Halloween seems like a good time to resurrect old blog posts that haven’t seen the sunlight for several years. Creeping out of the tomb is my first blog post about Genes, DNA, Memes, and GMO foods. Rather than post it here, I decided to post it over on my Medium site to see if it can catch some new eyes.
Take a look: Linked Memes
Buy this poster print at: http://fictionalnape.deviantart.com/art/ReAnimator-Poster-359280577
In the novel, Carrie, Stephen king attempts to explain telekinetic ability in terms of a real genetically inherited trait. OK, this is fiction, I have no problem with Carrie’s telekinetic ability … where would this story be without it after all?
Explaining this ability in terms of science was a mistake for two reasons. For one thing, it undermines the very idea of ‘supernatural’ that the reader has already bought into. This was exactly the problem that fans of Star Wars had with the prequel trilogy’s explanation of ‘The Force’ in terms of sub-cellular microorganisms. The second reason he shouldn’t have done this is because he didn’t understand it well himself.
Characters:
Carrie White – The protagonist, who possesses telekinetic (TK) ability
Margaret Brigham – Carrie’s mother
Ralph White – Carrie’s father
From Stephen King’s Carrie (please don’t sue me Mr. King)
It is now generally agreed that the TK phenomenon is a genetic-
recessive occurrence-but the opposite of a disease like hemophilia,
which becomes overt only in males. In that disease, once called “King’s
Evil,” the gene is recessive in the female and is carried harmlessly.
Male offspring, however, are “bleeders.” This disease is generated only
if an afflicted male marries a woman carrying the recessive gene. If the
offspring of such union is male, the result will be a hemophiliac son. If
the offspring is female, the result will he a daughter who is a carrier. It
should be emphasized that the hemophilia gene may be carried
recessively in the male as a part of his genetic make-up. But if he
marries a woman with the same outlaw gene, the result will be
hemophilia if the offspring is male.In the case of royal families, where intermarriage was common, the
chance of the gene reproducing once it entered the family tree were
high-thus the name King’s Evil. Hemophilia also showed up in
significant quantities in Appalachia during the earlier part of this
century, and is commonly noticed in those cultures where incest and
the marriage of first cousins is common.With the TK phenomenon, the male appears to be the carrier; the
TK gene may be recessive in the female, but dominates only in the
female. It appears that Ralph White carried the gene. Margaret
Brigham, by purest chance, also carried the outlaw gene sign, but we
may be fairly confident that it was recessive, as no information has ever
been found to indicate that she had telekinetic powers resembling her
daughter’s. Investigations are now being conducted into the life of
Margaret Brigham’s grandmother, Sadie Cochran-for, if the dominant/recessive
pattern obtains with TK as it does with hemophilia,
Mrs. Cochran may have been TK dominant.If the issue of the White marriage had been male, the result would
have been another carrier. Chances that the mutation would have died
with him would have been excellent, as neither side of the Ralph
White-Margaret Brigham alliance had cousins of a comparable age for
the theoretical male ottspring to marry. And the chances of meeting and
marrying another woman with the TK gene at random would be small.
None of the teams working on the problem have yet isolated the gene.Surely no one can doubt, in light of the Maine holocaust, that
isolating this gene must become one of medicine’s number-one
priorities. The hemophiliac, or H gene, produces male issue with a lack
of blood platelets. The telekinetic, or TK gene, produces female
Typhoid Marys capable of destroying almost at will….
Questions
Stephen King’s explanation of the genetics of hemophilia is not quite right.
1. How is hemophilia actually inherited? Explain in terms of dominant / recessive inheritance.
2. King suggests that hemophilia is inherited from two carrier parents. Is this correct? Describe, in genetic terms, how a boy can be born with disease.
3. Is it possible for a female child to inherit the disease?
Tomorrow in class, where we have recently been discussing Mendelian Genetics and its twisted perversion,Eugenics; we will be watching the dystopian film, GATTACA. The story is good enough, but what I find compelling is the way that society has become the way it is. The population has been recently ‘improved’ by the production (?) of ‘designer babies‘. The method seems very much like one that I can honestly imagine working its way into present society. These children aren’t fabricated, they’re yours. Only – just the best parts of you.
Society fell for Eugenics once – and not just Hitler. I know that’s where your mind is going. But there were plenty of Eugenics believers here in the USA as well. Just ask this happy family:
They’re smiling because they’ve just won the ‘medium family size’ medal for fittest family at the 1927 Kansas Free Fair.
