We, first of all, took our drugs into... human beings at St George's Hospital in London, now a big Lanesborough Hotel, and the first subject that we used it on was a young doctor. And, if you infuse isoprenaline into an artery in the arm, the... the blood flow... the blood vessels in this whole arm would dilate, and you could measure the big increase in blood flow which isoprenaline would produce, so you measure it and then you infuse the drug, just locally, and then you put the isoprenaline in again and be completely blocked in. And then we, almost without pausing for breath, then went to another young doctor and he is now given isoprenaline intravenously, so the whole body gets it, and on the control you... not only does his heart rate go whipping up and he gets a fall in blood pressure and an increase in blood flow to... to his arms, but he... he's restless. And afterwards I... I... you know, 'What's the problem?' He says, 'I feel I'm going to die'. And, so then we treated him with pronethalol and now – isoprenaline was given again – all is peace. Heart rate doesn't change, blood pressure doesn't fall, blood vessels don't dilate, and he's lying at peace. So, this... so, this was where, you know, one got the idea that one's heart is sending information into the brain all the time and relating, if you like, the appropriateness of what it's doing to what the whole body's doing, so if, in this case, the guy is lying on the bed and you stimulate the heart fast enough, as though he was running from a lion, but there's no lion, all hell goes loose upstairs, something's gone wrong here, and so they get this fear. And, this has always been one of the things which have in... been involved with beta blockers... is this business about using them to control fear for examinations, billiard players, musicians. I have a friend who's a concert pianist and when he... in the old days you would come on for the first part and you'd feel passionate, and then go off at the interval, your shirt was soaked, change it, shower, and you've come back on for the second half, and now you're washed out and you're passionless. And what beta blockers did was allow them to be much more intellectual, so the first half they could play but didn't get too worked up about it, and then... so they got a more uniform performance. Whether that was good or bad he wasn't sure, but that's what they did. So, that was the first thing. Then we... we moved to University College to a chap called Brian Prichard – a young clinical pharmacologist – and he found that when he took his patients and gave them pronethalol that the pulse rate would fall, but he found that only a few of the patients with the initial dose he... would the blood pressure... would the pulse rate fall. But he found if increased the dose more and then... so he was able to show that eventually, if you give a big enough dose, he could get the pulse rate down to 60 at rest in everybody.