“Rapid advances in technology have lowered the cost of sequencing an individual’s genome from the several billion dollars that it cost a decade ago to just a few thousand dollars today and have correspondingly greatly expanded the use of genomic information in medicine. Because of the lack of evidence available for assessing variants, evaluation bodies have made only a few recommendations for the use of genetic tests in health care. […] However, due to insufficient evidence, it has been challenging to recommend the use of a genetic test.”—Assessing Genomic Sequencing Information for Health Care Decision Making: Workshop Summary
“The emotion system in animals may thus have evolved by natural selection because it simultaneously enhances three important functions, the behavioural robustness of individuals, the evolvability of gene pools and the rate of evolutionary innovation at several architectural levels.”—The emotion system promotes diversity and evolvability
“In Arabic, as in many languages, the future is “ahead” and the past is “behind.” Yet in the research reported here, we showed that Arabic speakers tend to conceptualize the future as behind and the past as ahead of them, despite using spoken metaphors that suggest the opposite.”—When You Think About It, Your Past Is in Front of You
“We examined the relationship between self-reported sleep duration and false memories and the effect of 24 hr of total sleep deprivation on susceptibility to false memories. We found that under certain conditions, sleep deprivation can increase the risk of developing false memories.”—Sleep Deprivation and False Memories
“These results are similar to those reported previously for human infants, and predictive looking did not differ among the three species of great apes. Thus, great apes make on-line goal-based predictions about the actions of other individuals; this skill is not unique to humans but is shared more widely among primates.”—Great Apes Generate Goal-Based Action Predictions
“Contrary to the contentions of its proponents, no explicit, irreversible ecological thresholds allow distinctions between ‘novel ecosystems’ and ‘hybrid’ or ‘historic’ ones. Further, there is no clear message as to what practitioners should do with a ‘novel ecosystem’. In addition, ecosystems of many types are being conserved, or restored to trajectories within historical ranges of variation, despite severe degradation that could have led to their being pronounced ‘novel’.”—A critique of the ‘novel ecosystem’ concept: Trends in Ecology & Evolution
“What was most striking, though, was finding that Thoreau’s most Transcendentalist (or Romantic) moments, the ones proclaiming that the human mind and the natural world are braided in continuous harmony, are inspired by the very opposite of wilderness. These pronouncements, which made Thoreau such an apt saint for later environmentalists, come in Walden as responses to places where the world is ruptured, broken, split open by human powers. Thoreau’s Romanticism, in a way, was always Anthropocene.”—Jedediah Purdy: In the Shit With Thoreau: A Walden for the Anthropocene
People love to do hard work together and to feel that the work is real; that is to say primary, productive, needed. Knowing and enjoying the skills of our hands and our well-made tools is fundamental. It is a tragic dilemma that much of the best work men do together is no longer quite right. The fine information on the techniques of hand-whaling and all the steps of the flensing and rendering described in Moby Dick must now, we know, be measured against the terrible specter of the extinction of whales. Even the farmer or the carpenter is uneasy: pesticides, herbicides, creepy subsidies, welfare water, cheap materials, ugly subdivisions, walls that won’t last. Who can be proud? And our conservationist-environmentalist-moral outrage is often (in its frustration) aimed at the logger or the rancher, when the real power is in the hands of people who make unimaginably larger sums of money, people im- peccably groomed, excellently educated at the best universities— male and female alike—eating fine foods and reading classy litera- ture, while orchestrating the investment and legislation that ruin the world. As I grew into young manhood in the Pacific Northwest, advised by a cedar tree, learning the history of my region, practicing mountaineering, studying the native cultures, and inventing the little rituals that kept my spirit sane, I was often supporting myself by the woodcutting skills I learned on the Depression stump-farm.
Coghlan came to Maine from upstate New York, where it wasn’t uncommon for biologists to poison entire streams in hopes of exterminating lamprey. At Sedgeunkedunk, he has found them to be, unexpectedly, a keystone species: to build spawning nests they thrash rocks into place, in the process dislodging fish eggs and invertebrates for other creatures to eat, and loosening gravel for salmon to build their nests. When lamprey die, their decomposing bodies provide a burst of food for insects and microorganisms at the food chain’s base.
Downstream from the lampreys’ carcasses, Coghlan has discovered, biological productivity explodes. That productivity may extend onto land: alewives and lamprey fattened at sea may once have constituted a biomass comparable to the northwest Pacific salmon runs, which are thought to have fertilized the region’s great forests.
Something that didn’t fit in that section: all that thrashing also creates habitat. As Coghlan and colleagues recently wrote, “spawning sea lampreys are ecosystem engineers.” People hate them for killing fish — but in a sense, they bring those fish to life in the first place.
“We report a survey of climate-blog visitors to identify the variables underlying acceptance and rejection of climate science. Our findings parallel those of previous work and show that endorsement of free-market economics predicted rejection of climate science. Endorsement of free markets also predicted the rejection of other established scientific findings, such as the facts that HIV causes AIDS and that smoking causes lung cancer. We additionally show that, above and beyond endorsement of free markets, endorsement of a cluster of conspiracy theories (e.g., that the Federal Bureau of Investigation killed Martin Luther King, Jr.) predicted rejection of climate science as well as other scientific findings. Our results provide empirical support for previous suggestions that conspiratorial thinking contributes to the rejection of science.”—NASA Faked the Moon Landing—Therefore, (Climate) Science Is a Hoax
“I’ve been raising chickens for eight years, and since I let them roam across our five acres of pasture, forest and brush, I get to observe them all the time. Even though they have tiny brains, there is a lot more going on inside those brains than people give credit. When one of the hens laid and hatched a clutch of eggs under a porch, she changed my understanding of chickens as I watched her raise her chicks. I hesitate to use words like loving and caring, but the way she looked after those chicks and the way they responded to her is difficult to describe without using words like love and caring.
