Visualizing and teaching evolution through synteny

Embracing the rationalist and empirically-based perspective of science is not easy. Modern science generates disconcerting ideas that can be difficult to accept and often upsetting to philosophical or religious views of what gives meaning to existence [link]. In the context of biological evolutionary mechanisms, the fact that variation is generated by random (stochastic) events, unpredictable at the level of the individual or within small populations, led to the rejection of Darwinian principles by many working scientists around the turn of the 20th century (see Bowler’s The Eclipse of Darwinism + link).  Educational research studies, such as our own “Understanding randomness and its impact on student learning“, reinforce the fact that ideas involving stochastic processes relevant to evolutionary, as well as cellular and molecular, biology, are inherently difficult for people to accept (see also: Why being human makes evolution hard to understand). Yet there is no escape from the science-based conclusion that stochastic events provide the raw material upon which evolutionary mechanisms act, as well as playing a key role in a wide range of molecular and cellular level processes, including the origin of various diseases, particularly cancer [Cancer is partly caused by bad luck](1).

Teach Evolution

All of which leaves the critical question, at least for educators, of how to best teach students about evolutionary mechanisms and outcomes. The problem becomes all the more urgent given the anti-science posturing of politicians and public “intellectuals”, on both the right and the left, together with various overt and covert attacks on the integrity of science education, such as a new Florida law that lets “anyone in Florida challenge what’s taught in schools”.

Just to be clear, we are not looking for students to simply “believe” in the role of evolutionary processes in generating the diversity of life on Earth, but rather that they develop an understanding of how such processes work and how they make a wide range of observations scientifically intelligible. Of course the end result, unless you are prepared to abandon science altogether, is that you will find yourself forced to seriously consider the implications of inescapable scientific conclusions, no matter how weird and disconcerting they may be.

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There are a number of educational strategies, in part depending upon one’s disciplinary perspective, on how to approach teaching evolutionary processes. Here I consider one, based on my background in cell and molecular biology.  Genomicus is a web tool that “enables users to navigate in genomes in several dimensions: linearly along chromosome axes, transversely across different species, and chronologically along evolutionary time.”  It is one of a number of  web-based resources that make it possible to use the avalanche of DNA (gene and genomic) sequence data being generated by the scientific community. For example, the ExAC/Gnomad Browser enables one to examine genetic variation in over 60,000 unrelated people. Such tools supplement and extend the range of tools accessible through the U.S. National Library of Medicine / NIH / National Center for Biotechnology Information (NCBI) web portal (PubMed).

In the biofundamentals / coreBio course (with an evolving text available here), we originally used the observation that members of our subfamily of primates,  the Haplorhini or dry nose primates, are, unlike most mammals, dependent on the presence of vitamin C (ascorbic acid) in their diet. Without vitamin C we develop scurvy, a potentially lethal condition. While there may be positive reasons for vitamin C dependence, in biofundamentals we present this observation in the context of small population size and a forgiving environment. A plausible scenario is that the ancestral Haplorhini population the lost the L-gulonolactone oxidase (GULO) gene (see OMIM) necessary for vitamin C synthesis. The remains of the GULO gene found in humans and other Haplorhini genomes is mutated and non-functional, resulting in our requirement for dietary vitamin C.

How, you might ask, can we be so sure? Because we can transfer a functional mouse GULO gene into human cells; the result is that vitamin C dependent human cells become vitamin C independent (see: Functional rescue of vitamin C synthesis deficiency in human cells). This is yet another experimental result, similar to the ability of bacteria to accurately decode a human insulin gene), that supports the explanatory power of an evolutionary perspective (2).


In an environment in which vitamin C is plentiful in a population’s diet, the mutational loss of the GULO gene would be benign, that is, not strongly selected against. In a small population, the stochastic effects of genetic drift can lead to the loss of genetic variants that are not strongly selected for. More to the point, once a gene’s function has been lost due to mutation, it is unlikely, although not impossible, that a subsequent mutation will lead to the repair of the gene. Why? Because there are many more ways to break a molecular machine, such as the GULO enzyme, but only a few ways to repair it. As the ancestor of the Haplorhini diverged from the ancestor of the vitamin C independent Strepsirrhini (wet-nose) group of primates, an event estimated to have occurred around 65 million years ago, its ancestors had to deal with their dietary dependence on vitamin C either by remaining within their original (vitamin C-rich) environment or by adjusting their diet to include an adequate source of vitamin C.

At this point we can start to use Genomicus to examine the results of evolutionary processes (see a YouTube video on using Genomicus)(3).  In Genomicus a gene is indicated  by a pointed box  ; for simplicity all genes are drawn as if they are the same size (they are not); different genes get different colors and the direction of the box indicates the direction of RNA synthesis, the first stage of gene expression. Each horizontal line in the diagram below represents a segment of a chromosome from a particular species, while the blue lines to the left represent phylogenic (evolutionary) relationships. If we search for the GULO gene in the mouse, we find it and we discover that its orthologs (closely related genes) are found in a wide range of eukaryotes, that is, organisms whose cells have a nucleus (humans are eukaryotes).

We find a version of the GULO gene in single-celled eukaryotes, such as baker’s yeast, that appear to have diverged from other eukaryotes about ~1.500,000,000 years ago (1500 million years ago, abbreviated Mya).  Among the mammalian genomes sequenced to date, the genes surrounding the GULO gene are (largely) the same, a situation known as synteny (mammals are estimated to have shared a common ancestor about 184 Mya). Since genes can move around in a genome without necessarily disrupting their normal function(s), a topic for another day, synteny between distinct organisms is assumed to reflect the organization of genes in their common ancestor. The synteny around the GULO gene, and the presence of a GULO gene in yeast and other distantly related organisms, suggests that the ability to synthesize vitamin C is a trait conserved from the earliest eukaryotic ancestors.GULO phylogeny mouse
Now a careful examination of this map (↑) reveals the absence of humans (Homo sapiens) and other Haplorhini primates – Whoa!!! what gives?  The explanation is, it turns out, rather simple. Because of mutation, presumably in their common ancestor, there is no functional GULO gene in Haplorhini primates. But the Haplorhini are related to the rest of the mammals, aren’t they?  We can test this assumption (and circumvent the absence of a functional GULO gene) by exploiting synteny – we search for other genes present in the syntenic region (↓). What do we find? We find that this region, with the exception of GULO, is present and conserved in the Haplorhini: the syntenic region around the GULO gene lies on human chromosome 8 (highlighted by the red box); the black box indicates the GULO region in the mouse. Similar syntenic regions are found in the homologous (evolutionarily-related) chromosomes of other Haplorhini primates.synteny-GULO region

The end result of our Genomicus exercise is a set of molecular level observations, unknown to those who built the original anatomy-based classification scheme, that support the evolutionary relationship between the Haplorhini and more broadly among mammals. Based on these observations, we can make a number of unambiguous and readily testable predictions. A newly discovered Haplorhini primate would be predicted to share a similar syntenic region and to be missing a functional GULO gene, whereas a newly discovered Strepsirrhini primate (or any mammal that does not require dietary ascorbic acid) should have a functional GULO gene within this syntenic region.  Similarly, we can explain the genomic similarities between those primates closely related to humans, such as the gorilla, gibbon, orangutan, and chimpanzee, as well as to make testable predictions about the genomic organization of extinct relatives, such as Neanderthals and Denisovians, using DNA recovered from fossils [link].

It remains to be seen how best to use these tools in a classroom context and whether having students use such tools influences their working understanding, and more generally, their acceptance of evolutionary mechanisms. That said, this is an approach that enables students to explore real data and to develop  plausible and predictive explanations for a range of genomic discoveries, likely to be relevant both to understanding how humans came to be, and in answering pragmatic questions about the roles of specific mutations and allelic variations in behavior, anatomy, and disease susceptibility.spacer bar

Some footnotes (figures reinserted 2 November 2020, with minor edits)

(1) Interested in a magnetic bumper image? visit: http://www.cafepress.com/bioliteracy

(2) An insight completely missing (unpredicted and unexplained) by any creationist / intelligent design approach to biology.

(3) Note, I have no connection that I know of with the Genomicus team, but I thank Tyler Square (now at UC Berkeley) for bringing it to my attention.

The trivialization of science education

It’s time for universities to accept their role in scientific illiteracy.  

There is a growing problem with scientific illiteracy, and its close relative, scientific over-confidence. While understanding science, by which most people seem to mean technological skills, or even the ability to program a device (1), is purported to be a critical competitive factor in our society, we see a parallel explosion of pseudo-scientific beliefs, often religiously held.  Advocates of a gluten-free paleo-diet battle it out with orthodox vegans for a position on the Mount Rushmore of self-righteousness, at the same time astronomers and astrophysicists rebrand themselves as astrobiologists (a currently imaginary discipline) while a subset of theoretical physicists, and the occasional evolutionary biologist, claim to have rendered ethicists and philosophers obsolete (oh, if it were only so). There are many reasons for this situation, most of which are probably innate to the human condition.  Our roots are in the vitamin C-requiring Haplorhini (dry nose) primate family, we were not evolved to think scientifically, and scientific thinking does not come easy for most of us, or for any of us over long periods of time (2). The fact that the sciences are referred to as disciplines reflects this fact, it requires constant vigilance, self-reflection, and the critical skepticism of knowledgeable colleagues to build coherent, predictive, and empirically validated models of the Universe (and ourselves).  In point of fact, it is amazing that our models of the Universe have become so accurate, particularly as they are counter-intuitive and often seem incredible, using the true meaning of the word.

Many social institutions claim to be in the business of developing and supporting scientific literacy and disciplinary expertise, most obviously colleges and universities.  Unfortunately, there are several reasons to question the general efficacy of their efforts and several factors that have led to this failure. There is the general tendency (although exactly how wide-spread is unclear, I cannot find appropriate statistics on this question) of requiring non-science students to take one, two, or more  “natural science” courses, often with associated laboratory sections, as a way to “enhance literacy and knowledge of one or more scientific disciplines, and enhance those reasoning and observing skills that are necessary to evaluate issues with scientific content” (source).

That such a requirement will “enable students to understand the current state of knowledge in at least one scientific discipline, with specific reference to important past discoveries and the directions of current development; to gain experience in scientific observation and measurement, in organizing and quantifying results, in drawing conclusions from data, and in understanding the uncertainties and limitations of the results; and to acquire sufficient general scientific vocabulary and methodology to find additional information about scientific issues, to evaluate it critically, and to make informed decisions” (source) suggests a rather serious level of faculty/institutional distain or apathy for observable learning outcomes, devotional levels of wishful thinking,  or simple hubris.  To my knowledge there is no objective evidence to support the premise that such requirements achieve these outcomes – which renders the benefits of such requirements problematic, to say the least (link).

