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?

 

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?

 

RadioLab’s Inheritance Podcast

My son and I just listened to a completely engrossing podcast on inheritance from RadioLab. The episode had three stories about different aspects of inheritance and genetic control. The first didn’t capture my interest nearly as much as the next two, so I won’t discuss it here.

The second story proposed and interesting idea of Lamarckean inheritance based on the extraordinary record-keeping of a far-north town in Sweden. In this town, the church kept amazingly detailed records about births, deaths, disease, health and even crop production year to year. When all these data were analyzed, researchers found a strong correlation between the availability of food to men in the village and the health and wellbeing of that man’s children. What might seem unintuitive is that contrary to what you might think, the children of men who suffered through years of starvation when they were ~9-12 years old fared the best. If dad ate well, your health prognosis was poor. If dad ate poorly, your prognosis was better. The effect even seemed to trace down two generations.

The explanation for this was that at this time in a man’s life he is making the cells that will go on to make sperm. Somehow, these cells can receive genetic imprinting that improves the fitness of the offspring.

Let me stop here. I have to say, I think this is entirely unconvincing. I can think of at least one simpler explanation for these data. Further, I can easily imagine how if it was possible to turn on these beneficial changes, evolution would make this the norm rather than the exception.

Example data. A) Population lifespan following feast years, 100% survival. B) Population lifespan following famine years, 50% survival.

Consider a population of 100 kids in the target age group during a year of ‘feast.’ 100% of these kids survive and have children. These children have an average lifespan of 50yrs. Given the same group during a year of ‘famine.’ 50% of the kids survive and have children. The children live to an average age of 75 yrs. It appears that the famine during the elder generation improved the fitness of the younger.

But, if we examine the ‘feast’ population again, we might see that they can be broken up into two natural groups, one with a 75yr lifespan (the healthier 50%) and one with a 25yr lifespan (the less healthy). If the famine year selectively kills the weaker kids, then we are simply selecting our way to better health rather than causing it.

Because this is published research I expect that this simple answer was excluded somehow and I hope to find the original work to see that, but the burden of proof rests on the group proposing the more complex explanation.

I’ll see if I can research this a little and write again later, but I wanted to comment right away because I thought that it was an interesting example of how numbers can sometimes lead you astray if you’re not careful.

Oh, and very quickly, the last story…

The last story was about a woman who had adopted a baby girl, Destiny, from a mother who was addicted to drugs and couldn’t support the child. Amazingly, the next three years after that, the same mother gave birth to three more addicted babies that were all adopted by the same family. Because of her frustration about how this woman was so casually bringing more children into the world, one a year, each addicted to heroin et al. at the time of birth, the adoptive mother tried to pass a law to somehow prevent this from happening. When that failed, she worked directly to set up a fund to pay addicted women to undergo surgical sterilization or get long term birth control.

Many saw this as eugenics in action. Personally, I see no convincing connection to eugenics whatsoever based on the fact that the procedure was voluntary and based on a behavior rather than an innate characteristic of the women. Nevertheless, the conversation went places I never expected – mostly because I thought Jad and Robert would not get drawn into such ridiculous speculations and extensions of logic as they did. It was still good listening though.

I highly recommend checking out this episode.

 

Making Better Babies – A pragmatic solution to a problem and the ethical firestorm it provokes

Let’s say you are a young person thinking about having a baby, but you know there is a genetic disease in your family that worries you. It’s a reasonable concern that people have recognized for some time. There have always been diseases to concern parents, but technology is changing how we think about and face these concerns.

A Downs Syndrome Karyotype

Once upon a time these was little more to do but cross your fingers and hope for a good result. Then chromosomal testing (Karyotyping) of a developing fetus became possible allowing parents to know what is happening inside the womb. Getting this information was not without risk, and even with the results in hand, would-be parents are faced with terrible choices. The way we dealt with this test in our family was to not have it done. We really wanted a baby and thought that  that having test results would not change our behavior. So we chose not to be put in a position of having to make that choice. It was what worked for us, but we also didn’t have specific concerns other than the fact that we were getting older.

Following the advent of chromosomal tests, it became possible to test the DNA of a fetus for specific, known problems. For example, If caner runs in the family, you could check to see if the baby’s p53 gene was normal. Having one or more bad copy of this gene dramatically raises the probability of developing cancer relatively early in life. Today, this is something we can know for certain.

But there are several sources of DNA in us. We typically think of the vast amount of DNA carried in the form of linear chromosomes that are packaged inside the nucleus of our cells. This is definitely the lion’s share of the DNA passed from one generation to the next, but there is another source as well: The Mitochondria. You may have learned about these organelles (little organs) as the ‘Powerhouse of the Cell’ for its role in generating much of the energy (ATP) your cells need to do their jobs. These organelles have a strange history in us. It is thought that many eons ago those things that are now mitochondria inside our cells were once free living organisms (possibly parasites, possibly a bigger cell’s dinner). However it happened these microbes were taken inside of our cells, but not digested as food or harmful enough to kill the host either.

Powerhouse

Why am I talking about this? Because those organelles still carry remnants of their former selves. They still have their own protein-making machinery and even their own DNA. This DNA isn’t large, but it does carry genes coding for vital proteins. And this is how we get back to our original story, because sometimes these mitochondrial genes are no good. If these genes aren’t right, they can’t make healthy, functional proteins. If they can’t make good proteins, then the host cell and the while organism can die.

Interestingly, all the mitochondria in every cell of your body came from your mother. This is one place where dad makes no contribution. Even though sperm have mitochondria, they don’t get incorporated into the new zygote, only those from the egg will remain.

Enter The Future of Fertility Medicine

Recent developments have shown that it is possible to replace the unhealthy mitochondria with healthy versions from a donor cell to make good eggs that can be fertilized and result in a healthy child. This was the subject of an excellent review in Nature and also discussed on the Nature Podcast this week. So how many parents is that? One mom, one dad and one mitochondria donor (I guess this could conceivably come from dad, but I just don’t know). This procedure has been done successfully with non-human primates, but so far not with humans.

So, pursuing a simple line of work aimed at helping parents make healthy babies is suddenly possible and suddenly a great ethical question. Have you ever seen Gattaca? If not, go out and watch it. I was sure this film was going to be miserable and be a poor representation of science, but I was totally wrong. They ask the same questions in that film that we are beginning to face in real life:

This isn’t the first time people have thought about this

When does Medicine become tampering with life? And does it matter? Don’t we want healthier, more able bodied people? Is it wrong to replace bad genes? What constitutes ‘bad’?

Personally, I don’t believe that there are universally right and wrong answers to these questions. Even if we decide that there are some less desirable consequences for mankind, that doesn’t mean that we wouldn’t do it. Much of plastic surgery isn’t really necessary and some might call it a perversion of medicine, but that doesn’t stop tons of people from getting it.