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Kako to da stanična linija WI-38 koju je izolirao Hayflick 1962. još uvijek postoji i nije pod utjecajem 'Hayflickove granice'?

Kako to da stanična linija WI-38 koju je izolirao Hayflick 1962. još uvijek postoji i nije pod utjecajem 'Hayflickove granice'?



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Trazio sam po netu i nisam uspio doci do jasnog odgovora.

Uredi: Ovdje je paragraf citiran iz Nature http://www.nature.com/news/medical-research-cell-division-1.13273 "Tako je počeo WI-38, vrsta stanica koja je nedvojbeno pomogla spasiti više života od bilo kojeg drugog stvorenog od strane istraživača. Mnoge eksperimentalne stanične linije dostupne u to vrijeme, poput poznate linije HeLa, uzgojene su iz karcinoma ili inače su bili genetski abnormalni. *WI-38 stanice postale su prve dostupne 'normalne' ljudske stanice u gotovo neograničenim količinama znanstvenicima i industriji i, kao rezultat toga, postale su do danas najopsežnije opisane i proučavane normalne ljudske stanice."*


Odgovor je da je većina stanica bila zamrznuta vrlo rano u svom Hayflickovom životu, npr. nakon 9 udvostručenja stanovništva. Odmrznute su razborito i samo prema potrebi, čime je sačuvano mnogo smrznutih zaliha. Kada se ampula stanica smrznutih na, na primjer, 9 udvostručavanja populacije, odmrzne, stanice nastavljaju tamo gdje su stale i još uvijek imaju 41 udvostručenje a. Tako je čarolija eksponencijalnog rasta u kombinaciji s činjenicom da se nastavljaju dijeliti nakon odmrzavanja stvorila desetljećima dugu zalihu. Je li ovo odgovor na pitanje na vaše zadovoljstvo?


WI-38 su stanične linije koje su dovele do prijedloga Hayflickove granice i klasični su primjer stanica koje će se podijeliti samo ~40 puta. oni nisu izuzeti - oni su primjer koji je dokazao pravilo.

Puno staničnih linija je obično dostupno, ali se moraju redovito rekultivirati iz životinjskog/tkivnog izvora. Ako se mogu zamrznuti, tada se ekstrakcija novih stanica ne događa tako često bez prekoračenja granice dioba. To omogućuje da se stanične linije široko koriste za eksperimente unatoč ograničenjima na njihovu podjelu u kulturi.

Druge stanične linije poput HeLa i drugih tumorskih stanica ili matičnih stanica mogu se, pod odgovarajućim uvjetima, dijeliti bez ograničenja i lakše ih je uzgajati u velikim količinama, ali su često neprikladne za određeni istraživački projekt.


Svake godine postoji nova cjepiva protiv gripe. Što se događa sa svim tim različitim “sojevima” i što sve to znači?

Postoje četiri različite vrste gripe: A, B, C i D. Influenca D se nalazi u goveda, a gripa C uzrokuje blagu respiratornu infekciju. To ostavlja A i B. Obje vrste A i B uključene su u cijepljenje protiv gripe svake godine. U četverovalentnoj snimci (četiri virusa) nalaze se dva A i dva B soja. U trovalentnoj snimci (tri virusa) nalaze se dva A’ i jedan B.

Influenca tipa B nije podijeljena na podtipove, ali gripa tipa A jest. Kada čujete za tip A, često ga čujete povezano s dva slova: H i N. Cjepivo protiv sezonske gripe ima dva podtipa gripe A: H1N1 i H3N2. Ovo su dvije najčešće podvrste koje inficiraju ljude.

H označava hemaglutinin (HA), a N označava neuraminidazu (NA). To su dva proteina na površini virusa gripe. Postoji 18 različitih HA proteina i 11 različitih N proteina, tako da možete zamisliti sve mogućnosti kombinacija H’s i N’s koje možete imati.

Malo virusa izgleda poput kugličastog virusa koji često vidite na slici (poput emotikona na vašem telefonu). Gripa, međutim, radi. To je zbog HA i NA proteina na njegovoj površini. Moja kći obožava crtati ovaj virus, kao što možete vidjeti na fotografiji!

Problem s virusom gripe je što može lako mutirati. Mutacije u H’s i N’s su ono što nazivamo “sojovima”. Sojevi koji kruže ono su što znanstvenici pokušavaju predvidjeti za cjepivo protiv gripe svake godine. Na primjer, jedan od sojeva gripe A, soj H1N1, u cjepivu ove godine je virus sličan H1N1 A/Brisbane/02/2018.

Znanstvenici uzimaju u obzir sojeve koji su kružili južnom hemisferom tijekom njihove posljednje zime, kao i ono što je cirkuliralo sjevernom hemisferom tijekom naše prethodne zime kada odlučuju o ovogodišnjim sojevima cjepiva protiv gripe.

Zato vam svake godine treba novo cjepivo protiv gripe.

Možete tvrditi da znanstvenici ponekad pogrešno pogađaju cirkulirajuće sojeve i da je cijepljenje protiv gripe besmisleno. Iako cirkulirajući sojevi nisu uvijek na mjestu, jer imaju tendenciju da budu slični onome što cirkulira, cjepivo protiv gripe i dalje će ponuditi barem neki zaštita. Čak i ako dobijete gripu i primili ste cjepivo, postoji velika šansa da je cjepivo pomoglo skratiti vrijeme koje ste bili bolesni, kao i koliko ste bili bolesni.

Nema razloga čak ni da sebi ne pružite neku zaštitu ako možete.

Imamo i druge oblike gripe A koji ne uzrokuju velike epidemije i nisu u godišnjem cjepivu protiv gripe.

Postoje slučajevi kada životinjska gripa, poput svinjske ili ptičje gripe, uskoči u ljudsku populaciju. Ova vrsta gripe, iako se ne prenosi lako s osobe na osobu, posebno je smrtonosna kod zaraženih. Na primjer, ptičja gripa (H5N1) 1997. godine ubila je oko 60% zaraženih.

Cilj je univerzalno cjepivo protiv gripe– koje nudi zaštitu za sve tipove A i B. Možda je na horizontu. Za sada, dajte sve od sebe da zaštitite sebe, svoju obitelj i svoju zajednicu cijepljenjem.


Potomci ljudskih fetalnih stanica u izradi cjepiva

Ima li fetalnih stanica u cjepivima? Ne. Sadrže li neka cjepiva viruse uzgojene u stanicama ljudskog fetalnog podrijetla? Da. Ali, smatram da ovo treba neko objašnjenje.

I prije nego što počnem, ovo ne bi trebao biti članak o raspravi ili mišljenju. Ovo su samo činjenice kako sam ih ja istraživao. I prije nego što se upustim u problem, imat ćete lekciju iz mikrobiologije…

Stanična teorija kaže: Sve stanice nastaju iz već postojećih stanica.

Zapamtite termin mitoza sa sata biologije? Tako roditeljske stanice stvaraju svoje stanice kćeri. Roditeljska stanica replicira sve svoje kromosome u dva skupa, a zatim se dijeli na dvije stanice, ostavljajući po jedan skup kromosoma u svakoj stanici. To je to, ukratko. To se događa iznova i iznova: roditelji formiraju kćeri, a kćeri postaju roditelji i formiraju još kćeri.

U pravim uvjetima, stanice se vole razmnožavati. Znanstvenici mogu uzeti sve vrste stanica i uzgajati ih u laboratoriju pod kontroliranim uvjetima. Stanice koje se uzgajaju u umjetnom okruženju, kao što je posuda za kulturu, u otopini bogatoj hranjivim tvarima koja podržava rast stanica i pod kontroliranim/idealnim uvjetima temperature, vlage i plinovite atmosfere nazivaju se stanična kultura.

Stanice u kulturi mogu se uzgajati izravno iz živih tkiva. To se zove primarna stanična kultura. I često će primarna stanična kultura sadržavati mnogo vrsta stanica u jednoj posudi.

Tim se primarnim kulturama može manipulirati u laboratoriju dok ne ostane samo jedna vrsta stanica. Kultura stanica sa samo jedna vrsta ćelije naziva se a stanični soj.

