You've Been Lied To About Genetics

Summary

The video script explores the complexities of genetics beyond the traditional Mendelian model. It discusses the Human Genome Project's unfulfilled promises and critiques the oversimplified view of genetics taught in schools. The script introduces Waddington's landscape as a more accurate metaphor for gene expression, emphasizing the interplay of multiple genes and environmental factors. It argues for updating educational curricula to reflect modern genetic understanding and warns against the deterministic thinking that can lead to eugenics.

Takeaways

• 🧬 The Human Genome Project aimed to sequence the entire human genetic code, but the relationship between DNA and human traits is more complex than initially thought.
• 🔎 The expectation in the mid-90s was that by 2020, individuals would carry genome cards for doctors to diagnose genetic issues, but this has not come to pass.
• 🤔 The simplistic view of genetics, where traits like blue eyes or red hair are determined by single genes, is not accurate for most human characteristics.
• 🌱 Gregor Mendel's pea plant experiments laid the foundation for understanding inheritance, but his findings were based on specific, controlled conditions that do not always apply to complex traits in humans.
• 🎲 Mendel's laws of inheritance, such as the 3:1 ratio, are useful for understanding certain genetic patterns, but they do not account for the complexity of gene-environment interactions.
• 👁 Eye color, often cited as a simple Mendelian trait, is actually influenced by multiple genes, demonstrating the complexity of genetic inheritance.
• 🤹‍♂️ Conrad Hal Waddington's 'landscape' model of genetics emphasizes the complex interplay of genes and environmental factors in determining traits, moving away from the blueprint analogy.
• 🎢 Waddington's landscape metaphor illustrates how traits are the result of a developmental process influenced by many genes and environmental factors, not just single genes.
• 🧬 The Y chromosome, often thought to 'determine' male sex, actually works in concert with other genes and environmental factors, highlighting the non-deterministic nature of genetics.
• 🔄 Modern genetics education should incorporate the complexity and interplay of genes and environment, rather than relying on outdated, oversimplified models.
• 📚 The Genetics Pedagogies Project has developed a curriculum that presents the entangled nature of genes, environments, and organisms, providing a more accurate and modern view of genetics.

Q & A

What was the primary goal of the Human Genome Project?

The primary goal of the Human Genome Project was to sequence the entire human genetic code, often referred to as the 'human blueprint'.

What did science journalist Laurie Garrett predict would happen by 2020 in relation to the Human Genome Project?

Laurie Garrett predicted that by 2020, everyone would be carrying their own genome cards, which doctors could use to diagnose genetic mutations and provide gene therapy.

Why did the Human Genome Project's vision not materialize as expected?

The vision did not materialize because the link between DNA and human traits is far more complex than initially imagined, with no direct connection between genes and traits for most characteristics.

Who is considered the father of genetics and what was his significant contribution?

Gregor Mendel is considered the father of genetics, and his significant contribution was his work with pea plants, where he discovered patterns of inheritance that laid the foundation for understanding genetic traits.

What was the issue with the simplistic view of genetics that was taught in schools and portrayed in the media?

The issue was that this view oversimplified genetics by suggesting direct connections between single genes and traits, which is not accurate given the complexity of gene interactions and environmental influences.

What is the 'Waddington landscape' and how does it differ from Mendelian genetics?

The 'Waddington landscape' is a metaphor that represents genes as a complex system influencing development, with traits resulting from the interaction of many genes and environmental factors. It differs from Mendelian genetics by acknowledging the complexity and interplay of genes rather than viewing them as simple blueprints with direct outcomes.

How does the Y chromosome's role in determining sex illustrate the complexity of genetic traits?

The Y chromosome, often considered to 'determine' male sex, actually functions in concert with many other genes and environmental factors. Cases like Caster Semenya, who has XY chromosomes but is female, show that the Y chromosome alone does not guarantee a specific sex, highlighting the complexity of genetic traits.

What is the significance of the Genetics Pedagogies Project in teaching genetics?

