It is nearly 102 years since the death of Paul Ehrlich.”So what? ” you might say. But it was Ehrlich who gave the name “Complement” to the part of the immune system that aHUS patients ,and others , are all too well familiar.
Ehrlich did not discover Complement though; that had been done in 1888 by a George Nuttall , who observed that blood lost certain bacterial killing properties when it was heated. He was not the first to give it a name either ,that was done by Hans Ernst August Buchner who called it “Alexin” ( sounds familiar!) in 1895.
Ehrlich correctly theorised there were two parts to the immune system and in 1899 he renamed the part of the blood that Nuttall had found was heat sensitive- “Complement”, and also identified somethings that today we know as antibodies. He thought that that each antibody had it own Complement to help it ( complement it) do its job ; but it would take a few years before it would be confirmed that there was only one Complement supporting all antibodies.
Ehrlich was not to know the structure of the Complement System and what it was composed of , nor that it also acted on its own in the fight against foreign organisms before antibodies were ready to join in .
A simplified diagram of the Complement System
In the nearly 130 years since that “something in the blood” was found, which became known as Complement, much more is known about Complement; its components , how these components, now identified e.g, C1 to C9 interact , and how other parts or factors are there keep them in check ,CFH, CFI for example.
More and more knowledge is being gathered about how variants of each of the components affect the way the components work and when that causes problems such as aHUS.
In it is only in the last few weeks of pregnancy does an unborn child begin to create the components of its Complement system. At 33 weeks of gestation usually no Complement can be found. Yet within one week of birth a child’s Complement can develop rapidly to reach 80% of its adult levels, although it can be as low as 10%. It is fixed in each of DNA , flaws and all.
What ever the starting point Complement continues to develop until it reaches its full potential as an important part of the immune system, as intended over hundreds if not thousands of millions of years of evolution in most living creatures, such is how ancient Complement is.
So in 130 years , i.e. less than two average life times, there has been an enormous amount of knowledge evolving about Complement; but still all the questions are not answered. Probably more is yet to be known than is known. The “known unknowns” quoting Donald Rumsfeld!
In another 130 years who knows what the aHUS ( if it is still called that) patient will think about early 21st century understanding about Complement.
Ehrlich also developed the concept of the “magic bullet” something that could be created that killed only the organism targeted. The concept of a “magic bullet” has to some extent been realized by the development of a monoclonal antibody ( MAB) linked to a biologically active drug which is “toxic” to living cells
The”Eculizu” monoclonal antibody being the aHUS patients’ magic bullet to stop Complement over complementing,so that it no longer is damaging to their own living cells instead of “foreign organisms”.