Pi­o­neers of pro­tec­tion we take for granted

Su­san Okie ap­plauds a de­tailed study of how vac­cines were de­vel­oped and the good they do

The Guardian Weekly - - Books -

The Vac­cine Race: Science, Pol­i­tics, and the Hu­man Costs of De­feat­ing Dis­ease by Mered­ith Wad­man Vik­ing, 436pp

Grow­ing up in the 1950s and 60s, I suf­fered through chicken pox and measles, like mil­lions of other Amer­i­can kids, and be­longed to the first gen­er­a­tion to re­ceive the new po­lio vac­cines in na­tional cam­paigns. My par­ents had friends per­ma­nently paral­ysed by po­lio; the mother of a school­mate gave birth to a baby who was deaf, nearly blind and suf­fer­ing a se­vere in­tel­lec­tual dis­abil­ity from rubella (Ger­man measles) con­tracted dur­ing preg­nancy.

Within a half-cen­tury, vac­cines have made these and other once-com­mon vi­ral dis­eases so rare in the US that doc­tors be­ing trained to­day may never see cases of them, and some par­ents worry more about the small or hy­po­thet­i­cal risks of vac­ci­nat­ing chil­dren than about the risks of leav­ing them un­pro­tected. It takes events such as the 2015 measles out­break among vis­i­tors to Dis­ney­land in Cal­i­for­nia or the emer­gence of the Zika virus to re­mind us not to take our free­dom from in­fec­tious dis­eases for granted.

In this metic­u­lously re­searched his­tory of the race to de­velop vac­cines against po­lio, rubella, ra­bies and other viruses, science writer and doc­tor Mered­ith Wad­man tells the story of these nearmirac­u­lous med­i­cal achieve­ments of the post-sec­ond world war era. The Vac­cine Race also de­tails the risks posed by some of the early prod­ucts – risks that arose, in part, be­cause to make the vac­cines, re­searchers first had to in­vent tech­niques for grow­ing viruses in liv­ing cells, with­out know­ing what other viruses those host cells might har­bour. Even when a gov­ern­ment sci­en­tist, Ber­nice Eddy, and col­leagues showed that mon­key cells used to pro­duce the Salk po­lio vac­cine and other vac­cines con­tained a virus, SV40, that could cause ma­lig­nant changes in hu­man cells, of­fi­cials at first dis­counted the ev­i­dence and al­lowed such vac­cines to re­main on the mar­ket. By 1963, when the fed­eral Di­vi­sion of Bi­o­log­ics Stan­dards in the US be­gan to re­quire that po­lio vac­cines be free of SV40, 98 mil­lion Amer­i­cans had re­ceived the Salk vac­cine, in­dis­putably pre­vent­ing tens of thou­sands of cases of paral­y­sis from po­lio. But be­tween 10 mil­lion and 30 mil­lion of them may have re­ceived a dose con­tam­i­nated by the SV40 virus. Whether such ex­po­sure in­creased their like­li­hood of de­vel­op­ing can­cer re­mains un­cer­tain. The In­sti­tute of Medicine “con­cluded in 2002 that although stud­ies that fol­lowed vac­cine re­cip­i­ents over the decades pro­vide no ev­i­dence of in­creased can­cer risk, these stud­ies were ‘suf­fi­ciently flawed’ that the ques­tion ... couldn’t be an­swered,” Wad­man writes.

Early vac­cines against vi­ral dis­eases were de­signed to stim­u­late the im­mune sys­tem by giv­ing the re­cip­i­ent ei­ther a dead or a weak­ened ver­sion of the virus they were in­tended to pro­tect against. In live-virus vac­cines, choos­ing the right strength and strain of the virus was a chal­lenge. If it was too strong, the vac­cine might cause full-blown cases of the ill­ness; if too weak, it might not pro­duce last­ing im­mu­nity. Live-virus vac­cines are used to­day to pro­tect against cer­tain in­fec­tions, in­clud­ing measles, mumps, rubella and chicken pox. Newer vac­cines against some other dis­eases are ge­net­i­cally en­gi­neered to con­tain only pro­teins from the coat of the virus. Thus, they can­not cause the in­fec­tion.

In the post­war decades, re­searchers and drug com­pa­nies com­peted in­tensely to be the first to li­cense vac­cines against cer­tain dis­eases. The need was ur­gent. Po­lio paral­ysed an av­er­age of 15,000 Amer­i­cans each year. Rubella epi­demics oc­curred ev­ery few years and were dev­as­tat­ing for women in­fected dur­ing preg­nancy. The na­tion­wide epi­demic of 1964-65 caused about 6,250 mis­car­riages or still­births, 2,100 deaths among new­borns, and 20,000 cases of con­gen­i­tal birth de­fects. An ad­di­tional 5,000 preg­nant women had abor­tions after con­tract­ing rubella. Ra­bies, con­sid­ered the most deadly of all in­fec­tions in hu­mans, was on the rise in wild an­i­mals in the early 1960s.

