T.M.S.Chang, O.C.,M.D., Editor-in-chief

(from: Artificial Cells, Blood Substitutes & Imm. Biotech. an international journal, 25:#4,i-ii,1997)

Public concerns regarding HIV in donor blood in 1986 have stimulated efforts to develop blood substitutes. Unfortunately, a product cannot be ready for clinical use without years of research and development followed by years of clinical trials. More than 10 years have passed and it will take another two years for one product and many more years for others to become available for routine use for patients.

Why should this happen, when the basic ideas of encapsulated hemoglobin and cross-linked hemoglobin (Chang,TMS.Science 146:524,1964;Bunn, HF, JH Jandl. Trans Assoc Am Physicians 81:147, 1968) were already available in the 1960's? Had there been a national priority for blood substitutes in blood supply policies 30 years ago, we would have blood substitutes ready in 1986 for the HIV crisis in donor blood. As it is, since 1986, the public has continued to be exposed to the rare though a potential hazard of HIV and hepatitis in donor blood. Even in 1997, blood substitutes are still not ready for routine clinical use for another two years or more. Even when they are ready, these are only first generation blood substitutes. Much still needs to be done for the 2nd and 3rd generations of blood substitutes.

Why should we go further than the present first generation blood substitute products now in clinical trials? One only needs to imagine what would have happened in other areas if we had followed the same line of question. What would have happened if we had stopped at penicillin and did not develop further generations of antibiotics? What would have happened if we had stopped at method of detecting hepatitis B in donor blood and did not go further with hepatitis C and HIV? The first generation blood substitutes are only for short-term uses in some surgery and trauma. Their circulation half-time is only 24-30 hours, compared with the red blood cell circulation time of more than 100 days. They do not have the red blood cell enzymes needed against oxidants. These are important in reperfusion injuries and in preventing methemoglobin formation. Furthermore, little is known about the physiopathological aspects of blood substitutes.

With the present economic problems around the world, granting agencies have to divert their resources to areas of national priorities. What is left is then divided among the many other nonpriority areas, including blood substitutes. Some even suggest that the blood substitute industries can support all the research in this area. Unfortunately, most of the industries in this area are small companies that are devoting their resources to the very expensive ongoing clinical trials. We are therefore facing the same problem for research and development on blood substitutes as in the 1960's. We cannot afford to repeat the mistake. The first thing to do is urgently to establish blood substitutes as a priority in the national blood supply system. Only this way can this area receive the urgently needed priority support.

In addition, we need urgently to pool the very limited resources and to bring together the different groups. The Bayer/Canadian Red Cross Society Research and Development Fund in collaboration with the Canadian Medical Research Council is one example of joint efforts. However, we urgently need a national priority for more extensive joint efforts. This should include the national research agencies, various federal and provincial agencies, the Red Cross Societies, the blood agencies, the industries, user groups and other concerned groups. It is only by doing this with the present limited resources that we can effectively move forward and not repeat the mistake of unnecessary delays in the public use of fully developed blood substitutes.

Researchers and developers of blood substitutes have already taken up their responsibility. They have organized an international network - the International Society for Artificial Cells, Blood Substitutes and Immobilization Biotechnology. This network has an international scientific committee on blood substitutes representing major research groups, agencies, industries and other interested groups from around the world. This international network organizes and holds the International Symposia on Blood Substitutes Series, besides the Congresses of the society. This group also publishes an international journal where a large proportion of the papers on blood substitutes are published - Artificial Cells, Blood Substitutes & Immobilization Biotechnology, an international journal. The web site for this group is: http://www.artcell.mcgill.ca It is now time for the many national committees and commissions in countries around the world to take up their responsibility. Several of them have already spent a tremendous amount of resources and time retrospectively to find and solve problems related to donor blood. It is now time to look to the future and to include blood substitutes as a priority area in national blood supply policies, on a long term basis.