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FTR #1115 Review of Some Information about AIDS as a Biological Warfare Agent

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FTR #1115 This pro­gram was record­ed in one, 60-minute seg­ment

Intro­duc­tion: Against the back­ground of our dis­cus­sion of the Covid-19 out­break as what Mr. Emory has termed a “Bio-Psy-Op,” we present archival mate­r­i­al about the devel­op­ment of AIDS as a bio­log­i­cal war­fare agent.

(Pro­grams con­tain­ing infor­ma­tion on AIDS as a BW weapon include: AFA #s 16 and 39, as well as FTR #‘s 16, 19, 63, 317, 324, 557, 597, 606, 642, 644, 682, 820, 912, 1012.)

The pro­gram begins with review of an inter­view with Dr. Wilbert Jor­dan of Mar­tin Luther King Hos­pi­tal in Los Ange­les (from AFA 16.) Done in Decem­ber of 1984, it gives per­spec­tive on the epi­demi­o­log­i­cal aspects of AIDS–information that under­mines the pre­vail­ing the­o­ries at the time con­cern­ing the ori­gins of the dis­ease.

Not­ing that a dis­ease as lethal as AIDS was at the time (before anti-virals devel­oped to treat HIV infec­tion), Dr. Jor­dan is dis­mis­sive of the notion that such a lethal ail­ment could have been present in either Zaire or Haiti and then ret­ro­spec­tive­ly traced there after being dis­cov­ered in the U.S.

The notions of Haiti and/or Zaire being the point of ori­gin of the dis­ease played into the anti-immi­grant/xeno­pho­bic dynam­ic that has become preva­lent in the era of Don­ald Trump.

Dr. Jor­dan con­cludes by hypoth­e­siz­ing that the dis­ease was cre­at­ed in a lab­o­ra­to­ry, in all prob­a­bil­i­ty in the Unit­ed States.

Next, the pro­gram high­lights infor­ma­tion from FTR #686, set­ting forth infor­ma­tion about the Nation­al Can­cer Insti­tute’s Spe­cial Viral Can­cer Research Project.

After the [offi­cial] aban­don­ment by the U.S. of offen­sive bio­log­i­cal war­fare research, the Nixon admin­is­tra­tion declared a “war on can­cer” in 1971. As part of the War on Can­cer Nixon turned Fort Det­rick (the Army’s top BW research cen­ter) over to the Nation­al Can­cer Insti­tute for its Viral Can­cer Project. The Viral Can­cer Project was inex­tri­ca­bly linked with bio­log­i­cal war­fare research and may well have served as a cov­er for ongo­ing BW work. (Lis­ten­ers inter­est­ed in this mate­r­i­al are encour­aged to check out, among oth­er pro­grams, FTR #‘s 606, 682.)

For the pur­pos­es of the present dis­cus­sion, it is worth not­ing that it was the Nation­al Can­cer Insti­tute’s VCP that was at the epi­cen­ter of AIDS research in the Unit­ed States.

The VCP/NCI bio­log­i­cal war­fare con­nec­tion uti­lized strong con­nec­tions to uni­ver­si­ty research facil­i­ties. The Naval Bio­sciences Lab­o­ra­to­ry (man­aged by the Uni­ver­si­ty of Cal­i­for­nia), as well as Fort Det­rick were pro­found­ly involved with the NCI’s VCP. The Cell Cul­ture Lab­o­ra­to­ry at the Naval Bio­sciences Facil­i­ty pro­vid­ed the seed stock for the pro­duc­tion of vast quan­ti­ties of car­cino­genic and immuno­sup­pres­sive virus­es that were gen­er­at­ed by the Nation­al Can­cer Insti­tute.

The pro­duc­tion of those virus­es for the NCI was over­seen by Drs. James Duff and Jack Gru­ber, both long­time vet­er­ans of Fort Det­rick and its bio­log­i­cal war­fare research.

The aer­i­al trans­mis­sion of dead­ly path­o­gen­ic agents was a major focal point of the NCI’s VCP, appar­ent­ly over­lap­ping BW research projects. Two oth­er key researchers for the NCI, Drs. Alfred Hell­man and Mark Chatigny also had bio­log­i­cal war­fare research back­grounds, includ­ing work with aer­i­al trans­mis­sion of path­o­gen­ic agents.

Yet anoth­er com­po­nent of the NCI/VCP/BW con­nec­tion was the incor­po­ra­tion of phar­ma­ceu­ti­cal com­pa­nies in the research pro­grams. The Pfiz­er com­pa­ny pro­duced virus­es for the NCI’s VCP, includ­ing the immuno­sup­pres­sive Mason-Pfiz­er mon­key virus, like HIV, a retro­virus.

Among the most sig­nif­i­cant and alarm­ing aspects of the NCI’s VCP pro­gram is the fact that, when Fort Det­rick was con­vert­ed to the Fred­er­ick Can­cer Research Cen­ter, it was admin­is­tered by Lit­ton Bio­net­ics, a biotech­nol­o­gy subi­sidiary of Lit­ton Indus­tries. Lit­ton was a major defense con­trac­tor and a fre­quent vehi­cle for covert oper­a­tions.

Pri­or to assum­ing stew­ard­ship of Fort Det­rick for the NCI, Lit­ton Bio­net­ics had employed Dr. Robert Gal­lo (the “dis­cov­er­er” of HIV).

Of para­mount impor­tance in this inves­ti­ga­tion is the fact that the NCI’s VCP pro­gram involved numer­ous exper­i­ments and oper­a­tions designed at get­ting organ­isms to “jump species.” Promi­nent researchers famil­iar with these efforts expressed alarm and the con­vic­tion that such work should be out­lawed, lest it lead to the cre­ation of new, dead­ly organ­isms that would infect humans.

Obvi­ous­ly, this broad­cast and the line of inquiry approached in Mr. Emory’s decades-long inves­ti­ga­tion of AIDS as a man-made dis­ease high­light the possibility/probability/near cer­tain­ty that HIV is just such an organ­ism.

The pro­gram con­cludes with review of an excerpt from tes­ti­mo­ny before a House appro­pri­a­tions sub­com­mit­tee that was draw­ing up the defense bud­get for the fol­low­ing year. (The hear­ings were in 1969.) The tes­ti­mo­ny dis­cuss­es the pos­si­bil­i­ty of using genet­ic engi­neer­ing to pro­duce a dis­ease that would be “refrac­to­ry” to the immune sys­tem. This is vir­tu­al­ly the clin­i­cal def­i­n­i­tion of AIDS. It is worth not­ing that the project was fund­ed, and just such a disease—AIDS—appeared in just the time frame posit­ed. It is also worth not­ing that, in the 2002 edi­tion of A High­er Form of Killing, this pas­sage is omit­ted!!

A High­er Form of Killing; Robert Har­ris and Jere­my Pax­man; Hill and Wang [SC]; ISBN 0–8090-5471‑X; p. 241 (p. 266 in e‑book).

. . . As long ago as 1962, forty sci­en­tists were employed at the U.S. Army bio­log­i­cal war­fare lab­o­ra­to­ries on full-time genet­ics research. ‘Many oth­ers,’ it was said, ‘appre­ci­ate the impli­ca­tions of genet­ics for their own work.’ The impli­ca­tions were made more spe­cif­ic that genet­ic engi­neer­ing could solve one of the major dis­ad­van­tages of bio­log­i­cal war­fare, that it is lim­it­ed to dis­eases which occur nat­u­ral­ly some­where in the world. ‘With­in the next 5 to 10 years, it would prob­a­bly be pos­si­ble to make a new infec­tive micro-organ­ism which could dif­fer in cer­tain impor­tant respects from any known dis­ease-caus­ing organ­isms. Most impor­tant of these is that it might be refrac­to­ry to the immuno­log­i­cal and ther­a­peu­tic process­es upon which we depend to main­tain our rel­a­tive free­dom from infec­tious dis­ease.’ [Ital­ics are Mr. Emory’s.] The pos­si­bil­i­ty that such a ‘super germ’ may have been suc­cess­ful­ly pro­duced in a lab­o­ra­to­ry some­where in the world in the years since that assess­ment was made is one which should not be too read­i­ly cast aside. . . .

Pro­gram High­lights Include: Lit­ton Bio­net­ics’ work on the Mason-Pfiz­er mon­key virus while under con­tract to the NCI and when it employed Dr. Robert Gal­lo; research empha­sis on “zoonoses” (dis­eases that jump from ani­mals to humans) by the joint military/civilian con­sor­tium; Gal­lo’s work with NCI VCP/Ft. Det­rick vet­er­an Dr. Jack Gru­ber in a mass viral inoc­u­la­tion pro­gram under­tak­en by Lit­ton Bio­net­ics; the use of the Mason-Pfiz­er mon­key virus in the Lit­ton Bio­net­ics mass inoc­u­la­tion pro­gram.

