How mixed-up cell lines are contaminating science
And why human anatomy has such bizarre names
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Thousands of scientific papers contain a fundamental error, according to a new study published in the online journal PLOS One.
In more than 33,000 publications, scientists unknowingly used the wrong types of cells for their experiments, and the mistakes remain uncorrected, contaminating the scientific literature.
It matters, the researchers say, because if scientists are using the wrong cells, their observations and conclusions might be inaccurate.
"We're not saying those 33,000 articles are wrong," said Willem Halffman from Radboud University in Nijmegen, the Netherlands.
"But among those 33,000 there are definitely some with wrong conclusions."
It's a dirty secret in science, one that many researchers don't like to talk about. The problem was first identified in the 1960s by early whistleblowers.
"They were all fiercely attacked. And we're a little nervous too."
Halffman said his team has found that about two dozen papers every week are still being published using the damaged cell lines.
"The problem is not going away."
There's a database that lists 488 known cases of misidentification, with examples of mosquito cells that are actually moth cells, and cells labelled as "horse" that turned out to be pig's cells. And sometimes the cell lines are classified as human, but they're actually mouse cells or monkey cells.
Part of the problem is that scientists swap cells between laboratories.
"Researchers keep exchanging cells among themselves and keep having their own stack of cells in their laboratories, which they've had for years in the freezer," he said "They're everywhere."
Some scientific journals have started demanding that scientists prove their cell types using a genetic test when they're submitting new research for publication.
But there is no requirement for the affected research to be red-flagged to alert other scientists about the mistakes.
"We should just add a little label, nothing too drastic, we don't want to damage anybody's reputation or claim any kind of major mistake, but all we're saying is those papers should get an expression of concern," Halffman said.
"That's one of the fantastic things about science is that it can make mistakes but it cleans them up. Why does it take decades for people to address this problem?"
Much of the contamination is caused by a famous cell line known as "HeLa," used by scientists all over the world. The cells were first harvested from Henrietta Lacks who died from cervical cancer in 1951.
The HeLa cells are so aggressive that they pollute other cell lines, creating situations where scientists think they're experimenting on lung cancer cells but are unknowingly working with the HeLa cervical cancer cells.
The story of how Lacks's uniquely aggressive cancer cells transformed biomedical research inspired a bestselling book and a recent movie starring Oprah Winfrey.
'A new alphabet' for cancer?
An international study led by researchers from Toronto's Sick Kids Hospital suggests a new way to classify different types of cancers, with direct implications for how they might be treated one day.
Right now, we define types of cancer by where they originate in the body — lung cancer, brain cancer, breast cancer, skin cancer, colon cancer — so treatment often focuses on what is known about cancer that occurs in those tissues.
"If you have a tumour of breast cancer, you get different treatment than prostate or brain [cancer], because that's the way we are used to doing it," said Dr. Uri Tabori, one of the study's co-principal investigators and a staff physician in hematology/oncology at Sick Kids Hospital.
The new research, published online in the journal Cell this week, used genetic sequencing to analyze more than 80,000 tumours from adults and children in different countries around the world, looking for patterns in the number and type of mutations that appeared in the tumours, regardless of their origin.
Tabori compared the finding to discovering a new alphabet.
"Think of it as a book that we didn't know how to read because the language was not known. Now we have a new knowledge about the language so we actually tell stories that we couldn't tell before," he said.
Those stories yield vital information, including whether a cancer is hereditary or what kinds of "mutagens" — such as UV radiation or smoking — caused the cellular mutations that can lead to cancer. Another critical piece of information is whether a cancer will be resistant to a specific type of drug.
"It's a very different way to look at cancer," Tabori said.
And, he said, the implications for treatment are enormous.
For example, if a tumour has a genetic signature indicating it is hereditary, family members need to be contacted to get genetic counselling and start prevention or early intervention measures, Tabori said. If a patient has a tumour that's been categorized as resistant to a type of chemotherapy, the planned treatment approach needs to be changed.
The researchers in this study were only able to classify hypermutant tumours, which are found in 17 per cent of adult cancers and five to 10 per cent of pediatric cancers.
But Tabori believes the classifications they found actually apply to many more human cancers — including those that don't have as many mutations.
Current treatments based on where the cancer originated should continue, Tabori emphasized, but the new classification offers another option if a tumour isn't responding. If that's the case, he said, doctors should consider taking a biopsy and sending it for genetic sequencing analysis to see if another treatment might be a better fit.
New immunotherapy drug approved, but not in Canada
Headlines this week announcing the approval of a new immunotherapy treatment might be raising expectations of cancer patients everywhere. But unfortunately for most patients right now, nothing will change.
The new treatment by Gilead, called Yescarta, is the second CAR-T cell therapy to become commercially available.