On the other hand, such requirements have clear and measurable costs; going beyond the simple burden of added and potentially ineffective or off-putting course credit hours. The frequent requirement for multi-hour laboratory courses impacts the ability of students to schedule courses.  It would be an interesting study to examine how, independently of benefit, such laboratory course requirements impact students’ retention and time to degree, that is, bluntly put, costs to students and their families.

Now, if there were objective evidence that taking such courses improved students’ understanding of a specific disciplinary science and its application, perhaps the benefit would warrant the cost.  But one can be forgiven if one assumes a less charitable driver, that is, science departments’ self-interest in using laboratory and other non-major course requirements as means to support graduate students.  Clearly there is a need for objective metrics for scientific, that is disciplinary, literacy and learning outcomes.

And this brings up another cause for concern.  Recently, there has been a movement within the science education research community to attempt to quantify learning in terms of what are known as “forced choice testing instruments;” that is, tests that rely on true/false and multiple-choice questions, an actively anti-Socratic strategy.  In some cases, these tests claim to be research based.  As one involved in the development of such a testing instrument (the Biology Concepts Instrument or BCI), it is clear to me that such tests can serve a useful role in helping to identify areas in which student understanding is weak or confused [example], but whether they can provide an accurate or, at the end of the day, meaningful measure of whether students have developed an accurate working understanding of complex concepts and the broader meaning of observations is problematic at best.

Establishing such a level of understanding relies on Socratic, that is, dynamic and adaptive evaluations: can the learner clearly explain, either to other experts or to other students, the source and implications of their assumptions?  This is the gold standard for monitoring disciplinary understanding. It is being increasingly side-lined by those who rely on forced choice tests to evaluate learning outcomes and to support their favorite pedagogical strategies (examples available upon request).  In point of fact, it is often difficult to discern, in most science education research studies, what students have come to master, what exactly they know, what they can explain and what they can do with their knowledge. Rather unfortunately, this is not a problem restricted to non-majors taking science course requirements; majors can also graduate with a fragmented and partially, or totally, incoherent understanding of key ideas and their empirical foundations.

So what are the common features of a functional understanding of a particular scientific discipline, or more accurately, a sub-discipline?  A few ideas seem relevant.  A proficient needs to be realistic about their own understanding.  We need to teach disciplinary (and general) humility – no one actually understands all aspects of most scientific processes.  This is a point made by Fernbach & Sloman in their recent essay, “Why We Believe Obvious Untruths.”  Humility about our understanding has a number of beneficial aspects.  It helps keep us skeptical when faced with, and asked to accept, sweeping generalizations.

Such skepticism is part of a broader perspective, common among working scientists, namely the ability to distinguish the obvious from the unlikely, the implausible, and the impossible. When considering a scientific claim, the first criterion is whether there is a plausible mechanism that can be called upon to explain it, or does it violate some well-established “law of nature”. Claims of “zero waste” processes butt up against the laws of thermodynamics.

Going further, we need to consider how the observation or conclusions fits with other well established principles, which means that we have to be aware of these principles, as well as acknowledging that we are not universal experts in all aspects of science.  A molecular biologist may recognize that quantum mechanics dictates the geometries of atomic bonding interactions without being able to formally describe the intricacies of the molecule’s wave equation. Similarly, a physicist might think twice before ignoring the evolutionary history of a species, and claiming that quantum mechanics explains consciousness, or that consciousness is a universal property of matter.  Such a level of disciplinary expertise can take extended experience to establish, but is critical to conveying what disciplinary mastery involves to students; it is the major justification for having disciplinary practitioners (professors) as instructors.

From a more prosaic educational perspective other key factors need to be acknowledged, namely a realistic appreciation of what people can learn in the time available to them, while also understanding at least some of their underlying motivations, which is to say that the relevance of a particular course to disciplinary goals or desired educational outcomes needs to be made explicit and as engaging as possible, or at least not overtly off putting, something that can happen when a poor unsuspecting molecular biology major takes a course in macroscopic physics, taught by an instructor who believes organisms are deducible from first principles based on the conditions of the big bang.  Respecting the learner requires that we explicitly acknowledge that an unbridled thirst for an empirical, self-critical, mastery of a discipline is not a basic human trait, although it is something that can be cultivated, and may emerge given proper care.  Understanding the real constraints that act on meaningful learning can help focus courses on what is foundational, and help eliminate the irrelevant or the excessively esoteric.

Unintended consequences arise from “pretending” to teach students, both majors and non-science majors, science. One is an erosion of humility in the face of the complexity of science and our own limited understanding, a point made in a recent National Academy report that linked superficial knowledge with more non-scientific attitudes. The end result is an enhancement of what is known as the Kruger-Dunning effect, the tendency of people to seriously over-estimate their own expertise: “the effect describes the way people who are the least competent at a task often rate their skills as exceptionally high because they are too ignorant to know what it would mean to have the skill”.

A person with a severe case of Kruger-Dunning-itis is likely to lose respect for people who actually know what they are talking about. The importance of true expertise is further eroded and trivialized by the current trend of having photogenic and well-speaking experts in one domain pretend to talk, or rather to pontificate, authoritatively on another (3).  In a world of complex and arcane scientific disciplines, the role of a science guy or gal can promote rather than dispel scientific illiteracy.

We see the effects of the lack of scientific humility when people speak outside of their domain of established expertise to make claims of certainty, a common feature of the conspiracy theorist.  An oft used example is the claim that vaccines cause autism (they don’t), when the actual causes of autism, whether genetic and/or environmental, are currently unknown and the subject of active scientific study.  An honest expert can, in all humility, identify the limits of current knowledge as well as what is known for certain.  Unfortunately, revealing and ameliorating the levels of someone’s Kruger-Dunning-itis involves a civil and constructive Socratic interrogation, something of an endangered species in this day and age, where unseemly certainty and unwarranted posturing have replaced circumspect and critical discourse.  Any useful evaluation of what someone knows demands the time and effort inherent in a Socratic discourse, the willingness to explain how one knows what one thinks one knows, together with a reflective consideration of its implications, and what it is that other trained observers, people demonstrably proficient in the discipline, have concluded. It cannot be replaced by a multiple choice test.

Perhaps a new (old) model of encouraging in students, as well as politicians and pundits, an understanding of where science comes from, the habits of mind involved, the limits of, and constraints on, our current understanding  is needed.  At the college level, courses that replace superficial familiarity and unwarranted certainty with humble self-reflection and intellectual modesty might help treat the symptoms of Kruger-Dunning-itis, even though the underlying disease may be incurable, and perhaps genetically linked to other aspects of human neuronal processing.


some footnotes:

  1. after all, why are rather distinct disciplines lumped together as STEM (science, technology, engineering and mathematics).
  2.  Given the long history of Homo sapiens before the appearance of science, it seems likely that such patterns of thinking are an unintended consequence of selection for some other trait, and the subsequent emergence of (perhaps excessively) complex and self-reflective nervous system.
  3.  Another example of Neil Postman’s premise that education is be replaced by edutainment (see  “Amusing ourselves to Death”.

Go ahead and “teach the controversy:” it is the best way to defend science.

as long as teachers understand the science and its historical context

The role of science in modern societies is complex. Science-based observations and innovations drive a range of economically important, as well as socially disruptive, technologies. Many opinion polls indicate that the American public “supports” science, while at the same time rejecting rigorously established scientific conclusions on topics ranging from the safety of genetically modified organisms and the role of vaccines in causing autism to the effects of burning fossil fuels on the global environment [Pew: Views on science and society]. Given that a foundational principle of science is that the natural world can be explained without calling on supernatural actors, it remains surprising that a substantial majority of people appear to believe that supernatural entities are involved in human evolution [as reported by the Gallup organization]; although the theistic percentage has been dropping  (a little) of late.

God+evolution

This situation highlights the fact that when science intrudes on the personal or the philosophical (within which I include the theological and the  ideological), many people are willing to abandon the discipline of science to embrace explanations based on personal beliefs. These include the existence of a supernatural entity that cares for people, at least enough to create them, and that there are reasons behind life’s tragedies.

 

Where science appears to conflict with various non-scientific positions, the public has pushed back and rejected the scientific. This is perhaps best represented by the recent spate of “teach the controversy” legislative efforts, primarily centered on evolutionary theory and the realities of anthropogenic climate change [see Nature: Revamped ‘anti-science’ education bills]. We might expect to see, on more politically correct campuses, similar calls for anti-GMO, anti-vaccination, or gender-based curricula. In the face of the disconnect between scientific and non-scientific (philosophical, ideological, theological) personal views, I would suggest that an important part of the problem has didaskalogenic roots; that is, it arises from the way science is taught – all too often expecting students to memorize terms and master various heuristics (tricks) to answer questions rather than developing a self-critical understanding of ideas, their origins, supporting evidence, limitations, and practice in applying them.

Science is a social activity, based on a set of accepted core assumptions; it is not so much concerned with Truth, which could, in fact, be beyond our comprehension, but rather with developing a universal working knowledge, composed of ideas based on empirical observations that expand in their explanatory power over time to allow us to predict and manipulate various phenomena.  Science is a product of society rather than isolated individuals, but only rarely is the interaction between the scientific enterprise and its social context articulated clearly enough so that students and the general public can develop an understanding of how the two interact.  As an example, how many people appreciate the larger implications of the transition from an Earth to a Sun- or galaxy-centered cosmology?  All too often students are taught about this transition without regard to its empirical drivers and philosophical and sociological implications, as if the opponents at the time were benighted religious dummies. Yet, how many students or their teachers appreciate that as originally presented the Copernican system had more hypothetical epicycles and related Rube Goldberg-esque kludges, introduced to make the model accurate, than the competing Ptolemic Sun-centered system? Do students understand how Kepler’s recognition of elliptical orbits eliminated the need for such artifices and set the stage for Newtonian physics?  And how did the expulsion of humanity from the center to the periphery of things influence peoples’ views on humanity’s role and importance?

