The rate at which microorganisms harmful to our health are adapting to the various treatment modalities (drugs) currently available is very alarming and dreading. It is unfortunate to say that it seems that we're not one step ahead of these tiny, invisible-to-the-naked-eye organisms that are behind the various diseases that have affected humans since the beginning of history.
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| Prof. Randy Schekman, Nobel Medicine Laureate. Image credit to Nobel.org |
Why it seems that we in the medical field are not one step ahead of these tiny organisms there can be many reasons. Topmost among them is the lag in basic fundamental research. Late last year,
Professors Randy Schekman, James Rothman and Thomas Suedhof who jointly shared the
2013 Nobel Prize in Medicine lamented over what they termed a neglect on basic research when the the US National Institute of Health created a Centre for Advancing Translational Sciences. In the words of Prof. Suedhof "......we don't have anything to 'translate' because we just don't understand the fundamental diseases of the brain....". His opinion is buttressed by the fact that there have emerged strains of the tuberculosis-causing organism, Mycobacterium tuberculosis, that are resistant to all known anti-TB drugs; the same could be said of some strains of the Staphylococcus species which cause myriads of diseases in humans. The problem here is that even the most recent drugs used in eradicating these organisms have the chemical structural framework and pharmacodynamics (a drug's way of carrying out its work in the body) that was developed in the 1960s and 70s; and there is no enemy being fought by its adversary with the same tactics over 4 to 5 decades, who will not evolve defence mechanisms that will one day confer on it total immunity from such tactics and also allow it to mount fatal attack on the adversary.
Another reason for this lag in our effort to be ahead of these disease-causing organisms is the lack of a large scale, collective and multidisciplinary undertaking to study in minute details the various ways in which these organisms evolve drug-resisting defence mechanisms. And what I mean here is an undertaking similar to the global Human Genome Project that saw to the successful sequencing of the whole human genome.
Having outlined these two reasons, I would now set out suggestions as regards how we can totally be in control of this fight against these human disease-causing organisms.
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| Prof. Kary Mullis. Image credit to NNDB |
While it may seem that basic research in the area of drug development is not blossoming as we expect it, some tiny silver linnings I can fathom from some corners around the world. The one that comes to my mind is the work being done by the Nobel Chemistry laureate,
Prof. Kary Mullis (he won the 1993 Nobel Prize in Chemistry for his invention of the Polymerase Chain Reaction, a technique used to create billions of a single DNA segment in a few hours).His concept of
Altermune which he explained on the TED talk show conference is something that will give our tiny, microscopic adversaries a surprisingly lethal blow. Prof. Kary Mullis is taking a new, novel and radical approach towards fighting drug resistance in bacteria and other disease-causing microorganisms. The Altermune concept is a technique that uses an artificially synthesized molecule called Alphamer or Altermune linker to re-direct our own immune system to destroy these invading bacteria and other disease-causing microorganisms. An Alphamer or Altermune linker consists of a short sugar chain (an alpha galactose oligosaccharide)---which normally is not attacked by the body's immune system despite the immune system producing antibodies in response to its exposure---linked to a synthetic DNA segment called an aptamer with a specificity for only a particular strain of a virus or bacterium such that once this particular microorganism (which may be resistant to all available antibiotics, antiviral agents and other drugs in this case) invades the body, the aptamer segment of the Altermune linker binds to it and the antibodies produced in response to the galactose oligosaccharide exposure (but which does not harm it) will in the process be exposed to fresh food (the invading disease-causing organism), destroying it, both personally and by inviting other hungry guys of the immune system---the macrophages, the cytotoxic T cells and the complement system. Prof. Mullis has tested his new work on mice infected with a strain of Staphylococcus aureus resistant to even the most potent antibiotic---this became his enemy because it killed his professor friend---and recorded almost 100% wipe out of this bacterium from the blood of the mice after a set period unlike in the controls which used various antibiotics such as doxycycline; further studies are going on in other animals such as chicken infected with the flu virus, using Altermune linkers designed for such microorganisms. Human trials will likely start soon, especially if there are emergency cases where the patient could be at the point of death because every other available option has been explored with no results. And this will unleash a whole new field of fighting against microorganisms causing disease in humans (if this works out well in human, Professor Mullis may win another Nobel Prize but this time in Medicine in about ten to fifteen years' time).
While this is ingenious, there is also great wisdom in exploring other ways so as to have several novel strategies for attacking these current-drug-resistant microorganisms. And I think one possible way to do this is to extend the kind of global interdisciplinary collaboration enjoyed by the
Human Genome Project to the study of drug resistance in every known disease-causing microorganisms, not just some small scale collaborative studies that are obtainable currently (however, this is not condemning small scale collaborative researches as they form the foundation for large scale collaborations). Drug resistance by microorganisms comes into play when these organisms undergo mutations. Mutation is a change in the framework of some portions of an organism's genetic architecture responsible for encoding proteins that make up the structure and function vital to its existence and continual survival in the face of factors (drugs and other therapeutic strategies) that threaten them. What if we have what I call the global MutaGenome Project in which researchers from all fields will collaborate at a global scale to map all the genetic mutations in all known disease-causing organisms over generations? These mutations will then be graded on a conventional scale, depending on the extent to which their phenotypic manifestations cause diseases in humans and mount resistance to our therapeutic strategies. By engaging in such large scale endeavour, we create what I call a mutagenomic database from which patterns in which these genetic mutations occur both among similar organisms and across different organism can be outlined, hence enabling us to use mathematical tools---such as the Nash Game Theory, Permutation and Combinations and so on already employed in evolutionary biology---to predict possible future genetic mutational patterns, outcomes, and understand clearly the working dynamics between each particular threat at the molecular level (in the form of therapeutic modalities) and mutational response (resistance development) in these organisms. This could then lead to different predictive therapeutic designs for a particular bacterium over time in response to its possible resistance development options. With this approach we can have centres for MutaGenomics and MutaGenomic Therapy (Mutational Genomics) in universities and research institutes around the world designing novel therapies for various diseases.
This is a very daunting and big ambition. But we did it in the Human Genome Project, and we can also do it in the global MutaGenome Project.
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