It was a time when Mendelian genetics was coming to be understood in principle by a wider audience following the work’s ‘rediscovery’ by Hugo de Vries and Carl Correns in 1900. The main idea behind Eugenics was that better people could be made through selective breeding of only the right kinds of folks. The term Eugenics was coined by Sir Frances Galton, who actually a great thinker contributing several key ideas in the field of statistics and inventing the sciences of meteorology and psychometrics. His books, Hereditary Genius (1869) and Essays on Eugenics (1909) lay the groundwork for thinking about which traits are inherited and which are learned in humans. In exploring the idea of hereditary greatness, he also explores the hereditary of less desirable genes.
What he concluded was that great, geniuses like himself simply aren’t having enough children while the lowly dregs of humanity were breeding like bunnies. Well, there’s a couple of ways to put an end to that nonsense.
Here is an excerpt from a Scientific American editorial of the time (1911) lauding Galton’s ideas:
ADA JUKE is known to anthropologists as the “mother of criminals.” From her there were directly descended one thousand two hundred persons. Of these, one thousand were criminals, paupers, inebriates, insane, or on the streets. That heritage of crime, disease, inefficiency and immorality cost the State of New York about a million and a quarter dollars for maintenance directly. What the indirect loss was in property stolen, in injury to life and limb, no one can estimate.
Suppose that Ada Juke or her immediate children had been prevented from perpetuating the Juke family. Not only would the State have been spared the necessity of supporting one thousand defective persons, morally and physically incapable of performing the functions of citizenship, but American manhood would have been considerably better off, and society would have been free from one taint at least.
The Free Kansas Fair of 1927 had more than just pretty families. It also proposed just how even prettier families could show up in the years to come:
Why is Blind in quotes? Is that, perhaps, a suggestion? Or is it just poor grammar?
Do you suppose ‘Pauperism’ is dominant or recessive? Either way, it’s bad. How can they go around having no money like that? Have they no shame?
A while ago I wrote two posts about the Lac Operon here. The first pointed to an animation by McGraw Hill Publishers that did a pretty good job illustrating how the operon works. In the second post, I highlighted the notion of polycistronic messages (more than one gene per mRNA molecule) and how this allows for control of a number of related genes at once – a trait not shared by eukaryotic cells. In that second post, I also finished with a graph of how cells grow in the presence of glucose and lactose.
Cell Growth in the presence of glucose + lactose – As glucose is depleted, cells adjust to lactose digestion
One feature of that graph (reproduced here) that is notable is a little bump in the growth rate as glucose runs out and the cell converts to lactose digestion. A second important feature is that the rate of growth slows when the cell is burning lactose as its primary fuel.
Together, these features suggest that the cell is regulating lactose digestion very closely. In fact, there are two primary mechanisms of this regulation to appreciate. The first is that the lactose-digesting enzymes are controlled together on an operon that is regulated by lactose itself (or at least we can assume so for simplicity’s sake). In the absence of lactose, no lactase enzymes are made and no lactose is used as fuel. The reason for this is obvious when you look at the slope of cell growth under glucose metabolism (left) and lactose metabolism (right). Clearly, growth is SLOWER when lactose is used as fuel.
Therefore, so long as there is glucose, it is pointless to digest lactose at the same time. So it is best to only turn on the lac operon in the ABSENCE of glucose – regardless of whether lactose is present of not.
If glucose is absent and lactose is absent, turning on lactase enzymes is still useless. However, slow growth is better than no growth. So we should have a mechanism to turn on the operon when there is lactose in the environment.
Here’s a matrix of ideal regulation:
How can a little, mindless bacteria achieve this exquisite control?
Simple: By using two regulators. One for glucose and one for lactose. Only when both conditions (glucose-, lactose+) are met do we make lactase.
Structure of the Lac Operon
First, lactose itself serves as an inducer. In the absence of lactose, a regulator protein binds to a DNA site between the polymerase binding site (the promoter) and the structural genes (the enzymes). When the regulator binds, its presence physically prevents the progress of RNA Polymerase.
When lactose is present, it binds the repressor protein in a way that causes its shape to change in a way that can no longer bind the DNA. The repressor then drifts away from its binding site allowing RNA Polymerase a clear shot to the structural genes.
However, RNA Polymerase is not always parked on the promoter waiting for the repressor to be removed. Its binding requires another protein to help stabilize its interaction with the DNA. This second protein is the CAP protein. The Catabolite Activated Protein. However, CAP alone will not bind either. It requires a signaling molecule called cyclic AMP (cAMP). cAMP is readily broken down when glucose is in the cell, so it only accumulates when glucose is absent. In that case, cAMP accumulates and binds to the CAP protein, which then binds to the CAP site. This site is located adjacent to the promoter, but on the side away from the structural genes. When CAP binds, it assists in recruiting the RNA polymerase to the promoter.
Therefore, if only one condition is met, it is insufficient to promote gene transcription. Only when the CAP+ cAMP protein is bound will the Polymerase be recruited. And only when lactose is present, will the repressor protein let the Polymerase pass.
