How to make a funny-looking mouse

I’m going to tell you about a paper that was brought to my attention by some poor science journalism, so first I have to complain about the article in the Guardian. Bear with me.

This is dreadfully misleading.

Though everybody’s face is unique, the actual differences are relatively subtle. What distinguishes us is the exact size and position of things like the nose, forehead or lips. Scientists know that our DNA contains instructions on how to build our faces, but until now they have not known exactly how it accomplishes this.

Nope, we still don’t know. What he’s discussing is a paper that demonstrates that certain regulatory elements subtly influence the morphology of the face; it’s an initial step towards recognizing some of the components of the genome that contribute towards facial architecture, but no, we don’t know how DNA defines our morphology.

But this is disgraceful:

Visel’s team was particularly interested in the portion of the genome that does not encode for proteins – until recently nicknamed “junk” DNA – but which comprises around 98% of our genomes. In experiments using embryonic tissue from mice, where the structures that make up the face are in active development, Visel’s team identified more than 4,300 regions of the genome that regulate the behaviour of the specific genes that code for facial features.

These “transcriptional enhancers” tweak the function of hundreds of genes involved in building a face. Some of them switch genes on or off in different parts of the face, others work together to create, for example, the different proportions of a skull, the length of the nose or how much bone there is around the eyes.

NO! Bad journalist, bad, bad. Go sit in a corner and read some Koonin until you’ve figured this out.

Junk DNA is not defined as the part of the genome that does not encode for proteins. There is more regulatory, functional sequence in the genome that is non-coding than there is coding DNA, and that has never been called junk DNA. Look at the terminology used: “transcriptional enhancers”. That is a label for certain kinds of known regulatory elements, and discovering that there are sequences that modulate the expression of coding genes is not new, not interesting, and certainly does not remove anything from the category of junk DNA.

Alok Jha, hang your head in shame. You’re going to be favorably cited by the creationists soon.

But that said, the paper itself is very interesting. I should mention that nowhere in the text does it say anything about junk DNA — I suspect that the authors actually know what that is, unlike Jha.

What they did was use ChIP-seq, a technique for identifying regions of DNA that are bound by transcription factors, to identify areas of the genome that are actively bound by a protein called the P300 coactivator — which is known to be expressed in the developing facial region of the mouse. What they found is over 4000 scattered spots in the DNA that are recognized by a transcription factor. A smaller subset of these 4000 were analyzed for their sequential pattern of activation, and three of these potential modulators of face shape were selected for knock out experiments, in which the enhancer was completely deleted.

The genes these enhancers modulate were known to be important for facial development — knocking them out creates gross deformities of the head and face. Modifying the enhancers only leaves the actual genes intact, so you wouldn’t expect as extreme an effect.

One way to think of it is that there are genes that specify how to make an ear, for instance. So when these genes are switched on, they initiate a developmental program that builds an ear. The enhancers, though, tweak it. They ask, “How big? How high? Round or pointy? Floppy or firm?” So when you go in and randomly change the enhancers, you’d expect you’d still get an ear, but it might be subtly shifted in shape or position from the unmodified mouse ear.

And that’s exactly what they saw. The mice carrying deletions had subtle variations in skull shape as a consequence. In the figures below, all those mouse skulls might initially look completely identical, because you aren’t used to making fine judgments about mousey appearance. Stare at ‘em a while, though, and you might begin to pick up on the small shifts in dimensions, shifts that are measurable and quantifiable and can be plotted in a chart.

Attanasio-face-enhancers-9

This is as expected — tweaking enhancers (which are not, I repeat, junk DNA) leads to slight variations in morphology — you get funny-looking mice, not monstrous-looking mice. Although I shouldn’t judge, maybe these particular shifts create the Brad Pitt of mousedom. That’s also why I say that implying that we now know exactly how DNA accomplishes its job of shaping the face is far from true: Attanasio and colleagues have identified a few genetic factors that have effects on craniofacial shaping, but not all, and most definitely they aren’t even close to working out all the potential interactions between different enhancers. You won’t be taking your zygotes down to the local DNA chop shop for prenatal genetic face sculpting for a long, long time yet, if ever.


