Here’s a set of arti­cles relat­ed to that Glob­al Research arti­cle by Lar­ry Romanoff describ­ing the the claims made by Chi­nese researchers that the virus may have orig­i­nat­ed from out­side the US. That Glob­al Research arti­cle also men­tioned a Tai­wan news pro­gram that had a pre­sen­ta­tion by a man the arti­cle described as a top virol­o­gist and phar­ma­col­o­gist who con­duct­ed his own research on the dif­fer­ent hap­lo­types (genom­ic ver­sions) of the virus and con­clud­ed the Unit­ed States was like­ly the ori­gin of the virus because it was the only coun­try that had all five known hap­lo­types:

...
Below is a rough trans­la­tion, sum­ma­ry and analy­sis of select­ed con­tent of that news­cast. (see map below)

The man in the video is a top virol­o­gist and phar­ma­col­o­gist who per­formed a long and detailed search for the source of the virus. He spends the first part of the video explain­ing the var­i­ous hap­lo­types (vari­eties, if you will), and explains how they are relat­ed to each oth­er, how one must have come before anoth­er, and how one type derived from anoth­er. He explains this is mere­ly ele­men­tary sci­ence and noth­ing to do with geopo­lit­i­cal issues, describ­ing how, just as with num­bers in order, 3 must always fol­low 2.

[see screen­shot of pre­sen­ta­tion with graph­ic show­ing the geo­graph­ic dis­tri­b­u­tion of dif­fer­ent hap­lo­types]

One of his main points is that the type infect­ing Tai­wan exists only in Aus­tralia and the US and, since Tai­wan was not infect­ed by Aus­tralians, the infec­tion in Tai­wan could have come only from the US.

The basic log­ic is that the geo­graph­i­cal loca­tion with the great­est diver­si­ty of virus strains must be the orig­i­nal source because a sin­gle strain can­not emerge from noth­ing. He demon­strat­ed that only the US has all the five known strains of the virus (while Wuhan and most of Chi­na have only one, as do Tai­wan and South Korea, Thai­land and Viet­nam, Sin­ga­pore, and Eng­land, Bel­gium and Ger­many), con­sti­tut­ing a the­sis that the hap­lo­types in oth­er nations may have orig­i­nat­ed in the US.

Korea and Tai­wan have a dif­fer­ent hap­lo­type of the virus than Chi­na, per­haps more infec­tive but much less dead­ly, which would account for a death rate only 1/3 that of Chi­na.
...

So here’s a few clar­i­fi­ca­tions on that report. First note that the man did­n’t actu­al­ly con­duct the study him­self. He was recount­ing the same study pub­lished by Chi­nese researchers a few days ear­li­er. You can find that graph­ic from his tele­vised seg­ment at the end of the pub­lished paper itself here (PDF down­load link here). Also note that the graph­ic fea­tured in the tele­vised seg­ment has a “2” cir­cle show­ing two of the hap­lo­types in Tai­wan so that’s pre­sum­ably where he got the data about the two strains found in Tai­wan. The Tai­wanese man also appears to be Pan Hawi-tzong, a politi­cian asso­ci­at­ed with a right-wing pro-reuni­fi­ca­tion Tai­wanese par­ty, the “New Par­ty”. Here’s Glob­al Times piece rehashed the find­ings of these Chi­nese researchers and men­tions Pan Hawi-tzong’s tele­vi­sion appear­ance describ­ing the research:

Glob­al Times

COVID-19 cas­es of unknown source per­plex researchers

By Shan Jie and Deng Xiao­ci
Pub­lished: 2020/2/29 20:50:30 Last Updat­ed: 2020/3/1 17:33:38

Stud­ies on the evo­lu­tion­ary rela­tions between the nov­el coro­n­avirus­es have pro­vid­ed more clues, sug­gest­ing it’s still dif­fi­cult to deter­mine the ori­gin of the virus, while experts called for more sol­id and author­i­ta­tive research­es.

The US has found at least four COVID-19 cas­es of unknown source, media report­ed Sat­ur­day.

“The two con­cerns should be put togeth­er to con­sid­er to avoid arbi­trary infor­ma­tion with­out ade­quate evi­dence,” Zhang said.

An Eng­lish paper sub­mit­ted by Yu Wen­bin, an asso­ciate researcher at the Chi­nese Acad­e­my of Sci­ences, to Chi­naX­iv on Feb­ru­ary 21 indi­cat­ed that the Hua­nan Seafood Mar­ket in Wuhan, the epi­dem­ic epi­cen­ter, might not be where the virus was orig­i­nal­ly from.

The arti­cle said the hap­lo­types of the 58 new coro­n­avirus­es, num­bered H1-H58, were divid­ed into five groups: A, B, C, D, and E, with A being the old­est and E the youngest.

How­ev­er, in Hubei, only coro­n­avirus from Group C are detect­ed, but in the US the virus­es from all five groups have been found.

There­fore, Yu and his col­leagues believe that the nov­el coro­n­avirus which caused the epi­dem­ic in Hubei might be import­ed from some oth­er places.

Zhou fur­ther explained that the research is sci­ence based. “If all the test results of nov­el coro­n­avirus in the US are found to be Group C, then it might be trans­mit­ted from Chi­na. But if not, it might be local.”

The arti­cle was echoed by Pan Hwai-tzong, a phar­ma­col­o­gist in Tai­wan in a recent local TV show, who not­ed that more mul­ti­ple genet­ic types of the new coro­n­avirus have been found in the COVID-19 cas­es in the US than those in the Chi­nese main­land.

Wuhan virol­o­gist Yang Zhan­qiu told the Glob­al Times on Sat­ur­day that unknown cas­es of the US influen­za deaths need fur­ther ret­ro­spec­tive exam­i­na­tion before a con­clu­sion could be made where it orig­i­nat­ed.

...

————-

“COVID-19 cas­es of unknown source per­plex researchers” by Shan Jie and Deng Xiao­ci; Glob­al Times; 02/29/2020

“The arti­cle was echoed by Pan Hwai-tzong, a phar­ma­col­o­gist in Tai­wan in a recent local TV show, who not­ed that more mul­ti­ple genet­ic types of the new coro­n­avirus have been found in the COVID-19 cas­es in the US than those in the Chi­nese main­land.”

If you google “Pan Hwai-tzong + New Par­ty” you can find lots of news arti­cles ref­er­enc­ing him being a New Par­ty can­di­date (here’s an exam­ple). So he appears to be some­one in Tai­wan who would actu­al­ly be pret­ty sym­pa­thet­ic to the Chi­nese gov­ern­ment.

That said, the rel­e­vant ques­tion is not whether or not the peo­ple mak­ing these asser­tions might be car­ry­ing water for the Chi­nese gov­ern­ment. The research should stand on its own regard­less of which gov­ern­ment they might have sym­pa­thy towards. And it turns out the analy­sis of the Chi­nese researchers was based on sam­ples sub­mit­ted to the GISAID Epi­Flu data­base. GISAID is the Glob­al Ini­tia­tive on Shar­ing All Influen­za Data set up by the Ger­man gov­ern­ment. So it appears that the data these Chi­nese researchers were bas­ing their analy­sis on was tak­en from a Ger­man gov­ern­ment-backed glob­al ini­tia­tive that any­one has access to. Whether or not their analy­sis was done well is a sep­a­rate ques­tion best left to peer review­ers. But it’s the kind of analy­sis that can be repli­cat­ed by any­one with the prop­er train­ing since the data is all pub­licly avail­able.

That said, as we’re going to see in the fol­low­ing arti­cles, even when research is based on pub­licly avail­able data that any­one can access, there’s still a big dis­pute over the inter­pre­ta­tion of the data and analy­ses. Because vari­a­tions of the type of analy­sis done by those Chi­nese researchers — com­par­ing viral genom­ic sequences to make infer­ences about how the virus has spread and evolved — is high­ly open to inter­pre­ta­tion and there are many dif­fer­ent sce­nar­ios that could explain the observed data.

So with all that in mind, here’s a sto­ry about anoth­er find­ing by a dif­fer­ent set of Chi­nese researchers that would appear to also raise ques­tions about whether or not the virus orig­i­nat­ed in Wuhan, Chi­na. Alarm­ing­ly, the researchers found that there appears to be two strains of the virus in Chi­na and one might be more vir­u­lent and aggres­sive than the oth­er: One strain — the ‘L‑type’ strain — is was the pre­dom­i­nant strain in Wuhan ear­ly on in the out­break. A sec­ond strain — the ‘S‑type’ straing — appears to be evo­lu­tion­ar­i­ly old­er and found much more out­side of Wuhan and around the world. About 70 per­cent of strains around the world are of the ‘L‑type’ but ini­tial­ly in the Wuhan out­break almost all of the sequenced strains were ‘L‑type’. So the evo­lu­tion­ar­i­ly old­er ‘S‑type’ strain appears to have increased in rel­a­tive fre­quen­cy as the pan­dem­ic spread around the world.

How do these two strains relate to the 5 sub­groups the researchers cit­ed in the above Glob­al Research arti­cle dis­cov­ered? The two strains basi­cal­ly encom­pass those five sub­groups: some of the sub­groups fall under one strain and some in the oth­er strain, deter­mined by whether or not the sub­groups have a par­tic­u­lar set of muta­tions on two adja­cent nucleotides.

So which strain came first? Well, these researchers have con­clud­ed that the ‘S‑type’ strain is evo­lu­tion­ar­i­ly clos­er to known bat coro­n­avirus­es so that would sug­gest it jumped to humans first. That would seem con­tra­dict that idea that Wuhan was the source of the jump of the virus from ani­mals to humans and would raise ques­tions of whether or not this has been float­ing around for longer than peo­ple expect­ed. Although the authors don’t explic­it­ly say they think the ‘S‑type’ actu­al­ly emerged first. Just that it’s evo­lu­tion­ar­i­ly ‘old­er’ in the sense that it genet­i­cal­ly more close­ly resem­bles a known bat coro­n­avirus. And it’s pos­si­ble the ‘S‑type’ strain emerged in Wuhan, then the ‘L‑type’ strain evolved and came to dom­i­nate that out­break. There are many pos­si­bil­i­ties.

The researchers also sug­gest that the evo­lu­tion­ar­i­ly new­er ‘L‑type’ strain found to be pre­dom­i­nant in the ini­tial Wuhan sam­ples was more vir­u­lent and aggres­sive, which would also be con­sis­tent with the obser­va­tion that the case fatal­i­ty rates in Wuhan appear to be much high­er than else­where in Chi­na (2–4% vs 0.7%). This par­tic­u­lar sug­ges­tion is already being chal­lenged by oth­er researchers who ques­tion their meth­ods so it’s very pos­si­ble these find­ings won’t pan out. It sounds like the Chi­nese team used a rel­a­tive­ly new method in a rapid­ly devel­op­ing area of sci­ence that relies on algo­rithms that com­pare viral genom­ic sequences to build fam­i­ly-trees and make infer­ences about the spread and evo­lu­tion of a virus and that’s a sit­u­a­tion ripe for mis­takes. As Uni­ver­si­ty of Edin­burgh geneti­cist Andrew Ram­baut argues, the rea­son­ing behind the researchers infer­ence that the ‘L‑type’ strain has become more vir­u­lent was a leap too far. The researchers made that infer­ence based on the obser­va­tion that almost all of the viral sam­ples from Wuhan (26 out of 27) are of the L‑type strain but only about 70 per­cent of the sam­ples from else­where in Chi­na and out­side Chi­na were of the L‑type. The researchers hypoth­e­size that this sig­nif­i­cant drop in the fre­quen­cy of the ‘L‑type’ strain was due to some sort of evo­lu­tion­ary selec­tive pres­sure placed on the virus as a result of the extreme mea­sures the Chi­nese author­i­ties took to lim­it the spread of the virus (i.e. if the ‘L‑type’ can spread more eas­i­ly in crowds than the ‘S‑type’, ban­ning crowds is going to cause a rel­a­tive drop in the fre­quen­cy of the ‘L‑type’). That pos­si­ble expla­na­tion for why the bal­ance between these two strains between is so dif­fer­ent in Wuhan — where out­break is assumed to have bro­ken out and it’s almost all L‑type — and the rest of Chi­na and the world — where it’s only about 70% L‑type — is what led the researchers to sug­gest that the addi­tion­al muta­tions in the L‑type made it more vir­u­lent and aggres­sive and it’s that line of rea­son­ing that Andrew Ram­baut takes issue with.

And Ram­baut is cor­rect that there are many oth­er pos­si­ble expla­na­tions for that dif­fer­ence in the bal­ance between the ‘L‑type’ and ‘S‑type’ strains with­in Wuhan and in the rest of the world. There are all sorts of issues like ‘founder effects’ that can cause dif­fer­ent strains of virus­es to have dif­fer­ent observed fre­quen­cies around the world. Per­haps peo­ple car­ry­ing the ‘S‑type’ strain are more effec­tive asymp­to­matic spread­ers that were more like­ly to trav­el around the world and spread it? Or maybe there was an issue with how the viral sam­ples were col­lect­ed in Wuhan that sig­nif­i­cant­ly under­count­ed the pres­ence of the ‘S‑type’ strain there. But it’s also pos­si­ble the research is indeed cor­rect and we real­ly are look­ing at two dif­fer­ent strains with dif­fer­ent lev­els of vir­u­lence. And whether or not the ‘L‑type’ strain found in Wuhan is more vir­u­lent, the fact the ‘L‑type’ strain is genet­i­cal­ly more dis­im­i­lar to known bat coro­n­avirus than the ‘S‑type’ strain sure sug­gests that the ‘L‑type’ strain emerged after the ‘S‑type’ strain and if that’s would make it more plau­si­ble that the jump from ani­mal to human did­n’t orig­i­nate in Wuhan.

Ram­baut does­n’t appear to be tak­ing issue with the idea that the ‘S‑type’ strain is more close­ly relat­ed to the bat coro­n­avirus and there­fore evo­lu­tion­ar­i­ly old­er. Although it’s impor­tant to note that oth­er researchers who take issue with the research do specif­i­cal­ly take issue with that infer­ence that greater sim­i­lar­i­ty to a bat coro­n­avirus strain means the ‘S‑type’ strain is old­er than the ‘L‑type’ strain. Instead, these crit­ics — from the MRC-Uni­ver­si­ty of Glas­gow Cen­ter for Virus Research in Scot­land — assert it’s entire­ly plau­si­ble that the ‘S‑type’ strain evolved from the ‘L‑type’ strain and mutat­ed back in the direc­tion of the inferred ances­tral state of the virus (i.e. back to the bat coro­n­avirus sequence) in part because we don’t actu­al­ly know what the ances­tral sequence was from this virus (we’re just guess­ing) and in part because ‘back-muta­tions’ are entire­ly plau­si­ble and nat­ur­al. You can actu­al­ly read a back and forth debate between the Chi­nese team and their crit­ics in the com­ments to their cri­tique and it (at this point) appears to have descend­ed into a debate over the method­olog­i­cal approach­es and assump­tions used by evo­lu­tion­ary geneti­cists vs epi­demi­ol­o­gists.

The point is that there’s this out­break is hap­pen­ing in a time when unprece­dent­ed details about nov­el virus­es are now glob­al­ly avail­able and researchers and that cre­ates a new oppor­tu­ni­ty for all sorts of infer­ences and edu­cat­ed guess­es as these epi­demics unfold. And that means there’s a big new oppor­tu­ni­ty for devel­op­ing new method­olo­gies to gen­er­ate valu­able insights as nov­el virus­es emerge but also big oppor­tu­ni­ties for mis­takes. We don’t know yet whether or not the find­ings by this research team in Chi­na was a valu­able insight or a mis­take. But if it the infer­ence that the ‘S‑type’ strain is indeed tru­ly old­er than the ‘L‑type’ strain pans out, that points toward the ani­mal-to-human jump hap­pen­ing some­where out­side of Wuhan:

The Los Ange­les Times

Here’s why Chi­nese sci­en­tists say there’s a sec­ond, more dan­ger­ous coro­n­avirus strain

By MELISSA HEALY
STAFF WRITER
MARCH 5, 2020 9:47 PM

The glob­al out­break that has sick­ened near­ly 100,000 peo­ple across six con­ti­nents may actu­al­ly be fueled by two vari­ants of the same coro­n­avirus: one old­er and less aggres­sive and a new­er ver­sion whose muta­tions may have made it more con­ta­gious and more dead­ly, accord­ing to a con­tro­ver­sial new study.

Chi­nese sci­en­tists who com­pared the genet­ic sequences of 103 viral sam­ples from patients infect­ed with COVID-19 said their evi­dence sug­gests that the vir­u­lent ver­sion of the coro­n­avirus — which they tagged the “L‑type” ver­sion — was the dom­i­nant strain in the ear­li­est phase of the out­break that began in Wuhan late last year. That strain, they said, appeared to recede as the epi­dem­ic pro­gressed.

But among sam­ples col­lect­ed lat­er, as COVID-19 spread across Chi­na and into oth­er coun­tries, a vari­ant of the virus they dubbed the “S‑type” was more com­mon, the sci­en­tists report­ed. They sug­gest­ed that the genet­ic make­up of the S ver­sion more close­ly resem­bles coro­n­avirus­es cir­cu­lat­ing in bats and pan­golins, the ani­mals that are thought to have incu­bat­ed the virus before it jumped to humans. And they sur­mised that it is a less vir­u­lent ver­sion.

The find­ings sug­gest the S‑type ver­sion of the coro­n­avirus may have escaped its ani­mal hosts ear­li­er than pre­vi­ous­ly believed — and that it may have been cir­cu­lat­ing longer with­out caus­ing enough ill­ness to set off alarm bells.

The Chi­nese sci­en­tists report­ed their analy­sis Thurs­day in the jour­nal Nation­al Sci­ence Review. The team was led by Peking University’s bioin­for­mat­ics researcher Jian Lu in Bei­jing.

The study authors acknowl­edged that their con­clu­sions are very pre­lim­i­nary and are based on a very small sam­ple of virus­es. The vari­a­tions they found will need to be observed in many more spec­i­mens tak­en from oth­er patients, and their genet­ic dif­fer­ences will need to be com­pared with physi­cians’ reports and epi­demi­o­log­i­cal notes. Only then can their sus­pi­cions can be con­firmed, they wrote.

Offi­cials at the World Health Orga­ni­za­tion warned that “it’s impor­tant we don’t over­in­ter­pret” the sci­en­tists’ find­ings.

...

Some sci­en­tists were far more crit­i­cal, with some call­ing for the paper to be retract­ed.

The new analy­sis comes from sci­en­tists in a rel­a­tive­ly new and fast-mov­ing field that’s devot­ed to the genet­ic inves­ti­ga­tion of dis­ease-caus­ing germs.

Using a tech­nique called phy­lo­dy­nam­ic analy­sis, researchers col­lect and sequence the genomes of many sam­ples of a giv­en microbe and scour them for tiny sub­sti­tu­tions in their DNA or RNA. By track­ing those genet­ic shifts, they can recon­struct a rough pic­ture of a germ’s pas­sage through a pop­u­la­tion, and detect turn­ing points along the way.

The authors of the new study com­pared genet­ic sequences of viral sam­ples tak­en from 27 patients in Wuhan, 33 patients from else­where in main­land Chi­na, three from Tai­wan and 40 from patients out­side Chi­na.

Com­par­ing all those sam­ples to those tak­en from bats, they found rel­a­tive­ly lit­tle evi­dence of vari­abil­i­ty. That sug­gests the nov­el coro­n­avirus has cir­cu­lat­ed in humans for only a few months, chang­ing lit­tle as it jumped from per­son to per­son and repli­cat­ed itself, they wrote.

But when the sci­en­tists com­pared the 30,000 nucleotides of each sam­ple to one anoth­er and focused on find­ing dif­fer­ences among them, they found a much greater degree of vari­abil­i­ty. That’s a sign that the changes in the virus since it began to infect humans were “much larg­er than pre­vi­ous­ly esti­mat­ed,” they wrote.

Of the 103 viral genomes they scoured, 70% were of the L‑type vari­ant. But by ear­ly Jan­u­ary, the sci­en­tists wrote, it appears that “human inter­ven­tion” — pos­si­bly the “rapid and com­pre­hen­sive pre­ven­tion and con­trol mea­sures” adopt­ed by Chi­na — had begun to lim­it the spread of this strain.

By late Jan­u­ary, doc­tors and health author­i­ties were on high alert and test­ing wide­ly for COVID-19 infec­tion. But at that point, the Chi­nese sci­en­tists spec­u­lat­ed, they were col­lect­ing sam­ples from patients who were sick­ened by the old­er, less dan­ger­ous S‑type ver­sion of the virus.

Some geneti­cists who weren’t involved in the study argued that the data could sup­port an alter­na­tive inter­pre­ta­tion: that the virus has sim­ply spread more wide­ly than they had real­ized, pick­ing up ran­dom muta­tions along the way. Those muta­tions may or may not make the virus behave dif­fer­ent­ly.

If the S‑type of the virus is the old­er ver­sion that was cir­cu­lat­ing first, a final mys­tery remains: Why would the major­i­ty of sam­ples tak­en from the ini­tial patients in Wuhan have fall­en into the L‑type cat­e­go­ry? Shouldn’t there be more S‑types in the mix?

This is where the Chi­nese sci­en­tists make a hot­ly debat­ed leap: They sur­mise that the new­er L‑type ver­sion prob­a­bly picked up more muta­tions, and evolved fur­ther from the bat coro­n­avirus from which it orig­i­nat­ed, because it either infects peo­ple more read­i­ly or it repli­cates more vig­or­ous­ly once it infects.

In oth­er words, it’s more trans­mis­si­ble or more aggres­sive — or both.

Uni­ver­si­ty of Edin­burgh geneti­cist Andrew Ram­baut urged cau­tion about that con­clu­sion. When genet­i­cal­ly sequenced sam­ples rep­re­sent a small and hap­haz­ard­ly col­lect­ed sub­set of all infec­tions, the kinds of genet­ic vari­a­tions not­ed by the sci­en­tists are “entire­ly expect­ed,” he wrote on Twit­ter.

To claim that such muta­tions nec­es­sar­i­ly make a virus behave dif­fer­ent­ly, he added, “is a flawed infer­ence.”

A group of researchers from the MRC-Uni­ver­si­ty of Glas­gow Cen­ter for Virus Research in Scot­land offered a more detailed rebut­tal of the new paper. Among oth­er things, they said the study authors mis­in­ter­pret­ed their data and failed to account for lim­i­ta­tions in their sta­tis­ti­cal meth­ods.

“Giv­en these flaws, we believe that Tang et al. should retract their paper, as the claims made in it are clear­ly unfound­ed and risk spread­ing dan­ger­ous mis­in­for­ma­tion at a cru­cial time in the out­break,” the Glas­gow team wrote.

————

“Here’s why Chi­nese sci­en­tists say there’s a sec­ond, more dan­ger­ous coro­n­avirus strain” by MELISSA HEALY; The Los Ange­les Times; 03/05/2020

“The find­ings sug­gest the S‑type ver­sion of the coro­n­avirus may have escaped its ani­mal hosts ear­li­er than pre­vi­ous­ly believed — and that it may have been cir­cu­lat­ing longer with­out caus­ing enough ill­ness to set off alarm bells.”