In terms of the matrix we set forth above, we can see that these molecular interactions result in exactly the regulation that is optimal:
In class this week we are discussing genes alleles homologous genes between species and pseudogenes. In order to organize my thoughts (to the extent that I can), I sketched out this diagram to model the flow of information from DNA into proteins and tie this together with the idea that DNA undergoes mutations from time to time and that these mutations are the source of new alleles in the population.
1.Recall the central dogma
DNA –> RNA –> Protein
Information flows from the DNA out of the nucleus giving rise to proteins that make up the body and do its work. For EVERY gene, you have two alleles, one from mom, one from dad. We tend to only talk about the ones that give us distinct traits that we can see from the outside, but every gene these.
2. Mutations are altered forms leading to altered function
All genes are subject to mutations. Mutations may change the protein that the gene encodes or not. In cases when it does change the protein, we may see a change in function (Form dictates Function). Once we have two different versions of a gene that remain for any period of time, we call these forms alleles of the gene.
3. Interaction of Alleles
Mutations result in these new alleles that may function differently. This may manifest in a form of dominance. If one allele codes for a protein and a second suffered a mutation such that no protein is made, we may look for the protein and say that the form that makes the protein is dominant because one copy should be sufficient to get it made.
4. How can Alleles become Pseudogenes?
Sometimes, genes mutate into a nonfunctional allele that has no impact on the organism (e.g. vitamin C synthesis is not required when the animal eats sufficient vitamin C) in this case, there will be no selective pressure against the non-functional allele resulting in more mutations occurring without consequence. Over time, these alleles can be made completely non-functional. Pseudogenes are the remnants of these old genes that we can find in the DNA, but that are no longer functional due to an accumulation of mutations. (Only if both copies are mutated and there is no functional copy of the gene in the population do we can this a pseudogene).
5. Speciation and Relationships
As time passes, and speciation occurs, we can still see similarities between the genes of the descendent species, whether these are functional, or sometimes even when they are non-functional. My analyzing the similarities between shared genes, it is possible to infer some relationships between species and even quantitate these relationships in a way that can be used to construct a phylogenetic tree.
I was spending some time on stack exchange’s biology section the other day, when I saw an interesting question that someone had about how genes are arranged on chromosomes.
In answering his question, I picked up a couple of screen shots and links that I thought I should share here.
The query was included the following (paraphrased):
How are genes arranged on the chromosome, are they were all in a single direction and how does the cell ‘know’ which direction they are in?
The best way to approach this question is to take advantage of the amazing amount of resources compiled at the NIH’s National Library of Medicine…
One fun place to start is the Genome Page, which looks like this:
Note the 22+ X and Y chromosomes on the lefthand side of the page. Each chromosome is clickable and will take you to a chromosome page that looks like this:
Map view of H. sapiens Chromosome 14
Genes are listed on the right side of this map with locations of each indicated through a set of nested maps on the left. Each gene is clickable, providing links to the research done supporting these map placements and functions of the gene/protein. You can also easily use this information to jump to the homologous gene found in any of a number of fully sequenced organisms.
Below the map of the chromosome is a legend that indicates additional information and shows how much detail that each of the maps you are observing provides.
The amount of data is overwhelming, but you can adjust how much detail is shown in order to get the ‘lay of the land’ for a specific chromosome without getting too lost. If you have a gene you want to find, you can also pinpoint it this way and see what other genes are located nearby (and therefor ‘linked’ to your gene).
huMMR gene, chromosome 10
I searched for the Human Macrophage Mannose Receptor (a protein I made antibodies against when I worked for Medarex). This gene is located on chromosome 10, as indicated by the red dots. 212 references provide sequence information about this gene and protein.
If you keep going down the rabbit hole, you can see each of the DNA sequences that were used to identify and locate this gene on the chromosome (I omitted providing an illustration of this page because it is hard to get anything from it if shrunk down of prevented piecemeal. However, you can go to this page by following this link).
Finally, you are given the links to the complete coding sequence (cds), which has the actual sequence of the gene and protein as well as notes about how it is put together. In my mind, these are the bread and butter of this site, and probably the oldest reference pages that have provided gene hunters data for several decades now.
Ahh, data I can use!!
…
A slice of sequence info
It’s easy to see this as way too much information to be useful (hence the problem of ‘Big Data’ in Biology), but it’s also extremely cool, and I have to admit that I’ve gotten just as lost in tracing the data on genes using this site as I did walking from topic to topic in the Encyclopedia when I was a kid.
