Researchers warn that large parts of biomedical science could be invalid due to a cascading history of flawed data in a systemic failure going back decades.
A new investigation reveals more than 30,000 published scientific studies could be compromised by their use of misidentified cell lines, owing to so-called immortal cells contaminating other research cultures in the lab.
The problem is as serious as it is simple: researchers studying lung cancer publish a new paper, only it turns out the tissue they were actually using in the lab were liver cells. Or what they thought were human cells were mice cells, or vice versa, or something else entirely.
If you think that sounds bad, you're right, as it means the findings of each piece of affected research may be flawed, and could even be completely unreliable.
"Most scientists don't intentionally publish findings on the wrong cells," explains one of the researchers, Serge Horbach from Radboud University in the Netherlands.
"It's an honest mistake. The more concerning problem is that the research data is potentially invalid and impossible to reproduce."
Horback and fellow researcher Willem Halffman wanted to know how extensive the phenomenon of misidentified cell lines really was, so they searched for evidence of what they call "contaminated" scientific literature.
Using the research database Web of Science, they looked for scientific articles based on any of the known misidentified cell lines as listed by the International Cell Line Authentication Committee's (ICLAC) Register of Misidentified Cell Lines.
There are currently 451 cell lines on this list, and they're not what you think they are – having been contaminated by other kinds of cells at some point in scientific history. Worse still, they've been unwittingly used in published laboratory research going as far back as the 1950s.
"After an extensive literary study, we believe this involves some 33,000 publications," Halffman explains.
"That means there are more than 30,000 scientific articles online that are reporting on the wrong cells."
In 1951, this 31-year-old mother of five from Virginia died from cervical cancer. But during treatment before her death, cells were taken from Lacks' cervix in a biopsy without her consent.
Later, cell biologist George Otto Gey discovered these cells could be kept alive and grow indefinitely in a lab – as such, HeLa cells became the first immortalised cell line, meaning they didn't eventually die due to cellular senescence.
That everlasting quality made them a valuable research specimen that was distributed across the world, ultimately contributing to the development of cell cloning, the polio vaccine and many other firsts.
It's estimated as many as 20 tonnes of HeLa cells were ultimately grown, with the discovery featuring in a stunning 11,000 patents, but the cells' undying nature came with a hidden cost.
Not only do the cells proliferate, they can also contaminate other exposed cell cultures in laboratory setting, and due to decades of use and misuse in the lab, HeLa cells and other contaminating and immortal cells have been estimated to have tainted up to 36 percent of cell lines scientists use in research.
"It's astonishingly easy for cell lines to become contaminated," ICLAC chair Amanda Capes-Davis explained in 2015 at Retraction Watch.
"When cells are first placed into culture, they usually pass through a period of time when there is little or no growth, before a cell line emerges. A single cell introduced from elsewhere during that time can outgrow the original culture without anyone being aware of the change in identity."
Over decades, these cases of mistaken identity have in turn contaminated some 33,000 scientific papers by Horback and Halffman's count, and it's something that not enough in the research community know about.
"Employees at [biomedical cell distribution] centres recognise the problem, but claim no one will listen to them," says Halffman.
"Sometimes it involves semi-private companies that refuse to disclose anything for fear of reputation or financial damage. The biggest factor by far is pride and fear of reputation damage."
Another contributing issue is pressure to publish, with researchers not having the time or money to verify their cell cultures adequately before they begin their research.
Of course, the tendency to skip that all-important verification is only something that worsens the broader reproducibility crisis plaguing science.
The researchers suggest published research using misidentified cell lines could be clarified with notices that highlight the issue, and say future publications need to implement systems that make the source of the cell lines investigated more transparent.
Whatever course of action the research community decides upon, it's a huge problem to fix – but it's not something we can ignore.
"Nearly half a century after the first concerns about misidentified cell lines, the initiatives to improve authentication need to be complemented by attention to the already contaminated literature," the authors write.
"Our analysis shows that the task is sizeable and urgent."
The findings are reported in PLOS ONE.
