Belgian virologist De Clercq remembers Czech chemist Antonín Holý and their work on revolutionary HIV drug

Czech scientist Antonín Holý, who played an important role in creating drugs to treat HIV and AIDS, died five years ago this week -on July 17, 2012. Among his biggest achievements was the drug Tenofovir used to treat HIV sufferers that has helped millions of people the world over. In developing the drug Holý worked closely with the Belgian virologist Erik De Clercq. Prof. De Clercq gave Czech Radio’s correspondent in Brussels Filip Nerad an interview recalling his collaboration and personal friendship with Antonín Holý.

Antonín Holý, Erik De Clercq, photo: archive of Erik De ClercqAntonín Holý, Erik De Clercq, photo: archive of Erik De Clercq “I would describe my good friend Tony as a suspicious man. I think in the beginning he felt rather insecure about our cooperation. When I talked to him about working together on the development of anti-viral compounds he hesitated and he eventually sent me three compounds. He could have sent me many more but he wanted to see whether it would work, whether I was really sincere about this collaboration. So he wanted to test me with three compounds (laughs). Our collaboration started in 1976 but accelerated in 1985, i.e. ten years later. And from then on it was a productive collaboration. At that time also there was interest from an American company Bristol-Myers and that was later on taken over by Gilead Sciences. This was the third party in our team which actively collaborated on this project– Holý was the first, we were the second and the third party was Gilead Sciences.”

So something like the Holy Trinity?

“Actually I came up with that name and I got the idea when we were once in Olomouc and I saw the monument there of the Holy Trinity. When Tony Holý told me it was called the Holy Trinity I got the idea of calling us the Holy trinity – with the accent on the y as in Holý. Holy was a real chemist, an organic chemist, I myself am a doctor of medicine, but I am very dedicated to chemistry. I never got a degree in chemistry but I love chemistry and that was of very big importance in my career. And the third person, John Martin who is CEO of Gilead Sciences is also a chemist. So the Holy Trinity is made up of two chemists and what I would call a ritual chemist –and that’s me.“

How complicated was your cooperation when you were in the West and Professor Holý was behind the Iron Curtain?

“In the beginning this was indeed a kind of handicap, but it did not present a real difficulty. We had no problems exchanging compounds and there was no problem me getting the results of the tests to him, even though he was behind the Iron Curtain. I do not know if the situation was different for Holý but for me it did not present a problem. At the border when I came over I was never questioned, nor was I harassed when leaving the country. The situation was quite different with East Germany. I also collaborated with East Germans but there there was a ban on sending compounds. I never got any compounds from my friends in East Berlin. That was not possible.”

Did you ever try to persuade Professor Holý to leave Czechoslovakia and join you here in Belgium?

HIV, photo: NIAID via Foter, CC BY 2.0HIV, photo: NIAID via Foter, CC BY 2.0 “No, I never did. Hollý, according to what he told me, appeared to be quite happy with the situation. In the beginning he often complained that he did not have many financial means for his research but nevertheless he could survive. He never really complained and he never ever hinted anything about wanting to come to Belgium. He never did that.”

Which of your discoveries do you consider to be revolutionary? Was it Tenofovir?

“Yes, I think I cherish Tenofovir as my greatest discovery. But I would even go a little bit further. I would say that my greatest discovery was my discovery of the chemists –including doctor Holý –when I met them in Göttingen. I was the only non-chemist among them, I was a medical doctor –the only medical doctor present at this meeting. So the biggest discovery I ever made was the discovery of the chemists.“

Do you have any idea how many drugs have been developed thanks to your research?

”Well, I have several compounds that I developed in cooperation with other chemists, which are of course overshadowed by those that I discovered with Holy. I think that I have something like ten drugs on the market, efficient drugs and at least three quarters of them are those that I have developed in cooperation with Holý.”

You started your research on HIV drugs very soon after the virus was discovered. Was it a coincidence? Could you have envisaged at the time how widespread a problem HIV would become?

“Well, I stared my career on Interferon that was around about 1967 – 1968 and Interferon was at the time considered a miraculous drug for the treatment of viral infections. AIDS did not exist at the time. So in the 1970s I described several compounds as inhibitors of the enzyme which is crucial in the replication of certain tumour viruses and which would later be shown to be also crucial in the replication of HIV, the causative agent of AIDS. But the term AIDS only popped up in 1981. The disease must have existed before but it was only recognized in 1981 and the origin of AIDS –HIV -was only ascertained in 1983. So when we started our collaboration the purpose was not to find a cure for AIDS but to find a solution to several viral infections. Later on, of course, we added the HIV to our arsenal of viruses for which we did biological evaluation.”

Do you have any idea how many lives you helped to prolong or save with the drugs that you invented?

“Well, it is difficult to assess this but we can certainly talk about millions of lives that were saved by our compounds. Certainly Tenofovir was a major discovery. It was not what we expected when we started our collaboration, but as we went further and further we realized that thanks to our efforts and this unique collaboration – what we can call East-West collaboration –we helped save the lives of millions of people.”

Is present-day research in this area going in the same direction or is it focussing on something else? How do you evaluate present day developments in virus research and anti-viral drugs?

Antonín Holý, photo: Jiří SuchomelAntonín Holý, photo: Jiří Suchomel “Well, things are changing now. I would even say that while the AIDS problem is not completely solved it has been solved to a great extent thanks to the availability of anti-viral compounds. Now we have to turn our attention to other virus infections. Another virus infection is for example Hepatitis C, but that again is now going to be resolved not thanks to Tenofovir but thanks to the discovery of other very effective compounds that can even guarantee a complete cure for Hepatitis C. So we are near a complete cure for Hepatitis C –which we should have in the next few years. Hepatitis B remains a problem because –as in the case of HIV – we can cure the disease and even guarantee life-long survival for those afflicted but we cannot guarantee that we can cure the virus. That means even patients with HIV who have been treated with Tenofovir and who can live for a long time - even as long as the normal life-span –they will still harbour the virus. We are unable to eradicate the virus. That is because the virus becomes part of the genome, of the normal genes and then you can immediately understand that we cannot get rid of all the bad genes we have and that is true of all those that have been infected with HIV. Even if we can keep the virus under control and guarantee a normal life this does not mean that the patient can become virus-free. That is not possible.”

To what do you attribute your enormous successes when you and Prof. Holy worked far apart, when he was in a communist country with limited means of keeping abreast of new discoveries, restricted technical possibilities and so on?

“I would say it was based on a personal attraction. Holý trusted me and I trusted him. When I started this collaboration he was, let us say, the most important chemist in Eastern Europe. That is the reason why I was attracted to him. I am not going to say that I was the best in the field of biology but certainly he trusted me and he once wrote and said that he considered me to be the best chemist he had ever met among the medical doctors. So I think the reason behind our success was the fact that I am a chemist at heart, that I understood him and that I spoke his language. That is the reason why we were complementary – and the fact that he was behind the Iron Curtain, that did not matter.”