bird flu

October 15, 2005

Thought this was interesting, so decided to share

http://news.independent.co.uk/uk/health_medical/article319716.ece

Why an exotic fruit is the world's only weapon against bird flu

By Jeremy Laurance, Health Editor

Published: 15 October 2005

A rare herb grown in China used to flavour duck dishes and treat

infants for colic is at the centre of a worldwide search for a cure

for avian flu.

Star anise, the unusual fruit of a small oriental tree, is sold in

supermarkets in the UK to consumers seeking its pungent,

liquorice-like flavour.

But the herb has a vital function as the source of shikimic acid from

which the drug Tamiflu is made, the only defence the world currently

has against the threatened flu pandemic.

Tamiflu cannot prevent infection with avian flu but it can reduce its

severity. In the absence of an effective vaccine - which has not yet

been developed - it is all that stands between the world and what

could become a modern plague.

Yesterday it emerged that a shortage of star anise is one of the key

reasons why countries including Britain cannot obtain enough Tamiflu

to protect their populations. European Union ministers met yesterday

to discuss measures to reduce contact between wild birds and poultry

to curb its spread.

The deadly H5N1 strain of the virus, which has infected more than 100

humans, killing more than 60, in the Far East, was identified this

week in poultry in Turkey. Results of tests on infected birds in

Romania are expected to be revealed on Monday. EU scientistsagreed

measures that could lead to millions of chickens and turkeys being

kept indoors to prevent contact with migrating birds.

In Britain, the Animal Welfare minister Ben Bradshaw said that the

Government had not ruled out ordering free-range poultry in Britain

to be moved indoors.

As moves to halt the growing threat of avian flu intensified,

governments sought to stockpile the only drug currently available to

offer any sort of defence for humans. The herb from which Tamiflu is

made is grown in four provinces in China and " huge quantities " of its

seeds are needed, according to the Swiss pharmaceutical manufacturer Roche.

It is harvested by local farmers between March and May, purified and

the shikimic acid extracted at the start of a 10-stage manufacturing

process which takes a year.

Only star anise grown in the four provinces of China is suitable for

manufacture into Tamiflu and 90 per cent of the harvest is already

used by Roche.

The company has faced demands to relax the patent on the drug to

allow other manufacturers to produce it.

Keith Taylor, of the Green Party, said: " Some countries have asked

the World Health Organisation to pressure Roche into relinquishing

the patent in order to allow a cheaper, generic version of the drug

to be produced on a national level.

" The WHO refuses, citing Roche's donation of three million treatment

courses as evidence that Roche is being responsible. This decision

jeopardises millions of lives in the name of profit and is anything

but responsible. "

However, Roche responded by saying: " Because of the shortage of the

raw material it would be very difficult for another manufacturer to

set up production. "

The UK Government has ordered 14.6 million courses of Tamiflu, enough

for 25 per cent of the population, but only 2.5 million courses have

so far been delivered. Other countries, including the United States,

are behind the UK in the queue. Roche said it had doubled production

of Tamiflu in 2004, doubled it again in 2005 and planned to double it

again next year. But it said calls for the patent on the drug to be

removed so that other companies could boost manufacturing capacity to

meet the worldwide demand would not work.

The spokeswoman said: " It would take two to three years for another

company to build the manufacturing capacity. The process is very

complicated and the drug takes us 12 months to produce. Once you have

built the facilities you have to get regulatory approval and the

manufacturing licences.

" And then there is the shortage of the raw material. "

Roche has developed a synthetic source of acidinic acid, made from

the bacterium E Coli. Vast quantities of E Coli are mixed with

glucose in vats the size of two buses. But star anise remains the

chief source, the company said.

Once shikimic acid is extracted from the seeds of star anise it is

converted to epoxide in a process requiring three chemical steps

carried out at low temperature on seven separate sites.

The most dangerous part of the process involves the conversion of

epoxide into azide in a reaction that produces highly explosive

material. This is carried out by specialist companies that handle the

material in small quantities to reduce the risk of explosion.

Currently only one US company and two European companies are approved

by the drug regulatory authorities in America and Europe to carry out

the process.

The final step involves the production of crystal strands of the

active ingredient of Tamiflu, whose chemical name is oseltamivir,

which are vacuum dried and converted to capsules.

The World Health Organisation yesterday declined to comment on

reports that it was in negotiation with Roche over the lifting of the

patent on Tamiflu.

" If we were in discussion with them it would be to relieve the supply

shortage of the drug and to help poorer countries.

" But it would not be helpful to do that in public, " a WHO spokesman said.