Bib: chap 3–7 – THE WONDERS WE CREATED AND THE POTHOLES WE DUG

Then, in 1981, Jacques Dubochet and Alasdair McDowall made a breakthrough in imaging macromolecular complexes with EM — introducing the rapid cryo-cooling of individual molecules in a thin layer of vitrified water –

Ruska electron microscope Ruska electron microscope

https://en.wikipedia.org/wiki/Ernst_Ruska https://authors.library.caltech.edu/5456/1/hrst.mit.edu/hrs/materials/public/ElectronMicroscope/EM_HistOverview.htm#:~:text=1.,the%20limitations%20of%20visible%20light.

Tobacco mosaic virus

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC408320/?page=6

Michael Riordan Wash U. magazine

https://riordangileadsciencesarticle.wordpress.com/

https://riordanclinic.org/books/

Schinazi –scientist who created two HIV drugs and was instrumental in finding cure for hepatitis C.

https://www.military.com/daily-news/2016/02/05/former-va-scientist-responds-to-lawmakers-suspicions-drug-sale.html

Schinazi compensation https://www.military.com/daily-news/2016/02/05/former-va-scientist-responds-to-lawmakers-suspicions-drug-sale.html

https://joncohen.org/2015/05/08/king-of-the-pills/

King of the Pills by Jon Cohen, Science May 8, 2015 (Shinazi interview)

DRUGS THAT TREAT VIRAL INFECTIONS Michael Riordan—the founder of Gilead.

Riordan Gilead https://riordangileadsciencesarticle.wordpress.com/https://en.wikipedia.org/wiki/Gilead_Sciences

Gilead remdesivir

https://www.gilead.com/-/media/gilead-corporate/files/pdfs/covid-19/gilead_rdv-development-fact-sheet-2020.pdf

https://en.wikipedia.org/wiki/Gilead_Sciences

nucleoside phosphanate –

Antonin Holy Czech scientist created the powerful HIV durgs—the nucleoside phoshanates

https://www.intmedpress.com/serveFile.cfm?sUID=7580f2bf-12b9-4a9c-840d-fb337dcb9873

https://en.wikipedia.org/wiki/Phosphonate

Antonin Holy and nucleoside phoshanates https://www.intmedpress.com/serveFile.cfm?sUID=7580f2bf-12b9-4a9c-840d-fb337dcb9873

Cold War Triangle: how scientists in east and west tamed HIV, by Renilde Loeckx; Leuven University Press

Riordan Gilead https://riordangileadsciencesarticle.wordpress.com/

https://www.intmedpress.com/serveFile.cfm?sUID=7580f2bf-12b9-4a9c-840d-fb337dcb9873 https://en.wikipedia.org/wiki/Phosphonate

HIV prevention Gilead

https://www.statnews.com/2020/02/26/newest-prep-pill-hiv-prevention-fuel-progress-or-profits/

https://www.ibtimes.com/hiv-drug-truvada-costs-2000-us-only-8-australia-2792684

Schinazi antivirals for hepatitis C and HIV

https://www.ft.com/content/e7925e46-fc86-11e3-86dc-00144feab7de

https://www.military.com/daily-news/2016/02/05/former-va-scientist-responds-to-lawmakers-suspicions-drug-sale.html

King of the pills by Jon Cohen. PUBLISHED MAY 8, 2015

https://joncohen.org/2015/05/08/king-of-the-pills/

Hepatitis C

https://www.scientificamerican.com/article/inventor-of-hepatitis-c-cure-wins-a-major-prize-and-turns-to-the-next-battle/

A Better Treatment for Hepatitis C (edited) Dec 9, 2013 New Yorker By Celine Gounder a physician, public-health specialist, and medical journalist

There are six genotypes of hepatitis C. Using interferon some were more responsive to treatment than others. “Sofosbuvir changed everything. One-pill-a-day therapy, very high cure rates, shorter treatment duration, and fewer side effects.” Sofosbuvir was invented by, and named after, Michael Sofia, the kind of person who daydreams about enzymes metabolizing drugs. Sofia was raised in a row house on the northeastern side of Baltimore. His parents, a barber and a payroll clerk, were both children of Italian immigrants, and born within a block of each other in Baltimore’s Little Italy. Although they instilled an immigrant’s appreciation for education in their three children, who would all go on to work in science, Sofia’s reading skills were so poor as a child that in the fourth grade he was put in a remedial reading class. Sofia credits the nun who taught him with transforming into a “completely different student.” Sofia eventually enrolled at Cornell and went on to earn his Ph.D. from the University of Illinois.

When he arrived at Pharmasset, the company had already started moving away from the H.I.V.-drug development that it was initially known for, since the market had become saturated with “nucleoside” drugs that worked reliably with manageable side effects. Nucleosides are the building blocks of D.N.A. and R.N.A.; they can be chemically altered to terminate chains of genetic code early, producing something like a defective Lego that can’t be build onto, stopping the growth of the virus. Though this chemistry had been used successfully to treat H.I.V., only a few labs were trying this approach with hepatitis C. Sofia noted that one of the company’s test drugs, PSI-6130, showed activity against hepatitis C. He realized that any effective hepatitis-C drug not only needed to get into the liver, where the virus was replicating, but stay there, to avoid unintended side effects elsewhere in the body. In their active form, nucleoside drugs don’t enter liver cells. Sofia hypothesized that if he could shroud a nucleoside with an “invisibility cloak” to get it into liver cells he could then count on the liver’s enzymes to break down the cloak and activate the drug. Once the cloak has been shed, the nucleoside would be trapped inside, protecting the rest of the body from exposure. “ He explicitly engineered sofosbuvir with this and a number of other goals in mind—that the drug would be taken orally, ten times more potent than PSI-6130, and effective against all six genotypes of hepatitis C. Beginning with a modified version PSI-6130, after three years of development, Sofia and his colleagues arrived at sofosbuvir in 2007. What’s remarkable, according to Sofia, is that it was not in fact a happy accident, but a product of explicit engineering. Following the Pharmasset acquisition in 2011, Sofia worked with Gilead for about a year to manage the transition process.

https://www.npr.org/sections/health-shots/2020/06/29/884648842/remdesivir-priced-at-more-than-3-100-for-a-course-of-treatment