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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."

40 of 252 comments (clear)

  1. Good News....right? by TripMaster+Monkey · · Score: 5, Insightful

    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:

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

    ~ |rip/\/\aster /\/\onkey

    1. Re:Good News....right? by Anonymous Coward · · Score: 4, Funny
      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.

    2. Re:Good News....right? by thebdj · · Score: 5, Insightful

      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.

      --
      "Some days you just can't get rid of a bomb."
    3. Re:Good News....right? by elmarkitse · · Score: 2, Funny

      wait a minute. You're suggesting that the best defense for a pandemic of BIRD FLU would be to consume CHICKEN Soup?

      That smacks of a vaguely Matrix 'human as the incubator' approach to a new 'mass produced' production technique of generating the necessary antibodies quickly, no?

    4. Re:Good News....right? by Pedrito · · Score: 4, Insightful

      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.

    5. Re:Good News....right? by Philip+K+Dickhead · · Score: 3, Interesting

      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.

      --
      "Speaking the Truth in times of universal deceit is a revolutionary act." -- George Orwell
    6. Re:Good News....right? by moro_666 · · Score: 3, Insightful

      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.

      --

      I'd tell you the chances of this story being a dupe, but you wouldn't like it.
    7. Re:Good News....right? by gg3po · · Score: 2, Informative
      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 another example of government corruption -- an excuse to funnel large quantities of taxpayer dollars into the pockets of chronies like Donald Rumsfeld and crew. Turns out all these huge orders placed by the federal government for an ineffective treatment are making certain "private" citizens very wealthy. Wake up, America, your wallet was just raped, again.

      --
      ---
  2. Is it almost over? by Phantombrain · · Score: 3, Funny

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

    --
    echo YOUR_OPINION > /dev/null
  3. Good news... by DaHat · · Score: 2, Insightful

    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.

    1. Re:Good news... by meringuoid · · Score: 5, Interesting
      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...

      --
      Real Daleks don't climb stairs - they level the building.
    2. Re:Good news... by mikeisme77 · · Score: 4, Insightful
      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.

    3. Re:Good news... by TheOtherChimeraTwin · · Score: 3, Interesting
      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 about H5N1, so it makes sense to take some precautions.

      The Great Influenza by John Barry will scare your socks off, and it is all historical fact.

      A good source of information about a possible pandemic is fluwikie.com

    4. Re:Good news... by ocbwilg · · Score: 2, Insightful

      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.

      Maybe it's flu, maybe it's something else. If we spent so much hype, time, energy, and effort preparing for every possible bug that could become an epidemic or pandemic, we would never get anything done. Personally, I am far more concerned about the epidemics that we know about (HIV for example) than I am about bird flu. I think that the main reason that bird flu (which has only infected a couple dozen people and killed even fewer) gets so much press is two fold:

      1. The majority of the media-embracing public understands the concepts of birds and flu.

      2. The Bush administration is zero for two on preventing, mitigating, or responding to major US disasters (9/11 and Katrina) and they're desperate to look like they're doing something to prepare for future disasters.

  4. Thanks, but... by gEvil+(beta) · · Score: 3, Funny

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

    --
    This guy's the limit!
  5. Biggest chance to save people? by mothlos · · Score: 2, Insightful

    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.

  6. This is nice work, but... by thisisfrankscortex · · Score: 5, Interesting

    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."

  7. We just need Yogi Bear. by Anonymous Coward · · Score: 3, Funny

    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!

  8. Real threat? Real solution? by hj43us · · Score: 3, Funny

    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?

    1. Re:Real threat? Real solution? by Tibor+the+Hun · · Score: 2, Interesting

      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 moderate success.)

      --
      If you don't know what AltaVista is (was), get off my lawn.
  9. Petrochemicals? by MOtisBeard · · Score: 2, Funny
    Tamiflu is made from petrochemicals???

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

  10. For anyone wanting expert info on the threat by brian0918 · · Score: 3, Interesting

    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

    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.

  11. Tamiflu Already Shown to be Ineffective by chromozone · · Score: 2, Interesting

    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/20051221/tamiflu_drug_051221/20051221

    Many top experts are advising to prepare for the worst. The US gov. is urging people to store food that could last for three months. In the UK mass graves are being planed openly. Forget Tamiflu:

    (BBC) http://news.bbc.co.uk/2/hi/uk_news/4869224.stm

  12. Re:So patent it quickly by TapeCutter · · Score: 2, Interesting

    Roche have dragged their heels with licenses for over a year, they finally issued a few licenses after several governments threatened to force a license agreement on them. Regardless of the eventual merits of the drug, Roche's lengthy "license negotiations" are an exercise in pure greed.

    --
    And did you exchange a walk on part in the war for a lead role in a cage? - Pink Floyd.
  13. RTFWA by PatrickThomson · · Score: 3, Informative

    from http://en.wikipedia.org/wiki/Tamiflu 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.

