August 8, 2025 • 23 mins
Explores the historical evolution of medical genetics in the postwar era, specifically focusing on how the field moved towards identifying, mapping, and preventing genetic diseases. It traces the development of infrastructures for organizing genetic information, from early heredity clinics and the visual analysis of chromosomes to advanced molecular techniques like DNA hybridization and microarrays. The text highlights the interplay between clinical observation and scientific advancements, demonstrating how conditions like Fragile X syndrome, Prader-Willi syndrome, and DiGeorge syndrome became understood through the lens of chromosomal abnormalities and gene mutations. Ultimately, the author examines the ongoing challenges and debates surrounding prenatal diagnosis and the one mutation–one disorder ideal in shaping medical practice and patient care.
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You can listen and download our episodes for free on more than 10 different platforms:
https://linktr.ee/book_shelter
Get the Book now from Amazon:
https://www.amazon.com/Life-Histories-Genetic-Disease-Prevention/dp/1421420740?&linkCode=ll1&tag=cvthunderx-20&linkId=932c98586912d0d880cc9657504d5a99&language=en_US&ref_=as_li_ss_tl
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Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Speaker 1 (00:00):
Have you ever stopped to think about how doctors actually
identify a genetic disorder, things like Down syndrome or fragile x,
sometimes even before baby's born.
Speaker 2 (00:10):
It's really quite a story, isn't it. How we went
from just seeing symptoms you know that word science, to
actually visualizing the problem right down at the cellular level.
Speaker 1 (00:19):
Yeah, and then even smaller exactly. And that's what we're
diving into today. This really fascinating history of medical genetics,
especially in the years after World War Two. We're looking
at how geneticists and doctors developed the tools and maybe
even the confidence to see these conditions, which well often
led to some pretty stark choices about prevention, right.
Speaker 2 (00:38):
And for this deep dive, we're drawing heavily from the
book Life Histories of Genetic Disease Patterns in Prevention in
Post War And like you said, it's not just a
science textbook story. It's really about evolving medicine, these incredible
tech breakthroughs, but also the really profound ethical questions that
came along with them, questions that shape health and family decisions.
Speaker 1 (00:59):
So our mission for you, the listener, is to kind
of walk through those key moments, the big shifts in
thinking that totally changed how we understood genetic diseases. We'll
start with peering down microscopes and end up well looking
at entire genomes. It's really about how chromosomes became this
central like an address book for our health.
Speaker 2 (01:20):
Yeah, that's a good way to put it. An address book.
Speaker 1 (01:23):
Okay, So let's set the scene after World War Two.
You have medical genetics really trying to step away from
the shadow of early twentieth century eugenics.
Speaker 2 (01:33):
Right, that history was definitely there. But while the impulse
to sort of identify and maybe even remove disease genes
didn't vanish entirely, the focus did shift more towards individual choice,
individual families, and this.
Speaker 1 (01:47):
Led to the establishment of actual heredity clinics, didn't it
often in universities, with doctors and geneticists starting to work
much more closely.
Speaker 2 (01:53):
Together exactly, And two new subspecialties really drove this early
work kind of in parallel dis morphology and human side
of genetics.
Speaker 1 (02:01):
Dys morphology that sounds complex.
Speaker 2 (02:03):
We'll think of it like detective work. John Ace, who
studied under a key figure named David Smith, actually compared
it to Sherlock Holmes. Smith taught doctors to look for
these really subtle, easily missed things, minor malformations, not big,
obvious defects, but things like, you know, the exact distance
between the eyes, or the shape of the ears, or
(02:24):
even where the nipples were placed.
Speaker 1 (02:25):
Wow, okay, so tiny details, tiny details.
Speaker 2 (02:29):
But the breakthrough was realizing that when you saw patterns
of these minor things together, they often pointed towards a
single underlying genetic cause. And because these syndromes were individually
quite rare, it became what they called an urban profession.
Experts needed to gather, compare notes, look at lots of
patients to build up that recognition.
Speaker 1 (02:47):
So while the dysmorphologists were becoming these pattern detectives, was
happening with human insider genetics.
Speaker 2 (02:53):
That was happening under the microscope. Literally in the nineteen fifties,
there was a lot of concern, especially from people like
Herman J. Muller, about nuclear radiation and what it might
be doing to our genes. So the push was on
to make human chromosomes visible, not just visible, but something
you could organize, arrange, classify. Ah.
Speaker 1 (03:16):
So that's where the carrier type comes in, lining them.
Speaker 2 (03:18):
All up precisely arranging them by size into those seven
groups A through G. It sounds simple now, maybe, but
getting that right, especially for the tricky ones like the
C group chromosomes that all looked pretty similar, was fundamental.
It was the first step to seeing differences.
Speaker 1 (03:32):
Yeah, those first steps were just huge. They needed a
common way to even talk about what they were seeing.
Speaker 2 (03:37):
Absolutely, and getting that standardized view.
Speaker 1 (03:39):
Was key, which brings us to the idea of mapping them.
Speaker 2 (03:42):
Right.
Speaker 1 (03:42):
Once you can see them, you want to map them exactly.
Speaker 2 (03:45):
Making that vision universally understood was the next big hurdle,
and that's where ideograms came, and these idealized drawings, maps
of each chromosome showing its key features.
Speaker 1 (03:55):
Like a universal language for geneticists.
Speaker 2 (03:58):
Precisely, it wasn't just about seeing, It was about communicating
what you saw accurately across labs, across countries. That laid
the foundation for everything that followed. Truly foundational.
Speaker 1 (04:10):
Okay, so they could see them, they had a way
to represent them. Then came the real mapping, right the
sixties and seventies, Yes.