The Genetics Pedagogies Project is significant because it created a curriculum that emphasizes the entangled nature of genes, environments, and organisms, presenting Mendelian traits as a rare special case. This approach helps students understand the subtleties of modern genetics and reduces the belief in genetic determinism.

Why is it important to teach a more accurate and modern view of genetics in schools?

Teaching a more accurate and modern view of genetics is important because it provides a true understanding of how genetics work, which is crucial for scientific literacy. It also helps to dispel myths and prevent the acceptance of deterministic thinking that can lead to harmful beliefs like eugenics.

How did Gregor Mendel achieve his clear inheritance results despite the complexity of genetics?

Gregor Mendel achieved clear inheritance results by purifying his pea plants through artificial breeding over two years, creating purebred lines that maintained their color across generations. This effectively simplified the genetic landscape, allowing Mendel's Laws of Inheritance to emerge in this specific context.

Outlines

00:00

🧬 The Human Genome Project and Genetic Expectations

The paragraph discusses the Human Genome Project, which aimed to sequence the entire human genetic code. It highlights the initial optimism of the project in the mid-90s, with predictions that by 2020, individuals would carry genome cards for personalized medical treatment. However, the reality has been more complex, with direct connections between genes and traits proving elusive. The paragraph challenges simplistic views of genetics, such as genes for specific traits like blue eyes or red hair, and introduces the complexity of the relationship between DNA and human characteristics.

05:03

🌱 Mendel's Legacy and the Limitations of Classical Genetics

This paragraph delves into the history of genetics, starting with Gregor Mendel's work with pea plants. It explains Mendel's findings on inheritance patterns, such as the 3:1 ratio for dominant and recessive traits, and how these were simplified into Mendelian genetics. The paragraph critiques the oversimplification of Mendel's laws, pointing out that they do not account for the complexity of genetic traits like eye color, which is influenced by multiple genes rather than a single gene with two forms.

10:04

🎪 Waddington's Landscape: A New Perspective on Genes and Traits

The paragraph introduces Conrad Hal Waddington's concept of the 'genetic landscape,' which offers a more nuanced view of genetics than the traditional Mendelian model. Waddington's landscape is described as a complex system where genes act as pegs and guyropes that shape the developmental path of an organism, akin to a marble rolling down a landscape. The paragraph discusses how this model accounts for the interaction of multiple genes and environmental factors in determining traits, and how it can lead to a better understanding of genetic variation and the development of new traits.

🔍 Beyond Mendel: The Complexity of Genetic Inheritance

This paragraph further explores the complexity of genetic inheritance, using the example of the Y chromosome and sex determination to illustrate that even traits thought to be controlled by a single gene are influenced by a network of genes and environmental factors. It discusses how identical twins can exhibit different traits due to random developmental variations and environmental influences, challenging the idea of genetic determinism. The paragraph also touches on the development of new mathematical models inspired by Waddington's landscape, which aim to describe real developmental patterns more accurately.

📚 Rethinking Genetics Education: From Mendel to Modern Understanding

The final paragraph argues for an updated approach to teaching genetics, advocating for a curriculum that emphasizes the complexity and interplay of genes and the environment from the outset. It references the Genetics Pedagogies Project, which developed a modern genetics course that resulted in students having a less deterministic view of genetics and a better understanding of its subtleties. The paragraph concludes by suggesting that teaching Mendelian genetics as a special case, rather than the norm, would better prepare students for understanding the complexities of modern genetics and critical thinking about genetic claims.

Keywords

💡Human Genome Project

The Human Genome Project was an international scientific research project aimed at determining the sequence of the human genome and identifying the genes it contains. The project was completed in 2003, and it has been a cornerstone in understanding human genetics. In the video, the Human Genome Project is discussed as a source of high hopes for personalized medicine and genetic understanding, with expectations that by 2020, individuals would carry their genome information on cards for medical use.

💡Genetic Code

The genetic code refers to the set of rules by which information encoded in genetic material (DNA or RNA sequences) is translated into proteins by living cells. In the video, the sequencing of the human genetic code is mentioned as a significant achievement, which was expected to lead to a better understanding of human traits and diseases.