Both are only available in the U.S. and only for a subset of patients — adults with a form of lymphoma and children with acute lymphoblastic leukemia (ALL) — who don't respond to the standard chemotherapy regimes.
But it does signal an important direction in cancer therapy overall — the first of what scientists predict will be a new toolkit of genetic, viral and immunotherapy options.
"It's heralding in a new wave of therapeutics which are biologically based. They're designed to be given only once or twice, and they essentially cure the patient if they work well," said John Bell, who is working on a Canadian version of CAR-T (an acronym for "chimeric antigen receptor T-cell therapy.)
"It's different than the standard of care, which generally is you get treated with chemotherapy, and it's an ongoing kind of treatment," said Bell.
"This is really designed therapy to try to cure the patient with a limited number of treatments and not have the patient be on drugs for the rest of their life."
The CAR-T cell approach uses the body's immune system to attack cancer by genetically manipulating a patient's white blood cells and then reinjecting them. The procedure is risky, and some patients have died from the devastating immune response.
"This one can be pretty challenging," Bell said. "We're trying to find ways to make it better. But the upside is that if it works well you could be cured of your disease.
The new therapy is also expensive, priced at almost $400,000 US for the treatment alone. After adding in all the medical costs the total price has been estimated to exceed $1 million per patient.
In Canada, scientists are hoping to start CAR-T trials within the next year or so.
"We're certainly pushing it forward as fast as we can so people in Canada will have a chance to access the therapy," said Bell, who is scientific director of BioCanRX, a research network based at the Ottawa Hospital that is funding some Canadian CAR-T projects.
Bell estimates that there at least a dozen research teams are working on CAR-T cell therapy in Canada.
Journal apologizes for publishing Canadian vaccine-autism study
There's more reaction this week to a controversial paper by a Canadian research team linking an ingredient in vaccines to autism in mice.
Researchers from the University of British Columbia decided to withdraw their paper last Friday after questions were raised by Retraction Watch, a scientific watchdog blog.
As the CBC's Rhianna Schmunk reported, co-author Dr. Chris Shaw said he realized some of the figures in the study appeared to be altered before publication. In an interview, he said he doesn't know why or how that may have happened.
Shaw claimed he can't check the original data because it's inaccessible in China with a former student who worked on the paper. UBC has a policy requiring researchers to retain original data on file at the university for at least five years after it is collected.
UBC's vice-president of research Gail Murphy said she can't comment on specific cases, but that the university does investigate allegations like this.
Shaw, his co-author and the editor-in-chief of the Journal of Inorganic Biochemistry have all agreed to the retraction.
A statement from Elsevier, one of the world's largest scientific publishing companies, said they agreed to retract due to "evidence of incorrect data."
The data of gel images in at least two figures "are incorrectly presented," according to the notice.
Elsevier also apologized to readers of the journal for the fact that "this was not detected" before the paper was published.
Why did they call it that?
Have you ever fallen on your backside and hurt your coccyx? Did you know your atrium is full of blood? (Don't worry — it's supposed to be. Also, you have two of them. The plural is atria.)
How parts of our body came to get their names is the subject of The Secret Language of Anatomy, a new book published by three medical experts at the University of Cambridge in the U.K.
The idea was born out of an effort to help medical students trying to grasp the overwhelming number of anatomical terms. The university's clinical anatomist, Dr. Cecilia Brassett, thought a guide explaining the origins of the words, which are largely derived from Latin and Greek, might be useful, since fewer students take courses in those languages than in past decades.
"What happened was that when they started medical school, they're finding that they have to learn a lot of new terms," Brassett told CBC News. "And they're struggling already with the new concepts they've got to take in, but then even the language they're finding difficult."
The book breaks down the origin of anatomical words into categories, including architecture and animals, and provides illustrations.
Atrium, for example, is Latin for the main room of a home, where visitors would be received. In the human body, the atrium is a main chamber of the heart that receives blood.
As for the coccyx? It's more commonly known as the tailbone, but the name is ancient Greek for cuckoo, because the physician that named the bone thought it looked like the bird's bill.
Here are five anatomical terms: what they mean and where their names come from
Fibula: Means "clasp." The fibula is a long bone in the leg, and the shape it makes with another leg bone — the tibia — resembles a clasp.
Hippocampus: A part of the brain involved in memory. The name means "seahorse" because early anatomists thought that's what the shape of the hippocampus resembled.
Pterygoid: Means "wing or feather shaped." The pterygoid is the attachment point for the pterygoid muscles in the jaw, which are shaped like a feathered wing.
Philtrum: Means "love potion." It's the vertical groove on the upper lip below the nose. The name likely came from the romantic connotation of the mouth and lips.
Trochlea: Means "pulley." The trochlea is a deep groove in the humerus bone in the arm, which looks like a pulley and helps form the elbow joint.
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