Stanični soj se zatim koristi za uspostavljanje stanične linije. Stanična linija je stanična kultura formirana od a pojedinačna stanica, i stoga će svaka stanica u kulturi biti kćeri te stanice. To znači da će svaka stanica u kulturi imati potpuno isti genetski sastav. Ova uniformnost omogućuje eksperimentalnu kontrolu.

Shvaćam? U redu. Sada se samo usredotočite na stanična linija, kćeri samo JEDNE STANICE. Kćeri postaju roditelji i stvaraju još kćeri…

I sporedna napomena: Stanice se ne reproduciraju do beskonačnosti. Postoji određeni broj puta da se stanica može reproducirati prije nego što više ne može stvarati stanice kćeri (naziva se Hayflickova granica). Dakle, znanstvenici moraju uvesti genetsku mutaciju u stanične linije koja im omogućuje neograničeno razmnožavanje, to se zove ovjekovječen stanična linija.

Sada prelazimo na virologiju. Virusu nedostaje sposobnost samostalnog razmnožavanja. Treba upotrijebiti stanicu kako bi napravio mnogo, mnogo kopija sebe kako bi izazvao bolest. Stoga, da biste napravili cjepivo za stvaranje imuniteta na virus, prvo morate imati mnogo kopija virusa, a da biste imali mnogo kopija virusa, potrebne su vam stanice da zarazite virus.

Dakle, istraživači inficiraju stanice virusom kako bi dobili više virusa za korištenje u cjepivu. U redu. Ali, ne možete koristiti virus kao što je u cjepivu jer će to dovesti do infekcije bolešću, pa se mora nešto učiniti s virusom kako ne bi mogao uzrokovati bolest. Virus nije u stanju izazvati bolest ako ne može napraviti dovoljno kopija da zarazi dovoljno stanica u tijelu. Dakle, najbolji način za slabljenje, odn prigušiti virus, je učiniti ga tako da se ne može razmnožavati u tijelu.

Stanična linija je zaražena virusom. Nakon što se virus uspostavi i počne se razmnožavati u stanicama, polako se mijenjaju uvjeti pod kojima se stanice uzgajaju. To uzrokuje mutaciju virusa tako da virus najbolje raste u promijenjenim uvjetima. To su stanja koja se razlikuju od onih u normalnom ljudskom tijelu. Ovaj novi virus nazivamo atenuiranim (oslabljenim) virusom.

Oslabljeni virus je virus koji se sada može ubrizgati u tijelo kao a živo atenuirano cjepivo. Oslabljeni virus izaziva imunološki odgovor tijela, ali se ne može učinkovito replicirati, pa nije u stanju izazvati bolest. Ova vrsta cjepiva izaziva najsnažniji i najdugotrajniji od svih imunoloških odgovora povezanih s cjepivom na današnjem tržištu, zahtijevajući najmanje pojačivača.

Na stvar o kojoj je riječ: stanice koje se koriste za stvaranje staničnih linija.

Tamo su dva soja ljudskih stanica korištena za stvaranje cjepiva koja se danas koriste. Stanice koje se koriste za uzgoj virusa za ova cjepiva potomci su pobačenih fetalnih stanica. I želim naglasiti činjenicu da NE SVA cjepiva koriste patogene koji su uzgojeni ljudski stanične linije.

Prvu staničnu liniju, WI-38 (Winstar Institute 38), razvio je Leonard Hayflick 1962. Ove stanice su potomci plućnih stanica (ljudski diploidni fibroblasti pluća) iz četveromjesečnog ženskog fetusa pobačenog jer je obitelj smatrala da su imao previše djece. 6

Obratite pažnju na izraz "potomci". Sve stanice u ovoj staničnoj liniji su kćeri jedna stanica pronađeno u plućnom tkivu fetusa, generacije uklonjene iz izvorne stanice.

Utvrđeno je da stanična linija, WI-38, vrlo dobro uzgaja mnoge viruse, uključujući virus rubeole. Povijest i stvaranje cjepiva protiv virusa rubeole daje sjajnu sliku o tome kako se atenuirano virusno cjepivo proizvodi pomoću ljudske stanične linije:

Virus rubeole izolirao je nepovezani liječnik, Stanley Plotkin, koji također radi na Winstar institutu. Plotkin je uzgajao virus rubeole u stanicama WI-38 na mnogo nižoj temperaturi [86°F (30°C)] od normalne ljudske temperature [98,6°F (37°C)]. To je stvorilo virus rubeole koji je najbolje rastao na temperaturi nižoj od normalne, a koji je rastao vrlo slabo pri normalnoj tjelesnoj temperaturi. Nakon 25 ciklusa rasta stanica u kulturi, smatralo se da se virus ne može učinkovito razmnožavati i uzrokovati bolest kod čovjeka. Ipak, može izazvati popriličan imunološki odgovor i ostaviti tijelu moćna protutijela za pamćenje na virus rubeole.

Ovo cjepivo protiv rubeole i danas se koristi u Sjedinjenim Državama.

Sljedeća su cjepiva stvorena pomoću WI-38 stanica:

Živa cjepiva protiv rubeole 2:

  • monovalentna cjepiva protiv rubeole Meruvax® (Merck), Rudivax® (Sanofi Pasteur, Fr.) i Ervevax® (RA 27/3) (GlaxoSmithKline, Belgija)
  • kombinirano cjepivo MR protiv rubeole i ospica, M-R-VAX® (Merck, SAD) i Rudi-Rouvax® (AVP, Francuska)
  • kombinirano cjepivo protiv rubeole i zaušnjaka, na tržištu pod imenom Biavax® (Merck, SAD)
  • kombinirano cjepivo MMR (ospice, zaušnjaci, rubeola) protiv ospica, zaušnjaka i rubeole, koje se prodaje pod imenom MMR® II (Merck, SAD), ROR®, Trimovax® (Sanofi Pasteur, Fr.) i Priorix® ( GlaxoSmithKline UK).

Druga ljudska stanična linija koja se koristi za uzgoj virusa za cjepiva zove se MRC-5 (Medical Research Council 5), koju je razvio J.P Jacobs 1966. 5 Ova stanična linija također je potomak ljudskog fibroblasta pluća. Stanice su potjecale od 14-tjednog muškog fetusa abortiranog iz "psihijatrijskih razloga" od 27-godišnje žene u Velikoj Britaniji.

Cjepiva proizvedena s virusima uzgojenim u MRC-5 stanicama uključuju:

  • dva cjepiva protiv hepatitisa A, jedno koje proizvodi Merck (VAQTA), drugo proizvodi GlaxoSmithKline (HAVRIX)
  • jedno cjepivo protiv vodenih kozica, Varivax®, koje proizvodi Merck (koristeći WI-38 i MRC-5)
  • jedno inaktivirano poliovirusno cjepivo Poliovax® (Aventis-Pasteur, Fr.)
  • jedno cjepivo protiv bjesnoće, Imovax®,
  • jedno cjepivo protiv velikih boginja, AC AM 1000 (još u probi)

Stanične linije WI-38 i MRC-5 jedine su dvije ljudske stanične linije koje se koriste u izradi cjepiva.

  • Ove stanične linije počele su koristiti fetalne stanice pobačene prije više od 50 godina i od tada stanične linije su rasle neovisno.
  • Niti pobačaj korišten za stvaranje ovih staničnih linija nije izveden u svrhu razvoja cjepiva. To su učinili po majčinom izboru.
  • Nisu sva cjepiva napravljena pomoću virusa uzgojenih u stanicama ljudskog fetalnog podrijetla.
  • Fetalne stanice nisu sadržane u cjepivima.
  1. “Sojevi ljudskih stanica u razvoju cjepiva”. Povijest cjepiva. Koledž liječnika u Philadelphiji. 31. srpnja 2014.
  2. Sgreccia, E. Moralne refleksije o cjepivima pripremljenim od stanica dobivenih iz pobačenih ljudskih fetusa. 9. lipnja 2005. Pismo pronađeno pod "Zabrinutošću cjepiva" Koalicije za akciju imunizacije. www.immunize.org/concerns.
  3. Plotkin. "Povijest cijepljenja." Pnas. 5. veljače 2014. Vol. 111, br. 34, str. 12283-12287.
  4. Sven, G., S. Plotkin, K. McCarthy. “Proizvodnja inaktiviranog virusa rubeole za profilaksu gama globulina i biološka kontrola živih atenuiranih cjepiva protiv virusa rubeole”. American Journal of Diseases of Children. kolovoza 1969. sv. 118, br. 2, str. 372-381.
  5. Jacobs, J.P., C.M. Jones, J.P. Bailie. “Karakteristike ljudske diploidne stanice označene kao MRC-5”. Priroda. 11. srpnja 1970. sv. 277, str.168-170.
  6. Wadman, M. “Medicinska istraživanja: Podjela stanica.” 27. lipnja 2013. Vol. 498. Str. 422-426.
  7. Plotkin, S., D. Cornfield i T. Ingalls. “Studije imunizacije živim virusom rubeole.” Amer J Dis Child. listopada 1965. sv. 110. Str. 381-389 (prikaz, stručni).
  8. “Prvi korak prema cjepivu za hepatitis A.” Novi znanstvenik. 31. svibnja 1979. sv. 82. broj 1157. str. 730.
  9. Nunnally, B.K., V.E. Turula i R.D. Sitrin. Analiza cjepiva: strategije, principi i kontrola. 27. studenog 2014. str. 54-57.