Is the ‘S‑type’ the orig­i­nal strain that jumped to humans, cir­cu­lat­ing unbe­knownst to med­ical offi­cials for longer than rec­og­nized? That’s what these researchers sug­gest­ed in their analy­sis. They also found that the ‘L‑type’ strain was over­whelm­ing­ly dom­i­nant in Wuhan but far less dom­i­nant out­side of Chi­na. In their paper they write that they found the ‘L‑type’ strain in 26 out of 27 Wuhan strains but of the 73 sam­ples col­lect­ed from out­side Wuhan only 45 of them were of the ‘L‑type’. It’s this obser­va­tion that made them con­clude the ‘L‑type’ strain appeared to recede as the epi­dem­ic pro­gressed while the ‘S‑type’ strain, which appears to be genet­i­cal­ly more close­ly relat­ed to the coro­n­avirus­es cir­cu­lat­ing in bats and pan­golins, became much more com­mon:

...
Chi­nese sci­en­tists who com­pared the genet­ic sequences of 103 viral sam­ples from patients infect­ed with COVID-19 said their evi­dence sug­gests that the vir­u­lent ver­sion of the coro­n­avirus — which they tagged the “L‑type” ver­sion — was the dom­i­nant strain in the ear­li­est phase of the out­break that began in Wuhan late last year. That strain, they said, appeared to recede as the epi­dem­ic pro­gressed.

But among sam­ples col­lect­ed lat­er, as COVID-19 spread across Chi­na and into oth­er coun­tries, a vari­ant of the virus they dubbed the “S‑type” was more com­mon, the sci­en­tists report­ed. They sug­gest­ed that the genet­ic make­up of the S ver­sion more close­ly resem­bles coro­n­avirus­es cir­cu­lat­ing in bats and pan­golins, the ani­mals that are thought to have incu­bat­ed the virus before it jumped to humans. And they sur­mised that it is a less vir­u­lent ver­sion.

...

And they weren’t bas­ing their find­ings on data only avail­able in Chi­na. They were using data avail­able to every­one from viral genet­ic data­bas­es that allow peo­ple to upload viral sequences from around the world. This is new and was­n’t avail­able in past epi­demics. Tak­ing that data and con­duct­ing some­thing called phy­lo­dy­nam­ic analy­sis, they were able to cre­ate a rough pic­ture of how the virus spread. Com­par­isons of the viral sequences to bat coro­n­avirus­es sug­gest the human ver­sion has only been float­ing around for a few months. But com­par­ing the human viral sequences to each oth­er also sug­gests that the ‘L‑type’ virus’s spread was slowed dra­mat­i­cal­ly com­pared to the ‘S‑type’, pos­si­bly due to aggres­sive con­trol mea­sure imposed on Wuhan:

...
The new analy­sis comes from sci­en­tists in a rel­a­tive­ly new and fast-mov­ing field that’s devot­ed to the genet­ic inves­ti­ga­tion of dis­ease-caus­ing germs.

Using a tech­nique called phy­lo­dy­nam­ic analy­sis, researchers col­lect and sequence the genomes of many sam­ples of a giv­en microbe and scour them for tiny sub­sti­tu­tions in their DNA or RNA. By track­ing those genet­ic shifts, they can recon­struct a rough pic­ture of a germ’s pas­sage through a pop­u­la­tion, and detect turn­ing points along the way.

The authors of the new study com­pared genet­ic sequences of viral sam­ples tak­en from 27 patients in Wuhan, 33 patients from else­where in main­land Chi­na, three from Tai­wan and 40 from patients out­side Chi­na.

Com­par­ing all those sam­ples to those tak­en from bats, they found rel­a­tive­ly lit­tle evi­dence of vari­abil­i­ty. That sug­gests the nov­el coro­n­avirus has cir­cu­lat­ed in humans for only a few months, chang­ing lit­tle as it jumped from per­son to per­son and repli­cat­ed itself, they wrote.

But when the sci­en­tists com­pared the 30,000 nucleotides of each sam­ple to one anoth­er and focused on find­ing dif­fer­ences among them, they found a much greater degree of vari­abil­i­ty. That’s a sign that the changes in the virus since it began to infect humans were “much larg­er than pre­vi­ous­ly esti­mat­ed,” they wrote.

Of the 103 viral genomes they scoured, 70% were of the L‑type vari­ant. But by ear­ly Jan­u­ary, the sci­en­tists wrote, it appears that “human inter­ven­tion” — pos­si­bly the “rapid and com­pre­hen­sive pre­ven­tion and con­trol mea­sures” adopt­ed by Chi­na — had begun to lim­it the spread of this strain.

By late Jan­u­ary, doc­tors and health author­i­ties were on high alert and test­ing wide­ly for COVID-19 infec­tion. But at that point, the Chi­nese sci­en­tists spec­u­lat­ed, they were col­lect­ing sam­ples from patients who were sick­ened by the old­er, less dan­ger­ous S‑type ver­sion of the virus.
...

And it’s the obser­va­tion of the rel­a­tive fall in fre­quen­cy of the ‘L‑type’ as the epi­dem­ic pro­gressed that led them to sug­gest that the muta­tions that dif­fer­en­ti­ate the ‘S‑type’ from ‘L‑type’ strain (two adja­cent nucleotides) make the ‘L‑type’ more vir­u­lent and aggres­sive. That’s where oth­er researchers are tak­ing issue with their con­clu­sions and point out that that the infer­ence that the two strains have dif­fer­ent lev­els of vir­u­lence is just a guess and there are plen­ty of oth­er expla­na­tions for the observed data, like the expla­na­tion that the virus may have sim­ply spread more wide­ly than they real­ized (which, again, would raise ques­tions about whether or not it orig­i­nat­ed in Wuhan). And a group from the MRC-Uni­ver­si­ty of Glas­gow Cen­ter for Virus Research in Scot­land is call­ing for an out­right retrac­tion of the paper:

...
Some geneti­cists who weren’t involved in the study argued that the data could sup­port an alter­na­tive inter­pre­ta­tion: that the virus has sim­ply spread more wide­ly than they had real­ized, pick­ing up ran­dom muta­tions along the way. Those muta­tions may or may not make the virus behave dif­fer­ent­ly.

If the S‑type of the virus is the old­er ver­sion that was cir­cu­lat­ing first, a final mys­tery remains: Why would the major­i­ty of sam­ples tak­en from the ini­tial patients in Wuhan have fall­en into the L‑type cat­e­go­ry? Shouldn’t there be more S‑types in the mix?

This is where the Chi­nese sci­en­tists make a hot­ly debat­ed leap: They sur­mise that the new­er L‑type ver­sion prob­a­bly picked up more muta­tions, and evolved fur­ther from the bat coro­n­avirus from which it orig­i­nat­ed, because it either infects peo­ple more read­i­ly or it repli­cates more vig­or­ous­ly once it infects.

In oth­er words, it’s more trans­mis­si­ble or more aggres­sive — or both.

Uni­ver­si­ty of Edin­burgh geneti­cist Andrew Ram­baut urged cau­tion about that con­clu­sion. When genet­i­cal­ly sequenced sam­ples rep­re­sent a small and hap­haz­ard­ly col­lect­ed sub­set of all infec­tions, the kinds of genet­ic vari­a­tions not­ed by the sci­en­tists are “entire­ly expect­ed,” he wrote on Twit­ter.

To claim that such muta­tions nec­es­sar­i­ly make a virus behave dif­fer­ent­ly, he added, “is a flawed infer­ence.”

A group of researchers from the MRC-Uni­ver­si­ty of Glas­gow Cen­ter for Virus Research in Scot­land offered a more detailed rebut­tal of the new paper. Among oth­er things, they said the study authors mis­in­ter­pret­ed their data and failed to account for lim­i­ta­tions in their sta­tis­ti­cal meth­ods.

“Giv­en these flaws, we believe that Tang et al. should retract their paper, as the claims made in it are clear­ly unfound­ed and risk spread­ing dan­ger­ous mis­in­for­ma­tion at a cru­cial time in the out­break,” the Glas­gow team wrote.
...

Note, you can read the back and forth between the Chi­nese team and their Glas­gow crit­ics in the com­ments of the Glas­gow teams rebut­tal. Nei­ther side appears to be con­vinced by the oth­er at this point. It high­lights how much this type of analy­sis relies on sta­tis­ti­cal guess­work.

Now here’s a New Sci­en­tist paper that describes oth­er work being done by researchers using the same GISAID data­base of sam­ples used by the Chi­nese researchers. The arti­cle describes how this emerg­ing field of real-time analy­sis of viral sam­ples — some­thing that was­n’t real­ly avail­able in past epi­demics — is use­ful but also poten­tial­ly leads to false infer­ences about which virus came first from where. They giv­en the exam­ple of the analy­sis done by Chris­t­ian Drosten, a virol­o­gist in Berlin, who sequenced a viral sam­ple in a Ger­man patient infect­ed in North­ern Italy. The viral genome looked sim­i­lar to a virus found in a patient in Bavaria a month ear­li­er and both Ger­man sam­ples shared three muta­tions no seen ear­ly on in Chi­na. Drosten real­ized that this obser­va­tion could give rise the idea that the out­break in Italy was actu­al­ly “seed­ed” by an ear­li­er out­break in Bavaria but also found it just as like­ly that the strains car­ry­ing these three muta­tions had tak­en inde­pen­dent routes from Chi­na to both Ger­many and Italy.

Drosten post­ed his find­ings on twit­ter, remain­ing con­cerned that some­one in the research com­mu­ni­ty might see the results and tweet out the the­o­ry that the out­break in Italy came from Bavaria. And sure enough, that’s exact­ly what hap­pened when anoth­er researcher, Trevor Bed­ford of the Fred Hutchin­son Can­cer Research Cen­ter, saw Drosten’s results and tweet­ed out that the Bavar­i­an out­break how not been con­tained and may have led to the North­ern Italy out­break. Bed­ford’s sug­ges­tion led to all sorts of calls for apolo­gies by Ger­many for not con­tain­ing the Bavar­i­an out­break despite claims that it had done so. Bed­ford end­ed up get­ting chas­tised by a bunch of his col­leagues for jump­ing the gun and it’s being seen as a case study of how easy it is to arrive at erro­neous con­clu­sions based on the phy­lo­ge­net­ic analy­sis of com­par­ing viral sequences and mak­ing infer­ences of how the virus spread and evolved based pri­mar­i­ly just on those sequences. But, in fair­ness, no one is say­ing that the idea that there was a hid­den spread of the virus from Bavaria to North­ern Italy has been ruled out. Instead, the crit­ics are say­ing that there are oth­er expla­na­tions for the observed data that they view as more plau­si­ble. In oth­er words, every­one is still left mak­ing edu­cat­ed guess­es here, it’s just that the broad­er researcher com­mu­ni­ty views some guess­es as more plau­si­ble than oth­ers.

The arti­cle also notes that Bed­ford used sim­i­lar phy­lo­ge­net­ic analy­sis when exam­in­ing sam­ples in Wash­ing­ton state and arrived at a con­clu­sion that did indeed pan out. Bed­ford saw a viral sam­ple in a Wash­ing­ton patient that appeared to be a direct evo­lu­tion­ary descen­dant of a viral sam­ple found in Wash­ing­ton state a month ear­li­er. It was the same sequence as before with a few more muta­tions. Based on this, Bed­ford con­clud­ed that the out­break in Wash­ing­ton state might be far more wide­spread than peo­ple real­ize. And, sure enough, that’s what was found. Wash­ing­ton state is now rec­og­nized as have a far more wide­spread out­break than was real­ized at the time Bed­ford made this con­clu­sion. So it’s not like phy­lo­ge­net­ic analy­sis is use­less. It’s just very ambigu­ous at time. And a big rea­son for that ambi­gu­i­ty is that there sim­ply haven’t been that many viral sam­ples col­lect­ed and uploaded yet. The analy­sis in the above paper by the Chi­nese researchers on the ‘L‑type’ and ‘S‑type’ strains was based on 103 sam­ples in GISAID. The analy­sis by Chris­t­ian Drosten in the fol­low­ing arti­cle was based on 350 GISAID sam­ples. But there have been over 100,000 glob­al­ly. The take home mes­sage is that many, many more viral sam­ples from the around the world are going to be required to make phy­lo­ge­net­ic analy­sis more con­clu­sive in these emerg­ing virus sit­u­a­tions:

s
New Sci­en­tist

Muta­tions can reveal how the coro­n­avirus moves—but they’re easy to over­in­ter­pret

By Kai Kupfer­schmidt
Mar. 9, 2020 , 1:00 PM

Imme­di­ate­ly after Chris­t­ian Drosten pub­lished a genet­ic sequence of the nov­el coro­n­avirus online on 28 Feb­ru­ary, he took to Twit­ter to issue a warn­ing. As the virus has raced around the world, more than 350 genome sequences have been shared on the online plat­form GISAID. They hold clues to how the new virus, named severe acute res­pi­ra­to­ry syn­drome coro­n­avirus 2 (SARS-CoV­‑2), is spread­ing and evolv­ing. But because the sequences rep­re­sent a tiny frac­tion of cas­es and show few tell­tale dif­fer­ences, they are easy to over­in­ter­pret, as Drosten real­ized.

A virol­o­gist at the Char­ité Uni­ver­si­ty Hos­pi­tal in Berlin, he had sequenced the virus from a Ger­man patient infect­ed with COVID-19 in Italy. The genome looked sim­i­lar to that of a virus found in a patient in Munich, the cap­i­tal of Bavaria, more than 1 month ear­li­er; both shared three muta­tions not seen in ear­ly sequences from Chi­na. Drosten real­ized this could give rise to the idea that the Ital­ian out­break was “seed­ed” by the one in Bavaria, which state pub­lic health offi­cials said had been quashed by trac­ing and quar­an­ti­ning all con­tacts of the 14 con­firmed cas­es. But he thought it was just as like­ly that a Chi­nese vari­ant car­ry­ing the three muta­tions had tak­en inde­pen­dent routes to both coun­tries. The new­ly sequenced genome “is not suf­fi­cient to claim a link between Munich and Italy,” Drosten tweet­ed.

His warn­ing went unheed­ed. A few days lat­er, Trevor Bed­ford of the Fred Hutchin­son Can­cer Research Cen­ter, who ana­lyzes the stream of viral genomes and dis­cuss­es them in Twit­ter threads, wrote that the pat­tern sug­gest­ed the out­break in Bavaria had not been con­tained after all, and appeared to have led to the Ital­ian out­break. The analy­sis spread wide­ly. Tech­nol­o­gy Review assert­ed that “the Munich event could be linked to a decent part of the over­all Euro­pean out­break” and Twit­ter users called on Ger­many to apol­o­gize. (This Sci­ence cor­re­spon­dent retweet­ed Bedford’s thread as well.)

Virol­o­gist Eeva Broberg of the Euro­pean Cen­tre for Dis­ease Pre­ven­tion and Con­trol agrees with Drosten that there are more plau­si­ble sce­nar­ios for how the dis­ease reached north­ern Italy than an unde­tect­ed spread from Bavaria. Oth­er sci­en­tists say Bed­ford jumped the gun as well. “I have to kick his butt a bit for this,” says Richard Neher, a com­pu­ta­tion­al biol­o­gist at the Uni­ver­si­ty of Basel who works with Bed­ford. “It’s a cau­tion­ary tale,” says Andrew Ram­baut, a mol­e­c­u­lar evo­lu­tion­ary biol­o­gist at the Uni­ver­si­ty of Edin­burgh. “There is no way you can make that claim just from the phy­loge­ny alone.” Bed­ford lat­er clar­i­fied he believed it was equal­ly plau­si­ble there had been two sep­a­rate intro­duc­tions from Chi­na. “I think I should have been more care­ful with that Twit­ter thread,” he says.

It was a case study in the pow­er and pit­falls of real-time analy­sis of viral genomes. “This is an incred­i­bly impor­tant dis­ease. We need to under­stand how it is mov­ing,” says Bette Kor­ber, a biol­o­gist at Los Alam­os Nation­al Lab­o­ra­to­ry who is also study­ing the genome of SARS-CoV­‑2. “With very lim­it­ed evo­lu­tion dur­ing the out­break, [these researchers] are doing what they can and they are mak­ing sug­ges­tions, which I think at this point should be tak­en as sug­ges­tions.”

The sequence data were most infor­ma­tive ear­ly on, says Kris­t­ian Ander­sen, a com­pu­ta­tion­al biol­o­gist at Scripps Research. The very first sequence, in ear­ly Jan­u­ary, answered the most basic ques­tion: What pathogen is caus­ing the dis­ease? The ones that fol­lowed were almost iden­ti­cal, strong­ly sug­gest­ing there was a sin­gle intro­duc­tion from an ani­mal into the human pop­u­la­tion. If the virus had jumped the species bar­ri­er mul­ti­ple times, sci­en­tists would see more vari­ety among the first human cas­es.

Now, more diver­si­ty is emerg­ing. Like all virus­es, SARS-CoV­‑2 evolves over time through ran­dom muta­tions, only some of which are caught and cor­rect­ed by the virus’s error cor­rec­tion machin­ery. Over the length of its 30,000-base-pair genome, SARS-CoV­‑2 accu­mu­lates an aver­age of about one to two muta­tions per month, Ram­baut says. “It’s about two to four times slow­er than the flu,” he says. Using these lit­tle changes, researchers can draw up phy­lo­ge­net­ic trees, much like fam­i­ly trees. They can also make con­nec­tions between dif­fer­ent cas­es of COVID-19 and gauge whether there might be unde­tect­ed spread of the virus.

For instance, when researchers sequenced the sec­ond virus genome in Washington—from a teenag­er diag­nosed with COVID-19 on 27 February—it looked like a direct descen­dant of the first genome, a case found 6 weeks ear­li­er, that had acquired three fur­ther muta­tions. Bed­ford tweet­ed that he con­sid­ered it “high­ly unlike­ly” that the two genomes came from sep­a­rate intro­duc­tions. “I believe we are fac­ing an already sub­stan­tial out­break in Wash­ing­ton State that was not detect­ed until now,” he wrote. That analy­sis turned out to be cor­rect: Wash­ing­ton has now report­ed more than 100 cas­es and 15 deaths and addi­tion­al genomes from oth­er patients have bol­stered the link. In this case, Bedford’s hypoth­e­sis was much stronger because the two patients both came from Sno­homish Coun­ty, Ram­baut says: “It’s very unlike­ly that this high­ly relat­ed virus would trav­el to exact­ly the same town in Wash­ing­ton,” he says.

Few oth­er firm con­clu­sions about the virus’s spread have emerged, in part because the wealth of genomes is still a tiny sam­ple of the more than 100,000 cas­es world­wide. Although Chi­na accounts for 80% of all COVID-19 cas­es, only one-third of the pub­lished genomes are from Chi­na—and very few of them are from lat­er cas­es. And because it’s ear­ly in the out­break, most genomes are still very sim­i­lar, which makes it hard to draw con­clu­sions. “We just have this hand­ful of muta­tions, which makes these group­ings so ambigu­ous,” Neher says. “As the out­break unfolds, we expect to see more and more diver­si­ty and more clear­ly dis­tinct lin­eages,” he says. “And then it will become eas­i­er and eas­i­er to actu­al­ly put things togeth­er.”

Sci­en­tists will also be scour­ing the genom­ic diver­si­ty for muta­tions that might change how dan­ger­ous the pathogen is or how fast it spreads. There, too, cau­tion is war­rant­ed. A paper pub­lished by Lu Jian of Peking Uni­ver­si­ty and col­leagues on 3 March in the jour­nal Nation­al Sci­ence Review ana­lyzed 103 virus genomes and argued that they fell into one of two dis­tinct types, named S and L, dis­tin­guished by two muta­tions. Because 70% of sequenced SARS-CoV­‑2 genomes belong to L, the new­er type, the authors con­clud­ed that virus has evolved to become more aggres­sive and to spread faster.

But they lack evi­dence, Ram­baut says. “What they’ve done is basi­cal­ly seen these two branch­es and said, ‘That one is big­ger, [so that virus] must be more vir­u­lent or more trans­mis­si­ble,’” he says. How­ev­er, just because a virus is export­ed and leads to a large out­break else­where does not mean it is behav­ing dif­fer­ent­ly: “One of these lin­eages is going to be big­ger than the oth­er just by chance.” Some researchers have called for the paper to be retract­ed. “The claims made in it are clear­ly unfound­ed and risk spread­ing dan­ger­ous mis­in­for­ma­tion at a cru­cial time in the out­break,” four sci­en­tists at the Uni­ver­si­ty of Glas­gow wrote in a response pub­lished on http://www.virological.org. (In a response, Lu wrote the four had mis­un­der­stood his study.)

Most genom­ic changes don’t alter the virus’s behav­ior, Drosten says. The only way to con­firm that a muta­tion has an effect is to study it in cell cul­tures or ani­mal mod­els and show, for instance, that it has become bet­ter at enter­ing cells or trans­mit­ting, he says. And if the virus does change in an impor­tant way, it could go either way, mak­ing it more or less dan­ger­ous. In 2018, Drosten’s group pub­lished a paper show­ing that ear­ly in the SARS out­break of 2002-03, that virus lost a small chunk of its genome, 29 base pairs in one gene. Adding those base pairs back in the lab made the virus much bet­ter at repli­cat­ing in sev­er­al cell cul­ture mod­els.

....

———-

“Muta­tions can reveal how the coro­n­avirus moves—but they’re easy to over­in­ter­pret” by Kai Kupfer­schmidt; New Sci­en­tist; 03/09/2020

“It was a case study in the pow­er and pit­falls of real-time analy­sis of viral genomes. “This is an incred­i­bly impor­tant dis­ease. We need to under­stand how it is mov­ing,” says Bette Kor­ber, a biol­o­gist at Los Alam­os Nation­al Lab­o­ra­to­ry who is also study­ing the genome of SARS-CoV­‑2. “With very lim­it­ed evo­lu­tion dur­ing the out­break, [these researchers] are doing what they can and they are mak­ing sug­ges­tions, which I think at this point should be tak­en as sug­ges­tions.””

A case study in hte pow­er and pit­falls of real=time analy­sis if viral genomes. That’s how the ker­fuf­fle was described involv­ing Chris­t­ian Drosten’s tweet­ing of his find­ings that was inter­pret­ed by Trevor Bed­ford as evi­dence that the out­break in North­ern Italy came from Bavaria. Of course, no one has proven that the out­break did­n’t come from Bavaria. It’s just that there were many oth­er pos­si­ble, and per­haps more plau­si­ble, expla­na­tions for the obser­va­tion that a Ger­man patient in North­ern Italy was infect­ed with a strain that looked very sim­i­lar to the strain asso­ci­at­ed with an out­break in Bavaria a month earlier...an out­break that was sup­posed to be con­tained:

...
Imme­di­ate­ly after Chris­t­ian Drosten pub­lished a genet­ic sequence of the nov­el coro­n­avirus online on 28 Feb­ru­ary, he took to Twit­ter to issue a warn­ing. As the virus has raced around the world, more than 350 genome sequences have been shared on the online plat­form GISAID. They hold clues to how the new virus, named severe acute res­pi­ra­to­ry syn­drome coro­n­avirus 2 (SARS-CoV­‑2), is spread­ing and evolv­ing. But because the sequences rep­re­sent a tiny frac­tion of cas­es and show few tell­tale dif­fer­ences, they are easy to over­in­ter­pret, as Drosten real­ized.

