September 20, 2025 • 29 mins
Genes can be a metaphor for our sense of self. But they are also real, physical, things made up of DNA parts, locked inside the cells of every living organism. In this episode we explore the materiality of genes, as well as some of the human stories behind the science.
References:
Waclaw Szybalski on Martha Chase - Cold Spring Harbor laboratory - Oral history collections.
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Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
(00:00):
It's a chilly winter night, January 1952.
(00:03):
A young woman stands on the shore of Cold Spring Harbor, New York.
She lights the cigarette.
Her ferd since she's been standing out by the shore.
She takes long draws from the cigarette and plays through everything she did over the
day.
All the tweaks to her experiment that she'll need to make tomorrow as she gets all the
data ready for publication.
(00:26):
They had almost all the data they needed and the findings were conclusive.
She had poured over them multiple times in the last few weeks.
And during the long icy silences of meetings with her supervisor Alfred Hershey.
He was never dismissive, but he always seemed to need time to mull over her ideas, reshape
(00:47):
them until he could restogest them as his own.
Nevertheless, they were both pleased by the results of the experiment they've been
running for weeks now.
Every time they ran the experiment, the radio-label DNA was transferred from the virus into
the bacteria, and the radio-labeled protein never was.
It was really that simple.
She turned her over and over and felt quite satisfied, though not all that excited.
(01:11):
Why was she here?
Wasting her time and her energy on this cabal of dull men should leave next year, maybe
this year, just as soon as she tied things up with this paper.
She stamped out the cigarette under her heel and headed back to her car.
She had a long day in a lab tomorrow, best to get some sleep.
(01:36):
Welcome to Modified.
I'm your host, Dr. Orlando D'Alanche.
I worked for 10 years in plant biotechnology research, who worked as sometimes involved
making genetically modified plants.
Now I'm a science teacher, training students for future careers in biotechnology and
other areas of life science.
This podcast is my attempt to share some of what I know and how I think.
(01:57):
To guide you through the science of GMOs and hopefully just enough of the history and social
context to give you a part forward in your own thinking.
And if all else fails, I hope you'll enjoy some of the surprising stories and fascinating
facts in the world of genetically modified plants.
This is Episode 2, Ward Jeans are made of.
If you're tuning in for the first time, I would recommend heading back to Episode 1 and
(02:19):
starting there.
Otherwise, let's go.
The woman I described in the introduction was Martha Chase.
The laboratory scientist who carried out the experiments, the definitively showed that
DNA, not proteins, is the hereditary material.
She worked under the supervision of Alfred Hershey.
He was 44 at the time.
(02:40):
She was 24 and she was still starting out in her scientific career.
They did that work together at Cold Spring Harbor Laboratory in New York in 1952.
90 years and 4,000 miles away from the lab in Tubing and Germany were free to meet her first
isolated DNA in 1869 as we learnt in Episode 1.
(03:03):
Alfred Hershey went on to win a Nobel Prize in 1969 for proving that DNA is the hereditary
material.
Martha Chase was not included in that prize.
Rosalind Franklin, if some of you might have heard of, is often cited as a case of Nobel
Institute misogyny for her exclusion from the Nobel Prize for discovering the structure
(03:24):
of DNA.
Unfortunately, Rosalind Franklin had died of cancer before the prize was awarded and since
Nobel Prizes are not awarded posthumously, she would not have been included even if the
Nobel Committee had been so inclined.
Alfred Hershey was awarded the Nobel Prize in 1969 in no small part due to the experiments
(03:44):
that Martha Chase conducted, and unlike Rosalind Franklin, Martha Chase was alive at the time
the prize was awarded.
My personal hunch is a combination of misogyny and the fact that Martha Chase didn't go
on to run her own prestigious research lab.
After her work at Cold Spring Harbor, she moved around the country, continuing to pursue
genetic research, then nothing as splashy as the experiment she carried out at the very
(04:08):
start of her career as a research assistant in the Hershey lab.
If you remember back to last episode, the hereditary material is just a name for some substance
inside cells, and it carries information for traits down generations, down generations
of cells and down generations of individuals, whether humans, seals or sugarcane.
(04:30):
The idea that such a thing exists has a long history, and for the roughly 100 years from
1850 to 1950, most scientists thought the proteins, not DNA, were the hereditary material, with
the tide of opinion shifting more and more towards DNA over time, but without solid proof.
The trick used by Martha Chase was to make use of the viruses that Alfred Hershey worked
(04:54):
on in his lab.
These viruses, bacteria, are their known, infect bacteria.
Since the early 20th century, geneticists had worked with them because it was clear that
when they infect a host bacterium, they transmit genetic information that is stored inside
the virus particles.
Once transferred into the host bacterium, the hereditary material could be tracked down generations.
(05:18):
But by this time, the word genes was being used, so they would have said that the virus
transfers its genes into the host rather than hereditary material, that slightly clunky
phrase.
This is in fact how most viruses operate.
These viruses are essentially mobile packets of genes, which makes them a useful tool for
geneticists.
And so by the 1940s it was clear that these viruses call bacteria-fages, infect genes into
(05:42):
the host bacteria and they infect them.
But wasn't clear is what those genes are actually made of.
Remember that all of this is too small to see.
Proving what a gene is actually made of would require some careful detective work.
Cell analysis had already shown that a bacterium-fage, like most viruses, is just a packet of DNA and
(06:05):
protein.
So the experiments the Martha chase carried out at the simple goal of tracking, which of
these two molecule types is the one that goes into the host bacterium and stays there
down generations.
Is it the DNA or the protein?
The problem is the bacteria have their own DNA and proteins, so how can you tell apart
the DNA and proteins that come from the bacterium and the DNA from proteins that come
(06:27):
from the virus?
All of these events are happening at a scale so tiny that there's no way to discern what's
happening by eye or even by microscope.
So Martha chase relied on radio isotopes.
Radio for radiation, isotopes meeting a slightly different version of an atom.
