Bane of the Garden Gnomes

Last week, we discussed the use of the Hardy Weinberg equations to estimate the rate of change in population under conditions of extreme selection, i.e. total elimination of one phenotype. This is essentially the goal of any sort of eugenics program. As an example of a way that this kind of policy could creep into culture, we watched GATTACA. Besides, it’s just a good film.

The purpose of the Hardy Weinberg equations is to model conditions under which allele frequencies can NOT change from one generation to the next. Therefore, it is evident that these are exactly those conditions that are responsible for allele frequency changes.

These conditions are:

1. No Mutation
2. No Selection (survival)
3. No Sexual Selection
4. No Genetic Drift –due to occasional fluctuations occurring by chance
5. No Gene Flow – immigration / emigration

In order to prevent the random changes in allele populations stipulated in #4, we also need a sufficiently large population, where sufficient is likely definable by someone with better probability-computing skills than my own. (I feel like going off half-cocked on notions of probability and finite vs infinite time, but I’ll spare you).

Anyway, if we know something about the population, we might be able to work out the allele frequencies and then compute our theoretical proportions for the next generation from the equations…

p+q = 1,

where p and q are the frequencies of the (only) two alleles we are calculating.

and

p²+2pq+q² = 1

where each unit above represents the proportion of that genotype.

Mathematically, these equations provide insight into how rapidly the rate of an allele in a population could be eliminated if reproduction was prevented in a specific group. (This sounds completely esoteric without using an example, so let’s come up with one…)

A Healthy Gnome Couple

Imagine a population of fictional creatures – Garden Gnomes.

These gnomes have a recessive allele that makes them susceptible to a fungal disease. We’ll call the two alleles for this trait H – hearty (resistant) and h– weak (susceptible)

There was recently a new law passed amongst the gnomes forbidding susceptible gnomes from breeding (let’s imagine that the H allele is apparent by a normal complexion and the h allele is apparent by a jaundiced complexion. Like susceptibility to disease, jaundice only appears in the homozygous recessive (hh) gnomes.)

Imagine a population starting with equal allele frequencies, p=q=0.5.

p²+2pq+q² = 1

will give us genotype frequencies of:

25% HH   + 50% Hh + 25%hh = 1

for the present generation.

Now, if we start our draconian, anti-jaundiced gnome policy and prevent breeding of these individuals, then this generation‘s breeding population only consists of the HH and Hh gnomes, where only the heterozygotes will contribute the h allele to the next generation.

If we call the next generation q₁, we can estimate the new proportion of the q allele in the population as the frequency of the heterozygote over the total population excluding the hh gnomes:

No wonder they want to get rid of these guys

After one generation, the frequency of the H allele is now 67%.

Since the same process would occur generation after generation (as long as the law was in place – and followed), we can determine the frequency of q at any generation, where n is the generation number.

1. From this information, try calculating the frequency of both alleles after the policy has been in place for 5 generations.
2. How long will it take to completely eliminate the h allele?
3. How would this change if the susceptible (h) allele is dominant?

 

A Pointer to My Post After Watching GATTACA

Today’s post about the film, GATTACA, is just as much a movie review as it is a discussion of eugenics, so I thought I’d post that on my other blog instead. Go on over and check that out. That and my thoughts on an ungodly number of bad movies that I watch all the time. 

 

Eugenics in film: GATTACA

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?

 

Science on Screen

You know, I’m pretty happy with the present state of science on the small screen. This week, we had the opportunity to choose between three excellent shows with real scientists explaining fundamental principles to a wide audience. These shows are:

Cosmos with Neil Tyson

Your Inner Fish with Neil Shubin

Wonders of Life with Brian Cox

 

Of the three, I think Brian Cox is probably the best spokesperson for science – meaning he has a very casual and unassuming presence and speaks in a slow, measured pace that draws the listener in, eager to hear what’s coming. The camerawork in the Wonders of Life series is also good. It’s more artsy than you would expect from a science show, often putting the Sun behind Dr. Cox’ head to create moments of strong flares that’s muted post-production (I suspect). This technique works wonders when properly utilized. It creates drama and a bit of mystique because it flies in the face of one cardinal rule of photography. In many ways it reminds me of the cooking show Nigella Bites. Besides its production value, the science is solid, well presented and clearly explained. Here Dr. Cox explains the apparent retrograde motion of the planets (wanderers).

 

Cosmos works well because it is a reprise of a previously well-received series by the much-beloved Carl Sagan. How could it miss? So much is done well. I especially like the simple animations that bring history alive for us. People are hardwired for storytelling, so I firmly believe that science is learned best when it is part of a well-crafted story – and the stories told in Cosmos are right on. And one last word: wow. This is on Fox! Frankly, I’m amazed. Maybe Neil can teach O’Reilly why the tide goes in and out.