A virol­o­gist at the Char­ité Uni­ver­si­ty Hos­pi­tal in Berlin, he had sequenced the virus from a Ger­man patient infect­ed with COVID-19 in Italy. The genome looked sim­i­lar to that of a virus found in a patient in Munich, the cap­i­tal of Bavaria, more than 1 month ear­li­er; both shared three muta­tions not seen in ear­ly sequences from Chi­na. Drosten real­ized this could give rise to the idea that the Ital­ian out­break was “seed­ed” by the one in Bavaria, which state pub­lic health offi­cials said had been quashed by trac­ing and quar­an­ti­ning all con­tacts of the 14 con­firmed cas­es. But he thought it was just as like­ly that a Chi­nese vari­ant car­ry­ing the three muta­tions had tak­en inde­pen­dent routes to both coun­tries. The new­ly sequenced genome “is not suf­fi­cient to claim a link between Munich and Italy,” Drosten tweet­ed.

His warn­ing went unheed­ed. A few days lat­er, Trevor Bed­ford of the Fred Hutchin­son Can­cer Research Cen­ter, who ana­lyzes the stream of viral genomes and dis­cuss­es them in Twit­ter threads, wrote that the pat­tern sug­gest­ed the out­break in Bavaria had not been con­tained after all, and appeared to have led to the Ital­ian out­break. The analy­sis spread wide­ly. Tech­nol­o­gy Review assert­ed that “the Munich event could be linked to a decent part of the over­all Euro­pean out­break” and Twit­ter users called on Ger­many to apol­o­gize. (This Sci­ence cor­re­spon­dent retweet­ed Bedford’s thread as well.)

Virol­o­gist Eeva Broberg of the Euro­pean Cen­tre for Dis­ease Pre­ven­tion and Con­trol agrees with Drosten that there are more plau­si­ble sce­nar­ios for how the dis­ease reached north­ern Italy than an unde­tect­ed spread from Bavaria. Oth­er sci­en­tists say Bed­ford jumped the gun as well. “I have to kick his butt a bit for this,” says Richard Neher, a com­pu­ta­tion­al biol­o­gist at the Uni­ver­si­ty of Basel who works with Bed­ford. “It’s a cau­tion­ary tale,” says Andrew Ram­baut, a mol­e­c­u­lar evo­lu­tion­ary biol­o­gist at the Uni­ver­si­ty of Edin­burgh. “There is no way you can make that claim just from the phy­loge­ny alone.” Bed­ford lat­er clar­i­fied he believed it was equal­ly plau­si­ble there had been two sep­a­rate intro­duc­tions from Chi­na. “I think I should have been more care­ful with that Twit­ter thread,” he says.
...

And it’s not like the log­ic that Bed­ford used to arrive at his con­clu­sion about the Bavar­i­an case was fun­da­men­tal­ly flawed. He made a sim­i­lar con­clu­sion about Wash­ing­ton state that turned out to be cor­rect. There real­ly was a hid­den epi­dem­ic going on in Wash­ing­ton state that had­n’t yet been found and it was based on com­par­ing the viral genomes of patients and mak­ing infer­ences that Bed­ford arrived at that cor­rect and pre­scient con­clu­sion. And since the virus start­ed off rel­a­tive­ly homo­ge­neous in Chi­na and has been acquir­ing new muta­tions as it spreads around the world, about one to two new muta­tions per month, it seems rea­son­able that this form of analy­sis is only going to become more and more use­ful for track­ing the spread:

...
The sequence data were most infor­ma­tive ear­ly on, says Kris­t­ian Ander­sen, a com­pu­ta­tion­al biol­o­gist at Scripps Research. The very first sequence, in ear­ly Jan­u­ary, answered the most basic ques­tion: What pathogen is caus­ing the dis­ease? The ones that fol­lowed were almost iden­ti­cal, strong­ly sug­gest­ing there was a sin­gle intro­duc­tion from an ani­mal into the human pop­u­la­tion. If the virus had jumped the species bar­ri­er mul­ti­ple times, sci­en­tists would see more vari­ety among the first human cas­es.

Now, more diver­si­ty is emerg­ing. Like all virus­es, SARS-CoV­‑2 evolves over time through ran­dom muta­tions, only some of which are caught and cor­rect­ed by the virus’s error cor­rec­tion machin­ery. Over the length of its 30,000-base-pair genome, SARS-CoV­‑2 accu­mu­lates an aver­age of about one to two muta­tions per month, Ram­baut says. “It’s about two to four times slow­er than the flu,” he says. Using these lit­tle changes, researchers can draw up phy­lo­ge­net­ic trees, much like fam­i­ly trees. They can also make con­nec­tions between dif­fer­ent cas­es of COVID-19 and gauge whether there might be unde­tect­ed spread of the virus.

For instance, when researchers sequenced the sec­ond virus genome in Washington—from a teenag­er diag­nosed with COVID-19 on 27 February—it looked like a direct descen­dant of the first genome, a case found 6 weeks ear­li­er, that had acquired three fur­ther muta­tions. Bed­ford tweet­ed that he con­sid­ered it “high­ly unlike­ly” that the two genomes came from sep­a­rate intro­duc­tions. “I believe we are fac­ing an already sub­stan­tial out­break in Wash­ing­ton State that was not detect­ed until now,” he wrote. That analy­sis turned out to be cor­rect: Wash­ing­ton has now report­ed more than 100 cas­es and 15 deaths and addi­tion­al genomes from oth­er patients have bol­stered the link. In this case, Bedford’s hypoth­e­sis was much stronger because the two patients both came from Sno­homish Coun­ty, Ram­baut says: “It’s very unlike­ly that this high­ly relat­ed virus would trav­el to exact­ly the same town in Wash­ing­ton,” he says.
...

Also keep in mind that the fact that the viral genome appeared to be almost iden­ti­cal ear­ly on could itself be a ‘founder effect’ where it hap­pened to be the case that a par­tic­u­lar strain infect­ed Wuhan and there­fore almost all the sam­ples col­lect­ed were of that strain and seemed iden­ti­cal. It does­n’t nec­es­sar­i­ly mean that there weren’t pre­vi­ous strains that had been qui­et­ly spread­ing around before hit­ting Wuhan.

The arti­cle also men­tions the con­tro­ver­sy over the above ‘L‑type’ and ‘S‑type’ paper by the Chi­nese researchers. Note how it describes the ‘L‑type’ strain as the ‘new­er’ one. And Andrew Ram­baut, who is again quot­ed with his crit­i­cism of that paper, was real­ly just focus­ing his crit­i­cisms on the infer­ence by the researchers that the ‘L‑type’ strain was more aggres­sive. Now, the Glas­gow team crit­ics of the paper do indeed ques­tion whether or not the ‘L‑type’ strain real­ly is new­er, but almost every­one else seems to accept the like­li­hood that it real­ly did emerge after the ‘S‑type’ strain. This is going to be one of the key things to watch in this ongo­ing debate in terms of deter­min­ing where the virus jumped to humans:

...
Sci­en­tists will also be scour­ing the genom­ic diver­si­ty for muta­tions that might change how dan­ger­ous the pathogen is or how fast it spreads. There, too, cau­tion is war­rant­ed. A paper pub­lished by Lu Jian of Peking Uni­ver­si­ty and col­leagues on 3 March in the jour­nal Nation­al Sci­ence Review ana­lyzed 103 virus genomes and argued that they fell into one of two dis­tinct types, named S and L, dis­tin­guished by two muta­tions. Because 70% of sequenced SARS-CoV­‑2 genomes belong to L, the new­er type, the authors con­clud­ed that virus has evolved to become more aggres­sive and to spread faster.

But they lack evi­dence, Ram­baut says. “What they’ve done is basi­cal­ly seen these two branch­es and said, ‘That one is big­ger, [so that virus] must be more vir­u­lent or more trans­mis­si­ble,’” he says. How­ev­er, just because a virus is export­ed and leads to a large out­break else­where does not mean it is behav­ing dif­fer­ent­ly: “One of these lin­eages is going to be big­ger than the oth­er just by chance.” Some researchers have called for the paper to be retract­ed. “The claims made in it are clear­ly unfound­ed and risk spread­ing dan­ger­ous mis­in­for­ma­tion at a cru­cial time in the out­break,” four sci­en­tists at the Uni­ver­si­ty of Glas­gow wrote in a response pub­lished on http://www.virological.org. (In a response, Lu wrote the four had mis­un­der­stood his study.)
...

Over­all, the mes­sage appears to be that we need to have far more viral sequences avail­able for researchers if this form of analy­sis is going to yield more con­clu­sive results:

...
Few oth­er firm con­clu­sions about the virus’s spread have emerged, in part because the wealth of genomes is still a tiny sam­ple of the more than 100,000 cas­es world­wide. Although Chi­na accounts for 80% of all COVID-19 cas­es, only one-third of the pub­lished genomes are from Chi­na—and very few of them are from lat­er cas­es. And because it’s ear­ly in the out­break, most genomes are still very sim­i­lar, which makes it hard to draw con­clu­sions. “We just have this hand­ful of muta­tions, which makes these group­ings so ambigu­ous,” Neher says. “As the out­break unfolds, we expect to see more and more diver­si­ty and more clear­ly dis­tinct lin­eages,” he says. “And then it will become eas­i­er and eas­i­er to actu­al­ly put things togeth­er.”
...

So, relat­ing this all back to that orig­i­nal Chi­nese paper cit­ed by Lar­ry Romanof­f’s Glob­al Research arti­cle, it’s worth not­ing that more viral sam­ples — espe­cial­ly sam­ples from across the US — would prob­a­bly be real­ly help­ful in con­firm­ing whether or not the virus real­ly did emerge from the Unit­ed States first as sug­gest­ed by their analy­sis.

And that’s part of what is mak­ing the US fed­er­al gov­ern­men­t’s incred­i­ble blun­ders on releas­ing ade­quate num­bers of COVID-19 test kits or non-func­tion­ing kits in the US so scan­dalous: thanks to the Trump admin­is­tra­tion’s appar­ent lack of inter­est in detect­ing new cas­es, we’re los­ing invalu­able oppor­tu­ni­ties for assess­ing which strains are float­ing around the US and, in turn, the abil­i­ty to infer how long they’ve been float­ing there. Keep in mind that the infer­ences by the Chi­nese researchers — that because only two out of the 5 sub­groups were found in Hubei but all 5 were found in the US and there­fore the US was like­ly the orig­i­na­tor or the virus — is only pos­si­ble expla­na­tion for the data. For exam­ple, per­haps the virus evolved as it spread around the world from Chi­na and, thanks in part of the US’s lax atti­tude on test­ing and the large num­ber of peo­ple that trav­el to the US from around the world, the US sim­ply became a des­ti­na­tion spot for pret­ty much every ver­sion of the virus that mutat­ed else­where. In an age of air­plane trav­el the con­clu­sion that more viral diver­si­ty in a loca­tion means the virus was there longer does­n’t nec­es­sar­i­ly apply. But it could apply. Again, it’s all guess. We don’t know. What we know is that a lot more data, espe­cial­ly from the US, would be very use­ful in assess­ing whether or not the virus broke out in the US ear­li­er than rec­og­nized and that data col­lec­tion has been sys­tem­at­i­cal­ly thwart­ed by the Trump admin­is­tra­tion’s incred­i­ble blun­der­ing with the test kits. If we don’t know some­one has the virus we can’t sequence their viral genomes. So while many have under­stand­ably inferred that the Trump admin­is­tra­tion’s lack­adaisi­cal atti­tude towards the test kits is dri­ven by Trump’s desire not to find new cas­es in the US, it’s worth keep­ing in mind that the Trump admin­is­tra­tion might also not want to find out which strains have been cir­cu­lat­ing in the US and how long they’ve been cir­cu­lat­ing too.

@Pterrafractyl–

Good show! This explains some of the back and forth via the sci­en­tif­ic research in some­thing oth­er than the “weaponized” media cov­er­age we have been see­ing.

I will add a note about this to the descrip­tion for FTR #1118.

Best,

Dave

As glob­al finan­cials mar­kets con­tin­ue to melt down over the COVID-19 coro­n­avirus achiev­ing pan­dem­ic sta­tus, one of the big ques­tions that has yet to be answered by any world leader is what a mean­ing­ful Big Pic­ture plan for address­ing the virus might actu­al­ly look like and what kind of time­frame we should expect for impos­ing the most extreme mea­sures like shut­ting down trav­el, clos­ing schools, and min­i­miz­ing crowds. Beyond ‘slow­ing the spread’, we haven’t real­ly heard much about what the end game is for what could end this kind of emer­gency now that it’s hit pan­dem­ic sta­tus, a sta­tus the virus was prob­a­bly always was going to hit giv­en its lev­el of infec­tious­ness and abil­i­ty to spread asymp­to­mati­cal­ly. So is the plan to just slow the spread down as much as pos­si­ble so health sys­tems aren’t over­whelmed while we wait for a vac­cine to be devel­oped? Because it sounds like a vac­cine isn’t going to be avail­able at least until next year. Are we look­ing at a glob­al lock­down sit­u­a­tion for the rest of 2020?

It’s that ambi­gu­i­ty about the time­frame of these extreme mea­sures that’s prob­a­bly going to make the devel­op­ment of drugs to treat the most severe cas­es a major fac­tor in how the world responds to this. After all, the aspect of this dis­ease that makes it such an emer­gency is its high lethal­i­ty for cer­tain demo­graph­ics. The vast major­i­ty of peo­ple should be large­ly fine if they get the dis­ease but for the elder­ly or peo­ple with com­pro­mised immune sys­tems and med­ical con­di­tions like dia­betes it has an alarm­ing­ly high fatal­i­ty rate. That alarm­ing­ly high fatal­i­ty rate for cer­tain demo­graph­ics com­bined with its high lev­el of infec­tious­ness makes this the kind of virus that can shut a soci­ety down. So if there’s a drug avail­able that can effec­tive­ly treat those severe cas­es that could real­ly fun­da­men­tal­ly shift the nature of the cur­rent glob­al alarm. In oth­er words, the devel­op­ment of an effec­tive drug for the severe cas­es is prob­a­bly the devel­op­ment that could fun­da­men­tal­ly shift the dynam­ic of this pan­dem­ic the soon­est.

And that’s why the glob­al focus on Gilead­’s drug remde­sivir as the top can­di­date for treat­ing the drug con­tin­ues to be rather dis­turb­ing. Because at this point the world real­ly should be aggres­sive­ly pur­su­ing as many clin­i­cal tri­als on as many promis­ing treat­ments as pos­si­ble. And yet the WHO has declared remde­sivir to be the ONLY can­di­date drug show­ing promise as a treat­ment We still have no expla­na­tion as to why there con­tin­ues to be almost no appar­ent inter­est in the “Thai cock­tail” of treat­ment that demon­strat­ed a dra­mat­ic improve­ment in two severe­ly ill patients in Thai­land. It’s remde­sivir or bust it seems, which means if the remde­sivir clin­i­cal tri­als under­way don’t show the hoped for results that’s going to extend the cur­rent state of glob­al hyper-alarm that much longer.

With that in mind, here’s an arti­cle about the focus on Gilead­’s drug remde­sivir and how it’s being tout­ed as our best hope for an effec­tive drug to treat COVID-19. The arti­cle isn’t exact­ly reas­sur­ing. It describes how remde­sivir was orig­i­nal­ly devel­oped by Gilead to treat Ebo­la vic­tims a decade ago but it turned out to be a sur­pris­ing dis­ap­point­ment. Part of what made it sur­pris­ing was that the drug respond­ed well when test­ed against the virus in labs and with ani­mals. But when tried on human Ebo­la vic­tims it just did­n’t seem to help very much.

Here’s why that his­to­ry with Ebo­la treat­ments does­n’t exact­ly bode well in terms of the prospects of remde­sivir’s clin­i­cal tri­als on COVID-19 vic­tims: A big part of the rea­son the World Health Orga­ni­za­tion (WHO) has already declared remde­sivir its top can­di­date drug for treat­ing COVID-19 is because of its demon­strat­ed suc­cess against oth­er virus­es and is seen as a “broad spec­trum” antivi­ral that has a bet­ter chance than oth­er can­di­date drugs of gener­i­cal­ly work­ing against new­ly emerg­ing virus­es. And those are all good rea­sons for opti­mism. “Broad spec­trum” antivi­rals are kind of ide­al when you’re deal­ing with a virus you don’t under­stand. The prob­lem is those demon­strat­ed suc­cess­es against oth­er virus­es were in the lab and with ani­mals. Remde­sivir has­n’t been test­ed on humans at all for oth­er coro­n­avirus­es like SARS or MERS. In oth­er words, the cur­rent opti­mism looks a lot like the opti­mism about its effi­ca­cy towards Ebo­la.

Now, Ebo­la isn’t COVID-19 and it’s entire­ly pos­si­ble the drug real­ly will be effec­tive. Recall that there has indeed been a sin­gle report­ed case of a severe­ly ill COVID-19 patient improv­ing after receiv­ing the drug.

But it’s note­wor­thy that one of the finan­cial ana­lysts who has been bull­ish on Gilead­’s stock said last week that he only sees a 50 per­cent chance of remde­sivir’s clin­i­cal tri­als actu­al­ly suc­ceed­ing as a treat­ment. Grant­ed, this is a finan­cial ana­lysts we’re talk­ing about and not a med­ical expert. But that ana­lyst, Bri­an Abra­hams, is still some­one who spe­cial­ized in biotech stocks so he’s pre­sum­ably has a back­ground in biol­o­gy and a lot of expe­ri­ence watch­ing these kinds of clin­i­cal tri­als play out.

One pos­si­ble source of opti­mism is that we’re told that the poor results in the Ebo­la tri­al on humans may have had less to do with the effec­tive­ness of the drug against the virus and more to do with the dif­fi­cul­ty in trans­port­ing and admin­is­ter­ing the drug in the remote loca­tions where the Ebo­la vic­tims were get­ting treat­ed. It sounds like the drug need­ed to freeze dried for trans­porta­tion and then recon­sti­tut­ed on sight and admin­is­tered to patients with an IV. That’s a lot more prone to com­pli­ca­tions than just giv­ing some­one a pill. So it’s pos­si­ble there were tech­ni­cal dif­fi­cul­ties in treat­ing Ebo­la patients that would­n’t be faced in a hos­pi­tal set­ting. Of course, that also means remde­sivir may not be very use­ful in much of devel­op­ing world even if it does work in first-world hos­pi­tals. And if this virus ends up remain­ing a pan­dem­ic in the devel­op­ing world that’s still going to be a human­i­tar­i­an and cre­ate chaos when it comes to inter­na­tion­al trav­el and trade even if first world coun­tries can effec­tive­ly treat patients.

The arti­cle also men­tions that Gilead is get­ting flood­ed with requests for sam­ples of the drug in the mean time on a “com­pas­sion­ate use” basis. It’s unclear how many of those requests are being made but the Gildead issued a state­ment that it is review­ing indi­vid­ual requests from physi­cians to pro­vide it a “com­pas­sion­ate use” basis but only to patients who are hos­pi­tal­ized and show­ing “sig­nif­i­cant clin­i­cal man­i­fes­ta­tions.” So Gilead is “review” requests, which sounds like no one has actu­al­ly received the drug from com­pas­sion­ate use yet.

And these urgent requests for com­pas­sion­ate use of a drug that has­n’t been ver­i­fied in clin­i­cal tri­als again rais­es the ques­tion of why we aren’t hear­ing more reports about the “Thai cock­tail” being used on these patients. It seems like we should be hear at least some­thing about the most severe patients hav­ing the cock­tail tried on them, whether or not the results are pos­i­tive or neg­a­tive. The drugs that make of the cock­tail are read­i­ly avail­able for use in humans. That’s part of what makes them poten­tial­ly so appeal­ing as an imme­di­ate rem­e­dy. So if doc­tors are will­ing to request an unver­i­fied drug from Gilead for com­pas­sion­ate use, why is there seem­ing­ly so lit­tle inter­est in the “Thai cock­tail”? It’s gen­uine­ly baf­fling.

The first clin­i­cal tri­al results for remde­sivir are expect­ed to be com­plet­ed some time in April. If it’s a suc­cess, it seems like a good chance that could be the kind of event that would dra­mat­i­cal­ly change the nature of the sit­u­a­tion. But if it’s not a suc­cess, well, we bet­ter hope one of the oth­er drugs under­go­ing tri­als ends up demon­strat­ing suc­cess­es soon because it’s the devel­op­ment of a that’s like­ly the soon­est devel­op­ment that could fun­da­men­tal­ly shift the nature of this glob­al pan­ic:

The Wash­ing­ton Post

The best hope for coro­n­avirus treat­ment is an exper­i­men­tal drug that fiz­zled against Ebo­la

By Christo­pher Row­land
March 11, 2020 at 10:28 AM EDT

Med­ical researchers spent much of the past year try­ing to save Ebo­la vic­tims in Con­go using a clutch of exper­i­men­tal drugs. Of the four med­ica­tions being test­ed, researchers said, one demon­strat­ed espe­cial­ly poor abil­i­ty to save patients from the dead­ly virus.

The drug, called remde­sivir, had blocked the Ebo­la virus in lab­o­ra­to­ries and in ani­mal exper­i­ments. But it did such a bad job extend­ing sur­vival in humans com­pared to two of the oth­er treat­ments that researchers decid­ed in August not to try it on any more patients.

Now the drug, cre­at­ed by phar­ma­ceu­ti­cal giant Gilead Sci­ences, is being test­ed in new clin­i­cal tri­als, and glob­al health author­i­ties deem it the most promis­ing of pos­si­ble treat­ments for peo­ple who are severe­ly ill with the nov­el coro­n­avirus, which caus­es the covid-19 dis­ease. Because it is a “broad spec­trum’’ drug that has been effec­tive against mul­ti­ple viral tar­gets in the lab and in ani­mals, the strat­e­gy could work, experts said.

The drug’s jour­ney — from fail­ing to pro­long the lives of Ebo­la patients in sub-Saha­ran Africa just last year to being rushed into coro­n­avirus clin­i­cal tri­als in Chi­na and the Unit­ed States this year — sym­bol­izes a dire lack of antivi­ral drugs that can fight emerg­ing infec­tious threats.

As the out­break spreads world­wide, a vac­cine to pre­vent infec­tion remains at least a year away. Mean­while, there is no approved treat­ment to stop the virus once some­one is infect­ed, and the severe and some­times fatal res­pi­ra­to­ry dis­tress that afflicts a minor­i­ty of patients.

The hope is that remde­sivir will show bet­ter results with the coro­n­avirus than it did with Ebo­la, which is from a dif­fer­ent viral fam­i­ly, offi­cials said. The first tri­al results could be avail­able in April.

Gilead, the Nation­al Insti­tutes of Health and Chi­nese health author­i­ties are rac­ing to test it on hun­dreds of peo­ple in con­trolled clin­i­cal tri­als, includ­ing a patient who was quar­an­tined in Nebras­ka after being removed from the Dia­mond Princess cruise ship. Axios report­ed this month that Gilead act­ed so quick­ly that it did not even wait for required approval by the Food and Drug Admin­is­tra­tion before it shipped dos­es to Chi­na. Asked to respond, Gilead said it thinks its “lim­it­ed ship­ments’’ were made in com­pli­ance with U.S. law.

