Check one of the following two statements you believe to be true:

( ) “There is an absolute certainty that we will have an avian flu pandemic. We just don’t know where or when.”

( ) “The probability of there being an avian flu epidemic is negligible.”

The author of the first statement is John Beadle, MD, CEO of PowderMed Vaccine, Inc., the U.S. subsidiary of PowderMed Ltd, Oxford, U.K. The voice behind the second statement is that of Alan Zelicoff, MD, a senior scientist at Ares Corporation, Albuquerque, N.M., and author of Microbe: Are We Ready for the Next Plague?

Before exploring these two views, which are as radically different as they sound, let’s start with the basics.

According to PowderMed, influenza (the flu) is an acute viral infection of the respiratory tract. There are many different strains of influenza viruses, differentiated by proteins on the surface of the virus—the hemagglutinin, or “HA” protein, and the neuraminidase, or “NA” protein. To date, 16 H and nine N strains have been identified. Strains of flu viruses continually change over time and every year small modifications (“antigenic drifts”) are responsible for seasonal outbreaks or flu ‘’epidemics.”

Flu spreads between humans through infected air masses, such as coughing or sneezing. The flu can also be transmitted by touching a contaminated surface such as a telephone or door knob.

Most people infected with the flu will suffer similar symptoms, including fever, headache, fatigue, dry cough, sore throat, and body aches. Although most people recover from the flu, the Centers for Disease Control and Prevention (CDC) estimates that in the United States more than 100,000 people are hospitalized and approximately 36,000 people die from the flu and its complications every year.

An influenza pandemic is a unique infectious disease event that can spread to every country in the world within months, and cause thousands, if not millions, of deaths. There are three documented influenza pandemics—the first believed to have originated in birds and the latter known to be a combination of bird and human viruses.

• 1918-1919: Spanish flu (H1N1), caused 50 million deaths worldwide.

• 1957-58: Asian flu (H2N2), caused 70,000 deaths in the United States.

• 1968-69: Hong Kong flu (H3N2), caused 34,000 deaths in the United States.

The current avian flu, referred to as A (H5N1), is a viral infection spread from bird to bird through feces. Avian viruses do not normally infect species other than birds and pigs. However, there have been documented infections of humans.

The first transmission of avian flu to humans was reported in 1997 in Hong Kong, where it caused severe respiratory disease in 18 humans, resulting in six deaths. Close contact with live infected poultry was the source of human infection. Studies at the genetic level further determined that the virus had jumped directly from birds to humans.

The next major outbreak was in South Korea in December 2003. From there it spread to southeast Asia. As of this past July, the World Health Organization has reported 105 human cases, resulting in 55 deaths.

The CDC estimates that an avian flu pandemic could sicken 80 million people and kill 16 million worldwide. Other estimates go even higher. National Geographic, which featured the disease on the cover of its October issue, quoted Michael T. Osterholm, PhD, MPH, of the University of Minnesota, predicting that the estimated deaths from the next pandemic range from 7.4 million to an apocalyptic 180 million to 360 million.

“Experts agree that another influenza pandemic—most likely the avian flu—is inevitable and possibly imminent,” says Beadle.

“This is exactly incorrect,” says Zelicoff. “I’m not saying the probability is zero. But it is very, very small. The talking heads have thoroughly overblown the situation. They are saying the sky is falling. The sky is not falling.”

Before examining the differences between Beadle and Zelicoff, let’s first focus on where they agree.

They both concur that the highly touted drug remedy, Oseltamavir (brand name Tamiflu) won’t really work. Beadle says Tamiflu has been effective in reducing symptoms in patients suffering from annual flu, and he acknowledges that it may even help with avian flu, but he doubts it. “There is a manufacturing output restriction on Tamiflu, meaning sufficient doses cannot be stockpiled,” he says. “Also, studies have demonstrated the emergence of flu strains resistant to Tamiflu. If widespread resistance emerges or the avian flu strain continues to mutate, then Tamiflu may not be useful.”

Beadle adds that Tamiflu must be given at the early onset of the disease. At best, he thinks Tamiflu may be appropriate as a secondary treatment, following the appropriate vaccination, to extinguish any breakthroughs of the disease.

Zelicoff’s response is more blunt. “There are two problems with Tamiflu. The first is that it has a very limited shelf life and the second is there is no evidence it will work against avian flu as there are already reports of Tamiflu-resistant H5N1 in Vietnam where the drug has been used only sparingly,” he says. “I can see the potential of billions of dollars being spent for drugs like Tamiflu, which will make the drug companies very happy, but these drugs are unproven.”

Zelicoff explains that vaccines are typically made by growing a pathogen in chicken eggs, a difficult task. Since the pathogen is avian, it tends to kill off the eggs, making it tricky to get material for the immune response. “It’s obviously very difficult and extremely time consuming to make,” Zelicoff says. “It just floats around in the bloodstream and engenders a very weak immune response.”

He says a better method would be to take the genetic material “and chop it up, which is easy to do and can be produced in large quantities. Then you squirt this genetic material into the muscle cells to translate the DNA into protein, which is the same protein on the surface of the virus cell, and this engenders an extremely powerful immune response.”