Speaker 2 (04:15):
That's when chromosomal cartography really took off, going from like
you said, broad strokes to finer and finer detail. There's
actually a fun little story from a conference in nineteen
sixty six, Lionel Penrose apparently quite humorously suggested naming the
short arm of a chromosome P for PET and the
long arm Q well, Q comes after P huh well.
(04:36):
He also linked it to the P plus Q one
equation from population genetics. It was partly a joke, partly practical,
and it just stuck. But it was part of these bigger,
often quite intense international efforts to agree on mapping conventions.
Speaker 1 (04:48):
And then came the staining the barcodes.
Speaker 2 (04:51):
Ah Yes, around nineteen seventy. That was revolutionary techniques like
quinna crene or Q banding, GEMSA or G banding, or
verse or R banding. Suddenly each chroma zone pair had
a unique reproducible banding pattern like a barcode.
Speaker 1 (05:04):
Okay, that sounds like a game change.
Speaker 2 (05:05):
It absolutely was, because now cytogeneticists could reliably tell every
single chromosome apart, no more guessing with the C group
and those bands they became landmarks addresses on the map so.
Speaker 1 (05:20):
They could pinpoint locations.
Speaker 2 (05:22):
Exactly, which led to the Paris conference in nineteen seventy one,
where they formalized the naming system like fifteen Q twelve
chromosome fifteen long arm Q region one band two super
specific addresses crucial for mapping genes.
Speaker 1 (05:35):
And did that lead directly to finding where genes were.
Speaker 2 (05:38):
It enabled it? For example, back in nineteen sixty eight,
even before banding was perfected, Roger Donahue, who worked with
Victor Mchuthick, managed to map the first gene not on
the X chromosome, the Duffy blood group gene to chromosome one,
just by noticing a subtle variation in its length in
one family. Banding made that kind of mapping much more systematic.
Speaker 1 (05:56):
Right, And wasn't there another technique around that time involving.
Speaker 2 (05:59):
Mice ah Yes, Somatic cell hybridization that started in the
sixties too, really clever. Actually, They figured out how to
fuse human cells and rodent cells usually mouse cells together
in a.
Speaker 1 (06:08):
Lab dish, use them like one big cell kind of.
Speaker 2 (06:11):
And the really interesting thing was, over time these hybrid
cells tended to randomly kick out most of the human
chromosomes but keep all the mouse ones.
Speaker 1 (06:21):
Okay, so how did that help?
Speaker 2 (06:23):
Well, you'd end up with the collection of hybrid cell lines,
each containing only one or a few different human chromosomes.
Then you could test those cells. Does this cell line
make human protein X. If it did and you knew
it only had say, humor chromosome seventeen left.
Speaker 1 (06:38):
Ah, then the gene for protein X must be on
chromosome seventeen exactly.
Speaker 2 (06:43):
It was a powerful tool, though initially hampered a bit
because distinguishing the chromosomes before banding was hard. But once
banding came along in the seventies, they could be certain.
That's how they pinned the gene for thymidan kines to
chromosome seventeen for instance.
Speaker 1 (06:56):
It sounds like things were really accelerating.
Speaker 2 (06:58):
Then there were you had figures like Victor mccusick, who
was originally a cardiologist but became this giant in medical genetics,
really championing the cause. He used these powerful metaphors talking
about cartographic exploration of the genome or studying its anatomy.
He even called for moonshot level investment to get the
human chromosomes fully mapped. He saw it as building essential infrastructure,
(07:23):
a map.
Speaker 1 (07:23):
For the future of medicine.
Speaker 2 (07:25):
Basically, that was the vision. Build the map, create the
reference system, and then you could really start to understand
genetic disease.
Speaker 1 (07:32):
But as we often find, not everyone saw this purely
as scientific progress, right.
Speaker 2 (07:36):
There were critics, Yes, absolutely, It's important to remember that
people like the bioethicist Abbi Lippman, writing in the early nineties,
raised serious concerns. She argued that this whole mapping enterprise
wasn't neutral science. It was, in her words, of political
and cultural activity, that it reflected certain societal values, particularly
a focus on identifying and potentially eliminating.
Speaker 1 (07:58):
Abnormality HMO built into the process itself.
Speaker 2 (08:01):
That was her argument that it could lead to a
kind of colonization of health, defining what's normal and what's not,
possibly pushing towards the sort of voluntary or liberal eugenics,
driven by individual choices, but shaped by these powerful new technologies.
A really important counterpoint to the purely celebratory narrative.
Speaker 1 (08:19):
That's a heavy thought. Let's maybe unpack a specific condition
to see how this played out. Fragile X syndrome seems
like a good example of this evolution.
Speaker 2 (08:27):
It really is. It shows the journey from a subtle
visual clue to a molecular understanding and the prevention focus
that came with it. So it starts back in nineteen
sixty seven, Herbert Loves at Yale spots this unusual marker
X chromosome in a boy with developmental delays, just a
little constriction near the end of the X chromosome. But
(08:47):
what did it mean? Sided geneticis were constantly finding little variations,
was this one significant or just normal human difference?
Speaker 1 (08:54):
Right? Separating the signal from the noise exactly?
Speaker 2 (08:58):
Then jumped to nineteen seventy. In Australia, pediatrician Gillian Turner
observed something clinically interesting. She sees families where boys have
X linked intellectual disability, but they look well physically normal,
no distinctive facial features like in Down syndrome.
Speaker 1 (09:14):
So the clinical picture didn't immediately scream syndrome.
Speaker 2 (09:17):
Not in the same way. It was initially considered maybe
something called rem Penning syndrome. But then by the mid seventies,
another clinical science started to be consistently noticed in these boys,
macro orchidism or unusually large tests after puberty. That became
a key distinguishing feature. Still no clear link to Lub's
marker X though.