Što se dogodilo u prošlosti s kulturom fetalnih stanica?

Godine 1972. kultura stanica uzgojena iz fetusa održava se i naširoko koristi za stvaranje raznih cjepiva za vodene kozice, bjesnoću i rubeolu gotovo 50 godina.

U 2016. godini objavljena su dva članka New England Journal of Medicine karakterizira fetuse elektivnih pobačaja, od kojih je jedan bio star 32 tjedna, od majki koje su zarazile Zika virusom u prvom tromjesečju trudnoće.

Prema Centrima za kontrolu i prevenciju bolesti (CDC), virus Zika se prenosi na ljude ubodom komaraca. Zasluge za sliku: Reuters

Rast stanične kulture također je obećavao u liječenju Alzheimerove bolesti, amiotrofične lateralne skleroze, dijabetesa i dječje leukemije, prema izvješću o Znanstveni petak. Dr. Eugene Gu, istraživač fetalnog tkiva, također je proučavao urođene bolesti srca i bubrega u dojenčadi.

Cjepiva temeljena na stanicama razvijena su iz staničnih linija sisavaca, a ne uobičajenom metodom - koja koristi stanice u embrionalnim kokošjim jajima za razvoj antigena koji pomažu aktiviranju imuniteta kada se ubrizgavaju kod ljudi.

Životinje su korištene u masovnoj proizvodnji ljudskih cjepiva otkako su ustanovljene farme cjepiva za prikupljanje virusa kravljih boginja od teladi kasnih 1800-ih.

Tijekom prve polovice 20. stoljeća većina cjepiva razvijena je uz korištenje životinja, bilo uzgojem patogena u živim životinjama ili korištenjem životinjskih stanica.

Mnoga cjepiva i proizvodi protiv toksina uspješno su razvijena na ovaj način. Korištenje životinja u razvoju cjepiva – osobito živih životinja – pokazalo se manje nego idealno.

Cjepiva stanične linije kasnije su razvijena iz pobačenih ljudskih fetusa.


Kako su "abortirane fetalne stanice" doprinijele cjepivima sprječavajući milijarde slučajeva bolesti i mnoge milijune smrti

Masovne su dezinformacije koje objavljuje pokret protiv cjepiva, a mnoge su i njegove laži. Na primjer, antivakseri tvrde da cjepiva, na ovaj ili onaj način, uzrokuju autizam, autoimune bolesti, sindrom iznenadne smrti dojenčadi (SIDS), rak i široku paletu drugih stanja i bolesti kada nema vjerodostojnih dokaza da uzrokuju i mnogo dokaza da nemaju. Jedan od omiljenih metoda koje antivakseri koriste kako bi uplašili roditelje da ne cijepe svoju djecu poznat je kao gambit "toksina", u kojem antivakseri navode popise zastrašujućih sastojaka u cjepivima kao što je formaldehid kako bi tvrdili da su cjepiva puna "toksina" i da su ti toksini ti koji uzrokuju sve loše stvari za koje neispravno krive cjepiva. Naravno, doza stvara otrov, a količine tih kemikalija u cjepivima su vrlo male. Konkretno, jedan primjer, formaldehid, čak je normalan proizvod ljudskog metabolizma i prisutan je u krvi na razinama daleko višim od bilo kojeg cjepiva. Poanta je da ti "toksini", u dozama prisutnim u cjepivima, nisu štetni, ali kemijski nazivi sigurno zvuče zastrašujuće.

Postoji varijanta gambita o "toksinima" koja je osmišljena tako da se dopadne pripadnicima religija koje izjednačavaju pobačaj s ubojstvom, a to je tvrdnja da postoje "pobačene fetalne stanice" u cjepivima ili, još izrazitije (i zbunjuju kultivirane stanice i stvarne tkivo) "pobačeno fetalno tkivo" u cjepivima. Ideja je naslikati sliku proizvođača cjepiva kako melju mrtve fetuse kako bi napravili svoje odvratne izmišljotine koje će staviti u cjepiva, bez sumnje se zlobno cerečući dok to rade i zahtijevaju više pobačaja kako bi im osigurali svoje užasne sirovine. (Pretjerujem, ali samo malo.) Ideja je naravno prikazati cjepiva ne samo kao kontaminirana nečim odvratnim, već i kao proizvod zla.

Kao i kod većine anticjepiva, i ovdje postoji zrno istine iskrivljeno do neprepoznatljivosti. Zalihe virusa koji se koriste za izradu nekih cjepiva uzgajaju se u staničnim linijama kao što je stanična linija WI-38, ljudska diploidna stanična linija fibroblasta izvedena iz tromjesečnog fetusa pobačenog terapeutski 1962. Naravno, postoji ogromna razlika između stanična linija koja je izvedena iz fetusa prije 55 godina i stvarne "fetalne stanice". Iako je ispravno reći da su stanice WI-38 izvedene iz fetusa, one su mnoge generacije (replikacije) uklonjene iz izvornih stanica iz izvornog fetusa. Iako ta većina religija protiv pobačaja, Katolička crkva nije oduševljena cjepivima napravljenim od WI-38 stanica i potiče znanstvenike da razviju cjepiva koja ne koriste takve stanične linije, prepoznaje veliku dobrobit cjepiva i zaključuje da ekstremno dobro zaštite dječjih života od smrtonosnih bolesti daleko nadmašuje daleko zlo koje je stvorilo stanične linije. Također napominjem da je u slučaju WI-38 pobačaj bio terapeutski, odnosno medicinski indiciran. Nije bilo izborno.

Ali zašto se koristi WI-38 stanična linija? I koja je bila korist? Koliko god antivakseri inače bili nerazumni, ova pitanja nisu nerazumna. Stoga sam s velikim zanimanjem pročitao studiju koju mi ​​je poslao čitatelj (i, dok sam jutros posljednji put pregledavao ovu studiju, vidio sam da je moj dobar blog Skeptical Raptor također obradio ovu studiju, iako iz nešto drugačije gledište), Uloga stanične vrste WI-38 u spašavanju života i smanjenju morbiditeta/. Otvoren je pristup tako da ga možete sami pročitati. U osnovi, autori S. Jay Olshansky i Leonard Hayflick, sa Sveučilišta Illinois u Chicagu i UCSF, smatraju razvoj stanične linije WI-38 kao temeljni događaj u povijesti cjepiva, ističući da s porastom novi pokret protiv cjepiva spremni smo napraviti veliki korak unatrag u javnom zdravstvu:

Ako pokret protiv cijepljenja dobije dodatnu snagu, razvijene zemlje i zemlje u razvoju učinit će opasan korak unatrag u zaštiti javnog zdravlja, posebno zdravlja djece. Postoji mnogo načina da se ponovno naglasi zdravstvene prednosti cijepljenja, ali jedan novi pristup koji predstavlja savršen primjer primijenjene demografije u javnom zdravstvu jest ilustrirati koliko je života spašeno i koliko je ljudi danas živo, kao rezultat jednog jedinog proboja u lancu povijesnih događaja koji su doveli do razvoja i uspješnog širenja živih atenuiranih virusnih cjepiva. Ovdje ilustriramo kako je otkriće i korištenje jednog staničnog soja koji se koristi za uzgoj većine virusnih cjepiva u upotrebi danas (WI-38 [8] i kasniji derivat [9]), već imalo snažan utjecaj na ljudski život na veličine bez presedana u povijesti javnog zdravstva. Ova izravna primjena primijenjene demografije bacit će novo svjetlo na (1) važnost cjepiva u spašavanju života, (2) lanac slučajnih događaja koji su se dogodili kako bi stvorili proboj u javnom zdravstvu ove veličine i (3) razjasniti da pokret protiv cijepljenja predstavlja ozbiljnu prijetnju dokazanoj javnozdravstvenoj intervenciji.

