As more people receive the H1N1 shot, an earlier vaccine is casting a mysterious shadow over the attempt to immunize 200 million people in the next few months. A vaccine made in 1976 in response to a different strain of H1N1 influenza led to an outbreak of a rare form of paralysis. Of the 43 million people who were vaccinated, about 400 developed Guillain-Barre syndrome (GBS), and 25 died. Whether an equally unexpected surprise might be lurking in this year's swine flu shot is a big -- although not publicly acknowledged -- question hanging over the current immunization effort. That possibility is why the Centers for Disease Control and Prevention routinely reports, as it did Wednesday, on whether any notable side effects to the new vaccine have been discovered. (None have.) Unlike today's bug, the 1976 virus never took off from where it originated at an army base in New Jersey. With nothing to be gained from vaccination, the widespread campaign was halted after less than three months. For the 15 years after the 'swine flu affair,' scientists sought to nail down whether and how much the 1976 vaccine increased a person's risk of GBS. Almost nothing, however, was done to figure out how and why the flu shot had that effect. It's an oversight some public health officials are coming to regret. 'We should have made an exhaustive attempt to understand what happened from a biological standpoint,' said Michael Osterholm, a physician who heads the Center for Infectious Disease Research and Policy. Both the 1976 strain and the new H1N1 strain are closely related to viruses carried by pigs, making some wonder whether that 'swinishness' makes their vaccines more likely to cause unusual effects. 'That is the right question to ask,' said Peter Palese, an influenza virologist at Mount Sinai School of Medicine in New York. 'And I would like to say that no one really knows.' Researchers stopped looking back at 1976, Osterholm said, when there were no subsequent problems with flu vaccines. 'After we had a couple of seasons under our belt when there was no unusual risk to regular flu vaccines, we just let it go,' he said. Today's H1N1 vaccine is made, tested and administered the same way the seasonal flu vaccine is. There's no reason to think it's any more dangerous than the regular flu shot, whose risk of serious side effects is essentially zero. But that was true of the 1976 vaccine, too. Named after two French physicians who described it in 1916, Guillain-Barre (GEE-yan bah-RAY) syndrome causes weakness and tingling that starts in the legs, but over weeks can affect most of the body's muscles. The symptoms occur because the insulation on the outside of nerve fibers breaks down, damaging the normal conduction of impulses. In normal times, GBS occurs at a rate of roughly 2 cases per 100,000 people per year. Although only about 5 percent die, up to a third spend time in an intensive care unit on a ventilator before they get better. Nearly a third still have some weakness three years later. After the 1976 vaccination campaign was halted on Dec. 16 of that year, much work went into figuring out whether the increase in GBS cases was real, or just a random upward blip. Careful counting in defined populations -- most important, the entire states of Minnesota and Michigan -- proved beyond doubt that it was real: The risk of developing the condition rose four- to seven-fold in the six weeks after getting the swine flu shot. The number of cases attributable to the vaccine ranged from 5 to 12 per million people vaccinated. Studies of vaccines before they go on the market have too few people in them to uncover adverse events occurring at such very low frequency. That's why the GBS risk was not detected in the testing of the 1976 vaccine -- and why it would not be caught in this year's testing, either. Researchers looked for spikes in GBS among people vaccinated for flu in subsequent seasons and did not find any. The only exceptions were 1992-93 and 1993-94. When those two seasons were combined, people getting flu shots had a slightly higher risk of GBS -- about 1 extra case per million. The conclusion was that 1976 was a fluke, unlikely to happen again. There's some evidence that the 1976 vaccine may have triggered GBS through a mechanism known as molecular mimicry. About two-thirds of cases of GBS arise after an intestinal or respiratory infection (including flu). The biggest cause is a bacterium responsible for food-borne illness, (begin ital) Campylobacter jejuni. (end ital) Campylobacter can stimulate the immune system to make antibodies against a nerve-sheath substance called ganglioside, and that presumably leads to the condition. However, not all people with the syndrome have nerve-attacking antibodies, and millions of people get Campylobacter infections without getting GBS. So clearly there are unknown factors -- some almost certainly genetic -- involved in the disease. The 1976 vaccine may have triggered GBS in much the way that Campylobater does. Today, both the federal government's epidemiologists and pretty much every neurologist in America have eyes wide open for cases of GBS. As of last week, six cases of GBS in people who had gotten the H1N1 vaccine had been reported to the federal government's Vaccine Adverse Event Reporting System. (Four more are under investigation.) The six people with confirmed cases live in Maryland, Virginia, New York, Connecticut, Florida and Illinois. In each case, the person came down with neurological symptoms within two days of being vaccinated -- almost certainly too soon to be a consequence of the vaccine. 'At this point, we are not seeing any evidence there is an increase in Guillain-Barre syndrome,' said James Sejvar, the physician leading the CDC's surveillance for it. 