So… to answer the questions posed above, you can use this site to see that many genes lie in different direction along the chromosome. Why the cell doesn’t get ‘confused’ is because the cell doesn’t try to arrange data like we do in volumes of books meant to be read in order. Each gene is regulated, transcribed and translated according to its own local rules, as if ‘unaware’ of all that’s going on around it.
Although we still have work to do discussing chapter 23 and associated material, I have been looking ahead and considering a new path for this semester. Typically, in general biology, we introduce Mendelian Genetics as Mendel observed it (i.e. at the level of the phenotype with only speculations about the genotype). We finish this chapter with pedigree analysis and how we might track traits through a family tree and then segue into the molecular mechanism underlying these observations.
This year, I am considering skipping to Population ecology and the Hardy-Weinberg equation before delving into the molecular elements. I’d like to see if this is as natural a course to take as the other and would then favor this because it ensures that we get to talk about gene pools and evolution before the end of the semester.
Thomas Malthus 1766 – 1834
To explore this idea, I was looking through the lectures ahead and came across the dire warning from Rev. Thomas Malthus that predicted hard times ahead for humans as our population reached an inflection point between exponential growth and a new stationary phase and eventually a ‘death phase’.
Malthus wrote of this, “…a population will grow (or decline) exponentially as long as the environment experienced by all individuals in the population remains constant.”
And, when the environment can no longer support the growth of the population, ” sickly seasons, epidemics, pestilence, and plague advance in terrific array, and sweep off their thousands and tens of thousands … [and] … gigantic inevitable famine stalks in the rear, and with one mighty blow levels the population with the food of the world”.
Although Jonathan Swift predated Malthus by about half a century, his Modest Proposal seems as if it was written in answer to Malthus. The entirety of Swift’s essay is provided below by Project Gutenberg (see below). Kindle or other ePub formats of the same material are available here.
A MODEST PROPOSAL For preventing the children of poor people in Ireland, from being a burden on their parents or country, and for making them beneficial to the publick. by Dr. Jonathan Swift 1729 It is a melancholy object to those, who walk through this great town, or travel in the country, when they see the streets, the roads and cabbin-doors crowded with beggars of the female sex, followed by three, four, or six children, all in rags, and importuning every passenger for an alms. These mothers instead of being able to work for their honest livelihood, are forced to employ all their time in stroling to beg sustenance for their helpless infants who, as they grow up, either turn thieves for want of work, or leave their dear native country, to fight for the Pretender in Spain, or sell themselves to the Barbadoes. I think it is agreed by all parties, that this prodigious number of children in the arms, or on the backs, or at the heels of their mothers, and frequently of their fathers, is in the present deplorable state of the kingdom, a very great additional grievance; and therefore whoever could find out a fair, cheap and easy method of making these children sound and useful members of the common-wealth, would deserve so well of the publick, as to have his statue set up for a preserver of the nation. But my intention is very far from being confined to provide only for the children of professed beggars: it is of a much greater extent, and shall take in the whole number of infants at a certain age, who are born of parents in effect as little able to support them, as those who demand our charity in the streets. As to my own part, having turned my thoughts for many years, upon this important subject, and maturely weighed the several schemes of our projectors, I have always found them grossly mistaken in their computation. It is true, a child just dropt from its dam, may be supported by her milk, for a solar year, with little other nourishment: at most not above the value of two shillings, which the mother may certainly get, or the value in scraps, by her lawful occupation of begging; and it is exactly at one year old that I propose to provide for them in such a manner, as, instead of being a charge upon their parents, or the parish, or wanting food and raiment for the rest of their lives, they shall, on the contrary, contribute to the feeding, and partly to the cloathing of many thousands. There is likewise another great advantage in my scheme, that it will prevent those voluntary abortions, and that horrid practice of women murdering their bastard children, alas! too frequent among us, sacrificing the poor innocent babes, I doubt, more to avoid the expence than the shame, which would move tears and pity in the most savage and inhuman breast. The number of souls in this kingdom being usually reckoned one million and a half, of these I calculate there may be about two hundred thousand couple whose wives are breeders; from which number I subtract thirty thousand couple, who are able to maintain their own children, (although I apprehend there cannot be so many, under the present distresses of the kingdom) but this being granted, there will remain an hundred and seventy thousand breeders. I again subtract fifty thousand, for those women who miscarry, or whose children die by accident or disease within the year. There only remain an hundred and twenty thousand children of poor parents annually born. The question therefore is, How this number shall be reared, and provided for? which, as I have already said, under the present situation of affairs, is utterly impossible by all the methods hitherto proposed. For we can neither employ them in handicraft or agriculture; we neither build houses, (I mean in the country) nor cultivate land: they can very seldom pick up a livelihood by stealing till they