Back in the mid-1960s when I first came across the clinical
use of antibodies what was frequently employed was gamma globulin, a massive
amount of mixed IgG, immunoglobulin G, from many people and it was somewhat
tried as another treatment for a variety of disorders including some cases of
mumps. However the specificity of IgGs and the other immunoglobulins had not
yet been ascertained.
As this identification progressed it became apparent that
specificity of the antibodies could perhaps be a tool to attack certain
disorders, including cancers. This then led to many examinations of ways to
produce large volumes of specific antibodies. The result was the development of
monoclonal antibodies. Simply this is the chimeric combination of antibodies
developed to attack a specific target and a vehicle cell that had immortality
to bind this product to so it became a small factory for production. From this
came, after a significant amount of effort, the monoclonal antibody, and in
turn the new therapeutics ending in –mab.
The work of Marks, The Lock and Key of Medicine, is an
effort to tell this story. It starts with some of the early researchers in the
UK who persevered to get some of the initial samples available and the ever
changing dynamic of researchers and clinicians. As with so many efforts of this
type, there is an ever challenging set of steps that the researchers and the
clinicians go through, some winning and some losing. The early days of the late
1960s, when in the practice of medicine little was truly understood but the
tools for the researchers were coming on quickly.
The author takes the reader through the many individuals and
the many crises and victories as they progressed. The book focuses on the many
individuals and their steps in developing MABs and the ultimate
commercialization of them and their application to human therapeutics.
As we progress we have seen basically four classes of Mabs.
They are: murine or mouse versions with therapeutics ending in –omab, chimeric
murine and human Mabs with the ending –ximab, the humanized Mabs ending in –zumab,
and finally all human Mabs ending in –umab. Mabs are now one of the arms in
treating a variety of diseases from cancer to arthritis and colitis. At the
same time they have become “big pharma” and the author takes the reader through
this process in some detail.
Overall, the book and an excellent articulation of the
people, the conflicts, the achievement, and the institutional progress. From that
perspective is an excellent contribution.
On the other side it would have been more helpful to have
provided some simpler introductions to Mabs and the immune system. For a well-educated
reader this is an interesting tale of scientific and clinical development. It
does lack a feeling of personal involvement. The description of the individuals
is in my opinion quite arm’s length and unlike other works of similar genre
this is a discussion of facts and events and dates.
What I especially missed was the recent explosion of
applications. For example in advanced melanoma there is the use of Mabs and
pathway control therapeutics such as BRAF inhibitors and MEK inhibitors. This
raises the issue of how does one see a blending of these two or are they not so
complementary. On the other hand there are certain cancers such a prostate
cancer which may be so complex and changing at such a rapid rate that Mabs
would just not work. It would have been useful for the author to have
contributed some substance to the debate.
Overall, again, this is an excellent book albeit for
possibly a smaller community of engaged readers.
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