Attanasio C, Nord AS, Zhu Y, Blow MJ, Li Z, Liberton DK, Morrison H, Plajzer-Frick I, Holt A, Hosseini R, Phouanenavong S, Akiyama JA, Shoukry M, Afzal V, Rubin EM, FitzPatrick DR, Ren B, Hallgrímsson B, Pennacchio LA, Visel A. (2013) Fine tuning of craniofacial morphology by distant-acting enhancers. Science 342(6157):1241006. doi: 10.1126/science.1241006.

Cloning brains with Science

While we’ve been waiting and waiting for the physicists to get their act together and deliver on Mr Fusion home energy sources and flying cars, the biologists have been making great progress on the kinds of things that turn biologists on. The latest development: growing tiny little human brains in a bucket. Only let’s not call them brains…they are cerebral organoids. Hugo Gernsback would be so proud.

Here’s the latest development. Start with embryonic human stem cells, or induced pluripotent stem cells (cells which you’ve reset to a kind of embryonic state by using a virus to transfect them with the genes OCT4, SOX2, KLF4 and MYC, which trigger a change to a pluripotent state). Culture them in a cocktail of chemicals like basic fibroblastic growth factor and retinoic acid, which induces the cells to become neurectoderm, a precursor tissue of the nervous system. Imbed these cells in a gelatinous capsule that gives them a framework on which to grow, and also prevents them from just sprawling out into an amorphous neurectodermal sheet. Let them grow in a spinning bioreactor which circulates nutrients around them, and watch. They begin to form structures resembling those of the embryonic human brain, all by themselves.

organoid_method

They show many of the properties of normal embryonic brains. Brains develop from the inside out; new neurons arise deep inside, and then migrate outwards along radial glia to the surface. These mini-brains show similar behavior, forming the beginnings of a laminar structure with roughly the same pattern of growth. They exhibit regional specification. We have a forebrain, midbrain, and hindbrain, for instance, and there are molecular markers for these areas; those molecular markers are selectively expressed in areas of the mini-brains, too. During development, our neurons exhibit fleeting electrical activity, especially the production of calcium action potentials (we gradually switch to sodium action potentials as the nervous system matures). These brains have bursts of calcium activity which can be diminished with tetrodotoxin, a nerve poison that affects signal transmission in neurons.

organoid

Awesome. Before you start imagining growing complete adult human brains in a vat to the point where they start doing philosophy, though, there are realistic limitations.

While there are regions expressing markers for typical human brain regions, they aren’t well organized — I looked at the sections of cerebral organoids, and while bits and pieces looked familiar, they weren’t in their canonical relationships to one another. It’s a kind of scrambled brain.

The laminar structure of the brain doesn’t fully form — it’s just the rough beginnings. It really is like a very early embryonic brain, and is not going to function to generate thoughts and perceptions.

It’s only brain tissue. They aren’t growing elements of the circulatory system, for instance, so there are no blood vessels delivering nutrients. That limits growth, and the largest cerebral organoids are only about 4mm in diameter. That might only be enough to generate an assistant professor of philosophy. (I joke! Don’t come after me, philosophy fans.)

Now this is pretty darned cool, and would be a shoo-in to win first prize at the Mad Science Fair, but you might be wondering what you can use it for. These are not functional brains, so no, you militarists, you can’t use them to control cruise missiles. What they are good for is studying developmental processes that build human brains (pure science!) and for figuring out the mechanistic causes of serious brain disorders (medical science!).

And the authors turned around and started doing just that. There are known defects that affect the proliferation of cells building structures in the brain, genetic diseases like microcephaly. You cannot do experiments on microcephalic human beings, and it’s been very difficult to generate good animal models of microcephaly — we have such unusual brains to begin with that it’s hard to find a brain analogous in sufficient detail in mice. But here’s what they can do.

