Austrian Scientist and One of the Inventors of the Antiviral Drug Tamiflu
In 1990 Norbert Bischofberger, a highly regarded Austrian scientist, joined Gilead Sciences, a biopharmaceutical company specializing in antivirals, as head of the research team. In 1993 the team initiated work on influenza and was successful in developing the antiviral drug Tamiflu three years later in 1996. After clinical studies were carried out the drug was released on the U.S. market in 1999 as the first orally active, broad-spectrum anti-influenza agent for both treatment and prophylaxis of imfluenza infections. It is the main medication currently on the market used to inhibit the H1N1 virus or swine flu.
In 1999 the rights to market and develop Tamiflu were sold to Roche with Gilead retaining the intellectual property rights. Meanwhile, governments around the world have stockpiled Tamiflu. Today, Roche estimates that some 50 million people have been treated with Tamiflu, and the company is currently considering an increase in production. Bischofberger also helped develop the first HIV treatment manufactured by Gilead Sciences called Atripla, a once-a-day, single tablet regime that vastly simplified the treatment of AIDS. It was approved by the U.S. Federal Drug Administration (FDA) in 2006.
In an interview with Austrian Information, Dr. Bischofberger talked about the beginning of his scientific career, the development of Tamiflu, the threat that swine flu currently poses and the scientific innovation and entrepreneurial spirit which he found so attractive in the U.S.
What influenced you to pursue science? And what motivated you to come to the United States?
I was always interested in science. I was experimenting with chemicals or disassembling old radios when I was a very young boy. Those were the days before semiconductors existed and we had vacuum tubes in radios. One thing led to another. I went to Innsbruck for my Master’s degree in Chemistry. But then I always wanted to explore other universities and experience different scientific environments and ended up doing my Ph.D. in Switzerland at the Swiss Federal Insitute of Techology (ETH) in Zürich.
It was in the early 1980s, and my ultimate interest always was to go to the United States in large part because many big technological inventions in the 20th century originated in the U.S. We had a lot of researchers from America who came to visit ETH, Zürich, and I felt that this was the land where things were happening. Progress came from the United States and they were always two steps ahead. This was in the 1980s; it might be a little different today. I met a researcher from Harvard in Zurich, and I wanted to go to work for him. So I did a postdoctoral fellowship at Harvard. During that time I developed a fascination with California, the west coast attitude and outlook on life.
I gave the keynote speech at the Austrian Science Talk 2009, organized by the University of New Orleans in October of this year. It highlighted the differences between California and Austria – in Austria one is much less prepared to take a risk compared to California. Look over the last thirty-fifty years: what are some of the major technological advances – semiconductors, computers, software, internet, biotechnology, information technology - most companies that have made a big name come from the West Coast: Google, Apple, Hewlett-Packard, and so on. I was very much enthused about this new environment of risktaking, and that’s why I ended up in California.
How did you decide to enter the field of developing drugs, in particular the Tamiflu?
The fields of Biotech and Chemistry are my background and I was always interested in infectious diseases. The early eighties saw the beginning of biotechnology. We reprogrammed bacteria or yeast by reinserting other genes into them, and that brought me in contact with Microbiology; thus it was a natural thing I always wanted to do – work on infectious diseases. Within infectious diseases we were working on Hepatitis and HIV, but the major area of focus in the eighties was Influenza, an RNA virus. It is seasonal and comes every year, resulting in significant morbidity and mortalities.
Thus, it is the accepted wisdom in the medical community that one of these days we are going to have a big pandemic again. Pandemics have been around for a long time. The worst pandemic was the Spanish Flu in 1918 which killed 40 million people worldwide. Influenza changes from year to year, so it is only a question of time before a strain emerges that is highly pathogenic, easily transmittable from one person to the other and for which there is no preexisting immunity in the population. So we started to work on Influenza in the early 1990s, and with that came the discovery of Tamiflu.
Drug development typically takes five-ten years. We started development of Tamiflu in 1994 after it was first synthesized in the lab and after in vitro and preclinical testing. The clinical studies took two-three years, and once this was all finished, we applied to USFDA for approval. That takes another six to eight months. Tamiflu was approved in the U.S. in 1999 and in the European Union in the year 2000.
Tamiflu was a kind of “sleeper” because following the approval of Tamiflu, the flu seasons were very mild. There was not a lot of disease, and so people just forgot about it until a few years ago when the bird flu HVN1 surfaced. All of a sudden Tamiflu became more talked about, and now we have the swine flu.
Is Tamiflu still the most efficient and recommended medicine?