“I just hope remde­sivir works, because we real­ly need a ther­a­peu­tic that can inter­vene in this cri­sis,’’ said Richard Whit­ley, direc­tor of an NIH-fund­ed research effort involv­ing the world’s most dan­ger­ous virus­es.

...

Invent­ed by Gilead about a decade ago, remde­sivir has been proven to stop cer­tain virus­es from repli­cat­ing in lab exper­i­ments and in ani­mals. It has been researched in aca­d­e­m­ic labs in North Car­oli­na and Ten­nessee with back­ing from fed­er­al tax­pay­ers since 2014, as part of a $37.5 mil­lion effort by NIH to find treat­ments for infec­tious dis­eases.

Until Mon­day, when it fell in a bru­tal mar­ket rout, Gilead’s stock price had defied the over­all mar­ket decline of recent weeks, ris­ing almost 20 per­cent from Feb. 21 to March 6, on hopes that the drug could pro­vide the first treat­ment for covid-19.

The lack of treat­ment helps explain why. The stock price increased 5 per­cent on Feb. 24 alone when a top offi­cial of the World Health Orga­ni­za­tion pinned much of the world’s hopes for a treat­ment on the drug.

“There is only one drug right now that we think may have real effi­ca­cy, and that’s remde­sivir,” said Bruce Ayl­ward, WHO’s assis­tant direc­tor gen­er­al. Ten days lat­er, RBC Cap­i­tal Mar­kets gave it only a 50 per­cent chance of suc­ceed­ing as a treat­ment.

The mixed sig­nals have done lit­tle to damp­en inter­est. There have been des­per­ate pleas for sup­plies to treat patients on a “com­pas­sion­ate use’’ basis.

Although Gilead leads the pack on treat­ments, large drug com­pa­nies such as Mer­ck, John­son & John­son and Sanofi, as well as less­er-known com­pa­nies Regen­eron and Mod­er­na, are pur­su­ing coro­n­avirus vac­cines and med­ica­tions, and exec­u­tives esti­mate that at least 40 small biotech com­pa­nies are devel­op­ing drugs to fight it.

Every time there is a new virus, “we get start­ed, but we don’t cross the fin­ish line,’’ Julie Ger­berd­ing, a for­mer direc­tor of the Cen­ters for Dis­ease Con­trol and Pre­ven­tion who is now the exec­u­tive vice pres­i­dent and chief patient offi­cer at Mer­ck, said at a news brief­ing in Wash­ing­ton last week. This time, she said, indus­try is com­mit­ted to push­ing a vac­cine to cross the line for reg­u­la­to­ry approval.

“If we don’t cross it, it will be because it’s sci­en­tif­i­cal­ly hard,’’ she said, “not because of the will or the invest­ment.’’

But drug com­pa­nies also have been accused of not pur­su­ing vac­cines and antivi­ral treat­ments aggres­sive­ly because the com­mer­cial mar­kets for such drugs are weak.

The poten­tial patient pool for clin­i­cal tri­als dries up once a new infec­tious out­break sub­sides, so invest­ment can be frozen in part­ly com­plet­ed projects. And the pool of med­ical cus­tomers for a drug can be short-lived, if a sea­son­al epi­dem­ic quick­ly dis­ap­pears, offer­ing lit­tle chance to recoup an invest­ment of what could be hun­dreds of mil­lions of dol­lars.

Vac­cine and treat­ment devel­op­ment tailed off after out­breaks of the ear­li­er coro­n­avirus cousins, severe acute res­pi­ra­to­ry syn­drome (SARS) and Mid­dle East res­pi­ra­to­ry syn­drome (MERS). The drug industry’s lob­by­ing arm, the Phar­ma­ceu­ti­cal Research and Man­u­fac­tur­ers of Amer­i­ca (PhRMA), said that at least half of its mem­bers have mobi­lized in var­i­ous ways to fight the new coro­n­avirus in recent weeks.

“We need to encour­age as many shots on goal as pos­si­ble,’’ Stephen J. Ubl, PhRMA’s chief exec­u­tive offi­cer, told reporters.

Gov­ern­ment efforts to spur devel­op­ment have pro­duced spo­radic progress. In the near­ly 20 years since the SARS out­break, the Nation­al Insti­tutes of Health has spent near­ly $700 mil­lion on research and devel­op­ment efforts around coro­n­avirus, accord­ing to a sur­vey by the advo­ca­cy group Pub­lic Cit­i­zen, which crit­i­cized the phar­ma­ceu­ti­cal indus­try for a “lack of inter­est that has left us lag­ging behind.’’

Every epi­dem­ic presents uncer­tain­ty for drug com­pa­nies, said Amesh Adal­ja, a senior schol­ar for the Cen­ter for Health Secu­ri­ty at Johns Hop­kins Uni­ver­si­ty.

“You nev­er know how long it’s going to last. You nev­er know what the mar­ket size is going to be,’’ he said. “Every con­ver­sa­tion about price is when you’re in the mid­dle of an emer­gency.’’

Giv­en the large degree of pub­lic finan­cial sup­port, debates are already flar­ing about how much Gilead should charge for its treat­ment if it ever makes it to mar­ket.

Con­gress and Pres­i­dent Trump autho­rized up to $3 bil­lion last week for efforts by aca­d­e­m­ic researchers and drug com­pa­nies to devel­op vac­cines and treat­ments for coro­n­avirus, part of an $8.3 bil­lion emer­gency spend­ing bill. The indus­try suc­cess­ful­ly opposed efforts by some House Democ­rats to attach guar­an­tees for afford­able prices for vac­cines or treat­ments that result.

Gilead said it is too soon to dis­cuss poten­tial mar­kets, in writ­ten respons­es to The Wash­ing­ton Post.

“We are focused on the poten­tial clin­i­cal val­ue that remde­sivir may bring to patients and doing our part to respond to the coro­n­avirus out­break,’’ the com­pa­ny said.

Ear­li­er test­ing of remde­sivir has been per­formed by a part­ner­ship of uni­ver­si­ty aca­d­e­mics and the Nation­al Insti­tutes of Health called the Antivi­ral Drug Dis­cov­ery and Devel­op­ment Cen­ter, coor­di­nat­ed by the Uni­ver­si­ty of Alaba­ma at Birm­ing­ham. It is focused on find­ing treat­ments for the fam­i­ly of coro­n­avirus­es, as well as Ebo­la, Zika, dengue and chikun­gun­ya.

Gilead said it donates free drug sam­ples for the gov­ern­ment-fund­ed research of remde­sivir and helps design sci­en­tif­ic stud­ies and clin­i­cal tri­als. Whit­ley, an infec­tious-dis­ease expert who leads the drug devel­op­ment cen­ter in Alaba­ma, cred­it­ed Gilead for stay­ing focused on fight­ing viral infec­tions despite the poor mar­ket incen­tives.

“Drug com­pa­nies don’t have an inter­est in emerg­ing infec­tious dis­eases,’’ he said.

The pub­lic should not be exces­sive­ly dis­cour­aged by the neg­a­tive Ebo­la results last year, Whit­ley added. The tri­al in rur­al areas of Con­go, a con­flict zone with rudi­men­ta­ry con­di­tions, was com­pli­cat­ed by the fact that remdesivir’s cor­rect dosage was unknown, he said. Also, it required a cum­ber­some dai­ly IV admin­is­tra­tion, after being recon­sti­tut­ed from a freeze-dried form used for ship­ping in the uncon­trolled cli­mate con­di­tions.

The drug has not been stud­ied in human tri­als for SARS or MERS, because there are not enough patients, Gilead said.

“The num­ber of clin­i­cal MERS infec­tions was lim­it­ed, with almost exclu­sive local­iza­tion in the King­dom of Sau­di Ara­bia, and there were no SARS infec­tions,’’ the com­pa­ny said.

In the new coro­n­avirus out­break, it said, it is review­ing indi­vid­ual requests from physi­cians to pro­vide the drug on a “com­pas­sion­ate use’’ basis but only to patients who are hos­pi­tal­ized and show­ing “sig­nif­i­cant clin­i­cal man­i­fes­ta­tions.’’

———–

“The best hope for coro­n­avirus treat­ment is an exper­i­men­tal drug that fiz­zled against Ebo­la” by Christo­pher Row­land; The Wash­ing­ton Post; 03/11/2020

““I just hope remde­sivir works, because we real­ly need a ther­a­peu­tic that can inter­vene in this cri­sis,’’ said Richard Whit­ley, direc­tor of an NIH-fund­ed research effort involv­ing the world’s most dan­ger­ous virus­es.”

As Richard Whit­ley expressed, we real­ly have to just hope remde­sivir works because some­thing that works is need­ed as soon as pos­si­ble. And since remde­sivir has been the drug that’s been most aggres­sive­ly pushed through the clin­i­cal tri­al pipeline it’s out best shot at the moment. It also hap­pened to be a drug that dra­mat­i­cal­ly failed expec­ta­tions when test­ed on Ebo­la patients, but Whit­ley encour­ages us not to be too dis­cour­aged by that because that fail­ure does­n’t mean remde­sivir was­n’t poten­tial­ly effec­tive against Ebo­la. Oth­er fac­tors may have thwart­ed its suc­cess:

...
The pub­lic should not be exces­sive­ly dis­cour­aged by the neg­a­tive Ebo­la results last year, Whit­ley added. The tri­al in rur­al areas of Con­go, a con­flict zone with rudi­men­ta­ry con­di­tions, was com­pli­cat­ed by the fact that remdesivir’s cor­rect dosage was unknown, he said. Also, it required a cum­ber­some dai­ly IV admin­is­tra­tion, after being recon­sti­tut­ed from a freeze-dried form used for ship­ping in the uncon­trolled cli­mate con­di­tions.
...

Still, the fact of the mat­ter is that remde­sivir appeared to be effect against Ebo­la in the lab and in ani­mal tests and that did­n’t pan out at all when test­ed in humans. And it has­n’t been clin­i­cal­ly test­ed on humans with coro­n­avirus­es like SARS and MERS. So while remde­sivir has indeed demon­strat­ed antivi­ral activ­i­ty in the lab and in ani­mals, it does­n’t sound like the drug has demon­strat­ed that capac­i­ty in live human tri­als yet:

...
The drug, called remde­sivir, had blocked the Ebo­la virus in lab­o­ra­to­ries and in ani­mal exper­i­ments. But it did such a bad job extend­ing sur­vival in humans com­pared to two of the oth­er treat­ments that researchers decid­ed in August not to try it on any more patients.

Now the drug, cre­at­ed by phar­ma­ceu­ti­cal giant Gilead Sci­ences, is being test­ed in new clin­i­cal tri­als, and glob­al health author­i­ties deem it the most promis­ing of pos­si­ble treat­ments for peo­ple who are severe­ly ill with the nov­el coro­n­avirus, which caus­es the covid-19 dis­ease. Because it is a “broad spec­trum’’ drug that has been effec­tive against mul­ti­ple viral tar­gets in the lab and in ani­mals, the strat­e­gy could work, experts said.

...

The hope is that remde­sivir will show bet­ter results with the coro­n­avirus than it did with Ebo­la, which is from a dif­fer­ent viral fam­i­ly, offi­cials said. The first tri­al results could be avail­able in April.

...

Invent­ed by Gilead about a decade ago, remde­sivir has been proven to stop cer­tain virus­es from repli­cat­ing in lab exper­i­ments and in ani­mals. It has been researched in aca­d­e­m­ic labs in North Car­oli­na and Ten­nessee with back­ing from fed­er­al tax­pay­ers since 2014, as part of a $37.5 mil­lion effort by NIH to find treat­ments for infec­tious dis­eases.

...

The drug has not been stud­ied in human tri­als for SARS or MERS, because there are not enough patients, Gilead said.

“The num­ber of clin­i­cal MERS infec­tions was lim­it­ed, with almost exclu­sive local­iza­tion in the King­dom of Sau­di Ara­bia, and there were no SARS infec­tions,’’ the com­pa­ny said.
...

Still, let’s not for­get that there was indeed a sin­gle report­ed case of remde­sivir alle­vi­at­ing COVID-19 symp­toms in a patient. That suc­cess was report­ed on Feb­ru­ary 1. A cou­ple of days lat­er Gilead was send­ing sam­ples to Chi­na for offi­cial clin­i­cal tri­als with the Chi­nese gov­ern­ment. So that’s a rea­son to be hope­ful. But it’s still pret­ty remark­able that a sin­gle suc­cess result­ed in remde­sivir sud­den­ly being deemed not just the top can­di­date but seem­ing­ly the only real can­di­date. That’s lit­er­al­ly what WHO’s assis­tant direc­tor gen­er­al declared in late Feb­ru­ary when he announced that “There is only one drug right now that we think may have real effi­ca­cy, and that’s remde­sivir.” It’s a sen­ti­ment that was­n’t shared by one of Gilead­’s biggest bulls at RBC Cap­i­tal, who only gave the clin­i­cal tri­al a 50/50 chance of suc­cess:

...
Gilead, the Nation­al Insti­tutes of Health and Chi­nese health author­i­ties are rac­ing to test it on hun­dreds of peo­ple in con­trolled clin­i­cal tri­als, includ­ing a patient who was quar­an­tined in Nebras­ka after being removed from the Dia­mond Princess cruise ship. Axios report­ed this month that Gilead act­ed so quick­ly that it did not even wait for required approval by the Food and Drug Admin­is­tra­tion before it shipped dos­es to Chi­na. Asked to respond, Gilead said it thinks its “lim­it­ed ship­ments’’ were made in com­pli­ance with U.S. law.

...

Until Mon­day, when it fell in a bru­tal mar­ket rout, Gilead’s stock price had defied the over­all mar­ket decline of recent weeks, ris­ing almost 20 per­cent from Feb. 21 to March 6, on hopes that the drug could pro­vide the first treat­ment for covid-19.

The lack of treat­ment helps explain why. The stock price increased 5 per­cent on Feb. 24 alone when a top offi­cial of the World Health Orga­ni­za­tion pinned much of the world’s hopes for a treat­ment on the drug.

“There is only one drug right now that we think may have real effi­ca­cy, and that’s remde­sivir,” said Bruce Ayl­ward, WHO’s assis­tant direc­tor gen­er­al. Ten days lat­er, RBC Cap­i­tal Mar­kets gave it only a 50 per­cent chance of suc­ceed­ing as a treat­ment.
...

Those state­ments of con­fi­dence in the drug by the WHO also raise ques­tions of why we aren’t hear­ing about severe­ly ill patients being giv­en the drug in the mean time while we wait for the clin­i­cal tri­als to be com­plet­ed. After, that ini­tial patient in Wash­ing­ton state who received the drug and respond­ed well did it with­out clin­i­cal tri­al approval. Why not oth­er patients? Who knows, but it sounds like Gilead is being flood­ed with “com­pas­sion­ate use” requests and Gilead is cur­rent­ly “review­ing” indi­vid­ual requests. It’s the kind of state­ment from the com­pa­ny that makes it sound like no one has actu­al­ly received any “com­pas­sion­ate use” sup­plies yet. Giv­en that pos­i­tive results from these com­pas­sion­ate use cas­es would only bol­ster con­fi­dence in the drug’s promise you have to won­der if Gilead­’s appar­ent hes­i­ta­tion in dis­trib­ut­ing the drug is due to inter­nal con­cerns over its effec­tive­ness:

...
The mixed sig­nals have done lit­tle to damp­en inter­est. There have been des­per­ate pleas for sup­plies to treat patients on a “com­pas­sion­ate use’’ basis.

...

Gilead said it donates free drug sam­ples for the gov­ern­ment-fund­ed research of remde­sivir and helps design sci­en­tif­ic stud­ies and clin­i­cal tri­als. Whit­ley, an infec­tious-dis­ease expert who leads the drug devel­op­ment cen­ter in Alaba­ma, cred­it­ed Gilead for stay­ing focused on fight­ing viral infec­tions despite the poor mar­ket incen­tives.

“Drug com­pa­nies don’t have an inter­est in emerg­ing infec­tious dis­eases,’’ he said.

...

In the new coro­n­avirus out­break, it said, it is review­ing indi­vid­ual requests from physi­cians to pro­vide the drug on a “com­pas­sion­ate use’’ basis but only to patients who are hos­pi­tal­ized and show­ing “sig­nif­i­cant clin­i­cal man­i­fes­ta­tions.’’
...

And if remde­sivir does indeed turn out to be an effec­tive treat­ment, there’s still the ques­tion of whether or not it will even be afford­able for most peo­ple. We’ve already seen how Big Phar­ma and the GOP blocked a bill that would ensure any treat­ments are rea­son­ably priced. And now we’re hear­ing from Gilead that it’s too soon to dis­cuss pos­si­ble prices. It’s the kind of sit­u­a­tion that makes it sound like Gilead is plan­ning on charg­ing as much as it can get away with:

...

Giv­en the large degree of pub­lic finan­cial sup­port, debates are already flar­ing about how much Gilead should charge for its treat­ment if it ever makes it to mar­ket.

Con­gress and Pres­i­dent Trump autho­rized up to $3 bil­lion last week for efforts by aca­d­e­m­ic researchers and drug com­pa­nies to devel­op vac­cines and treat­ments for coro­n­avirus, part of an $8.3 bil­lion emer­gency spend­ing bill. The indus­try suc­cess­ful­ly opposed efforts by some House Democ­rats to attach guar­an­tees for afford­able prices for vac­cines or treat­ments that result.

Gilead said it is too soon to dis­cuss poten­tial mar­kets, in writ­ten respons­es to The Wash­ing­ton Post.

“We are focused on the poten­tial clin­i­cal val­ue that remde­sivir may bring to patients and doing our part to respond to the coro­n­avirus out­break,’’ the com­pa­ny said.

...

So that’s all why we should all be very hope­ful­ly that remde­sivir’s clin­i­cal tri­als suc­ceed but prob­a­bly should­n’t assume that’s going to hap­pen at this point. And that’s going to be a mas­sive dis­as­ter. The one real­is­tic fix for the cur­rent glob­al state of hyper-alarm that’s shut­ting down civ­i­liza­tion is an effec­tive drug for severe cas­es. There’s no stop­ping the spread of a virus this infec­tious with­out and vac­cine and a vac­cine is over year away. Drugs for severe cas­es could be avail­able in months. That should be the area that author­i­ties are aggres­sive­ly focused on and yet it sounds like almost all of the hopes are being placed on a drug that might work but could eas­i­ly not work. Or, in the case of the “Thai cock­tail”, it could be avail­able basi­cal­ly now.

And that points towards some­thing ran­dom doc­tors treat­ing severe­ly ill patients can poten­tial­ly do now to both help find an effec­tive treat­ment and lim­it the glob­al pan­ic: try out the “Thai cock­tail” (and any oth­er treat­ment with promis­ing reports) on severe­ly ill patients who look like they’re going to die any­way. If it turns out those Thai­land cas­es were flukes, well, ok, that sucks but it’s impor­tant to know. And if it turns out the “Thai cock­tail” is broad­ly effec­tive for the severe­ly ill that could rad­i­cal­ly change the alarm­ing nature of this pan­dem­ic and per­haps ward off the need to shut to civ­i­liza­tion, which seems like a com­pas­sion­ate approach all around.

A small biotech com­pa­ny in Rochester, New York, just made the kind of announce­ment yes­ter­day that should be rock­et­ing around the world. And yet there does­n’t real­ly appear to be hard­ly any excite­ment at all: The com­pa­ny, Oya­Gen, Inc., announced that it dis­cov­ered that a drug devel­oped back in the 1960’s to treat can­cer has demon­strat­ed a remark­able effi­ca­cy against the SARS-CoV­‑2 virus that caus­es COVID-19. The drug was nev­er approved for use against can­cer due to low effi­ca­cy but in this case it sounds like exact­ly the drug we need at the moment. It appar­ent­ly just com­plete­ly wiped it out in the cul­tured human cells in the lab test. They describe the drug as effec­tive­ly ster­il­iz­ing the cells.

The drug, which they now named Oya‑1, is described as a “broad spec­trum” antivi­ral that works on all sorts of dif­fer­ent virus­es. Recall how one of the fea­tures of of Gilead­’s remde­sivir drug that has the World Health Orga­ni­za­tion (WHO) almost entire­ly plac­ing its hopes on the drug is that remde­sivir is also a “broad spec­trum” antivi­ral.

None of the reports indi­cate if Oya‑1 can be tak­en as a pill form or has to be deliv­ered via IV. But if it does end up being deliv­er­able as a pill that will be anoth­er big advan­tage over remde­sivir. Recall how remde­sivir is deliv­ered via an IV and that may have actu­al­ly lim­it­ed its effi­ca­cy when tri­als were con­duct­ed in the field on Ebo­la patients. Giv­ing out pills, as opposed to IVs, is going to be WAY eas­i­er for the over­bur­dened health sys­tem to han­dle, espe­cial­ly in the devel­op­ing world.

Even bet­ter, it appears that Oya‑1 is slow­ly metab­o­lized by the liv­er so a sin­gle dose works at around full strength for eight days and half-strength for anoth­er four days. That sug­gests a sin­gle dose might be enough for most patients. So if it does have to be deliv­ered via IV at least it will hope­ful­ly only have to hap­pen once

Here’s the best part: since it was devel­oped in the 1960s as a can­cer drug, it’s already gone through the clin­i­cal tri­als and is deemed safe in humans. The only health com­pli­ca­tions they found were in chil­dren if you gave them a dai­ly dose. It’s con­ve­nient that chil­dren are the one group that seems least affect­ed by COVID-19 and there­fore the least like­ly to need it in the first place. And since a sin­gle dose might all be that’s required those dai­ly dos­es prob­a­bly won’t be nec­es­sary for chil­dren any­way.

We also don’t need to wait for these results to be con­firmed by any gov­ern­ment author­i­ties because the tests on SARS-CoV­‑2 done by the com­pa­ny were done in part­ner­ship with the fed­er­al gov­ern­men­t’s inte­grat­ed research facil­i­ty at Fort Det­rick. Yep, these tests show­ing the drug ster­il­iz­ing were done at Fort Det­rick. That should address any ques­tions about the verac­i­ty of the results. The Fort Det­rick lab had pre­vi­ous­ly test­ed it against Ebo­la and found it to be effec­tive against the virus in the lab so this is at least the sec­ond time Fort Det­rick test­ed the drug.

At this point it sounds like some sort of dream drug giv­en the sit­u­a­tion. The com­pa­ny is seek­ing to have it fast-tracked for human test­ing. So will it be fast-tracked? And are we going to see all sorts of cel­e­bra­tions about its promise and rapid clin­i­cal tri­al test­ing on patients? How about “com­pas­sion­ate use” on the sick­est patients while we wait for those clin­i­cal tri­als to com­plete? We’ll see. As the founder of the com­pa­ny, Dr. Harold Smith, put it, “You’ve got this com­pound that’s absolute­ly lethal to the virus, and we know it has a mar­gin of safe­ty in people...What are we wait­ing for?”:

13WHAM News

ROC biotech com­pa­ny says lab tests of for­mer can­cer drug con­firm it stops COVID-19

by Jane Flasch
Wednes­day, March 11th 2020

*
Rochester, N.Y. — A vac­cine for COVID-19 is like­ly years away. Yet a drug test­ed in a lab three weeks ago has been found to stop the virus from spread­ing from cell to cell.

The stun­ning announce­ment comes from a Rochester biotech com­pa­ny called Oya­Gen, Inc. The com­pa­ny is seek­ing to fast-track the for­mu­la to treat peo­ple who become infect­ed.