Zelicoff says the pharmaceutical company Sanofi-Pasteur, in conjunction with the National Institute for Health (NIH), has produced a vaccine based on the old egg incubation method. The only problem is that “enough would never be able to be made on time.”

Beadle agrees. He says the NIH recently conducted a study in which it hoped only 15 micrograms of the Sanofi-Pasteur vaccine would be needed. However, it was discovered that 90 micrograms would be required. “This means there is only one-sixth the amount of this vaccine as was hoped, with the result that only 75 million doses are available worldwide, but most of these are available only in Europe,” Beadle says. “The U.S. government has stockpiled 20 million doses, but a sixth of those is [equal to] only about 3.3 million.”

Beadle says that whereas the Sanofi-Pasteur vaccine needs to be refrigerated, which allows it to last for one year, the PowderMed vaccine can be stored at room temperature and will last for three years. Moreover, the PowderMed vaccine can be produced with exceptionally small amounts (2) of DNA. “So,” says Beadle, “the entire U.S. could be vaccinated twice for somewhere less than 1.5 kilograms.”

How does PowderMed’s DNA-based vaccine work?

“PowderMed delivers DNA directly to the powerful immune network in the outer layer of skin [the epidermis] through a proprietary technology platform device called PMED [particle mediated epider-mal delivery],” says Beadle. “Gold particles coated with the DNA are propelled into the skin using high-pressure helium. Using the PMED delivery system, vaccination is needle-free, virtually painless, and can be easily administered without the need for trained medical personnel. The vaccine is injected via a needle-free device rather than via an intramuscular injection.” Beadle adds that no specialized medical training is necessary to use the vaccine delivery device in an emergency situation.

Zelicoff agrees that the PowderMed vaccine is the solution—should it be needed. “There has been the fear that if you inject avian DNA into the human genome in small pieces it might cause infections the way HIV does,” he says. “But after billions of doses of DNA into mammals through vaccines, this has never happened.”

Zelicoff says the PowderMed product is “an ace in the hole” should it ever be needed. However, he doesn’t see that becoming a reality. Why not?

Zelicoff begins by explaining the chemistry of H5NI. The H protein, or hemagglutinin, is what is needed to bind the flu cell to the human cell. “Without this intercellular action, no transmission can take place,” he says. The N protein or neuraminidase releases the virus from the infected cells so they can invade the healthy ones.

“What we’re told is that immunity to H is more important than immunity to N. That’s the lore and I know the lore,” Zelicoff says. “But no one ever has or ever will experiment with a new strain of N and vaccinate a human against it, for fear he will die. But it’s been proven that animals that are immune to N1 are protected against any combination of H with N. Just about all of us are immune to N1, for we have yet been exposed to the flu or vaccine. Therefore, since we are already immune to N1, we already have partial immunity to H5N1.”

Zelicoff’s second argument is that there are hundreds of millions, if not trillions, of these birds wandering freely in Asia through gardens, farms, and ponds with bird droppings and other conditions that have created killing fields where countless birds become infected and die. “Millions of these birds have been sold in the live animal market,” says Zelicoff, “but how many humans have contracted the disease? About a hundred. Now I’m not saying the mutation can’t occur, but it takes extraordinary, intense exposure.”

He cites the 1918 Spanish flu outbreak as a reason why the avian flu is nothing to fear. “People are so concerned about 1918 when we had our last major pandemic,” he notes. “But the reason 1918 was so devastating is that it represented a rare mutation that no one had an immunity to. And this is the key point: people lived crowded together. They lived in tenement houses, in trenches, on troop ships, and in hospitals with hundreds of other people who were also infected.

“Look at it from the point of view of the virus. It always works to change the organization of the body it invades. The best [viruses] are actually multiple subtypes or clones. So if people are living close to each other and breathing on each other, as in 1918, the fastest reproducing virus spreads rapidly. But if people are spread out, as they are today—except perhaps in Southeast Asia—if the virus kills a particular organism, it comes to an end. This is why the worse fatalities are not among geese or ducks who are out in the open. Dead ducks don’t fly. It’s in the chicken houses that the disease is so devastating. For there are hundreds of thousands or millions of birds packed into an environment filled with a mist of respiratory and fecal excretions. If you are a chicken in a chicken house, that is not a good place to be to avoid avian flu.”

Zelicoff points out that when avian flu victims in Vietnam were placed in hospitals, the hospital staff did not contract the disease. “In the case of alleged human transmissions, as in Thailand, these were circumstances in which family members were in a small house sitting by the bedside for hours with a stricken family member,” he says.

Beadle acknowledges that even these cases do not prove human transmission of the disease, since these were rural families who lived in close proximity to fowl and other livestock.

In other words, despite the staggering numbers of birds that have become infected with the virus, only approximately 100 humans have contracted the disease, all of whom lived in congested conditions. There have been no reported incidents of one human passing the virus to another.

According to Zelicoff, “There is a way to resolve this debate: real-time data, comprehensive surveillance of animal and human health that will, in turn, allow us to remove the speculation about mutations, species ‘jumping,’ and all the rest by building better mathematical models.”

So, what’s the real story?

Are we in for an apocalyptic pandemic that could kill 360 million people?

Or is the avian flu, when all is said and done, strictly for the birds?