Heroic Innovators

In 1907 the first evidence that warts were caused by a virus was found by Guiseppi Ciuffo in Italy, who showed transmission via cell-free filtrate, indicating this could not be a bacterial infection. This can be taken as an important milestone marking discovery of the first human virus. It would ultimately be called a papilloma virus, following the medical name for warts. (My inspiration for much of this is an excellent article by Dr. Kristen Kiersiek. )

In 1911 F. Peyton Rous published his discovery of what became known as the Rous sarcoma virus in chickens. Not only was this the first oncovirus, it would later be identified as a retrovirus. Despite work ultimately showing three different cancers in chickens could be transmitted by cell-free filtrates there was essentially no follow up by medical researchers.

In 1933 Richard Shope discovered papilloma virus in rabbits. This evidence of a mammalian virus led Rous to resume work on tumors caused by viruses. By 1935 he had demonstrated that papilloma virus could cause a skin cancer in rabbits.

By 1949 electron micrographs definitely showed that these viruses without envelopes were intimately involved in forming papillomas, including human papillomas. What was missing was an understanding at the molecular level. This is understandable since the structure and replication of DNA was scarcely elucidated at all until 1953. (I'm not trying to belittle contributions like Erwin Chargaff's rules, without which this would have scarcely been possible.) Even then, understanding of retroviruses and epigenetic control of genes was entirely lacking. Barbara McClintock was met with such sheer incomprehension that she stopped publishing her work on transposons and regulation of genes that year. This hiatus lasted 20 years.

By 1966 enough of a consensus had emerged that Peyton Rous had done important work to garner the Nobel Prize. The discovery of reverse transcriptase, needed to convert viral RNA into DNA inserted in chromosomes, did not take place until 1970, the year of Rous' death. At this point retrovirology might first be said to exist as a subject. McClintock received the Nobel Prize in 1983, an unshared award which may still be unique for a woman in that field.

By the late 1970s, enough work on the molecular biology of viruses had taken place to associate human papilloma virus (HPV) with cervical cancer, though controversy continued. Harald Zur Hausen defined subtypes of HPV, and the connection with cervical cancer, well enough to make development of a vaccine practical. Such a vaccine was approved in 2006 (though controversy still continues.) Zur Hausen received the Nobel Prize in 2008, just over a century after the discovery of a human papilloma virus (though not the specific one causing cervical cancer.)

While most researchers and medical practitioners view themselves as heirs to an heroic tradition of innovation in health care, this is unlikely. Those innovators had little direct influence on more than a small number of students. Much larger numbers of people graduated from medical or graduate schools during the same period, trained according to the prevailing consensus. While there is plenty of room for caution concerning new treatments, this should be always viewed against the background of known consequences of existing practice. Alternatives to risks still exist even if ignored. (At present, about 500,000 new cases of cervical cancer are diagnosed each year, globally. It remains the second largest cause of cancer deaths in women.) I'm rather afraid the vast majority of both researchers and doctors are heirs to the much larger and longer medical tradition of impeding research which violates preconceptions.


It's all b..... viruses - when will they learn ! Heroic innovators very welcome in what seems to defeat ordinary mortals.
I must presume you're implying an epithet Henry Higgins used regularly, but off-stage.
Mrs. Pierce: "Only this morning, sir, you applied it to your boots, to the butter and to the brown bread."

Higgins: "Oh, that! Mere alliteration, Mrs. Pierce, natural to a poet."
Of course, I couldn't be expected to know. To quote the same sage:
"There even are places where English completely disappears; in America they haven't used it for years. "
The serious point I was making is that it has taken approximately a century for the idea of cancer-causing viruses to go from speculation to the point of taking action. During half that time research was accomplished by isolated individuals bucking the prevailing consensus. Recently a study at the Karolinska Institute Center for Molecular Medicine found active cytomegalovirus (CMV) in 99% of gliobastomas and 90% of both medulloblastomas and neuroblastomas, all generally lethal forms of cancer for which there has been little progress in treatment or prevention. This has led to a prediction that 40% of the 200 or so types of cancer will be found to be caused by viruses.

The surprise in all this is that CMV (or HHV-5) has been known and studied for a long time. It now appears to fit in the category of oncogenic viruses, along with EBV (HHV-4) and HHV-8. If it follows the pattern of other oncogenic viruses, I predict it will be found to integrate into chromosomes, like EBV, HHV-6 and HPV. If this turns out to be true, I would then predict a retroviral cofactor, since none of the herpes virus family has the integrase needed to insert genes in chromosomes.

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