Također napominju da pokrivaju samo jedan proboj i njegove učinke:

Koristimo WI-38 kao referentnu točku zbog njegove specifične veze s određenim cjepivima u ranoj fazi pokreta cjepiva i zato što je njegov razvoj ranih 1960-ih poslužio kao katalizator za to područje. Pune zasluge za spasonosne učinke cjepiva pripadaju otkrićima, znanstvenim napretcima i teškom radu nebrojenih znanstvenika i zdravstvenih djelatnika, koji su svi zajedno pridonijeli izgradnji lanca razvoja i uporabe cjepiva.

Autori počinju s kratkom poviješću cjepiva. Prije nego je stanična linija WI-38 izolirana, zalihe virusa za cjepiva poput poliomijelitisa uzgajane su u stanicama izoliranim iz bubrega majmuna. Međutim, ubrzo je otkriveno da su te stanice majmuna često bile kontaminirane virusima majmuna. Najpoznatiji od njih je SV-40, koji bi, kako su znanstvenici uočili početkom 1960-ih, mogao uzrokovati tumore kod pokusnih životinja. Nikada nije pokazano da je SV-40 u cjepivima korištenim za stvaranje živog virusnog cjepiva protiv dječje paralize 1950-ih i ranih 1960-ih doveo do porasta raka, kao što sam već raspravljao, ali je ipak česta tema među pokret protiv cjepiva da je SV40 u tim serijama cjepiva protiv dječje paralize kasnih 1950-ih i ranih 1960-ih odgovoran za "epidemiju raka", ili, što je još rizičnije, bio je izvor HIV-a, virusa odgovornog za AIDS. Teorije zavjere i danas su u izobilju. U svakom slučaju, u to vrijeme znanstvenici nisu znali da tumorogena svojstva SV40 opažena na životinjskim modelima u to vrijeme nisu prevedena na ljude, pa je razvoj stanica bez SV40 za rast zaliha virusa brzo postao visok prioritet. U osnovi, razvoj WI-38 bio je dio šireg nastojanja da se pronađu načini za eliminaciju SV40 iz cjepiva protiv dječje paralize.

Suprotno onome što antivakseri tvrde, postoji mnogo prednosti korištenja WI-38 za uzgoj virusnih zaliha za cjepiva kako autori govore:

Prvi soj ljudskih stanica korišten za proizvodnju licenciranih cjepiva protiv ljudskih virusa bio je WI-38 koji je razvio jedan od nas (LH) na Wistar Institutu u Philadelphiji 1962. Za razliku od primarnih staničnih kultura, WI-38 se prenosi iz jedne posude u dodatne posude ad seriatim, čime se proizvodi gotovo neograničen broj stanica iz jednog izvora za proizvodnju mnogih cjepiva protiv ljudskih virusa. Budući da se jedan soj stanica može zamrznuti na neodređeno vrijeme, WI-38 je zamrznut 55 godina, što je najduži vremenski period u kojem su normalne ljudske stanice bile zamrznute. Od velike važnosti, za razliku od primarnih stanica, WI-38 je iscrpno ispitan na sigurnost i učinkovitost prije upotrebe [18]. Zamrzavanje primarnih stanica za testiranje je nepraktično. Od ranih 1960-ih, velika većina cjepiva protiv humanih virusa uzgajana je u WI-38 ili njegovim derivatima, što je njegovo otkriće i nastavak korištenja učinilo kritičnom inovacijom u povijesnom lancu događaja potrebnih za razvoj cjepiva [19]. Za razliku od primarnih kultura bubrega majmuna, važnost WI-38 je u tome što (1) potječe od jednog donora, (2) nije kontaminirajućih virusa i (3) može se zamrznuti na neodređeno vrijeme i testirati za sigurnost i djelotvornost prije uporabe u proizvodnji cjepiva velikih razmjera [20]. WI-38 je besplatno distribuirao dr. Hayflick svjetskim proizvođačima cjepiva protiv ljudskih virusa.

Treba priznati da je jedan od autora članka, dr. Leonard Hayflick, zapravo razvio WI-38, koji je želio znati koliko je života spašeno cjepivom dobivenim od WI-38. Istaknuto je to, na samu studiju. U osnovi, kako bi procijenili broj slučajeva bolesti i broj smrtnih slučajeva spriječenih cjepivima razvijenim pomoću W-38, Olshansky i Hayflick su koristili postojeće objavljene podatke o učestalosti i broju smrtnih slučajeva za svaku bolest u SAD-u 1960. godine, dva godine prije nego što je razvijen WI-38. Pod pretpostavkom da bi stope prevalencije ostale konstantne bez cjepiva, procijenili su koliko je slučajeva bolesti i smrti spriječeno u SAD-u i diljem svijeta. Uzeli su u obzir godinu uvođenja svakog cjepiva, te analize provedene do 2015. kako bi se procijenili učinci cjepiva. Sad, znam što misliš. Je li razumno pretpostaviti da bi incidencija i stope smrtnosti zbog ovih cjepiva ostale iste bez cjepiva? Zasigurno je malo razloga za pretpostavku da bi se incidencija znatno promijenila, iako su poboljšanja u medicinskoj skrbi mogla smanjiti stopu smrtnosti neovisno o cjepivu. Također postoji problem da incidencija može varirati iz godine u godinu, ponekad (kao u slučaju dječje paralize prije cjepiva) dramatično. Stoga rezultate ove studije moramo promatrati kao grubu procjenu broja spašenih života. To bi moglo precijeniti učinak, ili bi također moglo podcijeniti koliko je života spašeno. Mogao bi čak učiniti oboje, podcjenjujući učinak cjepiva za neke bolesti i precjenjujući ga od drugih. Kako god bilo, rezultati su zapanjujući, kao što pokazuje ključna tablica iz studije za SAD (kliknite za prikaz):

Sveukupno, autori procjenjuju da je ukupan broj slučajeva poliomijelitisa, ospica, zaušnjaka, rubeole, varičele, adenovirusa, bjesnoće i hepatitisa A spriječenih ili liječenih cjepivima povezanim s WI-38 između 1960. i 2015. iznosio 198 milijuna u SAD-u i 4,5 milijardi u svijetu (720 milijuna u Africi 387 milijuna u Latinskoj Americi i na Karibima 2,7 milijardi u Aziji i 455 milijuna u Europi). Osim toga, procijenjeni ukupan broj izbjegnutih smrtnih slučajeva od ovih istih bolesti bio je približno 450.000 u SAD-u i 10,3 milijuna u svijetu (1,6 milijuna u Africi, 886 tisuća u Latinskoj Americi i na Karibima 6,2 milijuna u Aziji i 1,0 milijuna u Europi). To su nevjerojatne brojke i nisu u skladu s drugim procjenama. Na primjer, podaci iz projekta Tycho pokazuju da su samo u SAD-u brojke vjerojatno daleko veće. Naravno, Tycho Project se nije ograničio samo na cjepiva povezana s WI-38 nego je promatrala sva cjepiva. Poanta je da je Tycho Project koristio rigorozniju metodologiju i došao do procjena istog reda veličine. Druge su procjene također veće od onih Olshanskyja i Hayflicka. Suština je da cjepiva djeluju. Spriječili su milijarde slučajeva bolesti i milijune smrti. Jedini razlog zašto antivakseri mogu zvučati čak i najmanje uvjerljivo kada koriste gambit "cjepiva nas nisu spasila" je taj što, zahvaljujući cjepivima, danas ne vidimo taj ogroman broj slučajeva bolesti i smrti.