So a version of an atom that is radioactive.
(06:49):
Without going into too much detail in radio chemistry, just know that you can use radiation
to label and track specific molecules, in this case DNA or protein, by using versions
that contain radio isotopes.
You might have heard some of these radio isotopes, things like carbon-14 or phosphorus-32.
Essentially, you can grow up a bunch of virus on a bacterial food that is rich in these
(07:11):
radio isotopes, and they will end up with virus particles that contain those radio isotopes
also that incorporate them into their bodies.
And we say that these viruses are now radio labelled.
Specifically, Chase and Hershey fed the viruses with phosphate-32 and sulfur-35.
DNA contains a lot of phosphate, so phosphate-32 labels DNA.
(07:33):
Proteins don't contain phosphate, but they do contain small amounts of sulfur, so the
sulfur-35 labels proteins.
Then they took these radio labelled viruses and mixed them with normal non-radio labelled
bacteria, weight some time and then see which label becomes incorporated into the bacteria
after they were infected with the virus.
(07:54):
Every time after they grew the bacteria for some days and then isolated the cells and
analyzed whether they contained the radio labelled carbon from the proteins or the radio labelled
phosphate ions that were used to mount the DNA, they found that the signature of radio labelled
phosphate was there, not sulfur.
That showed that it was only DNA that was transferred, not protein, genes and made of DNA, definitive
(08:18):
proof or lust.
It was an elegant experiment and the immediate years that followed many other scientists
showed in a whole range of ways that yes, indeed DNA is their harder-to-room material.
In fact, just one year later, in 1953, James Watson and Francis Crick published a structure
of DNA, building on data by Roslyn Franklin.
Remember that by the 1950s scientists were very aware that DNA existed, even if they were
(08:43):
absolutely sure that it was their harder-to-room material.
And also, solving the impossibly tiny structures of molecules using a technique called x-ray
crystallography was not new, it had been used for a decade or so by this point.
And so on its face, the structure of DNA was just using the existing method to show the
structure of a molecule that people already knew a fair bit about from a chemical viewpoint.
(09:05):
But because Hershey and Chase had just shown a year before, the DNA is what genes are made
of.
That 3D structure of DNA, that famous double helix, was an immediate sensation.
In 1953, people around the world could visualize and understand what this thing is inside all
of ourselves.
This hereditary material that seems to shape so much of who we are.
(09:28):
We all have genes that are made out of DNA and its shape is a double helix.
A few times so far, I've used the word gene without explaining what I mean by that.
And despite my instinct to define every single scientific term I use, I don't feel too
worried about using the word gene because it's a part of everyday language and it has been
(09:49):
for decades.
Most people have a sense of a gene as something related to DNA and something that makes you
you.
Genes are units of biological fate, or to use that slightly more technical term, units
of heredity.
At a physical level, what is a gene?
That was worked out over the next couple of decades after it was proven that DNA is a hereditary
(10:13):
material and the physical structure of DNA was solved, which immediately suggested a lot
of ideas about how it might function at the molecular level.
For instance, DNA is a double helix, meaning it forms a structure of two strands or chains,
each with an identical repetitive structure of sugar phosphate backbone units that directly
(10:33):
linked together.
And then there is a bit sticking off the side of every unit and we call that the side chain.
For DNA, those side chains can be A, G, C or T. Now, those are just letters that we use
as a shorthand for four similar but slightly different carbon-based molecules and they
have the longer names adenine guanine, cytosine and thymine.
(10:55):
And while I know this may seem obvious that ourselves are not full of the little letters,
years as a science teacher has taught me not to shame or belittle anyone from this understanding.
Because whenever DNA comes up in visual media, the image is normally either a double helix
or it's some matrix of letters, those A's, G's, C's and T's.
And indeed, scientists who work within the world of DNA do tend to think in terms of sequences
(11:18):
of letters and don't concern themselves too much with what the physical reality is that
those letters represent.
Those letters are referred to by scientists as DNA bases.
And yes, there's a logic to where that word comes from but it's not really worth spending
time on.
So you can just know that the DNA has these four different bases, the side chains, A, G,
(11:39):
C and T. A base plus the constant sugar phosphate section is called a nucleotide technically.
But if we avoid having to say the word nucleotide too often, we'll just use the word base to mean
one unit of DNA that's either an A, G, C or T. But back to our DNA molecule, you have
these two chains that have constant identical sugar phosphate backbones with different
(12:00):
side chains, the side chains pointed each other in the middle of the twisting helix.
And that's where the real molecular magic happens.
The bases are attracted to each other and form strong molecular bonds that only in two
specific combinations.
The two combinations the form complementary pairs are A, T, and C to G. That complementary
(12:21):
base pairing, that molecular rule that A pairs of T and C pairs of G was far more exciting
than just showing that DNA is a double helix.
A double helix is a nice shape for complementary base pairing or is it sometimes called
Watson Crick base pairing is fundamental to how DNA works as we'll see how genes work
too.
(12:41):
Imagine you took a DNA molecule and separated its two chains.
Now you have just one chain of sugar phosphate links and all these side chains just hang
it out in space.
A is G, C and T's in a seemingly random order up the chain.
That is unstable, DNA that is naked like that, or single stranded as we call it, is quickly
(13:03):
dissolved inside a cell.
But because of complementary base pairing, it would be very easy to fix this problem.
You'd know how to form the matching DNA chain by just going along one DNA space at a time,
wherever you find an A, put a T opposite it, wherever you find a G, put a C opposite it,
T opposite A and C opposite G, and then just stitch together all the sugar phosphate
(13:25):
back bones.
And that is actually how DNA gets replicated in all cells.
The two chains are pulled apart and then complementary base pairing allows new complementary
chains to fill in the gaps, turning one original DNA molecule into two, each one identical
to the original, each one containing one chain from the parent molecule and then one newly
(13:47):
synthesized with the molecular logic of complementary base pairing.