At the time, gov­ern­ment stan­dards on the ethics of hu­man re­search were rudi­men­tary to nonex­is­tent. As Wad­man de­scribes, vac­cines were tested in cir­cum­stances shock­ing to a reader to­day. Ex­per­i­men­tal vac­cines were given to new­born or pre­ma­ture ba­bies, to pris­on­ers, and to men­tally or phys­i­cally dis­abled res­i­dents of in­sti­tu­tions, of­ten with­out con­sent, and with min­i­mal in­sti­tu­tional over­sight. The first hu­mans to re­ceive a live po­lio vac­cine, in 1950, were 20 in­tel­lec­tu­ally dis­abled chil­dren at Letch­worth Vil­lage, an in­sti­tu­tion in ru­ral New York. Ba­bies born to women im­pris­oned at Clin­ton State Farms in New Jersey were given an ex­per­i­men­tal po­lio vac­cine over a five-year pe­riod in the late 1950s. The prison’s pop­u­lar fe­male war­den and med­i­cal di­rec­tor “were ex­tremely help­ful in ob­tain­ing per­mis­sion” from the moth­ers, the re­searchers later noted.

Wad­man relates this fas­ci­nat­ing his­tory as lived by a hand­ful of sci­en­tists at the cen­tre of it all, es­pe­cially Leonard Hayflick, an in­de­fati­ga­ble cell bi­ol­o­gist who re­fined tech­niques for grow­ing, main­tain­ing and in­fect­ing hu­man cells with viruses to make safer, bet­ter vac­cines, and Stan­ley Plotkin, a pae­di­a­tri­cian and vac­ci­nol­o­gist who stud­ied the rubella virus and de­vel­oped a safe vac­cine against it.

Hayflick rea­soned that cells taken from hu­man foe­tuses, which are pro­tected from most in­fec­tions (though not rubella) in the womb, would prob­a­bly be free of viruses and thus far less risky than an­i­mal cells for vac­cine pro­duc­tion. Through con­nec­tions in Swe­den, he ob­tained tis­sue from aborted foe­tuses, in­clud­ing, in 1963, lung tis­sue from the foe­tus of a Swedish woman re­ferred to as Mrs X. The cul­tured lung cells gave rise to a cell line called WI38 – vig­or­ous, healthy and virus-free. It is still used to­day. Even­tu­ally, as bi­ol­ogy be­came big busi­ness, the am­poules of frozen WI-38 founder cells proved a valu­able com­mod­ity, spark­ing an ugly tug-of-war over their own­er­ship among Hayflick; his long­time boss, Hi­lary Ko­prowski of Phil­a­del­phia’s Wis­tar In­sti­tute; and of­fi­cials at the Na­tional In­sti­tutes of Health. Wad­man traces the twists in this colour­ful dis­pute with ad­mirable bal­ance.

Plotkin used Hayflick’s WI-38 cells to grow a weak­ened strain of rubella virus that he needed to make his vac­cine. The strain he chose came from the in­fected kid­ney cells of an­other foe­tus, one whose mother had un­der­gone an abor­tion after con­tract­ing rubella dur­ing preg­nancy. Thus, the pro­tec­tion from dis­ease con­ferred by Plotkin’s rubella vac­cine, and by other vac­cines made us­ing WI38 cells, is di­rectly linked to the use of these cells from aborted foe­tuses. “I am moved by the in­ti­mate in­ter­ac­tion be­tween the WI-38 cells and the hun­dreds of mil­lions of peo­ple who have ben­e­fited from ... vac­cines made us­ing them,” Wad­man writes. “When they are vac­ci­nated, they are lit­er­ally, phys­i­cally con­nected to Mrs X’s foe­tus.” Although de­bate con­tin­ues over the use of foetal tis­sue in re­search, it is le­gal in the United States and is con­tribut­ing to sci­en­tists’ un­der­stand­ing of nu­mer­ous dis­eases, as well as de­vel­op­ment of new treat­ments.

At al­most 400 pages of text plus abun­dant end­notes, this book is so rich in sci­en­tific anec­dotes, his­tor­i­cal de­tail and quirky char­ac­ters that I can’t

do it jus­tice in a short re­view. Wad­man con­jures the wiz­ardry of Hayflick’s cell lab­o­ra­tory; the brick vast­ness of long-gone Phil­a­del­phia Gen­eral Hospi­tal, which cared for the city’s work­ers and poor; the med­i­cal acu­men of Aus­tralian eye sur­geon Nor­man McAlis­ter Gregg, who made the con­nec­tion be­tween preg­nant women with rubella and ba­bies born blind. She con­veys the era’s no-holds­barred ap­proach to science, as well as the al­tru­ism of in­di­vid­ual sci­en­tists and doc­tors at a time when no one had yet thought of patent­ing a gene or a liv­ing cell. Her dis­sec­tion of the role played by abor­tion in vac­cine de­vel­op­ment pro­vides valu­able con­text for to­day’s abor­tion pol­i­tics, and her chap­ter on the stir­rings of en­trepreneur­ship among bi­ol­o­gists and uni­ver­si­ties is an en­light­en­ing primer on the birth of the biotech in­dus­try. Wash­ing­ton Post

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