Premature & Crippled

The nation's top polio experts and health authorities got around last week to telling the public what had gone wrong, and how and why, with the grandiose plan to inoculate tens of millions of children with Salk polio vaccine in 1955. For the most part, they confirmed what critics have suspected for a long time: it was a mistake to try the whizbang jump in little more than a year from laboratory production of the vaccine to manufacturing in tank-car volume. Many vital facts simply were not known when the leap to factory-scale production was made. In the light of this new knowledge, they implied, not only the methods of making and testing the vaccine but also the vaccine itself will be drastically altered as soon as possible.

Surgeon General Leonard A. Scheele of the U.S. Public Health Service and his deputy, James Shannon, picked a polio symposium at the American Medical Association's convention in Atlantic City as the forum for their first report. Then Dr. Scheele released a 163-page "white paper" for President Eisenhower. After that, he and Shannon spelled out for the press the detailed meaning of their revelations. The week's main disclosures:

P:In producing vaccine for 1954's trial vaccinations, authorities had many a moment of anguished doubt, because multiple testing in three separate laboratories (using supposedly identical methods) got conflicting results with the same material.

P:When P.H.S. licensed six firms to manufacture vaccine last April, both P.H.S. and the vaccine's developer. Dr. Jonas E. Salk, urged that manufacturers be required to show that they could produce safe vaccine consistently, in batch after batch. But this requirement was neither defined by P.H.S. nor was it enforced by the Government agency. As a result, manufacturers told P.H.S. only about the batches they considered safe, did not report on those that went down the drain as obviously dangerous. Hence, P.H.S. was not aware of how the odds were running against safe vaccine.

P:Until requirements were tightened recently, different manufacturers were operating with apparently different safety factors: two companies made such faithful tests that they had a 99.9% or better chance of detecting a bad batch; one had only a 65% chance, another 70%.

P:Even when manufacturers used every precaution known, the process of making a potentially deadly virus into a safe vaccine proved unexpectedly tricky. When three separate strains of virus, all officially dead by available tests, were pooled to make the final polyvalent vaccine, the mixture sometimes showed live virus. And some virus defied every effort to kill it.

Straight-Line Theory. How could all this be? The 1,000-odd doctors who sat in on the polio symposium learned something of this from Dr. Salk himself. They had gone there, full of admiration and curiosity, to hear him and see him get a $10,000 award* for his achievements. They listened attentively, some with obvious puzzlement, as he read a long and tightly technical report. Its net: mass manufacture was not the same as making vaccine in his precisely controlled laboratory at the University of Pittsburgh.

Dr. Salk re-examined his straight-line theory of how the virus is inactivated to make vaccine. According to this, he can start with a virus brew so potent that there are 4,000,000 virus particles in every teaspoonful. But after 1 1/2 days in formaldehyde there should only be 4,000 alive, after three days only four, and after nine days only a single active particle in a ton. If things did not work this way in practice. Dr. Salk argued, it must be because of ''fractional inactivation." This might result from the clumping of virus particles (leaving a broth that was not homogenized). In this way, virus particles could survive the formaldehyde bath if they were in the middle of a clump and protected by dead brethren.

Weakening Strain. This sort of thing apparently had not happened in Dr. Salk's own labs. But if it could happen anywhere, it raised a fundamental question: should any strain of virus that is likely to cause paralysis be used in the vaccine? Dr. Salk had long contended that the Mahoney strain which he picked to represent all the Type I strains, was safe because it was killed; critics had damned it in the live state as the most virulent form known, and the likeliest to cause paralysis. Now, Dr. Salk wavered: Mahoney was a good strain because it multiplied in liveliest fashion in monkey kidney material and therefore yielded a good "crop" for the vaccine-maker. But he seemed resigned to abandoning it; he was checking scores of other Type I strains to find a replacement.

