Can Science Be Trusted?

Can the scientific literature be trusted?

Can the scientific literature be trusted? In "Why Most Published Research Findings Are False," Dr. John P. A. Ioannidis, Professor of Medicine and Director of the Stanford Prevention Research Center at Stanford University School of Medicine, basically says no, it cannot.


Far from a kook or an outsider, Dr. Ioannidis is considered one of the world’s foremost experts on the credibility of medical research. His work has been published in top journals (where it is heavily cited) and his efforts were favorably reviewed in a 2010 Atlantic article called "Lies, Damned Lies, and Medical Science."

What kinds of analysis would allow Ioannidis to reach the conclusions he has reached? First know that a huge amount of work has been done in recent years to develop analytical methods for inferring publication bias by a variety of statistical methods. For example, there are now such accepted methodologies as Begg and Mazumdar’s rank correlation test, Egger’s regression, Orwin’s method, "Rosenthal's file drawer," and the now widely used "trim and fill" method of Duval and Tweedie. (Amazingly, at least four major software packages are available to aid detection of publication bias, for researchers doing meta-analyses. Read about it all here.)

There are many factors to consider when looking for publication bias. Take trial size. People who do meta-analysis of scientific literature have wanted, for some time, to have some reasonable way of compensating for the trial size of studies, because if you give small studies (which often have large variances in results) the same consideration as larger, more statistically significant studies, a handful of small studies with large effects sizes can unduly sway a meta-analysis. Aggravating this is the fact that studies showing a negative result are often rejected by journals or simply withheld from publication by their authors. When data goes unpublished, the literature that surfaces can give a distorted view of reality.

If you do a meta-analysis of a large enough number of studies and plot the effect size on the x-axis and standard error on the y-axis (giving rise to a "funnel graph"; see the graphic above, which is for studies involving Cognitive Behavioral Therapy), you expect to find a more-or-less symmetrical distribution of results around some average effect size, or failing that, at least a roughly equal number of data points on each side of the mean. For large studies, the standard error will tend to be small and data points will be high on the graph (because standard error, as usually plotted, goes from high values at the bottom of the y-axis to low numbers at the top; see illustration above). For small studies, the standard error tends (of course) to be large.

What meta-analysis experts have found is that quite often, the higher a study's "standard error" (which is to say, the smaller the study), the more likely the study in question is to report a strongly positive result. So instead of a funnel graph with roughly equal data points on each side (which is what you expect statistically), you get a graph that's visibly lopsided to the right, indicating that publication bias (from non-publication of "bad results") is likely. Otherwise how do you account for the points mysteriously missing from the left side of the graph, in a graph that should (by statistical odds) have roughly equal numbers of points on both sides?

Small studies aren't always the culprits. Some meta-analyses, in some research fields, show funnel-graph asymmetry at the top of the funnel as well as the bottom (in other words, across all study sizes). Data points are missing on the left side of the funnel. Which is hard to account for in a statistical distribution that should show points on both sides, in roughly equal amounts. The only realistic possibility is publication bias.

Then there's the problem of spin-doctoring in studies that are published. This takes various forms, from changing the chosen outcomes-measure after all the data are in (to make the data look better, via a different criterion-of-success; one of many criticisms of the $35 million STAR-D study of depression treatments), "cherry-picking" trials or data points (which should probably be called pea-picking in honor of Gregor Mendel, who pioneered the technique), or the more insidious phenomenon of HARKing, Hypothesizing After the Results are Known, which often occurs with selective citation of concordant studies.

So is Dr. Ioannidis right? Are most published research findings false? I don't think we have to go that far. I think it's reasonable to say that most papers are probably showing real data, obtained legitimately. But we also have to admit there is a substantial phantom literature of unpublished data out there. (This is particularly true in pharmaceutical research, where it's been shown that unflattering studies simply don't get published.) And far too many study authors practice HARKing, cherry-picking, and post hoc outcome-measure swapping.

All of which is to say, it's important to read scientific literature with a skeptical (or at least critical) eye. Fail to do that and you're bound to be led astray, sooner or later.

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Homo sapiens have been on earth for 200,000 years — give or take a few ten-thousand-year stretches. Much of that time is shrouded in the fog of prehistory. What we do know has been pieced together by deciphering the fossil record through the principles of evolutionary theory. Yet new discoveries contain the potential to refashion that knowledge and lead scientists to new, previously unconsidered conclusions.