Koliko god da je to moglo biti sebično, ono što Hayflick i Olshansky pridonose podacima jest procjena koliko su te zle "pobačene fetalne stanice" bile važne za ukupno smanjenje bolesti, patnje i smrti zbog cjepiva. Autori također primjećuju kako bi drugi antiznanstveni trendovi, osim pokreta protiv cjepiva, učinili razvoj stanične linije WI-38 teškim ili nemogućim u SAD-u i zaključuju primjećujući koliko života cjepiva svake godine spašavaju. Vrijedi opširno citirati:

Svako otkriće ili proboj u lancu događaja koji su doveli do toga da cjepiva postanu priča o uspjehu u javnom zdravstvu možda se na kraju i dogodila. Međutim, vrijeme je važno i nema sumnje da je, kada je stanični soj WI-38 postao dostupan 1962., slučajno otkriveno u isto vrijeme da je utvrđeno da su primarne stanice bubrega majmuna korištene za proizvodnju cjepiva protiv poliomijelitisa kontaminirane. . Stoga je korištenje WI-38 predstavljalo katalizator za kasniji razvoj cjepiva. Zapravo, uspjeh istraživanja koje je rezultiralo razvojem WI-38 1962. dogodio se kada savezni istraživački fondovi nisu bili zabranjeni za proučavanje biologije tkiva dobivenog od pobačenih ljudskih fetusa. Međutim, tijekom nekoliko kasnijih predsjedničkih administracija ta se zabrana provodila. Da je ta zabrana bila na snazi ​​1962., malo je vjerojatno da bi u sljedećih 55 godina postojale milijarde ljudi koji bi imali koristi od cjepiva protiv virusa proizvedenog u WI-38.

Odgoda od čak godinu dana u razvoju nekontaminiranog staničnog soja za razvoj cjepiva stajalo bi čovječanstvo milijune života i nebrojeno više slučajeva morbiditeta koji se može spriječiti cjepivom. Danas je većina od 7,5 milijardi ljudi na svijetu cijepljena protiv virusnih bolesti korištenjem soja stanica WI-38 i njegovih derivata. Gotovo svi rođeni u razvijenom svijetu od 1962. primili su barem jedno cjepivo proizvedeno sa staničnim sojem WI-38, zajedno s rastućim udjelom stanovništva u zemljama u razvoju. WI-38 i njegovi derivati ​​još uvijek se koriste za proizvodnju mnogih virusnih cjepiva koja se danas distribuiraju diljem svijeta.

Danas su žive milijarde ljudi koji bi inače ili umrli u djetinjstvu ili bi bili osakaćeni ili onesposobljeni zbog bolesti koje se mogu spriječiti cjepivom. Svjetska zdravstvena organizacija procjenjuje da sva cijepljenja koja su sada dostupna sprječavaju oko 2,5 milijuna smrtnih slučajeva među djecom svake godine, ali bi se još mnogo života moglo spasiti da su cjepiva univerzalno dostupna. Zapravo, ironično je da se cjepivu protiv rubeole (koje se proizvodi u staničnom soju WI-38 koji potječe od pobačenog ljudskog fetusa) snažno protive zagovornici anti-choice, iako je ovo cjepivo spriječilo više od 633 000 pobačaja samo u SAD-u , and countless more across the globe, and it has prevented tens of millions of clinical health issues in children (eg, encephalitis, autism, deafness, diabetes, etc.) linked to congenital rubella syndrome [27].

Indeed. WI-38 is an excellent example of the sorts of discoveries that ill-advised restrictions on federal funding of research into fetal cells could inadvertently delay and the hypocrisy of some anti-abortion antivaccine activists, who mischaracterize the use of WI-38 cells in vaccine manufacturing as "fetal cells" or "fetal tissue" in vaccines. More recently, perhaps realizing how silly this mischaracterization is, some have started fear mongering about incredibly tiny amounts of "fetal DNA" (i.e., DNA fragments from WI-38 cells that can, if you do really, really sensitive PCR, be detected) as though it were somehow dangerous. The isolation of WI-38 cells is also an excellent example of serendipity in science in that its discovery just so happened to coincide with a time when the safety of the existing vaccines in use was being questioned because of the discovery of SV40 contamination. If not for SV40, vaccine scientists and manufacturers might have had much less incentive to change (or at least to change rapidly) their methods of producing vaccines to using WI-38 cells to grow the viruses used.

So when an antivaxer asks why "aborted fetal cells" are used to make vaccines, point them to this paper. The reasons are simple. Using WI-38 cells to make vaccines against viral diseases facilitated manufacturing huge quantities of much more standardized and safer vaccines that have saved millions and millions of lives and prevented billions of cases of disease over the last 55 years.


Is the measles outbreak that occurred in Disney Land of a different strain than what’s in the vaccine?

Here is a question I got recently that I want to publicly respond to:

Is the measles outbreak that occurred in Disney Land of a different strain than what’s in the vaccine? Are those who are vaccinated not protected?

The measles virus has many different genotypes, but only one serotype. When you say, “different strain,” that means different variation in genotype.

The virus can vary a bit genetically, but they all “look” the same when it comes to our immune systems. When a virus is all of the same serotype, they have the same antigens (proteins that our bodies recognize and make an immune response to) on the outside.


Sažetak

The main questions posed in ageing theories are how ageing evolved and whether or not it is programmed. While these questions have not yet been clearly resolved, several groups of possible theories have been published on this topic. However, most of these theories do not consider plants, and the specific traits involved in their ageing mechanisms. The first trait covers clonality and sectoriality and the second concerns the lack of a differentiated germ line. The lack of a germ line prevents telomere shortening which can lead to the transfer of somatic mutations into sexual offspring, while sectoriality in trees causes isolation of potentially catastrophic events in one tree part, thus creating a population of more or less independent modules within one axis. The processes of population dynamics, including ageing, can act within the framework of an individual tree as well as in that of the population as a whole, although the processes involved differ and consequently result in different effects.


Epithelial Cells: Growth in Culture of Normal and Neoplastic Forms 1

This chapter deals with the division potential of different cell types in vivo, and with the factors that may be responsible for some of the unexplained differences that are found in the culturing cells of different origins. The behavior of cultured normal epithelial cells is of particular importance for the in vitro study of carcinoma, because it is only occasionally that permanent human carcinoma cell lines can be established, using current methodology. The chapter discusses whether carcinoma cells in vivo have unlimited growth potential, as is usually assumed to be the case. Biologically and kinetically there is no need for such an assumption because a limited number of cell divisions in an expanding population of logarithmically dividing cells are quite sufficient for very large amounts of tumor tissue. Division potential in renewing epithelia is potentially instructive in understanding the biology of the carcinoma cell. There is evidence that several stem cell populations may be in continuous rapid division throughout the lifetime of the organism, requiring a very high limit of division potential and perhaps no limit at all. This possibility is a subject of study in human material and might yield very instructive results.

Supported by NIH Research Grant No. CA06008 from the Division of Research Grants, by Institutional General Research Support Grant 485, and by American Cancer Society Institutional Grant 9M–1.


Corvelva and “Vaccinegate”: Italian antivaxers produce a dubious “scientific report” on fetal DNA in vaccines

The Italian antivaccine group Corvelva published a really bad “scientific report” claiming fetal DNA in vaccines is dangerous based on a dubious next generation sequencing analysis whose methods are not described. It’s not. To believe its claims, you have to believe that DNA can do anything.

Antivaccine misinformation never dies. It’s just continuously recycled into another form. As I like to say, whenever you think you’ve seen the last of a particular bogus antivaccine claim, think of the end of a 1980s slasher film and what happens to the killer at the end, you know, Jason Voorhees, Michael Myers, or Freddie Krueger. YOu know what happens. It looks for all the world as though the killer is dead or otherwise eliminated, but he always—always!—comes back to kill more teenagers in the sequel. So it is with antivaccine claims. This time around, I’ve been sensing a stirring in the antivaccine crankosphere, with a particular bit of antivaccine pseudoscience appearing in multiple places. I first saw it late last week at Health Impact News. Then I saw it on Robert F. Kennedy Jr.’s repository of antivaccine propaganda, Children’s Health Defense. Then I saw it it at Mike Adam’s repository of conspiracy theories, quackery and vileness. (I had missed it there because I rarely bother to check out Natural News any more.) Basically, it’s a new spin on the claim that there are “fetal cells” in vaccines involving the MRC-5 cell line, and it’s a really dumb one, courtesy of an Italian group called Corvelva.