And the reason that this is so important to genes is that it allows DNA molecules to
be copied indefinitely between cells in one body and down generations, all by preserving
the exact same sequence of A's, G's, C's and T's in the original.
(14:09):
In that process, genes are protected, preserved and passed on.
So now reconnecting with this talk of DNA bases back to genes.
What is a gene?
A gene is a section of a DNA molecule, a series of anything from a few hundred to tens
of thousands of DNA bases.
So now let's reconnect all of this background on DNA bases back to genes.
(14:32):
A gene is a section of a DNA molecule, a series of anything from a few hundred to tens
of thousands of DNA bases.
They have a specific sequence, with that sequence defining the functional impact of the gene.
To picture it, you may know that humans have 23 different chromosomes, with two copies
(14:52):
of each and most of ourselves.
Each one of these 23 chromosomes is a separate DNA chain, a double helix, and each one is
roughly 100 million DNA bases long.
Within those 100 million bases and one chromosome, there are a lot of genes, and there's also
a lot of DNA that isn't genes.
(15:13):
If you started at position zero, they're going to start with a chromosome arbitrarily defined
you start going up the chain, you might find a gene starting at position 50 that goes
until 750, so 700 base pairs, and then another one that starts at 1200 and goes till 2500.
And intervening between these genes is sections of DNA that is not a gene can have other
(15:35):
functions that could spend a whole podcast going into all the other stuff that DNA can
do apart from being a gene.
This process of scanning up a chromosome and seeing where the genes are is something you
could actually do right now with a little bit of training and a computer, because thanks
to decades of research and billions of dollars of government research funding, there are
(15:58):
publicly available maps of the human genome, the genomes of many, many organisms on our planet.
But let's say somehow you could actually look inside a cell, and you weren't working
at a computer, you're looking into the cell, and you did that same thing of looking along
a DNA chain. You wouldn't exactly see signposts that says gene starts here or gene ends here,
(16:19):
but there would be some visible signs. Specifically you'd see a large molecule is called transcription
factors congregating at the start of the gene, in a section we call the promoter. We'll
learn a little bit more about transcription factors in episode 4.
Then in the middle of the gene you would see that the DNA double helix has been pulled apart,
and a large molecular complex, we call this RNA plenaries, would be chugging away through
(16:45):
the central section of the gene. Trailing behind would be a newly formed strand of something
that looks very similar to DNA, but has a few tweaks to it, and that would be a molecule
of RNA. RNA also has bases that are almost the same as DNA, and crucially RNA molecules
can be made from DNA templates during the exact same complementary base pairing that allows
(17:10):
DNA replication to work. So we can say that the RNA molecule that is being made at this
gene is complementary to the DNA sequence of the gene. Specifically the central section
of the gene, the bit we call the coding sequence, and it's called that precisely because it is
the sequence of DNA that contains the information or code used to make the complementary RNA
(17:32):
molecule. Then at the end of the gene it's the all of this complex molecular ballet ceasing,
molecules is associating from the DNA and the two DNA chains being zipped back together
into a nice double helix. That end section is called the terminator. The promoter we saw
earlier contains specific sequences of DNA that the molecular machinery of the cell can
(17:54):
read to know where to start the process of making an RNA molecule, and the terminator has
different sequences that give the stop signal. So the promoter and terminator basically
frame and define the section of DNA that is used to make a complementary RNA molecule.
And that information is retained down generations because the sequence of DNA is preserved as it
(18:17):
is copied. So there we have it. A gene is a section of DNA that has all the information
necessary to make an RNA molecule that will have a specific sequence of RNA bases complementary
to the DNA template. Okay, so what do we do with this RNA? Well, RNA is very cool and deserving
of its own podcast. For now, we'll just skip right over it and explaining why this matters
(18:41):
or at least the most important reason because ultimately the RNA is short lived and itself
is just uses a template to make a totally different type of molecule a protein. So our
DNA and RNA are very similar at the molecular level. RNA and proteins are not. I could spend
another 20 minutes or so explaining exactly how this works, but for now, just know that
(19:02):
the sequence of bases in the RNA is used as a guide for a different set of molecular machinery
to make a specific protein molecule, reading and translating the information in the RNA
into the molecular language of proteins. And indeed, translation is the scientific term
used for this process. Going from DNA to protein is called gene expression. If a gene is expressed,
(19:27):
that means that inside the cells of that organism, the DNA of that gene is being constantly
used as a template to turn our complementary RNA molecules that are then translated
to corresponding protein molecules. Proteins are similar to DNA and they're also long
chains made of similar subunits as in similar to each other within the chain. But whereas
(19:49):
DNA is chains of A, G, C, or T, protein chains include 20 or more different types of subunits.
These subunits are called amino acids. They are also more diverse in the 4 DNA bases,
both in terms of physical shape and size and also chemistry. So even though proteins are
all just chains of amino acids, they are functionally extremely diverse, and they do most of the
(20:14):
actual stuff involved in being alive. In episode 4, we'll see some specific examples of how
these genes work, and we'll recap on how genes make proteins and how those specific proteins
contribute to making a plant. And the later on in the series, we'll look at examples of
specific genes used to modify crop plants and the proteins that those genes encode.
(20:35):
So, you know, if you're wondering why you've been learning about basic molecular biology
and you thought you would be learning about GMOs, it's because I want to make sure that when
I start diving into talking about EPSP synthase, a protein produced by GMO corn because of a
trans gene and how that makes them herbicide tolerant, I'll be able to go into the
molecular details of all that without completely losing anyone. So anyway, that is the physical
(21:00):
side of genes. A gene is a piece of DNA that codes for RNA, that codes for a specific protein,
or more simply, a gene is a piece of DNA that codes for a specific protein, and proteins
from the molecular machines that shape the traits of living things.