“A treat­ment right now is the pri­or­i­ty,” said Dr. Harold Smith of Oya­Gen. He added the drug already has FDA approval for anoth­er use.

The tests were con­duct­ed at the fed­er­al gov­ern­men­t’s inte­grat­ed research facil­i­ty in Fort Det­rick, Md. A drug called Oya 1 had already been proven in lab tests there to be effec­tive against Ebo­la.

“If it worked for Ebo­la, is it absolute­ly unique to Ebo­la, or would it work on oth­er virus­es?” asked Dr. Smith — though he said an actu­al drug for human con­sump­tion was nev­er pur­sued.

The coro­n­avirus was still new and con­tained to Wuhan, Chi­na when a sam­ple of the live virus was shipped to the gov­ern­ment lab for test­ing with Oya 1. Test sam­ples viewed under a micro­scope show a clear “before” and “after” that indi­cates prop­er­ties that allowed the virus to grow and spread were neu­tral­ized.

“The drug was so effec­tive that, even though we got through our dose-test­ing, we had lit­er­al­ly ster­il­ized the cul­ture of the virus, so we knew this was a pow­er­ful thing,” said Dr. Smith.

Under a dif­fer­ent name, Oya‑1 was first devel­oped in the 1960s as a treat­ment for can­cer. It was lat­er shelved as inef­fec­tive, but not before it received approval from the Food and Drug Admin­is­tra­tion. Safe dosage lev­els were deter­mined for men, women and chil­dren.

“Clin­i­cal tri­als have already been done on this com­pound and, if safe­ty is a main issue, we feel safe­ty has been addressed years ago,” said Dr. Smith.

He said pre­lim­i­nary research indi­cates a sin­gle dose of the med­i­cine stops the pro­gres­sion of COVID-19 for eight days and con­tin­ues to work at half-strength for anoth­er four days.

The ques­tion is whether the drug will react to the virus the same way in the body as it has in the lab. When an approved drug is pro­posed for a new use, the FDA usu­al­ly requires new clin­i­cal tri­als.

...

Oya­Gen says the live virus tests were con­duct­ed and val­i­dat­ed by a third par­ty — the U‑S gov­ern­ment, and argue that is also a rea­son the drug should be fast-tracked.

“You’ve got this com­pound that’s absolute­ly lethal to the virus, and we know it has a mar­gin of safe­ty in peo­ple,” said Dr. Smith. “What are we wait­ing for?”

———-

“ROC biotech com­pa­ny says lab tests of for­mer can­cer drug con­firm it stops COVID-19” by Jane Flasch; 13WHAM News; 03/11/2020

“The stun­ning announce­ment comes from a Rochester biotech com­pa­ny called Oya­Gen, Inc. The com­pa­ny is seek­ing to fast-track the for­mu­la to treat peo­ple who become infect­ed.”

Are we going to see this fast-tracked for treat­ment? If not, there had bet­ter be a very good expla­na­tion and it’s hard to imag­ine what that could pos­si­bly be giv­en the results so far. But giv­en the near com­plete lack of inter­est in the “Thai cock­tail” rem­e­dy that’s already been report­ed, who knows, maybe this announce­ment of a pos­si­ble won­der drug will just be met with a col­lec­tive shrug. Again.

And much like that “Thai cock­tail”, which con­sist­ed of three drugs that already passed FDA approval for use in humans, this Oya‑1 drug has already been received FDA approval. They already know what the safe dosage lev­els are for men, women, and chil­dren:

...
“A treat­ment right now is the pri­or­i­ty,” said Dr. Harold Smith of Oya­Gen. He added the drug already has FDA approval for anoth­er use.

...

Under a dif­fer­ent name, Oya‑1 was first devel­oped in the 1960s as a treat­ment for can­cer. It was lat­er shelved as inef­fec­tive, but not before it received approval from the Food and Drug Admin­is­tra­tion. Safe dosage lev­els were deter­mined for men, women and chil­dren.

“Clin­i­cal tri­als have already been done on this com­pound and, if safe­ty is a main issue, we feel safe­ty has been addressed years ago,” said Dr. Smith.
...

And it was none oth­er than the researchers at Fort Det­rick who con­duct­ed the new tests on the SARS-CoV­‑2 virus and found that it effec­tive­ly ster­il­ized the cells of the virus just as they pre­vi­ous­ly found it also worked on Ebo­la. In oth­er words, these are gov­ern­ment val­i­dat­ed results:

...
The tests were con­duct­ed at the fed­er­al gov­ern­men­t’s inte­grat­ed research facil­i­ty in Fort Det­rick, Md. A drug called Oya 1 had already been proven in lab tests there to be effec­tive against Ebo­la.

“If it worked for Ebo­la, is it absolute­ly unique to Ebo­la, or would it work on oth­er virus­es?” asked Dr. Smith — though he said an actu­al drug for human con­sump­tion was nev­er pur­sued.

...

The coro­n­avirus was still new and con­tained to Wuhan, Chi­na when a sam­ple of the live virus was shipped to the gov­ern­ment lab for test­ing with Oya 1. Test sam­ples viewed under a micro­scope show a clear “before” and “after” that indi­cates prop­er­ties that allowed the virus to grow and spread were neu­tral­ized.

“The drug was so effec­tive that, even though we got through our dose-test­ing, we had lit­er­al­ly ster­il­ized the cul­ture of the virus, so we knew this was a pow­er­ful thing,” said Dr. Smith.
...

And pre­lim­i­nary results indi­cate a sin­gle dose stops the pro­gres­sion of COVID-19 at full strength for eight days and half strength for four days. That’s a nice dura­tion. The big ques­tion is how it works in actu­al humans. A ques­tion that can be answered a lot faster if the drug gets fast-tracked:

...
He said pre­lim­i­nary research indi­cates a sin­gle dose of the med­i­cine stops the pro­gres­sion of COVID-19 for eight days and con­tin­ues to work at half-strength for anoth­er four days.

The ques­tion is whether the drug will react to the virus the same way in the body as it has in the lab. When an approved drug is pro­posed for a new use, the FDA usu­al­ly requires new clin­i­cal tri­als.
...

Ok, now here’s anoth­er local Rochester report on the announce­ment that includes Oya­Gen’s press release. It men­tions that the drug has demon­strat­ed “broad spec­trum” antivi­ral activ­i­ty against the coro­n­avirus­es SARS-CoV­‑2 and MERS-CoV and also is a dual tar­get-spe­cif­ic antivi­ral against filovirus­es such as Ebo­la virus. A dual tar­get-spe­cif­ic antivi­ral is a com­pound that attacks a virus in mul­ti­ple ways so that’s a great fea­ture, espe­cial­ly when it comes to avoid­ing drug resis­tant strains of the virus so hope­ful­ly it even­tu­al­ly demon­strates dual tar­get activ­i­ty against COVID-19 too.

Along those lines, the press release also notes that the drug could be very use­ful at this ear­ly stage in the out­break for use in con­junc­tion with oth­er ther­a­pies for avoid­ing the devel­op­ment of drug-resis­tant strains. It’s a reminder that we should­n’t real­ly be look­ing for a sin­gle won­der drug. We need as many dif­fer­ent drugs as pos­si­ble that act on the virus in as many dif­fer­ent ways as pos­si­ble and ide­al­ly can be tak­en togeth­er. Which is also anoth­er rea­son why the lack of inter­est in the “Thai cock­tail” is so bewil­der­ing since that’s already a cock­tail of three dif­fer­ent drugs tak­en togeth­er. It seems like that should be ide­al from a drug-resis­tance stand­point.

The press release also men­tions how the only side-effects found when the drug was test­ed on humans was poten­tial car­diac tox­i­c­i­ty in chil­dren if the drug is tak­en dai­ly. And while car­diac tox­i­c­i­ty is def­i­nite­ly some­thing you want to avoid, the fact that a sin­gle dose of the drug lasts and 12 days and chil­dren are the least like­ly to be impact­ed by COVID-19 makes those side-effects seem rel­a­tive­ly minor. All in, the more we’re learn­ing about this drug, the more it seems like exact­ly the kind of thing we need right now:

WROC

Local biotech com­pa­ny test­ing treat­ment for COVID-19

by: WROC Staff
Post­ed: Mar 11, 2020 / 07:30 PM EDT / Updat­ed: Mar 12, 2020 / 11:49 AM EDT

ROCHESTER, N.Y. (WROC) — A Rochester based biotech com­pa­ny called Oya­gen, Inc. has been test­ing a for­mer can­cer treat­ment drug as a treat­ment for COVID 19 — and they say it’s work­ing.

The com­pa­ny is not prepar­ing a vac­cine, but a treat­ment that they say would stop the cell-to-cell spread of the virus in infect­ed per­sons.

The drug, called Oya1 would serve as a ‘stop-gap’ treat­ment until vac­cines are avail­able.

The com­pa­ny said in a release:

“Oya­Gen, Inc. announced today new unpub­lished results from col­lab­o­ra­tive research with the Nation­al Insti­tute of Aller­gy and Infec­tious Dis­eases’ Inte­grat­ed Research Facil­i­ty at Fort Det­rick, MD, sug­gest­ing strong dose-depen­dent antivi­ral activ­i­ty of its lead com­pound OYA1 against live SARS-CoV­‑2, the causative agent for COVID-19, based on in cell cul­ture infec­tiv­i­ty stud­ies.

About OYA1. OYA1 has broad-spec­trum antivi­ral activ­i­ty in lab­o­ra­to­ry-based assays against the coro­n­avirus­es SARS-CoV­‑2 and MERS-CoV and also is a dual tar­get-spe­cif­ic antivi­ral against filovirus­es such as Ebo­la virus. OYA1 was strong­ly more effec­tive than a pos­i­tive-con­trol com­pound, chlor­pro­mazine HCl, at inhibit­ing SARS-CoV­‑2 from repli­cat­ing in cell cul­ture. OYA1 had pri­or FDA approval as an inves­ti­ga­tion­al new drug for treat­ing can­cer in the 1960s but was aban­doned for a lack of effi­ca­cy. Stud­ies at that time demon­strat­ed safe­ty in non­hu­man pri­mates and human adults when dosed dai­ly or week­ly. Side effects may include car­diac tox­i­c­i­ty in chil­dren when dosed every day. Side effects may be due to the slow meta­bol­ic turnover of OYA1 as demon­strat­ed in ear­li­er stud­ies in mice, which sug­gest­ed the com­pound may per­sist in tis­sues for greater than 12 days fol­low­ing a sin­gle dose, espe­cial­ly in heart tis­sue where cell turnover is low. How­ev­er, its long half-life in tis­sues sug­gests that a sin­gle dose or week­ly dos­ing may be suf­fi­cient for antivi­ral treat­ments.

Oya­Gen, Inc. will con­duct fur­ther stud­ies for the safe­ty and effi­ca­cy of OYA1 in treat­ing COVID-19 as nec­es­sary for reg­u­la­to­ry approval. The com­pa­ny antic­i­pates that inhi­bi­tion of SARS-CoV­‑2 using OYA1 will serve as a stop-gap treat­ment until appro­pri­ate vac­cines are devel­oped. OYA1 may also prove time­ly in address­ing the need for com­bi­na­tion ther­a­py for SARS-CoV­‑2 to avoid the emer­gence of drug-resis­tant virus.

...

———–

“Local biotech com­pa­ny test­ing treat­ment for COVID-19” by WROC Staff; WROC; 03/11/2020

“Oya­Gen, Inc. will con­duct fur­ther stud­ies for the safe­ty and effi­ca­cy of OYA1 in treat­ing COVID-19 as nec­es­sary for reg­u­la­to­ry approval. The com­pa­ny antic­i­pates that inhi­bi­tion of SARS-CoV­‑2 using OYA1 will serve as a stop-gap treat­ment until appro­pri­ate vac­cines are devel­oped. OYA1 may also prove time­ly in address­ing the need for com­bi­na­tion ther­a­py for SARS-CoV­‑2 to avoid the emer­gence of drug-resis­tant virus.”

Yes indeed, OYA1 may prove time­ly. May prove time­ly. That all depends on whether or not it’s actu­al­ly fast-tracked and allowed to be used in a time­ly man­ner. We’ll see if that hap­pens but the fact we’re large­ly hear­ing about this remark­ably time­ly devel­op­ment from local Rochester news out­lets and the com­pa­ny’s own press releas­es sug­gests this is going to be anoth­er extreme­ly untime­ly lost oppor­tu­ni­ty.

Sci­en­tists believe they’ve made a huge break­through in coro­n­avirus vac­cine effort
By Lau­ra Ital­iano

March 13, 2020 | 5:59pm

In what is becom­ing an increas­ing­ly sur­re­al sit­u­a­tion, that seem­ing­ly mirac­u­lous announce­ment by Oya­Gen that it devel­oped a drug that proved remark­able effec­tive­ly against COVID-19 has con­tin­ued to received vir­tu­al­ly NO nation­al or inter­na­tion­al atten­tion. The inter­est is seri­ous­ly lim­it­ed exclu­sive­ly to local Rochester news reports. This is two days after the ini­tial news reports about the stun­ning­ly suc­cess­ful test results on human cell cul­tures and over three weeks after those results. As Harold Smith, the sci­en­tist who found­ed the com­pa­ny, plead­ed with health author­i­ties and the worlds, “You’ve got this com­pound that’s absolute­ly lethal to the virus, and we know it has a mar­gin of safe­ty in people...What are we wait­ing for?” That ques­tion has yet to be acknowl­edged, let alone answered, by pret­ty much any­one. What are we wait­ing for? The risk of over­whelm­ing hos­pi­tals with patients in need of ven­ti­la­tors and oth­er life-sav­ing treat­ment is very real and the pri­ma­ry basis of the sud­den lock­down of soci­ety. Drugs like OYA1 are pre­cise­ly the solu­tion that is urgent­ly required. There should have been a crash pro­gram to super-fast track this drug for use on dying patients the day after those pos­i­tive results.

And the drug has lit­er­al­ly been test­ed for safe­ty in humans decades ago, with known safe lev­els for men, women, and chil­dren and ver­i­fied by Fort Det­rick which means it real­ly could be made avail­able for “com­pas­sion­ate use” cas­es almost imme­di­ate­ly. You almost could­n’t have a sce­nario where an drug could be eth­i­cal­ly test on exist­ing patients in a rush man­ner. We’re talk­ing about a con­tain­ing a con­ta­gion that has been dou­bling in case num­bers each week. Wast­ing three weeks is like casu­al­ly let­ting the case num­bers triple before we even both­er work­ing on turn­ing this drug into real­i­ty.

So here’s one of the few reports out­side of Rochester about the drug dis­cov­ery that gives us a sense of the time­frame for how long before this drug might be made avail­able for COVID-19 suf­fer­ers: three months to a year before it can be peer-reviewed and only at that point will it be ready for clin­i­cal tri­als. Isn’t this a sit­u­a­tion for super-expe­dit­ed peer-review? Like have some experts talk to the folks at Fort Det­rick, quick­ly review the results, and then move on to crash clin­i­cal tri­als and imme­di­ate “com­pas­sion­ate use”? Appar­ent­ly not. Instead, it sounds like they are forc­ing a peer-review delay on Oya­Gen’s results that might take three months to a year. And only then will clin­i­cal tri­als start, which will take a few more months at a min­i­mum. That’s accord­ing to the report by WBFO, the Buf­fa­lo sta­tion for Nation­al Pub­lic Radio. Buf­fa­lo is like 67 miles from Rochester so, yay!, at least this sto­ry has made it to Buf­fa­lo.

The report also includes an inter­view with Harold Smith. WXXI News, the NPR affil­i­ate for Rochester, also car­ried the report and includes the audio of the inter­view with Smith. You can hear the exas­per­a­tion in his voice. The guy lit­er­al­ly stum­bled across the poten­tial cure for an emerg­ing pan­dem­ic that’s almost ready to use right out of the box and he can’t get author­i­ties to care. Despite devel­op­ing it in part­ner­ship with author­i­ties.

As Smith — a tenure pro­fes­sor of bio­chem­istry and bio­physics at the Uni­ver­si­ty of Rochester — puts it in the inter­view, “When we are in a dire sit­u­a­tion as we are at this time, with coro­n­avirus, we can’t be flat-foot­ed and look at this as we’ve got an aca­d­e­m­ic leisure approach to this”:

WBFO
Nation­al Pub­lic Radio Buf­fa­lo

Rochester biotech com­pa­ny says it’s test­ing com­pound with ‘high-poten­tial’ as coro­n­avirus cure

By Veron­i­ca Volk • Mar 13, 2020

A Rochester com­pa­ny is work­ing on find­ing a treat­ment for coro­n­avirus — and appears close to a cure.

The biotech com­pa­ny Oya­Gen has been work­ing with a com­pound called OYA1 that they say could treat coro­n­avirus in a new way.

...

The com­pound has only been test­ed in a lab­o­ra­to­ry set­ting and has not been peer-reviewed. It’s pos­si­ble that it could take any­where from three months to a year to be avail­able for clin­i­cal tri­als.

Oya­Gen Pres­i­dent and CEO Harold Smith said the com­pound has been test­ed for safe­ty in the 1960s, when it was being con­sid­ered for use on can­cer patients. He is hop­ing this infor­ma­tion will encour­age the FDA to fast-track OYA1 for clin­i­cal test­ing in humans.

“When we are in a dire sit­u­a­tion as we are at this time, with coro­n­avirus, we can’t be flat-foot­ed and look at this as we’ve got an aca­d­e­m­ic leisure approach to this,” Smith said..

Smith is a tenured pro­fes­sor of bio­chem­istry and bio­physics at the Uni­ver­si­ty of Rochester. He pre­vi­ous­ly has worked on iden­ti­fy­ing com­pounds to treat the Ebo­la virus and MERS. Those com­pounds nev­er went to tri­al, either, but he said they were also effec­tive in lab­o­ra­to­ry set­tings.

“Our long­stand­ing effort has been to cap­i­tal­ize on what was my aca­d­e­m­ic strength, that every­one has the inate abil­i­ty to pro­tect them­selves against infec­tion,” said Smith.

Smith said he has been work­ing with the fed­er­al gov­ern­ment to devel­op these treat­ments.

————

“Rochester biotech com­pa­ny says it’s test­ing com­pound with ‘high-poten­tial’ as coro­n­avirus cure” by Veron­i­ca Volk; WBFO; 03/13/2020

“The com­pound has only been test­ed in a lab­o­ra­to­ry set­ting and has not been peer-reviewed. It’s pos­si­ble that it could take any­where from three months to a year to be avail­able for clin­i­cal tri­als.”

Three months to a year. That’s a 12 to 52 week delay...on top of the three week delay already. Again, this is some­thing that poten­tial­ly spreads expo­nen­tial­ly, with the num­ber of cas­es dou­bling each week (every six days, accord­ing to some recent stud­ies).

And note the dis­turb­ing way Smith is pub­licly forced to plead with the gov­ern­ment to fast-track it by point­ing out that the drug’s safe­ty in humans has already been ver­i­fied by the gov­ern­ment. He is lit­er­al­ly telling reporters that he hopes this infor­ma­tion will encour­age the FDA to fast-track OYA1 for clin­i­cal test­ing in humans. Which means it’s not being fast-tracked yet. He has to pub­licly beg for that to hap­pen:

...
Oya­Gen Pres­i­dent and CEO Harold Smith said the com­pound has been test­ed for safe­ty in the 1960s, when it was being con­sid­ered for use on can­cer patients. He is hop­ing this infor­ma­tion will encour­age the FDA to fast-track OYA1 for clin­i­cal test­ing in humans.

“When we are in a dire sit­u­a­tion as we are at this time, with coro­n­avirus, we can’t be flat-foot­ed and look at this as we’ve got an aca­d­e­m­ic leisure approach to this,” Smith said..

...

Smith said he has been work­ing with the fed­er­al gov­ern­ment to devel­op these treat­ments.
...

So it’s becom­ing increas­ing­ly clear that we aren’t just in the midst of a glob­al pan­dem­ic of a mys­tery con­ta­gion that’s shut­ting down civ­i­liza­tion. No, we’re clear­ly in the mid­dle of a new episode of The Twi­light Zone. An episode star­ring Harold Smith, a sci­en­tist and entre­pre­neur who set out to make the world a bet­ter place by find­ing treat­ments for dis­ease. And he did it. He found a mir­a­cle treat­ment for one of the biggest pub­lic health emer­gen­cies in record­ed his­to­ry. He found it ear­ly on in the out­break right when it could have the great­est impact. He found it in part­ner­ship with the gov­ern­ment agency best posi­tioned to ver­i­fy its effi­ca­cy and safe­ty. AND HE CAN’T GET THE WORLD TO CARE.

As sur­re­al as this sit­u­a­tion is for every­one in gen­er­al, just imag­ine what this is like for Smith. He found the poten­tial solu­tion to a glob­al pan­dem­ic that’s ready to go and he lit­er­al­ly can’t get the world to care.

And it’s not just the gov­ern­ment that’s appar­ent­ly ignor­ing this amaz­ing dis­cov­ery. Or the nation­al and inter­na­tion­al media. Pret­ty much EVERYONE ON THE PLANET is ignor­ing this amaz­ing sto­ry. If you go to Oya­Gen’s Face­book page as of today, the top post is the announce­ment of these amaz­ing results from two days ago. There’s two com­ments on the post. Both are com­ments by Oya­Gen itself link­ing to BUSINESS WIRE pub­lic rela­tions posts by the com­pa­ny itself on the their find­ings. That’s it. It’s the inter­net age, the age of viral sto­ries, and the inter­net does­n’t care about the mir­a­cle cure for the virus shut­ting civ­i­liza­tion down.

So as we can see, it’s two days after this mir­a­cle announce­ment and vir­tu­al­ly no one on the plan­et cares. Because we’re now liv­ing in Twi­light Zone episode. Star­ring Harold Smith. The rest of us are also in the episode but we’re the idi­ot­ic extras that unfath­omably don’t care. It’s def­i­nite­ly one of the more dis­turb­ing episodes.

Pres­i­dent Trump report­ed­ly tried to recruit Ger­man sci­en­tists work­ing on a cure for the coro­n­avirus and offered large sums of mon­ey to secure exclu­sive rights to their work for the US, accord­ing to a report which was con­firmed by the Ger­man gov­ern­ment.

https://www.businessinsider.com/trump-administration-tried-to-pay-germans-scientists-for-coronavirus-cure-2020–3?amp&__twitter_impression=true

@ Pter­rafractyl
This is not a “cure”. It’s mere­ly a stop-gap mea­sure until a vac­cine can be devel­oped. Oth­er stop-gap mea­sure drugs are remde­sivir and chlo­riquine (gener­ic) and oth­er antivi­rals can be used cur­rent­ly under “com­pas­sion­ate use”. Harold Smith is the CEO of the com­pa­ny and there’s an obvi­ous con­flict of inter­est here as the com­pa­ny stands to reap huge prof­its off this drug if it makes it onto the mar­ket. And the rea­son this has not been wide­ly dis­sem­i­nat­ed is because the results are unpub­lished. There has to be a paper writ­ten to doc­u­ment the effi­ca­cy of this drug and then peer reviewed. Final­ly, the fact that this com­pa­ny is involved in AIDs treat­ments and Fort Det­rick should be con­cern­ing in light of past infor­ma­tion about the ori­gins of AIDs.