Then there was the question of injecting the vaccine in 1 cc. ( 1/4-teaspoonful) doses into the arm muscle--the method now in use. Dr. Salk had tried using only one-tenth of this amount in a tricky intradermal injection--between the layers of the skin. This, he found, was not enough.

(Danish authorities think they have got around this by using 1/3 cc. under the skin.) Some experts oppose injections of any kind into the muscle during the polio season because they fear that the needle may provoke a flare-up by a latent polio infection that otherwise would have done no harm. Dr. Salk did not feel that this objection was decisive, but would leave the verdict to local health officers.

Suspected Agent. More cautious was the University of Michigan's Dr. Thomas Francis Jr., grand evaluator of the 1954 Salk vaccine trials. He warned against indiscriminately beginning vaccination programs (i.e., giving the first of two shots) until the return of cold weather. Local health officers, he said, must weigh the risk of provoking polio against the number of cases they hope to prevent.

Drs. Scheele and Shannon of P.H.S. gave short shrift to the Salk straight-line inactivation theory. It simply does not work that way in practice, they said: a minute quantity of live.virus may always remain in the vaccine. However, they hastened to add, the vaccine can be made so safe that the chances of its causing polio will be negligible compared with the protection it will offer against polio.

The P.H.S.'s top men were not entirely satisfied with formaldehyde as the killing agent: ironically, it may actually favor the clumping of virus particles that makes a vaccine unsafe. And they had little patience with the Mahoney strain (which has caused most of the polio in the Cutter-vaccinated cases).* Denmark, they noted, has inoculated its 400,000 schoolchildren with a Salk-type vaccine, but with the Brunhilde strain substituted for Mahoney, and with no mishap. And since the U.S. authorities were not satisfied with present testing methods, it was clear that major changes in the Salk vaccine were imminent.

Boil It Down. Yet another change, in the method of manufacture, was recommended by Pediatrician Joseph Stokes Jr. He was worried about the random sampling in huge lots of vaccine. Philadelphia's Children's Hospital has a method, he said, of reducing seven or eight gallons of virus solution down to half a teaspoonful or less--99% pure virus. This can be inactivated and tested far more readily. So why not concentrate the stuff? He got no immediate answer, but P.H.S. and Dr. Salk are studying it.

Cincinnati's Dr. Albert Sabin, outspoken champion of a live-virus vaccine (TIME, May 23), suggested that all three paralysis-causing strains used in the Salk preparation be thrown out. In their place he would put nonvirulent strains, which may be found in nature or "bred" selectively in the laboratory. Knowing that his audience was far from ready to accept live viruses, Dr. Sabin cannily reminded them that these too could be treated with formaldehyde. This would give double protection, and a Swedish researcher is working on such a vaccine right now.

Private Hope. Before week's end, Dr. Scheele announced that the P.H.S.'s testing unit, the Laboratory of Biologics Control, was being overhauled, given new direction, status and staff (with a budget boost of $750,000). All this in the hope that in future it could handle vaccines for polio and other diseases with a new sureness and efficiency.

But it would take time for changes in the setup to be reflected in improved safety in the vaccine and certainty on the part of the vaccinators. P.H.S. men were privately hoping that public clamor for the vaccine, by some unforeseeable magic, would peter out by August, when the National Foundation for Infantile Paralysis will finish inoculating first-and second-graders. Said Dr. Scheele. in a thinly veiled reference to the foundation's widely known determination to get an effective vaccine within Founder-President Basil O'Connor's lifetime: "You cannot make viruses meet deadlines." Largely because of this hasty effort, the 1955 polio vaccination schedule had been dangerously premature. Now, said Dr. Stokes, we have "a crippled vaccination program."

*Offered by Mutual of Omaha (insurance), and presented by the A.M.A.'s incoming President Elmer Hess, who sternly advised Dr. Salk: "For heaven's sake, put it on the mortgage."

*For news of the effects of the vaccine controversy on the fortunes of the Cutter Laboratories, see BUSINESS.

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