So now I replenish the flock by letting mothers hatch and raise chicks. After watching how much richer chicks’ lives are when they have a mother, I want all the chickens I have to have the experience being raised by a mother. It’s odd using terms like emotional stability and self confidence with animals like chickens, but you end up resorting to those terms when you compare mother-raised chickens versus chickens which grow up without a mother. Since humans and chickens have a common ancestor somewhere back in time, it’s not surprising that there are some ancient behavioral traits that are shared by both. And jumping into sexual politics, I sometimes joke that watching rooster behavior has given me an understanding of straight men and the way they compete with each other. They just can’t help it. It’s as hard wired in their brains as it is in roosters.”—A comment on Dogs and Cats Are Blurring the Lines Between Pets and People
“Officials at England’s Gloucestershire Airport had been using recordings of avian distress calls to frighten birds away from landing strips, with only limited success. However, when they switched to recordings of rock star Tina Turner’s voice, there was an immediate and dramatic effect. “What the birds really hate is Tina Turner,” said Airport Chief Fire Officer Ron Johnson.”—The Loss of Natural Soundscapes
“How do geese know when to fly to the sun?
Who tells them the seasons?
How do we, humans know when it is time to move on?
As with the migrant birds, so surely with us, there is a voice within if only we would listen to it, that tells us certainly when to go forth into the unknown.”—Elisabeth Kubler-Ross, from Light Pollution Kills Birds in the Environment
Inspired by the movie “Her,” I recently wrote an article entitled, “Can a Computer Fall in Love if It Doesn’t Have a Body?” The movie’s premise is that an artificial intelligence can feel love; but research on embodied cognition suggests this might not be such a straightforward affair. Love is not abstract; it’s very much shaped by body and biology, and computers are largely disembodied.
Q: Could a disembodied human brain could understand physical love?
EY: With respect to the first question, I would guess that a body isn’t necessary to achieve something like the kinds of experiences that embodied brains experience. The research line that seems related to this is the stuff on mirror neurons (e.g., Rizzolatti & colleagues — you’re probably familiar with this) — the main related finding is that when one monkey sees a second monkey reach towards, e.g., some food, neurons fire in the first monkey’s motor cortex that would control the kind of reaching motion that he is watching. The critical question, which this research doesn’t address, is whether a monkey that had never reached for anything (e.g., a paralyzed monkey) would also activate these same motor cortex neurons. (Sian Bielock’s work on professional athletes and fans may be semi-related too.) And then even if those same neurons *were* activated in the paralyzed monkey, what would that monkey be experiencing? That is, we know that the brain is plastic enough that congenitally blind people activate visual cortex when reading braille — and we wouldn’t interpret this as them experiencing what a sighted person experiences when activating the same parts of visual cortex.
Q: Could an artificial brain love?
EY: Something that seems related is the behaviorist perspective on psychology — if a computer acts exactly in a way that appears to be love, how is that different than love? We have the intuition that it is, but what really makes it different? This is also indirectly related to the Turing test — if a computer could completely convince its correspondent into thinking that it’s human (and in this example, that it is in love) would it be? Would the programming necessary to create that “illusion” constitute love? How can we know that our partner loves us other than through their behavior?
I thought my friend Paul Allopenna [a cognitive scientist at Brown University] would find this interesting, so I passed along your question and he had this interesting comment:
"So, what I would want to know is, could an embodied brain really be "embodied" if it didn’t need to survive? That is, how much of a functional role to our biological (particularly metabolic) predicates play in motivating/organizing/ and executing our behaviors (including our emotive behaviors)?"
So as I understand it, Paul’s question essentially comes down to: if, despite having a body, a brain didn’t need that body to provide it with anything (e.g,. fuel) to survive, what kind of behaviors would it instruct that body to perform? That is, would it demonstrate love (or anything else we normally demonstrate)?