Speaker 1 (09:35):
Okay, so you have a clinical picture emerging and this
separate chromosome marker floating around.
Speaker 2 (09:39):
And then bingo. In nineteen seventy six seventy seven, other
geneticists start reporting finding similar to Lubbs's original marker X,
and now they're calling it a fragile site. That term
fragile site had actually been coined a few years earlier,
in nineteen seventy by Ellen Majanis and Frederick Hecht for
a different fragile spot on chromosome sixteen. These were just
points on romosomes that seemed prone to breaking when cells
(10:01):
were grown in certain lab media.
Speaker 1 (10:03):
So Lupps's marker was rediscovered and named a fragile site
on the X chromosome.
Speaker 2 (10:09):
Yes, and suddenly the clinical picture in the subtgenetic finding
started to come together. By nineteen seventy eight, Gillian Turner
and her colleagues were describing how you could use this
fragile site for targeted prevention.
Speaker 1 (10:21):
How did that work?
Speaker 2 (10:22):
Well? If you identified a boy with the characteristic features,
the intellectual disability, the macro orchidism, you check his chromosomes
for the fragile site on the X. If it was there,
you could then test female relatives like his sisters or
mother to see if they were carriers. A carrier female
would have a fifty percent chance with each pregnancy of
passing on that fragile X chromosome, so they could then
(10:44):
off for prenatal diagnosis, usually ameosentesis to check the fetus's chromosomes.
If the fetus had the fragile x.
Speaker 1 (10:51):
They faced the choice of terminating the pregnancy.
Speaker 2 (10:54):
Correct Because importantly there was no treatment, prevention through identification
and selective abortion was the only medical option presented, and the.
Speaker 1 (11:02):
Name fragile x syndrome solidified around then.
Speaker 2 (11:05):
It became widely adopted in the early eighties, thanks in
part to a book by Randy Hagerman and Lauris mcgavern
in nineteen eighty three, but the story still had twists.
Stephanie Sherman made this really puzzling observation. The condition seemed
to get worse or show up earlier in later generations
within the same family.
Speaker 1 (11:24):
It was called anticipation, which didn't fit standard genetic inheritance patterns.
Speaker 2 (11:29):
Not at all. It baffled everyone became known as the
Sherman paradox. It wasn't until nineteen ninety one that the
molecular basis was found. An international team pinpointed the actual
gene FMR one and discovered he had this unstable section
a repeating sequence of cgg ah.
Speaker 1 (11:45):
And the repeat could expand from one generation to the next.
Speaker 2 (11:48):
Exactly that expansion explained the Sherman paradox and anticipation a
huge molecular breakthrough.
Speaker 1 (11:53):
But going back to the earlier point, fragile x really
became a sort of poster child for this new focus
on prevention, didn't.
Speaker 2 (11:59):
It absolutely did. As Lubes and Felix Dela Cruz stated
in a big NIH report in nineteen seventy seven, we
were entering the age of prevention. The thinking was curing
these things is incredibly hard, maybe impossible for now, but
preventing them through diagnosis that seemed achievable. Gene therapy was
still seen as a distant dream, as Acoustic put it,
(12:21):
so diagnosis leading to prevention became the dominant approach.
Speaker 1 (12:25):
Let's look at another complex case, Prater Willie syndrome. This
sounds like it also involved piecing together a complicated puzzle,
very much so.
Speaker 2 (12:32):
It was first described in nineteen fifty six by Swiss
doctors Praterer, lab Heart and Willie and it has this
really distinct, challenging life course starts with severe muscle weakness,
hypotonian infancy, babies or floppy have trouble feeding, but then
usually in early childhood, there's this dramatic switch to uncontrollable
appetite leading to severe obesity, often accompanied by intellectual disability
(12:55):
and behavioral issues. A really difficult trajectory.
Speaker 1 (12:57):
Defining that must have been tricky, especially differential it from
other causes of obesity.
Speaker 2 (13:02):
Absolutely, you know, physicians have always wanted clear disease categories.
You see these attempts to look back at old paintings
like La Monstrue or historical cases like one of John
Langdon downs and say, ah, that must have been this syndrome.
And there was confusion with things like foolish syndrome, which,
as the physician hilde Bruce pointed out, had become this
kind of catch all diagnosis for almost any childhood obesity,
(13:24):
losing its specific meaning.
Speaker 1 (13:25):
So what made Praeter Willy stand out It was that
really specific transition from the infantile floppiness to the later
hyperphagia and obesity.
Speaker 2 (13:35):
That two stage pattern was the defining clinical feature that
frater lap heart and Willy delineated.
Speaker 1 (13:40):
And how did genetics come into the picture? When did
they find a cause?
Speaker 2 (13:44):
That took time and again relied on advances in seeing
the chromosomes more clearly. There were early hints or report
in nineteen eighty one by Holly and Smithy's of a
chromosomal translocation involving chromosome fifteen in one patient, but the
big push came from people like Orgey Unis mid seventies
arguing for high resolution cidedgenetics, getting more bands visible maybe
(14:05):
three hundred, five hundred, even more per kariotype. He wanted
to bridge that gap between genes and chromosomes see smaller changes.
Speaker 1 (14:12):
And did that work for Prayer Willy Yes.
Speaker 2 (14:15):
In nineteen eighty one, David Ledbetter and vincent Riccardi, using
these high revolution techniques, were able to consistently identify a
tiny deletion on the long arm of chromosome fifteen, specifically
in the region fifteen Q eleven thirteen in most patients
with Peter Willi syndrome.
Speaker 1 (14:29):
Found it a specific genetic address.
