Science changes to take on virus

Re­searchers shift to pro­vide data quicker

USA TODAY US Edition - - NATION’S HEALTH - Jor­dan Nut­ting Mil­wau­kee Jour­nal Sen­tinel USA TODAY NET­WORK

MIL­WAU­KEE – In June 2019, a team of sci­en­tists and ed­i­tors launched an on­line server where med­i­cal re­searchers could sub­mit ar­ti­cles. The team’s goal was to help the med­i­cal com­mu­nity more quickly share re­search find­ings and learn from one an­other.

By the end of the year, the team re­ceived about 75 sub­mis­sions per week.

Then COVID-19 ap­peared. Now, nearly that many sub­mis­sions come in each day.

“I’m thrilled, I’m re­ally thrilled!” said Har­lan Krumholz, one of the founders of the server, medRxiv (pro­nounced “med ar­chive”). “It’s re­ally speed­ing the abil­ity for sci­en­tists to be able to com­mu­ni­cate with each other and un­der­stand what each other is do­ing.”

Just as ev­ery­day life has been af­fected by COVID-19, science it­self has changed.

Sci­en­tists have had to learn how to pro­duce mean­ing­ful in­for­ma­tion for a world clam­or­ing for speedy re­sults.

A month af­ter the first cases of COVID-19 were re­ported, re­searchers deter­mined the en­tire genome of the new virus and shared their re­sults on­line.

In March, oxy­gen and ven­ti­la­tors were the only treatment op­tions for pa­tients hos­pi­tal­ized with COVID-19. Physi­cians have added con­va­les­cent plasma, remde­sivir and dex­am­etha­sone to their arse­nal.

This speed and open­ness is not typ­i­cal of sci­en­tific re­search and re­quired fun­da­men­tal changes in the work sci­en­tists do.

“Science im­me­di­ately re­or­ga­nized it­self in a pur­pose­ful way to ad­dress a global threat,” James Brad­ner, presi

dent of the In­sti­tutes for Bio­Med­i­cal Re­search at No­var­tis, said in a we­bi­nar hosted by Chem­i­cal & En­gi­neer­ing News.

In most cases, sci­en­tists wel­come the changes and are proud of what has been ac­com­plished in such a short time.

“You had a bio­med­i­cal re­search es­tab­lish­ment that was, and con­tin­ues to be, hob­bled by un­der­fund­ing,” said Ar­turo Casade­vall, a pro­fes­sor at the Johns Hop­kins Bloomberg School of Pub­lic Health. Yet in light of the COVID-19 cri­sis, there has been “a tremen­dous gen­er­a­tion of knowl­edge very rapidly.”

Casade­vall is one of the re­search lead­ers for a na­tion­wide con­va­les­cent­plasma trial.

These ef­forts must be pur­sued with cau­tion and thought­ful­ness – a chal­lenge when the world is des­per­ate for re­sults.

Pi­lar Os­so­rio, a pro­fes­sor of law and bioethics at the Univer­sity of Wis­con­sin-Madi­son, wor­ries there is so much pres­sure to pro­duce pos­i­tive re­sults that con­di­tions are ripe for cut­ting corners. She noted that in an emer­gency when peo­ple are suf­fer­ing, there can be re­sis­tance to hav­ing con­trol groups that don’t get an ex­per­i­men­tal treatment in a study.

“But it doesn’t work sci­en­tif­i­cally,” Os­so­rio said. “It doesn’t pro­duce good enough data that you can ac­tu­ally have any con­fi­dence that the test in­ter­ven­tion is safe or ef­fec­tive.”

Any fail­ure to main­tain sci­en­tific rigor can have last­ing reper­cus­sions, in­clud­ing how the pub­lic views science. Ear­lier in the pan­demic, poorly de­signed clin­i­cal tri­als us­ing hy­drox­y­chloro­quine as a COVID-19 treatment con­trib­uted to con­tro­ver­sies over the ef­fec­tive­ness of the medicine.

Main­tain­ing re­search stan­dards is an eth­i­cal man­date, ac­cord­ing to Os­so­rio.

Science at ‘warp speed’

Science is largely a me­thod­i­cal and it­er­a­tive process. It’s slow. The process of go­ing from a hy­poth­e­sis to con­sen­sus can take years.

But a pan­demic doesn’t wait years for the first treat­ments to come out.

One so­lu­tion that has re­vealed it­self: Share in­for­ma­tion openly and find ways to in­no­vate.

