Bird Flu Drug Mass Production Technique Discovered

creepygeek writes to mention a New Scientist article detailing a new process for creating Tamiflu, an antiviral drug currently thought to be our best defense against the bird flu. From the article: "Making Tamiflu is slow, partly because shikimic is hard to get, but also because one step in the process involves a highly explosive chemical called an azide. As a result, Tamiflu can be made only in small batches of a few tens of litres at a time. But Elias Corey of Harvard University - who won a Nobel prize in 1990 for chemical synthesis - and colleagues have devised a new way to make the drug from two cheap, plentiful petrochemicals, acrylate and butadiene."

Good News....right?

From TFA:

The biggest hope for saving people at the start of a bird flu pandemic, before a vaccine is available, is the antiviral drug Tamiflu

It's too bad that our 'biggest hope' is not up to the task, as the following articles assert:

• Flu drugs 'will not work' if pandemic strikes [guardian.co.uk]
  
• Tamiflu May Not Be So Effective Against Bird Flu [medicalnewstoday.com]
  
• Bird flu proving resistant to Tamiflu treatment [msn.com]
  

It might be better to just stock up on old-fashioned Jewish penicillin [ivillage.co.uk].

Re:Good News....right?

It might be better to just stock up on old-fashioned Jewish penicillin.

Not a good plan. If Bird Flu strikes, chicken will be rarer than shikimic acid.

Re:Good News....right?

Yeah, but Tamiflu is a great scam for Rumsfeld, who made millions as a former Executive with Gilead - the developer of this nonsense.

Take two Vioxx, and call me from Iraq in the morning.

Re:Good News....right?

how do these articles even get posted ?


Tamiflu, an antiviral drug currently thought to be our best defense against


AFAIK Tamiflu doesn't Defend you from the virus, it just makes easier for the body to Fight it once you're already infected. you can still die, and if you've been illusional enough to waste your Tamiflu before you got ill the chances will be even better (since there won't be any on the market when/if it will/should ever hit in).

There's still no birdflu here that could move from one mammal to another via air. There are lots of other viruses around that deal much greater damage at the time being, perhaps we should pay attention at them aswell ?

ps. even if you buy a ton of tamifly, the animals that you need around for the farming industry to work, won't be protected, and if it's half as bad as it supposedly could be, you'll just die into hunger. hopefully wild animals have better protection against it than the worthless humans.

Re:Good News....right?

Two of the three articles reference to the same write-up from the NEMJ. It is also possible, though I cannot be sure, that the third article's journal reference could be a submission from the same individual. Now, I do not know how much to trust what they say about Tamiflu still being the best option, because saying otherwise would just lead people to freak out when the pandemic comes, but I believe it would probably still be one of the better options.

Drug resistances happen because virii and bacteria mutate over time. This is a big reason why many traditional antibiotics are becoming less useful against certain bacteria, and a possible cause for some of the "super bugs." And if your idea for fighting bird flu is with chicken soup, we truly are screwed.

Re:Good News....right?

What we really need to do is beef up our local emergency response system across the entire country. Unfortunately, this costs real money. We seem tempted to think the right pill will fix all other aspects of our lives, and another flu pandemic is no differ

Re:Good News....right?

It's impossible at this point to determine how resistant the bird flu will be to Tamiflu if it becomes an easily contagious pandemic form. The reason? Because to become easily contagious, it has to mutate. When it mutates, it becomes a different virus which may be more resistant than the current strain, less resistant, or the same.

The difference from a mutation can be enormous. For example, the current virus has about a 50% mortality rate. It is very like when that when it mutates, this mortality rate will go down. The Spanish Flu epidemic of 1918 had only a 2.5-5% mortality rate and that was without Tamiflu. That doesn't mean this one will mutate into only having a 2.5-5% rate. It will likely have a higher rate, and frankly, I think a lot of the predictions of how many will die from an H5N1 mutant pandemic are lowball figures because they do tend to assume a pretty low mortality compared to what it's currently at.

But you're basically comparing apples and oranges at this point. A pandemic flu will not be the current strain because the current strain simply isn't contagious enough.