In school, you might have learned it as a gene codes for a trait, and just to recap,
(21:22):
traits are the things we can see that define an organism, e.g. you could say a gene for eye color
or a gene for grain size. That is kind of a relic of how genes were first studied in the early
20th century. There was no other option but to connect each gene to a single trait to make it possible
to conceptualize and track the effect of the gene. However, to try and summarize decades and decades
(21:47):
of research in three words, biology is complicated. Almost every trait, especially at the level of traits
that we humans could see or care about, is influenced by multiple genes. Each trait is the product of
many proteins working together, influenced by each other, and by the environment. That's because
the information genes carry is not for a whole trait, but just for one protein. But in cases where
(22:12):
things are kept identical, except for tweaking just one due to the time, then you can often see that
effect in the observable traits of the organism. That is never really the case in nature,
or in real human populations, but it is the case in selective breeding where humans deliberately
inbreed populations of plants and animals till they are genetically identical. So then when a change,
(22:35):
or we call it a mutation, arises in one gene, you can actually see that impact as say a change in
flower color. So as you'll see in the next episode, episode three, if you happen to be a patient,
Augustinian, Frey, named Gregor Mendel, you can track and study that flower color variant and deduce
a set of rules about the inheritance of things you'll have first call factors and what will later come
(22:59):
to be known as genes. The machinery that supports gene replication and gene expression is remarkably
similar across all of life, which is one of the reasons it's almost certain that all living things
on earth are directly related to one another in a literal sense. Every bacterium, human and mushroom
on earth are family, distant family, sure, you'd have to go back billions of years to find out
(23:23):
common ancestor, but family just the same. We all have genes made of DNA and we all have a pretty
similar set of machinery to read the DNA to make proteins. And that's DNA's primary job because
otherwise it can't really do anything. The proteins are the exciting stuff. The 20th century was an
(23:43):
extremely busy period for biology. In the 19th century, biology was a newcomer to the natural
sciences, struggling to compete in prestige and attention against the more well established
fields of physics and chemistry, which had already more than proven their own value to human life
and to making money. The industrial revolutions of the 19th century were intimately tied up with
(24:06):
scientific research into physics and chemistry and both supported in turn by mathematics. Biology
had contributed relatively little to value. The study of living things didn't seem to be yielding
much even to the field of medicine the most obvious area of application. That shifted fundamentally
over the 20th century with DNA at the vanguard of that change. In our next episode, we'll explore
(24:32):
Mendels's pioneering work in what we now call genetics, but that work was largely ignored at the
time and underappreciated until its rediscovery at the very start of the 20th century. In practice,
genetics as a field of biological research was born in the first decade of the 20th century.
In the year 1900, a trio of plant scientists read and promoted the work of Mendel
(24:56):
triggering broader scientific interest in the topic. In the year 1900, a trio of plant scientists
read and promoted the work of Mendel triggering broader scientific interest in the topic.
And in the year 2000, a century later, the first working draft was published on the human genome,
with the human genome project wrapping up three years later in 2003 with a well annotated,
(25:21):
publicly available digital database of a complete human genome.
The result of almost four billion dollars of government investment,
as well as a private corporate interest, and the work of thousands of scientists across multiple
countries. And all the way across that century from the birth of genetics of the human genome project,
(25:42):
incremental discoveries are made, the work of thousands and thousands of people, some of them
incredibly famous, most of them anonymous to all about colleagues in their particular niche field.
More and more over the century, DNA moved into the center of biology.
There are many biologists who spend a whole career interacting and thinking about DNA only rarely
(26:04):
if ever, but they are numerically in the minority. Most biology today is molecular biology,
both the basic research that mostly happens at universities, as well as the applied research that
happens in the R&D labs of private companies. Molecular biology isn't a field of study,
but a category of practice. It is biology that takes place in laboratories where questions are
(26:27):
answered and problems are solved using biomolecules, most notably DNA.
More and more of this work in the laboratory is connected with work at a computer,
studying and designing gene sequences, or the proteins encoded by those genes.
One of the common methods used by molecular biologists is the creation of genetically modified
(26:48):
organisms, though that usually means genetically modified bacteria or other single-celled organisms.
One of the most effective ways to understand how a gene functions is to deliberately modify it
and see what traits inside the cell are impacted by the modification.
That is one of the reasons that many biologists can get frustrated and defensive about opposition to
(27:08):
GMO crops. If genetically modifying organisms is part of your everyday work, then it seems crazy
to say the GMOs are something dangerous and unknown, and it can seem more frustrating to those
biologists who are working directly or indirectly on saving lives, for improving understanding of
the human body, or developing new types of life-saving treatments for everything from cancer to
(27:30):
COVID. Genetics and genetic modification have embedded themselves into the heart of biology.
Thank you for listening to Modified. This was episode 2, what genes are made of,
is written by me or landed along. I use many sources to help you research this episode,
and want to particularly acknowledge the Cosprin carbuloboratory oral history collection,
(27:52):
which you use for inspiration in the section of Martha Chase and Alfred Hershey.
This is the tiny one person's podcast, so please leave a review if you're enjoying it
and tell a friend. If you have notes, well I'd love to hear them. You can email me at Orlando and
modifypod.com. That's O-R-L-A-N-D-O at ModifiedPod.com. I'd love to hear from you. You can find
(28:14):
that more about me and the podcast on our website, ModifiedPod.com. That's ModifiedPODORNWR.com.
That's the end of the talk today's episode. Our round things out with five take-home messages,
so if you're stopping here, thanks for listening until next time.
For those sticking around, here are your five take-home messages.
(28:35):
Number one, DNA is the hereditary material, and this was finally proven in the 1950s.
Number two, physically DNA is too long-chains to form a double helix. The chains are connected
by complementary base pairing, age to tease, and geostasis. Number three, complementary
base pairing allows DNA to be replicated indefinitely while maintaining the same sequence of age,
(29:00):
G-C's, and P's. Number four, complementary base pairing also works to create complementary RNA
molecules. This is how genes work. They are sections of DNA, the code for a specific protein,
via an intermediate RNA molecule. Number five, proteins are molecular machines that play a
dominant role in defining the traits of an organism, so there's a reasonable short-term to say
(29:24):
the genes to find traits. Okay, that wraps up our second episode. I hope you're listening
for episode three, the one with Mendel and his P's. Bye!