Speaker 2 (14:32):
A specific address in the genome's morbid anatomy as some
called it a huge step, but like always it opened
up new questions.
Speaker 1 (14:38):
Like was the deletion definitely the.
Speaker 2 (14:39):
Cause right or just associated? And it also led to
the idea of continuous gene syndromes proposed by Roy Schmikel
in nineteen eighty six. He suggested that maybe complex syndromes
like Praeter Willy weren't caused by losing just one gene,
but by losing several genes located next to each other
in that deleted segment. Seeing the deletion was one thing,
(15:01):
Understanding its functional consequence was another layer of complexity.
Speaker 1 (15:04):
It really highlights that even seeing the problem doesn't immediately
give you all the answers.
Speaker 2 (15:09):
Not at all. Observation then interpretation than understanding the mechanism.
It's a continuous process.
Speaker 1 (15:14):
Okay, let's shift gears slightly. What about cases where different
clinical syndrome seemed to merge genetically speaking, like do George
and Velo cardiofacial syndromes. Ah.
Speaker 2 (15:23):
Yes, that's a fascinating story about the one mutation, one
disorder ideal versus clinical reality and well professional identities. So first,
you have DiGeorge syndrome, described in nineteen sixty five by
pediatrician Angelo to George. He noted this pattern of birth defects,
crucially including absence or underdevelopment of the fymasin parathyroid glans,
often leading to immune problems in the low calcium and.
Speaker 1 (15:46):
The name stuck, even if he didn't push for it.
Speaker 2 (15:48):
Apparently he demurred the eponym, but yeah, the George syndrome
caught on. It described this constellation of symptoms, but with
quite a bit of variability between patients.
Speaker 1 (15:56):
Then along comes VCF.
Speaker 2 (15:58):
Right in nineteen seventy eight, Robert Schrenzen, a speech pathologist
using that dys morphology approach looking for patterns, identified what
he saw as a new syndrome. He called it Velo
cardio facial or VCF syndrome based on the common features
he saw pallid abnormalities, vello heart defects, cardio and characteristic
(16:19):
facial features facial often with learning difficulties too.
Speaker 1 (16:22):
So initially seen as distinct things, yes, but then.
Speaker 2 (16:25):
The genetics started pointing towards chromosome twenty two, especially for
to George. And then in the early nineteen nineties came
the big convergence. Using feesh Age probes, those fluorescent tags
that can stick to specific DNA sequences, researchers found the
same small deletion on chromosome twenty two in the twenty
two kleven region in patients diagnosed with de George and
d impatients diagnosed with VCF WHOA.
Speaker 1 (16:47):
So genetically they look like the same thing.
Speaker 2 (16:49):
Powerful evidence for it. It really seemed to support that
idea one specific mutation, the twenty two Q eleven deletion
causing one disorder, even if it looked a bit different
in different people.
Speaker 1 (17:00):
But did everyone just say, Okay, it's one thing now.
Speaker 2 (17:04):
Not quite. This is where the social side of science
comes in. Unifying the genetic cause didn't automatically unify the
names or the communities built around them. Sprintson, for instance,
argued quite strongly that VCF syndrome was the more accurate
description the true syndrome caused by the deletion. Others preferred
the more neutral, genetically precise name twenty two Q eleven
(17:25):
point two deletion syndrome.
Speaker 1 (17:26):
Like the blind men and the elephant, different specialists focusing
on different aspects.
Speaker 2 (17:30):
That's a great analogy. Different specialists cardiologists, immunologists, speech pathologists,
geneticists were maybe emphasizing different features, and you had clinics,
research programs, family support groups all established around these separate names.
Speaker 1 (17:43):
Merging them wasn't simple, So even definitive genetic proof doesn't
always settle things neatly.
Speaker 2 (17:48):
Not always. And interestingly this contrast with Crater, Willy and
Angelman syndromes. They share the exact same deletion region on
chromosome fifteen that fifteen Q eleven thirteen area, but.
Speaker 1 (17:58):
They look completely different clinically right.
Speaker 2 (18:00):
Totally different due to genomic imprinting. Whether the deletion is
inherited from the mother or the father determines which syndrome
you get. So in that case, despite the identical deletion,
the distinct clinical pictures kept them firmly separate. Shows a complexity.
Sometimes the genetics unites, sometimes the clinic still divides.
Speaker 1 (18:17):
Fascinating. Okay, let's zeemat again. We've moved from blurry chromosomes
to specific bands and deletions. What happened when the Human
Genome Project came along in the raindeies.
Speaker 2 (18:27):
Ah, the HGP that really ushered in the era of
the molecular gaze a whole new level of seeing. While
fish probes let you look for one specific known deletion
like twenty two Q eleven the HGP aim for the
whole picture, all the DNA.
Speaker 1 (18:42):
Sequence, and how did they start to look at that
whole picture for variations beyond sequencing everything for everyone?
Speaker 2 (18:48):
Well, techniques emerged, like comparative genomic hybridization CGH, developed around
nineteen ninety two by people like Joe Gray and and
Ali Calioniumi. The idea was to compare a patient's entire
DNA load against a standard reference genome, looking for regions
where the patient had too much or too little DNA
gains or.
Speaker 1 (19:06):
Losses, so finding deletions or duplications genome wide, not just
at known spots exactly.
Speaker 2 (19:12):
And then came DNA chips or microarrays, pioneered by Edwin
Southern and commercialized by companies like a Fi Matrix around
nineteen ninety four. These could test thousands, eventually millions, of
tiny DNA spots simultaneously. This allowed for finding much smaller
gains and losses what we now call copy number variants cnbs,
things way too small to see even with high resolution banding.
Speaker 1 (19:33):
Right, But the raw output of the HGP, all those
a's tcs and gs wasn't exactly user friendly?