1. The pro­gram begins with review of an inter­view with Dr. Wilbert Jor­dan of Mar­tin Luther King Hos­pi­tal in Los Ange­les. Done in Decem­ber of 1984, it gives per­spec­tive on the epi­demi­o­log­i­cal aspects of AIDS–information that under­mines the pre­vail­ing the­o­ries at the time con­cern­ing the ori­gins of the dis­ease.

Not­ing that a dis­ease as lethal as AIDS was at the time (before anti-virals devel­oped to treat HIV infec­tion), Dr. Jor­dan is dis­mis­sive of the notion that such a lethal ail­ment could have been present in either Zaire or Haiti and then ret­ro­spec­tive­ly traced there after being dis­cov­ered in the U.S.

The notions of Haiti and/or Zaire being the point of ori­gin of the dis­ease played into the anti-immi­grant/xeno­pho­bic dynam­ic that has become preva­lent in the era of Don­ald Trump.

Dr. Jor­dan con­cludes by hypoth­e­siz­ing that the dis­ease was cre­at­ed in a lab­o­ra­to­ry, in all prob­a­bil­i­ty in the Unit­ed States.

2. Next, the pro­gram high­lights infor­ma­tion from FTR #686, set­ting forth infor­ma­tion about the Nation­al Can­cer Insti­tute’s Spe­cial Viral Can­cer Research Project.

After the [offi­cial] aban­don­ment by the U.S. of offen­sive bio­log­i­cal war­fare research, the Nixon admin­is­tra­tion declared a “war on can­cer” in 1971. As part of the War on Can­cer Nixon turned Fort Det­rick (the Army’s top BW research cen­ter) over to the Nation­al Can­cer Insti­tute for its Viral Can­cer Project. The Viral Can­cer Project was inex­tri­ca­bly linked with bio­log­i­cal war­fare research and may well have served as a cov­er for ongo­ing BW work. (Lis­ten­ers inter­est­ed in this mate­r­i­al are encour­aged to check out, among oth­er pro­grams, FTR #‘s 606, 682.)

For the pur­pos­es of the present dis­cus­sion, it is worth not­ing that it was the Nation­al Can­cer Insti­tute’s VCP that was at the epi­cen­ter of AIDS research in the Unit­ed States.

The VCP/NCI bio­log­i­cal war­fare con­nec­tion uti­lized strong con­nec­tions to uni­ver­si­ty research facil­i­ties. The Naval Bio­sciences Lab­o­ra­to­ry (man­aged by the Uni­ver­si­ty of Cal­i­for­nia), as well as Fort Det­rick were pro­found­ly involved with the NCI’s VCP. The Cell Cul­ture Lab­o­ra­to­ry at the Naval Bio­sciences Facil­i­ty pro­vid­ed the seed stock for the pro­duc­tion of vast quan­ti­ties of car­cino­genic and immuno­sup­pres­sive virus­es that were gen­er­at­ed by the Nation­al Can­cer Insti­tute.

The pro­duc­tion of those virus­es for the NCI was over­seen by Drs. James Duff and Jack Gru­ber, both long­time vet­er­ans of Fort Det­rick and its bio­log­i­cal war­fare research.

The aer­i­al trans­mis­sion of dead­ly path­o­gen­ic agents was a major focal point of the NCI’s VCP, appar­ent­ly over­lap­ping BW research projects. Two oth­er key researchers for the NCI, Drs. Alfred Hell­man and Mark Chatigny also had bio­log­i­cal war­fare research back­grounds, includ­ing work with aer­i­al trans­mis­sion of path­o­gen­ic agents.

Yet anoth­er com­po­nent of the NCI/VCP/BW con­nec­tion was the incor­po­ra­tion of phar­ma­ceu­ti­cal com­pa­nies in the research pro­grams. The Pfiz­er com­pa­ny pro­duced virus­es for the NCI’s VCP, includ­ing the immuno­sup­pres­sive Mason-Pfiz­er mon­key virus, like HIV, a retro­virus.

Among the most sig­nif­i­cant and alarm­ing aspects of the NCI’s VCP pro­gram is the fact that, when Fort Det­rick was con­vert­ed to the Fred­er­ick Can­cer Research Cen­ter, it was admin­is­tered by Lit­ton Bio­net­ics, a biotech­nol­o­gy subi­sidiary of Lit­ton Indus­tries. Lit­ton was a major defense con­trac­tor and a fre­quent vehi­cle for covert oper­a­tions.

Pri­or to assum­ing stew­ard­ship of Fort Det­rick for the NCI, Lit­ton Bio­net­ics had employed Dr. Robert Gal­lo (the “dis­cov­er­er” of HIV).

Of para­mount impor­tance in this inves­ti­ga­tion is the fact that the NCI’s VCP pro­gram involved numer­ous exper­i­ments and oper­a­tions designed at get­ting organ­isms to “jump species.” Promi­nent researchers famil­iar with these efforts expressed alarm and the con­vic­tion that such work should be out­lawed, lest it lead to the cre­ation of new, dead­ly organ­isms that would infect humans.

Obvi­ous­ly, this broad­cast and the line of inquiry approached in Mr. Emory’s decades-long inves­ti­ga­tion of AIDS as a man-made dis­ease high­light the possibility/probability/near cer­tain­ty that HIV is just such an organ­ism.

Dis­cus­sion High­lights Include: Lit­ton Bio­net­ics’ work on the Mason-Pfiz­er mon­key virus while under con­tract to the NCI and when it employed Dr. Robert Gal­lo; research empha­sis on “zoonoses” (dis­eases that jump from ani­mals to humans) by the joint military/civilian con­sor­tium; Gal­lo’s work with NCI VCP/Ft. Det­rick vet­er­an Dr. Jack Gru­ber in a mass viral inoc­u­la­tion pro­gram under­tak­en by Lit­ton Bio­net­ics; the use of the Mason-Pfiz­er mon­key virus in the Lit­ton Bio­net­ics mass inoc­u­la­tion pro­gram.

3. The pro­gram con­cludes with review of an excerpt from tes­ti­mo­ny before a House appro­pri­a­tions sub­com­mit­tee that was draw­ing up the defense bud­get for the fol­low­ing year. (The hear­ings were in 1969.) The tes­ti­mo­ny dis­cuss­es the pos­si­bil­i­ty of using genet­ic engi­neer­ing to pro­duce a dis­ease that would be “refrac­to­ry” to the immune sys­tem. This is vir­tu­al­ly the clin­i­cal def­i­n­i­tion of AIDS. It is worth not­ing that the project was fund­ed, and just such a disease—AIDS—appeared in just the time frame posit­ed. It is also worth not­ing that, in the 2002 edi­tion of A High­er Form of Killing, this pas­sage is omit­ted!!

A High­er Form of Killing; Robert Har­ris and Jere­my Pax­man; Hill and Wang [SC]; ISBN 0–8090-5471‑X; p. 241 (p. 266 in e‑book).

. . . As long ago as 1962, forty sci­en­tists were employed at the U.S. Army bio­log­i­cal war­fare lab­o­ra­to­ries on full-time genet­ics research. ‘Many oth­ers,’ it was said, ‘appre­ci­ate the impli­ca­tions of genet­ics for their own work.’ The impli­ca­tions were made more spe­cif­ic that genet­ic engi­neer­ing could solve one of the major dis­ad­van­tages of bio­log­i­cal war­fare, that it is lim­it­ed to dis­eases which occur nat­u­ral­ly some­where in the world. ‘With­in the next 5 to 10 years, it would prob­a­bly be pos­si­ble to make a new infec­tive micro-organ­ism which could dif­fer in cer­tain impor­tant respects from any known dis­ease-caus­ing organ­isms. Most impor­tant of these is that it might be refrac­to­ry to the immuno­log­i­cal and ther­a­peu­tic process­es upon which we depend to main­tain our rel­a­tive free­dom from infec­tious dis­ease.’ [Ital­ics are Mr. Emory’s.] The pos­si­bil­i­ty that such a ‘super germ’ may have been suc­cess­ful­ly pro­duced in a lab­o­ra­to­ry some­where in the world in the years since that assess­ment was made is one which should not be too read­i­ly cast aside. . . .

