOCs will not be ideal as they are not protected by a red blood cell membrane. Future research involves enclosing the haemoglobin, with the required enzymes, inside an artificial cell membrane- a lipid vesicle- to increase the circulation time. gizmag.com

Areas of Research Artificial red cells are currently being developed as microcapsules of phospholipid into which haemoglobin can be placed, but research is still in early stages. attach.sciencedirect.com

Current Research At present there is no safe and effective artificial blood products being used in Australia and the USA, where scientists continue to develop and test possible blood replacements. However, the AIDS crisis in South Africa has been a driving force in it becoming one of the first countries in the world to clear artificial blood for limited use in patients. thecommonwealth.org

Current Research The brand Haemopure is made from stabilised bovine (cattle) haemoglobin in a balanced salt solution. It has a shelf life of 36 months and can be stored at room temperature. The haemoglobin molecule is 1000 times smaller than a red blood cell, allowing it to flow through partly blocked arteries and so it may be useful in heart surgery.

Current Research Polyheme, currently awaiting approval in Australia and the USA, is a brand of artificial blood that has been produced in laboratories in South Australia. It is made from modified haemoglobin from human red blood cells. It can deliver oxygen up to three times more efficiently than red blood cells. Both of these have a very short circulation time (12-24 hours) compared with 50 days for donated red blood cells. phlebotomists.co.uk

Current Research Another area of current research is the study of crocodile red blood cells. Using a ‘neutron-scattering’ technique, scientists have found that crocodile haemoglobin molecules can link together to form more stable haemoglobin. Raw human haemoglobin tends to break up and enter the kidneys (which is bad), linked crocodile haemoglobin molecules do not enter the kidneys. medicineworld.org

Advantages of Artificial Products The main advantages of the current artificial bloods available is that they meet the following expectations: They can be sterilised They can be stored for long periods of time No cross-matching is needed (no cell membranes) There is no risk of infection Perfluorocarbons are relatively cheap to produce inhabitat.com

Advantages of Artificial Products No substitutes have been developed as yet to carry out immune defence or clotting of blood. These are areas for future research. mazecordblood.com

Activity/Homework Complete DOT Point 2.10 Artificial Blood -Students to present a 2 minute presentation to the class next lesson about the progress of research into artificial blood.