💡Gregor Mendel

Gregor Mendel, often referred to as the father of genetics, was a scientist who discovered the fundamental laws of inheritance through his work with pea plants. His findings laid the groundwork for the field of genetics. The video discusses Mendel's work and how it has been simplified and sometimes misinterpreted in modern education, leading to a deterministic view of genetics that doesn't fully represent the complexity of gene-trait relationships.

💡Dominant and Recessive Traits

In genetics, dominant and recessive traits refer to the way certain characteristics are expressed in offspring. A dominant trait will mask the expression of a recessive trait in the presence of a dominant allele. The video uses the example of yellow and green peas to illustrate this concept, explaining how all offspring of a cross between a yellow and green pea plant would be yellow, with the green trait being recessive.

💡Punnett Squares

Punnett squares are a tool used in genetics to predict the genotypes and phenotypes of offspring in a breeding experiment. They are named after Reginald C. Punnett, who developed them. The video mentions Punnett squares as a method used to demonstrate simple inheritance patterns, but also points out their limitations when explaining more complex genetic traits.

💡Waddington's Landscape

Waddington's landscape, or epigenetic landscape, is a metaphor developed by Conrad Hal Waddington to describe how genes and environmental factors interact to influence development. The video uses this concept to illustrate the complexity of gene-trait relationships, suggesting that traits are not simply determined by single genes but are the result of a complex interplay of many genes and environmental influences.

💡Gene Therapy

Gene therapy is a medical technique that involves changing a person's genes to treat or prevent disease. The video references the early hopes for gene therapy following the Human Genome Project, where it was imagined that individuals could be cured of genetic diseases by altering their genetic code.

💡Genetic Determinism

Genetic determinism is the belief that an individual's characteristics or behavior are determined by their genetic makeup. The video critiques this idea, arguing that the relationship between genes and traits is far more complex than simple deterministic models suggest, and that environmental factors play a significant role in development.

💡Epigenetics

Epigenetics refers to changes in gene expression that do not involve alterations to the underlying DNA sequence but can still be passed down to future generations. The video touches on epigenetics as part of the broader discussion about the complexity of gene-trait relationships and how environmental factors can influence gene expression.

💡Genetic Pedagogies Project

The Genetic Pedagogies Project is an initiative mentioned in the video that aims to update the way genetics is taught, focusing on the entangled nature of genes, environments, and organisms. The project developed a curriculum that presents Mendelian genetics as a special case rather than the norm, helping students to understand the nuances of modern genetics.

💡Eugenics

Eugenics is the belief in improving the genetic quality of the human population through selective breeding. The video warns against deterministic thinking in genetics, which can lead to harmful ideologies like eugenics, by promoting a more nuanced understanding of how genes and the environment interact.

Highlights

The Human Genome Project sequenced the entire human genetic code between 1990 and 2003.

High hopes for personalized genome cards by 2020 were not realized.

The complexity of the link between DNA and human traits is greater than initially thought.

Traits like eye color are not determined by single genes but by multiple genes interacting.

Gregor Mendel's pea plant experiments laid the foundation for understanding genetics.

Mendelian genetics suggests a direct link between genes and traits, which is often not the case.

Conrad Hal Waddington introduced the concept of genes as a complex system influencing development.

Waddington's landscape metaphor visualizes gene expression and trait development.

The environment plays a significant role in gene expression and trait development.

Traits like sex determination are not solely基因-based but involve complex gene-environment interactions.

Randomness in development can lead to variations even among individuals with the same genetic makeup.

Mendel's pea experiments produced clear inheritance patterns due to the specific selection of traits.

Modern genetics education should move beyond Mendelian models to reflect the complexity of gene-trait relationships.

The Genetics Pedagogies Project developed a curriculum that emphasizes the complexity of genetics.

Outdated genetics models can lead to misconceptions and deterministic thinking in the public.

Waddington's landscape is being used to develop mathematical models that describe real developmental patterns.