A set of 8-million-year-old teeth may have done just that. Researchers recently inspected the upper and lower jaw of an ancient European ape. Their conclusions suggest that humanity's forebearers may have arisen in Europe before migrating to Africa, potentially upending a scientific consensus that has stood since Darwin's day.

Rethinking humanity's origin story

The frontispiece of Thomas Huxley's Evidence as to Man's Place in Nature (1863) sketched by natural history artist Benjamin Waterhouse Hawkins. (Photo: Wikimedia Commons)

As reported in New Scientist, the 8- to 9-million-year-old hominin jaw bones were found at Nikiti, northern Greece, in the '90s. Scientists originally pegged the chompers as belonging to a member of Ouranopithecus, an genus of extinct Eurasian ape.

David Begun, an anthropologist at the University of Toronto, and his team recently reexamined the jaw bones. They argue that the original identification was incorrect. Based on the fossil's hominin-like canines and premolar roots, they identify that the ape belongs to a previously unknown proto-hominin.

The researchers hypothesize that these proto-hominins were the evolutionary ancestors of another European great ape Graecopithecus, which the same team tentatively identified as an early hominin in 2017. Graecopithecus lived in south-east Europe 7.2 million years ago. If the premise is correct, these hominins would have migrated to Africa 7 million years ago, after undergoing much of their evolutionary development in Europe.

Begun points out that south-east Europe was once occupied by the ancestors of animals like the giraffe and rhino, too. "It's widely agreed that this was the found fauna of most of what we see in Africa today," he told New Scientists. "If the antelopes and giraffes could get into Africa 7 million years ago, why not the apes?"

He recently outlined this idea at a conference of the American Association of Physical Anthropologists.

It's worth noting that Begun has made similar hypotheses before. Writing for the Journal of Human Evolution in 2002, Begun and Elmar Heizmann of the Natural history Museum of Stuttgart discussed a great ape fossil found in Germany that they argued could be the ancestor (broadly speaking) of all living great apes and humans.

"Found in Germany 20 years ago, this specimen is about 16.5 million years old, some 1.5 million years older than similar species from East Africa," Begun said in a statement then. "It suggests that the great ape and human lineage first appeared in Eurasia and not Africa."

Migrating out of Africa

In the Descent of Man, Charles Darwin proposed that hominins descended out of Africa. Considering the relatively few fossils available at the time, it is a testament to Darwin's astuteness that his hypothesis remains the leading theory.

Since Darwin's time, we have unearthed many more fossils and discovered new evidence in genetics. As such, our African-origin story has undergone many updates and revisions since 1871. Today, it has splintered into two theories: the "out of Africa" theory and the "multi-regional" theory.

The out of Africa theory suggests that the cradle of all humanity was Africa. Homo sapiens evolved exclusively and recently on that continent. At some point in prehistory, our ancestors migrated from Africa to Eurasia and replaced other subspecies of the genus Homo, such as Neanderthals. This is the dominant theory among scientists, and current evidence seems to support it best — though, say that in some circles and be prepared for a late-night debate that goes well past last call.

The multi-regional theory suggests that humans evolved in parallel across various regions. According to this model, the hominins Homo erectus left Africa to settle across Eurasia and (maybe) Australia. These disparate populations eventually evolved into modern humans thanks to a helping dollop of gene flow.

Of course, there are the broad strokes of very nuanced models, and we're leaving a lot of discussion out. There is, for example, a debate as to whether African Homo erectus fossils should be considered alongside Asian ones or should be labeled as a different subspecies, Homo ergaster.

Proponents of the out-of-Africa model aren't sure whether non-African humans descended from a single migration out of Africa or at least two major waves of migration followed by a lot of interbreeding.

Did we head east or south of Eden?

Not all anthropologists agree with Begun and his team's conclusions. As noted by New Scientist, it is possible that the Nikiti ape is not related to hominins at all. It may have evolved similar features independently, developing teeth to eat similar foods or chew in a similar manner as early hominins.

Ultimately, Nikiti ape alone doesn't offer enough evidence to upend the out of Africa model, which is supported by a more robust fossil record and DNA evidence. But additional evidence may be uncovered to lend further credence to Begun's hypothesis or lead us to yet unconsidered ideas about humanity's evolution.