Speaker 2 (19:39):
Was it?
Speaker 1 (19:39):
Not?
Speaker 2 (19:39):
At all? Just a massive string of letters. That's where
genome browsers became absolutely essential. Things like the UCSC genome
Browser or ensemble that provided a visual interface way to
navigate this ocean of data. And crucially, what do they
use as the main organizing.
Speaker 1 (19:53):
Principle The chromosomes, those ideograms.
Speaker 2 (19:55):
Yes, they kept that familiar structure, the chromosome maps, the
banding patterns. They became the signposts as side of geneticist
Dorothy Warburton called them, the familiar neighborhood to orient yourself
within the molecular data. The visual chromosome map remained central
even in the molecular age.
Speaker 1 (20:13):
Okay, so this ability to see tiny CNV's genome wide
inevitably it moved towards prenatal testing.
Speaker 2 (20:20):
Right it did. Starting significantly in the two thousands, companies
like Signature Genomic Laboratories led by Lisa Schaeffer and Bessembajohnny
developed microarrays specifically for prenatal diagnosis. Initially they might target
known regions associated with intellectual disability, like their Signature chip,
but soon the technology allowed for whole genome backbone coverage.
(20:42):
The promise being, as Arthur Bode put it, the promise
was essentially to do every known for PIRSH test in
the world at once, plus find new things you weren't
even looking for. Catch everything.
Speaker 1 (20:50):
But that sounds like it could open a huge can
of worms, exactly.
Speaker 2 (20:54):
The peril the anxiety. Bioethicist Eveline Schuster wrote about this
in two thousand and seven, warning about a potential roadblock
for life. Her concern was this what happens when you
get a flood of information back from a prenatal micro array.
You might find the specific thing you were testing for,
but you might also find several CNVs of unknown clinical significance,
(21:15):
tiny bits of DNA missing or extra, but nobody knows
if they actually cause a problem or are just harmless variations.
Speaker 1 (21:22):
And parents facing a ticking clock on pregnancy decisions.
Speaker 2 (21:25):
Right they can be faced with terrifying uncertainty. Schuster worried
it could lead parents to terminate wanted, potentially healthy pregnancies
out of fear of the unknown, causing them to have
no baby at all.
Speaker 1 (21:35):
So who does benefit from seeing the whole picture prenatally,
It's still debated very much.
Speaker 2 (21:39):
So it's this constant balancing act. On one hand, discovering
new causes of disease. On the other the huge ethical
burden of interpreting uncertain results for anxious parents. Even when
the American College of Obstetricians and Gynecologists ACOG cautiously endorsed
micro array as a first tier test in some prenatal
cases in twenty thirteen, they stressed heavily the absolute need
(22:01):
for extensive genetic counseling beforehand and afterwards. The information is
powerful but potentially overwhelming.
Speaker 1 (22:08):
So wrapping this up, we've journeyed from doctors squinting at
physical traits, to peering through microscopes at chromosomes, adding stains
and bands, finding deletions, and now scanning the entire molecular code.
Speaker 2 (22:18):
Yeah, this whole complex infrastructure of the techniques, the classifications,
the maps, built piece by piece over decades has really
become this monumental edifice for prevention, as the book calls it.
Speaker 1 (22:28):
But that one mutation, one disorder idea, while powerful, hasn't
always been the full story, has it.
Speaker 2 (22:34):
No, As we saw with Peter Willy Engelman or the
did George vcf saga, the clinical picture how a condition
actually manifests, and even the social structures around diagnosis, they
still matter immensely in defining what a genetic identity means.
It's rarely just the DNA sequence.
Speaker 1 (22:50):
Ultimately, this deep dive really shows how the genomic gaze
lets us see ourselves genetically in incredible detail. The potential
for diagnosis, maybe even future treatment is huge, but it
forces these really profound questions on us.
Speaker 2 (23:04):
What information do we actually want, how do we handle uncertainty?
What choices do we make based on this incredibly detailed
but sometimes ambiguous blueprint.
Speaker 1 (23:13):
So for you the listener, maybe the takeaway thought is this,
as these technologies get ever more powerful, letting us see
our own unique genetic makeup in ever greater detail, how
might that change your personal understanding of what health or
disease even means? And what might that imply for the
kinds of choices you or society might face down the road.
Have you ever stopped to think about how doctors actually
identify a genetic disorder, things like Down syndrome or fragile x,
sometimes even before baby's born.
Speaker 2 (00:10):
It's really quite a story, isn't it. How we went
from just seeing symptoms you know that word science, to
actually visualizing the problem right down at the cellular level.
Speaker 1 (00:19):
Yeah, and then even smaller exactly. And that's what we're
diving into today. This really fascinating history of medical genetics,
especially in the years after World War Two. We're looking
at how geneticists and doctors developed the tools and maybe
even the confidence to see these conditions, which well often
led to some pretty stark choices about prevention, right.
Speaker 2 (00:38):
And for this deep dive, we're drawing heavily from the
book Life Histories of Genetic Disease Patterns in Prevention in
Post War And like you said, it's not just a
science textbook story. It's really about evolving medicine, these incredible
tech breakthroughs, but also the really profound ethical questions that
came along with them, questions that shape health and family decisions.
Speaker 1 (00:59):
So our mission for you, the listener, is to kind
of walk through those key moments, the big shifts in
thinking that totally changed how we understood genetic diseases. We'll
start with peering down microscopes and end up well looking
at entire genomes. It's really about how chromosomes became this
central like an address book for our health.
Speaker 2 (01:20):
Yeah, that's a good way to put it. An address book.
Speaker 1 (01:23):
Okay, So let's set the scene after World War Two.