Mendel's work should be understood historically without projecting later doctrinaire Mendelism.

Transcripts

Between 1990 and 2003, the Human Genome Project sequenced our entire genetic code, or, as

they call it, the 'human blueprint'.

During the mid 90s, the hopes for the project were high.

Science journalist Laurie Garrett imagined [that] by 2020, everyone would be carrying

around their own little genome cards.

So, if you ever ended up in hospital, doctors would be able to swipe your card to see which

mutation was causing the problem, and you'd then be sent off for gene therapy to be cured.

Easy peasy.

*That* was the promise of the Human Genome Project.

But, 2020 was now three years ago and no-one's carrying around a genome card.

The harsh reality for the project was that the link between our DNA and who we are is

way more complicated than we imagined.

For the vast majority of the characteristics that make you, *you*, there just isn't a direct

connection between gene and trait.

That seems to go against what we get taught at school and what we see in the media, where

it seems as though there's genes for blue eyes, genes for red hair, genes for Scottish-ness

… /My DNA comes from Scotland and Ireland/ … genes for sexuality, even genes for dog

ownership.

It's all encoded in the programming language of life.

So, what's wrong with this picture?

The father of genetics was Gregor Mendel – an Augustinian friar who also had a keen interest

in science.

Although he initially wanted to become a teacher, his (highly relatable) fear of oral presentations

caused him to fail the certification exam … Twice.

With a teaching career seemingly out of grasp, he decided to go about conducting his own

research in the monastery garden in Brno.

Between 1856 and 1863, Mendel used over 28,000 pea plants to study plant hybridisation.

And, his results are familiar to anyone who's studied high-school genetics today.

He found that the hybridisation of different coloured peas, as well as other traits, followed

regular patterns.

For instance, if a yellow pea plant was crossed to a green pea plant, all the offspring would

be yellow.

You might remember this from school as yellow being a dominant trait and green being a recessive

one.

The offspring of these hybrid yellow plants, when crossed to each other, would then have

a 3:1 ratio of yellow peas to green ones.

This is the origin of the infamous concept of 'skipping a generation'.

Green was present in the first generation, disappeared in the second, only to reappear

in the third.

Another common example of this kind of inheritance is eye colour.

Much like Mendel's peas, brown eyes are dominant to blue ones and using special tables known

as Punnett squares, we can quickly find out that it's possible for two brown-eyed parents

to have a blue-eyed child (because they happen to carry hidden or recessive blue[-eyed] genes)

But it's impossible for two blue-eyed parents to have a brown-eyed child.

Altogether, Mendel's picture of inheritance (as it was interpreted by his followers) gave

the following picture of genetics: One, genes are tightly linked to traits and act like

blueprints.

If you find a specific gene in your genetic blueprint, you know exactly what trait will

occur.

Two, inheritance can be easily tracked using Mendel's laws of inheritance, giving us phenomena

like the famous 3:1 ratio.

Three, the impact of the environment is minimal.

Traits can be determined using Punnett squares in *any* environmental context.

Butttttt none of those three things are actually true.

Not even for a seemingly simple trait like eye colour.

For one, eyes can come in all shades of blue, brown, grey, multicoloured, two different

colours and can even change throughout your lifetime with some babies being born with

blue eyes and going on to develop brown eyes.

Discrete categories like blue and brown are actually decided pretty arbitrarily by ignoring

all other variation.

In reality, eye colour is the product of many genes acting together.

Not a single gene, with two forms, that can be modelled with a Punnett square.

As a result, it's entirely possible for blue-eyed parents to have brown eyed children.

This fact is not really surprising to geneticists and has been well known for over 100 years,

but it doesn't fail to freaks parents out.

But if Mendel's story doesn't even work for eye colour, then what is the right way to

think about how genes work in humans and other organisms?

In 1957, Conrad Hal Waddington published 'The Strategy of the Genes' whose key argument

can be summarised in these two figures.

Waddington suggests that we should think of our genes, not in terms of blueprints or Punnett

squares.

