Thursday, 19 December 2013

Back in the freezer

A change in responsibilities wiped out the time I had to write for this blog. Thanks for the all the interest and comments here, I hope I will be able to return to it at a later time, though unfortunately not in time for JMG's Krampus competition, which ended last month.

Thursday, 5 September 2013

Hurdles on the course

This post is a summary of what I already know about the challenges involved in attempting sustainable antibiotic production. I am imagining this might be possible for example for a group of people with relevant knowledge and access to relevant literature, who have a small premises such as a garage which can be devoted to the enterprise.

I noticed in the recent edition of 'Microbiology Today' (2013, 40:3) an article by Simon Park, who has recently produced a short booklet 'Microbiology at home: a short non-laboratory manual for enthusiasts and bioartists', [pdf]. It describes the basics of sterile technique and media preparation, and how these can be done in a home context.

Theoretical viability

I know I need to read up about the evolution of resistant strains, and the genetics of resistance mechanisms,  and their likelihood of surviving post-selection. Although my thinking so far is based on a sense of correlation between antibiotic use and maintenance of resistance, it may be that there are mechanisms which would largely persist even in the absence of anthropogenic selection due to other kinds of usefulness to the microbe. Lots of information already exists in the literature, this is a matter of reading up, putting it together as best-guesses, and perhaps suggesting some experimental designs that would answer further questions.

Technological feasibility

Many skills and technologies are needed to contribute to the process of antibiotic manufacture from isolation to production of any antibiotic. Ways to overcome several of these could be investigated through interviewing elderly scientists from the time before disposable laboratory equipment.

Microscopy; lens-production technology. Light sources for illuminating microscopy, which could be as simple as a laboratory with a big window. Microscopy did exist before electric light.

Glass crafts -- microscopes slides and all kinds of culture vessels. I think this stuff still exists, even though all the lab biology I've done used disposable plastics. Something to look into.

Sterile culture equipment -- bunsen burner or equivalent heat source, wire loops, autoclave (also known as pressure cooker), clean bench and work area; sterile distilled water.

Culture broths and gel media of various kinds for isolation and growing on; recipes and components.

Incubators; thermometers/thermostats.

Fridges, freezers or other methods for storing cultures or spores, in glycerol or otherwise.

Fume hood for working with hazardous fumes.

Production of antibiotic therapeutics

This is the stuff I know less about, so this is not such a detailed list. I have heard that an early penicillin was used to save the lives of some people who had suffered severe burns -- the culture supernatant was used as a topical treatment. That's a use that does not require such great precision and quality control as the production of a reliable dose of an oral or intravenous antibiotic. Some of the pre-requisites I already know about:
Production strains: general knowledge of types of antibiotic and their microbial origins; this is something which could be addressed through a literature review.
Production chemistry & chemical engineering: specifics for production of quanties ie the deep vat innovation.
Product screening, quality control and dose testing.
Pharmacy prep -- pill-making kits etc.


What kind of facilities are needed, and how will they be economically viable? For example microscopy and culture lab could be useful for medical microbiology, water safety testing (fecal contamination screen) and so on. Would a converted garage or large shed be a suitable premises, or not? Can a business plan be put together that would allow such an enterprise to emerge? Could it attract funding as science-inspired art or history of science, or be funded through subscriptions from those interested?

Laboratory technologies don't have to be much more complicated that kitchen equipment -- but a biology enterprise would need safe and separate premises. Strains shouldn't be stored in fridges that are used for food, for example.

Friday, 30 August 2013

Post-industrial antibiotic production?

This week's post on the Archdruid Report blog has inspired me to begin publishing this blog, which I have been considering for a while. John Michael Greer, the blog's author, uses the rise of antibiotic resistance as an example of the futility of ideas of 'conquering Nature'. This is a subject close to my heart because following the completion of my PhD in 2010, which included a study of genes for antibiotic production, I have been wondering about the possibilities for production of antibiotics in the age beyond globalisation. 

After the fall of the Roman Empire, the availability of many commercial products declined in quality, described beautifully in a previous post on the Archdruid Report blog.  I think it is likely that unless a strong program of innovation arises based on the reality of resource limitation and the post-oil age, that many of the fruits of technological developments in the previous centuries may be lost to people in the next few centuries, and thus of course the availability of these advantages to ordinary people may vanish entirely over time. The global empire that is collapsing in our times is the one built by the availability of oil: an energy source dwarfing all of those whose production is sustainable. There are several examples in the comments following JMG's post this week illustrating the way antibiotic production has already declined, in line with the economic contraction, for example this story about Wyeth's production of injectable Penicillin G. It may be that the antibiotic resistance crisis is a product of the economics of the pharmaceutical industry colliding with natural selection carrying on as usual.

It has occurred to me that since production of early antibiotics was achieved in the middle of the twentieth century, and hence before many of the energy-guzzling habits of today's big science had become routine, that it might be possible for a group of amateurs to do garage-scale, or at least some kind of low-tech production. I can see possibilities which may echo those of radio communication networks which have been discussed in the comments of the Archdruid Report blog at least since this post in 2008.

I think it would be possible to set up a microbiology lab for ongoing discovery: microscope, incubators, broth-making, gels, and tests for isolating producer organisms (soil organisms being the source of the original clinical antibiotics, which are thought to function in the soil community as communication and resource-defence innovations); and a pharmacy lab for production. Careful adaption of innovations in chemical engineering that allowed upscaling of production in the 1950s would be essential, such as Margaret Hutchinson Rousseau's. The technicalities of quality control are also important, of course. I can see that careful investigation into the history of antibiotic production, for example by interviewing researchers whose work contributed to the so-called Golden Age of antibiotic discovery, may allow the recovery of techniques that would allow this kind of technology transfer.