“Although the primary function of mating is gamete transfer, male ejaculates contain numerous other substances that are produced by accessory glands and transferred to females during mating. Studies with several model organisms have shown that these substances can exert diverse behavioural and physiological effects on females, including altered longevity and reproductive output, yet a comprehensive synthesis across taxa is lacking.”—The influence of male ejaculate qua… [Biol Rev Camb Philos Soc. 2011] - PubMed - NCBI
“We conclude that individual signatures seem to be advantageous in terms of managing group movements. Giant otters might additionally benefit from discriminating individuals within their social group, where kin recognition is insufficient to identify equally related individuals that cooperate in hunting and rearing of the young.”—Vocal individuality in cohesion calls of giant otters, Pteronura brasiliensis
“Such a massive reorganization of atmospheric convection, which we define as an extreme El Niño, severely disrupted global weather patterns, affecting ecosystems4, 5, agriculture6, tropical cyclones, drought, bushfires, floods and other extreme weather events worldwide. Potential future changes in such extreme El Niño occurrences could have profound socio-economic consequences. Here we present climate modelling evidence for a doubling in the occurrences in the future in response to greenhouse warming”—Increasing frequency of extreme El Nino events due to greenhouse warming : Nature Climate Change : Nature Publishing Group
“Many species are capable of using observational learning to copy another’s goal-directed action. Rats can learn to run a maze by observing another rat (Zentall and Levine, 1972). Some birds socially learn each other’s songs (Zentall, 2004). Guppy fish can socially learn foraging innovations (Laland and Reader, 1999). Wild macaques learn to wash sand off sweet potatoes by watching other macaques (Kawamura, 1959). Both capuchin monkeys and chimpanzees learn to use tools by watching conspecifics (Fragaszy and Visalberghi, 1989; Inoue-Nakamura and Matsuzawa, 1997)”—What can other animals tell us about human social cognition? An evolutionary perspective on reflective and reflexive processing
“Directly across the road, a mammoth boar rises when he sees us coming. He lumbers over, either to say hello or to shoo us away from his harem; in a hutch, three sows are sleeping soundly. “He’s a pretty busy guy,” says Haney proudly, stepping over the wire to rub his back. The boar, its tan bristles caked in dirt, shuts its eyes and submits. He’ll likely live to a ripe old age, and the sows he mates with will be put down humanely and butchered for sausage at Blue Hill at Stone Barns. The farm’s pork will cost more than the pork at Key Food, but that isn’t the worst thing in the world. Maybe we’ll eat less of it and cook it at home, instead of gorging our kids on fast food. Like the livestock we raise, we’ve grown fat and sick, dependent on a bitches’ brew of drugs. We’ve got a choice to make, and it only means our lives: We can treat our animals better and heal our bodies in the bargain, or become the last of the planet’s finite resources gone hopelessly to seed.”—Animal Cruelty Is the Price We Pay for Cheap Meat | Rolling Stone
Earlier this fall, the (most excellent editor Eliza Strickland at IEEE Spectrum) invited me to write an article about the BRAIN Initiative. Initially I had many reservations: I knew about the project mostly through news articles written when its original, nebulously-defined-but-mostly-about-neuron-recording incarnation was announced in April, and what I’d read had irritated me. The proposal seemed much too narrow (what about data storage? interpretation? and everything that’s not a neuron?) and the grand-challenge-of-our-time rhetoric swollen with hype.
I also had, and still have, reservations about the importance attached to neuroscientific explanations, particularly of complex human behaviors. What’s so condescendingly referred to as “folk psychology” might better be called “knowledge produced through other social processes than the institution of science,” and includes all those endeavors encompassed by literature, history, art, the social sciences and collectively distilled experience. To illustrate this, I like to use the example of love: What if we had a billion-dollar love project, intended to better understand and promote love? Neuroscience would have just one of many seats at the table, and it probably wouldn’t be at the table’s head.
That said, after poring through various NSF and NIH documents associated with BRAIN, and speaking to roughly a dozen neuroscientists, I feel much better about the project. I’m impressed by its scope, fascinated by the questions seeks to answer and those it might generate. It is, in a word, exciting. I also feel that the people involved are more thoughtful and modest than I’d expected. And of all the scientists, I was profoundly impressed by Cori Bargmann, the Rockefeller University neuroscientist who oversaw the NIH’s interim BRAIN report. Below is the interview we conducted by email.
Q: Something I wanted to ask first, in case the other questions turn the discussion dry, is: What scientific questions are the most exciting to you? What it is that fascinates you, that keeps you thinking late at night … and do you hope the BRAIN Initiative will answer these questions?
Bargmann: The human brain is a miracle. It gives rise to infinitely many thoughts, emotions, memories, actions. How can one biological organ, a collection of cells, do all that? No matter how long you’ve been a neuroscientist, it is still an amazing that this complexity emerges from such mundane biological components. That’s what motivates me. Yes, I think the answer will come from understanding brain circuits and dynamics, and electrical and chemical signaling, and theory. (I have a mental picture of how this works in the tiny worm, but it’s not proved yet; in larger brains, even the mental picture is elusive.)
Q: The Initiative has evolved a great deal since its conception (and, as an aside, it’s been tremendously heartening to see criticisms articulated and incorporated into the interim NIH report; that sort of thoughtful, constructive, perspective-harnessing process is really science at its best, and makes this bystander proud.)
Bargmann: Thank you! We were very fortunate because many people were willing to give us advice. On very short notice, flying around the country. It’s also been heartening that several other independent groups have arrived at overlapping ideas (NSF, the Allen Brain Institute, the Kavli think tank, others). It gives us more confidence that we’re on the right track.
Q: Do you expect it to continue to evolve over the next year, and in what ways — will we continue to see substantive additions, such as the attention newly paid to glia, or are the next stages more about deciding how to apportion emphasis among the research priorities?
Bargmann: This is an interim report. We hope this is the right direction, but we want feedback. We may realize that we’ve missed something important, and add an area. We will definitely try to sharpen and focus the ideas.
This will be both informal and formal. Formally, we will meet with “partners” and “stakeholders” (Washington-speak). For example, in theory we are just an advisory group to NIH, but there are many groups involved in the BRAIN Initiative. All of these groups should talk about what everyone will be doing, and who else should be involved. This will happen soon — the people who are already in the loop are NSF, DARPA, Allen, Kavli, HHMI. In the longer tern, I’m excited to say that several tech companies are expressing interest in being part of the BRAIN Initiative! Microsoft, Google, Intel would have a lot to provide. And then there is broader input from neuroscientists (eg SFN), clinical and translational scientists (eg AAN), and patient advocacy groups.
Q: Timeline-wise, assuming the shutdown ends tomorrow, what do you expect this year from the agencies and foundations? Do you think we’ll see priorities set and grants reviewed by year’s end?
Bargmann: Oh, this is so upsetting. We worked hard on the interim report, with much advice, all pro bono, from leaders across the field. The interim report went in, it was accepted with enthusiasm, and now it’s in the hands of the government. NIH was poised to formulate and issue requests for proposals. Scientists across the country were getting ready to submit grants and review them (which needs to get set up by NIH). And if that all went well, we could have been starting the science in months! And then the government shut down, and now the start of the BRAIN project in 2014 is definitely at risk. No external force could do as much damage to research in the US as this is doing — can you imagine how we’d react if a foreign government sabotaged our scientific enterprise for this kind of time?