Mortality rates

For example, the current virus has about a 50% mortality rate. It is very like when that when it mutates, this mortality rate will go down.

I have problems with these mortality figures. It's very easy to determine who died from bird flu - you have a body, death certificate, medical records, etc. It is NOT easy to work out who has had the bird flu and has survived in the general populace - not all sick people will have seen a doctor and some may not even have developed symptoms. Without doing a massive study looking for bird-flu antibodies, the mortality figures are almost certainly overblown, maybe by orders of magnitude. This applies whether we are talking about the impact on birds or on humans.

Cheers,
Toby Haynes

Don't worry, the gov't is prepared

They have a plan [borowitzreport.com]

Better solution - universal vaccine

A new vaccine [yahoo.com] has been developed that targets the part of a flu virus that is conserved between mutations. Admittedly it might not be as effective as a targeted vacciene for a particular strain, but it would likely provide general protection against most flu viruses. So far it's been tested in ferrets (a good human model) and protects against H5N1 avian influenza.

Re:Good News....right?

It's too bad that our 'biggest hope' is not up to the task...

This is because the purpose of all this "bird flu" fear-mongering, and particularly in relation to Tamiflu®, has nothing to do with protecting the public. It appears to be really just anot

Is it almost over?

Can I come out of my air-tight bubble yet?

Good news...

If we believe the hype that the bird flu is a real threat to the health of the people of the world... which despite the hype from the media and the upcoming ABC made for tv movie... I have yet to see any credible evidence of despite much looking.

Re:Good news...

If we believe the hype that the bird flu is a real threat to the health of the people of the world... which despite the hype from the media and the upcoming ABC made for tv movie... I have yet to see any credible evidence of despite much looking.

Every so often, a mutant flu strain arises that kills millions of people. Most famously in 1919, when more people died from flu than were killed in the entire four years of unprecedentedly bloody warfare just past. IIRC there were two more major flu pandemics in the twentieth century, although neither were as devastating.

Sooner or later there WILL be another flu with the ability to kill millions. The only way we have of preventing another 1919 is to spot the threat before it gets going and prepare a vaccine. Hence the worry over H5N1. It's entirely possible that it will all blow over. It's also possible that it will mutate to a form that can spread from one human to another, and become pandemic. If it doesn't, well, great. If it does, we'll be glad we prepared.

For myself, I'm far more afraid of a mutant strain of bird flu killing me than I am of terrorists killing me. That said, I'm more afraid of being hit by a car than I am of either of them, but that doesn't stop me crossing the road...

Exactly

There aren't too many people around that still remember the 1918 pandemic, but if you have records of your relatives that were alive at the time, odds are at least one of them died of the flu.

Re:Good news...

Well said. Our society tends to ignore events with a low probability of occuring. (What are the odds a hurricane could hit New Orleans, right?) A pandemic will happen again someday; we just don't have a schedule.

Experts like Robert G. Webster are worried

Re:Good news...

Sooner or later there WILL be another flu with the ability to kill millions. The only way we have of preventing another 1919 is to spot the threat before it gets going and prepare a vaccine. Hence the worry over H5N1. It's entirely possible that it will al

Re:Good news...

Exactly. The media is always blowing something out of proportion as the next big threat to humanity (or the US):

-Killer bees (there was a movie on this one too)
-SARS
-AIDs (several movies)
-Terrorism
-Anthrax (related to the above)
-Small Pox coming back
-Etc.

While they're all threats, they aren't just going to all of a sudden just break out all over the place. The media loves to feed off our fears--as it sells almost as well as sex. When it explodes, THEN freak out about it, but until then enjoy life.

Educate yourself

"Influenza
o The "Asiatic Flu", 1889-1890. Was first reported in May of 1889 in Bukhara, Russia. By October, it had reached Tomsk and the Caucasus. It rapidly spread west and hit North A

Re:Educate yourself

And all of those examples, the largest death toll was still "only" 50 million or so world wide. That's a far cry from shutting down 3/4 of the US and such that the media predicts.

