In poking around to support my response to this, I came across an excellent example of why this is not just a political or regulatory problem.
In my head, I started to go through a "use case analysis" of a hypothetical research project. I wanted to come up with something practical, that might even be a project someone here is willing to take on. So I chose diabetes as the problem, and settled on galegine, a natural anti-diabetic found in galega officianalis. or French lilac. http://en.wikipedia.org/wiki/Galega_officinalis. Not surprisingly, after a little searching on publicly accessible journals, I found a link to "Furman and Coxon et al"- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2438274/ and, according to the article, pure galegine is hard to get but is "easily synthesized" from "benzyl amine" and 2-methylpseudourea sulphate, both available from Sigma.
But wait- I thought galegine was also known as N-dimethylallyl guanidine: I woundered how they could have gotten an allyl from a benzene, which if you have synthetic chemistry experience is a huge red flag. So I managed to find a non-free publication, "Coxon and Furman et al"- http://www.ncbi.nlm.nih.gov/pubmed/19422230 which correctly shows the rather complicated synthesis of galegine. I quote:
1-(3-Methylbut-2-enyl)guanidine Hemisulfate 1 (Galegine) and General Procedure for Synthesis of Guanidine Hemisulfates.A mixture of 4-bromo-2-methyl-2-butene (19.4 g, 1.0 equiv, 130 mmol) and potassium phthalimide (29.8 g, 1.2 equiv, 161 mmol) were suspended in DMF (200 mL) and stirred at 120 C for 1 h before heating to 160 C and stirring for a further 18 h. The mixture was poured over ice and washed with dichloroethane (5 × 50 mL), and the organic phases were separated and combined before washing with sodium hydroxide solution (0.1 N) (2 × 100 mL) and water (2 × 50 mL). The organic extracts were separated, dried over anhydrous magnesium sulfate, filtered, and concentrated to leave a crude solid that was crystallized from cold ethanol to give the intermediate 2-(3-methylbut-2-enyl)isoindoline-1,3-dione (25.6 g, 93%) as a white solid; mp 100-101C
A mixture of 2-(3-methylbut-2-enyl)isoindoline-1,3-dione (10 g, 1.0 equiv, 46.6 mmol), ethanol (100 mL), and hydrazine hydrate (85%) (2.9 mL, 1.2 equiv, 51.1 mmol) were stirred under reflux for 1 h, cooled, hydrochloric acid (1M) (5.2 mL, 1.2 equiv, 51.1 mmol) added, and then refluxed for a further 1 h. The mixture was allowed to cool, filtered, and the residue washed with cold water (100 mL) before reducing the filtrate under vacuum to give the intermediate 3-methylbut-2-en-1-amine hydrochloride (4.4 g, 78%) as a white solid; mp 95-97C2-Methylthiopseudourea sulfate (6.95 g, 1.0 equiv, 150 mmol) and 3-methylbut-2-en-1-amine (9.1 g, 2.0 equiv, 100 mmol) were dissolved in water (100 mL) and ethanol (100 mL). The mixture was stirred at reflux for 18 h, connected to a series of bleach traps, before cooling and reducing under vacuum to give a white crude solid. The compound was suspended in water (30 mL) and heated until it barely dissolved before allowing to slowly cool upon which a white solid began to form. After allowing the formation of the solid to continue overnight, it was collected by filtration and dried in the oven to give the title compound (5.4 g, 62%) as a white solid; mp 216-218C
It turns out that you get a related compound, N-benzylguanidine. The class of all the compounds has been patented http://www.google.com/patents/US5373008 but this patent is now expired and the entire class of compounds should be free of patent, including the leading indication and first line therapy, metformin http://en.wikipedia.org/wiki/Metformin.
So why do I mention this? Let's start off thinking about some of the research plans someone might take toward finding "open source" diabetes drugs. They might just be tempted to hack the minimal procedure from "F&Cetal" instead of following the correct procedure of "C&Fetal". The lingering doubt I have about this work is, what if the paper principally authored by Furman actually studied benzylguanidine instead of galegine? What is the differences of approach between Furman's lab and Coxon's lab that results in the difference in reported experimental procedure? Who edited and checked these papers? By simply following published research, it would be so easy to fool yourself when synthesizing drugs.
At least with synthetic chemistry, I can fall back on the methods of chemistry to give myself at least some confidence that what I think I have, I can be sure I have, because proton and carbon NMR and mass spec and melting point and FTIR, while they all have flaws, eventually suss out the truth.
Now move on to bioengineering: let's say you engineer a recombinant cell line to produce galegine. As with the chemical synthesis, actually recovering the free base is not easy, and when you add up all the possible side reactions that might make various contaminants, it could be really difficult to isolate the multigram quantities of any compound you would need to do a study n=1. You might just get a mixture. You might get poison. You don't know- and even if you are successful, the next person you give the drug to might die of lactic acidosis because you "happen" to have a gene that prevents that side effect. Who knows? Although we know metformin inhibits a particular enzyme(s?) involved in gluconeogenesis, we don't really know what giving somebody metformin does to the body, or why some people react so badly to it. As much as we don't know about metformin, we know even less about galegine, except that every animal reacts slightly differently to it.
So, even in a pure libertarian utopia, drug research is fraught with difficulties on where to start and tons of conflicting theories on what we know. That's not to say doing some basic investigation in a DIY lab couldn't do some of the groundbreaking early stage research that might gain us some critical insights into the why and how of diabetes. There are GREAT projects to be had. But DIY medicine is more than just bad politics: hacking ceases to be science when you stop following scientific best practices. N=1 experiments are interesting and all, but they're not science. The politics and regulation is, in large part, a way to shut down random people from poisoning each other, as happened all the time at the turn of the 20th century. For the chemical example, google "elixir sulfanilamide". For the biohack example, google "a horse named Jim", the ultimate in N=1 biohacked medicine and a case study on where biohacking could go very, very wrong.
Do you really want to get your medical care from "a horse named Jim?"
-matt
On Monday, May 27, 2013 3:45:05 PM UTC-7, Reason wrote:
http://www.fightaging.org/--archives/2013/05/civil- disobedience-and-diybio.php
From a point of view of materials and time it is not costly to set up a home
laboratory for the purposes of synthesizing chemical compounds or even
perform simple procedures in biotechnology - raising bacteria, assaying
genes in lower animals, and so on. It is, however, illegal to just forge
ahead and do this in most US states or in much of Europe due to the many
prosaic, stupid laws that encrust the body politic....
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