Here is a great commentary on the Flu scare that sums up all the facts, probably a lot better than I have....
Enjoy...
Dr Bawa
Reasons to Be Fearful
By HENRY I. MILLER
October 17, 2005; Page A18, Wall Street Journal
During the past several years, an especially virulent strain of avian flu has ravaged flocks of domesticated poultry in Asia and spread to migratory birds. Fortunately, only rarely has it been transmitted from bird to human, and probably not at all between humans ? yet. But flu virus mutates readily, and virologists expect that sooner or later it will acquire the ability to spread from person to person.
This is potentially catastrophic. The avian flu strain H5N1 already has two of the three characteristics needed to cause a pandemic: It can (1) jump from bird to human and (2) produce an often fatal illness; more than 60 deaths have been attributed to H5N1. If additional genetic evolution makes the virus highly transmissible among humans -- the third characteristic of a pandemic strain -- a worldwide outbreak could become reality. (The operative term here is highly transmissible; a flu virus that spreads as readily as the common cold would spell real trouble, but one that spreads less readily would be more manageable.)
H5N1 is an extraordinarily deadly variant: The mortality rate for persons infected with the existing H5N1 appears to be around 50%, whereas the garden-variety annual flu kills less than 1%. This gives us plenty to worry about. The acquisition of the genetic change(s) needed to become transmissible from human to human is stochastic -- i.e., essentially random, therefore unpredictable. The more viruses there are, the greater the chances that one will acquire the "open-sesame" genetic changes, either by mutation or by exchanging genes during simultaneous infection of a person or animal with H5N1 and another flu virus. And there is more H5N1 around every day: In recent months it has spread over much of Asia and into Russia. Only last week, it was discovered in birds in Turkey.
We are ill-prepared for a flu pandemic. Reserve capacity is grossly inadequate for vaccines, drugs and hospital beds. The best and most cost-effective intervention -- prevention with a vaccine -- presents technological, economic and logistical obstacles. Anti-flu drugs exist but are not a panacea. Unlike vaccines, which confer long-term immunity after one or two doses, drugs need to be taken for long periods. The only drug that has been shown to prevent the flu is Tamiflu, the effect lasting only as long as one takes the drug. (The other major anti-flu medicine, Relenza, has only been shown to be effective to treat, but not prevent, flu.)
Yet a recent paper in the journal Nature reported a patient in Vietnam infected with a strain of H5N1 partially resistant to Tamiflu, so our primary prophylactic drug might already be compromised. This is dismaying, because the viral isolate was collected earlier this year when the drug had not yet been widely used in Asia, so H5N1 hadn't yet had much opportunity to develop resistance. It's possible that the drug was used improperly -- administered in a lower dose than prescribed, or intermittently instead of continuously -- or that the recommended prophylactic dose is too low. Whatever the cause, the result is bad news.
So where do we go from here? In the face of a potentially cataclysmic pandemic, we need multiple strategies that offer various alternatives to prophylaxis and treatment. But the constraints of current vaccine-production methods slow our response to new variants of flu virus. The conventional approach would be to grow the actual pandemic strain in millions of fertilized chicken eggs, and weaken or kill it to make a vaccine. But this takes time, and because H5N1 is highly toxic to the eggs, we would have first to tinker with its genetics and then ensure that it would still function as a vaccine. In the face of a pandemic, the time-lag could be catastrophic.
A few companies are taking innovative approaches to vaccine development. Scientists at Chiron Corp. have proposed making a kind of prototype vaccine against the current, pre-pandemic strain of H5N1 -- which has already been done experimentally by the National Institutes of Health -- and adding boosters called adjuvants to boost immune response: Here, there might well be a significant protective effect even after a single dose, although the virus in the vaccine would not be a perfect match to the pandemic strain. We could begin to produce this adjuvant-boosted vaccine almost immediately.
Another scientifically elegant approach is gene-splicing, to make "subunit" flu vaccines. Used to produce hepatitis B vaccine, this approach involves moving a single gene (or a small number) from the virus into bacteria or yeast; then, grown large-scale, these organisms would be the source of the viral gene product(s) which, after being isolated and purified, would be used as vaccine. The Holy Grail of this tack is a vaccine that elicits an immune response to the proteins of flu virus that are highly conserved from strain to strain. Finally, another approach would be to construct a vaccine from naked DNA, which is being tried by several companies.
Industry's efforts need a federal boost. Grant-giving agencies should fund "proof of concept" research on cultured cells to supplant eggs for growing virus; and also on flu subunit vaccines, especially those that are effective against many strains. Regulators should waive registration fees on flu-related products, and should pursue agreements on "reciprocity" of approvals so that vaccines and antiviral drugs licensed in certain foreign countries can be marketed in the U.S. The government should indemnify vaccine- and drug-producers against liability claims and guarantee purchases of approved products. Government scientists should study whether during periods of vaccine scarcity it makes sense to inoculate the elderly early on as a "high risk group," although many of them fail to mount a vigorous immune response. A more effective approach would be to vaccinate their caregivers and household contacts (as well as first responders and health-care workers, of course).
We need to be aggressive, innovative and, above all, resilient. In society, as in biology, resilience means survival.
Mr. Miller, a physician and fellow at the Hoover Institution, was founding director of the Office of Biotechnology at the FDA, 1989-1993.