 

Your Inner Fish was initially a book that I use every semester I teach General Biology. As a book it functions well, the story is clear and filled with examples – although we do get lost in the details from time to time. Overall, I like it and think it’s a great introduction to scientific thinking. As a series, the same story is told, but with a greater clarity and excellent use of digital effects to complement the story without getting in the way.

 

All three are excellent – and more than anything, I just enjoy knowing that popular television, reaching a wide audience, is seeing a surplus of high quality, entertaining, educational material that is not soft on science.

 

Epidemiology: Should farmers try to do more work near noon?

The CDC has a wealth of classroom information (case studies, discussion material) regarding epidemiology. No surprise there. It’s what they do.

In my Microbiology class we’re starting a unit on epidemiology that students are working on in their free time either alone or in groups. We will talk about the project as questions come up, but mostly, I wanted people to have an opportunity to think freely – i.e. without me forcing my own ideas on them.

In my Ecology (population genetics, etc) class, we just spent some time last week discussing how data is just data, and in the absence of a reason to mistrust it, it probably makes sense to assume that the data is correct. However, this leaves the interpretation of the data up for much debate. ‘How so?’ I was asked. ‘Because people run experiments with certain ideas in mind that they would like to support or undermine. There can be many ways to misinterpret data.’

With this in mind, I ask you…

Should farmers try doing more work near noon?

Data suggests that this is the safest time of day. Yet, anecdotally, fewer farmers are putting time in the field at this hour than any other hour of the day(8am-8pm). What’s going on?

 

A pointer into the past

Opps – post removed to alternate blog.

 

An Epidemiological Method: Using RFLP to Identify Strains of Pathogens

An excellent classroom resource for a case study in epidemiology is presented by the CDC. This study walks students through an outbreak of E. coli O157:H7 in Michigan.

The purpose of this study is to provide student investigators with the opportunity to walk through the procedures and rationale behind investigating the etiology and to develop experiments testing hypotheses generated by the students.

I am using this exercise as an end-of-semester project for my microbiology students to work through collaboratively now that we have completed our discussion of Paul Offit’s Vaccinated.

The study begins:

PART I – OUTBREAK DETECTION

 

Escherichia coli O157:H7 was first identified as a human pathogen in 1982 in the United States of America, following an outbreak of bloody diarrhea associated with contaminated hamburger meat. Sporadic infections and outbreaks have since been reported from many parts of the world, including North America, Western Europe, Australia, Asia, and Africa. Although other animals are capable of carrying and transmitting the infection, cattle are the primary reservoir for E. coli O157:H7. Implicated foods are typically those derived from cattle (e.g., beef, hamburger, raw milk); however, the infection has also been transmitted through contact with infected persons, contaminated water, and other contaminated food products.

Infection with E. coli O157:H7 is diagnosed by detecting the bacterium in the stool. Most laboratories that culture stool do not routinely test for E. coli O157:H7, but require a special request from the health care provider. Only recently has E. coli O157:H7 infection become nationally notifiable in the U.S. Outside the U.S., reporting is limited to a few but increasing number of countries.

In the last week of June 1997, the Michigan Department of Community Health (MDCH) noticed an increase in laboratory reports of E. coli O157:H7 infection. Fifty-two infections had been reported that month, compared with 18 in June of 1996. In preliminary investigations, no obvious epidemiologic linkages between the patients were found.   The increase in cases continued into July.

Students are then asked a number of introductory questions and then presented with the following problem:

Compare the DNA fingerprints in Figure 2 from seven of the Michigan E. coli O157:H7 cases. Each isolate has its own vertical lane (i.e., column). Controls appear in lanes #1, 5, and 10. Which Michigan isolates appear similar?

This question requires some background in DNA Fingerprinting (aka Restriction Fragment Length Polymorphisms, or RFLPs), which I want to take some time to explain.

As the source material states, The purpose of this test is to identify common strains of organisms through their DNA banding pattern. “Different DNA composition will result in different PFGE banding patterns. Bacteria descended from the same original parent will have virtually identical DNA and their DNA fingerprints will be indistinguishable. Identification of a cluster of isolates with the same PFGE pattern suggests that they arose from the same parent and could be from the same source. “ (emphasis mine).

The method involves two core techniques. First, DNA from the target organism must be isolated and cut with one or more restriction enzyme(s). This will create a number of DNA fragments, where the precise number and size of fragments is determined by the sequence of that organism’s DNA.

As an example, let’s imagine a 10,000 base pair (bp) chromosome that we intend to cut with the restriction enzyme, EcoRI. EcoRI recognizes and cuts double stranded DNA at a specific sequence of 6 bases.

Figure: DNA cut by the Restriction Enzyme, EcoRI. A. DNA sequence with EcoRI recognition site highlighted and cut pattern illustrated. B. Enzyme binds to DNA at the recognition site. C. DNA has been cleaved.