Watafiti wanahofia kwamba sehemu kubwa ya sayansi ya biomedical inaweza kuwa halali kutokana na historia ya data isiyofaa katika kushindwa kwa mfumo kwenda nyuma kwa miongo kadhaa. Uchunguzi mpya unaonyesha zaidi ya masomo ya kisayansi 30,000 yaliyochapishwa yanaweza kuathiriwa na matumizi yao ya mistakenly-identified cell lines, kutokana na seli za kudumu zinazochafua mimea mingine ya utafiti katika maabara. "Tatizo ni kubwa kama ni rahisi: watafiti wanaochunguza kansa ya mapafu kuchapisha karatasi mpya, tu ni kugeuka nje tishu walikuwa kweli kutumia katika maabara walikuwa seli ya ini. """ Au kile walichofikiri kuwa ni chembe za binadamu ni chembe za panya, au kinyume chake, au kitu kingine kabisa. Ikiwa unafikiri hiyo inaonekana mbaya, unakosea, kwani inamaanisha matokeo ya kila kipande cha utafiti unaoathiriwa inaweza kuwa na kasoro, na inaweza hata kuwa ya kutoaminika kabisa. "Wanasayansi wengi hawachapishi kwa makusudi matokeo juu ya chembe zisizo sahihi, ""anaeleza mmoja wa watafiti, Serge Horbach kutoka Chuo Kikuu cha Radboud nchini Uholanzi." "Ni kosa la unyoofu. Tatizo lenye kusumbua zaidi ni kwamba data za utafiti hizo huenda zisiwe na matokeo na haziwezi kutolewa tena". "Hofman na Willem Halffman, wanaochunguza, walitaka kujua jinsi tatizo la ""mstari wa seli uliotambuliwa vibaya"" lilivyoenea, kwa hiyo wakachunguza maandishi ya kisayansi yaliyochafuliwa." Kwa kutumia hifadhidata ya utafiti wa Web of Science, walitafuta makala za kisayansi kulingana na yoyote ya mistakes zinazojulikana za seli kama ilivyoorodheshwa na Kamati ya Kimataifa ya Uhalali wa Seli (ICLAC) ya Usajili wa Mistakes. Kuna sasa 451 mistari ya seli katika orodha hii, na wao si nini unafikiri wao ni - kuwa kuambukizwa na aina nyingine ya seli wakati fulani katika historia ya kisayansi. Hata hivyo, kwa bahati mbaya, kwa sababu ya matumizi ya dawa za kulevya, utafiti wa maabara umefanywa tangu miaka ya 1950. "Baada ya utafiti wa kina wa fasihi, tunaamini hii inahusisha machapisho kama 33,000,"" Halffman anaelezea." "Hiyo inamaanisha kuna zaidi ya makala 30,000 za kisayansi mtandaoni ambazo zinaripoti juu ya seli zisizo sahihi. """ Mwaka 1951 mwanamke huyo mwenye umri wa miaka 31 kutoka Virginia, Marekani, alikufa kutokana na kansa ya shingo ya tumbo la uzazi. Lakini wakati wa matibabu kabla ya kifo chake, chembe zilichukuliwa kutoka kwa shingo ya tumbo la uzazi la Lacks katika upasuaji bila idhini yake. Baadaye, mwanabiolojia wa seli George Otto Gey aligundua kwamba seli hizi zinaweza kuhifadhiwa hai na kukua kwa muda usiojulikana katika maabara - kwa hivyo, seli za HeLa zilikuwa mstari wa kwanza wa seli zisizo na kifo, ikimaanisha kwamba hatimaye hazikufa kwa sababu ya kuzeeka kwa seli. Ubora huo wa kudumu uliwafanya kuwa sampuli ya utafiti yenye thamani ambayo iligawanywa ulimwenguni kote, hatimaye ikichangia maendeleo ya kloni ya seli, chanjo ya polio na mengine mengi ya kwanza. Inakadiriwa kuwa hadi tani 20 za seli za HeLa zilipandwa, na uvumbuzi huo ulionyesha hati miliki 11,000 za ajabu, lakini asili ya seli hizo isiyo na mwisho ilikuja na gharama iliyofichwa. Seli hizo hazizidi kuongezeka tu, lakini pia zinaweza kuchafua mimea mingine ya seli iliyofunuliwa katika mazingira ya maabara, na kwa sababu ya miongo kadhaa ya matumizi na matumizi mabaya katika maabara, seli za HeLa na seli nyingine za uchafuzi na zisizo na kifo zimekadiriwa kuwa zimechafua hadi asilimia 36 ya safu za seli ambazo wanasayansi hutumia katika utafiti. "Ni rahisi sana kwa mstari wa seli kuambukizwa, ""msimamizi wa ICLAC Amanda Capes-Davis alielezea mnamo 2015 katika Retraction Watch." "Wakati chembe zinawekwa kwa mara ya kwanza katika utamaduni, kwa kawaida hupita kipindi cha wakati ambapo kuna ukuzi mdogo au hakuna, kabla ya mstari wa chembe kutokea. Chembe moja tu iliyoletwa kutoka mahali pengine wakati huo inaweza kukua zaidi ya utamaduni wa awali bila mtu yeyote kujua mabadiliko katika utambulisho. Katika miaka ya hivi karibuni, ripoti za makosa ya utambulisho zimehusisha karatasi za kisayansi 33,000 na ni jambo ambalo jamii ya watafiti haijui. "Wafanyakazi katika vituo vya [kugawanya chembe za matibabu ya kibiolojia] wanatambua tatizo hilo, lakini wanadai kwamba hakuna mtu atakayewasikiliza", asema Halffman. "Nyakati nyingine inahusisha makampuni ya nusu-binafsi ambayo hukataa kufunua chochote kwa kuogopa sifa au uharibifu wa kifedha. Jambo kubwa zaidi ni kiburi na hofu ya kuharibiwa kwa sifa". "Hata hivyo, kuna tatizo la ""kuchapisha"" kwa sababu watafiti hawana muda au pesa za kuthibitisha utamaduni wao wa seli kabla ya kuanza utafiti wao." Bila shaka, mwelekeo wa kuruka kwamba uthibitisho wote muhimu ni kitu tu kwamba huzidisha pana reproducibility mgogoro plaguing sayansi. Watafiti wanasema utafiti uliochapishwa kwa kutumia mistakenly-kujulikana mistari ya seli inaweza kuwa wazi na taarifa kwamba kuonyesha suala hilo, na kusema machapisho ya baadaye haja ya kutekeleza mifumo ambayo kufanya chanzo cha mistari ya seli kuchunguzwa zaidi uwazi. Chochote mwelekeo wa hatua jamii ya utafiti anaamua juu, ni tatizo kubwa ya kurekebisha <unk> lakini si kitu tunaweza kupuuza. "Karibu nusu karne baada ya wasiwasi wa kwanza kuhusu mistakenly line ya seli, mipango ya kuboresha uthibitisho haja ya kuongezwa na tahadhari ya tayari kuambukizwa fasihi, "waandika waandishi. "Uchambuzi wetu unaonyesha kwamba kazi hiyo ni kubwa na ya haraka". Matokeo ya utafiti huo yameripotiwa katika jarida la PLOS ONE.