More than 100 million pints of blood are
transfused into patients each year during emergencies or in surgery. But as
recently as 1999, patients were forced to postpone elective surgery because of
a shortage of blood. Whole blood only lasts six weeks at the most. In
addition, donated blood can carry diseases or produce dangerous immune
responses. Donating blood is a life-saving effort, but it comes with a host of
problems, and no real way to solve them has emerged.
What has emerged is a decades-long
effort to create a substitute for blood that the body can use until it can
naturally replace its own supply when blood is lost. It began in the 1930s,
when a biochemistry student at Cambridge University, Max Perutz, gradually
worked out the structure of hemoglobin and received a Nobel Prize for that work
in 1962.
Human hemoglobin is made up of two
sub-units, each of which contains an iron atom. Iron readily binds with
oxygen, which is how the blood carries that gas around the body. A fully
saturated molecule can carry four oxygen molecules. Various factors influence
how much oxygen the hemoglobin molecule will carry, such as temperature and
pH.
A chemical called DPG causes hemoglobin
to bind less firmly to oxygen. That is a key factor to consider when
developing artificial blood, because in order for hemoglobin to deliver oxygen
to the body, it must let go of the oxygen it carries. If the oxygen is too
tightly attached to the hemoglobin, the blood will carry it, but won’t
give it up when the body needs it.
So when hemoglobin picks up fresh oxygen
in the lungs, it has to deactivate DPG. As it moves toward the delivery site
for oxygen, it has to reactivate the DPG, which also facilitates picking
up carbon dioxide, a waste product. The carbon dioxide is then carried back to
the lungs, and the process begins again.
Clearly, the way the blood carries oxygen
is an amazingly complex process, and attempts to synthesize it have been met
with severe challenges. By the 1980s, researchers were solving the problems
with hemoglobin-based oxygen carriers (HBOCs), through chemically or
genetically engineered molecules. These molecules had the desired
characteristics for carrying and delivering oxygen, as well as extending the
time they lasted in the circulatory system.
HBOCs...