Q: Among the priorities, are there some that strike you as being preconditionally necessary — e.g., we can’t start collecting large-scale data without the platform for sharing it? Is there any concern that early priorities may preclude others — e.g., if the push is to develop technologies for recording electrical activity in brain cells, it’ll divert attention from the potential importance of chemical activity?
Bargmann: Science is always creative chaos — you can’t wait for things to be perfect to get started! Parallel work has the best history of success. The nature of the data determines the best design for data platforms, for example. Some areas will have great new ideas and a spurt of growth, other may take a while to reach the next level. This is how bottom-up science works best — set out the problems, and then find the people who have the best solutions.
Q: In the report, you point out the difficulty of measuring internal cognitive processes and mental states in animals, and the importance of doing so in a careful way. This difficulty has certainly received much attention over the last few years, particularly in regards to the limitations of mouse models for complex psychological states. Are those concerns something that the Initiative can address directly — e.g., by making more-informative use of animal models possible, or even reducing our reliance upon them — or are the concerns simply something to keep in mind?
Bargmann: Not sure I have a great answer to this. We’re getting pretty good at interpreting certain complex processes in the mouse brain, such as representation of space in the hippocampus. We can even tell based on brain activity when a mouse is “thinking” about going right versus going left in a maze, which is pretty cool. However, at this point we can’t say with confidence that we can recognize a complex psychological state like depression, let alone schizophrenia in a mouse. What we can say is that we recognize patterns of brain activity and behavior that are similar to those we might observe in a depressed person, and that respond to some of the same medications. I just want to point out that these states can also be challenging to identify in humans! We need to be appropriately humble at every level.
Q: A concern I’ve heard raised by researchers who are supportive of the BRAIN Initiative is the gap between what we now understand and the project’s ambitions. The C. elegans example is the usual one — “We can record every neuron in a C. elegans brain, and still can’t explain _____.”
Bargmann: Well, we can’t do that in a worm yet, or at least no one has yet done so. We have fragments, one neuron at a time. We need a more global picture of their relationships. That’s exactly why we need a multi-pronged approach: structural maps, activity maps, the ability to record and manipulate in the context of behavior, and theory
Q: The C. elegans reservation isn’t offered as a reason not to pursue the Initiative, but a restraint on what to expect from it in the near future (and perhaps not without more money than is presently being discussed.) What are your thoughts on this? How does one walk the line between overpromising in order to secure funding, or being so restrained in expectation as to discourage it?
Bargmann: I think that in ten years of the Brain Initiative, we could have a fundamentally different picture of how information flows through the brain in space and time, and what that means. I do not think we should promise that cures will come tumbling out of this initiative in the short term. I think we should promise that we will shed light on many core properties of the normal, active brain. And that with that illumination, we can turn to translational researchers, physicians, engineers, biotech, and big pharma, and begin a new era of translation into the brain disorders that cast a shadow on all of our lives — because even if you aren’t affected, your grandmother or nephew or best friend may be suffering from Alzheimer’s, or autism, or post-traumatic stress disorder.
Q: Do you get a sense of whether the NIH, NSF and DARPA funds will be new, or coming from existing budgets? To what extent, if any, are they guaranteed beyond 2014?
Bargmann: Not really — but I think everyone knows that a grand challenge takes more than one year! Ten years seems more like it.
Q: It’s certainly very early, but it seems some themes are emerging: a general unity of purpose/sense of what’s necessary between the NIH and NSF, with the NIH leaning towards the “wet” side of things — working with organisms, collecting the data, making the connections to disease, behavior and cognition — and the NSF leaning towards the “dry”: developing the recording technologies, data-analysis techniques, data-sharing platforms, and so on. Does that seem like a fair assessment to you? Do you have a sense of what DARPA and the private foundations will emphasize?
Bargmann: I like this formulation but it’s not my place to tell anyone what to do, especially not outside the NIH! My sense is that DARPA has a major commitment to injured veterans, and therefore has a big push on brain-machine interfaces and brain-computer interfaces, for example. Private foundations have their own interests, some overlapping closely with the Brain Initiative’s goals. HHMI/Janelia is making genetic reagents for the fruit fly, and developing sophisticated new microscopes. Allen is mapping long-range physical connections throughout the brain with their new tracing methods.
Q: In the interview with Eliza you referred to the multi-agency, public-private collaborative nature of this as “an interesting experiment.” Is there a precedent for this type of collaboration? So far it seems the various players have listened to the conversations each has led, but remained autonomous in setting their own priorities; do you get a sense of how everyone will continue to interact, especially when it comes time to decide what gets funded?
Bargmann: There’s plenty for everyone to do. Right now there is also a lot of good will; the tone of the conversations between different partners has been positive and collaborative. We know that resources are limited — we will get much further if we share ideas, technologies, and data.
Q: I’ve had a question bouncing around my head for a while, and wasn’t sure whether to pose it because I don’t think it bears directly on what I’ll write for IEEE … but what the heck:
Why should brain science deserve such a prominent seat at the table when it comes to understanding “the interior terrain of thinking, feeling, perceiving, learning, deciding, and acting to achieve our goals”?
For understanding behavioral disorders like extreme depression, to prevent and treat dementia and Parkinson’s, to help victims of stroke or brain-damaging circumstance, I can *absolutely* understand the paramount importance of neuroscientific research. But for understanding our inner lives, it seems to me like the sort of physical scales at which neuroscience works, the questions that can be asked within its methodological frameworks, and ultimately the answers generates, are not necessarily more illuminating than what emerges from the humanities.