arrive at six years old; except where they are of towardly parts, although I confess they learn the rudiments much earlier; during which time they can however be properly looked upon only as probationers: As I have been informed by a principal gentleman in the county of Cavan, who protested to me, that he never knew above one or two instances under the age of six, even in a part of the kingdom so renowned for the quickest proficiency in that art. I am assured by our merchants, that a boy or a girl before twelve years old, is no saleable commodity, and even when they come to this age, they will not yield above three pounds, or three pounds and half a crown at most, on the exchange; which cannot turn to account either to the parents or kingdom, the charge of nutriments and rags having been at least four times that value. I shall now therefore humbly propose my own thoughts, which I hope will not be liable to the least objection. I have been assured by a very knowing American of my acquaintance in London, that a young healthy child well nursed, is, at a year old, a most delicious nourishing and wholesome food, whether stewed, roasted, baked, or boiled; and I make no doubt that it will equally serve in a fricasie, or a ragoust. I do therefore humbly offer it to publick consideration, that of the hundred and twenty thousand children, already computed, twenty thousand may be reserved for breed, whereof only one fourth part to be males; which is more than we allow to sheep, black cattle, or swine, and my reason is, that these children are seldom the fruits of marriage, a circumstance not much regarded by our savages, therefore, one male will be sufficient to serve four females. That the remaining hundred thousand may, at a year old, be offered in sale to the persons of quality and fortune, through the kingdom, always advising the mother to let them suck plentifully in the last month, so as to render them plump, and fat for a good table. A child will make two dishes at an entertainment for friends, and when the family dines alone, the fore or hind quarter will make a reasonable dish, and seasoned with a little pepper or salt, will be very good boiled on the fourth day, especially in winter. I have reckoned upon a medium, that a child just born will weigh 12 pounds, and in a solar year, if tolerably nursed, encreaseth to 28 pounds. I grant this food will be somewhat dear, and therefore very proper for landlords, who, as they have already devoured most of the parents, seem to have the best title to the children. Infant's flesh will be in season throughout the year, but more plentiful in March, and a little before and after; for we are told by a grave author, an eminent French physician, that fish being a prolifick dyet, there are more children born in Roman Catholick countries about nine months after Lent, the markets will be more glutted than usual, because the number of Popish infants, is at least three to one in this kingdom, and therefore it will have one other collateral advantage, by lessening the number of Papists among us. I have already computed the charge of nursing a beggar's child (in which list I reckon all cottagers, labourers, and four-fifths of the farmers) to be about two shillings per annum, rags included; and I believe no gentleman would repine to give ten shillings for the carcass of a good fat child, which, as I have said, will make four dishes of excellent nutritive meat, when he hath only some particular friend, or his own family to dine with him. Thus the squire will learn to be a good landlord, and grow popular among his tenants, the mother will have eight shillings neat profit, and be fit for work till she produces another child. Those who are more thrifty (as I must confess the times require) may flea the carcass; the skin of which, artificially dressed, will make admirable gloves for ladies, and summer boots for fine gentlemen. As to our City of Dublin, shambles may be appointed for this purpose, in the most convenient parts of it, and butchers we may be assured will not be wanting; although I rather recommend buying the children alive, and dressing them hot from the knife, as we do roasting pigs. A very worthy person, a true lover of his country, and whose virtues I highly esteem, was lately pleased, in discoursing on this matter, to offer a refinement upon my scheme. He said, that many gentlemen of this kingdom, having of late destroyed their deer, he conceived that the want of venison might be well supply'd by the bodies of young lads and maidens, not exceeding fourteen years of age, nor under twelve; so great a number of both sexes in every country being now ready to starve for want of work and service: And these to be disposed of by their parents if alive, or otherwise by their nearest relations. But with due deference to so excellent a friend, and so deserving a patriot, I cannot be altogether in his sentiments; for as to the males, my American acquaintance assured me from frequent experience, that their flesh was generally tough and lean, like that of our school-boys, by continual exercise, and their taste disagreeable, and to fatten them would not answer the charge. Then as to the females, it would, I think, with humble submission, be a loss to the publick, because they soon would become breeders themselves: And besides, it is not improbable that some scrupulous people might be apt to censure such a practice, (although indeed very unjustly) as a little bordering upon cruelty, which, I confess, hath always been with me the strongest objection against any project, how well soever intended. But in order to justify my friend, he confessed, that this expedient was put into his head by the famous Salmanaazor, a native of the island Formosa, who came from thence to London, above twenty years ago, and in conversation told my friend, that in his country, when any young person happened to be put to death, the executioner sold the carcass to persons of quality, as a prime dainty; and that, in his time, the body of a plump girl of fifteen, who was crucified for an attempt to poison the Emperor, was sold to his imperial majesty's prime minister of state, and other great mandarins