• Question: How do you ensure your methods aren't injurious in the long run to the patients?

    Asked by trishbeanx to Jack on 17 Jun 2013.
    • Photo: Jack Miller

      Jack Miller answered on 17 Jun 2013:

      Hi Trishbeanx,

      Thanks for your question — it’s a good one! Moreover, it’s obviously something we have to worry about. Fortunately, there are lots of measures put in place to prevent anything bad happening to people. Whenever a new therapeutic agent is developed, it has to go through clinical trials to prove its safety and efficacy before it can be used. The first one of these trials, known as a Phase 1 clinical trial, can only take place once there’s a lot of evidence in the lab to show that the substance itself is safe. It’s then administered to volunteers in a hospital in an ascending dose fashion to show that it’s safe. The volunteers — who probably suffer from the disease that the substance is designed to treat — are then monitored for a long time, and any adverse affects noted. Phase 2 and Phase 3 trials are then carried out, to look at how effective the new substance is when tried out on patient cohorts, before it’s brought to the world as a whole.

      However, we’re quite lucky, in that the substance we administer — pyruvate — is something found inside every cell of your body. It’s said to be an ‘endogenous metabolite’, meaning it’s a small chemical that you’ve got buckloads of (literally…) inside you at any point. As there’s no functional difference, as far as your body is concerned, between the pyruvate I inject and the pyruvate in you already, it’s highly unlikely to cause any adverse effects, long term or otherwise. Moreover, a Phase 1 clinical trial was run in the states in 2010-11 to show the safety of this compound prepared in this way — and everything’s fine.

      Hope that answers your question!

      — Jack

Comments

  • Photo: trishbeanx

    trishbeanx commented on :

    So if both pyruvates are almost identical, why can’t you just use the one that is in the body already?

  • Photo: Jack

    Jack commented on :

    Because I can only see the pyruvate I inject with the scanner — the nuclear physics technique I use (dynamic nuclear polarisation, or DNP for short) makes it visible to the scanner. The process involves cooling a frozen, solid sample of pyruvate down to near absolute zero and irradiating it with microwaves. It’s then melted, and brought up to 37 degrees C very quickly, before being injected. I can’t do that with pyruvate already in your cells for two reasons: one, if I brought you down to 1K and irradiated you with microwaves, you’d be very, very dead, and two, the pyruvate I use has carbon 13 in place of one of the “ordinary” carbon nuclei. Carbon 13 is naturally abundant and isn’t radioactive (unlike carbon 14, which is used for radiocarbon dating), but it makes up only around 1% of the carbon in the world. Therefore, to avoid having to inject many times more pyruvate as we actually need to, we just use a sample of pyruvate that’s 100% carbon 13 in one place in the molecule, and 100% carbon 12 in the other two positions. This can be polarised by DNP and made visible to the scanner.