On­line pre­print servers such as medRxiv have emerged as one tool in get­ting in­for­ma­tion out fast. Re­searchers can sub­mit stud­ies di­rectly to on­line archives, cut­ting out pro­cesses such as peer re­view that typ­i­cally pre­cede publi­ca­tion of stud­ies.

Since De­cem­ber, more than 5,000 manuscript­s re­lated to COVID-19 re­search have been sub­mit­ted to medRxiv and an­other pre­print server, bioRxiv. On­line archives are where the first ge­netic se­quence of SARS-CoV-2, the virus that causes the disease, and data for the dex­am­etha­sone clin­i­cal trial were posted.

“I don’t know what we would have done with­out pre­prints,” Casade­vall said.

Crit­ics of pre­prints em­pha­size the im­por­tance of peer re­view in catch­ing bad stud­ies and pro­tect­ing pa­tients.

Krumholz noted that medRxiv ed­i­tors cu­rate sub­mis­sions, check­ing for stud­ies that ought to be peer-re­viewed or that could cause med­i­cal harm.

Re­search com­pa­nies are shar­ing more in­for­ma­tion and re­sources, nor­mally taboo in a field rife with com­pe­ti­tion.

To the “sur­prise and de­light” of David Liu, a pro­fes­sor of chem­istry at Har­vard Univer­sity, one com­pany agreed to share clin­i­cal trial can­di­dates with his lab for test­ing.

“I hope that choice to co­op­er­ate rather than com­pete be­comes part of our legacy,” Liu said in the Chem­i­cal & En­gi­neer­ing News we­bi­nar.

The pres­sures of the COVID-19 pan­demic have led some re­searchers run­ning clin­i­cal tri­als to change tra­di­tional pro­to­cols. Some of those changes may be­come stan­dard pro­ce­dures.

“We have this real brick-and-mor­tar view of how clin­i­cal re­search had to hap­pen, and I think COVID has re­ally chal­lenged that,” said Betsy Nu­gent, the di­rec­tor of clin­i­cal tri­als de­vel­op­ment for the Univer­sity of Wis­con­sin School of Medicine and Pub­lic Health and UW Health.

Telemedici­ne, for ex­am­ple, could help peo­ple liv­ing in re­mote ar­eas par­tic­i­pate in tri­als.

“In some ways, I hope this will stay be­cause it gives us an ac­cess point to many, many more pa­tients,” Nu­gent said.

Piv­ot­ing work

Some sci­en­tists have piv­oted their re­search to join the fight against COVID-19, even if their new work isn’t di­rectly re­lated to find­ing medicines and treat­ments.

Song Gao, an as­sis­tant pro­fes­sor of ge­o­graphic in­for­ma­tion science at UW-Madi­son, was among the first to study and map how peo­ple’s mo­bil­ity changed dur­ing the COVID-19 pan­demic.

Be­fore the pan­demic, Michael Joyner, an anes­the­si­ol­o­gist who leads the Mayo Clinic’s ef­forts in the na­tion­wide plasma trial, stud­ied the phys­i­ol­ogy of marathon­ers. Casade­vall stud­ied fun­gal dis­eases.

“I think all of us as sci­en­tists, don’t al­ways rec­og­nize the ex­per­tise that we do have,” said Alison But­ten­heim, an as­so­ciate pro­fes­sor of nurs­ing and health pol­icy at the Univer­sity of Penn­syl­va­nia.

Some sci­en­tists’ role in the COVID-19 cri­sis isn’t in the lab or clinic but in the world of so­cial me­dia and ed­u­ca­tion.

In March, But­ten­heim and Malia Jones, an epi­demi­ol­o­gist at UW-Madi­son, launched “Dear Pan­demic,” a so­cial me­dia group that com­mu­ni­cates the lat­est COVID-19 re­search.

The group is run by a vol­un­teer team of 10 self-styled “nerdy girls” who use pub­lic health train­ing and sci­en­tific lit­er­acy to counter the ef­fects of speedy re­search and what the World Health Or­ga­ni­za­tion has called an “in­fo­demic.”

“We work re­ally hard in our tone and in the se­lec­tion of sto­ries and in our cov­er­age to help make those nu­anced and com­pli­cated an­swers in­tel­li­gi­ble,” But­ten­heim said.

AD­VO­CATE AURORA HEALTH

Con­va­les­cent plasma was added to the treatment op­tions just months af­ter the pan­demic be­gan.

ELIZABETH FIS­CHER/NI­AID/NIH

Ten­ta­cles emerge on cells from the kid­ney of a fe­male African green mon­key that have been in­fected with SARS-CoV-2.

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