Scientists Aim to Mutate Avian Flu in Lab to Better Understand its Spread

Diane Barnes, Global Security Newswire
Aug. 8, 2013, 12:02 p.m.

WASH­ING­TON — Nearly two dozen vir­o­lo­gists from around the world on Wed­nes­day said they want to modi­fy an emer­ging form of avi­an in­flu­enza in ways that could pro­duce more con­ta­gious, vir­u­lent or drug-res­ist­ant forms of the dis­ease.

The stud­ies would aim to shed light on how the so-called H7N9 vir­us could threaten hu­mans as it mutates in nature, the 22 re­search­ers wrote in a let­ter pub­lished in the journ­als Sci­ence and Nature. Their an­nounce­ment came one day after sci­ent­ists said a Chinese wo­man ap­peared to have caught the vir­us dir­ectly from her fath­er, ul­ti­mately killing both in what might be first case of the germ leap­ing dir­ectly between hu­mans.

The vir­us as of late May had spread to 132 people, 37 of whom had died as a res­ult, ac­cord­ing to the World Health Or­gan­iz­a­tion. China re­por­ted H7N9’s ini­tial jump to a hu­man at the end of March, but that case and those to fol­low ap­peared to be in­stances of trans­mis­sion from in­fec­ted birds.

When dis­eases mutate and take on new cap­ab­il­it­ies — such as the emer­ging trans­mis­sion of avi­an flu from one hu­man to an­oth­er — sci­ent­ists typ­ic­ally seek to study that muta­tion’s “gain of func­tion.” Such ana­lyses aim to de­vel­op a fuller un­der­stand­ing of the muta­tion as a first step to­ward fight­ing it.

“The risk of a pan­dem­ic caused by an avi­an in­flu­enza vir­us ex­ists in nature,” the sci­ent­ists wrote this week. “To an­swer key ques­tions im­port­ant to pub­lic health, re­search that may res­ult in [gain of func­tion] is ne­ces­sary and should be done.”

The pro­pos­al has already pro­voked ques­tions from ex­perts doubt­ful that any sci­entif­ic be­ne­fits from such ex­per­i­ments would out­weigh the risk of a mod­i­fied vir­us es­cap­ing — or be­ing stolen — from a labor­at­ory.

In an in­ter­view with Sci­ence, Prin­ceton Uni­versity mo­lecu­lar bio­lo­gist Ad­el Mah­moud said the pro­pos­al’s sci­entif­ic ra­tionale “is very flimsy, to put it mildly.” He ad­ded: “The claims that it will lead to any­thing use­ful are light­weight.”

In an at­tempt to ad­dress safety and se­cur­ity con­cerns, the let­ter’s au­thors ar­gued that safe­guards and pre­par­a­tion for the new stud­ies have been sig­ni­fic­antly in­formed by earli­er de­bate over gain-of-func­tion stud­ies in­volving an older avi­an flu sub­type, dubbed H5N1. Earli­er this year, flu re­search­ers ended a one-year vol­un­tary morator­i­um on the modi­fic­a­tion of that vir­us, which has been cir­cu­lat­ing among hu­mans since 2003 in a hard-to-catch but highly vir­u­lent form.

“The World Health Or­gan­iz­a­tion is­sued labor­at­ory biosafety guidelines for con­duct­ing re­search on H5N1 trans­mis­sion and, in the United States, ad­di­tion­al over­sight policies and risk-mit­ig­a­tion prac­tices have been put in place or pro­posed,” the Wed­nes­day let­ter states.

Stud­ies should take place un­der strin­gent “Biosafety Level 3 en­hanced” con­di­tions, in­volving safe­guards used in hand­ling po­ten­tially leth­al dis­eases, the re­search­ers said in an ac­com­pa­ny­ing doc­u­ment. Per­son­nel should un­der­go “rel­ev­ant back­ground checks” be­fore be­ing cleared to work with mod­i­fied agent, they said.

Re­search in­sti­tu­tions seek­ing U.S. funds to carry out cer­tain kinds of changes to the vir­us would see their grant re­quests un­der­go spe­cial re­view, Health and Hu­man Ser­vices De­part­ment of­fi­cials said in a state­ment made pub­lic on Wed­nes­day. However, the as­sur­ances of ad­di­tion­al scru­tiny ap­plied solely to pro­posed ex­per­i­ments deemed likely to in­crease the agent’s air­borne trans­miss­ib­il­ity.

A Chinese study has re­vealed an H7N9 vir­us strain already cap­able of passing through the air between fer­rets, a mam­mal of­ten used as a mod­el for hu­man trans­mis­sion.

H7N9 pro­duces its most severe hu­man symp­toms after tak­ing root in the lungs, but vir­us particles can also cause loc­al­ized in­fec­tions on “any mu­cous mem­brane,” in­clud­ing in the mouth, eyes and up­per res­pir­at­ory tract, said Amesh Adalja, a seni­or as­so­ci­ate with the Cen­ter for Health Se­cur­ity at the Uni­versity of Pitt­s­burgh Med­ic­al Cen­ter.

The agent can­not spread ef­fect­ively through the di­gest­ive sys­tem, Adalja ad­ded by tele­phone on Thursday.

The pause in H5N1 re­search took ef­fect after a U.S. bi­o­se­c­ur­ity pan­el aired wor­ries that find­ings from such re­search could po­ten­tially help bad act­ors en­gin­eer an en­hanced vir­us for an act of bi­o­ter­ror­ism.

However, de­bate dur­ing the morator­i­um “fo­cused over­whelm­ingly on the risks of ac­ci­dent­al re­lease of mod­i­fied mi­crobes,” ac­cord­ing to Der­rin Culp, a re­search as­so­ci­ate at Columbia Uni­versity’s Na­tion­al Cen­ter for Dis­aster Pre­pared­ness.

Bi­o­ter­ror­ism came up only “oc­ca­sion­ally” in dis­cus­sions among of­fi­cials and re­search­ers, and at no point was there any high-pro­file look at “the risk of de­lib­er­ate re­lease by an in­sider,” he wrote in April’s edi­tion of the Bul­let­in of the Atom­ic Sci­ent­ists.

Of­fi­cials and in­de­pend­ent ex­perts have gen­er­ally ad­vised giv­ing labor­at­ory man­agers con­sid­er­able free­dom in how they de­cide whom to en­trust with high-risk patho­gens. The ap­proach, he wrote, “would be deemed … naïve and ut­terly in­ad­equate” had more people died as a res­ult of the 2001 an­thrax at­tacks con­tro­ver­sially blamed on a U.S. Army mi­cro­bi­o­lo­gist.

Without ad­dress­ing wheth­er flu-modi­fic­a­tion ex­per­i­ments should be con­tin­ued, Culp said fed­er­al and state le­gis­lat­ors could al­ter pri­vacy stat­utes to “per­mit more in­trus­ive screen­ing and mon­it­or­ing” of in­di­vidu­als who handle dan­ger­ous bio­lo­gic­al agents. Such over­sight might be com­par­able to meas­ures fo­cused on people who work with nuc­le­ar weapons and re­lated ma­ter­i­als, he wrote.

“Mi­cro­bi­o­lo­gists can’t be ex­empt from such scru­tiny,” Culp said. “They lost that priv­ilege when they ac­quired the abil­ity — or merely the po­ten­tial — to gen­er­ate mass cas­u­al­ties.”

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