You have medical genetics really trying to step away from
the shadow of early twentieth century eugenics.
Speaker 2 (01:33):
Right, that history was definitely there. But while the impulse
to sort of identify and maybe even remove disease genes
didn't vanish entirely, the focus did shift more towards individual choice,
individual families, and this.
Speaker 1 (01:47):
Led to the establishment of actual heredity clinics, didn't it
often in universities, with doctors and geneticists starting to work
much more closely.
Speaker 2 (01:53):
Together exactly, And two new subspecialties really drove this early
work kind of in parallel dis morphology and human side
of genetics.
Speaker 1 (02:01):
Dys morphology that sounds complex.
Speaker 2 (02:03):
We'll think of it like detective work. John Ace, who
studied under a key figure named David Smith, actually compared
it to Sherlock Holmes. Smith taught doctors to look for
these really subtle, easily missed things, minor malformations, not big,
obvious defects, but things like, you know, the exact distance
between the eyes, or the shape of the ears, or
(02:24):
even where the nipples were placed.
Speaker 1 (02:25):
Wow, okay, so tiny details, tiny details.
Speaker 2 (02:29):
But the breakthrough was realizing that when you saw patterns
of these minor things together, they often pointed towards a
single underlying genetic cause. And because these syndromes were individually
quite rare, it became what they called an urban profession.
Experts needed to gather, compare notes, look at lots of
patients to build up that recognition.
Speaker 1 (02:47):
So while the dysmorphologists were becoming these pattern detectives, was
happening with human insider genetics.
Speaker 2 (02:53):
That was happening under the microscope. Literally in the nineteen fifties,
there was a lot of concern, especially from people like
Herman J. Muller, about nuclear radiation and what it might
be doing to our genes. So the push was on
to make human chromosomes visible, not just visible, but something
you could organize, arrange, classify. Ah.
Speaker 1 (03:16):
So that's where the carrier type comes in, lining them.
Speaker 2 (03:18):
All up precisely arranging them by size into those seven
groups A through G. It sounds simple now, maybe, but
getting that right, especially for the tricky ones like the
C group chromosomes that all looked pretty similar, was fundamental.
It was the first step to seeing differences.
Speaker 1 (03:32):
Yeah, those first steps were just huge. They needed a
common way to even talk about what they were seeing.
Speaker 2 (03:37):
Absolutely, and getting that standardized view.
Speaker 1 (03:39):
Was key, which brings us to the idea of mapping them.
Speaker 2 (03:42):
Right.
Speaker 1 (03:42):
Once you can see them, you want to map them exactly.
Speaker 2 (03:45):
Making that vision universally understood was the next big hurdle,
and that's where ideograms came, and these idealized drawings, maps
of each chromosome showing its key features.
Speaker 1 (03:55):
Like a universal language for geneticists.
Speaker 2 (03:58):
Precisely, it wasn't just about seeing, It was about communicating
what you saw accurately across labs, across countries. That laid
the foundation for everything that followed. Truly foundational.
Speaker 1 (04:10):
Okay, so they could see them, they had a way
to represent them. Then came the real mapping, right the
sixties and seventies, Yes.
Speaker 2 (04:15):
That's when chromosomal cartography really took off, going from like
you said, broad strokes to finer and finer detail. There's
actually a fun little story from a conference in nineteen
sixty six, Lionel Penrose apparently quite humorously suggested naming the
short arm of a chromosome P for PET and the
long arm Q well, Q comes after P huh well.
(04:36):
He also linked it to the P plus Q one
equation from population genetics. It was partly a joke, partly practical,
and it just stuck. But it was part of these bigger,
often quite intense international efforts to agree on mapping conventions.
Speaker 1 (04:48):
And then came the staining the barcodes.
Speaker 2 (04:51):
Ah Yes, around nineteen seventy. That was revolutionary techniques like
quinna crene or Q banding, GEMSA or G banding, or
verse or R banding. Suddenly each chroma zone pair had
a unique reproducible banding pattern like a barcode.
Speaker 1 (05:04):
Okay, that sounds like a game change.
Speaker 2 (05:05):
It absolutely was, because now cytogeneticists could reliably tell every
single chromosome apart, no more guessing with the C group
and those bands they became landmarks addresses on the map so.
Speaker 1 (05:20):
They could pinpoint locations.
Speaker 2 (05:22):
Exactly, which led to the Paris conference in nineteen seventy one,
where they formalized the naming system like fifteen Q twelve
chromosome fifteen long arm Q region one band two super
specific addresses crucial for mapping genes.
Speaker 1 (05:35):
And did that lead directly to finding where genes were.
Speaker 2 (05:38):
It enabled it? For example, back in nineteen sixty eight,
even before banding was perfected, Roger Donahue, who worked with
Victor Mchuthick, managed to map the first gene not on
the X chromosome, the Duffy blood group gene to chromosome one,
just by noticing a subtle variation in its length in
one family. Banding made that kind of mapping much more systematic.
Speaker 1 (05:56):
Right, And wasn't there another technique around that time involving.
Speaker 2 (05:59):
Mice ah Yes, Somatic cell hybridization that started in the
sixties too, really clever. Actually, They figured out how to
fuse human cells and rodent cells usually mouse cells together
in a.
Speaker 1 (06:08):
Lab dish, use them like one big cell kind of.
Speaker 2 (06:11):
And the really interesting thing was, over time these hybrid
cells tended to randomly kick out most of the human
chromosomes but keep all the mouse ones.
Speaker 1 (06:21):
Okay, so how did that help?
Speaker 2 (06:23):
Well, you'd end up with the collection of hybrid cell lines,
each containing only one or a few different human chromosomes.