The commenter 'Shining Hector' appears to be dismissive of the crisis of antibiotic resistance, having not yet seen its impact in his practice. Some of the points he makes are correct according to my understanding. Hector's assertion in the comments on this week's post by JMG that "when we ease up the selection pressure towards [antibiotic resistance], it will fall off" may be true in relation to some biochemical mechanisms of resistance. This is one of the views I have encountered in the discovery research community. Evolution of organisms includes the ongoing selection pressures on resistant forms, which in some cases are being maintained via inappropriate antibiotic use. I have heard of this approach being used by at least one physician treating stubborn infections in cystic fibrosis patients. I need to do some more reading to refresh my understanding of the biochemical mechanisms involved in resistance to the various classes of antibiotic drugs and their likely survival. It should be possible for example to do fermentation experiments in which a culture medium is innoculated with a mixture of phenotypes, to assess the survival rates of resistance traits in a non-selective environment. Those had not been done prior to 2010 as far as I am aware, and would usefully illuminate the viability of ongoing antibiotic discovery approaches.

I think Hector is also correct as I understand it in pointing to the economic dimensions of the difficulties in anti-microbial drug availability, also alluded to in at least one of the papers JMG linked to in his response to Hector in the comments, describing the problem: " ... the problem is exacerbated by a dry pipeline for new antimicrobials with bactericidal activity against gram-negative bacteria and enterococci", (from here).This supports JMG's points in previous posts about about the economic viability of scientific enterprises, for example: 
". . . the archipelago of university departments, institutes, and specialized facilities for research that provide the economic and practical framework for science as it’s practiced today—[face] massive challenges as we move forward into the deindustrial world. "
From here.

I think if we are willing to be good students of the organisms who produce these amazing compounds in the natural world, then for instance in two or three hundred years a monastic insitution or craft guild might be able to achieve production of a small range of oral antibiotic treatments. Such products are perhaps only a little more technically difficult than for example the Chartreuse liqueurs that economically maintain Carthusian monasticism. Some antibiotic production might be both possible and economically viable in the future if enough people work now to secure that possibility. Of course the problems of antibiotic resistance will persist, as these are the kinds of response we can expect to selection pressure on organisms which may reproduce a dozen times a day. Antibiotic resistance is the essential limitation on the power of antibiotic therapy. However I think that in the post-industrial future, there is a possibility that some useful antibiotics may re-emerge because of the way natural selection operates on these communities of organisms.

The present crisis of antibiotic resistance certainly is real, and the world before antibiotics was a very different place. Although many infections are still controllable, and the message about antibiotic resistance is being acted on in some places in the world, situations on the global stage are also producing uncontrollable infections. These are especially horrifying to progressive minds who have been trained to believe in the power of drugs and the inevitability of progressive triumph. The predicament of antibiotic resistance however is being engaged with by at least some interest groups: for example the call to action published in BMJ in 1998 was one of the factors that resulted in a complete EU ban on growth-promoting veterinary antibiotic use from 2006 onwards. Scientists in this area, like all others, are fighting for a share of shrinking research funding and must make the case that their apocalypse-defence programme is the most urgent. As the death toll from antibiotic resistance rises, it may be that this crisis acquires the power to command a continuing share of the resources available -- or it might be that this technology like many others may disappear into history.

At present I am still working on factors that I see as pre-requisites for the project -- researching and acquiring basic pre-digital laboratory equipment, gathering a community of interested people and so on. I see plenty of work to be done in studying the scope of the enterprise and developing a strategic approach. I have so far only been able to interest one other researcher in the sustainable antibiotic production enterprise (who is supporting my efforts with technical conversations and access to literature and textbooks). I have wondered whether I might be able at some stage to try offering a poster presentation at a professional society meeting. I have also heard of some institutions which address the challenges of fostering public health on an appropriate technology platform, for instance the Sustainable Sciences Institute which looks to me the right kind of thinking: science for a world of limitations.

Hello world

This blog is to communicate my thoughts about what kinds of technological innovations may be achievable for the medium-distant future. As the peak of the oil age recedes behind us, the industrialized world has a huge library of resources and innovations. How many of those can be adapted for use in a resource-hungry future?

Who is going to do that work of adaption when most people are struggling just to keep their families fed in the midst of economic contraction? The politicians seem to think that pretending business-as-usual is still an option is sufficient, while conducting a perpetual global war over the remains of the oil. We are all in a difficult predicament, but still those of us who can accept the predicament and respond to it can study and communicate our findings. What might still be possible?

This is only going to appeal to a tiny minority of people, only those who already share a view of the human world as being shaped by energy limitations and the natural systems that provide for life on this planet.

I'm inspired by the innovations of the mediaeval guild system in England, in which the kinds of innovation possible were constrained by a communities of skilled practitioners, as described for example in John Michael Greer's book 'Wealth of nature: economics as if survival mattered'. Those who were accepted to learn the skilled trades were known as apprentices, and they worked for a number of years for their keep, living in the household and studying from a full member of the guild who was accepted by their peers as a competent caretaker of that knowledge. I haven't yet found the guild, but I am apprenticing myself to what of the world I can study.