Reading, reading, typing, reading, reading, typing, reading…

I’m well into my literature review now. Lots of reading. Some typing. More reading. As such, I’m doing everything I can to avoid actually doing my literature review.

One of the things I’ll be doing, as part of the project, is setting up a microbiology lab. It’s kinda weird and Awesome (capital ‘A’ is required) that I get to set up what will effectively be my own lab. I want a lab in my own house in the way that my wife wants a library.

In pursuing this goal, I spent a whole day at the local Vet lab and it was one of the best days I’ve ever had that I can still get away with calling ‘work’. The head of the lab, Dawn, is what I would refer to as a ‘proper’ microbiologist: lots of experience, knows her stuff. She’s also, apparently, still as excited to be working in her field as I am. I basically spent the day getting shown around the small, but extremely functional building. It was impressive stuff. We talked about what might be possible with the resources I’ll have available, and she took me through some of  methods they use on a daily basis, many of which are relevant to my project and are likely transferable to my lab.

I then spent the next two days (Saturday and Sunday) researching official requirements and guidelines for Containment Level 2 laboratories, taking inventory of existing equipment, downloading catalogues for required equipment, measuring up and creating floor plans for suitable locations in the building, and writing up likely and potential methods to be employed. At the end of it, I had accidentally written a 9 page document, complete with floor plans, and methodology flow charts. It’s by no means a final document, but it gives a good idea of what I hope to achieve. I’ve passed it onto my supervisors and should be getting feeback in our next meeting.

The History Bit

After my pleasant diversion, I did some more reading and some more typing. Then some more reading. And in the process of a bit more writing, I discovered that I should probably do a wee bit about the history of penecillin. I mean, I know it’s not the first antibiotic ever used in medcine (and, admittedly, I probably didn’t know that a mere month ago), but it’s certainly the big one that everyone thinks of. And for good reason.

As I began my search for citable material on ‘The Big P’ (nobody calls it that, it just sounds funny right now), I came across a response to an article on the first clinical use of  penicillin, written by Dr Rex Lawrie. This led me on to find the original article, concerning  an account of these trials, written by Charles Fletcher. Fletcher was the first peson to administer penicillin in a clinical environment. Reading this account of those first administrations-the raw trail and error nature of them, and the ‘clinical miracle’ of some of the results-was utterly engrosing. I then went on, in true investigative reasearcher style, to find the original paper published by Fleming himself, along with the paper published by Florey.

Before I go further into this, it occurs to me that while everyone knows that Fleming discovered penecillin and heralded in the antibiotic era, very few people actually know the details. And, really, that’s fine. I’d happily argue that we don’t need to know all the details. We – the collective we – know that Fleming made an important discovery and it went on to change the state (and the sucess) of health care world wide. I hope that the collective we also know that this era is in danger of becoming just that: a distinct period of history. And if not, well, that’s part of what I’m working on.

Anyway, back to history…

Fleming, of course, was not the first to disover the antibiotic nature of a fungal substance, but he was the first to realise it for what it was, and to carry out some detailed analysis and experimentation with it. Interestingly, in Flemings paper, he focuses more upon potential usage of ‘penicillin’ (a term he defined to describe the flitrate of the broth grown, penecillium fungus) in the isolation of specific bacteria in culture, rather than for its potential medicinal use. However, he does suggest it’s use as an antisceptic wound dressing and states that its value against infection is under experimentation. What was most interesting to me is that many of the methods I’m planning on using in my own lab are simply refinements of the methods Fleming used in 1929.

From Flemings paper, I moved onto the paper by Chain and Florey (and others) that, complimenting the work of others in the field, decided to look specifically at bacterial an fungal substances. They started by looking at the mould analysed by Fleming, and point out that while several other scientists had looked at penicillin, none had isolated it for clinical analysis. The work they carried out gave clear results on the psitive benefits penecillin could have in treating certain bacterial infections. It was Florey who went on to initiate clinical trials with the help of the aforementioned Dr. Fletcher, in 1941.

Reading through these papers gave me a familiar feeling of excitment. It’s the excitment of discovering something new; I’ve felt it many times while researching various  subjects, but the brand of excitment I felt while reading these papers was of a particular flavour. I’ve only ever felt it in one other activity: family history research. Discovering something that is – or was – once clearly known, but was perhaps forgotten. Or maybe just deemed unimportant. I’m sure most people don’t feel it important to know that their great, great grandfather was a leather worker in a street that, actually, no longer exists, but finding documented proof of that gives a unique buzz – maybe that’s the connection with the past people talk about.

The Science Bit

From a scientists point of view, one of the most exciting moments was reading the followin sentence in the Chain and Florey paper:

Penicillin is not immediately bactericidal but seems to intefere with multiplication.

As we now know, penicillin antibiotics work by inhibiting cell membrane synthesis, specifically by interfering with peptidoglycan systhesis, and thus are largely only effective where bacteria are multiplying (though there is some evidence of penicillins activating cell lysis functions). Here, though, Chain and Florey identified and recorded a trait that others went on to confirm and, as the technology became available, explain in greater detail. It’s a simple thing, but it’s one of the reasons that I love working in science. I know that, so long as a I generate good data, and record it in a transparent and reliable fasion, it will always be there for others to use in their own work. I’m not saying it ever will be, but it’s nice to kow that I’ve added to the human pool of knowldge.

The Preachy Bit

Of course, the other striking thing about reading these decades old accounts, in particular the account of Dr Fletcher, is just how bad things use to be. Antibiotics really have been the ‘miracle cure’ for many diseases. We forget that a simple scratch could lead to life threatening illness; in some parts of the world, it still does. We have a habit of taking things for granted, and perhaps forgetting to focus on what’s important. With the benefits of antibiotics firmly established in the late 1900’s, little extra resources were directed towads further research.

In the same year that Chain and Florey carried out their analysis of penicillin’s antibiotic properties, Chain also described their discovery of penicillinase – an enzyme which inhibited penicillin. Though not fully understanding the implications a the time, such resistance mechanisms are now at the forefront of scientific research. And for good reason. With one exception, the last marketable* antibiotic was discovered in 1987. The exception was discovered, thanks to a novel culturing method, in Jan 2015. It is predicted that resistance to this new antibiotic, while unlikely to develop as fast as some,  will still be significant in within 30-40 years time.

Fletcher’s description of the ‘septic wards’ of he 1940s, while setting the scene of pre-antibiotic medicine admirably, should also serve to remind us of exactly how bad things were. The recent announcments by worldwide health and science agencies such as the World Health Organisation, the European Center for Disease Control, and the Center for Disease Control and Prevention, that antibiotic resistance is the greatest threat to human health we face, should remind us that unless we all act now, things could end up that way again.

*- we’ve discovered and created a fair few ‘new’ antibiotics, but since they all function in ways similar to those already in use, resistance for them already exists. It’s like saying, “I’ve discovered a new car”, but it still needs 4 wheels and roads to be useful. A hovercar, on the otherhand…

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