Put another way, to live with grief, or guide the education of my godchildren, I do appreciate the insights neuroscience (and cognitive science and psychology) provides me — but also those from literature, poetry, history, religion, philosophy and all those endeavors by which humans seek to understand ourselves. This isn’t a zero-sum, either-or choice, obviously — either science or humanities! — but when regarding the BRAIN Initiative, which right now seems like our society’s flagship expedition into the interior terrain, it feels disproportionately tilted toward one side.
Thanks for bearing with that ramble, and I hope it doesn’t sound combative — I think the BRAIN Initiative is an excellent and exciting thing, and would like to see it receive quite a bit more funding. And, like I said, the answer to the “Why brain science?” question isn’t immediately IEEE article-relevant; but if you’ve a chance to reply, I’d very much appreciate it for my own edification.
Bargmann: This is an excellent point. It is not either-or; science and human culture are both essential ventures. Recently I read the Bhagavat Gita, and there is nothing from brain science that helped me think about my relationship with the world as deeply as it did. On the other hand, writing the Gita did not require high-end microscopes, electrodes, and data analysis, and therefore it’s not the topic of a technological initiative. Science and technology make progress in different ways than the humanities and philosophy make progress, at least in our era.
You are right that much of our understanding of the mind is still more in the humanities than in the sciences. I also find it stupid when people take naive biological approaches to profound human questions. When people tell me my personal decisions are genetically determined by my ancestors on the African Savannah, I reach for my revolver. I suspect that the brain sciences will eventually lead to a deeper understanding of more profound issues. For example, the relationships between cognition and emotion don’t seem to me to be well-defined in either the sciences or the humanities yet. Biology may have something to say about that.
You are also right that in our time, the sciences are given priority over the humanities in our public discourse. But the humanities are also flowering compared to historical standards. Many more people are literate than at any time in the past. More voices and viewpoints are heard. Universal education is becoming a reality.
With respect to disorders of the brain, I think you and I agree that many, most, probably all have some biological cause and biological manifestation in the brain. That doesn’t mean it’s the only cause. I would say that the biological part may be the easiest to solve right now, and maybe that’s the reason to focus on it in our time. Memory is a rich, emotional, cognitive experience. But narrative memory is linked to the hippocampus in the most irreducible way. No hippocampus means none of that rich experience of personhood that comes from memory.
Q: Also, one other question, this one more article-relevant: Why weren’t more ethologists invited to the discussions? I’d think that with so much riding on animal models, and an acknowledged need for innovation in their use, it’d make sense to have some animal people there.
Bargmann: We had implicit ethology and what you might call techno-ethology. Implicit, through people like Eve Marder and David Anderson, who think about it extensively. Techno, Kristin Branson from HHMI spoke; she worked with Mike Dickinson, the ethologist who was featured in yesterday’s NY Times Science magazine. (High-throughput ethomics in large groups of Drosophila. Branson K, Robie AA, Bender J, Perona P, Dickinson MH. Nat Methods. 2009 Jun;6(6):451-7.). Plus Bill Newsome, my co-chair, considers himself a hard-core behaviorist. He’s the source of the “Nothing in the brain makes sense except in the light of behavior” line, a references to Dobzhansky of course, that appears in the report.
Even 80 neuroscientists is not very many when you consider that we were trying to go from math and physics to human brain imaging — we couldn’t invite very many of anything! We tried to find people who would take a broad view, and I have to say, the message of the importance of behavior came from many directions. That message is probably the biggest difference between the Brain Initiative in its current form and the original Kavli idea of the “Brain Activity Map” (BAM).
I started working as a blogger back in 2007, when online science journalism was still relatively new and bloggers were expected to be high-throughput link aggregators, adding perhaps a paragraph of pithy value. I’d crank out 10 or 12 posts per day; later on, I only had to write six, but was expected to have my own particular take on things. It wasn’t enough to link. I needed to have an opinion.
It’s not easy to produce insightful opinions on demand, day after day, especially with very little time to inform them. I sometimes fell into the trap — and still do too frequently, truth be told — of assuming my own knowledge to be more complete than it was. I’d pass judgement on people or research or other journalists without bothering to pick up a phone and call someone who might think differently than me, or know more. Neither did I especially want to; I knew I was right, had a point to make, and didn’t feel a need to challenge that.
Eventually I started working for an editor who didn’t want me to write casual takedowns, especially of other science coverage. I chafed a bit at first: the content beast demanded to be fed, and takedowns were fun! And poking holes in someone getting something wrong (cough British tabloid science coverage cough) was always good for quick content. But over time, I came to appreciate my editor’s requirements. It was good, old-fashioned wisdom regarding the limitations of one’s own knowledge and self-assurance, wrapped up in professional principle: Be careful about going negative unless you roll up your sleeves, put on your journalist’s hat, and talk to people with different perspectives than your own, even if you think you know plenty.
Good advice in any circumstance, but especially so when what you write can do damage. And I’ve been thinking of those days recently after seeing a takedown by Matthew Herper in Forbes of Moises Velasquez-Manoff, a science journalist and author of An Epidemic of Absence, a book about autoimmune diseases and a proposed explanation for what causes them. (You can read Velasquez-Manoff’s rejoinder here.)
Full disclosure: Velasquez-Manoff is a friend of mine as well as a colleague. We went to journalism school together, and we frequently talked about the book during its writing, which took more than two years. So I’m absolutely not a disinterested party, and am biased, and probably wouldn’t be writing this if there wasn’t a personal connection. But I’ve also got a good sense of the reporting and research that went into his book, have read large parts of it, and have also done some reporting of my own for several microbiome-and-disease articles.
