Of Mice and Men and Environments

Here is one of the most important issues we face. It effects a wide array of scientific research. But it also has vast implications for our lives and our entire society. It is about the power of environments, including even the slightest of differences.

A mouse’s house may ruin experiments
Environmental factors lie behind many irreproducible rodent experiments.
by Sara Reardon, Nature Journal

It’s no secret that therapies that look promising in mice rarely work in people. But too often, experimental treatments that succeed in one mouse population do not even work in other mice, suggesting that many rodent studies may be flawed from the start.

“We say mice are simpler, but I think the problem is deeper than that,” says Caroline Zeiss, a veterinary neuropathologist at Yale University in New Haven, Connecticut. Researchers rarely report on subtle environmental factors such as their mice’s food, bedding or exposure to light; as a result, conditions vary widely across labs despite an enormous body of research showing that these factors can significantly affect the animals’ biology.

“It’s sort of surprising how many people are surprised by the extent of the variation” between mice that receive different care, says Cory Brayton, a pathologist at Johns Hopkins University in Baltimore, Maryland. At a meeting on mouse models at the Wellcome Genome Campus in Hinxton, UK, on 9–11 February, she and others explored the many biological factors that prevent mouse studies from being reproduced.

I came across this issue in a book by David Shenk, The Genius in All of Us. The book is about genetics and IQ. But he brings up many other issues, such as the difficulties and problems of research.

He discusses a mouse study that demonstrates the power of environmental factors. It is far worse than the above article indicates. Even when all known factors are carefully controlled, the results can still be far different, to the point of being divergent in particular areas.

Below is the passage from Shenk’s book (Kindle Locations 1624-1657). I’ve shared before, but it bears repeating.

To say that there is much we don’t control in our lives is a dramatic understatement, roughly on the order of saying that the universe is a somewhat large place. To begin with, there are many influences we can’t even detect. In 1999 , Oregon neuroscientist John C . Crabbe led a study on how mice reacted to alcohol and cocaine. Crabbe was already an expert on the subject and had run many similar studies, but this one had a special twist: he conducted the exact same study at the same time in three different locations (Portland , Oregon; Albany, New York; and Edmonton, Alberta) in order to gauge the reliability of the results. The researchers went to “extraordinary lengths” to standardize equipment, methods, and lab environment: identical genetic mouse strains, identical food, identical bedding, identical cages, identical light schedule, etc. They did virtually everything they could think of to make the environments of the mice the same in all three labs.

Somehow, though, invisible influences intervened. With the scientists controlling for nearly everything they could control, mice with the exact same genes behaved differently depending on where they lived. And even more surprising: the differences were not consistent, but zigged and zagged across different genetic strains and different locations. In Portland, one strain was especially sensitive to cocaine and one especially insensitive , compared to the same strains in other cities. In Albany, one particular strain— just the one— was especially lazy. In Edmonton , the genetically altered mice tended to be just as active as the wild mice, whereas they were more active than the wild mice in Portland and less active than the wild mice in Albany. It was a major hodgepodge.

There were also predictable results. Crabbe did see many expected similarities across each genetic strain and consistent differences between the strains. These were, after all, perfect genetic copies being raised in painstakingly identical environments. But it was the unpredicted differences that caught everyone’s attention. “Despite our efforts to equate laboratory environments, significant and, in some cases, large effects of site were found for nearly all variables,” Crabbe concluded. “Furthermore, the pattern of strain differences varied substantially among the sites for several tests.”

Wow. This was unforeseen, and it turned heads . Modern science is built on standardization; new experiments change one tiny variable from a previous study or a control group, and any changes in outcome point crisply to cause and effect. The notion of hidden, undetectable differences throws all of that into disarray. How many assumptions of environmental sameness have been built right into conclusions over the decades?

What if there really is no such thing? What if the environment turns out to be less like a snowball that one can examine all around and more like the tip of an iceberg with lurking unknowables? How does that alter the way we think about biological causes and effects?

Something else stood out in Crabbe’s three-city experiment : gene-environment interplay . It wasn’t just that hidden environmental differences had significantly affected the results. It was also clear that these hidden environments had affected different mouse strains in different ways— clear evidence of genes interacting dynamically with environmental forces.