On average, this enzyme will cut a random sequence of DNA every 4096 bases (this can be estimated by 4 raised to the power of n, where n = the number of bases in the enzyme’s recognition sequence , or 4⁶ = 4096 in this case.) In our example, this suggests that a 10,000 bp chromosome will have two EcoRI sites by random chance.

The circular chromosome should be cut twice by this enzyme, resulting in two fragments of DNA (see note #2, below). Let’s say the two bands are 4000 bp and 6000 bp.

We can see these two fragments by running them through agarose, which works as a molecular sieve, to separate the two fragments by size

How does this work?

DNA is a negatively charged molecule with that charge spread uniformly across the length of the fragment. Therefore, there is no difference in charge between our two fragments, except in proportion to their length. This means that as they run through the sieve, the only difference between the molecules comes from their lengths. As any sieve, smaller objects go through easier, while larger ones are held up.

The result is that the two fragments will appear as distinct bands on a gel, with the smaller fragment running farther through the agarose that the larger. (here, the smaller band at the bottom of the gel has migrated farther toward the positive electrode)

If someone new were to become infected with this bacteria, we could isolate it from them, digest the DNA and get the same banding pattern. A closely related bacteria may have one additional EcoRI site. This would result in one of the two bands being cut into two smaller fragments, meaning that the two strains could be easily distinguished.

Back to the question posed above…

Given this, examine the following compilation of samples. Controls appear in lanes #1, 5, and 10. Which of the remaining isolates appear similar?

Definitions:

1. Restriction Enzyme or Restriction Endonuclease– an enzyme that can recognize and cut DNA.
2. Recognition Sequence – the sequence of bases that a restriction enzyme recognizes and binds to.

 

Notes:

1. In my example, we are using the restriction enzyme, EcoRI, to cut DNA from E. coli. As the name suggests, EcoRI actually derives from E.coli, where it functions as a defence against invading DNA, i.e. a virus. In order to do this successfully, E. coli will either not have any EcoRI restriction sites in its own DNA, or it will protect them by methylation so that the enzyme does not destroy the host’s own DNA. I am ignoring the possibility that the DNA we are dealing with in our experiment may not be cleavable with this enzyme.
2. Also note, that bacterial chromosomes are circular, rather than linear – interestingly, this means that they are not actually ‘chromosomes’ at all. Again, let’s ignore this.

 

Welcome back to Fargo, North Dakota.

The Metamorphosis of the TV Series

 

I had to show this to my wife

Some symptoms of hypoglycemia include headaches, weakness, nervousness, trembling and unclear thinking. Another thing you might notice is when you are hypoglycemic, it’s not a good time to talk with you spouse about finances.

A recent article, published (ahead of print) in the Proceedings of the National Academy of the Sciences by Brad Bushman, et al used voodoo dolls and loud noise blasts to measure the aggression spouses felt at one another.

[E]ach evening participants stuck between 0 and 51 pins into a voodoo doll that represented their spouse, depending how angry they were with their spouse. To measure aggression, participants competed against their spouse on a 25-trial task in which the winner blasted the loser with loud noise through headphones. As expected, the lower the level of glucose in the blood, the greater number of pins participants stuck into the voodoo doll, and the higher intensity and longer duration of noise participants set for their spouse.

I’m relating to the feelings of aggression thing a bit lately. No against my wife – or against anyone in particular, but just a low level sense of irritability most likely attributable to the diet I recently adopted. I’ve been trying to exercise more lately, but the more I exercised, the more I found myself ‘grazing’ in the kitchen, looking for just anything.

As I continued exercising and eating more to compensate, I was getting more and more frustrated by any return on my exercise investment, so I finally gave in and admitted that I needed to do something about the other end of the calorie equation. I considered a couple of methods, but finally settled on the ‘Lose It’ app for my iPhone. Basically, this app serves as a food and exercise journal with a little goal-oriented motivation thrown in for good measure. one of the things I liked best about the app was its use of graphs to follow weight loss and project how long, if trends continue, it will take to achieve a weight loss goal.

Really, there’s nothing like a food diary to limit what you eat.

But it’s not just hypoglycemia. Other work suggests that just engaging in self-limiting behavior – exerting self-control – leads to increased aggression. “In one study people who choose an apple instead of a chocolate bar were more likely to choose movies with anger and revenge themes than milder movies.”

Well, according to the app, I only have to keep things under control for another 100 days. Another 100 days of movies to line up.

 

Another Puzzle – about the interaction of host and pathogen

Ok, I realize that some of the past puzzles I’ve made either had errors or were simply too obscure in their clues (again, I’m a crossword novice). I tried to be a little more clear with this puzzle and also did my best to force as many clues into actually ‘crossing’ as possible.

Let me know what you think and if you suspect any errors. The topic is: the host-pathogen interaction, our first chapter on immunology.

 

Clues