So when Herper writes, regarding Velasquez-Manoff’s three New York Times op-eds about relationships between the human microbiome, immune system regulation and autoimmune diseases, that “scientists or experts might find Velasquez-Manoff’s conjectures, well, to be polite, to be conjectures,” I know that quite a few don’t. This isn’t hard to find out, really: aside from the scientists and experts Velasquez-Manoff cites, a Google Scholar search for “autoimmune microbiome etiology” returns a bounty of results from this space, both of single studies and large-scale literature reviews. (See this, this, this, this, this, this, this, this and this (1). And that’s just scraping the first few pages of results.)
To take these in order: Zuger’s credentials are impressive, yet she doesn’t seem to have understood quite what the book is about. According to Zuger, Velasquez-Manoff writes about the “hygiene hypothesis,” which holds that “the modern immune system … is stymied by the sudden absence of its customary microbial targets. With nothing constructive to do, it is crazily spinning its wheels, resulting in soaring rates” of autoimmune disease. This is, more or less, a 20-year-old version of the hygiene hypothesis, and not the one being discussed.
What Velasquez-Manoff is talking about, and what quite a few researchers are working on — also see this and this — is subtly but fundamentally different. It’s also described nicely by science writer Matt Ridley in a far more positive Wall Street Journal review of Epidemic: “Parasites have evolved to damp our immune responses so that they can stay in our bodies. Our immune system evolved to expect parasites to damp it. So in a world with no parasites, it behaves like a person leaning into the wind when it drops: The system falls over.”
As for Willingham’s critique, it raised some fair points, in particular that Velasquez-Manoff wrote incautiously, without the caveats and qualifications befitting a hypothesis — especially when it’s about a topic as important and sensitive as autism, and even if it’s an op-ed rather than a more formal journalistic form. Willingham also called the article “frequently unsourced and unreferenced.” That was true when the article came out, though Velasquez-Manoff subsequently posted a long list of sources on his website.
Whether those sources are satisfactory is a judgement call. To me, at an admittedly quick reading, they are: While any one study or observation is limited and imperfect, the weight of evidence, drawing from epidemiology and biological observation and animal model perturbation, makes it at least plausible that microbiome-mediated maternal inflammation may fuel autoimmune responses leading to autistic spectrum disorders in a subset of children with those symptoms. Correlation isn’t causation, but when multiple lines of evidence support a causal link, there’s reason to pay close attention.
Others, including Willingham, might disagree with this assessment of Velasquez-Manoff’s sourcing. Fair enough. Personally I’d have more confidence in certain of Willingham’s criticisms if there was some evidence she talked to a few of the scientists referenced, who might have provided a different perspective than her own. [Update: Willingham says she did speak without about 10 autism researchers, including Paul Patterson, about the maternal microbiome/autoimmunity/autism idea.] It feels to me that, having decided at the outset that Velasquez-Manoff’s article was poor and even dangerous — linking maternal immune disregulation to autism, says Willingham, echoes the “refrigerator mother" theory of the 1950s that blamed autism on emotionally distant moms — she then approached the references with an eye to finding flaws. Does that mean she’s wrong, or that there aren’t flaws? Of course not. But as a journalist, it’s the sort of critique I’d use as one of multiple sources, and not as a primary source without corroboration.
(For what it’s worth, in writing this post I emailed several researchers, among them Kevin Becker, an NIH geneticist who appears in Velasquez-Manoff’s autism article and who originally proposed, back in 2007, a possible link between autism, inflammation and exposures to microbes and parasites. Responded Becker, “In my view the pattern of aspects of autoimmune disorders is compelling for a portion of autism cases…. It is certainly not kooky science.” His full reply is reproduced below (3). On the broader question of whether microbiome-mediated immune dysregulation leading to autoimmune diseases is conjecture, Becker said, “In my view there is an enormous amount of epidemiological and immunological evidence,” a view echoed by other researchers who responded to my emails (4).)
At least Willingham, however, took some time to engage with Velasquez-Manoff’s actual work and the research he cited. That wasn’t the case with a number of science writers and journalists who, after Willingham’s original article came out, promptly circulated it without giving any indication of having taken more than a cursory look for themselves at the actual science (5). Herper’s article is just the latest example of this.
As for Velasquez-Manoff’s other two NYT articles, on microbiome links to celiac disease and to allergies, Herper has general criticisms — “overblown language about cures” in the allergies article, and a failure to “give readers a sense of the other side of an argument” in both. I think there’s some validity to the latter point, albeit limited: in the second paragraph of the celiac disease article, the microbiome link to is clearly identified as one of multiple “intriguing possibilities,” and a paragraph beginning “The caveats here are numerous” goes on to enumerate them. In the allergy article, the third paragraph reads, “What prompts some immune systems to err like this, while others never do? Some of the vulnerability is surely genetic” — and a primarily genetic explanation is addressed later in the article.
That said, I think Velasquez-Manoff could and should have talked more about the alternatives. A couple history-lesson paragraphs up top — “here’s some of the explanations that came before, they don’t seem to work very well, or are not mutually exclusive to this work, etc. etc.” — would have done wonders. He might also have done a better job addressing gaps and uncertainties that exist in the research, which on the clinical side is still in its very, very early stages. But there’s a big, unjustified leap from issues like these to dismissing Velasquez-Manoff’s reporting-based, general-audience translations of solid science as “conjecture,” his book (which Herper admittedly did not read) as “kooky” and Velasquez-Manoff as “a zealot” for an idea. It’s the sort of language usually reserved for homeopathy and water crystal healing. And to pass along that rush judgement uncritically is just as bad.