They had a patient with microcephaly, with a known genetic cause (a mutation in a gene called CDK5RAP2). They can’t experiment on his brain, obviously, but what they could do is take a few of his skin cells, transfect them with the four inducing genes, and produce a clone which could be cultured in a dish and put through the organoid production procedure and make little tiny copies of his embryonic brain state. Now you can do experiments.

What they observed was that some brain areas in the organoids were smaller (complicated by the fact that overall growth was reduced), and that there more more neurons and fewer glia in affected regions. The hypothesis is that CDK5RAP2 maintains cells in a dividing state, and it’s absence causes premature maturation of neurons, which leads to reduced total numbers of neurons in the adult. They also tried inducing greater CDK5RAP2 in the organoids to rescue the phenotype — the experiment was confused by the fact that CDK5RAP2 overproduction seems to trigger cell death, and they do not have precise control over dosages, but they do find suggestions that glial production is rescued. They also did the complementary experiment of RNAi knockouts of CDK5RAP2 in non-patient organoids, and they did see a surge of neuron production. So it looks like they’re getting a good handle on the cellular processes behind this form of microcephaly.

So what they’ve built is a useful model for studying early brain development in humans that doesn’t involve experimenting on any actual humans. This is going to be useful for all sorts of developmental disorders.

Also, Mad Science Fair contests.


Lancaster MA, Renner M, Martin C-A, Wenzel D, Bicknell LS, Hurles ME, Homfray T, Penninger JM, Jackson AP, Knoblich JA (2013) Cerebral organoids model human brain development and microcephaly. Nature doi:10.1038/nature12517.

Hamza Tzortzis can learn

Tzortzis has learned that claiming miraculous knowledge in the Qu’ran has “become an intellectual embarrassment for Muslim apologists”. Progress!

Regrettably, the scientific miracles narrative has become an intellectual embarrassment for Muslim apologists, including myself. A few years ago I took some activists to Ireland to engage with the audience and speakers at the World Atheist Convention. Throughout the convention we had a stall outside the venue and as a result positively engaged with hundreds of atheists, including the popular atheist academics Professor P. Z. Myers and Professor Richard Dawkins.  During our impromptu conversation with Professor Myers we ended up talking about God’s existence and the Divine nature of the Qur’ān. The topic of embryology came up, and Professor Myers being an expert in the field challenged our narrative. He claimed that the Qur’ān did not predate modern scientific conclusions in the field. As a result of posting the video[8] of the engagement on-line we faced a huge intellectual backlash. We received innumerable amounts of emails by Muslims and non-Muslims. The Muslims were confused and had doubts, and the non-Muslims were bemused with the whole approach. Consequently, I decided to compile and write an extensive piece on the Qur’ān and embryology, with the intention to respond to popular and academic contentions.[9] During the process of writing I relied on students and scholars of Islamic thought to verify references and to provide feedback in areas where I had to rely on secondary and tertiary sources. Unfortunately they were not thorough and they seemed to have also relied on trusting other Muslim apologists. When the paper was published it was placed under a microscope by atheist activists.[10] Although they misrepresented some of the points, they raised some significant contentions. I have since removed the paper from my website. In retrospect if this never happened, I probably wouldn’t be writing this essay now. It is all a learning curve and an important part of developing intellectual integrity.

Of course, he now has a new strategy:

  1. The Qur’ān allows multiple and multi-level meanings.

  2. Our understanding of natural phenomena and science changes and improves with time.

  3. The Qur’ān is not inaccurate or wrong.

  4. In the case of any irreconcilable difference between a Qur’ānic assertion and a scientific one, the following must be done:

    • Find meanings within the verse to correlate with the scientific conclusion.

    • If no words can match the scientific conclusion then science is to be improved.

    • Find a non-scientific meaning. The verse itself may be pertaining to non-physical things, such as the unseen, spiritual or existential realities.

#1 and #2 are correct. #3 is assuming what they want to demonstrate. #4 is an exercise in rationalization, and cannot generate new knowledge; it’s an admission that science will drive progress and understanding, while the religious apologists will follow along behind and try to steal the credit.