of the court in joints from the gibbet, at four hundred crowns. Neither indeed can I deny, that if the same use were made of several plump young girls in this town, who without one single groat to their fortunes, cannot stir abroad without a chair, and appear at a play-house and assemblies in foreign fineries which they never will pay for; the kingdom would not be the worse. Some persons of a desponding spirit are in great concern about that vast number of poor people, who are aged, diseased, or maimed; and I have been desired to employ my thoughts what course may be taken, to ease the nation of so grievous an incumbrance. But I am not in the least pain upon that matter, because it is very well known, that they are every day dying, and rotting, by cold and famine, and filth, and vermin, as fast as can be reasonably expected. And as to the young labourers, they are now in almost as hopeful a condition. They cannot get work, and consequently pine away from want of nourishment, to a degree, that if at any time they are accidentally hired to common labour, they have not strength to perform it, and thus the country and themselves are happily delivered from the evils to come. I have too long digressed, and therefore shall return to my subject. I think the advantages by the proposal which I have made are obvious and many, as well as of the highest importance. For first, as I have already observed, it would greatly lessen the number of Papists, with whom we are yearly over-run, being the principal breeders of the nation, as well as our most dangerous enemies, and who stay at home on purpose with a design to deliver the kingdom to the Pretender, hoping to take their advantage by the absence of so many good Protestants, who have chosen rather to leave their country, than stay at home and pay tithes against their conscience to an episcopal curate. Secondly, The poorer tenants will have something valuable of their own, which by law may be made liable to a distress, and help to pay their landlord's rent, their corn and cattle being already seized, and money a thing unknown. Thirdly, Whereas the maintainance of an hundred thousand children, from two years old, and upwards, cannot be computed at less than ten shillings a piece per annum, the nation's stock will be thereby encreased fifty thousand pounds per annum, besides the profit of a new dish, introduced to the tables of all gentlemen of fortune in the kingdom, who have any refinement in taste. And the money will circulate among our selves, the goods being entirely of our own growth and manufacture. Fourthly, The constant breeders, besides the gain of eight shillings sterling per annum by the sale of their children, will be rid of the charge of maintaining them after the first year. Fifthly, This food would likewise bring great custom to taverns, where the vintners will certainly be so prudent as to procure the best receipts for dressing it to perfection; and consequently have their houses frequented by all the fine gentlemen, who justly value themselves upon their knowledge in good eating; and a skilful cook, who understands how to oblige his guests, will contrive to make it as expensive as they please. Sixthly, This would be a great inducement to marriage, which all wise nations have either encouraged by rewards, or enforced by laws and penalties. It would encrease the care and tenderness of mothers towards their children, when they were sure of a settlement for life to the poor babes, provided in some sort by the publick, to their annual profit instead of expence. We should soon see an honest emulation among the married women, which of them could bring the fattest child to the market. Men would become as fond of their wives, during the time of their pregnancy, as they are now of their mares in foal, their cows in calf, or sow when they are ready to farrow; nor offer to beat or kick them (as is too frequent a practice) for fear of a miscarriage. Many other advantages might be enumerated. For instance, the addition of some thousand carcasses in our exportation of barrel'd beef: the propagation of swine's flesh, and improvement in the art of making good bacon, so much wanted among us by the great destruction of pigs, too frequent at our tables; which are no way comparable in taste or magnificence to a well grown, fat yearly child, which roasted whole will make a considerable figure at a Lord Mayor's feast, or any other publick entertainment. But this, and many others, I omit, being studious of brevity. Supposing that one thousand families in this city, would be constant customers for infants flesh, besides others who might have it at merry meetings, particularly at weddings and christenings, I compute that Dublin would take off annually about twenty thousand carcasses; and the rest of the kingdom (where probably they will be sold somewhat cheaper) the remaining eighty thousand. I can think of no one objection, that will possibly be raised against this proposal, unless it should be urged, that the number of people will be thereby much lessened in the kingdom. This I freely own, and 'twas indeed one principal design in offering it to the world. I desire the reader will observe, that I calculate my remedy for this one individual Kingdom of Ireland, and for no other that ever was, is, or, I think, ever can be upon Earth. Therefore let no man talk to me of other expedients: Of taxing our absentees at five shillings a pound: Of using neither cloaths, nor houshold furniture, except what is of our own growth and manufacture: Of utterly rejecting the materials and instruments that promote foreign luxury: Of curing the expensiveness of pride, vanity, idleness, and gaming in our women: Of introducing a vein of parsimony, prudence and temperance: Of learning to love our country, wherein we differ even from Laplanders, and the inhabitants of Topinamboo: Of quitting our animosities and factions, nor acting any longer like the Jews, who were murdering one another at the very moment their city was taken: Of being a little cautious not to sell our country and consciences for nothing: Of teaching landlords to have at least one degree of mercy towards their tenants. Lastly, of