    --
    I am one of many. My idea is not unique, nor do I expect my voice alone to sway you. I speak in a chorus of opinion.
  14. Re:Bird flu? by mgblst · · Score: 3, Funny

    *raised stump*

  15. Educate yourself by GuloGulo2 · · Score: 3, Informative

    "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 America in December 1889, South America in February-April 1890, India in February-March 1890, and Australia in March-April 1890. It was purportedly caused by the H2N8 type of flu virus and had a very high attack and mortality rate.
                        o The "Spanish flu", 1918-1919. First identified early March 1918 in US troops training at Camp Funstan, Kansas, by October 1918 it had spread to become a world-wide pandemic on all continents. Unusually deadly and virulent, it ended nearly as quickly as it began, vanishing completely within 18 months. In six months, 25 million were dead; some estimates put the total of those killed worldwide at over twice that number. An estimated 17 million died in India, 500,000 in the United States and 200,000 in the UK. The virus was recently reconstructed by scientists at the CDC studying remains preserved by the Alaskan permafrost. They identified it as a type of H1N1 virus.
                        o The "Asian Flu", 1957-58. An H2N2 caused about 70,000 deaths in the United States. First identified in China in late February 1957, the Asian flu spread to the United States by June 1957.
                        o The "Hong Kong Flu", 1968-69. An H3N2 caused about 34,000 deaths in the United States. This virus was first detected in Hong Kong in early 1968 and spread to the United States later that year. Influenza A (H3N2) viruses still circulate today"

    None of your other examples prove anything about flu. All it proves it that you never bothered to look up just how dangerous flu pandemics are.

    "While they're all threats, they aren't just going to all of a sudden just break out all over the place."

    Um, yes actually, that's exactly what will happen with the flu.

    "When it explodes, THEN freak out about it, but until then enjoy life."

    Yeah, great, why would we be developing effective treatments, exapnding our knowledge of virus pathology, and improving our procedures, when we could be drinking margaritas and listening to reggae.

    Newsflash, you lay the groundwork for dealing with outbreaks before they happen. Your stupid plan results in more deaths.

    1. Re:Educate yourself by meringuoid · · Score: 2, Interesting
      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 dispose of around 300,000 bodies, as a worst-case scenario: that's about one twentieth of the population. Doesn't seem so much on the face of it, does it? Surely we can cope without 5%.

      But for everyone killed, how many spend weeks off work on a sickbed? How many do not fall ill, but stay off work to minimise their potential exposure, at the office and on buses or the Tube? And what if the one killed happens to be the boss? Or the only guy who knows the root password? And remember also that with these diseases, the young and healthy - and hence economically active - are worst hit, because death is often caused by an over-reaction of the immune system.

      I can quite imagine that a flu killing one in twenty in this way could completely paralyse the national economy for the duration.

      --
      Real Daleks don't climb stairs - they level the building.
    2. Re:Educate yourself by vidarh · · Score: 2, Informative
      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%.

    3. Re:Educate yourself by meringuoid · · Score: 2
      The UK has 60 million inhabitants, not 6 million... So it's 0.5%, not 5%.

      See, here's why I probably shouldn't stick away a couple of pints at lunchtime and then try to do mental arithmetic. Misplaced decimal point, editing out 54 million people from the UK. Oops.

      That said, some among the Scots, Welsh and Not Quite Irish would probably appreciate the removal of 54 million people from the UK :-)

      --
      Real Daleks don't climb stairs - they level the building.
  16. Cytokine Storm == Deadly by gandreas · · Score: 2, Informative
    Check out what Michael Osterholm (the former Minnesota state epidemiologist) has to say: http://citypages.com/databank/27/1320/article14219 .asp:
    "H5N1 is the most powerful influenza virus we've seen in modern human history"
    and if you don't feel like reading the whole article:
    This virus is quite different from what we see with the standard annual flu, and what we saw in 1957 and 1968, because of the cytokine storm it causes. In 1918, the vast majority of the people who died were healthy young people, 20 to 40 years of age. And that was in large part because they had the strongest immune systems.
    So the fact that the more healthy you are, the more likely this thing could kill you. Yikes!
    1. Re:Cytokine Storm == Deadly by gEvil+(beta) · · Score: 2, Funny

      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...

      --
      This guy's the limit!
  17. The way I read those articles is by plopez · · Score: 2, Interesting

    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.

    --
    putting the 'B' in LGBTQ+
  18. Re:Why concentrate on bird flu.. by brian0918 · · Score: 2

    "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 form of bird flu. People only get that form if they live around chickens--swimming in chicken shit. The threat is if it mutates into a form that can be tranferred between humans. Care to inform yourself, so you don't sound so wrong? Watch this:

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

  19. reading between lines by LinuxRulz · · Score: 2, Funny

    "...from highly explosive..."
    hmmm I see... They plan to eliminate bird flu by making every sick bird explode. clever!

  20. Don't worry, the gov't is prepared by ThinWhiteDuke · · Score: 2, Funny
    --

    It would be nice to be sure of anything the way some people are of everything.
  21. some chemistry clarification by bodrell · · Score: 3, Informative
    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.

    --
    Si la vida me da palo, yo la voy a soportar Si la vida me da palo, yo la voy a espabilar
  22. Better solution - universal vaccine by PIPBoy3000 · · Score: 3, Informative

    A new vaccine 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.

  23. Mortality rates by tjwhaynes · · Score: 4, Insightful
    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

    --
    Anything I post is strictly my own thoughts and doesn't necessarily have anything to do with the opinions of IBM.
  24. It's always what you don't anticipate... by Dzimas · · Score: 2, Interesting
    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.