Spontaneous abortion explosion

Now that we’re regularly getting small numbers of eggs and embryos every day, we thought we’d test out all the other gear by making an extended timelapse video, letting it run overnight. Unfortunately, in the wee hours of the morning, God apparently struck and slaughtered the little baby fish in its chorion, and embryo went splat. We’ll show it anyway.

This happens spontaneously a few percent of the time, a bit more frequently in embryos we’ve poked and jostled and plopped into a stressful environment, so don’t be alarmed. Nature is not kind to embryos.

The MFAP Hypothesis for the origins of Homo sapiens

I know you’re thinking we’ve had more than enough discussion of one simplistic umbrella hypothesis for the origin of unique human traits — the aquatic ape hypothesis — and it’s cruel of me to introduce another, but who knows, maybe the proponents of each will collide and mutually annihilate each other, and then we’ll all be happy. Besides, this new idea is hilarious. I’m calling it the MFAP hypothesis of human origins, which the original author probably wouldn’t care for (for reasons that will become clear in a moment), but I think it’s very accurate.

A list of traits distinguishing humans from other primates
DERMAL FEATURES
Naked skin (sparse pelage)
Panniculus adiposus (layer of subcutaneous fat)
Panniculus carnosus only in face and neck
In “hairy skin” region:
 - Thick epidermis
 - Crisscrossing congenital lines on epidermis
 - Patterned epidermal-dermal junction
Large content of elastic fiber in skin
Thermoregulatory sweating
Richly vascularized dermis
Normal host for the human flea (Pulex irritans)
Dermal melanocytes absent
Melanocytes present in matrix of hair follicle
Epidermal lipids contain triglycerides and free fatty acids

FACIAL FEATURES
Lightly pigmented eyes common
Protruding, cartilaginous mucous nose
Narrow eye opening
Short, thick upper lip
Philtrum/cleft lip
Glabrous mucous membrane bordering lips
Eyebrows
Heavy eyelashes
Earlobes

FEATURES RELATING TO BIPEDALITY
Short, dorsal spines on first six cervical vertebrae
Seventh cervical vertebrae:
– long dorsal spine
– transverse foramens
Fewer floating and more non-floating ribs
More lumbar vertebrae
Fewer sacral vertebrae
More coccygeal vertebrae (long “tail bone”)
Centralized spine
Short pelvis relative to body length
Sides of pelvis turn forward
Sharp lumbo-sacral promontory
Massive gluteal muscles
Curved sacrum with short dorsal spines
Hind limbs longer than forelimbs
Femur:
– Condyles equal in size
– Knock-kneed
– Elliptical condyles
– Deep intercondylar notch at lower end of femur
– Deep patellar groove with high lateral lip
– Crescent-shaped lateral meniscus with two tibial insertions
Short malleolus medialis
Talus suited strictly for extension and flexion of the foot
Long calcaneus relative to foot (metatarsal) length
Short digits (relative to chimpanzee)
Terminal phalanges blunt (ungual tuberosities)
Narrow pelvic outlet

ORGANS
Diverticulum at cardiac end of stomach
Valves of Kerkring present in small intestines
Mesenteric arterial arcades
Multipyramidal kidneys
Heart auricles level
Tricuspid valve of heart
Laryngeal sacs absent
Vocal ligaments
Prostate encircles urethra
Bulbo-urethral glands present
Os penis (baculum) absent.
Hymen
Absence of periodic sexual swellings in female
Ischial callosities absent
Nipples low on chest
Bicornuate uterus (occasionally present in humans)
Labia majora

CRANIAL FEATURES
Brain lobes: frontal and temporal prominent
Thermoregulatory venous plexuses
Well-developed system of emissary veins
Enlarged nasal bones
Divergent eyes (interior of orbit visible from side)
Styloid process
Large occipital condyles
Primitive premolar
Large, blunt-cusped (bunodont) molars
Thick tooth enamel
Helical chewing

BEHAVIORAL/PHYSIOLOGICAL
Nocturnal activity
Particular about place of defecation
Good swimmer, no fear of water
Extended male copulation time
Female orgasm
Short menstrual cycle
Snuggling
Tears
Alcoholism
Terrestrialism (Non-arboreal)
Able to exploit a wide range of environments and foods