I, of course, have discussed the deception of the “aborted fetal cells” (which all too often morphs into “aborted fetal tissue” when antivaccine ignoramuses tell the tale) in vaccines. The origin of this particular antivaccine trope comes from a grain of truth, which antivaxers twist beyond recognition. In brief, viruses used to make certain vaccines are cultured in human cell lines derived from aborted fetuses, like the WI-38 cell line, which is a human diploid fibroblast cell line derived from the lung of a three month old fetus aborted therapeutically in 1962, while the MRC-5 cell line was derived from lung tissue of a 14 week old aborted caucasian male fetus in 1966. Of course, there’s a huge difference between a cell line that was derived from a fetus 57 or 53 years ago and actual “fetal cells.” While it’s correct to say that WI-38 and MRC-5 cells were derived from aborted fetuses, they are many generations (replications) removed from the original cells from the original fetuses used. Even though that most anti-abortion of religions, the Catholic Church, although not thrilled with vaccines made in these cell lines, recognizes the great good vaccines do and concludes that the extreme good of protecting children’s lives from deadly diseases far outweighs the distant evil—vaccines using fetal cells to grow virus have saved millions of lives and prevented billions of cases of disease—that created the cell lines, urging its members to vaccinate their children. This, of course, does not stop antivaxers from trying to appeal to those whose religions condemn abortion by claiming that there are “fetal parts” or “fetal cells” in vaccines and therefore vaccinating is against their religion.

The claim that fetal “parts” are in vaccines serves another purpose to antivaxers. A major strategy used by antivaxers to frighten parents into refusing vaccines is to portray vaccines as somehow “dirty,” “contaminated,” or just plain yucky. To that end, they like to claim that there are all sorts of horrendous “toxins” in vaccines, ignoring the adage that the dose makes the poison and that one of these “toxins” (formaldehyde) is a normal product of human metabolism and harmless in small amounts. Another tactic is to describe vaccines as being made using cultured cells and cell lines from chickens, dogs, monkeys, hamsters and insects. The “fetal parts” gambit has morphed into a variety of subclaims designed to portray vaccines as dirty, the most prominent of which is the claim that DNA from the fetal cells contaminates the vaccine, somehow gets into human neurons, recombines with the DNA there, producing foreign proteins that show up on the surface of the neurons and provoke an immune response (autoimmunity), thus damaging the neurons. I’ve already explained in my usual painful detail how utterly ignorant of biology and homologous recombination one has to be to accept this hypothesis as anything other than incredibly implausible at best, with no evidence to support it, to boot. Hilariously, one of the most cited (by antivaxers) articles pushing this idea left a typo in about “homologous recombinaltion tiniker” when it meant homologous recombination, the process by which DNA strands can break and recombine when stretches of DNA with the same sequence come together. In the minds of antivaxers, these minute bits of DNA from the fetal cell line used to grow certain vaccines truly have magical properties they can do almost anything!

Which brings us to MRC-5. To amuse myself, let me let Mike Adams be the first to tell you the claim, just because it’s so far over the top. Basically, a laboratory in Italy has apparently sequenced the genome of the MRC-5 cell line, and, according to Adams:

What’s clear from this genetic sequencing is that the vaccine industry is inoculating children with engineered cancer.

Adams gets this from Child Health Defense, which got it from a report by these Italian scientists. Basically, the Corvelva group claims to have found a complete human MRC-5 genome in a lot of Priorix Tetra vaccine (A71CB256A). Priorix Tetra is an MMRV (measles-mumps-rubella-varicella) vaccine made by GlaxoSmithKline. The rubella and varicella viral stocks for this vaccine are grown in MRC-5 cells, while the other two are grown in chick embryo cells. Here’s how RFK Jr.’s fever swamp described the findings:

  1. The fetal cell line was found to belong to a male fetus.
  2. The cell line presents itself in such a way that it is likely to be very old, thus consistent with the declared line of the 1960s.
  3. The fetal human DNA represented in this vaccine is a complete individual genome, that is, the genomic DNA of all the chromosomes of an individual is present in the vaccine.
  4. The human genomic DNA contained in this vaccine is clearly, undoubtedly abnormal, presenting important inconsistencies with a typical human genome, that is, with that of a healthy individual.
  5. 560 genes known to be associated with forms of cancer were tested and all underwent major modifications.
  6. There are variations whose consequences are not even known, not yet appearing in the literature, but which still affect genes involved in the induction of human cancer.
  7. What is also clearly abnormal is the genome excess showing changes in the number of copies and structural variants.

I’ll get to the report (PDF here) in a minute, although I will mention right here that this is not an article reporting medical research in the peer-reviewed medical literature. It wasn’t even published in a bottom-feeding predatory journal. Rather, it was published as a monography. (I wonder why.) I’ll also note that this group called it “Vaccinegate,” and that this isn’t Corvelva’s first antivaccine rodeo. As Vaxopedia described, late last year, the group published a highly dubious analysis of Infanrix Hexa and claimed to have found “65 signs of chemical contaminants of which only 35% is known” and “7 chemical toxins.” Basically, the scientists there are unnamed, and the group has a history of producing dubious “science” for Italian antivaxers.

Before I look at the findings and explain why they don’t say what Corvelva, RFK Jr., and Mike Adams think they say, I also feel obligated to note that Corvelva’s report includes nothing in the way of detailed methods, so that scientists can evaluate their findings. This is about all we get:

New generation sequencing have become the preferred tool for in-depth analysis in the field of biology and medical science, especially high precision ones. Thanks to these tools, we can approach in a more modern and comprehensive way a number of applications such as de novo sequencing, metagenomic and epigenomic studies, transcriptome sequencing and genome re-sequencing.

This last one (re-sequencing) is largely used in human field, both for research and diagnostic purposes and consists of NGS – Next Generation Sequencing of an entire single genome, to map the Single Nucleotide mutations (SNP), insertions and deletions of more or less long sequences that have occurred in certain locations of the genome, and variations in the number of copies of genomic portions/genes (CNV, Copy Number Variants).

This procedure helps to understand the development mechanism of some pathologies, in order to identify the directions for a future clinical treatment as in the case of cancer for example. Indeed, by this method the genetic heritage of a cancer patient can be fully decoded in both normal and cancerous tissue, thus allowing us to comprehend what exactly has changed within the genome, and, if possible, how to intervene with targeted measures.

I think they mean next generation sequencing (NGS), not “new generation sequencing,” but I’ll let it pass because English is clearly not their first language. Yes, NGS is a powerful tool that allows sequencing of whole genomes in a tiny fraction of the time that it used to take. In a study like this, methods matter. They matter a lot. How did Corvelva prepare the sample for NGS? How did it initially discover that there were human DNA sequences detectable? How did they amplify the DNA? (There’s an amplification step for NGS that can introduce noise.) How were the reads done? The sequencing analysis and computational methods? How did the authors make sure there wasn’t any cross contamination? These are all critical questions for which there are no answers. The “scientists” at Corvelva seem to think we should just trust that they know what they’re doing. Here’s the thing, though. In science, we never trust that other scientists know what they’re doing. They have to show us that they do, and part of the way they show us is by giving us the methods.

This same procedure has been performed on the human genome in Priorix​® Tetra lot n. A71CB256A, genome which belongs to cell line MRC-5 (of fetal origin) the work has been carried out by a company in the USA, that routinely deals with human genome re-sequencing analysis. *

* the name of the laboratory that has performed the analysis will be included in the next formal complaint we will file at the Public Prosecutor of Rome and as well at the Italian and European regulatory bodies. The associations who are filing the analysis funded by Corvelva will be promptly kept up to date with these shocking results too. We are no denying that we feel, especially as parents, distressed by these results we are reporting – as if what we have found out so far was not enough to worry about.

So basically Corvelva sent a sample to a lab in the US, paid it to do the work, and accepted whatever came back. That is not impressive, and there is no reason not to name the laboratory here in this report. Also, they only looked at one lot of vaccine. Replication is important, and there’s no way of knowing whether this result was just a fluke.