Local Biotech Com­pa­ny Test­ing Treat­ment for Covid-19
March 11, 2020
https://www.rochesterfirst.com/coronavirus/local-biotech-company-testing-treatment-for-covid-19/

ROCHESTER, N.Y. (WROC) — A Rochester based biotech com­pa­ny called Oya­gen, Inc. has been test­ing a for­mer can­cer treat­ment drug as a treat­ment for COVID 19 — and they say it’s work­ing.
The com­pa­ny is not prepar­ing a vac­cine, but a treat­ment that they say would stop the cell-to-cell spread of the virus in infect­ed per­sons.
The drug, called Oya1 would serve as a ‘stop-gap’ treat­ment until vac­cines are avail­able.
The com­pa­ny said in a release:
“Oya­Gen, Inc. announced today new unpub­lished results from col­lab­o­ra­tive research with the Nation­al Insti­tute of Aller­gy and Infec­tious Dis­eases’ Inte­grat­ed Research Facil­i­ty at Fort Det­rick, MD, sug­gest­ing strong dose-depen­dent antivi­ral activ­i­ty of its lead com­pound OYA1 against live SARS-CoV­‑2, the causative agent for  COVID-19, based on in cell cul­ture infec­tiv­i­ty stud­ies.
About OYA1. OYA1 has broad-spec­trum antivi­ral activ­i­ty in lab­o­ra­to­ry-based assays against the coro­n­avirus­es SARS-CoV­‑2 and MERS-CoV and also is a dual tar­get-spe­cif­ic antivi­ral against filovirus­es such as Ebo­la virus. OYA1 was strong­ly more effec­tive than a pos­i­tive-con­trol com­pound, chlor­pro­mazine HCl, at inhibit­ing SARS-CoV­‑2 from repli­cat­ing in cell cul­ture. OYA1 had pri­or FDA approval as an inves­ti­ga­tion­al new drug for treat­ing can­cer in the 1960s but was aban­doned for a lack of effi­ca­cy. Stud­ies at that time demon­strat­ed safe­ty in non­hu­man pri­mates and human adults when dosed dai­ly or week­ly. Side effects may include car­diac tox­i­c­i­ty in chil­dren when dosed every day. Side effects may be due to the slow meta­bol­ic turnover of OYA1 as demon­strat­ed in ear­li­er stud­ies in mice, which sug­gest­ed the com­pound may per­sist in tis­sues for greater than 12 days fol­low­ing a sin­gle dose, espe­cial­ly in heart tis­sue where cell turnover is low. How­ev­er, its long half-life in tis­sues sug­gests that a sin­gle dose or week­ly dos­ing may be suf­fi­cient for antivi­ral treat­ments.
Oya­Gen, Inc. will con­duct fur­ther stud­ies for the safe­ty and effi­ca­cy of OYA1 in treat­ing COVID-19 as nec­es­sary for reg­u­la­to­ry approval. The com­pa­ny antic­i­pates that inhi­bi­tion of SARS-CoV­‑2 using OYA1 will serve as a stop-gap treat­ment until appro­pri­ate vac­cines are devel­oped. OYA1 may also prove time­ly in address­ing the need for com­bi­na­tion ther­a­py for SARS-CoV­‑2 to avoid the emer­gence of drug-resis­tant virus.
Oya­Gen Inc is a pri­vate­ly held biotech­nol­o­gy com­pa­ny locat­ed in Rochester, NY.  Oya­Gen is focused on the iden­ti­fi­ca­tion and ear­ly devel­op­ment of nov­el ther­a­peu­tics for the treat­ment of viral dis­eases includ­ing HIV, Coro­n­avirus and Ebo­la.”

@Mother Muck­rak­er: Yes, tech­ni­cal­ly it’s a “treat­ment”, not a “cure”. But a treat­ment is real­ly all we need at this point and if OYA‑1 real­ly can effec­tive­ly ster­il­ize cells of the virus like Harold Smith claims that’s effec­tive­ly a cure.

And while it’s cer­tain­ly true that Harold Smith has a con­flict of inter­est in the sense that he owns the com­pa­ny and stands to prof­it, he’s also lit­er­al­ly the only per­son telling us about these stun­ning results. But who else is going to tell us about unpub­lished results? That’s Smith’s whole point. We don’t have time to wait for the peer reviewed process. In Smith’s inter­view with those local NPR affil­i­ates he was look­ing at three months to a year just for the peer reviewed process to be com­plet­ed. Should we seri­ous­ly be wait­ing that long in this sit­u­a­tion?

Cana­da just shut itself down from non-cit­i­zens enter­ing. That’s where we are. The globe is shut­ting itself down due to a virus that’s stealth spread­ing at a yet-to-be deter­mined rate. If we’re in “shut down the globe” mode to thwart the spread of a virus so we don’t get our health sys­tems over­loaded. The num­ber of cas­es appears to be dou­bling each week and, more recent­ly, every three days or so accord­ing to some esti­ma­tions. If we assume a week­ly dou­bling, that’s an 8‑fold jump in the num­ber of cas­es dur­ing the three week delay between the con­clu­sion of those test by Oya­Gen and Fort Det­rick researchers that demon­strat­ed a ster­il­iza­tion of the virus in the lab from the OYA‑1 drug and the pub­lic announce­ment by Oya­Gen of those results. If we assume a 3 day dou­bling peri­od that three weeks is sev­en dou­bling peri­ods, a poten­tial 128-fold growth in cas­es.

The point is that each day lost is a huge loss when we’re deal­ing with a virus that is spread­ing at at a seem­ing­ly accel­er­at­ing rate at this point. That expo­nen­tial growth is the key fea­ture of sit­u­a­tion we’re deal­ing with which is pre­cise­ly why pre­lim­i­nary unpub­lished find­ings of this nature should­n’t be expect­ed to go through a nor­mal peer review­ing process that can take months or years. Giv­en the cir­cum­stances, some sort of expe­dit­ed peer review should have hap­pened pret­ty much imme­di­ate­ly and con­clud­ed ASAP. Just get in con­tact with a group of rel­e­vant experts, send them results, ask them to imme­di­ate­ly review them in 24 hours, and if they don’t have any com­pelling issues with the results imme­di­ate­ly pro­ceed with expe­dit­ed clin­i­cal tri­als and, ide­al­ly, “com­pas­sion­ate use” appli­ca­tions for exist­ing severe cas­es. If the peer review­ers do have any ongo­ing issues with the results they just need to ask the OyaGen/Fort Det­rick researchers to address those con­cerns, maybe with new tests if nec­es­sary. But all of this can and should be done in a high­ly expe­dit­ed man­ner. Peer review­ing should have tak­en like a cou­ple days in this sit­u­a­tion if these results.

But per­haps the best exam­ple demon­strat­ing the absur­di­ty of the slow-walk­ing of these Oya­Gen results is look­ing at the fast-track­ing already tak­ing place with oth­er treat­ments. For exam­ple, look at how Gilead­’s remde­sivir was treat­ed. Recall how, on Jan­u­ary 31, after remde­sivir was found to help alle­vi­ate the symp­toms in sin­gle US patient with COVID-19, it was shipped off to Chi­na and clin­i­cal tri­als were announced with­in days. At that point in time remde­sivir had not yet been proven to be safe or effec­tive or any use and it was only allowed to be used on the patient in the US on a com­pas­sion­ate use basis. The evi­dence jus­ti­fy­ing the human clin­i­cal tri­als was just that sin­gle COVID-19 case. That’s it. At the time, He Gongx­in, the for­mer chief rep­re­sen­ta­tive of the Shang­hai office at Gilead, told reporters that, “remde­sivir is not a well-proven drug in either the U.S. or Chi­na...Since 2019-nCoV is a new virus, we’ll just try it. There are good sci­en­tif­ic rea­sons for us to believe it could be safe and effi­ca­cious...I believe this is the best chance we have for now.” That’s how this sit­u­a­tion was han­dled for Gilead­’s drug. It was deemed to be the best shot we have for now in an urgent sit­u­a­tion and clin­i­cal tri­als were start­ed almost imme­di­ate­ly despite the drug not being proven to be safe or effec­tive for any use:

BioWorld

Gilead’s remde­sivir enters Chi­na phase III tri­al to fight coro­n­avirus

By Elise Mak
Feb­ru­ary 3, 2020

BEIJING – Chi­na will kick­start a phase III tri­al Feb. 3 to deter­mine whether patients with 2019-nCoV can be treat­ed with Gilead Sci­ences Inc.’s NUC inhibitor, remde­sivir, which was orig­i­nal­ly devel­oped for Ebo­la, four days after a U.S. patient was said to have recov­ered by using the drug can­di­date.

The study, expect­ed to be com­plet­ed on April 27, is a phase III ran­dom­ized, dou­ble-blind, place­bo-con­trolled mul­ti­cen­ter study to eval­u­ate the effi­ca­cy and safe­ty of remde­sivir in hos­pi­tal­ized adult patients with mild and mod­er­ate 2019-nCoV infec­tions. It will enroll 270 patients and be car­ried out in the Chi­na-Japan Friend­ship Hos­pi­tal in Bei­jing.

Gilead said it is expe­dit­ing the lab­o­ra­to­ry test­ing of remde­sivir against 2019-nCoV sam­ples and work­ing with the Chi­nese author­i­ties.

...

Remde­sivir is yet to be approved any­where glob­al­ly and has not been demon­strat­ed to be safe or effec­tive for any use. How­ev­er, a paper in The New Eng­land Jour­nal of Med­i­cine pub­lished Jan. 31 sug­gest­ed there was a pos­si­bil­i­ty of using the drug can­di­date to help con­tain the dead­ly 2019-nCoV virus, which has killed 361 peo­ple so far.

On Jan 26, a 35-year-old patient in the U.S. with 2019-nCoV received remde­sivir, a week after he was admit­ted to the hos­pi­tal, accord­ing to reports. The fol­low­ing day, his fever went down from 39.4 degrees Cel­sius to 37.3 degrees Cel­sius, oxy­gen sat­u­ra­tion val­ues improved to 94% to 96%, and the pre­vi­ous bilat­er­al low­er-lobe rales were no longer present.

Five days after being treat­ed with remde­sivir, he was said to be afebrile, with all symp­toms resolved except for his cough, which was get­ting bet­ter.

The encour­ag­ing result prompt­ed Gilead and the Chi­nese author­i­ties to move the phase III tri­al ahead and expand it to a lot more patients who need treat­ment des­per­ate­ly.

“Remde­sivir is not a well-proven drug in either the U.S. or Chi­na,” He Gongx­in, for­mer chief rep­re­sen­ta­tive of the Shang­hai office at Gilead, told BioWorld. “Since 2019-nCoV is a new virus, we’ll just try it. There are good sci­en­tif­ic rea­sons for us to believe it could be safe and effi­ca­cious.

“I believe this is the best chance we have for now,” He added.

In Octo­ber 2015, a phase I study that eval­u­at­ed the safe­ty, tol­er­a­bil­i­ty and phar­ma­co­ki­net­ics of remde­sivir in healthy vol­un­teers demon­strat­ed promis­ing results and sup­port­ed fur­ther clin­i­cal stud­ies.

The drug can­di­date has been eval­u­at­ed in pre­clin­i­cal stud­ies for the poten­tial treat­ment of coro­n­avirus infec­tion.

“Remde­sivir has demon­strat­ed in vit­ro and in vivo activ­i­ty in ani­mal mod­els against the viral pathogens MERS and SARS, which are coro­n­avirus­es that are struc­tural­ly sim­i­lar to 2019-nCoV,” said Gilead’s chief med­ical offi­cer Mer­dad Parsey.

In mice, remde­sivir sig­nif­i­cant­ly decreased Mid­dle East res­pi­ra­to­ry syn­drome (MERS)-coronavirus lung viral loads and improved res­pi­ra­to­ry func­tion and dis­ease out­comes, where­as lopinavir/ritonavir plus IFN-beta only improved res­pi­ra­to­ry func­tion, accord­ing to the in vivo data pre­sent­ed at the 32nd Inter­na­tion­al Con­fer­ence on Antivi­ral Research in Bal­ti­more in May 2019.

The in vit­ro data pre­sent­ed at the same con­fer­ence in May 2017 showed that remde­sivir was high­ly active against mul­ti­ple coro­n­avirus­es, includ­ing severe acute res­pi­ra­to­ry syn­drome (SARS), MERS and murine hepati­tis with EC50 in the range of 0.02–0.07 mM, and exhib­it­ed selec­tiv­i­ty index­es of 135 to 1,600 in human and murine cell lines.

As for now, it remains to be seen if there is antivi­ral data for remde­sivir that show activ­i­ty against 2019-nCoV.

“The U.S. patient’s con­di­tions improved sig­nif­i­cant­ly, but that’s all we have,” He told BioWorld. “Once the clin­i­cal tri­al com­pletes in April, the con­clu­sion will be clear.”

He added the end of April would like­ly be the ear­li­est point to tell if remde­sivir works, as the clin­i­cal tri­al can­not go any faster. The treat­ment itself will take nine days, and the data analy­sis will also take time.

As of Feb 3., 17,242 peo­ple are con­firmed to be infect­ed and 361 have died. The num­bers have sky­rock­et­ed over the past few weeks.

Due to the enor­mous pres­sure to curb the spread of 2019-nCoV, remde­sivir could be the first drug used on Chi­nese patients under the com­pas­sion­ate use pro­gram, which was writ­ten into China’s Drug Admin­is­tra­tion Law in August 2019. The U.S. allowed remde­sivir to be used on the 35-year-old patient on a com­pas­sion­ate basis.

Remde­sivir had already been used on the same basis on a patient in the U.K. infect­ed with Ebo­la in Octo­ber 2015.

Glob­al efforts

Cur­rent­ly, there are more than 40 drugs under devel­op­ment glob­al­ly to fight the coro­n­avirus infec­tion, and efforts are con­cen­trat­ed on SARS and MERS. Among the drug can­di­dates, 65% are against MERS and 25% against SARS.

The glob­al pipeline will see two new drug can­di­dates tar­get­ing the nov­el coro­n­avirus 2019-nCoV, which will be devel­oped by Mod­er­na Ther­a­peu­tics Inc. as an mRNA vac­cine and Inovio Phar­ma­ceu­ti­cal Inc. as INO-4800.

Also join­ing the R&D efforts are John­son & John­son, Novavax Inc., Vir Biotech­nol­o­gy Inc., Regen­eron Phar­ma­ceu­ti­cals Inc., Wuxi Bio­log­ics Cay­man Inc., Stemir­na Ther­a­peu­tics Co. Ltd., Bravo­vax Co. and Geo­vax Labs Inc. Ltd.

In acad­e­mia, Hong Kong researchers led by micro­bi­ol­o­gist Yuen Kwok-yung have made progress in devel­op­ing a vac­cine for 2019-nCoV by mod­i­fy­ing an influen­za vac­cine with a part of the sur­face anti­gen of the coro­n­avirus. The Uni­ver­si­ty of Queens­land (UQ) in Aus­tralia is also aim­ing to devel­op one.

HIV drugs also play a part.

Lopinavir/ritonavir, a HIV‑1 pro­tease inhibitor mar­ket­ed by Abb­vie in 2000, will be inves­ti­gat­ed in a clin­i­cal tri­al in Chi­na for 2019-nCoV. Ascle­tis Phar­ma Inc. has also filed with reg­u­la­tors to include its riton­avir and ASC09 fixed-dose com­bi­na­tion for emer­gency use. The com­pa­ny said Feb. 3 it is in talks with med­ical researchers to assist them in ini­ti­at­ing clin­i­cal tri­als.

———–

“Gilead’s remde­sivir enters Chi­na phase III tri­al to fight coro­n­avirus” by Elise Mak; BioWorld; 02/03/2020

“Remde­sivir is yet to be approved any­where glob­al­ly and has not been demon­strat­ed to be safe or effec­tive for any use. How­ev­er, a paper in The New Eng­land Jour­nal of Med­i­cine pub­lished Jan. 31 sug­gest­ed there was a pos­si­bil­i­ty of using the drug can­di­date to help con­tain the dead­ly 2019-nCoV virus, which has killed 361 peo­ple so far.”

It was not proven to be safe or effec­tive. And yet a sin­gle pos­i­tive result from remde­sivir prompt­ed a crash pro­gram for human clin­i­cal tri­als with­in days of that pos­i­tive result. Even Gildead­’s He Gongx­in admit­ted that the ONLY evi­dence they had was the sin­gle patien­t’s improved con­di­tion. That’s not a triv­ial piece of evi­dence but it’s clear that more evi­dence would nor­mal­ly be required for human clin­i­cal tri­als to start for a com­pound that has­n’t yet been approved to be effec­tive or safe any­where in the world:

...
On Jan 26, a 35-year-old patient in the U.S. with 2019-nCoV received remde­sivir, a week after he was admit­ted to the hos­pi­tal, accord­ing to reports. The fol­low­ing day, his fever went down from 39.4 degrees Cel­sius to 37.3 degrees Cel­sius, oxy­gen sat­u­ra­tion val­ues improved to 94% to 96%, and the pre­vi­ous bilat­er­al low­er-lobe rales were no longer present.

Five days after being treat­ed with remde­sivir, he was said to be afebrile, with all symp­toms resolved except for his cough, which was get­ting bet­ter.

The encour­ag­ing result prompt­ed Gilead and the Chi­nese author­i­ties to move the phase III tri­al ahead and expand it to a lot more patients who need treat­ment des­per­ate­ly.

“Remde­sivir is not a well-proven drug in either the U.S. or Chi­na,” He Gongx­in, for­mer chief rep­re­sen­ta­tive of the Shang­hai office at Gilead, told BioWorld. “Since 2019-nCoV is a new virus, we’ll just try it. There are good sci­en­tif­ic rea­sons for us to believe it could be safe and effi­ca­cious.

“I believe this is the best chance we have for now,” He added.

...

As for now, it remains to be seen if there is antivi­ral data for remde­sivir that show activ­i­ty against 2019-nCoV.

“The U.S. patient’s con­di­tions improved sig­nif­i­cant­ly, but that’s all we have,” He told BioWorld. “Once the clin­i­cal tri­al com­pletes in April, the con­clu­sion will be clear.”

He added the end of April would like­ly be the ear­li­est point to tell if remde­sivir works, as the clin­i­cal tri­al can­not go any faster. The treat­ment itself will take nine days, and the data analy­sis will also take time.
...

And note how the US patient who received remde­sivir was allowed to take it on a com­pas­sion­ate use basis. That’s basi­cal­ly let­ting him use it despite NONE of the nor­mal safe­ty tests hav­ing been done:

...
As of Feb 3., 17,242 peo­ple are con­firmed to be infect­ed and 361 have died. The num­bers have sky­rock­et­ed over the past few weeks.

Due to the enor­mous pres­sure to curb the spread of 2019-nCoV, remde­sivir could be the first drug used on Chi­nese patients under the com­pas­sion­ate use pro­gram, which was writ­ten into China’s Drug Admin­is­tra­tion Law in August 2019. The U.S. allowed remde­sivir to be used on the 35-year-old patient on a com­pas­sion­ate basis.
...

So that’s how Gildead­’s drug was treat­ed. Giv­en the cir­cum­stances, it’s hard to see why Oya­Gen’s drug should­n’t be giv­en sim­i­lar rushed treat­ment. Espe­cial­ly since, unlike remde­sivir, OYA‑1 has actu­al­ly been test­ed on men, women and chil­dren and giv­en FDA approval. We know what the safe lev­els are and it’s been tried on humans decades ago. What pos­si­ble excuse is there for giv­ing Gilead­’s exper­i­men­tal drug that’s bare­ly been test­ed on human this spe­cial rush treat­ment while seem­ing­ly ignor­ing the OYA‑1 results?

Here’s anoth­er exam­ple of how the nor­mal pro­ce­dures are being ignored in light the urgency of the sit­u­a­tion: Mod­er­na, one of the com­pa­nies work­ing on a vac­cine, is being allowed to pro­ceed with human clin­i­cal tri­als of its vac­cine despite not hav­ing done tri­als on ani­mals that show their exper­i­men­tal vac­cine is even effec­tive. The ani­mal tri­als and human tri­als will instead take place in par­al­lel with each oth­er.

Part of the rea­son for this unusu­al deci­sion is because the ani­mal tri­als face a delay due to a lack of mice that are actu­al­ly sus­cep­ti­ble to coro­n­avirus­es. It turns out coro­n­avirus­es aren’t adept at infect­ing mouse cells so a strain of mice was bred years that was vul­ner­a­ble for test­ing SARS treat­ments. After con­cern about Ebo­la waned the num­ber of these mice dropped so much that there are hard­ly any left. So whole new colonies of these spe­cial mice need to be regrown for the ani­mal tests of the vac­cine’s effec­tive­ness to take place.

This deci­sion could prove to be par­tic­u­lar­ly con­tro­ver­sial because Mod­er­na’s vac­cine is an mRNA vac­cine. It’s a new approach to vac­cines where, instead of inject­ing some­one with some­thing like a a weak­ened form of a virus, an mRNA vac­cine is inject­ed into your cells where it car­ries the instruc­tion to pro­duce a pro­tein that looks like part of the virus. There’s no per­ma­nent change to some­one’s DNA. It’s just a one-time injec­tion of for­eign DNA that will be used by the body to pro­duce the viral-chunks and then the mRNA gets degrad­ed. It’s much cheap­er and eas­i­er to pro­duce mRNA vac­cines than the tra­di­tion­al kinds and it allows for the rapid devel­op­ment of new vac­cines based sole­ly on the virus’s sequence. It’s actu­al­ly a great inno­va­tion in vac­cine tech­nolo­gies. But it’s still new. And yet, despite that new­ness, Mod­er­na is being giv­en a pret­ty dra­mat­ic pass on the nor­mal vac­cine-devel­op­ment pro­ce­dures and is going to be allowed to test its mRNA vac­cines on healthy vol­un­teers despite any evi­dence from ani­mal mod­els that the vac­cine helps stop the COVID-19 virus at all. Because it’s real­ly urgent. And yet all this cor­ner-cut­ting is for a vac­cine that won’t be avail­able for anoth­er year at the ear­li­est:

STAT News

Researchers rush to test coro­n­avirus vac­cine in peo­ple with­out know­ing how well it works in ani­mals

By Eric Bood­man
March 11, 2020

As they race to test an exper­i­men­tal coro­n­avirus vac­cine, researchers aren’t wait­ing to see how well it pre­vents infec­tion in ani­mals before try­ing it in peo­ple, break­ing from the usu­al pro­to­col.

“I don’t think prov­ing this in an ani­mal mod­el is on the crit­i­cal path to get­ting this to a clin­i­cal tri­al,” said Tal Zaks, chief med­ical offi­cer at Mod­er­na, a Cam­bridge, Mass.-based biotech that has pro­duced a Covid-19 vac­cine can­di­date at record speed. He told STAT that sci­en­tists at the Nation­al Insti­tutes of Health are “work­ing on non­clin­i­cal research in par­al­lel.” Mean­while, the clin­i­cal tri­al start­ed recruit­ing healthy par­tic­i­pants in the first week of March.

That isn’t how vac­cine test­ing nor­mal­ly hap­pens. Reg­u­la­tors require that a man­u­fac­tur­er show a prod­uct is safe before it goes into peo­ple, and while it isn’t enshrined in law, researchers almost always check that a new con­coc­tion is effec­tive in lab ani­mals before putting human vol­un­teers at poten­tial risk.

