Big hope for the production of Tamiflu - a bird flu drug - on large scale
Elias Corey, professor at Harvard University and Nobel Prize winner in 1990 for chemical synthesis, is co-author of a letter published in the Journal of the American Chemical Society in May describing a cheap and efficient chemical synthesis to produce Tamiflu. He answers Scitizen?s questions.
words about the context first: in a case of a bird flu pandemic, is there any
vaccine or drug available at the moment?
There is no vaccine available for the virus that would infect humans because that virus hasn't formed yet as far as we know. The only avian flu virus that exists now is infective for birds. It would be a totally new virus that would have to arise through a mutation that would become infective for humans. Without knowing what that virus is, it's not possible to develop a vaccine. Once the virus does begin to infect humans, it may take some while for a vaccine to be produce, it could be anywhere from 1 year to 5 years, so even though vaccine allows a very desirable preventative for bird flu, it is not the ideal solution at this point.
What about drugs?
There is a kind of drug that blocks the entry of flu virus into human cells. There are 2 versions of that: one is in form of an oral pill and the other is given by inhalation of a spray. It is the oral drug that seems to be the more effective and the more practical. It is that compound that we have enabled to synthesize in a way that should make it more widely available.
Making this drug, called Tamiflu, is slow and hard. Why?
It is a complex organic structure and, as it's usually the case with such structures, you need to have an appropriate starting point for chemical synthesis. The synthesis must be carried out in several stages, it cannot all be done in one operation. At each stage some material is lost. In the case of Tamiflu, the starting material that has been used in the past is a very expensive complicated molecule. Its supply is limited. The synthesis process itself is long and the amount of material obtained at the end is not large. Finally, in the current manufacturing process, as I understand it, there are two steps that involve explosive intermediates. It is very dangerous to carry out those chemical steps on large scale. So at present, those two steps represent bottlenecks in the production.
In your article, you describe a new method to make this drug.
Yes. Our method uses some brand new chemistry that allows us to start with two very inexpensive ingredients obtained from petrol chemicals. These are also very widely available. The course of chemical synthesis is efficient and the recovery at the end is quite high. The number of steps involves in the overall process is lower than for the previous manufacturing process and also there are no bottleneck steps. So we think that this method can be carried out on quite large scale, and we think it should be more cost effective as a manufacturing process. It's our hope that the suppliers of Tamiflu will be greatly increased by the use of this synthesis process.
Do you think it can be scaled up easily? Can it be done shortly?
I believe it can be scaled up without any insurmountable problem but it does take time to carry out an industrial scale up of a chemical process. I don't know what the timetable will be. That depends on so many things. In the end, the questions are who does the manufacturing, where is it manufactured and how long does it take to get the regulatory approval of the method of manufacturing. That I don't know.
Did you file for an international patent?
No, I did not.
I think that in situations like this where the issue is a humanitarian issue, involving possible lost of many human lives, most important thing is to do anything one can to minimize those dangers and to increase the supply of the drug which should result in lowering the costs. So to me, it's just common sense that in a matter of public health one should do everything one can to make sure lives are saved.
Prof Elias Corey, thank you.
Elias Corey works at the Department of Chemistry and Chemical Biology at Harvard University. He won a Nobel Prize in 1990 for chemical synthesis.Interview by Gilles Prigent
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