But as a complex system of pegs and guyropes that hold up a surface like a circus tent.

The traits that we develop like blue or brown eyes, are then the result of a marble rolling

down this complicated landscape into one of the valleys.

As Waddington himself admits, following this three dimensional metaphor is tricky.

So to make things clearer, I've simplified his argument down to something familiar.

Here I've built a Steve Mould-style, 2D version of the Waddington landscape and it ends up

looking like the classic marble drop carnival game, where you place a marble at the top

and try and aim it into the highest score at the bottom.

In this modified version of Waddington's metaphor, genes are the paddles in the middle and the

bins at the bottom are different traits like different possible eye colours.

The ball falling then represents the process of development from single celled embryo to

adult.

As for the environment, Waddington was a little inconsistent in conceptualising its role.

But at least in one instance, another figure in 'The Strategy of The Genes', he uses an

arrow to show an environmental stimulus bumping the marble in a particular direction.

That'll do for us, and we can simulate it with a push from this hairdryer.

Waddington's landscape gives us quite a few useful insights that are missed by the Mendelian

picture.

First and foremost, we can clearly see that every trait has to be the product of many

genes working together to funnel the marble down a particular path.

You can imagine how complex this marble run would have to be to determine things like

cardiovascular disease for instance, as illustrated beautifully by this figure from the Genetics

Pedagogies Project (more on them later).

Or take the Y chromosome that's often considered to 'determine' the male sex.

XY chromosomes in your genetic blueprint give a male person, and XX chromosomes give a female.

We can visualise this on Waddington's landscape with this red paddle being the Y chromosome.

When it's there, the marble always goes into the male bin, and when it's not there the

marble always goes into the female bin.

But from cases like South African runner Caster Semenya, a woman with XY chromosomes, we already

know this picture is too simple.

This is because the Y chromosome has to function in concert with many other genes to *collectively*

determine sex.

But if these other genes were altered in some way, or if different amounts of hormones are

present through development, the landscape could shift in complex ways to get different

sexual patterning.

So the Y chromosome is hardly the only important factor in determining sex.

Even without changing the landscape, randomness can also arise naturally, by the marble happening

to fall into a different bin by pure chance.

This is partly what happens when identical twins - who have the same genetics - end up

with different handedness, different eye colours, different neurological conditions like schizophrenia,

even different sexes.

Of course, differing environments also play a role in generating variation between identical

twins too.

But either way, we can now see why it's misleading to call the Y chromosome or specifically SRY,

the gene "for" maleness.

It can certainly make a big difference in how sexual characteristics are determined,

but it can't act alone and it doesn't guarantee anything.

Really we shouldn't talk about genes "for" anything because the structure of all traits

look similar to sex.

They're the product of complex networks of genes acting together with the environment.

Even traits that are supposedly under the control of a single gene like cystic fibrosis,

PKU and Huntington's disease, can be modified in their severity by several other genes and

environmental factors.

Again highlighting the convoluted relationship between gene and trait.

It's a little annoying that Mendelian genetics follows such nice rules and it would seem

as though Waddington's landscape lacks the mathematical niceties of genotype ratios and

Punnett squares.

But in the past few years this has begun to change with the landscape moving from being

a mere metaphor to inspiring mathematically rigorous models that describe real developmental

patterns.

This has also been helped along by the development of new technologies, particular those that

allow us to study the gene expression of individual cells.

For instance, James DiFrisco and Yogi Jaeger have shown that the exact same genes in the

exact same network of interactions, can actually result in significantly different morphological

patterns in flies.

The reason behind this is a little hard to show on my 2D marble run diagram, but in Waddington's

original diagram, this is because the genes - the pegs - can pull with different tensions

on the guy-ropes to affect the landscape, where the tensions in the ropes represent

the "strengths, timings, and rates of interaction in the gap gene network."

The result of all this pulling of guyropes are qualitative changes in the genetic landscape.

For instance, it's possible for a bistable regime (where the marble can only roll down

into two valleys) to turn into a multistable one (where more valleys open up for the marble

to roll into).