I hear that the British government are setting up contingency plans to disp

Re:Educate yourself

I hear that the British government are setting up contingency plans to dispose of around 300,000 bodies, as a worst-case scenario: that's about one twentieth of the population.

The UK has 60 million inhabitants, not 6 million... So it's 0.5%, not 5%.

Mod parent down

Are we to trust a random person on /. to look for "credible evidence", or the opinion of several experts actively working on the subject:

http://video.google.com/videoplay?docid=234341498 8 689203314 [google.com]

Re:Cytokine Storm == Deadly

So the fact that the more healthy you are, the more likely this thing could kill you.

A collective sigh of relief is heard emanating from the readers of slashdot...

So patent it quickly

Before any useful medical advancement becomes available to the general public. Yes, this is a cynical remark. Is any other kind of a remark merited by the way things work today?

Re:So patent it quickly

From TFA:

The Tamiflu molecule itself is patented, regardless of how it is made, and Roche holds the rights to the patent. But in 2005 Roche said it would not stop other companies making Tamiflu under license, which is expressly permitted by international

Re:So patent it quickly

Roche have dragged their heels with licenses for over a year, they finally issued a few licenses [ip-watch.org] after several governments threatened to force a license agreement on them. Regardless of the eventual merits of the drug, Roche's lengthy "license negotiations

RTFWA

from http://en.wikipedia.org/wiki/Tamiflu [wikipedia.org] and tfa, it seems that the new process which this article is about has been released patent free. IAAOC (I am an organic chemist) and the new synthesis is safer and less dependant on difficult-to-obtain natural precursors. These guys should be applauded for sacrificing a profitable idea for the greater good.

Thanks, but...

Thanks, but no thanks. I prefer the highly explosive vaccine, thank you very much...

Biggest chance to save people?

How about education and municipal plans to regarding epidemics? Anti-virals might be the best chance of treating those who have bird flu, but the best practice is to contain the virus early and give the medical community time to develop a real vaccine defense.

This is nice work, but...

I think the most notable thing about this paper is that the last sentances read "It is our hope that the process described herein will be of value in improving the opply of oseltamivir and in reducing the cost. With regard to the latter, the process described herein in in the (unpatented) public domain."

We just need Yogi Bear.

I hear Yogi Bear is quite good at getting baskets full of shikimic. I might have heard wrong, though.

Hey Boo-Boo, let's go grab the shik-a-mic basket, the mi-grr-a-tor-ee birds are coming with the flooo!

Real threat? Real solution?

Till know aound 50 people worldwide had died of bird flu. I guess more people die being stroke by a lightning. But the worst thing is that nobody knows whether Tamiflu will cure bird flu or not. Meanwhile health authorities all over the wold had been doing massive buys of that medicine ... sounds weird. I, for one, start a business of selling a new drug that is suppossed to protect you against being struck by a lightning. I'm already taking orders. Anyone?

Re:Real threat? Real solution?

The problem with your argument is that chickens do not transmit lightning strikes to each other, nor has it ever been documented that one organizm can transmit a lightning strike to another. (Though there is a Sci-ops contingent known as E.E.L.S. that has

Nonsense

"Till know aound 50 people worldwide had died of bird flu."

The threat is not from this form of bird flu. The threat is from a form that can be transferred from human to human. If that happens, predictions are that it could kill upwards of 70 million peo

Petrochemicals?

Tamiflu is made from petrochemicals???

How long before we see a story about making bioTamiflu out of used vegetable oil from McDonald's?

Bird flu?

Who else read this and only saw "highly explosive" and spent 20 mins looking up stuff that exploded.

Bah to your end of the world disease, I was stuff that blows up.

Re:Bird flu?

*raises hand*

Re:Bird flu?

*raised stump*

For anyone wanting expert info on the threat

For anyone who believes that it is all hype, or knows little about bird flu, I highly recommend this extremely informative discussion Charlie Rose had with 3 experts on the subject. It is by no means overly technical.

http://video.google.com/videoplay?docid=2343414988 689203314 [google.com]

The truth is that it is not hype; just because we know about it well ahead of the time when it will actually affect us doesn't mean that it will not be a threat. The most interesting part of that discussion is the possibility that people with AIDS will be the least likely to be harmed by bird flu, since it is the overactive immune system--in response to the foreign disease--that ultimately kills you.