It's a chilly winter night, January 1952.
(00:03):
A young woman stands on the shore of Cold Spring Harbor, New York.
She lights the cigarette.
Her ferd since she's been standing out by the shore.
She takes long draws from the cigarette and plays through everything she did over the
day.
All the tweaks to her experiment that she'll need to make tomorrow as she gets all the
data ready for publication.
(00:26):
They had almost all the data they needed and the findings were conclusive.
She had poured over them multiple times in the last few weeks.
And during the long icy silences of meetings with her supervisor Alfred Hershey.
He was never dismissive, but he always seemed to need time to mull over her ideas, reshape
(00:47):
them until he could restogest them as his own.
Nevertheless, they were both pleased by the results of the experiment they've been
running for weeks now.
Every time they ran the experiment, the radio-label DNA was transferred from the virus into
the bacteria, and the radio-labeled protein never was.
It was really that simple.
She turned her over and over and felt quite satisfied, though not all that excited.
(01:11):
Why was she here?
Wasting her time and her energy on this cabal of dull men should leave next year, maybe
this year, just as soon as she tied things up with this paper.
She stamped out the cigarette under her heel and headed back to her car.
She had a long day in a lab tomorrow, best to get some sleep.
(01:36):
Welcome to Modified.
I'm your host, Dr. Orlando D'Alanche.
I worked for 10 years in plant biotechnology research, who worked as sometimes involved
making genetically modified plants.
Now I'm a science teacher, training students for future careers in biotechnology and
other areas of life science.
This podcast is my attempt to share some of what I know and how I think.
(01:57):
To guide you through the science of GMOs and hopefully just enough of the history and social
context to give you a part forward in your own thinking.
And if all else fails, I hope you'll enjoy some of the surprising stories and fascinating
facts in the world of genetically modified plants.
This is Episode 2, Ward Jeans are made of.
If you're tuning in for the first time, I would recommend heading back to Episode 1 and
(02:19):
starting there.
Otherwise, let's go.
The woman I described in the introduction was Martha Chase.
The laboratory scientist who carried out the experiments, the definitively showed that
DNA, not proteins, is the hereditary material.
She worked under the supervision of Alfred Hershey.
He was 44 at the time.
(02:40):
She was 24 and she was still starting out in her scientific career.
They did that work together at Cold Spring Harbor Laboratory in New York in 1952.
90 years and 4,000 miles away from the lab in Tubing and Germany were free to meet her first
isolated DNA in 1869 as we learnt in Episode 1.
(03:03):
Alfred Hershey went on to win a Nobel Prize in 1969 for proving that DNA is the hereditary
material.
Martha Chase was not included in that prize.
Rosalind Franklin, if some of you might have heard of, is often cited as a case of Nobel
Institute misogyny for her exclusion from the Nobel Prize for discovering the structure
(03:24):
of DNA.
Unfortunately, Rosalind Franklin had died of cancer before the prize was awarded and since
Nobel Prizes are not awarded posthumously, she would not have been included even if the
Nobel Committee had been so inclined.
Alfred Hershey was awarded the Nobel Prize in 1969 in no small part due to the experiments
(03:44):
that Martha Chase conducted, and unlike Rosalind Franklin, Martha Chase was alive at the time
the prize was awarded.
My personal hunch is a combination of misogyny and the fact that Martha Chase didn't go
on to run her own prestigious research lab.
After her work at Cold Spring Harbor, she moved around the country, continuing to pursue
genetic research, then nothing as splashy as the experiment she carried out at the very
(04:08):
start of her career as a research assistant in the Hershey lab.
If you remember back to last episode, the hereditary material is just a name for some substance
inside cells, and it carries information for traits down generations, down generations
of cells and down generations of individuals, whether humans, seals or sugarcane.
(04:30):
The idea that such a thing exists has a long history, and for the roughly 100 years from
1850 to 1950, most scientists thought the proteins, not DNA, were the hereditary material, with
the tide of opinion shifting more and more towards DNA over time, but without solid proof.
The trick used by Martha Chase was to make use of the viruses that Alfred Hershey worked
(04:54):
on in his lab.
These viruses, bacteria, are their known, infect bacteria.
Since the early 20th century, geneticists had worked with them because it was clear that
when they infect a host bacterium, they transmit genetic information that is stored inside
the virus particles.
Once transferred into the host bacterium, the hereditary material could be tracked down generations.
(05:18):
But by this time, the word genes was being used, so they would have said that the virus
transfers its genes into the host rather than hereditary material, that slightly clunky
phrase.
This is in fact how most viruses operate.
These viruses are essentially mobile packets of genes, which makes them a useful tool for
geneticists.
And so by the 1940s it was clear that these viruses call bacteria-fages, infect genes into
(05:42):
the host bacteria and they infect them.
But wasn't clear is what those genes are actually made of.
Remember that all of this is too small to see.
Proving what a gene is actually made of would require some careful detective work.
Cell analysis had already shown that a bacterium-fage, like most viruses, is just a packet of DNA and
(06:05):
protein.
So the experiments the Martha chase carried out at the simple goal of tracking, which of
these two molecule types is the one that goes into the host bacterium and stays there
down generations.
Is it the DNA or the protein?
The problem is the bacteria have their own DNA and proteins, so how can you tell apart
the DNA and proteins that come from the bacterium and the DNA from proteins that come
(06:27):
from the virus?
All of these events are happening at a scale so tiny that there's no way to discern what's
happening by eye or even by microscope.
So Martha chase relied on radio isotopes.
Radio for radiation, isotopes meeting a slightly different version of an atom.
So a version of an atom that is radioactive.
(06:49):
Without going into too much detail in radio chemistry, just know that you can use radiation
to label and track specific molecules, in this case DNA or protein, by using versions
that contain radio isotopes.
