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Research

      Two main topics are discussed on this page today, 1] Infectious disease and rapid diagnosis of bacterial infections, 2] cancer. There are strong links between the two in respect of the work being undertaken.
       

RAPID DIAGNOSIS OF INFECTION

              We are spoiled by the modern rapid and easy methods to diagnose infection by viruses. The specific DNA or RNA that constitutes the viral genome is picked out by hybridisation, amplified sufficiently, and then identified. The whole thing takes a few hours (compared to maybe several weeks, for viruses, only fifty years ago, if anything could be done at all). Is something like that possible for bacteria, fungi and single-cell parasites?
       Probably, yes; in fact it already is done in a few favourable cases. But we are looking at an alternative that may be even quicker, more certain, and more easily applied at the patient's bed-side in what may therefore be a complex and highly-contaminated environment. We believe that all the important microorganisms can be specified in terms of the epitopes present on the external cell surface equally well as by the genomic nucleic acid sequence. This means not merely the presence or absence of one particular epitope    -    which may cross species or strain boundaries or may change as a parasite such as Trypanosoma eludes immune surveillance    -    but by a constellation or assemblage of epitopes which if present simultaneously are sufficient to make identification conclusive. The means to do this exist in principle. We seek to develop this technology and its application.

      New threats? Really new? Yes. The development of air travel to the extent seen today means that there is potential for extremely rapid world-wide spread of emergent pathogens. That has happened wholly within the last 100 years, largely in the last 30 years. More important perhaps is the threat of biological terrorism or even outright warfare as segments of the world population lash out at others because they think themselves oppressed, or because of a real limitation on resources for survival. Whoever is right, we need to defend ourselves. As it happens, all the major new threats in recent years have been viral not bacterial and, by chance, one is slow-burning (HIV) while the other (H1N1 influenza or "swine 'flu") seems to be a pussy-cat compared with its predecssors. But no-one should underestimate the danger raised by the SARS outbreak a few years back, and how grateful we should be to those in Hong Kong who isolated the virus and contained the outbreak.
      There is no reason why cellular microbes should not form the basis of similar or artificial outbreaks: every reason why we should 'Be Prepared', with a system that allows rapid diagnosis of previously-known microorganisms and the extension of that possibility to new microbes also.     

CANCER

WHERE ARE WE NOW?

      The bio-research world is full of excitement about new approaches to treating cancer through building the body’s defences, eliminating weak points, restoring control and modifying the rogue DNA of each cancer cell. It’s a great time to be alive for a young research worker in the field: there is a real chance of success within one lifetime, though so far the practical results are disappointing in that the drugs produced are active against only a few rather rare cancers and still only occasionally curative. It is early days yet. There is a huge amount of fundamental research to do and no guarantees about when it will be complete or how useful.

       An older concept was that rather than merely tame or control them, we should simply kill off all the cancer cells. That can happen sometimes nowadays though when the writer qualified in medicine, over fifty years ago, there were no such treatments. Then, we could kill off most of the cells but never all of them, so the disease inevitably relapsed. Today, in spite of the unselective nature of the chemotherapy drugs available, it seems that in a few favourable cases we can actually destroy all the rogue cells. Though old, the concept is sound and can be applied at once without waiting decades for fundamental research to be completed. This essay is about how to improve selectivity and to personalise an attack drug for use in an individual patient, so as to improve the chances of success.

A SOLUTION EXISTS IN PRINCIPLE

     It is to hold a library of antibodies or other binding entities that can be put together in any desired combination within a few hours, using nucleic acid chains as the means of linking one fragment to its neighbours. The combination happens instantaneously and there are no complicated or dangerous chemical processes. A restricted number of antibody fragments in the library can yield a very large number of combinations, suitable to meet each individual case: for example, five fragments A, B, C, D and E yield ten pairings - AB, AC, AD, AE, BC, BD, BE, CD, CE, DE. Six antibody fragments would yield fifteen pairings and so on; much larger numbers if three or four fragments are combined to yield triplets or quartets.

      More about cancer? See www.cancerinfo.be.

      Would you like to help? Write or call.

Rapid diagnosis of infection, historical survey.

Microbiology was one of the handful of disciplines that led the whole of Medicine out of the dark ages and for many years was also a leader in precision and speed of diagnosis, made possible by culture on specially-selected media that allowed individual bacterial species or strains to be isolated and identified. In many cases, an answer could be had in 24 hours, though if the bacterium itself was slow-growing that might be extended to weeks (TB, fungi) and if scientists didn't yet know how to grow that particular organism, such diagnostic methods failed completely (Chlamydia, Leprosy). For those reasons, and because we are more impatient these days and because of new threats, the whole question of how to approach the diagnosis of infection has to be re-examined.

Cancer: The Problem

      Ordinary cells are so much like cancer cells that the available treatments attack both to some degree. That’s why many people get so ill on chemotherapy. One way that has been tried to improve things is to use antibodies to molecules on the outer surface of the cancer cell and then attach the chemotherapy agent so that it rides piggy-back on the antibody. It doesn’t work in the clinic, because the ordinary cell is so like the cancer cell that it carries a similar set of surface molecules.

Approaching a Solution

      In spite of what we just said, there are some differences between the surfaces of the ordinary cell and the cancer cell, especially as to the balance of different kinds of surface molecules. If we had antibodies that recognised two or more of these surface molecules only when present together at the same time, that would make a huge difference both to the selectivity and to the strength of binding. This means having two or several different binding potentialities on the same antibody molecule and is not possible naturally.

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