Antibodies and Scientific Credibility

There is no tweezer small enough, no pipette tip narrow enough, that can allow scientists to physically touch proteins. They’re just too dang small. So how do we get around that? Antibodies.

Without these small glycoproteins, modern biology as we know it would not exist. In fact, without antibodies you would not exist. These proteins recognize pathogens in your body, bind to them, and direct white blood cells to the pathogens to destroy them. This elegant defensive technique is called the adaptive immune system. The “adaptive” part of that name refers to the unique characteristic of B-cells to create new antigens based on interactions with pathogens. Basically, if your body recognizes something that will make you sick, it not only stores the molecular fingerprint of the offender, but also creates matches to that fingerprint carried by antibodies so that any similar attacker can be caught and destroyed.

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An antibody binding to a pathogen. Image from turbosquid.com

Scientists have learned how to take advantage of this adaptive quality of the immune system to make molecular fingerprints of proteins they are interested in. The take their protein, inject it into a rabbit or mouse or some other host animal, and then collect the antibodies that respond to the injection. Of course, this is a skimmed down version of antibody generation, but you get the idea.

You can imagine that doing this procedure is both expensive and time-consuming. A scientist has more pressing matters to attend to than generating antibodies for their experiments. It was logical then, for pharmaceutical companies to step in and take on that role.

Of course, once you allow the free market to step in you have multiple companies with competing antibodies. Some companies are definitely better than others, and this becomes a problem when, as a scientist, you are attempting to interpret results. It is not enough to trust the scientist doing the work, you have to trust the company who manufactured the antibody.

So, if you are looking at results from immunofluorescence staining, for example, not only do you have to question the results in terms of their biological relevance, but you also have to question the specificity and validity of the antibodies used.

Neurons!

Antibodies are used to highlight cellular structures, like the Schwann cell (red) in this neuromuscular junction.

 

 

This is not to say that our current modus operandi is inherently flawed. Rather, because of the lack of regulation and verification, commercial antibodies not only introduce waste into scientific endeavors (both in terms of time and money), but also introduce a layer of suspicion inherent in most results. If antibodies were vetted by some unbiased third party, much of the fat that goes into laboratory expenses could be trimmed, and that, I think, is worthwhile.

The intersection of -omics

One could argue that the art of Science is choosing which lens to view your subject with. For certain diseases you could apply a variety of -omics, (genomics, proteomics, metabolomics, etc.) to explore the mechanisms behind the pathology of your disease. Each -omic, each lens, will offer the investigator different insights into the same larger truth.

The problem is that people become deeply invested into their own particular lenses, and therefore they only see one angle of the deeper reality. Therefore, a geneticist may only consider a mutation as the only important finding in the same tumor sample that a metabolomics expert may be keenly interested in because he believes he can pinpoint how cancer cells use local lipid stores to fuel their progression. Both of these points of view provide insight into a larger truth- how the tumor grows in vivo, at the intersection and ultimate culmination of every -omic occurring simultaneously.

What is the answer to this problem? Undoubtedly collaboration is important. Bringing together experts from each of the -omics to provide a cohesive picture is not only helpful for contextualizing each others’ research, but imperative in establishing a framework with which to target interventions within.

But I like to think of a scientist as the person behind the microscope, able to flit between one lens and the next with practice and ease. To me, if you want to be able to attack a pathology with the keen scientific insight required to tackle Modern Science’s most difficult questions, you have to have a macro multi-faceted view of your subject.  It is not enough to know just one angle. A scientist must strive for the larger truth behind the sliver they normally see. That truth? It lies at the intersection of the -omics.