Discussion

3 comments for “FTR #1115 Review of Some Information about AIDS as a Biological Warfare Agent”

  1. For those Dave Emory lis­ten­ers who need a visu­al ref­er­ence to the CIA’s weaponized immuno­log­i­cal genet­ics research, par­tic­u­lar­ly in the ear­ly 1960’s, have fun with the fol­low­ing link:

    https://www.cia.gov/readingroom/docs/CIA-RDP80-00247A004200090001‑4.pdf

    Posted by Robert Ward Montenegro | March 22, 2021, 8:25 pm
  2. Has the US found a new home for its var­i­ous ‘dual use’ biode­fense projects? Projects like the Eco­Health Alliance and Metabio­ta? It sure sounds like it, although we don’t real­ly know yet. What we do know is that there’s a new ‘ARPA’ in town: ARPA‑H. It’s like DARPA for health and med­i­cine. At least that’s the sales pitch. The details have yet to be worked out. But we do know who will be lead­ing it: Dr. Renee Wegrzyn, a biotech exec­u­tive with exten­sive gov­ern­ment expe­ri­ence. Expe­ri­ence that includes work five years of as a pro­gram man­ag­er for DARPA, where she over­saw projects using syn­thet­ic biol­o­gy to counter infec­tious dis­ease and bol­ster biose­cu­ri­ty. And while it’s cer­tain­ly pos­si­ble Wegrzyn’s work had absolute­ly noth­ing to do with the kind of ‘gain-of-func­tion’ work that that Eco­Health Alliance was work­ing on in the years lead­ing up to the COVID19 pan­dem­ic, there’s also no deny­ing that her resume sounds a lot like the resume of some­one who would be very famil­iar with that kind of work.

    So in light of the NIH’s recent deci­sion to rescind the Eco­Health Alliance’s grant over con­cerns about a lack of over­sight with of the Wuhan Insti­tute of Virol­o­gy, while keep­ing open the pos­si­bil­i­ty of more grants in the future after these ‘over­sight issues’ get worked out, we have to ask: is ARPA‑H the intend­ed new home for for the US’s dual use ‘biode­fense’ research? Because if so, it sounds like they chose some­one with the appro­pri­ate expe­ri­ence to lead it:

    The New York Times

    Biden Picks Biotech Exec­u­tive to Lead New Bio­med­ical Research Agency

    Dr. Renee Wegrzyn is Pres­i­dent Biden’s choice to lead the Advanced Research Projects Agency for Health, which is aimed at dri­ving bio­med­ical inno­va­tion.

    By Sheryl Gay Stol­berg
    Sept. 12, 2022

    WASHINGTON — Pres­i­dent Biden, sketch­ing out a vision for “bold approach­es” to fight­ing can­cer and oth­er dis­eases, announced on Mon­day that he had select­ed Dr. Renee Wegrzyn, a Boston biotech exec­u­tive with gov­ern­ment expe­ri­ence, as the direc­tor of a new fed­er­al agency aimed at pur­su­ing risky, far-reach­ing ideas that will dri­ve bio­med­ical inno­va­tion.

    Mr. Biden made the announce­ment at the John F. Kennedy Pres­i­den­tial Library and Muse­um in Boston, on the 60th anniver­sary of the for­mer president’s “moon­shot” speech that ush­ered in an era of space trav­el. He used the occa­sion to reit­er­ate his call to “end can­cer as we know it” — the tag line for his own “can­cer moon­shot” ini­tia­tive.

    “Imag­ine the pos­si­bil­i­ties — vac­cines that could pre­vent can­cer, like there is for HPV,” the pres­i­dent said, refer­ring to the human papil­lo­mavirus, which can cause cer­vi­cal and oth­er can­cers. “Imag­ine mol­e­c­u­lar ZIP codes that could deliv­er drugs and gene ther­a­py pre­cise­ly, to the right tis­sues. Imag­ine sim­ple blood tests dur­ing an annu­al phys­i­cal that could detect can­cer ear­ly.”

    Mr. Biden, whose son Beau died of brain can­cer in 2015, has a deep per­son­al com­mit­ment to advanc­ing can­cer research, and the Kennedy library was a reminder of that. Anoth­er Kennedy, for­mer Sen­a­tor Edward M. Kennedy, whom Mr. Biden described as “one of my dear­est friends,” died in 2009 of the same kind of can­cer — glioblas­toma — as Beau Biden.

    Mr. Biden helped cre­ate the can­cer moon­shot when he was vice pres­i­dent. Its goal, which he described as “com­plete­ly doable,” is to cut can­cer death rates by at least 50 per­cent over the next 25 years, while turn­ing “death sen­tences into chron­ic dis­eases.”

    He pro­posed the new bio­med­ical research agency this year as part of an effort to rein­vig­o­rate the ini­tia­tive.

    Mod­eled after the Defense Advanced Research Projects Agency, the new agency is known as the Advanced Research Projects Agency for Health. (In the argot of Wash­ing­ton, where every agency has an acronym, the defense research agency is called DARPA and the health agency is ARPA‑H.)

    The agency is sup­posed to be nim­ble and flex­i­ble — a kind of “Shark Tank” for bio­med­ical research, pop­u­lat­ed by “bril­liant vision­ary tal­ents” who will invest in untest­ed approach­es, know­ing that “prob­a­bly a sig­nif­i­cant frac­tion of the projects are going to fail,” said Dr. Fran­cis Collins, the for­mer direc­tor of the Nation­al Insti­tutes of Health, who now serves as Mr. Biden’s act­ing sci­ence advis­er and who helped lead the search for the new direc­tor.

    Dr. Wegrzyn is a vice pres­i­dent for busi­ness devel­op­ment at Gink­go Bioworks and the head of inno­va­tion at Con­cen­tric by Gink­go, the company’s ini­tia­tive to advance coro­n­avirus test­ing and track the spread of the virus. She also worked at DARPA and its sis­ter agency, the Intel­li­gence Advanced Research Projects Activ­i­ty.

    “Some of the prob­lems we face every day — espe­cial­ly in health and dis­ease — are so large they can seem insur­mount­able,” Dr. Wegrzyn said in a state­ment pro­vid­ed by the White House. “I have seen first­hand the tremen­dous exper­tise and ener­gy the U.S. bio­med­ical and biotech­no­log­i­cal enter­prise can bring to solve some of the tough­est health chal­lenges.”

    Con­gress has appro­pri­at­ed $1 bil­lion for ARPA‑H, which is housed with­in the Nation­al Insti­tutes of Health but reports direct­ly to Xavier Becer­ra, the sec­re­tary of health and human ser­vices — an arrange­ment that is intend­ed to keep the new agency from get­ting too caught up in the fed­er­al bureau­cra­cy. While its direc­tor is not a Sen­ate-con­firmed posi­tion, Mr. Biden may face push­back from Repub­li­cans, some of whom have argued that the agency dupli­cates the N.I.H.’s efforts.

    The agency already has an act­ing deputy direc­tor, Adam H. Rus­sell, also a DARPA alum­nus, who has been lay­ing the tech­ni­cal infra­struc­ture and oth­er ground­work to get the new agency off the ground. Dr. Collins said Dr. Wegrzyn will begin work on Oct. 1. Her main goal will be to hire pro­gram man­agers who will bring bold ideas that the agency wants to pur­sue, and she will spend a lim­it­ed time, per­haps three years, at the agency, he said.

    “They will arrive, they will do a lit­tle bit of due dili­gence, and then they’ll have to pitch the idea to Dr. Wegrzyn,” Dr. Collins said. “If she says thumbs-up, then off they go with mon­ey to spend, to fig­ure out how to put togeth­er the appro­pri­ate part­ners to get the work done.”

    Com­ing up with suc­cess­ful new inno­va­tions, he said, will take time. But Steve Brozak, an invest­ment banker whose com­pa­ny, WBB Secu­ri­ties, spe­cial­izes in biotech­nol­o­gy, said that if the agency were going to be a suc­cess, Dr. Wegrzyn would have to move quick­ly to dis­tin­guish its work from the rest of the fed­er­al bureau­cra­cy.

    “What she needs to do is get a win on the board right away,” he said. “That does not mean mon­ey. That means some­thing that can be iden­ti­fi­able in advanc­ing health care for all, out­side of the cur­rent par­a­digm.”

    ...

    In addi­tion to announc­ing his intent to appoint Dr. Wegrzyn, Mr. Biden issued an exec­u­tive order on Mon­day estab­lish­ing a biotech­nol­o­gy and bio­man­u­fac­tur­ing ini­tia­tive intend­ed to posi­tion the Unit­ed States as a leader in the field and to cen­ter drug man­u­fac­tur­ing in the coun­try. The coro­n­avirus pan­dem­ic exposed crit­i­cal weak­ness­es in the sup­ply chain for drugs and life­sav­ing ther­a­pies.