 

So how can education adapt to better help students and the general public develop a more realistic understanding of how science works?  To my mind, teaching the controversy is a particularly attractive strategy, on the assumption that teachers have a strong grounding in the discipline they are teaching, something that many science degree programs do not achieve, as discussed below. For example, a common attack against evolutionary mechanisms relies on a failure to grasp the power of variation, arising from stochastic processes (mutation), coupled to the power of natural, social, and sexual selection. There is clear evidence that people find stochastic processes difficult to understand and accept [see Garvin-Doxas & Klymkowsky & Fooled by Randomness].  An instructor who is not aware of the educational challenges associated with grasping stochastic processes, including those central to evolutionary change, risks the same hurdles that led pre-molecular biologists to reject natural selection and turn to more “directed” processes, such as orthogenesis [see Bowler: The eclipse of Darwinism & Wikipedia]. Presumably students are even more vulnerable to intelligent-design  creationist arguments centered around probabilities.

The fact that single cell measurements enable us to visualize biologically meaningful stochastic processes makes designing course materials to explicitly introduce such processes easier [Biology education in the light of single cell/molecule studies].  An interesting example is the recent work on visualizing the evolution of antibiotic resistance macroscopically [see The evolution of bacteria on a “mega-plate” petri dish].bacterial evolution-antibiotic resistancepng

To be in a position to “teach the controversy” effectively, it is critical that students understand how science works, specifically its progressive nature, exemplified through the process of generating and testing, and where necessary, rejecting or revising, clearly formulated and predictive hypotheses – a process antithetical to a Creationist (religious) perspective [a good overview is provided here: Using creationism to teach critical thinking].  At the same time, teachers need a working understanding of the disciplinary foundations of their subject, its core observations, and their implications. Unfortunately, many are called upon to teach subjects with which they may have only a passing familiarity.  Moreover, even majors in a subject may emerge with a weak understanding of foundational concepts and their origins – they may be uncomfortable teaching what they have learned.  While there is an implicit assumption that a college curriculum is well designed and effective, there is often little in the way of objective evidence that this is the case. While many of our dedicated teachers (particularly those I have met as part of the CU Teach program) work diligently to address these issues on their own, it is clear that many have not been exposed to a critical examination of the empirical observations and experimental results upon which their discipline is based [see Biology teachers often dismiss evolution & Teachers’ Knowledge Structure, Acceptance & Teaching of Evolution].  Many is the molecular biology department that does not require formal coursework in basic evolutionary mechanisms, much less a thorough consideration of natural, social, and sexual selection, and non-adaptive mechanisms, such as those associated with founder effects, population bottlenecks, and genetic drift, stochastic processes that play a key role in the evolution of many species, including humankind. Similarly, more ecologically- and physiologically-oriented majors are often “afraid” of the molecular foundations of evolutionary processes. As part of an introductory chemistry curriculum redesign project (CLUE), Melanie Cooper and her group at Michigan State University have found that students in conventional courses often fail to grasp key concepts, and that subsequent courses can sometimes fail to remediate the didaskalogenic damage done in earlier courses [see: an Achilles Heel in Chemistry Education].

The importance of a historical perspective: The power of scientific explanations are obvious, but they can become abstract when their historical roots are forgotten, or never articulated. A clear example is that the value of vaccination is obvious in the presence of deadly and disfiguring diseases. In their absence, due primarily to the effectiveness of wide-spread vaccination, the value of vaccination can be called into question, resulting in the avoidable re-emergence of these diseases.  In this context, it would be important that students understand the dynamics and molecular complexity of biological systems, so that they can explain why it is that all drugs and treatments have potential side-effects, and how each individual’s genetic background influences these side-effects (although in the case of vaccination, such side effects do not include autism).

Often “controversy” arises when scientific explanations have broader social, political, or philosophical implications. Religious objections to evolutionary theory arise primarily, I believe, from the implication that we (humans) are not the result of a plan, created or evolved, but rather that we are accidents of mindless, meaningless, and often gratuitously cruel processes. The idea that our species, which emerged rather recently (that is, a few million years ago) on a minor planet on the edge of an average galaxy, in a universe that popped into existence for no particular reason or purpose ~14 billion years ago, can have disconcerting implications [link]. Moreover, recognizing that a “small” change in the trajectory of an asteroid could change the chance that humanity ever evolved [see: Dinosaur asteroid hit ‘worst possible place’] can be sobering and may well undermine one’s belief in the significance of human existence. How does it impact our social fabric if we are an accident, rather than the intention of a supernatural being or the inevitable product of natural processes?

Yet, as a person who firmly believes in the French motto of liberté, égalité, fraternité and laïcité, I feel fairly certain that no science-based scenario on the origin and evolution of the universe or life, or the implications of sexual dimorphism or “racial” differences, etc, can challenge the importance of our duty to treat others with respect, to defend their freedoms, and to insure their equality before the law. Which is not to say that conflicts do not inevitably arise between different belief systems – in my own view, patriarchal oppression needs to be called out and actively opposed where ever it occurs, whether in Saudi Arabia or on college campuses (e.g. UC Berkeley or Harvard).

This is not to say that presenting the conflicts between scientific explanations of phenomena and non-scientific, but more important beliefs, such as equality under the law, is easy. When considering a number of natural cruelties, Charles Darwin wrote that evolutionary theory would claim that these are “as small consequences of one general law, leading to the advancement of all organic beings, namely, multiply, vary, let the strongest live  and the weakest die” note the absence of any reference to morality, or even sympathy for the “weakest”.  In fact, Darwin would have argued that the apparent, and overt cruelty that is rampant in the “natural” world is evidence that God was forced by the laws of nature to create the world the way it is, presumably a worlDarwin to Grayd that is absurdly old and excessively vast. Such arguments echo the view that God had no choice other than whether to create or not; that for all its flaws, evils, and unnecessary suffering this is, as posited by Gottfried Leibniz (1646-1716) and satirized by Voltaire (1694–1778) in his novel Candide, the best of all possible worlds. Yet, as a member of a reasonably liberal, and periodically enlightened, society, we see it as our responsibility to ameliorate such evils, to care for the weak, the sick, and the damaged and to improve human existence; to address prejudice and political manipulations [thank you Supreme Court for ruling against race-based redistricting].  Whether anchored by philosophical or religious roots, many of us are driven to reject a scientific (biological) quietism (“a theology and practice of inner prayer that emphasizes a state of extreme passivity”) by actively manipulating our social, political, and physical environment and striving to improve the human condition, in part through science and the technologies it makes possible.

At the same time, introducing social-scientific interactions can be fraught with potential  controversies, particularly in our excessively politicized and self-righteous society. In my own introductory biology class (biofundamentals), we consider potentially contentious issues that include sexual dimorphism and selection and social evolutionary processes and their implications.  As an example, social systems (and we are social animals) are susceptible to social cheating and groups develop defenses against cheaters; how such biological ideas interact with historical, political and ideological perspectives is complex, and certainly beyond the scope of an introductory biology course, but worth acknowledging [PLoS blog link].

yeats quote

In a similar manner, we understand the brain as an evolved cellular system influenced by various experiences, including those that occur during development and subsequent maturation.  Family life interacts with genetic factors in a complex, and often unpredictable way, to shape behaviors.  But it seems unlikely that a free and enlightened society can function if it takes seriously the premise that we lack free-will and so cannot be held responsible for our actions, an idea of some current popularity [see Free will could all be an illusion ]. Given the complexity of biological systems, I for one am willing to embrace the idea of constrained free will, no matter what scientific speculations are currently in vogue [but see a recent video by Sabine Hossenfelder You don’t have free will, but don’t worry, which has me rethinking].

Recognizing the complexities of biological systems, including the brain, with their various adaptive responses and feedback systems can be challenging. In this light, I am reminded of the contrast between the Doomsday scenario of Paul Ehrlich’s The Population Bomb, and the data-based view of the late Hans Rosling in Don’t Panic – The Facts About Population.

All of which is to say that we need to see science not as authoritarian, telling us who we are or what we should do, but as a tool to do what we think is best and why it might be difficult to achieve. We need to recognize how scientific observations inform and may constrain, but do not dictate our decisions. We need to embrace the tentative, but strict nature of the scientific enterprise which, while it cannot arrive at “Truth” can certainly identify non-sense.

Minor edits and updates and the addition of figures that had gone missing –  20 October 2020

After the March for Science, What Now?

Recently, I contributed to a project that turned healthy human tissues into an earlier stage of pancreatic cancer—a disease that carries a dismal 5-year survival rate of 5 percent.

 

When I described our project to a friend, she asked, “why in the world would you want to grow cancer in a lab?” I explained that by the time a patient learns that he has pancreatic cancer, the tumor has spread throughout the body. At that point, the patient typically has less than a year to live and his tumor cells have racked up a number of mutations, making clinical trials and molecular studies of pancreatic cancer evolution downright difficult. For this reason, our laboratory model of pancreatic cancer was available to scientists who wanted to use it to find the biological buttons that turn healthy cells into deadly cancer. By sharing our discovery, we wanted to enable others in developing drugs to treat cancer and screening tests to diagnose patients early. The complexity of this process demonstrates that science is a team effort that involves lots of time, money, and the brainpower of highly-trained individuals working together toward a single goal.

 

Many of the challenges we face today—from lifestyle diseases, to the growing strains of antibiotic-resistant superbugs in hospitals, to the looming energy crisis—require scientific facts and solutions. And although there’s never a guarantee of success, scientists persist in hopes that our collective discoveries will reverberate into the future. However, as a corollary, hindering scientific progress means a loss of possibilities.

 

Unfortunately, the deceleration of scientific progress seems likely possibility. In March, the White House released a document called “America First: A Budget Blueprint to Make America Great Again,” which describes deep cuts to some of the country’s most important funding agencies for science.

 

As it stands, the National Institutes of Health is set to lose nearly a fifth of its budget; the Department of Energy’s Office of Science, $900 million; and the Environmental Protection Agency, a 31.5 percent budget cut worth $2.6 billion. Imagine the discoveries that could have saved our lives or created jobs, which will instead languish solely as unsupported hypotheses in the minds of underfunded scientists.

 

Scientists cannot remain idle on the sidelines; we must be active in making the importance of scientific research known. Last weekend’s March on Science drew tens of thousands of people around more than 600 rallies across the world, but the challenge now lies in harnessing the present momentum and energy to make sustained efforts to maintain government funding for a wide range of scientific projects.

 

The next step is to get involved in shaping public opinion and policy. As it stands, Americans on both sides of the political spectrum have expressed ambivalence about the validity of science on matters ranging from climate change to childhood vaccinations. Academics can start tempering the public’s unease toward scientific authority and increase public support for the sciences by stepping off the ivory tower. Many researchers are already engaging with the masses by posting on social media, penning opinion articles, and appearing on platforms aimed at public consumption (Youtube channels, TED, etc). A researcher is her own best spokesperson in explaining the importance of her work and the scientific process; unfortunately, a scientist’s role as an educator in the classroom and community is often shoved out by the all-encompassing imperative to publish or perish. As a profession, we must become more willing to step out of our laboratories to engage with the public and educate the next generation of science-savvy citizens.