Let’s go back and look at point #4, though, the “finding” that the allegedly MRC-5 human genome sequenced was “clearly, undoubtedly abnormal, presenting important inconsistencies with a typical human genome.” Let’s for the moment accept this finding as not an artifact. The only proper response to this is: So what? MRC-5 is a cell line that’s been passaged for well over 50 years. Cell lines develop genetic abnormalities with time. There’s an even more amusing thing to consider, though,. Reading the report, I noticed that Corvelva compared the sequence they claim to have found in the vaccine with the sequence of a normal human genome using a special circular plot that shows abnormalities in terms of deletions . What didn’t they compare it to? As far as I can tell, they didn’t compare it to DNA from a sample of MRC-5 cell line.

What about #5, the bit about � genes known to be associated with forms of cancer were tested and all underwent major modifications”?

The Corvelva report concludes:

The human genomic DNA contained in the Priorix lot vaccine. n. A71CB256A is evidently anomalous, presenting important inconsistencies if compared to a typical human genome, i.e. the one of a healthy human being. There are several unknown variants (not noted in public databases) and some of them are located in genes involved in cancer. What is also apparently anomalous, is the excess of genome that shows changes in the number of copies (CNV) and structural variants (SV), such as translocations, insertions, deletions, duplications and inversions, many of which involve genes.

Based on this, RFK Jr. claims:

What are we saying? We are saying that the DNA contained in these vaccines is potentially TUMORIGENIC and that the guidelines to which the supervisory bodies are appealing are NOT ADEQUATE. Moreover, we are publicly denouncing a SERIOUS OMISSION in taking those PRECAUTIONAL measures which, on the other hand, are urgently requested for antacid drugs.

Our results greatly reinforce the experimental observations of Dr. Theresa Deisher and especially the fact that the contaminant fetal DNA present in all samples analyzed in varying quantities (thus uncontrolled) is up to 300 times higher than the limit imposed by the EMA for carcinogenic DNA (10 ng/dose, corresponding to DNA contained in approximately 1000 tumor cells, derived from a statistical calculation, while the precautionary limit is 10 pg/dose), a limit that must also be applied to MRC-5 fetal DNA which inevitably contaminates Priorix tetra.

As a consequence, this vaccine should be considered defective and potentially dangerous to human health, in particular to the pediatric population which is much more vulnerable to genetic and autoimmune damage.

I laughed out loud when I read this. I’ve written about Theresa Deisher’s execrable science more times than I can remember. Remember, she’s the one who claims that tiny amounts of fetal DNA somehow make it to the brain (never mind that pesky blood-brain barrier), recombine in neurons with host DNA to make defective proteins that show up on the cell surface and provoke an autoimmune response leading to autism and other neurologic conditions. As for Corvelva’s claims that this DNA is tumorigenic? First, there’s no evidence that it is. Modifications in 560 genes known to be associated with forms of cancer? Which genes? Which modifications? Specifics matter. Look at the BRCA genes. Most of the variants detected are of unknown or no significance. In addition, even if this DNA were potentially carcinogenic, it’s not going anywhere. Remember, vaccines are injected intramuscularly, where the antigens basically stay. Ah, Corvelva implies, but what if they get into cells?

I have experience with working with DNA, human, mouse, and otherwise, including injecting it into tissues and trying to get it to express the protein for which it encodes. This is not a trivial matter. Think of it this way. If it were, gene therapy would be an almost trivial matter. But it’s not. In general, it’s difficult to induce human cells to take up foreign DNA in tissue. Even with viral vectors, it’s hard to get more than a small percentage of cells not only to take up the DNA but to express detectable levels of protein. Muscle is one tissue that can take up naked plasmid DNA and actually express it. Indeed, this technique has been used to generate cancer vaccines, where plasmid DNA is injected into the muscle in order to cause it to make a certain protein, which then provokes an immune response. But doing this is not easy, and the DNA is not detectably incorporated into the DNA of the muscle cells. Its gene expression is extranuclear (outside the nucleus).

But that’s not all. Even human cells that can take up random bits of extracellular DNA at very low efficiency (like muscle) do not integrate that DNA into their genome. Even if the DNA did reach the nucleus, recombination into the host genome would be both random and rare. Each cell would incorporate different bits of DNA into different locations in its genome. The bottom line is that, even if that tiny amount of fetal DNA had any carcinogenicity, most of it would simply be broken down in the extracellular space, and the only cells it might get into would be muscle cells and (maybe) immune cells.

In other words, it’s really, really, really hard to get naked DNA not in a virus to be expressed or even into cells, but, hey, to Covelva, it seems that this tiny, tiny amount of fetal DNA is magic. It can do everything above and then cause cancer too! Mike Adams, of course, goes even further:

This conclusion appears to confirm that MRC-5 cell lines used in vaccines have been genetically modified to make them more likely to cause cancer in vaccine recipients. Subsequently, vaccine mandates are actually forcing children to be injected with cancer genes so that they become future customers of Big Pharma’s for-profit cancer treatment “solutions” which are incredibly toxic to human health.

Human children, in other words, are being injected with the genetically modified DNA of another aborted human child in order to cause cancer on a nationwide scale, all to benefit the bottom line of the pharmaceutical industry that pushes total censorship about any criticism of vaccines or vaccine ingredients.

I also note that Corvelva is hosting this video on YouTube. So much for not being antivaccine. Of course, the name for which CORVELVA is an abbreviation is Coordinamento Regionale Veneto per la Libertà delle Vaccinazioni, which stands for “Veneto Regional Coordination for Vaccine Freedom,” and the group’s guiding principle is “the free choice of vaccinations.” This is, of course, Adams being Adams, overblown and full of conspiracy theories and nonsense. For one thing, Priorix Tetra isn’t even used in the US here the MMRV vaccine of choice is ProQuad, which is manufactured by Merck.

It just goes to show that everything old is new again. The claim that vaccines made using a fetal cell line is a (relatively) old claim used to appeal to the religious not to vaccinate. Failing that, adding the claim that these vaccines are somehow dangerous because of the tiny amounts of fetal DNA from the cell lines can cause autism (and now cancer) serves to appeal to the nonreligious antivaxers through a modified use of the “toxins gambit” commonly used to portray vaccines as “dirty,” “diseased,” and just plain gross, all to evoke disgust. I wouldn’t trust this report from Corvelva at all unfortunately, thanks to antivaxers good at fear mongering, it might end up being necessary for health authorities to redo this analysis with competent scientists who know how to do NGS, to include the proper controls, to prepare the samples properly, and, most importantly of all, to do the complex analysis properly. In the meantime, antivaxers will continue to make hay with this highly questionable report.

Finally, it figures. As I was finishing up this post, I an article published at Joe Mercola’s supplement story and quackery extravaganza that’s about—you guessed it—fetal DNA in vaccines. It’s not specifically about the Corvelva “study,” but rather a more general survey. I suppose I might have to take this one on too at some point soon.


How is it that the WI-38 cell line isolated by Hayflick in 1962 is still very much around and not affected by the 'Hayflick Limit'? - Biologija

As in other target cells (Haussler, 1986 Minghetti and Norman, 1988 Boland and Boland, 1994), 1α,25(OH)2D3 elicits responses in intestinal cells both through nuclear receptor-mediated gene transcription and a fast mechanism independent of new RNA and protein synthesis (Norman et al., 1992) 1α,25(OH)2D3 rapid responses include the activation of the adenylyl cyclase/cAMP/PKA, PLC/DAG/IP3/PKC signal transduction pathways and the Ca2+ messenger system (Boland et al., 1990a,b,c Boland and Nemere, 1992 Massheimer et al., 1994 Picotto, 2001).Many changes occur during cellular ageing, such as decreased membrane fluidity, increased protein oxidation, decreased DNA methylation and defects in mitogenic signaling (Kirkland, 1992 Lin and Beal, 2003).Aging is associated with increased circulating PTH levels (Chan et al., 1992) and decreased serum vitamin D metabolites (Armbrecht et al., 1984 Liang et al., 1989), intestinal calcium absorption (Bullamore et al., 1970 Armbrecht, 1990), and bone density (Hui et al., 1988).

The hormonally active form of vitamin D3, 1α,25(OH)2-vitamin D3, acts in intestine, its major target tissue, where its actions are of regulatory and developmental importance: regulation of intracellular calcium through modulation of second messengers and activation of mitogenic cascades leading to cell proliferation. Several causes have been postulated to modify the hormone response in intestinal cells with ageing, among them, alterations of vitamin D receptor (VDR) levels and binding sites, reduced expression of G-proteins and hormone signal transduction changes. The current review summarizes the actual knowledge regarding the molecular and biochemical basis of age-impaired 1α,25(OH)2-vitamin D3 receptor-mediated signaling in intestinal cells. A fundamental understanding why the hormone functions are impaired with age will enhance our knowledge of its importance in intestinal cell physiology.