    “The Unit­ed States has for too long relied heav­i­ly on for­eign mate­ri­als for bio­pro­duc­tion,” the White House said in a state­ment, “and our past off­shoring of crit­i­cal indus­tries, includ­ing biotech­nol­o­gy, presents a threat to our abil­i­ty to access key mate­ri­als like includ­ing the active phar­ma­ceu­ti­cal ingre­di­ents for life­sav­ing med­ica­tions.”

    ———–

    “Biden Picks Biotech Exec­u­tive to Lead New Bio­med­ical Research Agency” By Sheryl Gay Stol­berg; The New York Times; 09/12/2022

    Mod­eled after the Defense Advanced Research Projects Agency, the new agency is known as the Advanced Research Projects Agency for Health. (In the argot of Wash­ing­ton, where every agency has an acronym, the defense research agency is called DARPA and the health agency is ARPA‑H.)”

    A new DARPA. Or rather, the lat­est ‘ARPA’. And while Pres­i­dent Biden was empha­siz­ing its poten­tial role in his ‘can­cer moon­shot’ ini­tia­tive, it’s pret­ty clear that ARPA‑H isn’t lim­it­ed to can­cer. It’s also pret­ty clear that this new agency is going to be on the hunt for some high pro­file ear­ly ‘wins’ to jus­ti­fy its exis­tence. What isn’t clear is what exact­ly it’s actu­al­ly going to be focus­ing on. Because it sounds like the projects this agency could be involved with are basi­cal­ly any­thing tan­gen­tial­ly relat­ed to health and med­i­cine:

    ...
    Mr. Biden helped cre­ate the can­cer moon­shot when he was vice pres­i­dent. Its goal, which he described as “com­plete­ly doable,” is to cut can­cer death rates by at least 50 per­cent over the next 25 years, while turn­ing “death sen­tences into chron­ic dis­eases.”

    He pro­posed the new bio­med­ical research agency this year as part of an effort to rein­vig­o­rate the ini­tia­tive.

    ...

    “They will arrive, they will do a lit­tle bit of due dili­gence, and then they’ll have to pitch the idea to Dr. Wegrzyn,” Dr. Collins said. “If she says thumbs-up, then off they go with mon­ey to spend, to fig­ure out how to put togeth­er the appro­pri­ate part­ners to get the work done.”

    Com­ing up with suc­cess­ful new inno­va­tions, he said, will take time. But Steve Brozak, an invest­ment banker whose com­pa­ny, WBB Secu­ri­ties, spe­cial­izes in biotech­nol­o­gy, said that if the agency were going to be a suc­cess, Dr. Wegrzyn would have to move quick­ly to dis­tin­guish its work from the rest of the fed­er­al bureau­cra­cy.

    “What she needs to do is get a win on the board right away,” he said. “That does not mean mon­ey. That means some­thing that can be iden­ti­fi­able in advanc­ing health care for all, out­side of the cur­rent par­a­digm.”
    ...

    So what should we expect from ARPA‑H? At this point the biggest clue is prob­a­bly the per­son tapped to lead it: Renee Wegrzyn, biol­o­gist with exten­sive work in both gov­ern­ment and the pri­vate sec­tor. As the fol­low­ing piece describes, Wegrzyn spent more than five years work­ing as a pro­gramme man­ag­er at DARPA, where her port­fo­lio includ­ed projects that used syn­thet­ic biol­o­gy to counter infec­tious dis­ease and bol­ster biose­cu­ri­ty. Now, “syn­thet­ic biol­o­gy to counter infec­tious dis­ease and bol­ster biose­cu­ri­ty” could mean a lot of dif­fer­ent things. It’s not at all obvi­ous from those scant details that Wegrzyn was in any way involved in the Eco­Health Alliance’s gain-of-func­tion work on coro­n­avirus­es in the peri­od lead­ing up to the COVID19 pan­dem­ic. But boy does that port­fo­lio sound like some­one who would at least be aware of that kind of research and famil­iar with many of the tech­nolo­gies and risks involved.

    So giv­en that we already know that the NIH is crack­ing down on the Eco­Health Alliance’s work — but doing so in a man­ner that appears to be designed to end Eco­Health Alliance’s col­lab­o­ra­tion with labs in Chi­na and not end Eco­Health Alliance’s over­all work in cre­at­ing syn­thet­ic virus­es — we have to ask: is ARPA‑H the intend­ed des­ti­na­tion for the next gen­er­a­tion of dual use bio­log­i­cal war­fare ‘biose­cu­ri­ty’ research? It sure seems like an obvi­ous home for that kind of work. And while we don’t have clar­i­ty on Wegrzyn’s back­ground, it’s hard to ignore how well “syn­thet­ic biol­o­gy to counter infec­tious dis­ease and bol­ster biose­cu­ri­ty” could describe exact­ly what the Eco­Health Alliance has been doing all along:

    Nature

    Bil­lion-dol­lar US health agency gets new chief — but its direc­tion remains in lim­bo
    Biol­o­gist Renee Wegrzyn will take the reins at ARPA‑H as law­mak­ers bat­tle over its cul­ture and pri­or­i­ties.

    Max Kozlov
    12 Sep­tem­ber 2022

    US Pres­i­dent Joe Biden has select­ed Renee Wegrzyn, a biol­o­gist and for­mer gov­ern­ment sci­en­tist, as the inau­gur­al direc­tor of the Advanced Research Projects Agency for Health (ARPA‑H), an agency cre­at­ed by his admin­is­tra­tion to find inno­v­a­tive solu­tions to bio­med­ical prob­lems. Although researchers applaud Biden’s choice, they say that Wegrzyn will have her work cut out, because many details about the agency are still in lim­bo, includ­ing how it should be struc­tured and what health issues it should pri­or­i­tize.

    “Renee pos­sess­es a rare com­bi­na­tion of sci­en­tif­ic exper­tise, prac­ti­cal expe­ri­ence and inter­per­son­al skills that set her apart as a leader,” says Jen­nifer Doud­na, a bio­chemist and gene-edit­ing pio­neer at the Uni­ver­si­ty of Cal­i­for­nia, Berke­ley, who has served on a bio­engi­neer­ing advi­so­ry board with Wegrzyn.

    Launched in March with a US$1 bil­lion bud­get, ARPA‑H aims to shake up the con­ven­tion­al mod­el of fund­ing bio­med­ical research — deemed too slow and con­ser­v­a­tive in its scope and approach by some crit­ics — by fund­ing high-risk, high-reward research in the life sci­ences.

    The Biden admin­is­tra­tion intends the agency to emu­late the US Defense Advanced Research Projects Agency (DARPA), which has been laud­ed for help­ing to rapid­ly devel­op tech­nolo­gies such as the Inter­net and radar-evad­ing stealth capa­bil­i­ties. In con­trast to agen­cies such as the Nation­al Insti­tutes of Health (NIH) and the Nation­al Sci­ence Foun­da­tion — two of the largest US research-fund­ing agen­cies — DARPA does not fund projects on the basis of a stan­dard peer-review process. Instead, it relies on agency pro­gramme man­agers who award con­tracts that sup­port risky, rather than incre­men­tal, sci­ence — and that can be abrupt­ly with­drawn if researchers don’t meet desired mile­stones.

    Wegrzyn spent more than five years work­ing as a pro­gramme man­ag­er at DARPA, where her port­fo­lio includ­ed projects that used syn­thet­ic biol­o­gy to counter infec­tious dis­ease and bol­ster biose­cu­ri­ty. At the agency, Wegrzyn led its Safe Genes pro­gramme, a four-year, $65-mil­lion ini­tia­tive aimed at safe­guard­ing against the poten­tial dan­gers of the gene-edit­ing tech­nique CRISPR. Doud­na says that Wegrzyn was “gift­ed” at bring­ing dif­fer­ent types of researcher to the table — bioethi­cists and geneti­cists alike — to dis­cuss a new and eth­i­cal­ly chal­leng­ing tech­nol­o­gy.

    Since leav­ing DARPA in 2020, Wegrzyn has served as a vice-pres­i­dent at Gink­go Bioworks, a bio-engi­neer­ing com­pa­ny in Boston, Mass­a­chu­setts. Gink­go has not yet announced when Wegrzyn will step down.

    “I am deeply hon­ored to have the oppor­tu­ni­ty to shape ARPA‑H’s ambi­tious mis­sion and fos­ter a vision and approach that will improve health out­comes for the Amer­i­can peo­ple,” Wegrzyn said in a state­ment.

    Cul­ture is key

    Although ARPA‑H will soon have a leader, who will prob­a­bly serve a five-year term, many foun­da­tion­al details about the agency are yet to be final­ized. The US Con­gress allo­cat­ed the agency only $1 bil­lion in 2022 — rather than the $6.5 bil­lion that Biden request­ed last year — and has not yet passed leg­is­la­tion explic­it­ly autho­riz­ing its cre­ation.

