I would also work on something that interested me since graduate school days and that... and I’ll simplify it simply to say... is to try and convert progesterone, the female sex hormone, which is only active orally, into... is only active by injection parenterally into an orally effective one, and that’s a longer story and an entire... Listen, each of these books is largely about that and we accomplished that. I don’t really want to belabour that very much further other than to... well, I can actually show a little bit in this case here because I did use... was very daring into this... in this chemical... in this, in an ordinary literary autobiography. Not in a chemical one, which has a lot of chemical structures. But literary... to have a few structures and I decided to do it because I want to say, people should realise, you know, the Einstein quote [sic]... make things as simple as possible – don’t make them too simple. And I want to show that even if you know nothing about chemistry, if you look at... this is just geometry as a form of pictography. You can illustrate the complexity of the problem. In other words, C is testosterone. We learned how to convert testosterone into oestradiol, the female sex hormone, by removing this magic carbon atom and making a benzene ring. And then through another set of transformations were able to convert that back into this. You see it right here. These look like they are identical with one difference. That this angular position, which here... this is the shorthand for methyl, CH3, now became a hydrogen atom. So, what we really want to do is replace this by a hydrogen, which is really chemically extremely difficult... extremely difficult and the only way you could do it is via this. Now, each of this is about ten steps. So, you know, when I’m saying from here to here this isn’t just two steps, but these are the key transformations. So that... that way we made something that's called 90-nortestosterone and then did exactly the same thing with progesterone and made 90-nor-progesterone. So, these two are almost indistinguishable. But the tenet at that time was anything you do to this molecule would diminish biological activity, and this compound was an exception. This was even more active than that one so that destroyed the tenet that progesterone cannot be changed chemically without also producing deleterious biological properties. This was based on an observation by another German refugee, Maximilian Ehrenstein, who had worked in... in... at the University of Pennsylvania.

I belabour this point, always talking about refugees because it really shows you the sociological effect... negatively for Germany, positively for America that had... where literally a generation of really outstanding scientists were wiped out from one country and transferred at the height of their creative power into another one. And changed almost overnight the balance of organic chemistry where the United States was a second-rate country, without any question, until the Second World War into very quickly a first rate one. And taking a first rate one, Germany, and converting it pretty much into a third rate one within a period of just a few years in that area. So, it’s quite a dramatic demonstration.

Well, having discovered this, we then went one step further, and I want to show you that again. Again, showing this interesting difference, Germany and then transplanted in the United States. A German chemist in the Nazi days, so late 1930s, Hans Herloff Inhoffen chairing the pharmaceutical company Berlin had shown that he could take oestradiol, the female sex hormone, which is this substance minus what you’re seeing up here in black. And these black letters are the chemical structure for acetylene. If you add acetylene to oestradiol at this position, that was a discovery of his... you convert this into a highly effective, orally effective oestrogen. Again, the oestrogens are not very effective orally but with ethynyl... with acetylene – it’s called ethynylestradiol – it becomes orally active. That was his observation. He then tried to do the same thing with testosterone. In order to convert testosterone into one with acetylene here, because testosterone is not orally active. Again, and people are interested medicinally also take pills rather than injections, at least in the United States. So here was his rationale, but lo and behold while this now became orally active it was not a very good androgen. It was not a very good male sex hormone, but it had weak but perceptible progestational female sex hormone activities.

We put two and two together and said, ah if acetylene produces oral activity and we know from our earlier work I just showed you with progesterone that the removal of a methyl group converted into hydrogen increases biological activity, why not combine the two? And that is a substance. So, this is 19-nor. In other words, a 19 methyl group is lost. That’s what 19-nor means... minus the 19 methyl group. 19-nor 17 is ethynyl (that’s ethynyl in the abbreviation for acetylene) testosterone, and that is also called norethindrone, norethisterone, and that was the first orally effective, highly potent progestational hormone that represented the first synthesis of an oral contraceptive. That was done within a couple of months of the cortisone synthesis.

So I would say we really accomplished an awful lot in this third world country laboratory in Mexico, and it put Syntex really on the map scientifically. It became, within a few years, probably the most powerful industrial research laboratory in the world in the steroid field in competition with Merck and Ciba and so on.