RARE OR ABSENT IN NONHUMAN PRIMATES:
Heart attack
Atherosclerosis
Cancer (melanoma)

First, the author of this new hypothesis provides a convenient list of all the unique traits that distinguish humans from other primates, listed on the right. It falsely lists a number of traits that are completely non-unique (such as female orgasm and cancer), or are bizarre and irrelevant (“snuggling”, really?). It’s clearly a selective and distorted list made by someone with an agenda, so even though some items on the list are actually unusual traits, the list itself is a very poor bit of data.

But set those objections to the list aside for a moment, and let’s consider the hypothesis proposed to explain their existence, the MFAP Hypothesis of Eugene McCarthy, geneticist. I will allow him to speak for himself at length; basically, though, he proposes that the way novel traits appear in evolution is by hybridization, by crosses between two different species to produce a third with unique properties.

Many characteristics that clearly distinguish humans from chimps have been noted by various authorities over the years. The task of preliminarily identifying a likely pair of parents, then, is straightforward: Make a list of all such characteristics and then see if it describes a particular animal. One fact, however, suggests the need for an open mind: as it turns out, many features that distinguish humans from chimpanzees also distinguish them from all other primates. Features found in human beings, but not in other primates, cannot be accounted for by hybridization of a primate with some other primate. If hybridization is to explain such features, the cross will have to be between a chimpanzee and a nonprimate — an unusual, distant cross to create an unusual creature.

For the present, I ask the reader to reserve judgment concerning the plausibility of such a cross. I’m an expert on hybrids and I can assure you that our understanding of hybridization at the molecular level is still far too vague to rule out the idea of a chimpanzee crossing with a nonprimate. Anyone who speaks with certainty on this point speaks from prejudice, not knowledge.

Let’s begin, then, by considering the list in the sidebar at right, which is a condensed list of traits distinguishing humans from chimpanzees — and all other nonhuman primates. Take the time to read this list and to consider what creature — of any kind — it might describe. Most of the items listed are of such an obscure nature that the reader might be hard pressed to say what animal might have them (only a specialist would be familiar with many of the terms listed, but all the necessary jargon will be defined and explained). For example, consider multipyramidal kidneys. It’s a fact that humans have this trait, and that chimpanzees and other primates do not, but the average person on the street would probably have no idea what animals do have this feature.

Looking at a subset of the listed traits, however, it’s clear that the other parent in this hypothetical cross that produced the first human would be an intelligent animal with a protrusive, cartilaginous nose, a thick layer of subcutaneous fat, short digits, and a naked skin. It would be terrestrial, not arboreal, and adaptable to a wide range of foods and environments. These traits may bring a particular creature to mind. In fact, a particular nonprimate does have, not only each of the few traits just mentioned, but every one of the many traits listed in th sidebar. Ask yourself: Is it is likely that an animal unrelated to humans would possess so many of the “human” characteristics that distinguish us from primates? That is, could it be a mere coincidence? It’s only my opinion, but I don’t think so.

Look at the description of the putative non-primate parent in the last paragraph above. What animal are you thinking of? It’s probably the same one McCarthy imagined, which is why I’ve decided that this explanation for human origins must be called the Monkey-Fucked-A-Pig hypothesis, or MFAP for short.

Let’s be perfectly clear about this. McCarthy’s hypothesis is that once upon a time, these two met and had sex,

angrypigangrychimp

And that they then had children that were…us.

That’ll learn me. I thought this South Park clip was a joke.

One thing that struck me in reading McCarthy’s claim is how they are so similar to the claims of the soggy ape fans — they even use the very same physiological and anatomical features to argue for their delusion. For instance, I’ve read aquatic ape proponents’ arguments that the shape of our nose is adaptive for streamlining and for preventing water from flowing into the nostrils while propelling ourselves forward through the water…but compare that to the MFAP.

