To its victims, polio often seems sudden, capricious, unexpected; but public health experts dedicate careers to minimizing such surprise. They need to know where the virus comes from so they can guess where it is likely to hit next.

In the past it has not been possible to do this very well, but the polio outbreak among the Amish earlier this year was a striking exception that brought into play important new procedures for identifying particular strains of the polio virus.

While the disease was spreading, the virus that caused it was linked to an outbreak the year before in the Netherlands. The probable path of infection was traced across the Atlantic to Canada, thence to Pennsylvania, where many of the Amish live, and thereafter to Amish communities in several other states. Experts at the Federal Center for Disease Control in Atlanta were able to warn public health officials in all states that the estimated 75,000 members of the religious group in this country were at risk.

Polio, a disease of the central nervous system that can result in the loss of function in the muscles, including those that control breathing, was once given to frightening epidemics in this country. It has been rendered rare by 25 years of immunization, but an outbreak among an unimmunized group like the Amish was considered dangerous.

Even without so much of this polio strain's history, public health officials would probably have taken the precaution of vaccinating all of the Amish. But they would have been working in the dark. Without the new procedures to analyze the virus they would not have known where else it might have been introduced and be spreading. The knowledge of where the polio strain came from and how it got here gave them reasonable confidence that it was confined to the Amish — and that its elimination among them would stop its progress.

By now, about eight months after the American outbreak was detected, more than half of the Amish in the United States have been immunized. Experts at the center say the achievement by public health workers in Penn- sylvania and other states was all but incredible.

No further paralytic polio has been reported in the United States in the past two months. Probably the outbreak has ended.

Painstaking epidemiology — the medical detective work for which the Center for Disease Control is widely known—is given much of the credit for the success in coping with the outbreak, but there was also a significant new ingredient. Scientists at the center and elsewhere have developed laboratory tests that were important in con firming and pinning down the nature and origin of the specific polio virus that was doing the harm.

The main job of tracing was done by local, state and Federal epidemiologists, who checked contacts of persons who had been infected to see where the infection might have spread and studied immunization histories to see who might be susceptible, among other tasks.

But the new laboratory techniques gave a degree of solid confirmation to their suspicions that was not previously possible. Dr. Walter Dowdle, the center's assistant director for science, says the new techniques are ushering in a new era of “molecular epidemiology.”

One such test, developed by Dr. Jack Obijeski and colleagues at the center, permitted a virtual fingerprinting of the virus so that the expert observer could distinguish the specific strain of polio present in Pennsylvania from other “wild,” or natural, strains and from the intentionally modified virus used in vaccines. The method is expected to have many uses in the study of polio, perhaps someday even distinguishing those strains that are likely to be most dangerous and what makes them so.

The test involves taking the virus apart with the help of special enzymes and sorting out the resultant small fragments of its genetic material, ribonucleic acid. When these fragments are spread out according to their size and electrical charge they form a characteristic fingerprint‐like pattern that remains constant from specimen to specimen of the same virus strain.

Even earlier in the history of the recent outbreak a different test, developed by Dr. Anton van Wezel in the Netherlands, confirmed the nature of the virus and its probable origin at least an ocean away from Pennsylvania. His immunological test depended on the interaction of antibodies with different specific strains of polio.

Federal scientists in Atlanta say that tests as effective and definitive as these have not previously been available for tracing specific strains of polio virus although it has been possible for many years to identify the three main forms — polio viruses types 1, 2 and 3. The new tests can distinguish many minor variants of these three major viruses.

The Amish do not flatly reject immunization on religious grounds. But they tend to distrust secular governments and they adhere strictly to old ways dictated by the Bible. Thus, most were still unvaccinated in January when a woman in Franklin County, Pa., developed polio that paralyzed both her legs.

“We were particularly concerned,” said Dr. Melinda Moore, an epidemiologist at the center, “because an unimmunized community is a tinderbox for the spread of polio virus.”