This tendency has bothered me more than anything else in the whole affair involving Velasquez-Manoff and his NYT articles. Science writers and journalists are qualified — even obligated — to investigate claims made about science. The writers criticizing the articles have not done that. [Update: Willingham did.] The amount of actual reporting done in this debate by anyone other than Velasquez-Manoff [and Willingham] amounts, as best as I can tell, to zero.
Instead, the dynamics have felt like a high school cafeteria’s, with cool kids sitting together and circulating hearsay about someone outside their circle, repeating it so often it becomes assumed fact. And here’s where my friendship with Velasquez-Manoff definitely comes into play: I happen to know how, rather than going to science-writer conferences and building his personal brand and tweeting at the right people and cultivating relationships within the community, he put his head down and worked on his book, for two long, hard years. He’s not one of the gang.
If he were, I truly believe the situation would have played out differently. I think quite a few of his critics would actually find the science quite interesting, even compelling. At the very least, someone would have had the basic courtesy, or even just the curiosity, to pick up a phone before dismissing it and him.
(1) A neat synopsis of research in this space can be found in the beginning of this Trends in Ecology and Evolution article by John Pepper, an NIH cancer researcher interested in microbiome links to cancer. Writes Pepper: “The shared mechanism linking these disparate diseases” — inflammatory bowel disease, gastric ulcers, obesity, diabetes, esophogeal and colorectal cancers, central nervous system disorders, autism, major depressive disorder — “is apparently the immune system and its interactions with the gut microbiome during development.” Pepper also replied to my questions about the microbiome and autoimmune disease; see below.
(2) Herper did also quote, after posting the article on Facebook, the response of Jonathan Eisen, UC-Davis microbiome researcher who said of Velasquez-Manoff’s new piece, “Uggh. Him again.” It’s the sort of reaction that should inspire follow-up reporting — but this isn’t, in itself, good source material in a dismissal of someone’s work as “kooky” and “conjecture.” Eisen’s research emphasis is phylogenetics. He’s a sequencer and tree-calculator extraordinaire, a specialist in evolutionary and ecological dynamics. Of 67 publications on which he’s been a co-author since the beginning of 2007, I see just two — one on H. pylori infections and rhesus monkey microbiomes and another on the human microbiome and bowel transplants — that are germane to the research under discussion.
Interestingly enough, in Eisen’s blog post on the autism article, he criticized Velasquez-Manoff for failing to distinguish between correlation and causation … but also said, “Overall, I do like this current article.”
(3) I asked Becker two questions:
Q: Is the theory that many autoimmune diseases are produced by microbiome-mediated immune dysregulation a solid one, or merely ‘conjecture’?”
Becker: I think it is due to immune dysregulation in pregnancy and early infancy. There are multiple paths to dysregulation.
In my view there is an enormous amount of epidemiological, and immunological evidence to support the so-called “hygiene hypothesis”. As you probably know that name is unfortunate since it is misinterpreted as having to do with personal hygiene. It is almost certainly more related to population burden of types of microbial bugs. This alters immune T cell development and promotes a hypersensitive state, in early infancy.
In genetically susceptible people this can lead to autoimmune and allergic disorders. Early exposure to microbial and other organisms primes the immune system which protects against autoimmunity and allergic disease. This is pretty rock solid in experimental studies. Mice raised in germ free environments get an increased number of autoimmune diseases. You can protect them by exposing them to microbes in early life.
The whole hookworm thing, although probably very real, just grosses people out. I really don’t see why the probiotic industry is not all over early infancy to build immunity.
Q: Do you think there’s good evidence for a maternal inflammation-mediated mechanism in some significant subset of cases?”
Becker: This is weaker [than the links between microbiome-mediated immune dysregulation and established autoimmune diseases —BK] but in my view the pattern of aspects of autoimmune disorders is compelling for a portion of autism cases.
i) Large epidemiological studies of increased numbers of family members with an autoimmune disease in a family with an index case of an autoimmune disease. That is, if you take 1000 families with a family member with Type 1 diabetes, there will be an increase in other family members, not with Type 1 diabetes, but with any type of autoimmune disease/ inflammatory disorder… T1D, thyroiditis, multiple sclerosis, etc. It reflects the shared genetics of autoimmunity that leads to immune dysregulation. That is what you find in autism. Large independent epidemiological studies from multiple countries that show an increase in autoimmune diseases in families with an autistic kid. Does that mean it causes autism?
ii) Altered and increased immune response. All autoimmune disease patients, have many kinds of autoantibodies, altered T cell patterns, altered cytokines, etc.. That pattern is seen in autistic kids. Is it causative? Don’t know.
iii) Asthma has been associated with use of acetaminophen (paracetamol) in pregnancy or in early infancy in many large epidemiological studies worldwide. (I believe because it is due to the immune suppressive effects again leading to altered immune response). A recent large study just came out of Norway associating paracetamol with phenotypes of autism. More studies in different parts of the world are needed. They are beginning.
iv) Activation of microglia (immune cells) in the brain of autistic kids.
There are other intriguing aspects of similar features between autism and autoimmune/inflammatory disorders that suggest that there is a link. It is certainly not kooky science.”
(4) Also responding to the question of, “Is the theory that many autoimmune diseases are produced by microbiome-mediated immune dysregulation a solid one, or merely ‘conjecture’?” was Stephen Paget, a rheumatologist at New York City’s Hospital for Special Surgery, who has written about the microbiome and inflammation in arthritis. Paget didn’t mince words; he simply wrote, “Very sound and correct.”