putting a spirit of honesty, industry, and skill into our shop-keepers, who, if a resolution could now be taken to buy only our native goods, would immediately unite to cheat and exact upon us in the price, the measure, and the goodness, nor could ever yet be brought to make one fair proposal of just dealing, though often and earnestly invited to it. Therefore I repeat, let no man talk to me of these and the like expedients, 'till he hath at least some glympse of hope, that there will ever be some hearty and sincere attempt to put them into practice. But, as to my self, having been wearied out for many years with offering vain, idle, visionary thoughts, and at length utterly despairing of success, I fortunately fell upon this proposal, which, as it is wholly new, so it hath something solid and real, of no expence and little trouble, full in our own power, and whereby we can incur no danger in disobliging England. For this kind of commodity will not bear exportation, and flesh being of too tender a consistence, to admit a long continuance in salt, although perhaps I could name a country, which would be glad to eat up our whole nation without it. After all, I am not so violently bent upon my own opinion, as to reject any offer, proposed by wise men, which shall be found equally innocent, cheap, easy, and effectual. But before something of that kind shall be advanced in contradiction to my scheme, and offering a better, I desire the author or authors will be pleased maturely to consider two points. First, As things now stand, how they will be able to find food and raiment for a hundred thousand useless mouths and backs. And secondly, There being a round million of creatures in humane figure throughout this kingdom, whose whole subsistence put into a common stock, would leave them in debt two million of pounds sterling, adding those who are beggars by profession, to the bulk of farmers, cottagers and labourers, with their wives and children, who are beggars in effect; I desire those politicians who dislike my overture, and may perhaps be so bold to attempt an answer, that they will first ask the parents of these mortals, whether they would not at this day think it a great happiness to have been sold for food at a year old, in the manner I prescribe, and thereby have avoided such a perpetual scene of misfortunes, as they have since gone through, by the oppression of landlords, the impossibility of paying rent without money or trade, the want of common sustenance, with neither house nor cloaths to cover them from the inclemencies of the weather, and the most inevitable prospect of intailing the like, or greater miseries, upon their breed for ever. I profess, in the sincerity of my heart, that I have not the least personal interest in endeavouring to promote this necessary work, having no other motive than the publick good of my country, by advancing our trade, providing for infants, relieving the poor, and giving some pleasure to the rich. I have no children, by which I can propose to get a single penny; the youngest being nine years old, and my wife past child-bearing.
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The basic thesis of Your Inner Fish is that we can learn something about ourselves by studying other organisms and observing the similarities between us. Chapter 2 examines the anatomy of the limbs of a number of different organisms. That chapter began with the observations of Sir Richard Owens who saw how many diverse organisms shared a common body plan, as exemplified by the structure of the limbs.
Darwin explained these similarities by proposing that the source of this commonality was that there exists a real relationship between even apparently diverse species. If this hypothesis is correct, we can expect that more similarities can be found and that these comparisons go well beyond skin deep.
Chapter 3 expands on this theme, retaining the focus on limb / hand construction and moving from simple anatomical comparisons to the underlying genetics that control the development of these structures.
If you study genetics for long you will see patterns in the way that genes work together. There often exists a number of genes responsible for some specific structure that are all controlled by a more limited number of regulator genes, these too are controlled by some master regulator. The master regulator often acts as a toggle switch that turns on or off certain other genes in a system leading to a cascade of effects. Possibly even more interesting is that these same master regulator genes may be found again and again initiating different outcomes in different locations.
In the case of the ZPA, it was found that this patch of tissue secretes a substance that provides a gradient across the developing limb leading to differential developmental patterning in digits according to the dose of hormone cells receive. This effect was most clearly demonstrated by inserting a second ZPA in a fashion that creates a mirror image gradient, leading to a corresponding mirror image limb structure (see below.)
Shubin describes one of these regulatory pathways as being controlled by a patch of tissue called the zone of polarizing activity (ZPA). This patch controls the development of limbs by providing chemical cues to cells in the area. Later, the chemical entity that is secreted from the ZPA and controls this behavior was identified and named Hedgehog / Sonic Hedgehog. Further experiments have been performed using variable quantities of Sonic Hedgehog or modified hormone resulting in similar malformations of limbs.
One trick that Shubin highlights several times throughout Your Inner Fish is how genes or proteins from one animal may be swapped into another animal and work perfectly normally. The reason he likes to point out the success of these experiments is that that provide excellent support for his hypothesis that all life is related.
An alignment of Sonic Hedgehog proteins is presented below to illustrate the similarities across a number of species. Each organisms’ primary amino acid sequence is presented stacked upon other organisms’ sequences. Identical amino acids are highlighted in yellow.
