Friday, May 01, 2020

Pandemics: Forgotten vaccine hero saved millions of lives

Dr Anthony Fauci (born 1940), the director of the National Institute of Allergy and Infectious Diseases since 1984, enters the Press Briefing Room of the White House on April 13, 2020, as a member of White House Coronavirus Task Force. In April 2005, Dr Fauci paid tribute to Dr Maurice Hilleman (1919-2005) after the latter's death.
"Maurice literally changed the world with his extraordinary contributions in numerous disciplines: virology, epidemiology, immunology, cancer research, and, especially, vaccine research and development.
Maurice was perhaps the single most influential public health figure of the 20th century, if one considers the millions of lives saved and the countless people who were spared suffering because of his work. Over the course of his career, Maurice and his colleagues developed more than 40 vaccines. Of the 14 vaccines currently recommended in the United States, Maurice developed eight."

On the morning of April 17, 1957, microbiologist Maurice Hilleman was in his office at the Walter Reed Army Institute of Research, in Maryland, north of Washington DC, when he saw amidst other foreign news a short report from Hong Kong on Page 3 of his copy of The New York Times.

The chief of respiratory diseases at the institute read that 250,000 residents of the 2.5m population in the British colony were receiving treatment for flu. In particular, Dr Hilleman's attention was piqued by the concluding paragraph, "Throughout each day, thousands of sick people have stood in long lines awaiting treatment in clinics. Many women carried glassy-eyed children tied to their backs."

“They said, babies had glassy-eyed stares [and I thought], my God this is the pandemic, it’s here,” Hilleman said in an interview, for the book 'Vaccinated: One Man's Quest to Defeat the World's Deadliest Diseases,' (2007) not long before he died in 2005.

The book's author, Dr Paul Offit, the Maurice R. Hilleman professor of Vaccinology at the Perelman School of Medicine at the University of Pennsylvania, wrote:

"Pandemics of influenza are inevitable. During the past three hundred years, the world has suffered ten of them, about three per century. No century has ever avoided one. But despite their frequency and reproducibility, only one man has ever successfully predicted an influenza pandemic and done something about it."

The virus of what became known as the 'Asian flu' was first identified in Guizhou, a mountainous province in southwest China, in February 1957. It spread to Hunan Province and then to Hong Kong and Japan. It soon spread to the British-controlled Federation of Malaya (including Singapore), the Philippines, Taiwan and other Asian countries. The first cases in the UK and Ireland were in late June, with serious outbreaks in the general populations occurring in August. "As Hilleman had predicted, in September 1957 Asian flu entered the United States from both coasts. The first laboratory-proven cases occurred aboard naval vessels in San Diego, California, and Newport, Rhode Island," according to Dr Offit.

The outbreak was caused by a virus called influenza A subtype H2N2. Research showed that the virus was a reassortant (mixed species) strain, developing from strains of avian influenza and human influenza viruses.

Dr Maurice Hilleman, pictured centre, talking with his research team as they study the flu virus in a lab at Walter Reed Army Institute of Research in Silver Springs, Maryland, 1957. The surgeon general of the United States, Leonard Burney, later said: ``Many millions of persons we can be certain did not contact Asian flu because of the protection of the vaccine.''

A vaccine for a pandemic

In 1944 Hilleman's first job after university was at the Squibb pharmaceutical firm (known today as Bristol Myers Squibb) and he was involved in developing a vaccine for Japanese encephalitis, to protect American troops in the Pacific theatre of the war with Japan, as well as vaccines for rabies, smallpox, typhus, and influenza.

He joined the Walter Reed Army Medical Research Institute in 1948, which according to Dr Fauci "was then the global epicentre for infectious disease research."

One day after reading about the flu outbreak in Hong Kong, in The New York Times Hilleman cabled the army’s 406th Medical General Laboratory in Japan and a navy serviceman who had been exposed to the virus in Hong Kong, was back in Japan. A specimen from the serviceman reached Hilleman on May 17, 1957.

The scientist took an incubating hen’s egg, cut a small window in the shell and injected the egg with throat washings from the navy serviceman. Hilleman recognised that the new virus was a completely different strain of the flu and he cooperated with the World Health Organisation (WHO). They would discover that antibodies to the virus were difficult to find in people. However, elderly men and women, in the US and the Netherlands who had survived the influenza pandemic of 1889–1890 which had killed an estimated six million people were found to have antibodies.

The scientist made a crucial observation that the two key proteins in the flu virus — hemagglutinin and neuraminidase — undergo small changes or “drift,” between seasons and he saw a need for annual flu vaccinations.

Hilleman bypassed people in the government who were sceptical that he could make a vaccine that would work. He arranged production with six pharmaceutical firms and the first supplies were available in June 1957. By October, companies had distributed forty million doses.

In the US 50% of infections occurred in children and teenagers, at least a thousand of whom died of the disease.

Hilleman joined Merck Sharp & Dohme, the pharmaceutical firm in late 1957 and remained there until 1984.