    Law­mak­ers have been spar­ring over whether the agency should be housed in the NIH, viewed as a con­ser­v­a­tive fun­der of sci­ence, or be inde­pen­dent of it. Although US health sec­re­tary Xavier Becer­ra decid­ed in May that ARPA‑H would be part of the NIH, mem­bers of Con­gress are still mulling leg­is­la­tion that would make ARPA‑H a com­plete­ly sep­a­rate enti­ty. One such bill that has been pro­posed would house ARPA‑H out­side the Wash­ing­ton DC area, where the NIH is locat­ed, and would bar any per­son who had worked at the NIH in the past three years from work­ing at ARPA‑H.

    The inde­ci­sion under­scores a key con­cern about ARPA‑H — and that’s its cul­ture, says Ezekiel Emanuel, a bioethi­cist at the Uni­ver­si­ty of Penn­syl­va­nia in Philadel­phia and long-time observ­er of the US bio­med­ical fund­ing land­scape. He applauds Biden choos­ing some­one with exten­sive expe­ri­ence at DARPA, which will help to ensure that ARPA‑H is not a repli­ca of the NIH. But he hopes that Wegrzyn will keep the agency focused on a mis­sion to pri­or­i­tize health over med­i­cine. This would mean fund­ing projects that address social deter­mi­nants of health — such as inad­e­quate access to health care, afford­able hous­ing and edu­ca­tion — rather than sup­port­ing sole­ly the devel­op­ment of med­i­cines and treat­ments.

    ...

    ————

    “Bil­lion-dol­lar US health agency gets new chief — but its direc­tion remains in lim­bo” by Max Kozlov; Nature; 09/12/2022

    Wegrzyn spent more than five years work­ing as a pro­gramme man­ag­er at DARPA, where her port­fo­lio includ­ed projects that used syn­thet­ic biol­o­gy to counter infec­tious dis­ease and bol­ster biose­cu­ri­ty. At the agency, Wegrzyn led its Safe Genes pro­gramme, a four-year, $65-mil­lion ini­tia­tive aimed at safe­guard­ing against the poten­tial dan­gers of the gene-edit­ing tech­nique CRISPR. Doud­na says that Wegrzyn was “gift­ed” at bring­ing dif­fer­ent types of researcher to the table — bioethi­cists and geneti­cists alike — to dis­cuss a new and eth­i­cal­ly chal­leng­ing tech­nol­o­gy.”

    You can see why Biden picked her for the role with a back­ground like that. And note that Wegrzyn was work­ing at Booz Allen Hamil­ton at the time when she was work­ing as a pro­gram direc­tor for DARPA. She has exten­sive expe­ri­ence in both the pub­lic and pri­vate space, in par­tic­u­lar in the areas where the pri­vate sec­tor is con­tract­ing for the gov­ern­ment. It’s exact­ly the kind expe­ri­ence you expect for a pick like this. But, again, it’s also the kind of expe­ri­ence we would expect if the plan was to make ARPA‑H the new home for the US’s dual use biowar­fare ‘biose­cu­ri­ty’ research. So when we read that ARPA-H’s foun­da­tion­al details have yet to be estab­lished at the same time many basic ques­tions about the agency — like where it will be housed — remained unan­swered, it’s a reminder that the ARPA‑H isn’t sim­ply going to be an exten­sion of Joe Biden’s ‘can­cer moon­shot’. This is the kind of agency that could be lead­ing all sorts of bio­log­i­cal research. Espe­cial­ly ‘dual use’ research that would be dif­fi­cult to get approval for under agen­cies with more strin­gent over­sight:

    ...
    Although ARPA‑H will soon have a leader, who will prob­a­bly serve a five-year term, many foun­da­tion­al details about the agency are yet to be final­ized. The US Con­gress allo­cat­ed the agency only $1 bil­lion in 2022 — rather than the $6.5 bil­lion that Biden request­ed last year — and has not yet passed leg­is­la­tion explic­it­ly autho­riz­ing its cre­ation.

    Law­mak­ers have been spar­ring over whether the agency should be housed in the NIH, viewed as a con­ser­v­a­tive fun­der of sci­ence, or be inde­pen­dent of it. Although US health sec­re­tary Xavier Becer­ra decid­ed in May that ARPA‑H would be part of the NIH, mem­bers of Con­gress are still mulling leg­is­la­tion that would make ARPA‑H a com­plete­ly sep­a­rate enti­ty. One such bill that has been pro­posed would house ARPA‑H out­side the Wash­ing­ton DC area, where the NIH is locat­ed, and would bar any per­son who had worked at the NIH in the past three years from work­ing at ARPA‑H.

    The inde­ci­sion under­scores a key con­cern about ARPA‑H — and that’s its cul­ture, says Ezekiel Emanuel, a bioethi­cist at the Uni­ver­si­ty of Penn­syl­va­nia in Philadel­phia and long-time observ­er of the US bio­med­ical fund­ing land­scape. He applauds Biden choos­ing some­one with exten­sive expe­ri­ence at DARPA, which will help to ensure that ARPA‑H is not a repli­ca of the NIH. But he hopes that Wegrzyn will keep the agency focused on a mis­sion to pri­or­i­tize health over med­i­cine. This would mean fund­ing projects that address social deter­mi­nants of health — such as inad­e­quate access to health care, afford­able hous­ing and edu­ca­tion — rather than sup­port­ing sole­ly the devel­op­ment of med­i­cines and treat­ments.
    ...

    And let’s not for­get about ambi­tious ini­tia­tives like Metabio­ta. ARPA‑H is clear­ly about cre­at­ing new busi­ness­es too, not just research. And we already know Metabio­ta received funds from both the CIA’s In-Q-Tel and the Pen­tagons Defense Threat Reduc­tion Agency (DRTA). Are there going to be any Metabio­ta-relat­ed con­tracts issued by ARPA‑H? It sounds very pos­si­ble. But also keep in mind that if part of the unwrit­ten intent of this new agency is to house the US’s dual use ‘biode­fense’ research, the Eco­Health Alliance and Metabio­ta are just warmup acts for the big­ger and bet­ter ‘high-risk-high-reward’ projects to come.

    Posted by Pterrafractyl | September 17, 2022, 3:28 pm
  3. We just got an absolute­ly fas­ci­nat­ing update to the biol­o­gy of SARS-CoV­‑2. Although it’s real­ly an update to the biol­o­gy of how the human immune sys­tem responds to the virus and why it is that some peo­ple real­ly are ‘super­dodgers’ who don’t even show symp­toms no mat­ter how much expo­sure they have to the virus. New research appears to have elu­ci­dat­ed those super-dodg­ing bio­log­i­cal mech­a­nisms. And as the fol­low­ing arti­cle describes, their find­ing s once again show how unusu­al this virus real­ly is. Because it turns out SARS-CoV­‑2 is only the third virus ever dis­cov­ered with a ‘super-dodg­ing’ pop­u­la­tion. The oth­er two virus­es where this remark­able super-dodg­ing abil­i­ty has been observed is the norovirus and, of course, HIV. And as with HIV, a sin­gle muta­tion appears to be the source of this super-dodg­ing abil­i­ty.

    Now, the ‘super­dodg­ing’ isn’t quite the same between HIV and SARS-CoV­‑2. As we’ve seen, HIV super­dodgers have a muta­tion in the CCR5 gene that lit­er­al­ly blocks the abil­i­ty of the HIV virus to enter the cell at all. The virus­es just stick to the out­side of the cells with­out ever enter­ing. That muta­tion is found in 5–14% of Euro­peans but is very rare in African, Native Amer­i­can, or East Asian pop­u­la­tions.

    In the case of SARS-CoV­‑2 super­dodgers, the muta­tion does­n’t block the virus from infect­ing cells. Instead, it turns out some peo­ple have a muta­tion on the HLA‑B gene, which is deeply asso­ci­at­ed with your body’s immune response. And if you have this sin­gle muta­tion, your body just hap­pens to cre­ate T‑cells pre-pro­grammed to rec­og­nized SARS-CoV­‑2. Nor­mal­ly, when your body gets exposed to a virus, the prod­uct of those T‑cells cus­tomized to the invad­er takes days for your body to pro­duce, giv­ing the virus time to spread before your body can mount an effec­tive enough response to quell the infec­tion. But for these super­dodgers, their immune sys­tems are so primed to fight the virus right out of the gate that the infec­tion nev­er gets to the point where symp­toms appear. So they aren’t exact­ly super­dodgers but super­fight­ers.