This opens up the possibility for new traits to emerge in the population.

And visually, we can imagine how loosening the slack in this imaginary guy rope could

turn the landscape on the left into the one on the right.

All of this does leave one big historical question unturned.

How did Mendel end up with such nice inheritance results *despite* all of this complexity?

Well, the truth is that Mendel's peas were actually pretty special.

When other biologists tried to replicate Mendel's results, like Raphael Weldon tried to do in

1902, their peas looked nothing at all like Mendel's.

Weldon found that pea colour actually existed on a spectrum from yellow to green.

It definitely didn't seem like a binary trait like we see in today's textbooks or Mendel's

original paper.

Weldon wrote in a letter to statistician Karl Pearson that Mendel must either be a truly

astonishing man, or a black liar.

But this is being a little harsh on Mendel because, remember, he was only directly interested

in plant hybridisation, not heredity itself.

And to study hybrids, he first had to purify his pea plants to remove any intermediate

variation.

This wasn't easy and took him 2 years of artificial breeding to get purebred lines that maintained

their colour across generations.

Unknowingly, Mendel was essentially fudging the Waddington landscape of the pea colour

genes to the very boring case of a marble going into the same bin everytime.

And once he'd done that, the patterns we retrospectively call 'Mendel's Laws of Inheritance' do indeed

emerge.

But only in this very particular context.

To quote Annie Jamieson and Greg Radick, "These patterns do arise; but they arise only under

special conditions, notably when humans [like Mendel] have engineered artificially purified

lineages into being, by deliberately excluding unwanted variability."

It's therefore a pretty big mistake, you could even call it a misinterpretation of Mendel's

experiments, to extend these patterns to the entire biological world in the wild.

I can hear some of you saying: "Jake, this is the second video you've done critiquing

models in biology that have been hugely successful.

Yes ok, they have their flaws, but aren't we supposed to teach students the oversimplified

model first?"

And to that, I'll respond with a resounding no.

This line of thinking is based on the idea that students are these silly naïve souls

that are only ready for the truth once they're grown up.

Truth is, students are extremely receptive to being taught a more accurate and modern

genetics curriculum.

The Genetics Pedagogies Project did just that.

They created an introductory genetics course that placed the entangled nature of genes,

environments and organisms, front and centre and contextualised Mendelian traits as a rare,

special case.

And, compared to students who took the more traditional course, the 28 students who were

taught the new curriculum: "emerged as less believing of genetic determinism, and … better

prepared to understand the subtleties of modern genetics."

Surely the point of a good scientific education should be to do just that.

To teach students how to do modern science, not dwell in outdated paradigms.

Anyone that can understand how a marble run works is capable of understand how our genetics

*actually* work.

There's no need to lie.

Plus even if we eventually teach students the modern picture of genetics in later courses,

there's a very good chance that students never get exposed to these subtleties because they

never end up taking the more advanced courses.

I'm sure the vast majority of you only got exposed to the Mendel's peas style of genetics

at school and that was it.

With the Mendelian blueprint picture firmly ingrained in the minds of most students, the

public at large is much more prone to believe questionable headlines like: "genes determine

how young use internet and social media" and "scientists find 24 ‘golden’ genes that

help you get rich."

If instead we placed better metaphors, like Waddington's landscape, in the curriculum

from the beginning, these headlines would be quickly dismissed as nonsense.

Hopefully most of you realise there's something dodgy going on with the claim that something

as complex as income could be determined by genetics.

Not to mention how deterministic thinking like this can easily move across into talk

of /'good genes'/ and 'bad genes' and then blaming the poor for being poor because of

some innate genetic characteristics.

Aaaand we've mindlessly just slid into eugenics territory.

It's actually Mendel's 200th birthday this year, and it might seem like a pretty rotten

birthday present to suggest jettisoning his ideas from the genetics curriculum.

But as Greg Radick points out: "If we want to honour Mendel, then let us read him seriously,

which is to say historically, without back-projecting the doctrinaire Mendelism that came later.