“This is very unusu­al,” explained Akiko Iwasa­ki, a Yale Uni­ver­si­ty micro­bi­ol­o­gist who stud­ies the immune response to virus­es. “It reflects the urgency to devel­op vac­cines to counter the Covid-19 pan­dem­ic.”

To some, the sweep of out­break is emer­gency enough to jus­ti­fy simul­ta­ne­ous­ly work­ing on steps that would nor­mal­ly be done sequen­tial­ly. To oth­ers, jum­bling the order of the recipe seems moral­ly ques­tion­able, because there could poten­tial­ly be unknown haz­ards and it’s unclear how effec­tive this par­tic­u­lar for­mu­la­tion is.

“The tra­di­tion­al vac­cine time­line is 15 to 20 years. That would not be accept­able here,” said Mark Fein­berg, pres­i­dent and CEO of the Inter­na­tion­al AIDS Vac­cine Ini­tia­tive, whose work as chief pub­lic health and sci­ence offi­cer at Mer­ck Vac­cines was instru­men­tal in the devel­op­ment of the immu­niza­tion against Ebo­la. “When you hear pre­dic­tions about it tak­ing at best a year or a year and a half to have a vac­cine avail­able … there’s no way to come close to those time­lines unless we take new approach­es.”

He knows that it’s impor­tant to see how well a new vac­cine can stop infec­tion in ani­mals, but to him, giv­en the cur­rent emer­gency, it makes sense to start human safe­ty test­ing before those stud­ies are fin­ished. “I per­son­al­ly think that’s not only appro­pri­ate; I think that’s the only option we have,” Fein­berg went on.

Yet ethi­cists aren’t so sure that the even­tu­al ben­e­fits of rush­ing this unproven vac­cine into clin­i­cal tri­als will out­weigh the risks. “Out­breaks and nation­al emer­gen­cies often cre­ate pres­sure to sus­pend rights, stan­dards and/or nor­mal rules of eth­i­cal con­duct. Often our deci­sion to do so seems unwise in ret­ro­spect,” wrote Jonathan Kim­mel­man, direc­tor of McGill University’s bio­med­ical ethics unit, in an email to STAT.

The ques­tion is com­pli­cat­ed by the new­ness of the sci­ence at play. The tech­nol­o­gy that has allowed Mod­er­na to craft an exper­i­men­tal vac­cine so fast has not yield­ed a sin­gle immu­niza­tion that’s made it to mar­ket so far. It’s a trendy idea: Instead of inject­ing peo­ple with a weak­ened pathogen or pro­teins from the sur­face of a pathogen, so that our bod­ies will learn to fight off such infec­tions in the future, sci­en­tists are bet­ting on a kind of genet­ic hack, a lab-made con­coc­tion that gets the body to pro­duce its own virus-like bits which it will then train itself to com­bat.

At the cen­ter of it all is a mol­e­cule called mes­sen­ger RNA, or mRNA. Inside of us, its nor­mal func­tion is to trans­mit the instruc­tions con­tained with­in our DNA to the cel­lu­lar pro­tein-mak­ing fac­to­ries that car­ry them out. In Moderna’s recipe, the mRNA is syn­thet­ic, pro­grammed with the goal of get­ting our inner machin­ery to pro­duce cer­tain coro­n­avirus-like pro­teins — the very pro­teins that the pathogen uses to gain entry into our cells. Once those home­made dum­my virus par­ti­cles are there, the think­ing goes, our bod­ies will learn to rec­og­nize and clob­ber the real thing.

The method’s great­est advan­tage is its speed. The virus behind the out­break that began in Wuhan, Chi­na, was iden­ti­fied on Jan. 7. Less than a week lat­er — on Jan. 13 — researchers at Mod­er­na and the NIH had a pro­posed sequence for an mRNA vac­cine against it, and, as the com­pa­ny wrote in gov­ern­ment doc­u­ments, “we mobi­lized toward clin­i­cal man­u­fac­ture.” By Feb. 24, the team was ship­ping vials from a plant in Nor­wood, Mass., to the Nation­al Insti­tute of Aller­gy and Infec­tious Dis­eases, in Bethes­da, Md., for a planned clin­i­cal tri­al to test its safe­ty.

Though spon­sored by NIAID, the first-in-human exper­i­ment is tak­ing place in Seat­tle, at the Kaiser Per­ma­nente Wash­ing­ton Health Research Insti­tute. Researchers began recruit­ing healthy vol­un­teers in ear­ly March. Their plan is to enroll 45 peo­ple between 18 and 55, who will get two shots of Moderna’s inves­ti­ga­tion­al vac­cine, about a month apart. For their trou­ble, par­tic­i­pants will get $100 for each in-per­son study vis­it, for a total of $1,100.

That doesn’t mean the sci­en­tists have sped past ani­mal test­ing entire­ly. Virol­o­gists at NIAID tried the new vac­cine on run-of-the-mill lab mice, the insti­tute told STAT by email, on the same day that the tri­al began enrolling par­tic­i­pants. Bar­ney Gra­ham, direc­tor of NIAID’s vac­cine research cen­ter, lat­er added that those mice showed the same sort of immune response gen­er­at­ed by a sim­i­lar mRNA vac­cine against MERS, anoth­er coro­n­avirus. “That lev­el of immune response was suf­fi­cient to pro­tect mice from MERS CoV infec­tion,” Gra­ham wrote.

The trou­ble is, your aver­age lab mouse doesn’t seem sus­cep­ti­ble to the new virus. While the bug behind Covid-19 has no trou­ble co-opt­ing mol­e­cules on human cells to get inside and start mul­ti­ply­ing, it isn’t so good at latch­ing onto the mouse equiv­a­lent. Although Gra­ham can say the response pro­duced in every­day mice looks sim­i­lar to one that helped mice com­bat the virus in their bod­ies when infect­ed with MERS, he can’t yet say the same thing for the new coro­n­avirus, because the mice sus­cep­ti­ble to this pathogen aren’t ready yet.

These pathogen-sus­cep­ti­ble rodents were spe­cial­ly engi­neered in the wake of anoth­er coro­n­avirus out­break: SARS, in the ear­ly 2000s. To make them eas­i­er to infect, sci­en­tists adorned their cells with the human mol­e­cule that allows cer­tain coro­n­avirus­es to slip inside. But when coro­n­avirus research slowed between out­breaks, sci­en­tists couldn’t jus­ti­fy the expense of keep­ing many of them; so while these mice seem to be sus­cep­ti­ble to the new virus, too, there aren’t cur­rent­ly enough for exper­i­ments to start.

“Those mice in the U.S. are being bred so that the colony can be enlarged,” explained Gra­ham, adding, that they “will be avail­able for exper­i­ments with­in the next few weeks.”

The researchers have not said out­right that they’ll start dos­ing humans before they have results show­ing how well the vac­cine works in virus-sus­cep­ti­ble ani­mals, but when asked whether they would, Gra­ham replied, “Safe­ty and prod­uct integri­ty are the pri­ma­ry cri­te­ria for start­ing a Phase 1 tri­al and mRNA has now been used in sev­er­al clin­i­cal tri­als and shown to be safe and well tol­er­at­ed.”

Kaiser Per­ma­nente did not reply to STAT’s request for the informed con­sent form that tri­al par­tic­i­pants are sign­ing, which is sup­posed to describe the risks they will face, and like Mod­er­na, referred all ques­tions about pre­clin­i­cal test­ing for this vac­cine to NIAID.

To Hol­ly Fer­nan­dez Lynch, assis­tant pro­fes­sor of med­ical ethics at the Uni­ver­si­ty of Penn­syl­va­nia, start­ing human exper­i­ments before fin­ish­ing all of the usu­al ani­mal test­ing first rais­es a seri­ous ques­tion. “We may not be able to min­i­mize the risks as much as we would hope to, because we have the time pres­sure of the out­break,” she said. “Are the remain­ing risks accept­able in rela­tion to the ben­e­fits of the research?”

The poten­tial ben­e­fits are to have a vac­cine against Covid-19 ready for gen­er­al use as soon as pos­si­ble. That won’t hap­pen for a year at least. That time­line, Lynch went on, is “insane­ly fast,” but it prob­a­bly won’t be fast enough to help slow the cur­rent out­break.

If this research meant a vac­cine might be ready by this June, she said, peo­ple would prob­a­bly be all for it in spite of the cut cor­ners. “If we’re talk­ing about us get­ting a vac­cine in June of 2021 rather than March of 2021, that’s a much more uncer­tain sce­nario,” she said. “We shouldn’t delude our­selves into think­ing that skip­ping over steps is going to get a vac­cine into our hands by next week or next month.”

Even if researchers decide it’s worth forg­ing ahead and test­ing a new vaccine’s safe­ty in peo­ple while still fig­ur­ing out whether it works to pre­vent infec­tions in sus­cep­ti­ble ani­mals, they need to be ready to stop the human tri­al if the results don’t look good in mice, said Karen Maschke, a schol­ar at the Hast­ings Cen­ter, a non­par­ti­san think tank in Gar­ri­son, N.Y., and the edi­tor of the jour­nal Ethics & Human Research — whether that’s because there are bad side effects or sim­ply because the immu­niza­tion doesn’t work.

“There’s no rea­son to put peo­ple at risk in a study if there’s no effi­ca­cy,” she said, “even if it’s just the bur­den of being in a study. You don’t bur­den peo­ple to be in a study if the inter­ven­tion is not going to help.”

Then again, she point­ed out, ani­mal stud­ies are often lousy pre­dic­tors of what will be effec­tive in peo­ple.

Mod­er­na itself acknowl­edges that the task is daunt­ing, and this effort might not suc­ceed. “We have not pre­vi­ous­ly test­ed our rapid response capa­bil­i­ty and may be unable to pro­duce a vac­cine that suc­cess­ful­ly treats the virus in a time­ly man­ner, if at all,” the com­pa­ny wrote in a doc­u­ment filed with the Secu­ri­ties and Exchange Com­mis­sion.

What the com­pa­ny doesn’t say is that it has not yet brought a sin­gle prod­uct to mar­ket, even in non-emer­gency times. The major­i­ty of can­di­date vac­cines fail. If against all odds, this rushed project does work out, then the com­pa­ny needs to be extra care­ful about mon­i­tor­ing what hap­pens to those peo­ple who get it, said Arthur Caplan, head of med­ical ethics at New York University’s Gross­man School of Med­i­cine. “The more you speed it up … the greater the oblig­a­tion you have to track what’s going on when you get it out into the real world.”

He doesn’t see it as inher­ent­ly uneth­i­cal for ani­mal effi­ca­cy stud­ies and human safe­ty stud­ies to hap­pen at the same time, though he said vac­cine skep­tics might use this as fod­der.

...

———-

“Researchers rush to test coro­n­avirus vac­cine in peo­ple with­out know­ing how well it works in ani­mals” by Eric Bood­man; STAT News; 03/11/2020

“That isn’t how vac­cine test­ing nor­mal­ly hap­pens. Reg­u­la­tors require that a man­u­fac­tur­er show a prod­uct is safe before it goes into peo­ple, and while it isn’t enshrined in law, researchers almost always check that a new con­coc­tion is effec­tive in lab ani­mals before putting human vol­un­teers at poten­tial risk.”

This is not a nor­mal vac­cine devel­op­ment pipeline. The nor­mal vac­cine devel­op­ment time­line is like 15–20 years. And Mod­er­na’s vac­cine isn’t a nor­mal vac­cine. It’s a mRNA vac­cine tech­nol­o­gy, and there has­n’t been a sin­gle mRNA vac­cine that’s made it to mar­ket so far:

...
The ques­tion is com­pli­cat­ed by the new­ness of the sci­ence at play. The tech­nol­o­gy that has allowed Mod­er­na to craft an exper­i­men­tal vac­cine so fast has not yield­ed a sin­gle immu­niza­tion that’s made it to mar­ket so far. It’s a trendy idea: Instead of inject­ing peo­ple with a weak­ened pathogen or pro­teins from the sur­face of a pathogen, so that our bod­ies will learn to fight off such infec­tions in the future, sci­en­tists are bet­ting on a kind of genet­ic hack, a lab-made con­coc­tion that gets the body to pro­duce its own virus-like bits which it will then train itself to com­bat.

At the cen­ter of it all is a mol­e­cule called mes­sen­ger RNA, or mRNA. Inside of us, its nor­mal func­tion is to trans­mit the instruc­tions con­tained with­in our DNA to the cel­lu­lar pro­tein-mak­ing fac­to­ries that car­ry them out. In Moderna’s recipe, the mRNA is syn­thet­ic, pro­grammed with the goal of get­ting our inner machin­ery to pro­duce cer­tain coro­n­avirus-like pro­teins — the very pro­teins that the pathogen uses to gain entry into our cells. Once those home­made dum­my virus par­ti­cles are there, the think­ing goes, our bod­ies will learn to rec­og­nize and clob­ber the real thing.

The method’s great­est advan­tage is its speed. The virus behind the out­break that began in Wuhan, Chi­na, was iden­ti­fied on Jan. 7. Less than a week lat­er — on Jan. 13 — researchers at Mod­er­na and the NIH had a pro­posed sequence for an mRNA vac­cine against it, and, as the com­pa­ny wrote in gov­ern­ment doc­u­ments, “we mobi­lized toward clin­i­cal man­u­fac­ture.” By Feb. 24, the team was ship­ping vials from a plant in Nor­wood, Mass., to the Nation­al Insti­tute of Aller­gy and Infec­tious Dis­eases, in Bethes­da, Md., for a planned clin­i­cal tri­al to test its safe­ty.

Though spon­sored by NIAID, the first-in-human exper­i­ment is tak­ing place in Seat­tle, at the Kaiser Per­ma­nente Wash­ing­ton Health Research Insti­tute. Researchers began recruit­ing healthy vol­un­teers in ear­ly March. Their plan is to enroll 45 peo­ple between 18 and 55, who will get two shots of Moderna’s inves­ti­ga­tion­al vac­cine, about a month apart. For their trou­ble, par­tic­i­pants will get $100 for each in-per­son study vis­it, for a total of $1,100.
...

Now, it’s impor­tant to keep in mind that there’s noth­ing inher­ent­ly extra scary about mRNA vac­cines. It’s poten­tial­ly an extreme­ly use­ful tech­nol­o­gy. But this is still new vac­cine tech­nol­o­gy that those health vol­un­teers are going to be get­ting inject­ed with despite not have any evi­dence in ani­mals that the vac­cine is actu­al­ly effec­tive. It’s a real gam­ble being tak­en with those healthy vol­un­teers. A rea­son­able gam­ble, per­haps, based on the urgency of the sit­u­a­tion and what is known about the safe­ty of mRNA vac­cines (they appear to be safe). But this is still very out­side estab­lished pro­to­cols and it’s all being done out of a sense of urgency. And even if vac­cine is avail­able next year, that’s still not going to be near­ly soon enough to deal with the imme­di­ate issue that’s caus­ing the lock­down of the glob­al: avoid­ing severe cas­es that over­whelm health sys­tems. That is the most urgent issue and new drugs are the only viable solu­tion that could fea­si­ble be avail­able in the short-term:

...
The poten­tial ben­e­fits are to have a vac­cine against Covid-19 ready for gen­er­al use as soon as pos­si­ble. That won’t hap­pen for a year at least. That time­line, Lynch went on, is “insane­ly fast,” but it prob­a­bly won’t be fast enough to help slow the cur­rent out­break.

If this research meant a vac­cine might be ready by this June, she said, peo­ple would prob­a­bly be all for it in spite of the cut cor­ners. “If we’re talk­ing about us get­ting a vac­cine in June of 2021 rather than March of 2021, that’s a much more uncer­tain sce­nario,” she said. “We shouldn’t delude our­selves into think­ing that skip­ping over steps is going to get a vac­cine into our hands by next week or next month.”

...

What the com­pa­ny doesn’t say is that it has not yet brought a sin­gle prod­uct to mar­ket, even in non-emer­gency times. The major­i­ty of can­di­date vac­cines fail. If against all odds, this rushed project does work out, then the com­pa­ny needs to be extra care­ful about mon­i­tor­ing what hap­pens to those peo­ple who get it, said Arthur Caplan, head of med­ical ethics at New York University’s Gross­man School of Med­i­cine. “The more you speed it up … the greater the oblig­a­tion you have to track what’s going on when you get it out into the real world.”

He doesn’t see it as inher­ent­ly uneth­i­cal for ani­mal effi­ca­cy stud­ies and human safe­ty stud­ies to hap­pen at the same time, though he said vac­cine skep­tics might use this as fod­der.
...

So how many of the oth­er treat­ments being devel­oped for COVID-19 are going to be skip­ping the ani­mal tri­als in light of this mouse short­age? Or are oth­er researchers wait­ing on the mouse sup­ply for their ani­mal tri­als before pro­ceed­ing to peo­ple? Is Mod­er­na that only com­pa­ny that gets to jump straight to human tri­als? That would be inter­est­ing to know.

Either way, it’s clear that these nor­mal pro­ce­dures can be dra­mat­i­cal­ly sped up when author­i­ties have a sense of urgency. And it’s under­stand­able urgency in this case. So why has­n’t that that under­stand­able urgency giv­en to remde­sivir and the Mod­er­na vac­cine also applied to Oya­Gen’s incred­i­ble sound­ing results? Per­haps Harold Smith is over-hyp­ing those results. And as the fol­low­ing new arti­cle from today informs us, the gov­ern­ment agency that was work­ing with Oya­Gen — the Nation­al Insti­tute of Aller­gy and Infec­tious Dis­eases (NIAID) — con­firmed to reporters the remark­able results demon­strat­ed by OYA‑1 So this isn’t just Smith over-hyp­ing the find­ings. The NIAID also con­firmed that it vet­ted the Oya­Gen press release announc­ing those amaz­ing find­ings:

Sin­clair Broad­cast Group
Spot­light on Amer­i­ca

One com­pa­ny says they’re close in the race for a coro­n­avirus cure

by JOCE STERMAN and ALEX BRAUER, Sin­clair Broad­cast Group
Mon­day, March 16th 2020

WASHINGTON (SBG) —With the threat of coro­n­avirus grow­ing, the devel­op­ment of vac­cines and antivi­ral med­ica­tions to tack­le the dis­ease has become a huge pri­or­i­ty for gov­ern­ment offi­cials and pri­vate indus­try. With researchers fran­ti­cal­ly work­ing on options, one New York com­pa­ny says they believe they’re get­ting close to a cure.

...

At Novavax in Gaithers­burg, Mary­land, an all-female team talked with our affil­i­ate WJLA about its efforts to cre­ate a vac­cine. That facil­i­ty is in phase two of devel­op­ment, cur­rent­ly test­ing vac­cines on ani­mals. And inside the Texas Bio­med­ical Research Insti­tute in San Anto­nio, sci­en­tists are work­ing with sam­ples sent from an actu­al Coro­n­avirus case from Wash­ing­ton state, grow­ing sam­ples there in the ear­li­est stage of vac­cine devel­op­ment. Dr. Richard Car­rion told our affil­i­ate KABB, “The urgency is there.”

But even the bright­est minds can’t speed up the process. Although an $8 bil­lion dol­lar emer­gency fund­ing bill is chan­nel­ing big mon­ey into vac­cine devel­op­ment, experts from Johns Hop­kins Uni­ver­si­ty, who recent­ly briefed law­mak­ers on Capi­tol Hill, said it could still take as long as 18 months to devel­op an effec­tive option. Accord­ing to the Asso­ci­at­ed Press, clin­i­cal tri­als were slat­ed to begin Mon­day on at least one poten­tial vac­cine.

But vac­cines aren’t the only prod­uct that could help pro­tect us. Antivi­ral drugs, accord­ing to Ingles­by, could be devel­oped and approved faster than vac­cines. A com­pa­ny in New York claims it has one that works. Doc­tor Harold Smith, the founder of Rochester-based Oya­gen, told our affil­i­ate WHAM, “We knew this was a pow­er­ful thing.”

Smith wants the Food and Drug Admin­is­tra­tion to fast track a for­mer can­cer drug it serendip­i­tous­ly dis­cov­ered can stop COVID-19 in its tracks. Accord­ing to a press release put out by the com­pa­ny, unpub­lished results of test­ing done at a gov­ern­ment lab in coop­er­a­tion with the Nation­al Insti­tute of Aller­gy and Infec­tious Dis­eases showed suc­cess against coro­n­avirus in cell cul­tures. NIAID con­firmed the research to Spot­light on Amer­i­ca and said it had vet­ted Oya­gen’s press release to the pub­lic.

Human test­ing for one thing. The drug Oya­gen has been work­ing on would still need clin­i­cal tri­als if it’s giv­en the go-ahead. Spot­light on Amer­i­ca reached out to the FDA. We were told the agency won’t con­firm drugs in devel­op­ment. An FDA spokesman told us, gen­er­al­ly, “We con­tin­ue to work with inter­est­ed spon­sors to help expe­dite any addi­tion­al clin­i­cal tri­als for COVID-19 med­ical coun­ter­mea­sures that may be appro­pri­ate.”

But even if Oya­gen’s drug was fast-tracked, Smith says approval could still be six to eight months away, keep­ing the clock tick­ing on a poten­tial cure.

———–

“One com­pa­ny says they’re close in the race for a coro­n­avirus cure” by JOCE STERMAN and ALEX BRAUER; Sin­clair Broad­cast Group; 03/16/2020

“Smith wants the Food and Drug Admin­is­tra­tion to fast track a for­mer can­cer drug it serendip­i­tous­ly dis­cov­ered can stop COVID-19 in its tracks. Accord­ing to a press release put out by the com­pa­ny, unpub­lished results of test­ing done at a gov­ern­ment lab in coop­er­a­tion with the Nation­al Insti­tute of Aller­gy and Infec­tious Dis­eases showed suc­cess against coro­n­avirus in cell cul­tures. NIAID con­firmed the research to Spot­light on Amer­i­ca and said it had vet­ted Oya­gen’s press release to the pub­lic.”

That clears up whether or not we’re deal­ing with busi­ness own­er who was over-hyp­ing his results. The NIAID con­firmed the research and that it vet­ted Oya­Gen’s press release.

Also note that this is basi­cal­ly the only new arti­cle on the Oya­Gen claims in recent days. We’re still liv­ing in Harold Smith’s Twi­light Zone episode where no one cares. Hence, we still have Smith basi­cal­ly pub­licly beg­ging for the drug to get fast-tracked and yet there’s no indi­ca­tion that’s going to hap­pen. Instead, the FDA just gives a gener­ic non-response response when asked about it:

...
Human test­ing for one thing. The drug Oya­gen has been work­ing on would still need clin­i­cal tri­als if it’s giv­en the go-ahead. Spot­light on Amer­i­ca reached out to the FDA. We were told the agency won’t con­firm drugs in devel­op­ment. An FDA spokesman told us, gen­er­al­ly, “We con­tin­ue to work with inter­est­ed spon­sors to help expe­dite any addi­tion­al clin­i­cal tri­als for COVID-19 med­ical coun­ter­mea­sures that may be appro­pri­ate.”
...

So we know have gov­ern­ment con­fir­ma­tion of these stun­ning results found by gov­ern­ment researchers. And yet that’s the ONLY thing the gov­ern­ment is will to say about this remark­able find­ing at the same time Smith is con­tin­u­ing to pub­licly plea for this drug to get fast-tracked and at the same time oth­er drugs and vac­cines are them­selves get­ting fast-tracked. Isn’t this all real­ly, real­ly odd?

