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Tamiflu

A glass of Pernod against the avian flu?

Tamiflu (marketed since 2002 by the Swiss pharmaceutical company Roche (Hoffman-La Roche) seems to be one of the very few reasonably effective agents against the influenza virus (type A and B). It may not constitute a complete cure, but if taken very early on after the onset of symptoms, then it may reduce the severity of the illness. Reportedly it also works in a similar way against the H5N1 virus, which causes the avian influenza type A (the "bird flu" or "avian flu").

The active substance of Tamiflu is oseltamivir (in phosphate form). Isn’t that interesting? I thought so. Still, what is even more intriguing is that the ultimate raw material for oseltamivir is shikimic acid. This becomes outright fascinating, seeing that we are now able to fully appreciate the Pernod connection. Because, as you have already guessed, shikimic acid is extracted from the Chinese spice "Star anise" (Illicum verum). And the anise oil that gives the French aperitif Pernod its colour, flavour and fame is likewise extracted from Star anise.

However, stocking up on Pernod as a remedy against the avian flu would be a grave mistake (pun intended). The chemical path from shikimic acid to oseltamivir consists (according to the manufacturer Roche) of 12 complicated steps (some of which yield dangerously explosive intermediary products) and takes a full year to complete. So the shikimic acid in your glass of Pernod may, together with its ethanol, calm you down and unrealistically allay your fears in the face of a flu pandemic, but it won’t harm the H5N1 virus in the least. The extract it contains is just a distant raw material for the active drug itself.

Inhibiting a nasty protein

Tamiflu (the difficult-to-make oseltamivir) works by inhibiting the activity of a particularly nasty protein on the influenza virus' surface, a protein called neuraminidase. The virus uses neuraminidase for chemically dissolving a path through the cell wall of the patients body cells, thus trespassing into the cell. Once inside, it orders the cell to make replicas of itself. When sufficient numbers of replicas are made, then the new viruses again use their nasty neuraminidase to make their way through the cell wall and escape to the outside. Here they are ready to enter new body cells. The wall of the cell they leave behind is destroyed and the cell dies. Whenever this procedure turns into an efficient chain reaction, then you yourself will die.

Tamiflu (oseltamivir) inhibits the chemistry of the nasty protein that dissolves cell walls (neuraminidase), making it impossible for the virus to pass through the wall of a body cell. But don’t feel safe yet! Because there is no way in which a virus can be subjected to Tamiflu when the virus first hits you – the first viruses will get through and start making replicas of themselves in any case. You can’t do a thing to stop them.

Leaving the virus trapped within the cell –- really?

But if you (and hence all of your body cells) are reasonably stuffed with Tamiflu, then Tamiflu is able to inhibit the nasty protein, not the nasty protein of the original intruder, but that of the replicas. So the replicas can no longer pass through the cell wall to the outside and are unable to start infecting new cells. The virus replicas are simply trapped inside the cell walls, where the slowly fade away.

All of this looks wonderful on paper. The reality is better grasped by examining the word that the manufacturer uses in his description of the product: "Tamiflu is a neuraminidase inhibitor". The nasty protein is merely "inhibited", not "stopped".

So if just a few viruses have happened to hit you before you start stuffing yourself with Tamiflu, then the inhibition may be sufficient for preventing a full-scale virus chain reaction. But there is unfortunately also a point where the number of already infected cells is too large for the inhibition to make much difference. Hence it’s imperative to take the drug at the earliest possible time after the first symptoms of the disease have appeared. On the other hand, early symptoms are not all that easy to recognise. The cough you gave a moment ago, was that the onset of the avian flu, or was it just a nervous cough, triggered by the fact that you happen to be secretly in love with me?

Maybe no real shortage, but a severe anxiety gap

A problem with Tamiflu is that there is a severe shortage of Tamiflu in bird-flu-anxious Europe. Well, maybe there is no shortage in a real sense (the total number of bird flu patients to date is around 100, and zero in Europe), but there exists a sizeable gap between angry demand and actual supply. Roche (Hoffman-La Roche) holds the only license to the patent and is the sole manufacturer of the drug. In view of a possible bird flu pandemic, Roche has come under pressure to make Tamiflu available to other manufacturers as well. A problem with that is that Roche maintains that there is a severe shortage of raw material, i.e. of the Star anise grown in China –- some 90% of the harvest is reportedly already used by Roche, not leaving very much to other manufacturers (or to the makers of the aperitif Pernod, by the way -- horrible).

Reference:

http://pubs.acs.org/cen/coverstory/8029/8029finechemicals.html
www.fda.gov/cder/consumerinfo/druginfo/tamiflu.htm
www.tamiflu.com/

Due to the current avian flu scare, it is very interesting to note that there may be more politics involved in this than there is virus.

Specifically, the pharmaceutical company Roche is NOT the patent holder for the active ingredient in Tamiflu (oseltamivir phosphate). Roche however is the sole licensee of this patent.

The patent for oseltamivar is held by a Foster City, CA company called Gilead Sciences Inc. Gilead had been quiet about this association for good reason, but had also been critical of Roche for their marketing (or lack thereof) of Tamiflu. The exclusive license does not allow another company to produce this drug, and therefore Gilead's profits are at the mercy of Roche's ability to manufacture and push this drug.

Oseltamivar has NOT been approved by the FDA to fight avian flu. It is possible that at best it is minimally effective against it, and at worst, it could cause more lethal mutations.

What is REALLY interesting is the motivations that our government has for spending billions of dollars stockpiling this medicine. . .

In 1997, Donald Rumsfeld was named chairman of the board of directors for Gilead Sciences Inc. Yes, this is the same Don that currently controls the Pentagon as Secretary of Defense for the United States. He held his position at Gilead until he was appointed by Bush and still remains one of their major stock holders. Gilead, and therefore Rumsfeld, have much to gain from pressuring the government to allow others to produce this drug. They are also first in line to benefit from US contracts to purchase it.

This association is rarely mentioned by the media, and is played down by the White House, but it is obvious that there is something more sinister than a virus going on here:

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By THE NEW YORK TIMES
Published: October 28, 2005
WASHINGTON, Oct. 27 - Defense Secretary Donald H. Rumsfeld has recused himself from government decisions concerning medications to prevent or treat avian flu, rather than sell his stock holdings in the company that patented the antiviral agent Tamiflu, according to a Pentagon memorandum issued Thursday.
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