Reduction of exportin 6 activity leads to actin accumulation via failure of RanGTP restoration and NTF2 sequestration in the nuclei of senescent cells

Replicative senescence implies irreversible arrest of normal cell growth after a certain number of divisions, which is a paragon of the general process of cellular senescence [1–3].

We have previously reported that G-actin accumulation in nuclei is a universal phenomenon of cellular senescence. By employing primary culture of human diploid fibroblast (HDF) and stress-induced premature senescence (SIPS), we explored whether the failure of actin export to cytoplasm is responsible for actin accumulation in nuclei of senescent cells. Expression of exportin 6 (Exp6) and small G-protein, Ran, was significantly reduced in the replicative senescence, but not yet in SIPS, whereas nuclear import of actin by cofilin was already increased in SIPS. After treatment of young HDF cells with H2O2, rapid reduction of nuclear RanGTP was observed along with cytoplasmic increase of RanGDP. Furthermore, significantly reduced interaction of Exp6 with RanGTP was found by GST-Exp6 pull-down analysis. Failure of RanGTP restoration was accompanied with inhibition of ATP synthesis and NTF2 sequestration in the nuclei along with accordant change of senescence morphology. Indeed, knockdown of Exp6 expression significantly increased actin molecule in the nuclei of young HDF cells. Therefore, actin accumulation in nuclei of senescent cells is most likely due to the failure of RanGTP restoration with ATP deficiency and NTF2 accumulation in nuclei, which result in the decrease of actin export via Exp6 inactivation, in addition to actin import by cofilin activation.

Shift in sphingolipid metabolism leads to an accumulation of ceramide in senescence

One of the hallmarks of replicative senescence is the presence of growth factor receptors but a lack of their activity .

Ceramide mediates the effects of several agonists leading to differentiation, apoptosis or senescence. We previously showed that ceramide becomes elevated in senescent fibroblasts. In the present study, senescent cultures of Wi-38 fibroblasts and human umbilical-vein endothelial cells were compared to low-passage cultures in order to identify which of the several pathways is predominantly responsible for the increased ceramide. We found that senescent cells take up the ceramide precursor [ 3 H]palmitic acid and convert it to ceramide at essentially equivalent rates to their low-passage counterparts, suggesting that, as a whole, the inherent steps are unaltered. Analysis of subsequent steps, however, revealed changes in ceramide metabolism. The rate of ceramide conversion to sphingomyelin was reduced while glucosylceramide synthesis differed between the cell lines, while the rate of the reverse reactions tended to be increased in senescent cells. We also found a decrease in acidic but not alkaline ceramidase. The data show an overall change in favor increased ceramide levels. Of all of the pathways, neutral sphingomyelinase appears to be the most likely source of the senescence-associated ceramide. The relevance to mitosis and apoptosis are discussed.

Age-related changes in the response of intestinal cells to parathyroid hormone

Many changes occur during cellular ageing, such as decreased membrane fluidity, increased protein oxidation, decreased DNA methylation and defects in mitogenic signaling .

The concept of the role(s) of parathyroid hormone (PTH), has expanded from that on acting on the classical target tissues, bone and kidney, to the intestine where its actions are of regulatory and developmental importance: regulation of intracellular calcium through modulation of second messengers and, activation of mitogenic cascades leading to cell proliferation. Several causes have been postulated to modify the hormone response in intestinal cells with ageing, among them, alterations of PTH receptor (PTHR1) binding sites, reduced expression of G proteins and hormone signal transduction changes. The current review summarizes the actual knowledge regarding the molecular and biochemical basis of age-impaired PTH receptor-mediated signaling in intestinal cells. A fundamental understanding of why PTH functions are impaired with age will enhance our understanding of its importance in intestinal cell physiology.

Effect of ageing in the early biochemical signals elicited by PTH in intestinal cells

Many changes occur during cellular ageing, such as decreased membrane fluidity, increased protein oxidation, decreased DNA methylation and defects in mitogenic signalling .

In previous work, we have demonstrated that rPTH(1-34) increases cytoplasmic calcium concentration ([Ca 2+ ]i) in isolated rat enterocytes. In the present study, we have identified the sources of PTH-mediated increase in [Ca 2+ ]ja and the implication of Ca 2+ on hormone early signals in enterocytes isolated from young (3-month-old) and aged (24-month-old) rats. In young enterocytes, PTH raised [Ca 2+ ]i in a dose-dependent manner (1 pM–100 nM). In cells from aged rats, hormone concentrations higher than physiological (≥1 nM) were required to observe significant increases in [Ca 2+ ]i. Phospholipase C (PLC) inhibitors blocked the initial acute elevation of the [Ca 2+ ]i biphasic response to PTH of young enterocytes while in old cells, no effects were observed. The voltage-dependent calcium-channel blocker (VDCC), nitrendipine, suppressed PTH-dependent changes of the sustained [Ca 2+ ]i phase in young and aged animals. In this study, we analysed, for the first time, alterations in phosphatidylinositol 3-kinase (PI3K) activity and response to PTH in rat enterocytes with ageing. Basal PI3K activity was significantly modified by ageing. Acute treatment with 10 −8 M PTH increased enzyme activity, with a maximun at 2 min (+3-fold) in young rats and only elevated by less than 1-fold basal PI3K activity in aged animals. Hormone-induced tyrosine phosphorylation of p85α, the regulatory subunit of PI3K, as well as the phosphorylation on Thr 308 of its downstream effector Akt/PKB was evident in enterocytes from 3-month-old rats, whereas it was greatly reduced in the cells from 24-month-old animals. Intracellular Ca 2+ chelation (BAPTA-AM, 5 μM) affected the tyrosine phosphorylation of p85α and inhibited PTH-dependent PI3K activation by 75% in young rats and completely abolished the enzyme activity in aged animals, demonstrating that Ca 2+ is required for full activation of PI3K in enterocytes stimulated with PTH. The Thr phosphorylation of PI3K downeffector, Akt/PKB, was also fully dependent on Ca 2+ . Taken together, these results suggest that PTH regulation of enterocyte [Ca 2+ ]i involves Ca 2+ mobilization from IP3-sensitive stores and the influx of the cation from the extracellular milieu, the former pathway being blunted during ageing. The data also indicates a positive role for intracellular calcium in one of the early signals of PTH in rat enterocytes, the activation of PI3K, and that hormone regulation of PI3K activity and Akt/PKB phosphorylation on Thr 308 is impaired with ageing.

Changes in the expression of protein kinase C (PKC), phospholipases C (PLC) and D (PLD) isoforms in spleen, brain and kidney of the aged rat: RT- PCR and Western blot analysis

The age-dependent changes of expression of protein kinase C (PKC), phospholipase C (PLC) and phospholipase D (PLD) isozymes were analyzed in spleen, brain and kidney of young-adult (12–16 week-old) and aged (82–88 week-old) rats. The activities of spleen cPKC and nPKC were significantly decreased by nearly 35 and 30% in aged rats compared to those of young adults, respectively (P<0.05). The level of PKC β1 was significantly decreased in aged rats as assessed by RT-PCR and Western blot analyses. In aged rat brain where the activity of cPKC was significantly decreased by nearly 25% (P<0.05), PKC α i β1 isozymes were significantly down-regulated. In kidney, the level of PKC β2 was decreased. In spleen the both mRNA and protein levels of PLC β2 and γ2 were significantly down-regulated in aged rat (P<0.05). PLC β1 was also significantly lower in aged rat brain (P<0.05) as assessed by RT-PCR and Western blotting. Moreover, PLC β1 was significantly down-regulated in both mRNA and protein levels in aged rat kidney (P<0.05). In contrast, the tissues examined, the expressions of PLD isozymes (PLD1a, 1b and 2) were rather stable in the course of aging. These results indicate that mRNAs of PLD isozymes were rather stable but that particular PKC and PLC isozymes were down-regulated in different tissues during aging, suggesting age-dependent decline of specific PKC and PLC isozymes in organs which may, at least in part, be implicated in tissue dysfunction with aging.