 

In addition, many scientists have expressed interest in running for office, including UC Berkeley’s Michael Eisen (who also a co-founder of PLOS). When asked by Science why he was considering a run for senate, Eisen responded:

 

“My motivation was simple. I’m worried that the basic and critical role of science in policymaking is under a bigger threat than at any point in my lifetime. We have a new administration and portions of Congress that don’t just reject science in a narrow sense, but they reject the fundamental idea that undergirds science: That we need to make observations about the world and make our decisions based on reality, not on what we want it to be. For years science has been under political threat, but this is the first time that the whole notion that science is important for our politics and our country has been under such an obvious threat.”

 

If scientists can enter into the house and senate in greater numbers, they will be able to inject scientific sense into the discussions held by members of legislature whose primary backgrounds are in business and law.

 

Science is a bipartisan issue that should not be bogged down by the whims of political machinations. We depend on research to address some of the most pressing problems of our time, and America’s greatness lies in part on its leadership utilizing science as an exploration of physical truths and a means of overcoming our present limitations and challenges.

 

 

Check out Yoo Jung’s book aimed at helping college students excel in science, What Every Science Student Should Know (University of Chicago Press)

Science, Politics & Marches

Marching is much in the air of late. After the “Women’s March”, that engaged many millions and was motivated in part by misogynistic statements and proposed policies from various politicians, we find ourselves faced with a range of anti-science behaviors, remarks, and proposed policy changes that have encouraged a similar March for Science.  The March for Science has garnered the support of a wide range of scientific organizations, including the American Association for the Advancement of Science (AAAS) and a range of more march-logospecialized professional science organizations, including the Public Library of Science (PLoS).  There have been a number of arguments for and against marching for science, summarized in this PLoS On Science blog post, so I will not repeat them here.  What is clear is that science does not exist independently of humanity, and this implies a complex interaction between scientific observations and ideas, the scientific enterprise, politics, economics, and personal belief systems: it seems evident that not nearly enough effort is spent in our educational systems to help people understand these interactions (see PLoS SciEd post: From the Science March to the Classroom: Recognizing science in politics and politics in science).

What I want to do here is to present some reflections on the relationship between science and politics, by which I include various belief systems (ideologies).

The mystic Giordano Bruno, burnt at the stake by the Roman Catholic Church as a heretic in 1600, is sometimes put forward as a patron saint of science, mistakenly in my view.  Bruno was a mystic, whose ideas were at best loosely grounded in the observable and in no way scientific as we understand the term. His type of magical thinking is similar to that of modern anti-vaccination-ists who claim vaccination can cause autism (it does not)(1) or that GMOs are somehow innately “unhealthy” and more dangerous than “natural” organisms (see: The GMO safety debate is over).  A better model, particularly in the context of current political controversies, would be the many Soviet geneticists who suffered exile and often death (the famed geneticist N.I. Vavilov starved to death in a Soviet gulag in 1943) as a result of the state/party-driven politicization of science, specifically genetics, carried out by Joseph Stalin (1878-1953) and the Communist party/state of the Soviet Union (see: The tragic story of Soviet genetics shows the folly of political meddling in science). In response to the  implications of genetic and evolutionary mechanisms, Stalin favored Lamarckism (inheritance of acquired traits) posited by Ivan Michurin (1855–1935) and Trofim Lysenko (1898–1976)[see link]. Communist ideology required (or rather demanded) that traits, including human traits, be seen as malleable, that the “nature” of plants and people could be altered permanently with appropriate manipulations (vernalization for plants, political re-education for people)[see: The consequences of political dictatorship for Russian science).  No need to wait for the messy, multi-generational processes associated with conventional plant breeding (and Darwinian evolution).  In both cases, the unforgiving realities of the natural world intervened, but not without intense human suffering and starvation associated with both efforts.russion march for science

It is worth noting explicitly that there are, and likely always will be, pressures to politicize science, due in large measure to science’s success in explaining the natural world and providing the basis for its technology-based manipulation. Giordano Bruno was an early martyr in the evolution of a highly ideological world view (illustrated by the house arrest of Galileo and the suppression of heliocentric models of the solar system)(2). Eventually such forms of natural theology were replaced by the apolitical and empirical ideals implicit in Enlightenment science. Aspects of ideological (racist) influences can be seen in 19th century science, most dramatically illustrated by Gould (Morton’s ranking of races by cranial capacity. Unconscious manipulation of data may be a scientific norm)(see link). How racist policies were initially embraced, and then rejected by American geneticists during the course of the 20th century is described by Provine (Geneticists and the Biology of Race Crossing).

More recent events remind us of the pressures to politicize science.  A number of states (Kentucky in 1976, Mississippi in 2006,  Louisiana in 2008, and Tennessee in 2012) have passed bills that allow teachers to present non-scientific ideas to students (think intelligent design creationism and climate change denial).  Such bills continue to come up with depressing frequency.  Most recently an admitted creationist has been appointed to lead a federal  higher education reform task force in the United States [see link]. Is creationism simply alt-science? a position explicitly or tacitly supported by both the religiously orthodox and those of a post-modernist persuasion, such as left-leaning college instructors, who claim that science is a social construct [see: Is Science ‘Forever Tentative’ and ‘Socially Constructed’?].

While such recent anti-science/alt-science attitudes have not had quite the draconian effects found in the Soviet Union, Nazi Germany or eugenist America), I would argue that they have a role in eroding the public’s faith in the scientific understanding of complex processes, a faith that is largely justified even in the face of the so-called “reproducibility crises”, which in a sense is no crises at all, but an expected outcome from the size, complexity, and competing forces acting on scientists and  the scientific enterprise. That said, laws and various forms of coercion dictating right-wing/religious or left-wing/political correctness in science threaten to impact the education of a generation of students. Predictions of climate changed based on human-driven (anthropogenic) increases in atmospheric CO2 levels or the effects of lead in public water systems on human health [link] cannot simply be discarded or discounted based on ideological positions on the role of government in protecting the public interest, a role that neither unfettered capitalism or fundampolitics + science cartoonentalist communism seems particularly good at addressing. Similarly the lack of any demonstrable connection between autism and vaccination (see above), the physicochemical impossibility of homeopathic treatments (or various versions of “Christian Science”), and the lack of evidence for the therapeutic claims made for the rather startling array of nutritional supplements serve to inject a political, ideological, and economic  dimension into scientific discourse.  In fact science is constantly under pressure to distort its message.  Consider the European response to GMOs in favor of the “organic” (non-GMO); most GMOs have been banned from the EU for what appears to be ideological (non-scientific) reasons, even though the same organisms have been found safe and are grown in the US and most of Asia (see this Economist essay).

It is clear that the rejection of scientific observations is wide-spread on both the left and the right, basically whenever scientific observations, ideas, or models lead to disturbing or  discomforting conclusions or implications (link). Consider the violent response when Charles Murray was invited to speak at Middlebury College (see Andrew Sullivan’s Is intersectionality a religion?). That human populations might (and in fact can be expected to) display genetic differences, the result of their migration history and subsequent evolutionary processes, both adaptive and non-adaptive (see Henn et al., The great human expansion), is labelled racist and by implication beyond the pale of scientific discourse, even though it is tacitly recognized by the scientific community to be well established (no one, I think, gets particularly upset at the suggestion that noses are shaped by evolutionary processes and reflect genetic differences between populations (see Climate shaped the human nose) or that nose shape might play a role in human sexual selection (see Facial Attractiveness and Sexual Selection; and sexual dimorphism).  One might even speculate that studies of the role of nose shape in mate selection could form the basis of an interesting research project (see Beauty and the beast: mechanisms of sexual selection in humans.

What often goes undiscussed is whether differences in specific traits (different alleles and allele frequencies) between populations have any meaningful significance in the context f public policy – I would argue that they do not).  What is clear is that in a pre-genomic era recognizing such differences can be of practical value, for example in the treatment of diseases (see Ethnic Differences in Cardiovascular Drug Response). That said, the era of genomics-based personalized diagnosis and treatment is rapidly making such population-based considerations obsolete (see: Genetic tests for disease risks and ethical debate on personal genome testing), while at the same time raising serious issues of privacy and discrimination based on the presence of the “wrong” alleles (see: genome sequencing–ethical issues). In a world of facile genomic engineering the dangers of unfettered technological manipulations move more and more rapidly from science fiction to the boutique (intelligent?) design of people (see: CRISPR gene-editing and human evolution).

So back (about time, you may be thinking) to the original question – if we “march for science”, what exactly are we marching for [link]?  Are we marching to defend the apolitical nature of science and the need to maintain economic support (increased public funding levels) for the scientific enterprise, or are we conflating support for science with a range of social and political positions?  Are we affirming our commitment to a politically independent (skeptical) community of practitioners who serve to produce, reproduce, critically examine, and extend empirical observations and explanatory (predictive) models?

This is not to ignore the various pressures acting on scientists as they carry out their work. These pressures act to tempt (and sometimes reward) practitioners to exaggerate (if not fabricate) the significance of their observations and ideas in order to capture the resources (funds and people) needed to carry out modern science, as well as the public’s attention. Since resources are limited, extra-scientific forces have an increasing impact on the scientific enterprise – enticing scientists to make exaggerated claims and to put forth extra-scientific arguments and various semi-hysterical scenarios based on their observations and models.  In the context of an inherently political event (a march) the apolitical ideals of science can seem too bland to command attention and stir action, not to mention the damage that politicizing science does to the integrity of science.

At the end of the day my decision is not to march, because I believe that science must be protected from the politPearl quote - aegisical and the partisan(see: The pernicious effects of disrespecting the constraints of science); that the ultimate working nature (as opposed to delivered truth) of scientific observations and conclusions must be respected, something rarely seen in any political movement and certainly not on display in the Lysenkoist, climate change, anti-vaccination, or eugenics movements (see this provocative essay: The Disgraceful Episode Of Lysenkoism Brings Us Global Warming Theory.)

 


Thanks and footnotes
:

Thanks for help on this post from Glenn Branch @ National Center for Science Education.   Of course all opinions are mine alone.