Neither is it clear how a protrusive cartilaginous nose might have aided early humans in their “savannah hunter lifestyle.” As Morris remarks, “It is interesting to note that the protuberant, fleshy nose of our species is another unique feature that the anatomists cannot explain.” This feature is neither characteristic of apes, nor even of other catarrhines. Obviously, pigs have a nose even more protuberant than our own. In a pig’s snout, the nasal wings and septum are cartilaginous as ours are. In contrast, a chimpanzee’s nose “is small, flat, and has no lateral cartilages”. A cartilaginous nose is apparently a rare trait in mammals. Primatologist Jeffrey Schwartz goes so far as to say that “it is the enlarged nasal wing cartilage that makes the human nose what it is, and which distinguishes humans from all other animals.” The cartilaginous structure of the pig’s snout is generally considered to be an “adaptation” for digging with the nose (rooting). Rooting is, apparently, a behavior pattern peculiar to pigs. Other animals dig with their feet.

Point, MFAP. Of course, just as I would point out to aquatic ape people, we do have an explanation for the nose: recession of the facial bones associated with reduced dentition, along with retention of the bones associated with the respiratory apparatus. The protuberant nose is simply a ridge made apparent by the receding tide of our chewing apparatus. McCarthy uses evidence as badly as does every wet ape fan.

Now, why won’t this hybridization claim work? Well, there are the obvious behavioral difficulties, even if it were cytogenetically possible. We’d have to have pigs and chimps having sex and producing fertile offspring, and those human babies (remember, this is a saltational theory, so the progeny would have all the attributes of a third species, ours) would have to be raised by chimps. Or pigs. I don’t think either is a reasonable alternative, and a band of chimps would probably be no more charitable to a helpless fat blob of a baby than Mr Wu’s pigs.

However, no one reasonably expects pigs and chimps to be interfertile. The primate and artiodactyl lineages have diverged for roughly 80 million years — just the gradual accumulation of molecular differences in sperm and egg recognition proteins would mean that pig sperm wouldn’t recognize a chimpanzee egg as a reasonable target for fusion. Heck, even two humans will have these sorts of mating incompatibilities. Two species that haven’t had any intermingling populations since the Cretaceous? No way.

pig-chimp_lca

But further, even if the sperm of one would fuse with the egg of another, there is another looming problem: chromosome incompatibilities. Pigs have 38 chromosomes, chimpanzees have 48. Cells are remarkably good at coping with variations in chromosome number, and even with translocations of regions from one chromosome to another; and further, pigs and people even retain similar genetic arrangements on some of their chromosomes. There are pig chromosomes that have almost the same arrangement of genes as a corresponding human chromosome.

But there are limits to how much variation the cell division machinery can cope with. For instance, with fewer chromosomes than we primates have, that means you need to line up multiple primate chromosomes to match a single pig chromosome (this pairing up is essential for both mitosis and meiosis). Look at pig chromosome 7, for instance: it corresponds to scrambled and reassembled bits of human chromosomes 6, 14, and 15.

Blocks of conserved synteny between pig and human. (a) Pig SSC7 to human chromosomes 6, 14 and 15. (b) HSA13 compared to pig chromosome 11. Block inversions between pig and human are denoted with broken lines. Contig coverage is depicted by bars in the center of SSC7 and HSA13.

Blocks of conserved synteny between pig and human. (a) Pig SSC7 to human chromosomes 6, 14 and 15. (b) HSA13 compared to pig chromosome 11. Block inversions between pig and human are denoted with broken lines. Contig coverage is depicted by bars in the center of SSC7 and HSA13.

Maybe that would work in mitosis within the hybrid progeny — you’d have three chromosomes from the human/chimp parent twisted around one chromosome, but they would be able to pair up, mostly, and then separate to form two daughter cells. But meiosis would be total chaos: any crossing over would lead to deletions and duplications, acentric and dicentric chromosomes, a jumble of broken chromosomes. That would represent sterile progeny and an evolutionary dead end.