You might have heard some of these radio isotopes, things like carbon-14 or phosphorus-32.
Essentially, you can grow up a bunch of virus on a bacterial food that is rich in these
(07:11):
radio isotopes, and they will end up with virus particles that contain those radio isotopes
also that incorporate them into their bodies.
And we say that these viruses are now radio labelled.
Specifically, Chase and Hershey fed the viruses with phosphate-32 and sulfur-35.
DNA contains a lot of phosphate, so phosphate-32 labels DNA.
(07:33):
Proteins don't contain phosphate, but they do contain small amounts of sulfur, so the
sulfur-35 labels proteins.
Then they took these radio labelled viruses and mixed them with normal non-radio labelled
bacteria, weight some time and then see which label becomes incorporated into the bacteria
after they were infected with the virus.
(07:54):
Every time after they grew the bacteria for some days and then isolated the cells and
analyzed whether they contained the radio labelled carbon from the proteins or the radio labelled
phosphate ions that were used to mount the DNA, they found that the signature of radio labelled
phosphate was there, not sulfur.
That showed that it was only DNA that was transferred, not protein, genes and made of DNA, definitive
(08:18):
proof or lust.
It was an elegant experiment and the immediate years that followed many other scientists
showed in a whole range of ways that yes, indeed DNA is their harder-to-room material.
In fact, just one year later, in 1953, James Watson and Francis Crick published a structure
of DNA, building on data by Roslyn Franklin.
Remember that by the 1950s scientists were very aware that DNA existed, even if they were
(08:43):
absolutely sure that it was their harder-to-room material.
And also, solving the impossibly tiny structures of molecules using a technique called x-ray
crystallography was not new, it had been used for a decade or so by this point.
And so on its face, the structure of DNA was just using the existing method to show the
structure of a molecule that people already knew a fair bit about from a chemical viewpoint.
(09:05):
But because Hershey and Chase had just shown a year before, the DNA is what genes are made
of.
That 3D structure of DNA, that famous double helix, was an immediate sensation.
In 1953, people around the world could visualize and understand what this thing is inside all
of ourselves.
This hereditary material that seems to shape so much of who we are.
(09:28):
We all have genes that are made out of DNA and its shape is a double helix.
A few times so far, I've used the word gene without explaining what I mean by that.
And despite my instinct to define every single scientific term I use, I don't feel too
worried about using the word gene because it's a part of everyday language and it has been
(09:49):
for decades.
Most people have a sense of a gene as something related to DNA and something that makes you
you.
Genes are units of biological fate, or to use that slightly more technical term, units
of heredity.
At a physical level, what is a gene?
That was worked out over the next couple of decades after it was proven that DNA is a hereditary
(10:13):
material and the physical structure of DNA was solved, which immediately suggested a lot
of ideas about how it might function at the molecular level.
For instance, DNA is a double helix, meaning it forms a structure of two strands or chains,
each with an identical repetitive structure of sugar phosphate backbone units that directly
(10:33):
linked together.
And then there is a bit sticking off the side of every unit and we call that the side chain.
For DNA, those side chains can be A, G, C or T. Now, those are just letters that we use
as a shorthand for four similar but slightly different carbon-based molecules and they
have the longer names adenine guanine, cytosine and thymine.
(10:55):
And while I know this may seem obvious that ourselves are not full of the little letters,
years as a science teacher has taught me not to shame or belittle anyone from this understanding.
Because whenever DNA comes up in visual media, the image is normally either a double helix
or it's some matrix of letters, those A's, G's, C's and T's.
And indeed, scientists who work within the world of DNA do tend to think in terms of sequences
(11:18):
of letters and don't concern themselves too much with what the physical reality is that
those letters represent.
Those letters are referred to by scientists as DNA bases.
And yes, there's a logic to where that word comes from but it's not really worth spending
time on.
So you can just know that the DNA has these four different bases, the side chains, A, G,
(11:39):
C and T. A base plus the constant sugar phosphate section is called a nucleotide technically.
But if we avoid having to say the word nucleotide too often, we'll just use the word base to mean
one unit of DNA that's either an A, G, C or T. But back to our DNA molecule, you have
these two chains that have constant identical sugar phosphate backbones with different
(12:00):
side chains, the side chains pointed each other in the middle of the twisting helix.
And that's where the real molecular magic happens.
The bases are attracted to each other and form strong molecular bonds that only in two
specific combinations.
The two combinations the form complementary pairs are A, T, and C to G. That complementary
(12:21):
base pairing, that molecular rule that A pairs of T and C pairs of G was far more exciting
than just showing that DNA is a double helix.
A double helix is a nice shape for complementary base pairing or is it sometimes called
Watson Crick base pairing is fundamental to how DNA works as we'll see how genes work
too.
(12:41):
Imagine you took a DNA molecule and separated its two chains.
Now you have just one chain of sugar phosphate links and all these side chains just hang
it out in space.
A is G, C and T's in a seemingly random order up the chain.
That is unstable, DNA that is naked like that, or single stranded as we call it, is quickly
(13:03):
dissolved inside a cell.
But because of complementary base pairing, it would be very easy to fix this problem.
You'd know how to form the matching DNA chain by just going along one DNA space at a time,
wherever you find an A, put a T opposite it, wherever you find a G, put a C opposite it,
T opposite A and C opposite G, and then just stitch together all the sugar phosphate
(13:25):
back bones.
And that is actually how DNA gets replicated in all cells.
The two chains are pulled apart and then complementary base pairing allows new complementary
chains to fill in the gaps, turning one original DNA molecule into two, each one identical
to the original, each one containing one chain from the parent molecule and then one newly
(13:47):
synthesized with the molecular logic of complementary base pairing.
And the reason that this is so important to genes is that it allows DNA molecules to
be copied indefinitely between cells in one body and down generations, all by preserving
the exact same sequence of A's, G's, C's and T's in the original.
(14:09):
In that process, genes are protected, preserved and passed on.