Then you could test those cells. Does this cell line
make human protein X. If it did and you knew
it only had say, humor chromosome seventeen left.
Speaker 1 (06:38):
Ah, then the gene for protein X must be on
chromosome seventeen exactly.
Speaker 2 (06:43):
It was a powerful tool, though initially hampered a bit
because distinguishing the chromosomes before banding was hard. But once
banding came along in the seventies, they could be certain.
That's how they pinned the gene for thymidan kines to
chromosome seventeen for instance.
Speaker 1 (06:56):
It sounds like things were really accelerating.
Speaker 2 (06:58):
Then there were you had figures like Victor mccusick, who
was originally a cardiologist but became this giant in medical genetics,
really championing the cause. He used these powerful metaphors talking
about cartographic exploration of the genome or studying its anatomy.
He even called for moonshot level investment to get the
human chromosomes fully mapped. He saw it as building essential infrastructure,
(07:23):
a map.
Speaker 1 (07:23):
For the future of medicine.
Speaker 2 (07:25):
Basically, that was the vision. Build the map, create the
reference system, and then you could really start to understand
genetic disease.
Speaker 1 (07:32):
But as we often find, not everyone saw this purely
as scientific progress, right.
Speaker 2 (07:36):
There were critics, Yes, absolutely, It's important to remember that
people like the bioethicist Abbi Lippman, writing in the early nineties,
raised serious concerns. She argued that this whole mapping enterprise
wasn't neutral science. It was, in her words, of political
and cultural activity, that it reflected certain societal values, particularly
a focus on identifying and potentially eliminating.
Speaker 1 (07:58):
Abnormality HMO built into the process itself.
Speaker 2 (08:01):
That was her argument that it could lead to a
kind of colonization of health, defining what's normal and what's not,
possibly pushing towards the sort of voluntary or liberal eugenics,
driven by individual choices, but shaped by these powerful new technologies.
A really important counterpoint to the purely celebratory narrative.
Speaker 1 (08:19):
That's a heavy thought. Let's maybe unpack a specific condition
to see how this played out. Fragile X syndrome seems
like a good example of this evolution.
Speaker 2 (08:27):
It really is. It shows the journey from a subtle
visual clue to a molecular understanding and the prevention focus
that came with it. So it starts back in nineteen
sixty seven, Herbert Loves at Yale spots this unusual marker
X chromosome in a boy with developmental delays, just a
little constriction near the end of the X chromosome. But
(08:47):
what did it mean? Sided geneticis were constantly finding little variations,
was this one significant or just normal human difference?
Speaker 1 (08:54):
Right? Separating the signal from the noise exactly?
Speaker 2 (08:58):
Then jumped to nineteen seventy. In Australia, pediatrician Gillian Turner
observed something clinically interesting. She sees families where boys have
X linked intellectual disability, but they look well physically normal,
no distinctive facial features like in Down syndrome.
Speaker 1 (09:14):
So the clinical picture didn't immediately scream syndrome.
Speaker 2 (09:17):
Not in the same way. It was initially considered maybe
something called rem Penning syndrome. But then by the mid seventies,
another clinical science started to be consistently noticed in these boys,
macro orchidism or unusually large tests after puberty. That became
a key distinguishing feature. Still no clear link to Lub's
marker X though.
Speaker 1 (09:35):
Okay, so you have a clinical picture emerging and this
separate chromosome marker floating around.
Speaker 2 (09:39):
And then bingo. In nineteen seventy six seventy seven, other
geneticists start reporting finding similar to Lubbs's original marker X,
and now they're calling it a fragile site. That term
fragile site had actually been coined a few years earlier,
in nineteen seventy by Ellen Majanis and Frederick Hecht for
a different fragile spot on chromosome sixteen. These were just
points on romosomes that seemed prone to breaking when cells
(10:01):
were grown in certain lab media.
Speaker 1 (10:03):
So Lupps's marker was rediscovered and named a fragile site
on the X chromosome.
Speaker 2 (10:09):
Yes, and suddenly the clinical picture in the subtgenetic finding
started to come together. By nineteen seventy eight, Gillian Turner
and her colleagues were describing how you could use this
fragile site for targeted prevention.
Speaker 1 (10:21):
How did that work?
Speaker 2 (10:22):
Well? If you identified a boy with the characteristic features,
the intellectual disability, the macro orchidism, you check his chromosomes
for the fragile site on the X. If it was there,
you could then test female relatives like his sisters or
mother to see if they were carriers. A carrier female
would have a fifty percent chance with each pregnancy of
passing on that fragile X chromosome, so they could then
(10:44):
off for prenatal diagnosis, usually ameosentesis to check the fetus's chromosomes.
If the fetus had the fragile x.
Speaker 1 (10:51):
They faced the choice of terminating the pregnancy.
Speaker 2 (10:54):
Correct Because importantly there was no treatment, prevention through identification
and selective abortion was the only medical option presented, and the.
Speaker 1 (11:02):
Name fragile x syndrome solidified around then.
Speaker 2 (11:05):
It became widely adopted in the early eighties, thanks in
part to a book by Randy Hagerman and Lauris mcgavern
in nineteen eighty three, but the story still had twists.
Stephanie Sherman made this really puzzling observation. The condition seemed
to get worse or show up earlier in later generations
within the same family.
Speaker 1 (11:24):
It was called anticipation, which didn't fit standard genetic inheritance patterns.
Speaker 2 (11:29):
Not at all. It baffled everyone became known as the
Sherman paradox. It wasn't until nineteen ninety one that the
molecular basis was found. An international team pinpointed the actual
gene FMR one and discovered he had this unstable section
a repeating sequence of cgg ah.
Speaker 1 (11:45):
And the repeat could expand from one generation to the next.