    The only require for these ‘lucky’ indi­vid­u­als is that they pre­vi­ous­ly get infect­ed with a dif­fer­ent coro­n­avirus. So there’s some­thing about this muta­tion in the HLA‑B gene that caus­es these peo­ple to elic­it a some­what dif­fer­ent T‑cell response to coro­n­avirus­es in gen­er­al, and that dif­fer­ence in T‑cells makes all the dif­fer­ence when it comes to fight­ing off SARS-CoV­‑2. Recall how we’ve already seen indi­ca­tions that com­mon-cold coro­n­avirus expo­sure is help­ful is fight­ing off the virus and it’s spec­u­lat­ed that some of these com­mon-cold coro­n­avirus­es start­ed off as COVID19-like killers when they ini­tial­ly jumped to human pop­u­la­tions. So it would appear that the ben­e­fits of com­mon-cold coro­n­avirus expo­sure are super-ben­e­fits for these super­dodgers.

    This is also prob­a­bly a good time recall how the var­i­ous ‘gain-of-func­tion’ projects involved with Eco­Health Alliance’s coro­n­avirus research involved look­ing at coro­n­avirus­es as a broad group. And then there’s Mod­er­na’s law­suits over alleged patent infringe­ments of its the broad-spec­trum beta­coro­n­avirus vac­cine, includ­ing human clin­i­cal tri­als as far back as 2015. The point being that a lot of gener­ic coro­n­avirus research involv­ing syn­thet­ic coro­n­avirus­es took place over the past decade. What was learned about the genet­ics of the human immune response to coro­n­virus­es dur­ing this peri­od? Was this par­tic­u­lar muta­tion in the HLA‑B gene pre­vi­ous­ly rec­og­nized as hav­ing an impact on the nature of the T‑cells gen­er­at­ed in response to a coro­n­avirus expo­sure?

    There’s anoth­er impor­tant ele­ment of this sto­ry with dis­turb­ing echos of the high­ly race-strat­i­fied nature of the CCR5 muta­tion in HIV (where basi­cal­ly the pro­tec­tive muta­tion is only found in Euro­pean pop­u­la­tions): the muta­tion that con­fers SARS-COV‑2 super­dodg­ing abil­i­ties is found on the HLA‑B gene, in the HLA region of the genome. That HLA region has been sub­ject to the evo­lu­tion­ary pres­sures of local envi­ron­men­tal dan­gers and as a result is high­ly var­ied across human pop­u­la­tions. In oth­er words, we should expect poten­tial­ly very dif­fer­ent rates of this pro­tec­tive HLA‑B muta­tion across ances­tral pop­u­la­tions, much like what we saw with CCR5 and HIV.

    Now, at the end of the fol­low­ing arti­cle, we’re going to hear the lead researcher on this study make the obser­va­tion that “this muta­tion is quite com­mon. We esti­mate that maybe 1 in 10 peo­ple have it. And in peo­ple who are asymp­to­matic, that ris­es to 1 in 5.” But it’s impor­tant to rec­og­nize that their study appears to have been on self-iden­ti­fied White Euro­peans. So when we hear about this being a rel­a­tive­ly com­mon muta­tion, keep in mind that this is like­ly a state­ment spe­cif­ic to Euro­pean ances­try pop­u­la­tions. Whether or not this muta­tion hap­pens to be just as preva­lent across the world is anoth­er ques­tion. And, again, the muta­tions found in these HLA region genes are known for being high­ly strat­i­fied based on ances­try. This the part of the genome ded­i­cat­ed to fight­ing local envi­ron­men­tal insults. It’s going to be high­ly ances­try-spe­cif­ic.

    And that’s the big rev­e­la­tion: SARS-CoV­‑2, like HIV, is one of only three virus­es known to pro­duce super­dodgers cause by a sin­gle muta­tion. And the super­dodg­ing might be very eth­nospe­cif­ic. More data needs to be gath­ered to make that deter­mi­na­tion, but there’s a good chance of that being the case based on the high­ly race-strat­i­fied nature of the HLA region of the genome. What are the odds?:

    Nation­al Pub­lic Radio

    So you haven’t caught COVID yet. Does that mean you’re a super­dodger?

    Michaeleen Doucleff
    Sep­tem­ber 7, 2022 4:06 PM ET

    Back in the ear­ly 1990s, Nathaniel Lan­dau was a young virol­o­gist just start­ing his career in HIV research. But he and his col­leagues were already on the verge of a land­mark break­through. Sev­er­al labs around the world were hot on his team’s tail.

    “We were sleep­ing in the lab, just to keep the work going day and night because there were many labs all rac­ing against each oth­er,” Lan­dau says. “Of course, we want­ed to be the first to do it. We were total­ly stressed out.”

    Oth­er sci­en­tists had iden­ti­fied groups of peo­ple who appeared to be com­plete­ly resis­tant to HIV. “Peo­ple who knew they had been exposed to HIV mul­ti­ple times, main­ly through unpro­tect­ed sex, yet they clear­ly were not infect­ed,” Lan­dau explains.

    And so the race was on to fig­ure out why: “Are these peo­ple just lucky or did they real­ly have a muta­tion in their genes that was pro­tect­ing them from infec­tion?’ ” he asks.

    Now 25 years lat­er, sci­en­tists all over the world are try­ing to answer the same ques­tion but about a dif­fer­ent virus: SARS-CoV­‑2.

    By this point in the pan­dem­ic, most Amer­i­cans have had at least one bout of COVID. For chil­dren under age 18, more than 80% have been infect­ed, the Cen­ters for Dis­ease Con­trol and Pre­ven­tion esti­mates.

    But just as with HIV, some peo­ple have been exposed mul­ti­ple times but nev­er had symp­toms and nev­er test­ed pos­i­tive.

    “We’ve heard count­less anec­dotes about nurs­es and health-care work­ers, being exposed with­out any pro­tec­tion and remain­ing neg­a­tive over and over again,” says pedi­a­tri­cian Jean-Lau­rent Casano­va, who stud­ies the genet­ics of viral resis­tance at Rock­e­feller Uni­ver­si­ty. “Or peo­ple share a house­hold with some­one who’s been cough­ing for a cou­ple of weeks, and one per­son stays neg­a­tive.”

    So why haven’t these peo­ple caught COVID? .

    After two years of hunt­ing, a team at the Uni­ver­si­ty of Cal­i­for­nia, San Fran­cis­co has come pret­ty close to answer­ing the ques­tion.

    “These find­ings are like hot off the press­es,” says immuno­geneti­cist Jill Hol­len­bach, who led this research. “We haven’t pub­lished them yet. It’s all stuff that’s been hap­pen­ing this sum­mer.”

    Hol­len­bach and her team have found a genet­ic muta­tion does­n’t pre­vent the virus from infect­ing cells — that’s what Lan­dau was search­ing for — but still does some­thing remark­able: It pre­vents a per­son from hav­ing COVID symp­toms.

    Turns out, stop­ping an infec­tion alto­geth­er is an extreme­ly tough nut for our bod­ies to crack.

    What does it take to be a true super­dodger?

    Over the course of human his­to­ry, sci­en­tists have iden­ti­fied only two instances of true virus super­dodgers. That is, where a spe­cif­ic muta­tion in their genes makes peo­ple com­plete­ly resis­tant to a virus. So that it slides off their cells, “like water slid­ing off a glass win­dow,” as Casano­va puts it.

    In 2003, a team in Lon­don showed how some peo­ple nev­er get a stom­ach bug, called norovirus, which caus­es vom­it­ing and diar­rhea. The researchers found that one muta­tion in their genes pre­vents them from mak­ing a mol­e­cule the virus needs to infect the cell.

    (In 1995, researchers in France fig­ured out why some peo­ple appeared to nev­er be infect­ed with a species of malar­ia, known as Plas­mod­i­um vivax. How­ev­er, over the past decade, fur­ther stud­ies have clar­i­fied that these super­dodgers actu­al­ly do become infect­ed with the par­a­site, they sim­ply don’t show symp­toms.)

    By far, the most famous virus super­dodgers are peo­ple pro­tect­ed against HIV. The ones Lan­dau and his col­leagues were study­ing back in the ear­ly 1990s.

    In 1996, his team was get­ting real­ly close to solv­ing that puz­zle. One morn­ing they found a huge clue. The night before, they had set up an exper­i­ment to test which mol­e­cules HIV need­ed to infect a human cell. The exper­i­ment gar­nered spec­tac­u­lar results.

    It showed that HIV did­n’t enter cells the way sci­en­tists had believed. Instead it need­ed a lit­tle bit of extra help. Specif­i­cal­ly, HIV needs a spe­cif­ic mol­e­cule, called CCR5, on the sur­face of the cell to “open the door” and let the virus enter, Lan­dau says. With­out CCR5, the virus only sticks to the cel­l’s sur­face but can’t enter. “It’s kind of like the virus is knock­ing at the door, but nobody’s open­ing the door. The door is locked,” he says.