So now reconnecting with this talk of DNA bases back to genes.
What is a gene?
A gene is a section of a DNA molecule, a series of anything from a few hundred to tens
of thousands of DNA bases.
So now let's reconnect all of this background on DNA bases back to genes.
(14:32):
A gene is a section of a DNA molecule, a series of anything from a few hundred to tens
of thousands of DNA bases.
They have a specific sequence, with that sequence defining the functional impact of the gene.
To picture it, you may know that humans have 23 different chromosomes, with two copies
(14:52):
of each and most of ourselves.
Each one of these 23 chromosomes is a separate DNA chain, a double helix, and each one is
roughly 100 million DNA bases long.
Within those 100 million bases and one chromosome, there are a lot of genes, and there's also
a lot of DNA that isn't genes.
(15:13):
If you started at position zero, they're going to start with a chromosome arbitrarily defined
you start going up the chain, you might find a gene starting at position 50 that goes
until 750, so 700 base pairs, and then another one that starts at 1200 and goes till 2500.
And intervening between these genes is sections of DNA that is not a gene can have other
(15:35):
functions that could spend a whole podcast going into all the other stuff that DNA can
do apart from being a gene.
This process of scanning up a chromosome and seeing where the genes are is something you
could actually do right now with a little bit of training and a computer, because thanks
to decades of research and billions of dollars of government research funding, there are
(15:58):
publicly available maps of the human genome, the genomes of many, many organisms on our planet.
But let's say somehow you could actually look inside a cell, and you weren't working
at a computer, you're looking into the cell, and you did that same thing of looking along
a DNA chain. You wouldn't exactly see signposts that says gene starts here or gene ends here,
(16:19):
but there would be some visible signs. Specifically you'd see a large molecule is called transcription
factors congregating at the start of the gene, in a section we call the promoter. We'll
learn a little bit more about transcription factors in episode 4.
Then in the middle of the gene you would see that the DNA double helix has been pulled apart,
and a large molecular complex, we call this RNA plenaries, would be chugging away through
(16:45):
the central section of the gene. Trailing behind would be a newly formed strand of something
that looks very similar to DNA, but has a few tweaks to it, and that would be a molecule
of RNA. RNA also has bases that are almost the same as DNA, and crucially RNA molecules
can be made from DNA templates during the exact same complementary base pairing that allows
(17:10):
DNA replication to work. So we can say that the RNA molecule that is being made at this
gene is complementary to the DNA sequence of the gene. Specifically the central section
of the gene, the bit we call the coding sequence, and it's called that precisely because it is
the sequence of DNA that contains the information or code used to make the complementary RNA
(17:32):
molecule. Then at the end of the gene it's the all of this complex molecular ballet ceasing,
molecules is associating from the DNA and the two DNA chains being zipped back together
into a nice double helix. That end section is called the terminator. The promoter we saw
earlier contains specific sequences of DNA that the molecular machinery of the cell can
(17:54):
read to know where to start the process of making an RNA molecule, and the terminator has
different sequences that give the stop signal. So the promoter and terminator basically
frame and define the section of DNA that is used to make a complementary RNA molecule.
And that information is retained down generations because the sequence of DNA is preserved as it
(18:17):
is copied. So there we have it. A gene is a section of DNA that has all the information
necessary to make an RNA molecule that will have a specific sequence of RNA bases complementary
to the DNA template. Okay, so what do we do with this RNA? Well, RNA is very cool and deserving
of its own podcast. For now, we'll just skip right over it and explaining why this matters
(18:41):
or at least the most important reason because ultimately the RNA is short lived and itself
is just uses a template to make a totally different type of molecule a protein. So our
DNA and RNA are very similar at the molecular level. RNA and proteins are not. I could spend
another 20 minutes or so explaining exactly how this works, but for now, just know that
(19:02):
the sequence of bases in the RNA is used as a guide for a different set of molecular machinery
to make a specific protein molecule, reading and translating the information in the RNA
into the molecular language of proteins. And indeed, translation is the scientific term
used for this process. Going from DNA to protein is called gene expression. If a gene is expressed,
(19:27):
that means that inside the cells of that organism, the DNA of that gene is being constantly
used as a template to turn our complementary RNA molecules that are then translated
to corresponding protein molecules. Proteins are similar to DNA and they're also long
chains made of similar subunits as in similar to each other within the chain. But whereas
(19:49):
DNA is chains of A, G, C, or T, protein chains include 20 or more different types of subunits.
These subunits are called amino acids. They are also more diverse in the 4 DNA bases,
both in terms of physical shape and size and also chemistry. So even though proteins are
all just chains of amino acids, they are functionally extremely diverse, and they do most of the
(20:14):
actual stuff involved in being alive. In episode 4, we'll see some specific examples of how
these genes work, and we'll recap on how genes make proteins and how those specific proteins
contribute to making a plant. And the later on in the series, we'll look at examples of
specific genes used to modify crop plants and the proteins that those genes encode.
(20:35):
So, you know, if you're wondering why you've been learning about basic molecular biology
and you thought you would be learning about GMOs, it's because I want to make sure that when
I start diving into talking about EPSP synthase, a protein produced by GMO corn because of a
trans gene and how that makes them herbicide tolerant, I'll be able to go into the
molecular details of all that without completely losing anyone. So anyway, that is the physical
(21:00):
side of genes. A gene is a piece of DNA that codes for RNA, that codes for a specific protein,
or more simply, a gene is a piece of DNA that codes for a specific protein, and proteins
from the molecular machines that shape the traits of living things.