(1) While there is not doubt that vaccinations can, like all drugs and medical interventions, lead to side effects in certain individuals, there is unambiguous evidence against any link between autism and vaccination.

(2) It is worth noting that as originally proposed the Copernican (Sun-centered) model of the solar system was more complex than the Ptolemaic (Earth-centered) system it was meant to replace. It was Kepler’s elliptical, rather than circular, orbits that made the heliocentric model dramatically simpler, more accurate, and more aesthetically compelling.

From the Science March to the Classroom: Recognizing science in politics and politics in science

Jeanne Garbarino (with edits by Mike Klymkowsky)

Purely scientific discussions are hallmarked by objective, open, logical, and skeptical thought; they can describe and explain natural phenomena or provide insights into a broader questions. At the same time, scientific discussions are generally incomplete and tentative (sometimes for well understood reasons). True advocates of the scientific method appreciate the value of its skeptical and tentative approach, and are willing to revise even long-held positions in response to new, empirically-derived evidence or logical contradictions. Over time, science’s scope and conclusions have expanded and evolved dramatically; they provide an increasingly accurate working model of a wide range of processes, from the formation of the universe to the functioning of the human mind. The result is that the ubiquity of science’s impacts on society are clear and growing. However, discussing and debating the details of how science works, and the current consensus view on various phenomena, such as global warming or the causes of cancer or autism, is very different from discussing and debating how a scientific recommendation fits into a societal framework. As described in a recent National Academies Press report on Communicating Science Effectively  [link], “the decision to communicate science [outside of academia] always involves an ethical component. Choices about what scientific evidence to communicate and when, how, and to whom, are a reflection of values.”

Over the last ~150 years, the accelerating pace of advances in science and technology have enabled future sustainable development, but they have also disrupted traditional social and economic patterns. Closing coal mines in response to climate predictions (and government regulations) may be sensible when viewed broadly, but are disruptive to those who have, for generations, made a living mining coal. Similarly, a number of prognosticators have speculated on the impact of robotics and artificial intelligence on traditional socioeconomic roles and rules. Whether such impacts are worth the human costs is rarely explicitly considered and discussed in the public forum, or the classroom. As members of the scientific community, our educational and outreach efforts must go beyond simply promoting an appreciation of, and public support for science. They must also consider its limitations, as well as the potential ethical and disruptive effects on individuals, communities, and/or societies. Making policy decisions with large socioeconomic impacts based on often tentative models raises risks of alienating the public upon which modern science largely depends.

Citizens, experts or not, are often invited to contribute to debates and discussions surrounding science and technology at the local and national levels. Yet, many people are not provided with the tools to fully and effectively engage in these discussions, which involves critically analyzing the scope, resolution, and stability of scientific conclusions. As such, the acceptance or rejection of scientific pronouncements is often framed as an instrument of political power, casting a shadow on core scientific principles and processes, framing scientists as partisan players in a political game. The watering down of the role of science and science-based policies in the public sphere, and the broad public complacency associated with (often government-based, regulatory) efforts, is currently being challenged by the international March For Science effort. The core principles and goals of this initiative [link] are well articulated, and, to my mind, representative of a democratic society. However, a single march on a single day is not sufficient to promote a deep social transformation, and promote widespread dispassionate argumentation and critical thinking. Perspectives on how scientific knowledge can help shape current and future events, as well as the importance of recognizing both the implications and limits of science, are perspectives that must be taught early, often, and explicitly. Social or moral decisions are not mutually exclusive from scientific evidence or ideas, but overlap is constrained by the gates set by values that are held.

In this light, I strongly believe the sociopolitical nature of science in practice must be taught alongside traditional science content. Understanding the human, social, economic and broader (ecological) costs of action AND inaction can be used to highlight the importance of framing science in a human context. If the expectation is for members of our society to be able to evaluate and weigh in on scientific debates at all levels, I believe we are morally obligated to supply future generations with the tools required for full participation. This posits that scientists and science educators, together with historian, philosophers, and economists, etc., need to go beyond the teaching of simple facts and theories by considering how these facts and theories developed over time, their impact on people’s thinking, as well as the socioeconomic forces that shape societies. Highlighting the sociopolitical implications of science-based ideas in classrooms can also motivate students to take a greater interest in scientific learning in particular, and related social and political topics in general. It can help close the gap between what is learned in school and what is required for the critical evaluation of scientific applications in society, and how scientific ideas can and should be evaluated when it comes to social policy or person beliefs.

A “science in a social context” approach to science teaching may also address the common student question, “When will I ever use this?” All too often, scientific content in schools is presented in ways that are abstract, decontextualized, and can feel irrelevant to students. Such an approach can leave a student unable or unwilling to engage in meaningful and substantive discussions on the applications and limitations of science in society. The entire concept of including cost-benefit analyses when considering the role of science in shaping decisions is often over-looked, as if scientific conclusions are black and white. Furthermore, the current culture of science in classrooms leaves little room for students to assess how scientific information does and does not align with their cultural identities, often framing science as inherently conflicting or alien, forcing a choice between one way of seeing the world over the other, when a creative synthesis seems more reasonable. Shifting science education paradigms toward a strategy that promotes “education through science” (as opposed to “science through education”) recognizes student needs and motivations as critical to learning, and opens up channels for introducing science as something that is relevant and enriching to their lives. Centered on the German philosophy of Allgemeinbildung [link] that describes “the competence for participation in critical dialogue on currently important matters,” this approach has been found to be effective in motivating students to develop the necessary skills to implement empirical evidence when forming arguments and making decisions.

In extending the idea of the perceived value of science in sociopolitical debates, students can build important frameworks for effectively engaging with society in the future. A relevant example is the increasing accessibility of genome editing technology, which represents an area of science poised to deeply impact the future of society. In a recent report [link] on the ethics of genome editing, assembled by an panel of clinicians and scientists (experts), it is recommended that the United States should proceed — cautiously — with genome editing studies on human embryos. However, as pointed out [link], this panel failed to include ANY public participation in this decision. This effort, fundamentally ignores “a more conscious evaluation of how this impacts social standing, stigma and identity, ethics that scientists often tend to cite pro forma and then swiftly scuttle.” As this discussion increasingly shifts into the mainstream, it will be essential to engage with the public in ways that promote a more careful and thoughtful analysis of scientific issues [link], as opposed to hyperbolic fear mongering (as seen in regard to most GMO discussions)[link] or reserving genetic engineering to the hyper-affluent. Another, more timely example, involves the the level at which an individual’s genome be used to predict a future outcome or set of outcomes, and whether this information can be used by employers in any capacity [link]. By incorporating a clear description of how science is practiced (including the factors that influence what is studied, and what is done with the knowledge generated), alongside the transfer of traditional scientific knowledge, we can help provide future citizens with tools for critical evaluation as they navigate these uncharted waters.

It is also worth noting tcorrupted sciencehat the presentation of science in a sociopolitical contexts can emphasize learning of more than just science. Current approaches to education tend to compartmentalize academic subjects, framing them as standalone lessons and philosophies. Students go through the school day motions, attending English class, then biology, then social studies, then trigonometry, etc., and the natural connections among subject areas are often lost. When framing scientific topics in the context of sociopolitical discussions and debates, stu
dents have more opportunities to explore aspects of society that are, at face value, unrelated to science.

Drawing from lessons commonly taught in American History class, the Manhattan Project [link] offers an excellent opportunity to discuss the fundamentals of nuclear chemistry as well as sociopolitical implications of a scientific discovery. At face value, harnessing nuclear fission marked a dramatic milestone for science. However, when this technology was pursued by the United States government during World War II — at the urging of the famed physicist Albert Einstein and others — it opened up the possibility of an entirely new category of warfare, impacting individuals and communities at all levels. The reactions set off by the Manhattan Project, and the consequent 1945 bombing of Hiroshima and Nagasaki, are ones that are still felt in international power politics, agriculture, medicine, ecology, economics, research ethics, transparency in government, and, of course, the Presidency of the United States. The Manhattan Project represents an excellent case study on the relationship between science, technology, and society, as well as the project’s ongoing influence on these relationships. The double-edged nature often associated with scientific discoveries are important considerations of the scientific enterprise, and should be taught to students accordingly.

A more meaningful approach to science education requires including the social aspects of the scientific enterprise. When considering a heliocentric view of the solar system, it is worthwhile recognizing its social impacts as well as its scientific foundations (particularly before Kepler). If we want people to see science as a human enterprise that can inspire rather than dictate decisions and behaviors, it will require resifting how science — and scientists — are viewed in the public eye. As written here [link]. we need to restore the relationship between scientific knowledge and social goals by specifically recognizing how

'So... cutting my funding, eh? Well, I've got a pair of mutant fists that say otherwise!'
‘So… cutting my funding, eh? Well, I’ve got a pair of mutant fists that say otherwise!’

science can be used, inappropriately, to drive public opinion. As an example, in the context of CO2-driven global warming, one could (with equal scientific validity) seek to reduce CO2 generation or increase CO2 sequestration. Science does not tell us which is better from a human perspective (although it could tell us which is likely to be easier, technically). While science should inform relevant policy, we must also acknowledge the limits of science and how it fits into many human contexts. There is clearly a need for scientists to increase participation in public discourse, and explicitly consider the uncertainties and risks (social, economic, political) associated with scientific observations. Additionally, scientists need to recognize the limits of their own expertise.

A pertinent example was the call by Paul Ehrlich to limit, in various draconian ways, human reproduction – a political call well beyond his expertise. In fact, recognizing when someone has gone beyond what science can legitimately tell us [link] could help rebuild respect for the value of science-based evidence. Scientists and science educators need to be cognizant of these limits, and genuinely listen to the valid concerns and hesitations held by many in society, rather than dismiss them. The application of science has been, and will always be, a sociopolitical issue, and the more we can do to prepare future decision makers, the better society will be.

Jeanne Garbarino, PhD, Director of Science Outreach, The Rockefeller University, NY, NY

Jeanne earned herJGarbarino Ph.D. in metabolic biology from Columbia University, followed by a postdoc in the Laboratory of Biochemical Genetics and Metabolism at The Rockefeller University, where she now serves as Director of Science Outreach. In this role, she works to provide K-12 communities with equitable access to authentic biomedical research opportunities and resources. You can find Jeanne on social media under the handle @JeanneGarb.

Power Posing & Science Education

Developing a coherent understanding of a scientific idea is neither trivial nor easy and it is counter-productive to pretend that it is.