But the biggest lesson of all was how much complexity emerged from such a simple model. These were genetically pure mice in standard lab cages. Only a handful of known variables existed between groups. Imagine the implications for vastly more complex animals— animals with highly developed reasoning capability, complex syntax, elaborate tools, living in vastly intricate and starkly distinct cultures and jumbled genetically into billions of unique identities. You’d have a degree of GxE volatility that would boggle any scientific mind— a world where, from the very first hours of life, young ones experienced so many hidden and unpredictable influences from genes, environment, and culture that there’d be simply no telling what they would turn out like.

Such is our world. Each human child is his/ her own unique genetic entity conceived in his/ her own distinctive environment , immediately spinning out his/ her own unique interactions and behaviors. Who among these children born today will become great pianists, novelists, botanists , or marathoners? Who will live a life of utter mediocrity? Who will struggle to get by? We do not know.

To Control or Be Controlled

Control. A troubling word. To control or be controlled, the battleground of fate and freedom.

Most of us don’t feel like we have much control. We are influenced and manipulated by forces outside of our control. Some of those forces are human and others not.

In science, control is a good thing. Science represents the human desire for control in a world not solely designed for human purposes. The world doesn’t care about the fate of humanity or if we puny walking apes understand the greater cosmos. But science dares to seek what the old gods denied humanity, knowledge and power. Take that, ye old gods!

A scientific control is a simple concept. It is so simple as to be almost boring. Few care about the controls of the study. It is the results that everyone gets excited about. But without effective controls, there are no useful results. For probing minds, the real story of science is in the controls. It is the greatest challenge of science. Without control of conditions, scientists have a hard time making headway.

This touches most sensitively upon human research. Humans can’t be controlled in the way animals can, for ethical reasons and for other reasons as well. Humans as social animals are complex, and so not easily studied. The best animal research puts human research to shame.

I noted this problem recently in relation to race realism. Many people would want to know more than we do know or presently know how to know. We humans want to know. It really pisses us off how ignorant we still are. But we are always certain that it is the other a-hole who is ignorant and clueless. Not us.

Science is ambitious. You have to give it credit for that. We humans love knowledge. What little knowledge we are able to gain we make much ado about. While what we don’t know or can’t know we’d rather ignore.

People like race realists don’t deal well with uncertainty and ambiguity. Most of the data from human research doesn’t lead to clear simple conclusions. The mouse study I mentioned at the link above shows how far science has to go. That study is better controlled than any study has ever been done in the entire history of human research. Yet it proved how much remains uncontrolled.

Even many scientists get duped by this state of affairs. No scientist wants to admit how near futile is the endeavor to pin humans down. A lot of medical research is of low quality, not simply because much of it involves humans, but for other reasons as well. Those scientists who have dedicated their entire lives to the human research fields don’t want to admit how shaky is the ground upon which all human studies are based. So, scientists will sometimes speak confidently about all kinds of things about which they can’t possibly know (e.g., the percentage of genetic vs environmental influence).

Science isn’t well suited for dealing with society-wide problems that includes science itself. The challenge with scientists studying humans is that the scientists are also humans, a specific demographic of humans with attendant biases they rarely can see. The trickiest part is how do scientists control for the problems scientists themselves bring to their own research.

This confusion offers wonderful fodder for those invested in the status qo. It is a fog behind which to hide their intentions and self-interests, conscious and unconscious. This is why race realist research is the perfect match for those not wanting to face uncomfortable issues straight on.

Race realism is based on an entrenched racial social order and on an centuries-old legacy of racism. Race was an idea designed specifically for the purpose of control, that is to say social control of one set of humans by another. It was a product of the Enlightenment when science took hold.

Racism and science have intertwined pasts. The early rhetoric of science was about controlling nature and controlling the human world, the rhetoric often being quite explicit in its violence and visions of power. Nature was anthropomorized often as a woman to be forced into submission, often with sexual connotations of the male virility of the scientific hero. And certain humans were portrayed as animals, from Africans to the Irish.

It is unsurprising that very little scientific research has sought to control for racism itself in studying human differences. Racism is taken as a given, even an inevitability of human nature and human society. Humans are different, the differences often framed as superior and inferior. It is an old quest to prove that the inferior races, ethnicities, and classes are deserving of their oppression and impoverishment.

Anyway, we simply don’t know how to control for racism, even if those in power who give most of the funding wanted to control for it. It has been a slow slog for researchers to begin to grasp how pervasive is racism in our society, the prejudices and biases, the unconscious motivations and the more overt forms found in institutions. Racism is everywhere. Scientists ultimately can’t control for racism because there is no control group that exists outside of racism to compare against.

The mercurial nature of racism allows for plausible deniability. No one has to claim it for it claims our entire society, hidden at the root like a grub.

