Virologist Hilary Koprowski died on 11 April 2013 at the age of 96. His main accomplishments are nicely summarized in the New York Times, but for a more comprehensive overview of his life, I highly recommend his biography Listen to the Music by Roger Vaughan. I did not have many opportunities to interact with Dr. Koprowski, but I did follow his work on poliovirus vaccines and I have a few reminiscences.
In the 1930s Max Theiler had found that propagating yellow fever virus in an unnatural host – the chick embryo – dramatically reduced its capacity to cause disease in humans. Theiler’s work (which garnered him a Nobel Prize) lead to the production of the infectious, attenuated yellow fever vaccine which helped to vastly reduce the global incidence of yellow fever. Koprowski was inspired by Theiler’s work and decided to take a similar approach to developing a poliovirus vaccine – his first efforts involved passage of a type 2 strain of poliovirus in mice and then in cotton rats. After passage in rodents, the virus did not cause paralysis in monkeys. Koprowski tested the candidate vaccine strain in humans, and ultimately produced two other attenuated poliovirus strains. By the 1960s these attenuated poliovirus vaccine candidates had been tested in millions of humans. However, they were never licensed for use in the US. While Koprowski was carrying out his work, Albert Sabin was also developed attenuated vaccine strains of poliovirus. Both Sabin’s and Koprowski’s strains were tested side by side in a monkey neurovirulence test carried out by Joseph Melnick at Baylor University. Sabin’s virus strains were slightly more attenuated, and in 1961-62 those were selected for licensing in the US. Sabin’s oral poliovirus vaccines (OPV) have been the mainstay of the World Health Organization in its polio eradication campaign.
Koprowski’s polio vaccines were tested by human clinical trials, notably in the former Belgian Congo in 1957-58. It was subsequently suggested that this clinical trial initiated the AIDS pandemic. The idea, first proposed by Tom Curtis (19 March 1992 “The Origin of AIDS: A startling new theory attempts to answer the question, ‘Was it an act of God or an act of man?” Rolling Stone pp. 54–9, 61, 106, 108) and subsequently by Edward Hooper in ‘The River‘, was that Koprowski had propagated the vaccine strains in kidney cell cultures produced from locally captured chimpanzees. If these animals were infected with the precursor of HIV-1, simian immunodeficiency virus (SIV), then the virus might have entered the human population during the polio vaccine trials. This hypothesis was subsequently shown to be incorrect as phylogenetic analysis showed that the main group of HIV-1 viruses, the M group, clearly crossed from chimpanzees to humans in the early 1900s.
A committee was established to investigate the virological aspects of the HIV-polio vaccine controversy, and towards the end of its work I was asked to join. When it was discovered that samples of Koprowski’s polio vaccines were frozen at the Wistar Institute in Philadelphia, it was decided to determine whether these vaccines had been propagated in rhesus monkey or chimpanzee cells.
I was given the job of dividing and coding the samples. I met a representative of the Wistar Institute in the parking lot of a restaurant just off the New Jersey Turnpike, halfway between New York and Philadelphia. He handed me a white styrofoam box, packed with ice, that contained vials of the Koprowski vaccine. To the uninformed observer, it might have looked like a drug exchange.
I took the vials back to the lab (see photo), thawed them, separated them into aliquots, and gave each a code. I then returned them to the Wistar in the same way, after a second trip on the New Jersey Turnpike. The samples were sent to three different laboratories where experiments were done to determine the mitochondrial DNA type of the cells in which the viruses had been propagated (although the samples were free of cells, some mitochondrial DNA would still be present from virus induced cell lysis). The results, which have been published (reference one, two), clearly showed that the vaccines had not been grown in chimpanzee cells. I was pleased to have played a small role in this story.
Although I had spoken with Dr. Koprowski several times on the telephone, I did not meet him until 2005 when he presented a talk on the history of rabies in the History of Science series at Columbia University Medical Center. I was his host for that visit, during which I was photographed with Dr. Koprowski and Dr. Rich Kessin, another Columbia professor. We invited Dr. Koprowski to dinner after the seminar but he declined, but he did want to have a drink together. After being warned by his driver not to keep him too late, we walked to a local bar and Dr. Koprowski ordered a Boodles gin martini. The bartender noted that he didn’t receive many calls for that brand. Dr. Koprowski said it was his favorite gin. We talked for a while and then returned Dr. Koprowski to his car for the trip back to Philadelphia. During his visit I had Dr. Koprowski autograph my copy of Listen to the Music (photo). He wrote: “To my friend Vince, with warmest regards, Hilary, 4/14/05.” It was the first and last time I saw him.
I would like to relate one last story which has nothing to do with me, but is irresistible. It takes place in the opening pages of Listen to the Music. Koprowski and his technician Thomas Norton are about to drink an early version of his attenuated polio vaccine. The virus has been passaged in rats and appears to be attenuated in monkeys. On a January day in 1948 Koprowski and Norton are in a laboratory at Lederle Laboratories in Pearl River, NY., where they are blending the brains and spinal cords of rats that had been infected with the vaccine strain virus. They both drink a milliliter of the cold, greasy, mix which flows thickly over their tongues and is difficult to swallow.
Here is the best part:
When he can speak, Norton asks, “Have another?”
“Better not,” Koprowski says. “I’m driving.”
The World Health Organization has been publishing weekly reports on the avian influenza A(H7N9) outbreak which include the geographical location of each case, the cumulative number of cases, and the epidemiological curve. Go to this page at the WHO website for an archive of the weekly reports (there you will also find other useful information on the H7N9 outbreak). Images for report #3 of 24 April 2013 are reproduced below. Click each image for a larger view.
An outbreak of high-pathogenicity avian influenza H7N7 virus that took place on 255 poultry farms in the Netherlands during 2003 has been used to provide clues about the current avian influenza H7N9 viruses in China. During the Dutch outbreak 453 humans showed symptoms of illness and 89 were confirmed to have infection with the virus. Some interesting observations from that outbreak:
So far the H7N9 virus does not appear to be spreading from human to human. This observation suggests that the virus is widespread in poultry in China, and that there have been multiple introductions into humans. It seems likely that these novel viruses arose relatively recently in China and some time thereafter had to opportunity to infect humans.
The question on everyone’s mind is whether the avian influenza H7N9 viruses will acquire the ability to transmit among humans. On this subject the authors have the following comment:
Although human infections with H7 influenza viruses have occurred repeatedly over the last decades without evidence of sustained human-to-human transmission, the absence of sustained human-to-human transmission of A(H7N9) viruses does not come with any guarantee.
It is possible that during replication in birds or humans, the H7N9 viruses might randomly acquire a mutation that allows for transmission. In the right place at the right time, such a virus could spread through the human population. Alternatively, such a transmission-facilitating mutation might interfere with the overall fitness of the virus, thereby preventing it from spreading. I favor the latter hypothesis because the H7N9 viruses have been transmitting since at least February 2013; they have undergone many replication cycles without such a mutation arising. If the virus has not entered wild birds, culling poultry could eradicate it from China – assuming that it has not gone elsewhere.