For some time now the idea of “active learning” (as if there is any other kind) has become a mantra in the science education community (see Active Learning Day in America: link). Yet the situation is demonstrably more complex, and depends upon what exactly is to be learned, something rarely stated explicitly in many published papers on active learning (an exception can be found here with respect to understanding evolutionary mechanisms : link).  The best of such work generally relies on results from multiple-choice “concept tests” that  provide, at best, a limited (low resolution) characterization of what students know. Moreover it is clear that, much like in other areas, research into the impact of active learning strategies is rarely reproduced (see: link, link & link).

As is clear from the level of aberrant and non-sensical talk about the implications of “science” currently on display in both public and private spheres (link : link), the task of effective science education and rigorous scientific (data-based) decision making is not a simple one.  As noted by many there is little about modern science that is intuitively obvious and most is deeply counterintuitive or actively disconcerting (see link).  In the absence of a firm religious or philosophical perspective, scientific conclusions about the size and age of the Universe, the various processes driving evolution, and the often grotesque outcomes they can produce can be deeply troubling; one can easily embrace a solipsistic, ego-centric and/or fatalistic belief/behavioral system.

There are two videos of Richard Feynman that capture much of what is involved in, and required for understanding a scientific idea and its implications. The first involves the basis scientific process, where the path to a scientific understanding of a phenomena begins with a guess, but these are a special kind of guess, namely a guess that implies unambiguous (and often quantitative) predictions of what future (or retrospective) observations will reveal (video: link).  This scientific discipline (link) implies the willingness to accept that scientifically-meaningful ideas need to have explicit, definable, and observable implications, while those that do not are non-scientific and need to be discarded. As witness the stubborn adherence to demonstrably untrue ideas (such as where past Presidents were born or how many people attended an event or voted legally), which mark superstitious and non-scientific worldviews.  Embracing a scientific perspective is not easy, nor is letting go of a favorite idea (or prejudice).  The difficulty of thinking and acting scientifically needs to be kept in the mind of instructors; it is one of the reasons that peer review continues to be important – it reminds us that we are part of a community committed to the rules of scientific inquiry and its empirical foundations and that we are accountable to that community.

The second Feynman video (video : link) captures his description of what it means to understand a particular phenomenon scientifically, in this particular case, why magnets attract one another.  The take home message is that many (perhaps most) scientific ideas require a substantial amount of well-understood background information before one can even begin a scientifically meaningful consideration of the topic. Yet all too often such background information is not considered by those who develop (and deliver) courses and curricula. To use an example from my own work (in collaboration with Melanie Cooper @MSU), it is very rare to find course and curricular materials (textbooks and such) that explicitly recognize (or illustrate) the underlying assumptions involved in a scientific explanation.  Often the “central dogma” of molecular biology is taught as if it were simply a description of molecular processes, rather than explicitly recognizing that information flows from DNA outward (link)(and into DNA through mutation and selection).  Similarly it is rare to see stated explicitly that random collisions with other molecules supply the energy needed for chemical reactions to proceed or to break intermolecular interactions, or that the energy released upon complex formation is transferred to other molecules in the system (see : link), even though these events control essentially all aspects of the systems active in organisms, from gene expression to consciousness.

The basic conclusion is that achieving a working understanding of a scientific ideas is hard, and that, while it requires an engaging and challenging teacher and a supportive and interactive community, it is also critical that students be presented with conceptually coherent content that acknowledges and presents all of the ideas needed to actually understand the concepts and observations upon which a scientific understanding is based (see “now for the hard part” :  link).  Bottom line, there is no simple or painless path to understanding science – it involves a serious commitment on the part of the course designer as well as the student, the instructor, and the institution (see : link).

This brings us back to the popularity of the “active learning” movement, which all too often ignores course content and the establishment of meaningful learning outcomes.  Why then has it attracted such attention?  My own guess it that is provides a simple solution that circumvents the need for instructors (and course designers) to significantly modify the materials that they present to students.  The current system rarely rewards or provides incentives for faculty to carefully consider the content that they are presenting to students, asking whether it is relevant or sufficient for students’ to achieve a working understanding of the subject presented, an understanding that enables the student to accurately interpret and then generate reasoned and evidence-based (plausible) responses.

Such a reflective reconsideration of a topic will often result in dramatic changes in course (and curricular) emphasis; traditional materials may be omitted or relegated to more specialized courses.  Such changes can provoke a negative response from other faculty, based of often inherited (an uncritically accepted) ideas about course “coverage”, as opposed to desired and realistic student learning outcomes.  Given the resistance of science faculty (particularly at institutions devoted to scientific research) to investing time in educational projects (often a reasonable strategy, given institutional reward systems), there is a seductive lure to easy fixes. One such fix is to leave the content unaltered and to “adopt a pose” in the classroom.

All of which brings me to the main problem – the frequency with which superficial (low cost, but often ineffectual) strategies can act to inhibit and distract from significant, but difficult reforms.  One cannot help but be reminded of other quick fixes for complex problems.  The most recent being the idea, promulgated by Amy Cuddy (Harvard: link) and others, that adopting a “power pose” can overcome various forms of experienced- and socioeconomic-based prejudices and injustices, as if over-coming a person’sexperiences and situation is simply a matter of will. The message is that those who do not succeed have only themselves to blame, because the way to succeed is (basically) so damn simple.  So imagine one’s surprise (or not) when one discovers that the underlying biological claims associated with “power posing” are not true (or at least cannot be replicated, even by the co-authors of the original work (see Power Poser: When big ideas go bad: link).  Seems as if the lesson that needs to be learned, both in science education and more generally, is that claims that seem too easy or universal are unlikely to be true.  It is worth remembering that even the most effective modern (and traditional) medicines, all have potentially dangerous side effects. Why, because they lead to significant changes to the system and such modifications can discomfort the comfortable. This stands in stark contrast to non-scientific approaches; homeopathic “remedies” come to mind, which rely on placebo effects (which is not to say that taking ineffective remedies does not itself  involve risks.)

As in the case of effective medical treatments, the development and delivery of engaging and meaningful science education reform often requires challenging current assumptions and strategies that are often based in outdated traditions, and are influenced more by the constraints of class size and the logistics of testing than they are by the importance of achieving demonstrable enhancements of students’ working understanding of complex ideas.

In an age of rampant narcissism and social cheating – the importance of teaching social evolutionary mechanisms.

As socioeconomic inequality grows,  the publicly acknowledged importance of traits such as honesty, loyalty, self-sacrifice, and reciprocity appears to have fallen out of favor with some of our socio-economic and political elites. How many people condeHutton quotemn a person as dishonest one day and embrace them the next? Dishonesty and selfishness no longer appear to be taboo, or a source of shame that needs to be expurgated (perhaps my Roman Catholic upbringing is bubbling to the surface here).  A disavowal of shame and guilt and the lack of serious social censure appears to be on the rise, particularly within the excessively wealthy and privileged, as if the society from which they extracted their wealth and fame does not deserve their active participation and support [link: Hutton, 2009].  They have embraced a “winning takes all” strategy.

birds in a flockIf an understanding of evolutionary mechanisms is weak within the general population [link], the situation is likely to be much worse when it comes to an understanding of the role and outcomes of social evolutionary mechanisms. Yet, the evolutionary origins of social systems, and the mechanisms by which such systems are maintained against the effects of what are known as “social cheaters”, are critical to understanding and defending, human social behaviors  such as honesty, cooperation, loyalty, self-sacrifice, self-restraint, mutual respect, responsibility and kindness.

While evolutionary processes are often caricatured as favoring selfish behaviors, the facts tell a more complex, organism-specific story [link: Aktipis 2016]. Cooperation between organisms underlies a wide range of behaviors, from sexual reproduction and the formation of multicellular organisms (animals, plants, and people) to social systems, ranging from microbial films to bee colonies and construction companies [see Bourke, 2011: Principles of Social Evolution] [Wikipedia link].

One of the best studied of social systems involves the cellular slime mold Dictyostelium discoideum [Wikipedia link].  When life is good, that is when the world is moist and bacteria, the food of these organisms, are plentiful, D. discoideum live and reproduce happily as single celled amoeba-like individuals in soil.  Given their small size (~5 μm diameter), they cannot travel far, but that does not matter as long as their environment is hospitable.  When the environment turns hostile, however, an important survival strategy is to migrate to a new location – but what is a little guy to do?  The answer in this species is to cooperate.  Individual amoeba begin to secrete a chemical that acts to attract others; eventually thousands of individuals aggregate to form a multicellular “slug”; slugs migrate around to 1066px-Dicty_Life_Cycle_H01.svgfind a hospitable place and then differentiate into a fruiting body that stands ~1mm (20x the size of an individual amoeba) above the ground.  To form the stalk that lifts the “fruiting body” into the air, a subset of cells (once independent individuals) change shape. These stalk cells die, while the rest of the cells form the fruiting body, which consists of spores – cells specialized to survive dehydration.  Spores are released into the air where they float and are dispersed over a wide range.  Those spores that land in a happy place (moist and verdant), revert to the amoeboid life style, eat, grow, divide and generate a new (clonal) population of amoeboid cells: they have escaped from a hostile environment to inhabit a new world, a migration made possible by the sacrifice of the cells that became the stalk (and died in the process).  Similar types of behavior occur in a wide range of macroscopic organisms [Scrambling to the top: link].  Normally, who becomes a stalk cell and who becomes a spore is a stochastic process [see previous PLoS blog post on stochastics and biology education].

Cheaters in the slime mold system are individuals who take part in the aggregation process (they respond to the migration signal and become part of the slug), but have altered their behavior to avoid becoming a stalk cell – no self-sacrifice for them. Instead they become spores.  In the short run, such a strategy can be beneficial to the individual, after all it has a better chance of survival if it can escape a hostile environment.  But imagine a population made up only of cheaters – no self-sacrifice, no stalk, no survival advantage = death [see link: Strassmann & Queller, 2009].

A classic example of social cheating with immediate relevance to the human situation is cancer.  Within a sexually reproducing multicellular organism, reproduction is strictly restricted to the cells of the germ line – eggs and sperm.  The other cells of the organism, known collectively as somatic cells, have ceded their reproductive rights to the organism as a whole.  While somatic cells can divide, they divide in a controlled and strictly regulated (unselfish) way.  Somatic cells do not survive the death of the organism – only germ line cells (sperm and eggs) are able to produce a new organism.  In the end cellular cooperation has been a productive strategy, as witness the number of different types of multicellular organisms, including humans.  If a somatic cell breaks the social contract and cheats, that is, begins to divide (asexually) in an independent manner, it can lead to the formation of a  tumor and later, if the cells of the tumor start to migrate within the organism, to metastatic cancer.  More rarely (apparently) such cells can migrate between organisms, as in the case of transmissible cancers in dogs, Tasmanian Devils, and clams [see links: Murchison 2009 and Ujvari et al 2016).  The growth and evolution of the tumor cell leads to the death of the organism and the cancer cells’ own extinction, another example of the myopic nature of evolutionary processes.