    “That was what we call a eure­ka moment,” Lan­dau says. “That was the moment where we could say, ‘We found some­thing that had nev­er been seen before.’ ”

    Lan­dau and his col­leagues rushed to the com­put­er and wrote up the find­ings as quick­ly as pos­si­ble. Then he lit­er­al­ly ran to the FedEx store to sub­mit the paper to the jour­nal Nature, know­ing that oth­er teams were like­ly to have the same find­ing soon.

    “In those days you could­n’t just sub­mit your paper through your com­put­er,” he says. “You had to mail a hard copy of it to the jour­nal. And my job was to sprint over to the FedEx store so we could get the paper mailed on time.”

    Then only a few short weeks lat­er, Lan­dau and his col­leagues made anoth­er huge dis­cov­ery, and in the process solved the final piece of the HIV puz­zle. “We were quite amazed that it all hap­pened so quick­ly,” Lan­dau says.

    In col­lab­o­ra­tion with a research group down the hall, Lan­dau and his col­leagues sequenced the CCR5 gene in two peo­ple com­plete­ly resis­tant to HIV. Lo and behold! Both peo­ple had the same muta­tion in the gene — and it’s a pow­er­ful muta­tion. It com­plete­ly crip­ples the mol­e­cule so that it does­n’t appear on the cells’ sur­face, the group report­ed in the jour­nal Cell. Remem­ber, with­out CCR5, HIV can’t infect the cell.

    “You can put as many virus par­ti­cles as you want onto those cells, and they will not get infect­ed,” he says. “So in the case of resis­tance to HIV, the sto­ry was very clear.”

    The find­ing com­plete­ly shift­ed the field of HIV. It led to the first — and only — way to cure a per­son of HIV and sug­gest­ed a new route, using gene edit­ing with CRISPR. But it did some­thing else: It showed sci­en­tists that one muta­tion could make a per­son com­plete­ly resis­tant to an infec­tion. One muta­tion in their genes could make them a true super­dodger.

    ...

    Are there real­ly COVID super­dodgers?

    For COVID super­dodgers, the sit­u­a­tion appears to be more com­plex than for peo­ple resis­tant to HIV, Lan­dau says, because the way SARS-CoV­‑2 infects cells is dif­fer­ent from that of HIV.

    Instead of using CCR5 to “open the cel­l’s door,” SARS-CoV­‑2 uses the ACE2 recep­tor. Peo­ple can’t live with­out ACE2. “The recep­tor reg­u­lates your blood pres­sure,” Lan­dau explains. So, unlike CCR5, you can’t sim­ply knock out the ACE2 recep­tor, he says. “You’re not going to have many peo­ple walk­ing around that don’t have ACE2.

    “Of course, there may be more sub­tle muta­tions in ACE2 which could play a role in resis­tance to SARS-CoV­‑2,” he adds. “But there does­n’t seem to be an obvi­ous and dra­mat­ic muta­tion as is the case for HIV.”

    But per­haps what’s more like­ly, he says, is that peo­ple have muta­tions in genes oth­er than ACE2, and these muta­tions prob­a­bly don’t pro­tect them from get­ting infect­ed per se but do pro­tect them from get­ting sick.

    So hav­ing one of these muta­tions would make you a sort of COVID minidodger, if you will. There are oth­er ways to resist an infec­tion besides deny­ing the virus entrance into the cell, Lan­dau explains. And they like­ly involve your body’s immune sys­tem.

    That’s exact­ly what the team at UCSF has found.

    Since the pan­dem­ic began, Jill Hol­len­bach and her col­leagues at UCSF have been study­ing peo­ple who test pos­i­tive COVID but show no symp­toms. “Not even a snif­fle or a scratchy throat,” she says. “So they are entire­ly asymp­to­matic.”

    After ana­lyz­ing DNA from more than 1,400 peo­ple, they iden­ti­fied a muta­tion that helps a per­son clear out SARS-CoV­‑2 so fast that their body does­n’t have a chance to devel­op symp­toms.

    The muta­tion occurs in a gene called HLA, which is crit­i­cal dur­ing the ear­li­est stages of infec­tion. Hol­len­bach and her col­leagues found that hav­ing a par­tic­u­lar muta­tion in that gene increas­es a per­son­’s chance of being asymp­to­matic by almost 10 times. They report­ed those pre­lim­i­nary find­ings online last Sep­tem­ber.

    Since then, they’ve gone on to show how this muta­tion works. And it has to do with your immune sys­tem prepar­ing for SARS-CoV­‑2 before the pan­dem­ic even began back in 2019.

    When virus­es first enter cells, HLA sig­nals to the immune sys­tem that cells are invad­ed and need help. That sig­nal trig­gers a cas­cade of events that ulti­mate­ly leads your body to make potent weapons specif­i­cal­ly designed to fight SARS-CoV­‑2. These weapons include anti­bod­ies and T cells that unique­ly rec­og­nize pieces of this virus. Once these tar­get­ed weapons are avail­able, your immune sys­tem has a much eas­i­er time clear­ing up the infec­tion. But these weapons take time to man­u­fac­ture. And that delay allows the infec­tion to spread and symp­toms to devel­op.

    But what if, for some lucky rea­son, your immune sys­tem already had weapons specif­i­cal­ly tar­get­ed to SARS-CoV­‑2?

    This sum­mer, Hol­len­bach and her col­leagues demon­strat­ed that, with a spe­cif­ic muta­tion in HLA, some peo­ple have T cells that are already pre-pro­grammed to rec­og­nize and fight off SARS-CoV­‑2. So there’s no delay in gen­er­at­ing COVID-specf­ic weapon­ry. It’s already there.

    “Your immune response and these T cells fire up much more quick­ly [than in a per­son with­out the HLA muta­tion],” Hol­len­bach says. “So for lack of a bet­ter term, you basi­cal­ly nuke the infec­tion before you even start to have symp­toms.”

    But here’s the kick­er. For the HLA muta­tion to work (and for you to have these pre-armed T cells), you first had to have been infect­ed with anoth­er coro­n­avirus.

    “Most of us have been exposed to some com­mon cold coro­n­avirus at some point in life,” she explains. And we all gen­er­ate T cells to fight off these colds. But if you also have this muta­tion in your HLA, Hol­len­bach says, then just by mere luck, these T cells you make can also fight off SARS-CoV­‑2.

    “It’s def­i­nite­ly luck,” she says. “But, you know, this muta­tion is quite com­mon. We esti­mate that maybe 1 in 10 peo­ple have it. And in peo­ple who are asymp­to­matic, that ris­es to 1 in 5.”

    While Hol­len­bach and her team con­tin­ue to look for more minidodger genes, Casano­va over at Rock­e­feller Uni­ver­si­ty and his col­leagues are still try­ing to deter­mine if there are true super­dodger genes. And he’s look­ing for par­tic­i­pants right now for his study.

    “You fill out a ques­tion­naire online about your expo­sures to SARS-CoV­‑2,” he says. And then if you meet the cri­te­ria of a super­dodger, the team sends you a test­ing kit. Basi­cal­ly you spit in a cup and mail it back to Casano­va and his col­lab­o­ra­tors.

    ...

    And per­haps, like with HIV, that find­ing will one day shift the field of COVID research and lead to a vac­cine that does what every­one wish­es our cur­rent vac­cines do: turn every­one into a COVID super­dodger.

    ———–

    “So you haven’t caught COVID yet. Does that mean you’re a super­dodger?” by Michaeleen Doucleff; Nation­al Pub­lic Radio; 09/07/2022

    Over the course of human his­to­ry, sci­en­tists have iden­ti­fied only two instances of true virus super­dodgers. That is, where a spe­cif­ic muta­tion in their genes makes peo­ple com­plete­ly resis­tant to a virus. So that it slides off their cells, “like water slid­ing off a glass win­dow,” as Casano­va puts it.”

    Only two oth­er virus­es have ever been dis­cov­ered with this remark­able prop­er­ty: a sin­gle muta­tion can turn some­one into a ‘super-dodger’. It’s quite an exclu­sive club for SARS-CoV­‑2. Just SARS-CoV­‑2, the norovirus, and HIV get to join this club:

    ...
    In 2003, a team in Lon­don showed how some peo­ple nev­er get a stom­ach bug, called norovirus, which caus­es vom­it­ing and diar­rhea. The researchers found that one muta­tion in their genes pre­vents them from mak­ing a mol­e­cule the virus needs to infect the cell.

    (In 1995, researchers in France fig­ured out why some peo­ple appeared to nev­er be infect­ed with a species of malar­ia, known as Plas­mod­i­um vivax. How­ev­er, over the past decade, fur­ther stud­ies have clar­i­fied that these super­dodgers actu­al­ly do become infect­ed with the par­a­site, they sim­ply don’t show symp­toms.)