I just completed a survey on the HHMI website that introduced me to some of their resources that I have not yet explored. One that I thought was relevant to our current work is on chromosomes, genes and sex determination. It can be found here.
Follow this link to the BioInteractive Animation Page where you can find the animations of DNA Replication, Transcription and Translation (among others) that we watched and discussed in class.
A workable Theory
Gregor Mendel did the first documented, accurate analysis of how one generation inherits traits from their parents’. However, being so far ahead of his time, and possibly because he may have been considered an outsider to the scientific community, the value of his work was not grasped and it was quickly forgotten. Mendel had stated a couple of theories in his paper making theoretical assumptions of how ‘factors’ responsible for inheritance are segregated during the formation of gametes and then rejoined in the zygote. Together, the two factors that every individual had for each trait determined the expression of that trait.
Colorful Bodies
From Zellsubstanz, Kern und Zelltheilung, 1882
A couple decades later Walther Flemming observed, under his microscope, some curious movements of things called ‘chromosomes’ (or colorful bodies). Unfortunately, he did so without knowledge of Mendel’s work and thus didn’t recognize the greater meaning of his discovery. At this time Germ Plasm Theory (not to be confused with Germ Theory) was being debated as a means of inheritance. This theory suggested that special germ cells carried the hereditary material from one generation to the next and that these cells were uninfluenced by the other cells of the body. The plasm itself took the place of Mendel’s idea of factors, but functioned as a more inclusive measure of material, more akin to what we call the genome today. I say ‘plasm’ is replacing ‘factors’, but it should be noted that no one intentionally renamed Mendel’s factors. The real problem was that no one knew about his work at all.
Edouard Van Beneden had been investigating similar chromosomal movements during meiosis that produced the gametes, or germ cells. However, he too was having a difficult time constructing a cogent theory concerning how these movements led to inheritance.
August Weismann
August Weismann was in the best position at the time to put the pieces together as he was already turning the available information over in his mind to construct a big picture. He recognized that the nucleus was the likely source of the ‘plasm’ and even considered the chromosomes as a possible candidate for this material. Further, he was concerned with how it was that germ cells could join in a way that did not double the heritable material with every generation.
Connecting the Dots
It was not until Sutton and Boveri independently unearthed Mendel’s work and recognized the similarity of chromosome movement during gametogenesis (making sperm and egg cells) to his descriptions of ‘factors’ that The Chromosomal Theory of Inheritance was first seriously proposed.
Altogether, these observations led many to believe that it was, indeed, the chromosomes that carried the genetic material. Still, this did not pinpoint what molecule was responsible or how it accomplished this for chromosomes are comprised of long strings of DNA and a number of proteins. Given the simplicity of DNA, many refuted this as potential genetic material as it simply could not carry the required information. Perhaps it served as a scaffold for the more important protein molecules? This was consistent with the chromosomal theory and had the benefit of allowing for complicated proteins to bear the information required to build new cells and organisms.
Griffith with his pal Bobby
Fredrick Griffith was one of the earliest workers to begin the march to identify the specific molecules that functioned as heritable material. While working to develop a vaccine against Streptococcus pneumoniae, he discovered their curious capacity for communicating information laterally, from one organism to another.
Griffith’s Experiments: Glimpsing the Answer
Two forms of the bacteria were known: One a virulent smooth form that secreted a protective carbohydrate capsule, and Secondly, a rough strain that lacks this protective coating and is non-virulent. Predictably, mice he infected with the smooth strain died as a result of bacterial overgrowth. Mice infected with the rough strain overcame the infection and lived. Also, as one would predict, heat-killed bacteria of both strains had no ill effect on mice. But what Griffith did next was much more interesting…
He took heat killed smooth bacteria and combined it with the non-virulent rough form and found that the resulting cocktail of bacteria not only killed mice, but these mice were also found to be overgrown with the smooth form of the bacteria.
What are the possible explanations?
Griffith chose the simpler second option and suggested that some transforming factor was responsible. This factor was released by the dead S strain and carried heritable information.
Unfortunately, Griffith wasn’t around long enough to see the story play out as he perished during the German air raids of London during WWII. But one last experiment done by another group illustrated that he was one the right path. This experiment repeated Griffith’s work carefully, but instead of combining S strain and R strain bacteria, the S strain bacteria were spun down into a pellet using a centrifuge and only the liquid supernatant was moved in with the R strain bacteria. As Griffith might have suggested, this liquid carried his transforming factor and was sufficient to cause a change in the R strain to make it produce and secrete the carbohydrate capsule.
This last experiment and some others were done by the laboratory of Avery, MacLeod and McCarty at the Rockefeller Institute in New York and will have to be discussed in a future post.
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