In the case of cancer the organism’s defenses against social cheaters comes in two forms, intrinsic to the individual cheater cells, in the form of cell suicide (known through a number of technical terms including apoptosis, anoikis and necroptosis)[link: Su et al., 2015] and extrinsic and organismic processes, such as the ability of the organism’s immune system to identify and kill cancer cells – a phenomena with therapeutically relevant implications [link: Ledford, 2014].  We can think of these two processes as guilt + shame (leading to cellular suicide) and policing + punishment (leading to immune system killing).  For a cell to escape growth control and to evolve to produce metastatic disease, it needs to inactivate or ignore intrinsic cell death systems and to evade the immune system.

To consider another example, social systems are based on cooperation, often involving the sharing of resources with those in need.  A recent example is the sharing of food (blood) between vampire bats [see link: Carter & Wilkinson, 2013].  The rules, as noted by Aktipis, are simple, 1) ask only when in need and 2) give when asked and able.  In this context, we can identify two types of social cheaters – those who ask when they do not need and those you fail to give when asked and able.  People who refuse to work even when they can and when jobs are available fall into the first group, the rich who avoid taxes and fail to donate significant funds to charities the other.  It is an interesting question of how to characterize those who borrow money and fail to repay it.  Bankruptcy laws that protect the wealth of the borrower while leading to losses to the lender might be seen as acting to undermine the social contract (clearly philosophers’ and economists’ comments here would be relevant).

Given that social systems at all levels are based on potentially costly traits, such as honesty, loyalty, self-sacrifice, and reciprocity, the evolutionary origins of social systems must lie in their ability to increase reproductive success, either directly or through effects on relatives, a phenomena known as inclusive fitness [Wikipedia link]. Evolutionary processes also render social systems vulnerable to cheating and so have driven the development of a range of defenses against various forms of social cheaters (see above).  But recent political and cultural events appear to be acting to erode and/or ignore society’s defenses.

So what to do?  Revolution? From a PLoS Science education perspective, one strategy suggests itself:  to encourage (require) that students and the broader public be introduced to effective instruction on social evolutionary mechanisms, the traits they can generate (various forms of altruism and cooperation), the reality and pernicious effects of social cheaters, and the importance of defenses against them.  In this light, it appears that social evolutionary processes are missing from the Next Generation Science Standards [NGSS link]. Understanding the biology, together with effective courses in civics [see link: Teaching Civics in the Year of The Donald] might serve to bolster the defense of civil society.

December 22, 2016, minor update 23 October 2020 – Mike Klymkowsky

Featured image is used with permission from Matthew Lutz (Princeton University).

Army ants’ ‘living’ bridges span collective intelligence, ‘swarm’ robotics (PNAS)

The pernicious effects of disrespecting the constraints of science

By Mike Klymkowsky

Recent political events and the proliferation of “fake news” and the apparent futility of fact checking in the public domain have led me to obsess about the role played by the public presentation of science. “Truth” can often trump reality, or perhaps better put, passionately held beliefs can overwhelm a circumspect worldview based on a critical and dispassionate analysis of empirically established facts and theories. Those driven by various apocalyptic visions of the world, whether religious or political, can easily overlook or corrupted sciencetrivialize evidence that contradicts their assumptions and conclusions. While historically there have been periods during which non-empirical presumptions are called into question, more often than not such periods have been short-lived. Some may claim that the search for absolute truth, truths significant enough to sacrifice the lives of others for, is restricted to the religious, they are sadly mistaken – political, often explicitly anti-religious  movements are also susceptible, often with horrific consequences, think Nazism and communist-inspired apocalyptic purges. The history of eugenics and forced sterilization based on flawed genetic and ideological premises have similar roots.

Given the seductive nature of belief-based “Truth”, many turned to science as a bulwark against wishful and arational thinking. The evolving social and empirical (data-based) nature of the scientific enterprise, beginning with guesses as to how the world (or rather some small part of the world) works, then following the guess’s logical implications together with the process of testing those implications through experiment or observation, leading to the revision (or abandonment) of the original guess, moving it toward hypothesis and then, as it becomes more explanatory and accurately predictive, and as those predictions are confirmed, into a theory.  So science is a dance between speculation and observation. In contrast to a free form dance, the dance of science is controlled by a number of rigid, and oppressive to some, constraints [see Feynman &  Rothman 2020. How does Science Really work].

Perhaps surprisingly, this scientific enterprise has converged onto a small set of over-arching theories and universal laws that appear to explain much of what is observable, these include the theory of general relativity, quantum and atomic theory, the laws of thermodynamics, and the theory of evolution. With the noticeable exception of relativity and quantum mechanics, these conceptual frameworks appear to be compatible with one another. As an example, organisms, and behaviors such as consciousness, obey and are constrained by, well established and (apparently) universal physical and chemical rules.

endosymbiosis-1.fwA central constraint on scientific thinking is that what cannot in theory be known is not a suitable topic for scientific discussion. This leaves outside of the scope of science a number of interesting topics, ranging from what came before the “Big Bang” to the exact steps in the origin of life. In the latter case, the apparently inescapable conclusion that all terrestrial organisms share a complex “Last Universal Common Ancestor” (LUCA) makes theoretically unconfirmable speculations about pre-LUCA living systems outside of science.  While we can generate evidence that the various building blocks of life can be produced abiogenically (a process begun with Wohler’s synthesis of urea) we can only speculate as to the systems that preceded LUCA.

Various pressures have led many who claim to speak scientifically (or to speak for science) to ignore the rules of the scientific enterprise – they often act as if their are no constraints, no boundaries to scientific speculation. Consider the implications of establishing “astrobiology” programs based on speculation (rather than observations) presented with various levels of certainty as to the ubiquity of life outside of Earth [the speculations of Francis Crick and Leslie Orgel on “directed panspermia”: and the psuedoscientific Drake equation come to mind, see Michael Crichton’s famous essay on Aliens and global warming]. Yet such public science pronouncements appear to ignore (or dismiss) the fact that we know, and can study, only one type of life (at the moment), the descendants of LUCA. They appear untroubled when breaking the rules and abandoning the discipline that has made science a powerful, but strictly constrained human activity.

Whether life is unique to Earth or not requires future explorations and discoveries that may (or given the technological hurdles involved, may not) occur. Similarly postulating theoretically unobservable alternative universes or the presence of some form of consciousness in inanimate objects [an unscientific speculation illustrated here] crosses a dividing line between belief for belief’s sake, and the scientific – it distorts and obscures the rules of the game, the rules that make the game worth playing [again, the Crichton article cited above makes this point]. A recent rather dramatic proposal from some in the physical-philosophical complex has been the claim that the rules of prediction and empirical confirmation (or rejection) are no longer valid – that we can abandon requiring scientific ideas to make observable predictions [see Ellis & Silk]. It is as if objective reality is no longer the benchmark against which scientific claims are made; that perhaps mathematical elegance (see Sabine Hossenfelder’s Losts in Math) or spiritual comfort are more important – and well they might be (more important) but they are outside of the limited domain of science. At the 2015 “Why Trust a Theory” meeting, the physicist Carlo Rovelli concluded “by pointing out that claiming that a theory is valid even though no experiment has confirmed it destroys the confidence that society has in science, and it also misleads young scientists into embracing sterile research programs.” [quote from Massimo’s Pigliucci’s Footnotes to Plato blog].

While the examples above are relatively egregious, it is worth noting that various pressures for glory, fame, and funding can to impact science more frequently – leading to claims that are less obviously non-scientific, but that bend (and often break) the scientific charter. Take, for example, claims about animal models of human diseases. Often the expediencies associated with research make the use of such animal models necessary and productive, but they remain a scientific compromise. While mice, rats, chimpanzees, and humans are related evolutionarily, they also carry distinct traits associated with each lineage’s evolutionary history, and the associated adaptive and non-adaptive processes and events associated with that history. A story from a few years back illustrates how the differences between the immune systems of mice and humans help explain why the search, in mice, for drugs to treat sepsis in humans was so relatively unsuccessful [Mice Fall Short as Test Subjects for Some of Humans’ Deadly Ills]. A similar type of situation occurs when studies in the mouse fail to explicitly acknowledge how genetic background influences experimental phenotypes [Effect of the genetic background on the phenotype of mouse mutations], as well as how details of experimental scenarios influence human relevance [Can Animal Models of Disease Reliably Inform Human Studies?].

Speculations that go beyond science (while hiding under the aegis of science – see any of a number of articles on quantum consciousness) – may seem just plain silly, but by abandoning the rules of science they erode the status of the scientific process.  How, exactly, would one distinguish a conscious from an unconscious electron?

In science (again as pointed out by Crichton) we do not agree through consensus but through data and respect for critical analyzed empirical observations. The laws of thermodynamics, general relativity, the standard model of particle physics, and evolution theory are conceptual frameworks that we are forced (if we are scientifically honest) to accept. Moreover the implications of these scientific frameworks can be annoying to some; there is no possibility of a “zero waste” process that involves physical objects, no free lunch (perpetual motion machine), no efficient, intelligently-designed evolutionary process (just blind variation and differential reproduction), and no zipping around the galaxy. The apparent limitation of motion to the speed of light means that a “Star Wars” universe is impossible – happily, I would argue, given the number of genocidal events that appear to be associated with that fictional vision – just too many storm troopers for my taste.

Whether our models for the behavior of Earth’s climate or the human brain can be completely accurate (deterministic), given the roles of chaotic and stochastic events in these systems, remains to be demonstrated; until they are, there is plenty of room for conflicting interpretations and prescriptions. That atmospheric levels of greenhouse gases are increasing due to human activities is unarguable, what it implies for future climate is less clear, and what to do about it (a social, political, and economic discussion informed but not determined by scientific observations) is another.

As we discuss science, we must teach (and continually remind ourselves, even if we are working scientific practitioners) about the limits of the scientific enterprise. As science educators, one of our goals needs to be to help students develop an appreciation of the importance of an honest and critical attitude to observations and conclusions, a recognition of the limits of scientific pronouncements. We need to explicitly identify, acknowledge, and respect the constraints under which effective science works and be honest in labeling when we have left scientific statements, lest we begin to walk down the path of little lies that morph into larger ones.  In contrast to politicians and other forms of religious and secular mystics, we should know better than to be seduced into abandoning scientific discipline, and all that that entails.