In promoting a worldview of hyper-individualist self-control, the dominant social order wants to deny its own position of control. Those who have the most power would rather deny any responsibility and hence any blame. Shifting the focus to hypothetical racial genetics is just old bigotry taking new forms.

Control is the name of the game.

The Bouncing Basketball of Race Realism

There is a blog, Occidentalist, I’ve been occasionally commenting at this past month or so. The blogger, Chuck, is a race realist. He is fairly typical in holding a human biodiversity perspective, a semi-deterministic model of genetics. He is somewhat of true believer, but he occasionally expresses some niggling doubts about standard race realist beliefs. It is too bad he doesn’t take his own doubts seriously.

He also doesn’t take seriously some of the most interesting recent data. That is the strangest thing about this type of person. They are intellectual and knowledgeable to an extent, but they are committed to a particular worldview in a quite unscientific way. Science is used merely to express their certainty and so used selectively, instead of as a pathway of curiosity and learning.

I shared an analysis of some recent research that is paradigm-shattering (which I’ve previously posted about in my blog). None of the old theories can explain much of it, partly because it isn’t clear exactly what is in need of explanation, the unknowns being unknown. I highlighted one study in particular:

“Somehow, though, invisible influences intervened. With the scientists controlling for nearly everything they could control, mice with the exact same genes behaved differently depending on where they lived. And even more surprising: the differences were not consistent, but zigged and zagged across different genetic strains and different locations. In Portland, one strain was especially sensitive to cocaine and one especially insensitive , compared to the same strains in other cities. In Albany, one particular strain— just the one— was especially lazy. In Edmonton , the genetically altered mice tended to be just as active as the wild mice, whereas they were more active than the wild mice in Portland and less active than the wild mice in Albany. It was a major hodgepodge”

I made three basic points about this and the other studies:

1) We can no longer honestly claim percentage estimates about genetic vs environmental influence. It isn’t just that past research wasn’t controlling for all confounding factors. Genetic researchers are beginning to realize they don’t even know how to control for all confounding factors because quite a few apparently are unknown at present. We don’t even know how to attempt to disentangle these factors so as to isolate them all. More importantly, we can’t figure out how to separate genetics from the environmental background of this complex web of confounding factors.

2) It has typically been assumed that if researchers controlled for all obvious genetic and environmental factors it should lead to the same basic results. Slight variances are to be expected, but nothing to the extreme differences as found in that mouse study. It demonstrates possibly very minor differences, so small as to be presently undetectable, can lead to major alterations in end results. It demonstrates how powerful environmental conditions can be, even when they are being controlled for with the best methods researchers know how to use.

3) In the uncontrolled conditions of human lives, the environmental influences would be even more powerful. No human study of genetics has come even close to how well controlled this mouse study was done. Even most animal studies aren’t that well controlled. This relates to the issue of the poor quality of much medical research, specifically in terms of race realism.

His response was dismissal, as if it meant very little, just a mild curiosity at best:

“None of this is to say that epigenetics isn’t marginally interesting.”

Ho-hum… *yawn*… nothing interesting here, folks… just move along.

It was like he couldn’t even see it, not really. In his mind, it wasn’t there in some basic sense. He assumed he had seen it all before and so he didn’t need to look at this new data in order to take it seriously, because if he had seen it all before how could new data show him something he hadn’t already seen, right?

It wasn’t just about epigenetics. The study I highlighted brought up other issues about environmental conditions, confounding factors, and scientific controls. It challenges Chuck’s assumptions and conclusions at a fundamental level, and yet he could barely acknowledge what I had shared. He just went on repeating his same basic argument, like he has done a thousand times before.

I’m reminded of a social experiments about inattentional blindness, where focusing one thing makes people unaware of other things. One study had the subjects count the number of times a basketball was dribbled. While they were preoccupied, a person in a gorilla costume came out and began dancing where he was easily seen. When asked about it, most people didn’t remember a dancing gorilla, despite the extreme oddness of such an intrusion. It simply didn’t fit into the parameters of their focus of concern, the bounding basketball. Even if the subject was right about their claim of how many times the basketball bounced, they still missed the most interesting thing that was happening.

Race realists such as Chuck are like this. They share a lot of data that is correct, but the obsession about certain data disallows them from appreciating other data. They know what they know in great detail, and they often love to swamp discussions with a ton of data. The failure is that their knowledge lacks a larger context of understanding. Their opinions can never change, no matter the data, as long as they continue to narrowly focus on that bouncing basketball of race realism.