But we wouldn’t have to even get that far. Human and chimpanzee chromosomes are even more similar to one another, and there are no obvious chromosomal barriers to interfertility between one another. If hybridization in mammals were so easy that a pig and a chimp could do it, human-chimp hybrids ought to be trivial. Despite rumors of some experiments that attempted to test that, though, there have been no human-chimp hybrids observed, and I think they are highly unlikely to be possible. In this case, it’s a developmental problem.

For example, we have bigger brains than chimpanzees do. This is not a change that was effected with a single switch; multiple genes had to co-evolve together, ratcheting up the size in relatively incremental steps. So you could imagine a change that increased mitotic activity in neural precursors that would increase the number of neurons, but then you’d also need changes in how those cells are partitioned into different regions, and changes in the proliferation of cartilage and bone to generate a larger cranium, and greater investment in vascular tissue to provide that brain with an adequate blood supply.

Development is like a ballet, in which multiple players have to be in the right place and with the right timing for everything to come off smoothly. If someone is out of place by a few feet or premature by a few seconds in a leap, the dancers could probably compensate because there are understood rules for the general interactions…but it would probably come off as rough and poorly executed. A hybrid between two closely related species would be like mixing and matching the dancers from two different troupes to dance similar versions of Swan Lake — everything would be a bit off, but they could probably compensate and muddle through the performance.

Hybridizing a pig and a chimp is like taking half the dancers from a performance of Swan Lake and the other half from a performance of Giselle and throwing them together on stage to assemble something. It’s going to be a catastrophe.

But here’s the deal: maybe I’m completely wrong. This is an experiment that is easily and relatively cheaply done. Human sperm is easily obtained (McCarthy probably has a plentiful supply in his pants), while artificial insemination of swine is routine. Perhaps McCarthy can report back when he has actually done the work.


Humphray SJ, Scott CE, Clark R, Marron B, Bender C, Camm N, Davis J, Jenks A, Noon A, Patel M, Sehra H, Yang F, Rogatcheva MB, Milan D, Chardon P, Rohrer G, Nonneman D, de Jong P, Meyers SN, Archibald A, Beever JE, Schook LB, Rogers J. (2007) A high utility integrated map of the pig genome. Genome Biol. 8(7):R139.

For the ambitious budding cancer biologist

I’m teaching cancer biology in the fall, and if you want to get a head start over the summer, here are the texts we’re going to be using:

Biol 4103: Cancer Biology

Introduction to Cancer Biology, by Robin Heskith
Cambridge University Press, 1st ed.
ISBN 978-1107601482

The Emperor of All Maladies: A Biography of Cancer, by Siddhartha Mukherjee
Scribner, reprint ed.
ISBN 978-1439170915

Last time around, I used Weinberg’s The Biology of Cancer, which is an excellent, in-depth text, but was really heavy going for an undergraduate course — it’s more of a graduate/MD level reference book. The Heskith book is very good, giving more substantial introductions to the difficult concepts, and also as a bonus, is one third the price. Just having general chapters on cell signaling in normal cells, for instance, will be a big help in bringing students up to speed.

For you outside observers, sorry, but this class won’t be going the supplementary blogging route. I’ve got some other cunning schemes I’m going to try on the students instead.

The first day of the rest of my summer!

twitch

It’s going to be a good season, I can tell already. It’s finals week, so I’ll still have an abrupt pile of grading to do on Thursday, but otherwise, my teaching obligations are done for the semester. Now I’m trapped, trapped I tell you, in Morris for almost (I do have two quick trips to Europe planned) the entire summer with a collection of administrative responsibilities, but the good part of that is that I have ambitious plans for what I’ll be doing in the lab. I’m also going to be living the good life.

So this morning I slept in to 7:00. I know, it’s slothful of me, but I have the freedom to indulge myself a little bit now and then. After I got up, I took a nice brisk walk downtown, did some shopping, stocked up on some fresh vegetables, and once I got home, chopped them up and set them to soak in a tasty marinade. I’ll roast them up for dinner tonight.

Then I started reading up an accumulated mass of papers that’ll give me some implementation ideas for the work I have planned.