    By far, the most famous virus super­dodgers are peo­ple pro­tect­ed against HIV. The ones Lan­dau and his col­leagues were study­ing back in the ear­ly 1990s.

    ...

    The find­ing com­plete­ly shift­ed the field of HIV. It led to the first — and only — way to cure a per­son of HIV and sug­gest­ed a new route, using gene edit­ing with CRISPR. But it did some­thing else: It showed sci­en­tists that one muta­tion could make a per­son com­plete­ly resis­tant to an infec­tion. One muta­tion in their genes could make them a true super­dodger.
    ...

    But the sin­gle-muta­tion super-dodg­ing observed in SARS-CoV­‑2 patients dif­fers sig­nif­i­cant­ly from the mech­a­nism through which HIV and and the norovirus super-dodg­ing was oper­at­ing: instead of a muta­tion that blocks the abil­i­ty of the virus to enter the cell, the SARS-CoV­‑2 super­dodgers had a muta­tion that caused their bod­ies to coin­ci­den­tal­ly make T‑Cells in response to oth­er coro­n­avirus­es — like com­mon-cold coro­n­avirus­es — that are pre-pro­grammed to rec­og­nize and fight off SARS-CoV­‑2. The muta­tion allows these ‘super­dodger’ to imme­di­ate­ly fight off the virus so effec­tive­ly they don’t even devel­op symp­toms:

    ...
    Since the pan­dem­ic began, Jill Hol­len­bach and her col­leagues at UCSF have been study­ing peo­ple who test pos­i­tive COVID but show no symp­toms. “Not even a snif­fle or a scratchy throat,” she says. “So they are entire­ly asymp­to­matic.”

    After ana­lyz­ing DNA from more than 1,400 peo­ple, they iden­ti­fied a muta­tion that helps a per­son clear out SARS-CoV­‑2 so fast that their body does­n’t have a chance to devel­op symp­toms.

    ...

    This sum­mer, Hol­len­bach and her col­leagues demon­strat­ed that, with a spe­cif­ic muta­tion in HLA, some peo­ple have T cells that are already pre-pro­grammed to rec­og­nize and fight off SARS-CoV­‑2. So there’s no delay in gen­er­at­ing COVID-specf­ic weapon­ry. It’s already there.

    “Your immune response and these T cells fire up much more quick­ly [than in a per­son with­out the HLA muta­tion],” Hol­len­bach says. “So for lack of a bet­ter term, you basi­cal­ly nuke the infec­tion before you even start to have symp­toms.”

    But here’s the kick­er. For the HLA muta­tion to work (and for you to have these pre-armed T cells), you first had to have been infect­ed with anoth­er coro­n­avirus.

    “Most of us have been exposed to some com­mon cold coro­n­avirus at some point in life,” she explains. And we all gen­er­ate T cells to fight off these colds. But if you also have this muta­tion in your HLA, Hol­len­bach says, then just by mere luck, these T cells you make can also fight off SARS-CoV­‑2.
    ...

    Now here’s where things because eeri­ly sim­i­lar to the sto­ry of the HIV super­dodgers: As we’ve seen that CCR5 muta­tion that cre­ates the HIV super-dodgers is some­what com­mon in Euro­peans (5–14%) but very rare in African, Native Amer­i­can, and East Asian pop­u­la­tions. It’s the kind of obser­va­tion that should raise all sort of chill­ing ques­tions giv­en all the oth­er ques­tions about the ori­gins of HIV and the net­works involved in that research. So what do we find with this SARS-CoV­‑2 super­dodger muta­tion? Well, the muta­tion occurs in the HLA region of the genome. This HLA region is, in turn, deeply inter­twined with the func­tion­ing of the immune sys­tem. And when we’re talk­ing about genet­ics and the immune sys­tem, it’s impor­tant to real­ize that the immune sys­tem genet­ics is one of the most ances­try-strat­i­fied areas of the human genome. In oth­er words, it varies sig­nif­i­cant­ly depend­ing on where your ances­tors came from. That’s because the HLA region of the genome is where evo­lu­tion in response to local envi­ron­men­tal dan­gers hap­pens. So when we’re talk­ing about a sin­gle muta­tion in a sin­gle gene in the HLA region that induces this kind of super-dodg­ing capa­bil­i­ties, we’re implic­it­ly talk­ing about a region of the genome where we can expect the preva­lence of that muta­tion to poten­tial­ly vary sig­nif­i­cant­ly depend­ing on your ances­try. Put blunt­ly, this is a bio­log­i­cal recipe for a very race-spe­cif­ic form of super-dodg­ing, much like HIV:

    ...
    The muta­tion occurs in a gene called HLA, which is crit­i­cal dur­ing the ear­li­est stages of infec­tion. Hol­len­bach and her col­leagues found that hav­ing a par­tic­u­lar muta­tion in that gene increas­es a per­son­’s chance of being asymp­to­matic by almost 10 times. They report­ed those pre­lim­i­nary find­ings online last Sep­tem­ber.

    Since then, they’ve gone on to show how this muta­tion works. And it has to do with your immune sys­tem prepar­ing for SARS-CoV­‑2 before the pan­dem­ic even began back in 2019.

    When virus­es first enter cells, HLA sig­nals to the immune sys­tem that cells are invad­ed and need help. That sig­nal trig­gers a cas­cade of events that ulti­mate­ly leads your body to make potent weapons specif­i­cal­ly designed to fight SARS-CoV­‑2. These weapons include anti­bod­ies and T cells that unique­ly rec­og­nize pieces of this virus. Once these tar­get­ed weapons are avail­able, your immune sys­tem has a much eas­i­er time clear­ing up the infec­tion. But these weapons take time to man­u­fac­ture. And that delay allows the infec­tion to spread and symp­toms to devel­op.

    But what if, for some lucky rea­son, your immune sys­tem already had weapons specif­i­cal­ly tar­get­ed to SARS-CoV­‑2?
    ...

    And that brings us to this asser­tion by the researchers who iden­ti­fied this genet­ic con­nec­tion to super­dodg­ing that the muta­tion is “quite com­mon”, with maybe one in 10 hav­ing it. There’s an impor­tant caveat that should be append­ed to that claim: when this same search team pub­lished their ini­tial find­ings on the pro­tec­tive prop­er­ties of the muta­tion in the HLA‑B gene back in Sep­tem­ber of 2021, that study was done on a Euro­pean ances­try cohort. So when we are told that the muta­tion is ‘quite com­mon’ we should prob­a­bly be inter­pret­ing that state­ment as ‘quite com­mon in Euro­pean ances­try pop­u­la­tions (white peo­ple). For some­thing like HLA‑B, you should­n’t assume those kinds of rates glob­al­ly:

    ...
    “It’s def­i­nite­ly luck,” she says. “But, you know, this muta­tion is quite com­mon. We esti­mate that maybe 1 in 10 peo­ple have it. And in peo­ple who are asymp­to­matic, that ris­es to 1 in 5.”
    ...

    And that’s part of what makes this sto­ry some­thing to watch: just how glob­al­ly preva­lent are these super­dodg­ing genes? Did Euro­peans once again exclu­sive­ly get ‘lucky’ in the face of a nov­el virus, or will we find that this HLA‑B muta­tion (specif­i­cal­ly, HLA‑B*15:01) is also found in oth­er ances­tries?

    It’s also worth noth­ing anoth­er aspect of this ‘super-dodg­ing’ that dif­fers from the super-dodg­ing observed with HIV: It sound­ed like the HIV super­dodgers prob­a­bly did­n’t spread the virus either. The virus just could­n’t take hold in their bod­ies at all. But with these SARS-CoV­‑2 super­dodgers the SARS-CoV­‑2 virus is still able to infect their cells and repro­duce. The body just does an excep­tion­al job of clear­ing the infec­tion before symp­toms emerge. But don’t for­get that COVID19 is most infec­tious dur­ing the asymp­to­matic ear­ly peri­od. So it would be inter­est­ing to know if the super-doger­s’s immune sys­tems keep the virus at such a low lev­el that they are effec­tive­ly non-infec­tious too, or not. Are these super­dodgers infec­tious super­dodgers? Or is their super immune response effec­tive­ly lim­it­ing their infec­tious­ness too?

    We’ll see. There’s undoubt­ed­ly going to be a lot more research in this direc­tion now that these dis­cov­er­ies are being made. Which means a lot more knowl­edge about how ances­try, nov­el virus­es, and the immune sys­tem inter­act too. For good or ill.

    Posted by Pterrafractyl | September 21, 2022, 3:53 pm

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