In school, you might have learned it as a gene codes for a trait, and just to recap,
(21:22):
traits are the things we can see that define an organism, e.g. you could say a gene for eye color
or a gene for grain size. That is kind of a relic of how genes were first studied in the early
20th century. There was no other option but to connect each gene to a single trait to make it possible
to conceptualize and track the effect of the gene. However, to try and summarize decades and decades
(21:47):
of research in three words, biology is complicated. Almost every trait, especially at the level of traits
that we humans could see or care about, is influenced by multiple genes. Each trait is the product of
many proteins working together, influenced by each other, and by the environment. That's because
the information genes carry is not for a whole trait, but just for one protein. But in cases where
(22:12):
things are kept identical, except for tweaking just one due to the time, then you can often see that
effect in the observable traits of the organism. That is never really the case in nature,
or in real human populations, but it is the case in selective breeding where humans deliberately
inbreed populations of plants and animals till they are genetically identical. So then when a change,
(22:35):
or we call it a mutation, arises in one gene, you can actually see that impact as say a change in
flower color. So as you'll see in the next episode, episode three, if you happen to be a patient,
Augustinian, Frey, named Gregor Mendel, you can track and study that flower color variant and deduce
a set of rules about the inheritance of things you'll have first call factors and what will later come
(22:59):
to be known as genes. The machinery that supports gene replication and gene expression is remarkably
similar across all of life, which is one of the reasons it's almost certain that all living things
on earth are directly related to one another in a literal sense. Every bacterium, human and mushroom
on earth are family, distant family, sure, you'd have to go back billions of years to find out
(23:23):
common ancestor, but family just the same. We all have genes made of DNA and we all have a pretty
similar set of machinery to read the DNA to make proteins. And that's DNA's primary job because
otherwise it can't really do anything. The proteins are the exciting stuff. The 20th century was an
(23:43):
extremely busy period for biology. In the 19th century, biology was a newcomer to the natural
sciences, struggling to compete in prestige and attention against the more well established
fields of physics and chemistry, which had already more than proven their own value to human life
and to making money. The industrial revolutions of the 19th century were intimately tied up with
(24:06):
scientific research into physics and chemistry and both supported in turn by mathematics. Biology
had contributed relatively little to value. The study of living things didn't seem to be yielding
much even to the field of medicine the most obvious area of application. That shifted fundamentally
over the 20th century with DNA at the vanguard of that change. In our next episode, we'll explore
(24:32):
Mendels's pioneering work in what we now call genetics, but that work was largely ignored at the
time and underappreciated until its rediscovery at the very start of the 20th century. In practice,
genetics as a field of biological research was born in the first decade of the 20th century.
In the year 1900, a trio of plant scientists read and promoted the work of Mendel
(24:56):
triggering broader scientific interest in the topic. In the year 1900, a trio of plant scientists
read and promoted the work of Mendel triggering broader scientific interest in the topic.
And in the year 2000, a century later, the first working draft was published on the human genome,
with the human genome project wrapping up three years later in 2003 with a well annotated,
(25:21):
publicly available digital database of a complete human genome.
The result of almost four billion dollars of government investment,
as well as a private corporate interest, and the work of thousands of scientists across multiple
countries. And all the way across that century from the birth of genetics of the human genome project,
(25:42):
incremental discoveries are made, the work of thousands and thousands of people, some of them
incredibly famous, most of them anonymous to all about colleagues in their particular niche field.
More and more over the century, DNA moved into the center of biology.
There are many biologists who spend a whole career interacting and thinking about DNA only rarely
(26:04):
if ever, but they are numerically in the minority. Most biology today is molecular biology,
both the basic research that mostly happens at universities, as well as the applied research that
happens in the R&D labs of private companies. Molecular biology isn't a field of study,
but a category of practice. It is biology that takes place in laboratories where questions are
(26:27):
answered and problems are solved using biomolecules, most notably DNA.
More and more of this work in the laboratory is connected with work at a computer,
studying and designing gene sequences, or the proteins encoded by those genes.
One of the common methods used by molecular biologists is the creation of genetically modified
(26:48):
organisms, though that usually means genetically modified bacteria or other single-celled organisms.
One of the most effective ways to understand how a gene functions is to deliberately modify it
and see what traits inside the cell are impacted by the modification.
That is one of the reasons that many biologists can get frustrated and defensive about opposition to
(27:08):
GMO crops. If genetically modifying organisms is part of your everyday work, then it seems crazy
to say the GMOs are something dangerous and unknown, and it can seem more frustrating to those
biologists who are working directly or indirectly on saving lives, for improving understanding of
the human body, or developing new types of life-saving treatments for everything from cancer to
(27:30):
COVID. Genetics and genetic modification have embedded themselves into the heart of biology.
Thank you for listening to Modified. This was episode 2, what genes are made of,
is written by me or landed along. I use many sources to help you research this episode,
and want to particularly acknowledge the Cosprin carbuloboratory oral history collection,
(27:52):
which you use for inspiration in the section of Martha Chase and Alfred Hershey.
This is the tiny one person's podcast, so please leave a review if you're enjoying it
and tell a friend. If you have notes, well I'd love to hear them. You can email me at Orlando and
modifypod.com. That's O-R-L-A-N-D-O at ModifiedPod.com. I'd love to hear from you. You can find
(28:14):
that more about me and the podcast on our website, ModifiedPod.com. That's ModifiedPODORNWR.com.
That's the end of the talk today's episode. Our round things out with five take-home messages,
so if you're stopping here, thanks for listening until next time.
For those sticking around, here are your five take-home messages.
(28:35):
Number one, DNA is the hereditary material, and this was finally proven in the 1950s.
Number two, physically DNA is too long-chains to form a double helix. The chains are connected
by complementary base pairing, age to tease, and geostasis. Number three, complementary
base pairing allows DNA to be replicated indefinitely while maintaining the same sequence of age,
(29:00):
G-C's, and P's. Number four, complementary base pairing also works to create complementary RNA
molecules. This is how genes work. They are sections of DNA, the code for a specific protein,
via an intermediate RNA molecule. Number five, proteins are molecular machines that play a
dominant role in defining the traits of an organism, so there's a reasonable short-term to say
(29:24):
the genes to find traits. Okay, that wraps up our second episode. I hope you're listening
for episode three, the one with Mendel and his P's. Bye!
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