Enjoy...
Dr Bawa
Reasons to Be Fearful
By HENRY I. MILLER
October 17, 2005; Page A18, Wall Street Journal
During the past several years, an especially virulent strain of avian flu has ravaged flocks of domesticated poultry in Asia and spread to migratory birds. Fortunately, only rarely has it been transmitted from bird to human, and probably not at all between humans ? yet. But flu virus mutates readily, and virologists expect that sooner or later it will acquire the ability to spread from person to person.
This is potentially catastrophic. The avian flu strain H5N1 already has two of the three characteristics needed to cause a pandemic: It can (1) jump from bird to human and (2) produce an often fatal illness; more than 60 deaths have been attributed to H5N1. If additional genetic evolution makes the virus highly transmissible among humans -- the third characteristic of a pandemic strain -- a worldwide outbreak could become reality. (The operative term here is highly transmissible; a flu virus that spreads as readily as the common cold would spell real trouble, but one that spreads less readily would be more manageable.)
H5N1 is an extraordinarily deadly variant: The mortality rate for persons infected with the existing H5N1 appears to be around 50%, whereas the garden-variety annual flu kills less than 1%. This gives us plenty to worry about. The acquisition of the genetic change(s) needed to become transmissible from human to human is stochastic -- i.e., essentially random, therefore unpredictable. The more viruses there are, the greater the chances that one will acquire the "open-sesame" genetic changes, either by mutation or by exchanging genes during simultaneous infection of a person or animal with H5N1 and another flu virus. And there is more H5N1 around every day: In recent months it has spread over much of Asia and into Russia. Only last week, it was discovered in birds in Turkey.
We are ill-prepared for a flu pandemic. Reserve capacity is grossly inadequate for vaccines, drugs and hospital beds. The best and most cost-effective intervention -- prevention with a vaccine -- presents technological, economic and logistical obstacles. Anti-flu drugs exist but are not a panacea. Unlike vaccines, which confer long-term immunity after one or two doses, drugs need to be taken for long periods. The only drug that has been shown to prevent the flu is Tamiflu, the effect lasting only as long as one takes the drug. (The other major anti-flu medicine, Relenza, has only been shown to be effective to treat, but not prevent, flu.)
Yet a recent paper in the journal Nature reported a patient in Vietnam infected with a strain of H5N1 partially resistant to Tamiflu, so our primary prophylactic drug might already be compromised. This is dismaying, because the viral isolate was collected earlier this year when the drug had not yet been widely used in Asia, so H5N1 hadn't yet had much opportunity to develop resistance. It's possible that the drug was used improperly -- administered in a lower dose than prescribed, or intermittently instead of continuously -- or that the recommended prophylactic dose is too low. Whatever the cause, the result is bad news.
So where do we go from here? In the face of a potentially cataclysmic pandemic, we need multiple strategies that offer various alternatives to prophylaxis and treatment. But the constraints of current vaccine-production methods slow our response to new variants of flu virus. The conventional approach would be to grow the actual pandemic strain in millions of fertilized chicken eggs, and weaken or kill it to make a vaccine. But this takes time, and because H5N1 is highly toxic to the eggs, we would have first to tinker with its genetics and then ensure that it would still function as a vaccine. In the face of a pandemic, the time-lag could be catastrophic.
A few companies are taking innovative approaches to vaccine development. Scientists at Chiron Corp. have proposed making a kind of prototype vaccine against the current, pre-pandemic strain of H5N1 -- which has already been done experimentally by the National Institutes of Health -- and adding boosters called adjuvants to boost immune response: Here, there might well be a significant protective effect even after a single dose, although the virus in the vaccine would not be a perfect match to the pandemic strain. We could begin to produce this adjuvant-boosted vaccine almost immediately.
Another scientifically elegant approach is gene-splicing, to make "subunit" flu vaccines. Used to produce hepatitis B vaccine, this approach involves moving a single gene (or a small number) from the virus into bacteria or yeast; then, grown large-scale, these organisms would be the source of the viral gene product(s) which, after being isolated and purified, would be used as vaccine. The Holy Grail of this tack is a vaccine that elicits an immune response to the proteins of flu virus that are highly conserved from strain to strain. Finally, another approach would be to construct a vaccine from naked DNA, which is being tried by several companies.
Industry's efforts need a federal boost. Grant-giving agencies should fund "proof of concept" research on cultured cells to supplant eggs for growing virus; and also on flu subunit vaccines, especially those that are effective against many strains. Regulators should waive registration fees on flu-related products, and should pursue agreements on "reciprocity" of approvals so that vaccines and antiviral drugs licensed in certain foreign countries can be marketed in the U.S. The government should indemnify vaccine- and drug-producers against liability claims and guarantee purchases of approved products. Government scientists should study whether during periods of vaccine scarcity it makes sense to inoculate the elderly early on as a "high risk group," although many of them fail to mount a vigorous immune response. A more effective approach would be to vaccinate their caregivers and household contacts (as well as first responders and health-care workers, of course).
We need to be aggressive, innovative and, above all, resilient. In society, as in biology, resilience means survival.
Mr. Miller, a physician and fellow at the Hoover Institution, was founding director of the Office of Biotechnology at the FDA, 1989-1993.
