Wednesday, October 18, 2017

A lot of exciting medical "discoveries" may be false

Courtesy of a link at Vox's place, I came across this very troubling article.

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.

. . .

Serge Horbach from Radboud University in the Netherlands ... 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."

There's more at the link.

This has enormous implications for medical research.  For example, if the FDA approves a new drug to treat a certain illness, and it turns out that the drug was tested on the wrong cells, its usefulness may be overstated at best - perhaps even overturned entirely.  Furthermore, our understanding of certain diseases, like some types of cancer or tumors, might be completely wrong.  Doctors and scientists may have to revisit some issues from the ground up, repeating all the flawed research using cell lines that are proven to be correct - a massive, perhaps unsupportable expense.

The potential lawsuits stemming from this might be mind-boggling in their complexity.  I suspect medical malpractice lawyers are, right now, setting up urgent conference calls and preparing advertisements.  As far as they're concerned, this might just be bonanza time.



Old NFO said...

Not good, to put it mildly... And how many drugs are out there, based on invalid research???

mark leigh said...

The FDA is no friend of the people, they and the drug companies are more interested in protecting their turf than doing their jobs. While we pay four times the world average for pharmaceuticals because competition is not allowed.

Mad Jack said...

Between that and 'dry lab' testing, it's a wonder that anything works, or that the side effects may be a bit unexpected. Of course, when a medication doesn't seem to be working, your sawbones changes it out for something that's worked in the past.

John Webster said...

It is, no doubt, a problem, mostly for the understanding of the mechanisms of drug action and cellular responses.
However, FDA does not approve a drug based on testing in a single cell line. The proof of medical effect is more extensive and requires clinical trials on humans. Before testing on humans, there is testing on cell lines and animals.

The FDA is absolutely paranoid (in a good sense) when it comes to developing a product based on cell lines. For these cell lines, there is a very extensive testing, proof of identity, chain of custody, and repeated testing during manufacture. For biologics, you have to also demonstrate that there is no cellular DNA left, with sensitivity normally in pg (10^-12 gram) per dose and even then it cannot be in pieces larger than 100 nucleotides. I know that from personal experience developing a vaccine.

The problem of incorrect cell lines is mostly academic research problem since quality controls there are not that strong. There have been significant improvement in the last 15-20 years though.

Quartermaster said...

Some time ago I read about Cancer researchers being bedeviled by the tissue of one woman that had died many years ago, late 50s, or early 60s, IIRC, kept turning up in tissue cultures. I can't remember her name, but the last time I heard her tissue had turned up was in the 80s. It was a real headache.

Tal Hartsfeld said...

Contact the law offices of Amber, Lance and Chaser

John Webster said...

Quartermaster - the cell line is likely HeLa, it was widely used even as recently as 5-10 yr ago. Not sure if it is still used.

The woman's name is Henrietta Lacks.

exfarmkid said...

The lowliest polymer extrusion operation performs quality control on incoming materials - because you don't know who you can trust.

And now we find out that a goodly number of medical research establishments have no incoming quality control.

Verily the mind boggles.

exfarmkid said...

John Webster, I should have read your comment first.

So there is essentially a bifurcation between academia and industry as to operational common sense?

Aesop said...

This is what happens when you take the Argument From Authority Fallacy, and make it a government agency.

In a follow up, new research confirms cancer is hereditary in white laboratory mice.

Anonymous said...

1. PhD students are cheap labor.
2. They are required to produce a product, in order to graduate.
3. They are not trained to think scientifically, in most labs. They do what they are told.
4. Data = Federal Grants, More Data = More Federal Grants
5. Grants pay for students, profs salaries, and overhead (extra money to the university)
6. University admin only care about overhead. More overhead = happy admin.
7. Publish.
8. Repeat.

Scientific research is probably dead in this country.
What is the last medical cure you heard about?
The journals are full of miracles but no cures.

When you go to a scientific seminar and they introduce the speaker.
They say where he is from and how much Federal grant money he/she has.
The don't talk about accomplishments (he invented a cure for x or discovered y).
Then you have an intensely boring hour of meaningless trivialities.

John Webster said...

Yes there is a bifurcation between academia and industry. In my view it boils down to incentives. Scientists, like most people, are fairly reasonable and respond to economic drivers. Both academic and industry scientists are evaluated by output.
For academia the output is publications, which lead to grants.
For industry, the output is a product, which leads to sales.

The standard of proof is much lower for a publication (and it should be) than for a product. For example, when one develops a diagnostic assay in academia, a 1 week's worth of verification is sufficient. What is sufficient is defined by the researcher.
In industry, validation of the assay normally takes 3 month and 2 - 10 people depending on the assay. What is sufficient is defined by Code of Federal Regulations and FDA regulations.

Anonymous (@7:29AM): Scientific research is not dead yet, but is in trouble. And I agree with you comment about introductions of speakers. I try not to laugh out loud every time an "expert in the field" is introduced which spent 20-30-40 years developing something, say a vaccine, and there is still no vaccine or treatment!