And note that, even if it is fast-tracked, we’re still look­ing at a six-to-eight month time­line. That’s accord­ing to Smith’s own pro­jec­tions:

...
But even if Oya­gen’s drug was fast-tracked, Smith says approval could still be six to eight months away, keep­ing the clock tick­ing on a poten­tial cure.
...

And almost an entire month has already been wast­ed. Will we see any “com­pas­sion­ate use” appli­ca­tions for drug in the mean time like what that patient got for remde­sivir in Jan­u­ary? We’ll see, but it’s not look­ing like­ly giv­en that Smith is still pub­licly beg­ging for this dis­cov­ery to even receive any atten­tion at all.

Per­haps this will all blow over a cou­ple of months. A best case sce­nario is that the virus is so infec­tious that it just sweeps the pop­u­la­tion and almost every­one gets infect­ed in short order but is also far less dead­ly than cur­rent­ly pro­ject­ed. This could all be over in a cou­ple months at that point. But if it turns out this virus real­ly is as dead­ly as it appears to key demo­graph­ics (the elder­ly and peo­ple with health com­pli­ca­tions) and infec­tious but not super-infec­tious, we could be look­ing at this lock­down sit­u­a­tion going on for months and even into 2021 as fight­ing the spread remains the top pri­or­i­ty. We don’t know how this is going to play out yet. But if it’s the lat­ter case and we’re still deal­ing with waves of severe cas­es six to eight months from now while fight­ing the spread remains a top pri­or­i­ty, we’re prob­a­bly going to be wish­ing we did­n’t wait for OYA-1’s mir­a­cle test results to go through a slow and steady peer review first.

It would appear that one of Steve Ban­non’s close asso­ciates is the White Nation­al­ist Steven Hat­fill, oth­er­wise known as the orig­i­nal sus­pect in the 2001 Anthrax Attacks. Ban­non has had Hat­fill on his pod­cast, includ­ing recent­ly “the­o­riz­ing” about COVID-19: https://www.mediamatters.org/steve-bannon/virologist-tells-steve-bannon-his-coronavirus-conspiracy-theory-theory-crackpot

Hat­fil­l’s ties to White Nation­al­ism, Fort Det­rick and pre­vi­ous bioter­ror are detailed in the excel­lent Van­i­ty Fair arti­cle “Mes­sage in the Anthrax” at this link: https://www.ph.ucla.edu/epi/bioter/messageanthrax.html

Hat­fill was “exon­er­at­ed” after a “flubbed” FBI inves­ti­ga­tion, sev­er­al pre-raid tipoffs, and an attack in the New York Times, all of which are detailed in the arti­cle as well as at His­to­ry Com­mons’ Anthrax Time­line: http://www.historycommons.org/timeline.jsp?timeline=anthraxattacks&anthraxattacks_suspects=anthraxattacks_steven_hatfill

Hat­fill was fired from Fort Det­rick and went to work at S.A.I.C., oth­er­wise linked to Dick Cheney and Cheney’s pro­tege Duane Andrews.

Here is a rel­e­vant por­tion of Hat­fil­l’s White Nation­al­ist cre­den­tials (the rest of the arti­cle is high­ly rel­e­vant, espe­cial­ly per­tain­ing to Fort Det­rick and its attempts to blame Sad­dam Hus­sein for the Anthrax, a gam­bit that was also ham­mered repeat­ed­ly by none oth­er than Mike Pence, who was the only Repub­li­can to receive an Anthrax let­ter besides Democ­rats Daschle and Leahy):

“In its inter­view with Hat­fill, Insight report­ed that he had worked in Zim­bab­we in the late 1970s when “an epi­dem­ic of anthrax from nat­ur­al caus­es affect­ed 10,000 peo­ple.” In fact, Hat­fill had been in apartheid Rhode­sia from 1978 to 1980 (the year it was renamed Zim­bab­we), and wit­nessed the worst out­break of anthrax ever record­ed — in a part of Africa where anthrax was rarely encoun­tered. Dur­ing the civ­il war to top­ple the apartheid gov­ern­ment, the south­ern Trib­al Trust Lands were rav­aged by an epi­dem­ic that caused 10,738 record­ed human infec­tions in about two years. Today, black Zim­bab­weans and their live­stock are still becom­ing ill and dying from the bio­log­i­cal fall­out.

“...That the out­break was “nat­ur­al” is debat­able. In 1992, Dr. Meryl Nass, an Amer­i­can physi­cian, and Jere­my Brick­hill, a Zim­bab­wean jour­nal­ist, pub­lished sep­a­rate reports sup­port­ing what was already sus­pect­ed: that the Rhode­sian anthrax epi­dem­ic was delib­er­ate, a biowar­fare attack on the black town­ships, prob­a­bly car­ried out by Rhode­si­a’s noto­ri­ous gov­ern­ment-backed Selous Scouts mili­tia.

“...In Jan­u­ary 2002, while com­pil­ing doc­u­ments by and about Hat­fill, includ­ing his unclas­si­fied sci­en­tif­ic pub­li­ca­tions, I found a brief auto­bi­og­ra­phy. In it, Hat­fill, though Amer­i­can, boast­ed of hav­ing served in the late 1970s with the Selous Scouts in Rhode­sia. In that same brief bio, Dr. Hat­fill indi­cat­ed that he had tak­en his med­ical degree from the God­frey Hug­gins School of Med­i­cine in Harare, Rhode­sia, which he attend­ed from 1978 to ’84. Next I searched the Inter­net for a Green­dale School some­where in Africa and dis­cov­ered the Courteney Selous School, sit­u­at­ed in the wealthy, white Harare sub­urb of Green­dale, a mile from the med­ical school where Hat­fill spent six years obtain­ing his M.D. while serv­ing, by his own uncon­firmed account, with the Selous Scouts.”

@Port of Den­ver, TWGE and Pter­rafractyl–

Rumi­na­tion about Africa should be fac­tored in with Hat­fil­l’s affi­la­tion with the Afrikan­er Resis­tance Move­ment: https://spitfirelist.com/for-the-record/ftr-642-update-on-the-anthrax-attacks-aids-and-biological-warfare/

In addi­tion, Dr. Lar­ry Ford worked on behalf of CIA with Project Coast, the apartheid regime’s bio­log­i­cal war­fare project.

https://spitfirelist.com/for-the-record/ftr-317-aids-biological-warfare-and-apartheid‑2/

Steve Ban­non’s affil­i­a­tion with these ele­ments is VERY sig­nif­i­cant.

Great work, Port of Den­ver!

Best,

Dave

ANd let’s not for­get the shad­owy joint US Cen­tral Intel­li­gence Agency-UK MI6, “South African Insti­tute for Mar­itime Research”...

https://www.nytimes.com/2019/01/27/world/africa/hammarskjold-south-africa-aids.html

Here’s a devel­op­ing sto­ry worth keep­ing an on with tan­gen­tial ties to the sto­ry of the far right Shin­cheon­ji cult and the spread of the SARS-CoV­‑2 virus to South Korea:

The may­or of Seoul, Park Won-soon, just turned up dead. He did­n’t come into work on Thurs­day for unspec­i­fied rea­sons and can­celled all of his meet­ings, includ­ing a meet­ing with a pres­i­den­tial admin­is­tra­tion offi­cial. The search for Park was sparked after his daugh­ter informed police Thurs­day after­noon and that her father left her a will-like ver­bal mes­sage. No foul play is sus­pect­ed but no sui­cide note was found either.

The cause for his dis­ap­pear­ance isn’t known but sus­pi­cions are falling on the fact that one of Park’s sec­re­taries had just lodged a com­plaint with the police Wednes­day night over sex­u­al harass­ment alle­ga­tion against Park over unwant­ed phys­i­cal con­tact that began in 2017. The sec­re­tary also report­ed­ly told police inves­ti­ga­tors that an unspec­i­fied num­ber of oth­er female employ­ees at Seoul City Hall had suf­fered sim­i­lar sex­u­al harass­ment by Park. Police con­firmed that a harass­ment charge was indeed filed against Park Wednes­day night.

Part of what makes charges of this nature so notable for Park is that he’s a long-time human rights activist and was the coun­try’s first lawyer to secure a sex­u­al harass­ment con­vic­tion. In oth­er words, his pub­lic image is going to suf­fer in a way that a more tra­di­tion­al­ly sleazy and misog­y­nis­tic politi­cian might not.

But anoth­er part of what makes this sto­ry so intrigu­ing is that Park, a mem­ber of Pres­i­dent Moon Jae-in’s left-wing Demo­c­ra­t­ic Par­ty, is the first may­or of Seoul to have been elect­ed to a third term in 2018 and had been con­sid­ered a poten­tial pres­i­den­tial can­di­date in 2022 elec­tions. So this was a ris­ing left-wing star in South Kore­an pol­i­tics.

It’s also worth not­ing that Park is the kind of politi­cian with a num­ber of far right ene­mies. In addi­tion to being an out­spo­ken crit­ic of Japan’s colo­nial-era poli­cies toward Korea, Park was a fierce oppo­nent of for­mer right-wing Pres­i­dent Park Geun-hye and open­ly sup­port­ed the mil­lions of peo­ple who flood­ed the city’s streets in late 2016 and 2017 call­ing for her ouster over a cor­rup­tion scan­dal. And it’s that larg­er con­text — a ris­ing star left-wing politi­cian seen as a poten­tial pres­i­den­tial can­di­date in the next elec­tion and a long-stand­ing cham­pi­on of wom­en’s rights in South Korea is found dead a day after a sex­u­al harass­ment com­plaint is filed against him — that makes this a sto­ry to keep an eye on:

Asso­ci­at­ed Press

Miss­ing Seoul mayor’s body found after mas­sive search

By HYUNG-JIN KIM and KIM TONG-HYUNG
July 9, 2020 17:52:08

SEOUL, South Korea (AP) — The miss­ing may­or of South Korea’s cap­i­tal, report­ed­ly embroiled in sex­u­al harass­ment alle­ga­tions, was found dead ear­ly Fri­day, more than half a day after giv­ing his daugh­ter a will-like mes­sage and then leav­ing home, police said.

Police said they locat­ed Park Won-soon’s body near a tra­di­tion­al restau­rant in wood­ed hills in north­ern Seoul, more than sev­en hours after they launched a mas­sive search for him.

Choi Ik-su, an offi­cer from the Seoul Met­ro­pol­i­tan Police Agency, told reporters there were no signs of foul play and no sui­cide note had been found at the site or in Park’s res­i­dence. He refused to elab­o­rate on the cause of Park’s death.

Choi said res­cue dogs found Park’s body, and police had recov­ered his bag, cell­phone and busi­ness cards.

His daugh­ter called police on Thurs­day after­noon and said her father had giv­en her “a will-like” ver­bal mes­sage in the morn­ing before leav­ing home. She didn’t explain the con­tents of the mes­sage, said an offi­cer at the Seoul Met­ro­pol­i­tan Police Agency who was respon­si­ble for the search oper­a­tion.

Police said they mobi­lized about 600 police and fire offi­cers, drones and track­ing dogs to search for Park in the hills, where his cell­phone sig­nal was last detect­ed. They said the phone was turned off when they tried to call him.

His daugh­ter called police after he couldn’t reach her father on the phone, the Seoul police offi­cer said, request­ing anonymi­ty because she was not autho­rized to speak to the media about the mat­ter.

Kim Ji-hyeong, a Seoul Met­ro­pol­i­tan Gov­ern­ment offi­cial, said Park did not come to work on Thurs­day for unspec­i­fied rea­sons and had can­celed all of his sched­ule, includ­ing a meet­ing with a pres­i­den­tial offi­cial at his Seoul City Hall office.

The rea­son for Park’s dis­ap­pear­ance wasn’t clear. The Seoul-based SBS tele­vi­sion net­work report­ed that one of Park’s sec­re­taries had lodged a com­plaint with police on Wednes­day night over alleged sex­u­al harass­ment such as unwant­ed phys­i­cal con­tact that began in 2017. The SBS report, which didn’t cite any source, said the sec­re­tary told police inves­ti­ga­tors that an unspec­i­fied num­ber of oth­er female employ­ees at Seoul City Hall had suf­fered sim­i­lar sex­u­al harass­ment by Park.

MBC tele­vi­sion car­ried a sim­i­lar report.

Choi, the police offi­cer, con­firmed that a com­plaint was filed with police against Park on Wednes­day. He refused to pro­vide fur­ther details, cit­ing pri­va­cy issues.

Police offi­cer Lee Byeong-seok told reporters that Park was last iden­ti­fied by a secu­ri­ty cam­era at 10:53 a.m. at the entrance to the hills, more than six hours before his daugh­ter called police to report him miss­ing.

Fire offi­cer Jeong Jin-hyang told reporters on Thurs­day night that res­cuers used dogs to search dan­ger­ous areas on the hills.

Park, 64, a long­time civic activist and human rights lawyer, was elect­ed Seoul may­or in 2011. He became the city’s first may­or to be vot­ed to a third term in June 2018. A mem­ber of Pres­i­dent Moon Jae-in’s lib­er­al Demo­c­ra­t­ic Par­ty, he had been con­sid­ered a poten­tial pres­i­den­tial can­di­date in 2022 elec­tions.

Park had most­ly main­tained his activist col­ors as may­or, crit­i­ciz­ing what he described as the country’s grow­ing social and eco­nom­ic inequal­i­ties and cor­rupt ties between large busi­ness­es and politi­cians.

As a lawyer, he was cred­it­ed with win­ning the country’s first sex­u­al harass­ment con­vic­tion. He has also been an out­spo­ken crit­ic of Japan’s colo­nial-era poli­cies toward Korea, includ­ing the mobi­liza­tion of Kore­an and oth­er women as sex slaves for Japan­ese sol­diers.

Park also estab­lished him­self as a fierce oppo­nent of for­mer con­ser­v­a­tive Pres­i­dent Park Geun-hye and open­ly sup­port­ed the mil­lions of peo­ple who flood­ed the city’s streets in late 2016 and 2017 call­ing for her ouster over a cor­rup­tion scan­dal.

Park Geun-hye, a daugh­ter of late author­i­tar­i­an leader Park Chung-hee, was for­mal­ly removed from office in March 2017 and is cur­rent­ly serv­ing a decades-long prison term on bribery and oth­er charges.

...

————

“Miss­ing Seoul mayor’s body found after mas­sive search” by HYUNG-JIN KIM and KIM TONG-HYUNG; Asso­ci­at­ed Press; 07/09/2020

“Choi Ik-su, an offi­cer from the Seoul Met­ro­pol­i­tan Police Agency, told reporters there were no signs of foul play and no sui­cide note had been found at the site or in Park’s res­i­dence. He refused to elab­o­rate on the cause of Park’s death.”

No signs of foul play, but no sui­cide note either. There was, how­ev­er, a will-like mes­sage left with his daugh­ter and he can­celled all of his meet­ings Thurs­day. And this hap­pened a day after a sex­u­al harass­ment com­plaint was filed with the police. So over­all it does have the appear­ance of being a sui­cide:

...
His daugh­ter called police on Thurs­day after­noon and said her father had giv­en her “a will-like” ver­bal mes­sage in the morn­ing before leav­ing home. She didn’t explain the con­tents of the mes­sage, said an offi­cer at the Seoul Met­ro­pol­i­tan Police Agency who was respon­si­ble for the search oper­a­tion.

...

Kim Ji-hyeong, a Seoul Met­ro­pol­i­tan Gov­ern­ment offi­cial, said Park did not come to work on Thurs­day for unspec­i­fied rea­sons and had can­celed all of his sched­ule, includ­ing a meet­ing with a pres­i­den­tial offi­cial at his Seoul City Hall office.

The rea­son for Park’s dis­ap­pear­ance wasn’t clear. The Seoul-based SBS tele­vi­sion net­work report­ed that one of Park’s sec­re­taries had lodged a com­plaint with police on Wednes­day night over alleged sex­u­al harass­ment such as unwant­ed phys­i­cal con­tact that began in 2017. The SBS report, which didn’t cite any source, said the sec­re­tary told police inves­ti­ga­tors that an unspec­i­fied num­ber of oth­er female employ­ees at Seoul City Hall had suf­fered sim­i­lar sex­u­al harass­ment by Park.
...

But there’s also no avoid­ing the fact that Park cul­ti­vat­ed pow­er­ful ene­mies and was seen as a poten­tial future pres­i­dent. That’s exact­ly the kind of per­son we would expect to expe­ri­ence a mys­te­ri­ous ‘sui­cide’ of this nature:

...
Park, 64, a long­time civic activist and human rights lawyer, was elect­ed Seoul may­or in 2011. He became the city’s first may­or to be vot­ed to a third term in June 2018. A mem­ber of Pres­i­dent Moon Jae-in’s lib­er­al Demo­c­ra­t­ic Par­ty, he had been con­sid­ered a poten­tial pres­i­den­tial can­di­date in 2022 elec­tions.

Park had most­ly main­tained his activist col­ors as may­or, crit­i­ciz­ing what he described as the country’s grow­ing social and eco­nom­ic inequal­i­ties and cor­rupt ties between large busi­ness­es and politi­cians.

As a lawyer, he was cred­it­ed with win­ning the country’s first sex­u­al harass­ment con­vic­tion. He has also been an out­spo­ken crit­ic of Japan’s colo­nial-era poli­cies toward Korea, includ­ing the mobi­liza­tion of Kore­an and oth­er women as sex slaves for Japan­ese sol­diers.

Park also estab­lished him­self as a fierce oppo­nent of for­mer con­ser­v­a­tive Pres­i­dent Park Geun-hye and open­ly sup­port­ed the mil­lions of peo­ple who flood­ed the city’s streets in late 2016 and 2017 call­ing for her ouster over a cor­rup­tion scan­dal.
...

Did Park kill him­self in antic­i­pa­tion of the pub­lic shame of a wave of sex­u­al harass­ment alle­ga­tions that he feared com­ing out? It’s con­ceiv­able. But there are plen­ty of oth­er con­ceiv­able sce­nar­ios here’s too based on the avail­able facts and that’s why we can’t read­i­ly accept the sui­cide expla­na­tion quite yet with­out ask­ing whether or not it was a coerced ‘sui­cide’ that involved oth­er forms of per­sua­sion.

Along those lines, it’s worth not­ing anoth­er group of pow­er­ful ene­mies Park recent­ly acquired: the lead­ers of the Shin­cheon­ji fas­cist cult that was at the heart of the COVID-19 out­break in South Korea:

CNBC

Seoul may­or sues South Korea reli­gious group for ‘mur­der’ and ‘injury’ over spike in coro­n­avirus cas­es

Sahe­li Roy Choud­hury
Pub­lished Sun, Mar 1 202011:35 PM EST
Updat­ed Mon, Mar 2 20202:57 AM EST

Key Points

* Seoul City May­or Park Won-soon has sued key lead­ers of a church at the cen­ter of South Korea’s sud­den surge in the num­ber of con­firmed cas­es for the new coro­n­avirus that has infect­ed over 87,000 glob­al­ly.
* Park said on Face­book that he was suing the Shin­cheon­ji lead­ers “for mur­der, injury and vio­la­tion of pre­ven­tion and man­age­ment of infec­tious dis­eases.”

The may­or of Seoul has sued key lead­ers of the Shin­cheon­ji reli­gious group at the cen­ter of South Korea’s sud­den surge in the num­ber of con­firmed cas­es for the new coro­n­avirus.

May­or Park Won-soon said on Face­book he was suing the key lead­ers of Shin­cheon­ji “for mur­der, injury and vio­la­tion of pre­ven­tion and man­age­ment of infec­tious dis­eases,” accord­ing to a trans­la­tion from NBC News.

Park report­ed 12 lead­ers to the Seoul Cen­tral Dis­trict Prosecutor’s Office on Sun­day.

South Korea has the high­est num­ber of infec­tions out­side main­land Chi­na. On Mon­day morn­ing, the total num­ber of cas­es in South Korea stood at 4,212, and 22 had died from the infec­tion. Just two weeks ear­li­er, the num­ber of cas­es stood at around 30.

Con­tribut­ing to the expo­nen­tial rise in cas­es was the city of Daegu, and specif­i­cal­ly, the secre­tive reli­gious group called Shin­cheon­ji, accord­ing to the country’s Cen­ters for Dis­ease Con­trol and Pre­ven­tion. As of Sun­day morn­ing, the group account­ed for almost 60% of all cas­es in the coun­try, with most of them cen­tered in Daegu.

...

“We can han­dle the COVID-19 sit­u­a­tion as soon as pos­si­ble only when we force­ful­ly inves­ti­gate the twelve branch heads of the Shin­cheon­ji sect along with Lee Man Hee, the Chair­man of the sect,” Park said in his Face­book post on Sun­day. Lee is the founder and spir­i­tu­al leader of Shin­cheon­ji Church of Jesus.

“The pros­e­cu­tors need to car­ry out a rig­or­ous inves­ti­ga­tion and make sure it leads to a strict pun­ish­ment on the Shin­cheon­ji lead­er­ship that is at the cen­ter of this cri­sis,” Park added in a sep­a­rate state­ment post­ed to the mayor’s office web­site.

Lee apol­o­gized on Mon­day at a news con­fer­ence for his group’s inabil­i­ty to stop the spread of the virus and called the epi­dem­ic a “great calami­ty,” Reuters report­ed.

The may­or accused Lee and oth­ers of evad­ing tests for the virus and for fail­ing to take ade­quate mea­sures to get mem­bers of the group to work with health author­i­ties in pre­vent­ing trans­mis­sion of the infec­tion. Park also alleged that the Shin­cheon­ji pro­vid­ed false infor­ma­tion that obstruct­ed the work of the health author­i­ties.

The reli­gious group denied alle­ga­tions that its mem­bers hid their atten­dance at wor­ship ser­vice and car­ried out mis­sion­ary work in secret.

“The Gen­er­al Assem­bly Head­quar­ters of Shin­cheon­ji Church called for an imme­di­ate ban on all meet­ings, wor­ship gath­er­ings and access to its church­es through­out Korea after it was con­firmed that a believ­er in Shincheonji’s Daegu church had been infect­ed with COVID-19 (“Patient 31?) on 18th of Feb,” the group said in a state­ment.

...

———–

“Seoul may­or sues South Korea reli­gious group for ‘mur­der’ and ‘injury’ over spike in coro­n­avirus cas­es” by Sahe­li Roy Choud­hury; CNBC; 03/01/2020

““The pros­e­cu­tors need to car­ry out a rig­or­ous inves­ti­ga­tion and make sure it leads to a strict pun­ish­ment on the Shin­cheon­ji lead­er­ship that is at the cen­ter of this cri­sis,” Park added in a sep­a­rate state­ment post­ed to the mayor’s office web­site.”

A rig­or­ous inves­ti­ga­tion of the Shin­cheon­ji lead­er­ship over its role in the COVID out­break. And it sounds like it was Park him­self lead­ing this push to inves­ti­gate the group. That had ruf­fle quite a few feath­ers. Fas­cist feath­ers. What’s going to hap­pen with this inves­ti­ga­tion now that the per­son who ini­ti­at­ed it is dead? We’ll see, but it’s hard to imag­ine the Shin­cheon­ji lead­er­ship is very upset about May­or Park’s appar­ent sui­cide.