How We Got the Controversial HPV Vaccine

It took more than 30 years—and mice grafted with infected human foreskins.

By Emily Saarman|Thursday, May 17, 2007
RELATED TAGS: CANCER, INFECTIOUS DISEASES

Last year the FDA approved Gardasil, a vaccine effective against four strains of human papillomavirus (HPV) that cause 90 percent of genital warts and 70 percent of all cases of cervical cancer. Virginia soon made the vaccine mandatory for girls entering sixth grade (leaving parents the right to opt out), but a similar effort in Texas was derailed by arguments that the vaccine would encourage promiscuity. More than 20 other states began debating whether the vaccination should be mandatory.

Since then the vaccine has only become more controversial—especially after The New England Journal of Medicine published results on May 11 showing that the vaccine may not be as effective as was hoped. Now some lawmakers want to make it mandatory, some scientists think that's premature, some parents don’t want it anywhere near their daughters, and—at $360 a pop—many people can’t afford it.

How do we know HPV causes cervical cancer? Where did the vaccine come from? This timeline tracks the discoveries, twists, and setbacks that led to the controversial vaccine.

1842 –Domenico Rigoni-Stern looks at the patterns of disease in his hometown of Verona and notices that nuns get cervical cancer less often and breast cancer more often than married women. He guesses that sex causes cervical cancer and that the nuns’ tight corsets cause breast cancer.

1901 – One Dr. Braithwaite of London notices that cervical cancer is “seldom or never met with among the numerous Jewesses.” He concludes that eating salt causes the scourge and that Jews avoid it by passing on bacon. Perhaps kosher pickles were a well-kept secret.

1911 –When F. Peyton Rous takes a cell-free extract from a chicken sarcoma and injects it into another chicken, the chicken contracts cancer too. Soon Rous isolates the virus responsible for the cancer, known as the Rous sarcoma virus. In 1966he wins a Nobel Prize for finding the first cancer caused by a virus.

1932 –Reports of jackalopes—rabbits with horns—pique the interest of Richard Shope, a cancer researcher at the Rockefeller Institute. Working with Rous, he grinds up the tumors and injects the extract into other rabbits, which then develop the same deformity. This reveals that the “horns” are actually tumors caused by a contagious papillomavirus.

1930s – The discovery of two cancer-causing viruses spurs the search for more. Over the next few years several viruses, including herpes virus, are found to be responsible for cancers in frogs, chickens, and mice.

1950s –After the formation of Israel, scientists again wonder about the rarity of cervical cancer among Jewish women. Many epidemiologists think that male circumcision reduces the risk of cervical cancer by preventing a woman’s contact with smegma—goop that can accumulate under the foreskin.

1965 –The Epstein-Barr virus, which causes mononucleosis, is found in the cancerous lymph node cells of children with Burkitt’s lymphoma, making it the first known human cancer virus.

1967 – Kamal Abou-Daoud notices that Muslim women with circumcised husbands have higher rates of cervical cancer than Jewish women. Other studies in the U.S.S.R. show that Jewish women with uncircumcised husbands rarely get cervical cancer. These studies begin to erode the circumcision theory.

1970s – A close look at cervical cancer cells shows that women with cervical cancer often have traces of genital herpes as well. Some researchers conclude that herpes is the cause of cervical cancer, even though many women with herpes never develop cancer and only about half of cervical cancer patients have a herpes infection.

1975 –Harald zur Hausen begins looking beyond herpes for a viral cause of cervical cancer, focusing on HPV because of the rabbit studies from the 1930s.Eventually, he isolates two strains of HPV that are found in about 70 percent of cervical cancer biopsies.

1980s – Researchers at the University of Rochester try to experiment on HPV but are stymied by a dearth of the virus itself.

1986 –John Kreider finds a way to mass-produce HPV: He collects foreskins from infant circumcisions, infects them with HPV, and grafts them onto mice whose compromised immune systems cannot reject the graft or fight the virus.

1990 –Evidence that HPV causes of cervical cancer mounts, and the race to develop an HPV vaccine is on.

1990 –Researchers at the University of Rochester combine antibodies from infected rabbits with the live virus; the proof-of-concept vaccine successfully prevents foreskin-grafted mice from contracting HPV on their borrowed private parts.

1990-92 – Robert Rose and other Rochester researchers build a protein coat that mimics the shape of an HPV envelope without any viral DNA inside. Built by a harmless baculovirus that grows only on insect cells,the viruslike particles prevent future HPV infection but don’t carry any risk of disease.

1994 – Trials using killed strains of rabbit papillomavirus are close to 100 percent effective in preventing future infections in rabbits. Unfortunately, there’s arisk that some viral DNA could still cause disease, so researchers turn to the viruslike particles for a safer vaccine.

1998 – Alan Storey finds a genetic mutation that increases the risk of cervical cancer and is rare among Jewish women. So there was something significant about Jewish immunity after all—it just wasn’t smegma.

2002 –Studies show that circumcised men have 60% less chance of contracting HPV,which translates into a slight reduction in cervical-cancer risk for their partners. This may explain why some circumcision studies from the '50s showed a small reduction in cervical cancer among circumcised non-Jewish populations.

2005 –Merck and GlaxoSmithKline agree with the National Cancer Institute, Georgetown University,the University of Rochester, and the University of Queensland to cooperate on two different HPV vaccines.

2005-2006 –Merck and GSK report that the two HPV vaccines made from viruslike particles are 100 percent effective against the targeted HPV strains.

2006 – Merck’s HPV vaccine, Gardasil, is approved for use in the U.S., and physicians recommend vaccinating all young girls before they become sexually active. A second HPV vaccine, Cervarix, which is made by GSK and targets some different HPV strains, is still in review by the FDA.

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