It works against a large number of strains, and it is very easy to administer. It is a simple tiny capsule of 75 mg, which you take twice a day. And if you treat Influenza early enough, it is very effective. The way influenza works is that the virus gets into your system and starts to replicate in the lungs and upper respiratory tract and causes damage. But you really become sick after you have been infected by the virus. What is really important is that Tamiflu only inhibits the virus. Within 48 hours of symptom onset, you should take the drug. If you wait a few days, it may be too late and the compound is not as effective any more. It is safe, and it is easy to take. It is an amazing drug if you take it early enough.
Were you satisfied with the way the swine flu was handled in Europe and the U.S.?
It is hard to criticize public health care, but I feel that they have not done a good job – it has been unorganized and chaotic. Some people received the vaccine, others did not. And in Austria a reporter told me it was similarly chaotic. Thousands showed up at a vaccination site, but they did not have enough vaccines and people were upset and angry. What I hope the public health officials will learn from this for the future is that we really have a problem. One good thing about the swine flu is that it has not yet resulted in a very high mortality.
People have died, but the extent of the pandemic is still not known until the end of the flu season. We do know that the virus is a serious problem, that it causes mortality, is very infectious, and spreads easily from one person to another. We have a big problem, and I do not think that we are equipped to deal with it. A lot of countries like Austria have stockpiled Tamiflu. This is a fairly easy and straight forward decision, but how do you distribute it? What are the logistics? How do you get it to the general population? I don’t think the plans are as solid as they should be.
Vaccines typically have been effective and are safe. The flip side is that the development of vaccines takes a fairly long time. It takes eight to ten months until a vaccine is available. You have to administer it to healthy people. If you are infected, it is already too late. Sometimes vaccines don’t work because they fail to provide immunity against the circulating strain. When developing a flu vaccine, researchers look at the last strain in the spring and assume this is going to be the same strain in the fall. For the most part that has been fairly accurate but not always. Since vaccines are given to healthy people, there is more a motivation necessary for them to go to a clinic and be injected with the vaccine.
I have received dozens of emails from Europe, in particular Germany and Austria. They are all so confused and do not want to give the vaccination to their children. They speak of a “conspiracy, ” with statements like “they are lying to us” or “this is just a way to influence us.” These are educated people, and I am thinking this is unbelievable: we have a new flu strain; the flu strain circulates; it is widely distributed, and it causes a lot of morbidity. What do we do? We have a vaccine.
Having lived in the U.S. and having studied in Austria, what are some of the differences in regard to scientific research and the training of scientists?
If you are looking for a basic education, through ground school, high school and the undergraduate level at the university, I do believe there is no better place than Austria. What I would like is for Austria to do more on the elite end. There are certain people who are much more capable than others, and these are the ones we should push ahead more.
When I was studying at the university in the eighties, the idea was to equalize. You don’t want to have extremely good students and you don’t want extremely bad students. The ideal was for everyone to be the same, instead of eliminating the bad ones and pushing the good ones. In this regard they have done a better job in the U.S. People in Austria feel that social equality is very important. I don’t want to debate this, but at the educational level you have to be more elitist.
I have noticed that all the innovative companies like Google, Hewlett Packard or Apple are here in the U.S. and not in Austria. Part of it has to do with thinking more elitist. Give a few people the chance to do something big. And be more willing to take a risk. Along with the risk comes the chance of failure. In the U.S. the failure of outcome is more acceptable. In California bankruptcy is referred to as Chapter 11 or Chapter 13, whereas in German it is called “bankrott,” a word which has a personally bad connotation like you did something wrong. It shows very much that failure has to be avoided.
Do you frequently go to Austria?
I will be at the University of Innsbruck next Monday and will be giving a talk there. I am in Europe once a month.
Dr. Norbert Bischofsberger
Born in Vorarlberg, Dr. Norbert Bischofberger received a B.S. degree in Chemistry from the University of Innsbruck (1979), a Ph.D. degree in Organic Chemistry from the Swiss Institute of Technology in Zürich (1983), and a post doctoral fellowship at the Institute of Organic Chemistry at Syntex, Inc. (1983-84) as well as at Harvard University (1984-1986).
From 1986-88 he worked initially as a scientist with the Chemistry Group of the Molecular Biology Dept. at Genentech, Inc. in South San Francisco, and became Manager of DNA Synthesis at Genentech from 1988-90. He joined Gilead Sciences, Foster City, CA in 1993 where he worked in various capacities as Director and Vice President of Organic Chemistry, Vice President and Sr. Vice President of Research until the year 2000 when he became Executive Vice President of Research & Development as well as Chief Scientific Officer.
His many responsibilities include discovery, preclinical evaluation and antiviral clinical development. Dr. Bischofberger has published papers in many scientific journals, has been awarded patents, and has served on editorial boards, board of directors and advisory boards, including the Mount Sinai Dept. of Medicine, NY, NIH/NIAID Regional Centers for Biodefense and Emerging Infectious Diseases Research Program and Proligo LLC, Boulder, CO in Hamburg, Germany.