Re:For anyone wanting expert info on the threat

And by "3 experts", I meant 5 or 6 experts...

Oh, wonderful!

Now there's yet another thing to drive up the price of oil! Just what we needed!

(yes, that was sarcastic...)

Re:Oh, wonderful!

HAH!
The joke's on you.
With the truck maintainers, dispatchers, drivers, train loaders, controllers and engineers, grocery chain administrators, stockers, floorpeople and salespeople staying home either sick, hungry, scared or dying there won't be any need

petrochemical eh?

"a new way to make the drug from two cheap, plentiful petrochemicals, acrylate and butadiene"

Petrochemical eh? as in petro based? Does this mean gas price is going up more once we start making these drugs? :)

Re:petrochemical eh?

Yes, but the upside is that you'll be able to fuel your car with Tamiflu pills.

Tamiflu Already Shown to be Ineffective

Tamiflu won't work. The H5N1 virus can mutate into a form unaffected by Tamiflu. In Vietnam four out of eight avian flu patients who were given the medication died despite the treatment.

(CTV NEWS) http://www.ctv.ca/servlet/ArticleNews/story/CTVNew s/20051 [www.ctv.ca]

The way I read those articles is

1) There probably is no statisically significant data available to determine if tamuflu can stop an epidemic.
2) To rely on only one method is insane. This is just common sense.
3) The assumption is that over time the disease may be come resistant to tamuflu and so other measures are needed (see pt. #2).
4) Tamuflu failed when improper dosages were given.

So to throw out tamuflu would be silly. It would be a good thing to have around, thought the only way to really find out is to have a major outbreak. Only then will we *really* know if it would work.

No time for FUD, I must get on with life.

some chemistry clarification

Roche's current production methods use the azide (which is not as hazardous as news articles would have you believe), but their own scientists have already come up with an azide-free route (though it still uses shikimic acid). See for yourself:

J. Org. Chem. 2001, 66, 2044-2051.

"New, Azide-Free Transformation of Epoxides into 1,2-Diamino Compounds: Synthesis of the Anti-Influenza Neuraminidase Inhibitor Oseltamivir Phosphate (Tamiflu)"

Martin Karpf* and Rene Trussardi F. Hoffmann-La Roche Ltd., Pharmaceuticals Division, Non-Clinical Development, Chemical Process Research, Grenzacherstrasse 124, CH-4070, Basel, Switzerland

Google scholar should show at least the first page.

Corey's synthesis is pretty nifty. It just needs FDA approval and Roche has to adopt it. Given that Roche has had an azide-free route available since 2000, I'm thinking the process change is more than trivial. The Chemical and Engineering News article is much more informative, if you have access to that journal, and you like chemical structures.

It's always what you don't anticipate...

I wonder what the side-effects of injecting acrylate and butadiene into a few million people would be. My suspicion is that there will be a low but non-zero reaction rate. And even 0.01% of 100,000,000 people adds up to a hundred thousand individuals sickened by a protective measure that might prove ineffectual. It also seems that there's a genetic factor at play with bird flu susceptibility - some infected families were hit harder as a group than others who caught the same illness at the same time and place.

If I try on my tinfoil hat for a moment, it seems that the only winner in a Tamiflu stockpiling situation will be the manufacturer. We can be almost certain that the "next big pandemic" will blind side us. That is, after all, the nature of pandemics. It'll be a mutated form of *something*, probably something quite benign.

Re:Bird Flu, The Biggest Pandemic That Never Was!

Are you done? Watch this:

http://video.google.com/videoplay?docid=2343414988 689203314 [google.com]

Re:Why concentrate on bird flu..

"Yes, yes, yes. People have died to bird flu, but the amount dead is comparable to the amount of children dying from hunger in like 2 minutes. So fuck the bird flu. It's just another scam to make someone really rich."

The threat isn't from the current fo