Furthermore, she said, the Amish travel among themselves from community to community and state to state for weddings, funerals and other occasions. This mobility could spread the infection. Hence the effort to get ahead of the spreading virus.

The immediate question was whether or not the virus that appeared in Franklin County was a “wild” type. If, instead, it was one of those rare cases associated with vaccination there was little risk of epidemic.

But diligent questioning and searching for contacts revealed no vaccinations. The new laboratory tests at the Atlanta center and elsewhere pinned it down. It was a “wild” strain of type I polio virus. It was almost certainly spreading.

Indeed, said Dr. Lawrence Schonberger, the center's chief polio epidemiologist, blood samples taken from Amish in Pennsylvania and Maryland, showed that many had already been infected.

It was not surprising that no other cases of paralysis had yet appeared. It was not comforting either. As a rule of thumb, at least 100 and perhaps as many as 1,000 polio infections occur for every case of paralysis. Most people feel nothing more than transient headache, mild fever or muscle aches and stiffness. But this also meant polio could spread widely among the unimmunized before it was discovered. The spread had to be traced.

In fact, it was traced almost half way around the world. Dr. van Wezel tested his library of viruses and found specimens from Canada and the Netherlands similar to one from a case in Kuwait in 1977. Polio is still entrenched in that small nation on the Persian Gulf. It is still not clear whether the “Kuwait” virus is peculiar to that region or simply a strain circulating currently in much of the world. Dr. Milford Hatch of the Atlanta center, whose laboratory serves as a World Health Organization reference laboratory on polio, said Dr. van Wezel has more recently found that same strain of virus in Europe. Meanwhile Dr. Obijeski's group tested about 37 different specimens and found a common pattern in the viruses from Pennsylvania, Canada and the Netherlands.

The outbreak in the Netherlands last summer was among members of theDutch Reformed denomination who object to immunization on religious grounds, according to specialists at the Center for Disease Control. The public health experts had been watching that outbreak, but not with any great concern for the United States.

The American population is periodically sprinkled with polio virus from abroad, said Dr. Schonberger but the nation's high level of immunity usually snuffs out each import.

This safeguard would fail in a closely knit social group in which no members had been immunized.

Investigation of the January case by Pennsylvania health authorities and the center's epidemiologists showed that an Amish family from Ontario, Canada, had recently moved to Franklin County. It is believed that it was through this family that the virus spread. In Canada they had lived about 15 miles from a Dutch Reformed community. There had been a few cases of polio among these people not only in Ontario, but also in western Canada, including British Columbia. The source of the infection was traced to the religious denomination in the Netherlands.

Immunization efforts began as soon as the risks in Pennsylvania became clear. The first task was to persuade the Amish, first in Pennsylvania and then elsewhere, that there was a danger and that polio vaccine was needed. Meanwhile, from January to April, there was not another case of paralytic polio. The virus was circulating, but silently, giving no obvious warning of its presence.

When it did appear, the epidemiologists knew already that the problem was not a local concern, but cause for worry in 23 states, so widely do the Amish travel among their communities. Public health workers had the difficult task of persuading Amish people in states where polio had not yet appeared, many hundreds of miles from Pennsylania, that they were at greater risk of polio than the non‐Amish in Pennsylvania.

The Amish accepted the message. The immunization programs in Pennsylvania and elsewhere were largescale and effective.

From the first case in January to the latest, reported late in June, 17 cases polio were reported, 15 of them paralytic. Two of the latter were in Amish living in Canada. Most in the United States were in Pennsylvania, but there were also three in Iowa, three in Wisconsin and one in Missouri. The evidence indicates these cases were all part of the same outbreak. There was no reported case in Maryland during the period even though the virus evidently spread there early, as indicated by antibodies in blood samples.