I’ll have a student working with me, and we’ve got a couple of projects in the works.

  1. There’s some boring scut work to be done: lab cleanup, clearing out old reagents from the refrigerator, making up new stock solutions. Don’t be disillusioned, but part of the research life is janitorial…so much dishwashing.

  2. My grand plan requires an expansion of my fish colony to include multiple genetic strains, so we’re going to be scrubbing tanks, sterilizing surfaces, setting up new tanks with boring feeder fish to get the nitrogen cycle going and condition the water, getting the brine shrimp hatchery (live fish food!) thriving, all that sort of stuff that qualifies you to be a clerk in a pet store.

  3. Once all the tanks are bubbling away happily, we’re getting some new strains from the zebrafish stock center. Then it’s a few months of nursing them along, collecting eggs, propagating new generations and raising them to adulthood to get the whole colony self-sustaining, and to prepare for crosses to produce hybrid strains. After all this, my student will be well-trained to be a hobbyist aquarist.

  4. Concurrently, we’ll be doing some real science on the embryos we get, analyzing their behavior quantitatively to identify consistent differences between strains, and also in response to different environmental stresses. This is going to require a bit of computer work and — oh, no! — basic math to develop image analysis protocols. That’s what I’ve been reading about; I’ve done some of this in the past on an obsolete software system, so I’m going to have to piece together some custom bits to make it all work. I’ve been reading about Fourier analysis and power spectra all morning, and I’m kinda jazzed. Math! Computers! Embryos! Science!

  5. The dream is that once we’ve found some subtle differences between different strains, we can start doing crosses to dissect out and isolate the genetic components, if any, of the behavior. That’s going to take a couple of generations of crosses, which means that if I’m lucky we’ll get those results next year, or at worst, the year after. Behavioral Genetics! Yay! Long generation times! Boo!

It’s step #4 that’ll give us some quick quantitative results, I hope, and maybe something presentable at a meeting or even publishable. It’s all going to be preliminary and descriptive, but that’s what you need to do to establish a foundation for experiments.

Unfortunately for you, I won’t be blogging about any of the details of the work this summer — I’ve been scooped before when I foolishly posted protocols on the web, and especially when you have a very small lab with limited humanpower to throw at a problem, that costs. But I might just occasionally say a few general things about the kinds of analyses we’re doing.

Or I could talk about the moldy stuff we throw out of the refrigerator. That’s probably safe.

What I taught today: FINAL EXAM TIME!

I’m in Arizona, on my way to Orange County, but that doesn’t stop me: I’ve given my students a take home final exam. I wouldn’t want them to be bored over finals week, you know.

1. In the last lecture, I tried to give you a little context, and explained that a dynamic picture of biology would include evolution, ecology, and development, all subdisciplines that deal with change over time. You’re all upper level students; explain to me how developmental biology fits into the perspective on biology that your experience here at UMM has given you so far. Are there pieces you wish our curriculum emphasized more? Why?

2. We’ve spent most of the semester talking about animals — as it currently stands, evo-devo has an unfortunately limited emphasis on metazoans, with an occasional nod to higher plants. Explore a little deeper. What would an evo-devo of fungi, or bacteria, or protists talk about? Is the toolkit we’ve been talking about truly universal? Give me a brief precis of the developmental principles for any other kingdom.

3. Imagine that after you graduate, you find yourself in an unexpected job: you’re working in university press office or as a science journalist. You have to explain scientific research to the public every day. What general principles would guide you? These should be ideas about ethics, effective communication, psychology, etc. in addition to purely scientific concerns. Tell me what standards you’d have to become a great reporter of science.

There. That should make them think.

What I taught today: toroids!

Hox 11/13 expression in an echinoderm blastula

It was the last day of classes for us. I brought donuts.

Dammit, I just realized I missed a golden opportunity. I should have talked to them about Thrive and Pivar and Fleury and Andrulis. Crackpot fringe developmental biologists all seem to have a thing for donuts.

Rats. Well, I’ll just send all my students an email and tell them they have to come back. They don’t even realize the importance of our little snack together.