Minor update + figures reintroduced 20 October 2020

M.W. Klymkowsky  web site:  http://klymkowskylab.colorado.edu

Biology education in the light of single cell/molecule studies

By Mike Klymkowsky

from Stochastic Gene Expression in a Single Cell by Michael B. Elowitz, Arnold J. Levine, Eric D. Siggia & Peter S. Swain

Stochastic processes are often presented in terms of random, that is unpredictable, events.  This framing obscures the reality that stochastic processes, while more or less unpredictable at the level of individual events, are well behaved at the population level.  It also obscures the role of stochastic processes in a wide range of predictable phenomena; in atomic systems, for example, unknown factors determine the timing of the radioactive decay of a particular unstable atom, at the same time the rate of radioactive decay is highly predictable in a large enough population. Similarly, in the classical double-slit experiment the passage of a single photon, electron, or C60 molecule is unpredictable while the behavior of a larger population is perfectly predictable. The macroscopic predictability of the Brownian motion (a stochastic process) enabled Einstein to argue for the reality of atoms.  Similarly, the dissociation of a molecular complex or the occurrence of a chemical reaction, driven as they are by thermal collisions, are stochastic processes, whereas dissociation constants and reaction rates are predictable. In fact this type of unpredictability at the individual level and predictability at the population level is the hallmark of stochastic, as compared to truly random, that is, unpredictable behaviors.

stochastic wordle

Single cell and single molecule studies increasingly provide mechanistic insights into a range of biological processes, from evolutionary to cognitive and pathogenic mechanisms. The effects of stochastic events are complicated by the developing and adaptive

FIG.1  A schematic of the mutational origin of antibiotic resistance over time (and space) from McNally & Brown, 2016).

nature of biological systems and appears to be influenced by the genetic background. In some cases, homeostatic (feedback) mechanisms return the system to its original state.  In others, the stochastic expression (or mutation) of a particular gene (or set of genes) leads to a cascade of downstream effects that change the system, such that subsequent events become more or less probable, a process nicely illustrated in recent real time studies of the evolution of antibiotic resistance in bacteria (←FIG & a seriously cool video). The stochastic (molecular clock) nature of an organism’s intrinsic mutation rate has recently been used with the EXAC system to visualize the impact of selective and non-adaptive effects on human genes.

Pedagogical studies:  The “Framework for K12 science education”  ignores stochastic processes altogether, while the Vision and Change in Undergraduate Biology Education” document contains a single point that calls for “incorporating stochasticity into biological models” (p. 17), but omits details of what this means in practice. People (even scholars) often have a difficult time developing an accurate understanding of stochastic processes (see “Understanding Randomness and its Impact on Student Learning” and “Fooled by Randomness“.  The failure to appreciate the ubiquity of stochastic processes in biological system has been an obstacle to the acceptance of Darwinian evolution. In this light, it seems well past time to rethink the foundational roles of stochastic processes in biological (as well as chemical and physical) systems and how best to introduce such processes to students through coherent course narratives and supporting materials.

A number of studies indicate that students call upon deterministic models to explain a range of stochastic processes. The fact that all too often students are introduced to the behaviors of cellular and molecular level biological systems through depictions that are overtly deterministic does not help the situation. In the majority of instructional videos, for example, molecules appear to know were they are heading and move there with a purpose. Similarly the folding of polypeptides is often depicted as a deterministic process[1] although the proliferation of model-based simulations offers a more realistic depiction (see below).  That said the widespread involvement of chaperones is rarely acknowledged. Macromolecules are commonly depicted as rigid rather than as dynamic. The thermally driven opening and closing of the DNA double-helix (a consequence of the weakness of intermolecular interactions) is rarely illustrated.  Molecules recognize one another and (apparently) stay locked in their mutual embrace forever; the role of thermal collisions in driving molecular dissociation (and binding specificity) is rarely considered in most textbooks, and presumably, in the classes that use these books. Moreover, the factors involved in inter-molecular interactions are often poorly understood, even after the completion of conventional university level chemistry courses. The energetic factors that determine enzyme specificity and reaction rates and the binding of transcription factors to their target DNA sequences, as well as the effects of mutations on these and other processes, often go uncommented on. It is not at all clear whether students appreciate that thermal collisions are responsible for the reversal of molecular interactions or that they supply a reaction’s activation energy. Cells with the same genotype are implicitly expected to behave in identical ways (display the same phenotypes), a situation at odds with direct observation (see “Stochastic Gene Expression in a Single Cell” and “What’s Luck Got to Do with It: Single Cells, Multiple Fates, and Biological Non-determinism” and the general processes involved in cellular differentiation and social behaviors. Phenotypic penetrance and expressivity also involve stochastic behaviors, together with genetic background effects. It certainly does not help when instructors introduce a stochastic process, such as genetic drift, in the context of the Hardy-Weinberg model, a situation in which genetic drift does not occur. Such presentations are likely to increase student confusion.

FIG. 2 A comparison between the expression of lacZ as measured in a bulk population and in individual cells (adapted from Vilar et al., 2003).

It is our impression that the typical instructional approach is to present molecular level processes in terms of large populations of molecules that behave in a deterministic manner. Consider the bacteria Escherichia coli’s lac operon, a group of genes that has been a workhorse in modern molecular biology and a common context through which to present the regulation of gene expression. Expression of the lac operon results in the synthesis of two proteins (lactose permease and β-galactosidase) that enable lactose to enter the cell and convert lactose into the monosaccharides glucose and galactose (which can be metabolized futher) and allolactone, which binds to, and inhibits the binding of the lac repressor protein to DNA, allowing the expression of the lac operon. When the bulk behavior of a bacterial culture is analyzed, the expression of the lac operon increases as a smooth function over time (in the absence of other energy sources)(FIG. ↑). The result is that the expression of the proteins required for lactose metabolism is restricted to situations in which lactose is present.

The mechanistic quandary, rarely if ever considered explicitly as far as we can tell, is how the lac operon can “turn on” when the entry of lactose into the cell and the inactivation of the lac repressor both depend upon the operon’s expression?  The situation becomes clear only when we consider the behavior of individual cells; LacZ expression goes from off to fully on in a stochastic manner (FIG. 2↑).[2]  Given that there are ~5 to 10 lac repressor molecules and one to two copies of the lac operon per cell, the lac operon can be expressed when the operon is free of bound repressor.  If such a “noisy” event happens to occur when lactose is present in the media, expression of the lac operon allows lactose to enter the cell, the conversion of lactose into allolactone, the inactivation of the lac repressor, and stable expression of the lac operon. The stochastic behavior of the system enables individual cells to sample their environment and respond when useful metabolites are present while minimizing unnecessary metabolic expense (the synthesis of irrelevant polypeptides) when they are not. A similar logic is involved in the quorum sensing, the emission of light (via the luciferase system), the regulation of the DNA uptake system, the generation of persister phenotypes, and programmed cell death (to benefit genetically related neighbors).


What is a biology educator to do?
The question that faces the reflective educational designer and enlightened instructor is how should their course address the multiple roles of stochastic processes within biological systems?  I have a short set of recommendations that I think both designers and instructors might want to consider; many have been incorporated into ongoing efforts at course design, which I have only recently (2019) begun to think of as educational engineering. First, it should be explicitly recognized, and conveyed to students, that stochastic processes are difficult to understand, as witness the common belief in the Gambler’s fallacy and the “hot hand”. Students need to be given adequate time to work with, and appropriate feedback on the behavior of stochastic systems. Secondly, and rather obviously, instructors should illustrate and articulate the role of stochastic processes in range of biological systems, from phenotypic variation and evolutionary events, including the effects of mutations and various non-adaptive processes (such as genetic drift) to de novo gene formation, gene expression, drug-target interactions, and reaction kinetics. Finally, the stochastic behaviors of molecular (and cellular) level processes should be accurately and explicitly illustrated .[3] Among currently available examples there are those that illustrate the movement of a water molecule through a membrane either through an aquaporin molecule or on its own,[4] as well as a PhET applet that illustrates the Elowitz et al study on stochastic GFP-expression in E. coli (and allows for student manipulation of key regulatory parameters).[5]  A simulation of the nature of intermolecular interactions and the role of molecular collisions in their formation has been developed for use with the CLUE Chemistry curriculum.[6]

FIG.3 Students are asked to predict the trajectory of a cannon ball (A) or a molecule (B); few students recognize the transition from projectile to Brownian motion (adapted from Klymkowsky et al., 2016).

Students’ understanding of stochastic processes can be revealed to instructors (and their students) through the use of various targeted assessment tools (such as the Biology Concepts Instrument or BCI, the Genetic Drift Instrument, and diagnostic assessments of student thinking about stochastic processes). For example, students can be asked to draw a graph that reflects the movement of a macroscopic projectile FIG. 3A→) versus a molecular (microscopic) object (FIG.3B→); such a task can reveal whether students can make the transition from the well behaved (deterministic) to the stochastic.  Drawing (and explanation) has been used extensively in the analysis of student understanding with the context of the CLUE project (“lost in lewis structures“, “noncovalent interactions“, and “relationships between molecular structure and properties“).  In a similar vein, network dynamics, including the cascade effects driving cell level divergence and the feedback and regulatory interactions involved in limiting the effects of noise and generating various outcomes (cellular differentiation) can be presented to students (see “Network motifs: simple building blocks of complex networks“, “Using graph-based assessments within socratic tutorials” and “Noise facilitates transcriptional control under dynamic inputs“).  One can consider the role of stochastic events within social systems, including responses to various aberrant behaviors (social cheating, cancer) and in terms of social feedback mechanisms (apoptosis, positive and negative feedback, lateral inhibition of cell differentiation) and in the context of the decisions involved in stem cells division,  differentiation, and cancer formation.  By introducing students to the roles and implications of stochastic processes in biological systems, we can help them develop a coherent understanding of the predictable, but not completely deterministic, nature of such systems.

Some minor edits: 5 May 2019 and 2 October 2020 – figures re-inserted 20 June 2020

[1] Scientific animation: protein production and folding

[2] Lac repressor numbers

[3] See this recording of stem cells

[4] Aquaporin and a lipid membrane

[5] PhET gene expression basics  – see panel 3

[6] http://virtuallaboratory.colorado.edu/LDF+binding-interactions/1.2-interactions-0.html