A lengthier response came from Alessio Fasano, head of Massachusetts General Hospital’s Center for Celiac Research & Treatment. Wrote Fasano, “There is an ongoing heated debate (far from being settled) about the causes of the epidemics of immune-mediated diseases. The fact that recent changes of microbiome composition can be responsible, at least in part, of [sic] these epidemics, is recently gaining momentum within the scientific community. However, it should be pointed out that we only recently acquired the proper tools to move our studies on the microbiome from merely descriptive (simply learning about the composition of the microbiome) to mechanistic (linking specific changes of the microbiome composition to disease states (now we have evidence for several autoimmune diseases, including IBD, celiac disease, Type 1 diabetes, just to name a few).
As concern the “epidemics” of celiac disease, I think that dysbiosis (change in microbiome composition) is one of the possible reasons, but it is hard to exclude other environmental causes, including quantity and quality of gluten, feeding patterns (breast feeding vs. bottle feeding), time of introduction of gluten in the diet, maturation of the gut functions, including its intestinal barrier and immune functions (just to name a few).”
Finally, John Pepper, the aforementioned NIH cancer specialist interested in links between cancer and the microbiome, also replied. To the question of whether the idea that many autoimmune diseases are produced by microbiome-mediated immune dysregulation is solid, he said:
“There is substantial evidence that the immune system develops normally only if it interacts with microbes, or more specifically, with bacteria, that have been typical of the human environment during our evolutionary history. Unfortunately, writings about the hygiene hypothesis often muddle together two ideas that are different in important ways. One idea is that the bacteria that play a key role in immune development are pathogens (disease-causing bacteria). The other idea is that the bacteria that play a key role in immune development are species that have had a mutually beneficial relationship with humans for as long as humans have existed, that are normally present ( especially in the gut), and that promote health rather than causing disease.”
I also asked, “If you read Velasquez-Manoff’s NYT articles, particularly on allergies and celiac disease, do you feel they unfairly ignored alternative explanations?”
Replied Pepper, “I think it’s fair for anyone to push their own pet hypothesis as hard as they like, and to ignore others, unless they claim to be presenting a balanced review. Velasquez-Manoff certainly does push just one hypothesis, although to be fair, there aren’t many plausible alternatives for explaining the allergy epidemic, which does seem to be real.
To add one more strand to this complex story, I’ll throw in the fact that over-active immune systems, and the chronic inflammation they can create, are also strongly implicated in causing various kinds of cancer, as well as cardiovascular disease, etc.
Where the Forbes article asserts that “scientists or experts might find Velasquez-Manoff’s conjectures, well, to be polite, to be conjectures,” I prefer to hope that scientists might find the hypothesis to be worth urgently testing so that we can either discard it or use it as an avenue to address these pressing health problems.”
(5) Especially egregious were two Knight Science Journalism Tracker posts by Deborah Blum in which she described the science as “shaky” and said Velasquez-Manoff had apparently “built his theory by largely avoiding autism research." When Velasquez-Manoff left a comment in the post with links to research, including a response from Caltech neurobiologist Paul Patterson — who studies autism and immunity, and wrote that “the crucial importance of this article is that it gets the message of immune involvement in autism out there in the public eye” — Blum didn’t reply.
“It is sometimes assumed that ‘simple’ and ‘miniature’ nervous systems such as those of insects implement cognitive faculties by radically different mechanisms compared with vertebrates, rather relying on innate routines and elemental forms of associative learning. However, constructing a great division between simple and advanced nervous systems will lead us astray, because the basic logical structure of the processes underlying spontaneity, decision-making, planning and communication is similar in many respects in big and small brains.”—Conceptual learning by miniature brains
“Wilcox and Jackson (1998, 2002) have found extensive experimental and observational evidence of complex cognition in jumping spiders of the genus Portia, which often prey on web-building spiders. To solve the challenges of preying on larger venomous spiders, Portia must reach moderately complex and appropriate decisions about spatial relationships, taking long detours around obstacles to reach a favorable location even when this requires losing visual contact with the goal. They engage in a complex form of communicative exchanges with their prey that include elements of deception. They approach the web quietly and set some of its threads into vibrations similar to the vibrations used in the courtship of the web-builder. The Portia adjusts its own vibratory signals in response to those of the web-builder in many subtle ways, tending to emit a wide variety of vibratory signals but to repeat those that attract the web-builder to the edge of the web. Wilcox and Jackson (2002) conclude that their investigations “bring us closer than we initially expected to something like the cognitive implications of verbal language” (Wilcox and Jackson 2002, p. 31).”—Griffin & Speck — “New Evidence of Animal Consciousness”
“In summary, a particular set of elements at a particular spatio-temporal scale yielding a maximum of integrated conceptual information (max Φ MIP) constitutes a complex, a ‘locus’ of consciousness. The set of its concepts – maximally irreducible cause-effect repertoires (max φ MIP>0) specified by various subsets of elements within the complex – constitute a
maximally integrated conceptual information structure or quale (Fig. 4) – a shape or constellation of points in qualia (concept) space.”—Integrated information theory of consciousness: an updated account
“However, it should not be overlooked that radical forms of parsimony as applied to behavioral science were (and may still be, at least in part) a historical burden.”—Dimensions of Cognition in an Insect, the Honeybee — BCNR289522.qxd - 9 Menzel & Giurfa 2005.pdf
“Currently, not only has Strong AI failed in its endeavor to build a system that is as intelligent as you or I, but it cannot even build a system as intelligent as the ubiquitous cockroach. Instead of locating the failure in the lack of a proper theory of concepts, representation, or semantics, this paper locates the failure in the underestimation of how complex even relatively simple biological organisms, such as the cockroach, really are. The implications of biological complexity on research in Strong AI are briefly explored.”—Where are all the cockroaches? - Journal of Experimental & Theoretical Artificial Intelligence - Volume 16, Issue 1