As the immunization effort progressed, Dr. Schonberger recalls, was possible to see the campaign gaining on the virus. When a paralytic case was found before vaccination clinics had been organized, the virus was clearly ahead. But when a person just vaccinated proved to be already infected by “wild” virus, but so recently that no symptoms had yet developed, then the virus and the forces of public health were probably neck and neck and public health was going to win.

Bowing to pressure from federal health officials, leading AIDS researchers and AIDS activists, the Defense Department announced last night that it will scrap a controversial $20 million clinical trial of an experimental AIDS vaccine.

Defense Department spokeswoman Susan Hansen said the money will be transferred to the Department of Health and Human Services for a clinical trial involving 6,000 to 12,000 HIV-infected people to be conducted at the National Institutes of Health (NIH).

The study will involve testing several types of therapeutic vaccines and will be run by [Dr Anthony Stephen Fauci (born 1940)], head of the NIH Office of AIDS Research, said HHS spokeswoman Avis LaVelle.

Therapeutic AIDS vaccines contain either gp160 or gp120, substances made from part of the outer coating of the AIDS virus. They are intended not to prevent infection with HIV but to slow or halt the progression of full-blown AIDS in those already infected by the virus.

"It's too early to say which vaccines will be tested," Fauci said last night. But in order for the study to be scientifically sound and stay within the $20 million budget, he said, it will need to follow a protocol designed last year by an NIH committee.

The study would be limited to HIV-infected individuals with white blood cell counts between 200 to 500, and requires pharmaceutical companies to provide vaccine free.

All but one vaccine manufacturer -- [MicroGeneSys, Incorporated], maker of VaxSyn -- has offered to provide vaccines free, Fauci said. "If we have to buy the vaccine, that would chew up most of if not all of the $20 million," said Fauci, noting that the study could begin in the next several months.

"We are concerned about the transfer of responsibility away from the U.S. Army, the acknowledged leader in therapeutic vaccine research, to an agency which has repeatedly made clear that they consider therapeutic vaccine research to be a low priority at best," MicroGeneSys spokesman Jody Powell said. Requiring participating companies to donate vaccine "is a new barrier being raised by NIH," Powell said. "We can only view it as an effort to drive us out of the test."

But the decision drew strong support from other companies. "We applaud the recommendation," said Jack Obijeski of Genentech Inc., which makes a therapeutic AIDS vaccine that may be included in the trial. "We have said from the beginning that we would participate if asked and that we would supply vaccine free of charge."

The Defense Department decision ends a six-month debate about the controversial study, mandated last fall by Congress after extensive lobbying by MicroGeneSys. With its large system of medical facilities, the Defense Department plays a major role in AIDS drugs research, including trials on civilians. But the choice of which drugs to test is traditionally made by scientists at the NIH.

After MicroGeneSys hired former senator Russell B. Long (D-La.) to lobby key lawmakers, Congress added the $20 million trial to the defense budget. It also required that the trial proceed unless the NIH director, the Food and Drug Administration commissioner and the secretary of defense unanimously decided within six months not to proceed.

The congressionally mandated study drew sharp criticism from scientists and federal health officials because it specified testing only VaxSyn, even though several other therapeutic AIDS vaccines also were in development.

The controversy over the trial prompted a bitter feud between MicroGeneSys and Genentech in which MicroGeneSys claimed the Genentech vaccine caused levels of white blood cells to drop more quickly than with the disease. But a spokesman for Genentech said yesterday that there was no quicker fall in cell counts cells during a two-year study.

If industries celebrated birthdays, April 7 would be the day to light the candles for biotechnology.

On that day 25 years ago, financier [Robert Arthur Swanson (born 1947)] and scientist [Dr. Herbert Wayne "Herb" Boyer (born 1936)] incorporated [Genentech Incorporated], a company founded to use the revolutionary techniques of gene splicing to create a genre of medicines.

Before Genentech's birth in 1976, drugs were made from chemicals, extracted from leaves or molds, and pressed into pills. Swanson and Boyer proposed using living cells to make therapeutic proteins that would be administered in liquid form via transfusion.

