Dan Wilson remembers being a frightened 5-year-old, hearing grown-ups talking about tests as he lay on a daybed in the screened porch of his central Wisconsin home in 1955.

"One of the tests was whether you could lift your head off the bed," he said. "I remember not being able to do that, and wondering what that meant."

It meant polio, one of the most feared diseases of all time. The viral illness paralyzed tens of thousands of children in the United States and half a million worldwide each year.

Wilson was among the last Americans stricken. On April 12, 1955, scientists announced they had a successful vaccine.

They made it without even being able to see the virus - microscopes weren't powerful enough back then. They did it at great personal risk, without modern protective gear or fancy lab equipment.

It wasn't the first vaccine - ones for smallpox, diphtheria and the flu preceded it. But it became another "shot heard 'round the world," revolutionizing how people viewed science and launching a new war on germs.

Scientists headed to labs with fresh enthusiasm, convinced they could brew similar magic potions against other scourges of mankind.

"It seemed to say it was only a matter of time until we beat infectious diseases," said Wilson, now a historian at Muhlenberg College in Allentown, Pa., and author of a new book about polio.

Today, we have more vaccines than we did 50 years ago, and more tools and knowledge to make them. But we also have more and different kinds of germs. Hubris has turned into humility in the face of failure to develop vaccines for many of them.

In fact, many of the world's top killers - AIDS, malaria, tuberculosis - got that way because there aren't effective vaccines. Infectious diseases are still the third leading cause of death in the United States, and they kill more than 1 in 4 people worldwide.

Existing vaccines aren't panaceas either. Recent years have seen debate over resuming smallpox shots, the safety and effectiveness of other vaccines, and whether the widely used vaccine preservative thimerosal caused health problems.

The most common vaccine of all - the annual flu shot - is under intense scrutiny. Issues include the antiquated way it is made, a fragile supply system, worries about the threat of a pandemic, and research suggesting it might not help as much as had been believed.

Vaccines also are about money as much as medicine, sharply dividing the haves and have-nots. The world's richest man, Microsoft founder Bill Gates, has donated a staggering $1.5 billion for immunizations in poor countries, where more than 2 million children die each year of diseases largely vanquished from the United States.

Even the polio vaccine is only a partial success story. Officials have been unable to rid the world of "the Great Crippler" as they once did smallpox, and many doubt they ever will.

Despite these problems, vaccines clearly have changed the world and saved millions of lives. The challenge now isn't just developing new ones, but also getting parents to accept existing ones, said Dr. Neal Halsey, director of the Institute for Vaccine Safety in Baltimore.

"Here at Johns Hopkins Hospital," Halsey said, "we have a child who is basically on a ventilator and has severe pertussis. The child is lucky to have lived, almost died. Once you have seen children die from those diseases, you want to do what you can to help prevent other children from dying, and vaccines are our best tool to do that."

For many years, it seemed fairly simple.

Scientists would isolate a germ, kill or weaken it so it was no longer harmful, and give it to people so their immune systems would go on alert and be able to recognize and attack the real bug if they ever caught it.One by one, diseases began to fall. Measles, mumps, rubella. Hepatitis, meningitis, chickenpox. Even cancer turned out to be vulnerable: the hepatitis B vaccine wound up preventing liver cancer, too.Modern genetics gave the field a boost, cutting the time it takes to analyze a germ and providing a way to make vaccines from gene segments.But after decades of successes, reality set in. Each new germ posed unique challenges. A promising vaccine against rotavirus, a killer diarrheal disease, was withdrawn after it was linked to a rare but serious bowel problem.A Lyme disease vaccine lasted on the market only four years. Even though no science supported allegations that it was unsafe, its manufacturer didn't want to defend the product in the face of limited sales.There have been shortages of some childhood immunizations, and of companies to make them.Timing is a problem. Scientists rush to develop a vaccine when a scary new disease appears, often to see the germ diminish in later years and be eclipsed by newer threats. Today, the big worry is bird flu, said Dr. Gary Nabel, director of the Vaccine Research Center at the National Institutes of Health."A year from now it could be something else. A couple years ago it was West Nile virus, then SARS," he said.The biggest disappointment has been the long quest for an AIDS vaccine. Nothing has proved effective at preventing HIV infection, or preventing infection from developing into AIDS.Nabel refuses to give up."We can't afford to say, 'Oh, it's too hard,' and not work on it. We need to bring all we can bear in terms of the science to try to attack it rationally," he said.Several problems have been insurmountable. The virus attacks the immune system - the very thing vaccines depend on to work. HIV also constantly mutates, so giving a vaccine strain won't protect against other forms. In this respect, HIV is like flu viruses, which change so much that new vaccines continuously must be made."We were fairly lucky working on polio because we had a very genetically stable virus and we had a disease that induced long-term, permanent immunity itself. We just had to duplicate what mother nature did naturally," said Dr. Walter Orenstein, an Emory University vaccine expert.Polio itself is an unfinished victory. Seven years after Jonas Salk's vaccine - a shot that uses killed virus - Albert Sabin made a vaccine using live but weakened virus that could be given orally, an easier form for developing countries.Polio was eradicated in the United States in 1979, and the World Health Organization in 1988 launched a drive to do it globally. By 2001, polio had been confined to just 10 countries. But setbacks occurred.The Caribbean had outbreaks when the weakened vaccine virus mutated back into a form that caused disease. Parts of Nigeria stopped using the vaccine because of rumors it caused infertility. Polio resurged and now is in more than a dozen African countries that once were polio-free.Rotary International, which has given $500 million and raised another $123 million for the cause, "is in this till the very end," said spokeswoman Vivian Fiore.And it still believes the end is in sight.