The estimated number of deaths was at least 1.1m worldwide (some estimates are as high as 4m) and 116,000 in the United States according to the US Centers for Disease Control and Prevention.

In 1968, the third pandemic of the 20th century was called the Hong Kong flu pandemic (H3N2 virus) or Hong Kong flu. It had originated in China again and lasted until 1969–70. This pandemic resulted in an estimated 1m to 4m deaths, compared with estimates of between 25m and 50m deaths in 1918-1919 — the so-called 'Spanish flu' was caused by an H1N1 virus with genes of avian origin but it's unknown where it originated.

Dr Hilleman again developed a vaccine.

From a paper published in 2018 by the US National Institutes of Health: Maurice Hilleman: Creator of Vaccines That Changed the World

A scientist who saved more lives than all other scientists combined

Paul Offit in the Prologue to his book 'Vaccinated' wrote:

"Scientists aren’t famous. They never endorse products or sign autographs or fight through crowds of screaming admirers. But at least you know a few of their names, like Jonas Salk, the developer of the polio vaccine; or Albert Schweitzer, the missionary who built hospitals in Africa or Louis Pasteur, the inventor of pasteurization;or Marie Curie, the discoverer of radiation; or Albert Einstein, the physicist who defined the relationship between mass and energy. But I’d bet not one of you knows the name of the scientist who saved more lives than all other scientists combined — a man who survived Depression-era poverty; the harsh, unforgiving plains of southeast-ern Montana; abandonment by his father; the early death of his mother; and, at the end of his life, the sad realization that few people knew who he was or what he had done: Maurice Hilleman, the father of modern vaccines."

The word influenza means influence in Italian from Medieval Latin influentia — based on the belief that epidemics were due to the influence of the stars.

Edward Jenner (1749-1823), an English physician, is credited with developing the first vaccine to kill smallpox. He inoculated an 8-year-old boy with cowpox matter from a blister on the hand of an English milkmaid. Jenner highlighted immunisation by exposing the boy to smallpox material — but the boy never fell ill.

Louis Pasteur (1822-1895), a Frenchman, made the world's second vaccine, against rabies, and in the first half of the twentieth century, scientists made 6 more vaccines.

Dr Offit added:

"The second half of the twentieth century witnessed an explosion in vaccine research and development, with vaccines to prevent measles, mumps, rubella (German measles), chickenpox, hepatitis A, hepatitis B, pneumococcus, meningococcus, and Haemophilus influenzae type b (Hib). Before these vaccines were made, Americans could expect that every year measles would cause severe, fatal pneumonia; rubella would attack unborn babies, causing them to go blind or deaf or become mentally retarded; and Hib would infect the brain and spinal cord, killing or disabling thousands of young children. These 9 vaccines virtually eliminated all of this suffering and disability and death. And Maurice Hilleman made everyone of them."

Today many millions of children across the world receive the MMR — the vaccine for measles, mumps and rubella that Dr Hilleman invented.

Ralph Nader, the American consumer activist, wrote after Dr Hilleman's death, "There are many fascinating stories about this scientist. Yet almost no one knew about him, saw him on television, or read about him in newspapers or magazines. His anonymity, in comparison with Madonna, Michael Jackson, Jose Canseco, or an assortment of grade B actors, tells something about our society’s and media’s concepts of celebrity; much less of the heroic. This is not a frivolous observation."

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SARS-CoV-1 and SARS-CoV-2

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the name given to the 2019 novel coronavirus while Covid-19 is the name given to the disease caused by the virus.

The SARS-CoV-1 virus was first reported in China's Guangdong province (the Pearl River Delta's manufacturing hub), in November of 2002 but it had spread to neighbouring countries before it was reported to the World Health Organisation in March 2003. There were about 8,000 cases in 33 countries with a 10% fatality rate.

In 2007 scientists at the University of Hong Kong in a paper warned, that "The presence of a large reservoir of SARS-CoV-like viruses in horseshoe bats, together with the culture of eating exotic mammals in southern China, is a time bomb."

Dr Anthony Fauci, the director of the US National Institute of Allergy and Infectious Diseases (NIAID), has said that a vaccine for SARS-CoV-1 was produced but it was shelved as the epidemic had ended. The virus hasn't reappeared.

Fauci said in a 2017 interview that it took about 20 months from the time NIAID sequenced the SARS virus, to the time it was placed into a phase 1 trial.

“Then, if you go down the line, to the different challenges since then, it became less and less,” Fauci said. “Going from SARS to H5N1 to H7N9, then you get to Zika, which took about 3 to 4 months to go from the time we sequenced it to the time we had a DNA vaccine."

Bats host a range of coronaviruses and it's believed that the transmission to a wild animal may have happened in China about a half-century ago. 

Related

Deutsche Welle (DW), Germany’s international broadcaster, April 29, 2020: How deforestation can lead to more infectious diseases — The world's forests act as shields, keeping humans safe from coronaviruses and other diseases. Their destruction can unleash devastating consequences for global public health

New York Times May 1, 2020: What the Proponents of ‘Natural’ Herd Immunity Don’t Say — Try to reach it without a vaccine, and millions will die