Tom Perkins, co-founder of the Kleiner Perkins venture capital firm and one of the funding fathers of Silicon Valley, thought this notion might be beyond the pale when they approached him for capital.

"They wanted millions to start Genentech," Perkins said. "I remember telling them, 'It's not clear God will let us make a new form of life.' "

Instead, Perkins gave the two dreamers $100,000 to begin proving their idea with an experiment. In hindsight, they succeeded beyond anyone's wildest dreams.

"There are many people who start companies, but there are few who start industries," said Genentech Chief Executive Officer Art Levinson. "Bob and Herb didn't just pioneer a technology. They showed how to do great science in a commercial setting."

[Dr. William J. Rutter (born 1927)], who in 1981 co-founded Emeryville's [Chiron Corporation], the Bay Area's other biotech giant, sounded a similar refrain. Swanson and Boyer "started the industry. They established a wonderful culture, and the people within that culture have gone on to seed biotechnology."

Today, scores of Genentech veterans -- the call themselves GenenExers -- have founded dozens of biotech firms in the Bay Area alone, forming the nucleus of an industry that today numbers 1,100 companies worldwide -- with the greatest single concentration growing in a ring around Genentech's South San Francisco headquarters.

SAN FRANCISCO--(BUSINESS WIRE)--Presidio Pharmaceuticals, Inc, a specialty pharmaceutical company focused on developing and commercializing novel, small molecule compounds for the treatment of HIV-1, HCV and other chronic viral infections, announced today that it has closed a $26 million Series B financing led by Panorama Capital. Also participating in this round were Baker Brothers Investments, Bay City Capital, Ventures West Capital, Nexus Medical Partners, and several existing Series A shareholders including Sagamore Bioventures, George Rathmann Fund and Peninsula Overview Partners. Concurrent with the financing, Dr. Srinivas Akkaraju, Managing Director of Panorama Capital, Dr. Felix Baker, Managing Member of Baker Bros. Advisors LLC, Dr. Daniel Perez, Venture Partner of Bay City Capital and Kenneth Galbraith, Venture Partner of Ventures West Capital have been appointed to the Presidio Board of Directors, and Dr. John F. (Jack) Obijeski, who has been serving as a special adviser to the company, has joined the Board as an independent director.

"The response we have received from the investment community is a great reflection of our seasoned management team and the product portfolio we have assembled, which includes multiple programs that address the continued need for effective and safe medicines in the treatment of HIV, HCV and other viral infections," said Dr. Omar K. Haffar, President and CEO of Presidio Pharmaceuticals. "The proceeds of this financing will be used to advance two of our programs into human clinical studies, continue establishing alliances with outside partners, and expand our product portfolio through additional in-licensing transactions." Dr. Haffar went on to say, "As we advance our programs into clinical development, Presidio is in a strong position to both improve upon present treatments for patients with anti-viral infections and create substantial value for our investors by leveraging our technology and management expertise."

"Panorama is excited about backing a great management team and supporting the development of novel therapeutics to help patients," said Dr. Akkaraju of Panorama Capital. "And we look forward to helping to create a sustainable, antiviral therapeutic company with solid, long-term growth potential."

The Antiviral Market and HIV

Annual sales of pharmaceuticals for the treatment of antiviral infections are over $16 billion globally and are projected to approach $25 billion by 2011. HIV drugs currently account for the majority of annual sales, generating in excess of $8 billion, and should continue to help drive the overall antiviral market, with projected growth of almost 10% annually. Even after 25 years of increasing prevention, diagnosis, and treatment efforts, there are approximately one million individuals infected with HIV in the United States today, with approximately 40,000 new infections each year. In addition, over 20% of these newly-infected individuals are infected with strains that are already resistant to one or more existing therapies. HIV is expected to continue to adapt and develop resistance to current and future therapies, so that new approaches will continue to be needed within the existing combination treatment paradigm.