Speaker 2 (11:48):
Exactly that expansion explained the Sherman paradox and anticipation a
huge molecular breakthrough.
Speaker 1 (11:53):
But going back to the earlier point, fragile x really
became a sort of poster child for this new focus
on prevention, didn't.
Speaker 2 (11:59):
It absolutely did. As Lubes and Felix Dela Cruz stated
in a big NIH report in nineteen seventy seven, we
were entering the age of prevention. The thinking was curing
these things is incredibly hard, maybe impossible for now, but
preventing them through diagnosis that seemed achievable. Gene therapy was
still seen as a distant dream, as Acoustic put it,
(12:21):
so diagnosis leading to prevention became the dominant approach.
Speaker 1 (12:25):
Let's look at another complex case, Prater Willie syndrome. This
sounds like it also involved piecing together a complicated puzzle,
very much so.
Speaker 2 (12:32):
It was first described in nineteen fifty six by Swiss
doctors Praterer, lab Heart and Willie and it has this
really distinct, challenging life course starts with severe muscle weakness,
hypotonian infancy, babies or floppy have trouble feeding, but then
usually in early childhood, there's this dramatic switch to uncontrollable
appetite leading to severe obesity, often accompanied by intellectual disability
(12:55):
and behavioral issues. A really difficult trajectory.
Speaker 1 (12:57):
Defining that must have been tricky, especially differential it from
other causes of obesity.
Speaker 2 (13:02):
Absolutely, you know, physicians have always wanted clear disease categories.
You see these attempts to look back at old paintings
like La Monstrue or historical cases like one of John
Langdon downs and say, ah, that must have been this syndrome.
And there was confusion with things like foolish syndrome, which,
as the physician hilde Bruce pointed out, had become this
kind of catch all diagnosis for almost any childhood obesity,
(13:24):
losing its specific meaning.
Speaker 1 (13:25):
So what made Praeter Willy stand out It was that
really specific transition from the infantile floppiness to the later
hyperphagia and obesity.
Speaker 2 (13:35):
That two stage pattern was the defining clinical feature that
frater lap heart and Willy delineated.
Speaker 1 (13:40):
And how did genetics come into the picture? When did
they find a cause?
Speaker 2 (13:44):
That took time and again relied on advances in seeing
the chromosomes more clearly. There were early hints or report
in nineteen eighty one by Holly and Smithy's of a
chromosomal translocation involving chromosome fifteen in one patient, but the
big push came from people like Orgey Unis mid seventies
arguing for high resolution cidedgenetics, getting more bands visible maybe
(14:05):
three hundred, five hundred, even more per kariotype. He wanted
to bridge that gap between genes and chromosomes see smaller changes.
Speaker 1 (14:12):
And did that work for Prayer Willy Yes.
Speaker 2 (14:15):
In nineteen eighty one, David Ledbetter and vincent Riccardi, using
these high revolution techniques, were able to consistently identify a
tiny deletion on the long arm of chromosome fifteen, specifically
in the region fifteen Q eleven thirteen in most patients
with Peter Willi syndrome.
Speaker 1 (14:29):
Found it a specific genetic address.
Speaker 2 (14:32):
A specific address in the genome's morbid anatomy as some
called it a huge step, but like always it opened
up new questions.
Speaker 1 (14:38):
Like was the deletion definitely the.
Speaker 2 (14:39):
Cause right or just associated? And it also led to
the idea of continuous gene syndromes proposed by Roy Schmikel
in nineteen eighty six. He suggested that maybe complex syndromes
like Praeter Willy weren't caused by losing just one gene,
but by losing several genes located next to each other
in that deleted segment. Seeing the deletion was one thing,
(15:01):
Understanding its functional consequence was another layer of complexity.
Speaker 1 (15:04):
It really highlights that even seeing the problem doesn't immediately
give you all the answers.
Speaker 2 (15:09):
Not at all. Observation then interpretation than understanding the mechanism.
It's a continuous process.
Speaker 1 (15:14):
Okay, let's shift gears slightly. What about cases where different
clinical syndrome seemed to merge genetically speaking, like do George
and Velo cardiofacial syndromes. Ah.
Speaker 2 (15:23):
Yes, that's a fascinating story about the one mutation, one
disorder ideal versus clinical reality and well professional identities. So first,
you have DiGeorge syndrome, described in nineteen sixty five by
pediatrician Angelo to George. He noted this pattern of birth defects,
crucially including absence or underdevelopment of the fymasin parathyroid glans,
often leading to immune problems in the low calcium and.
Speaker 1 (15:46):
The name stuck, even if he didn't push for it.
Speaker 2 (15:48):
Apparently he demurred the eponym, but yeah, the George syndrome
caught on. It described this constellation of symptoms, but with
quite a bit of variability between patients.
Speaker 1 (15:56):
Then along comes VCF.
Speaker 2 (15:58):
Right in nineteen seventy eight, Robert Schrenzen, a speech pathologist
using that dys morphology approach looking for patterns, identified what
he saw as a new syndrome. He called it Velo
cardio facial or VCF syndrome based on the common features
he saw pallid abnormalities, vello heart defects, cardio and characteristic
(16:19):
facial features facial often with learning difficulties too.
Speaker 1 (16:22):
So initially seen as distinct things, yes, but then.
Speaker 2 (16:25):
The genetics started pointing towards chromosome twenty two, especially for
to George. And then in the early nineteen nineties came
the big convergence. Using feesh Age probes, those fluorescent tags
that can stick to specific DNA sequences, researchers found the
same small deletion on chromosome twenty two in the twenty
two kleven region in patients diagnosed with de George and
d impatients diagnosed with VCF WHOA.
Speaker 1 (16:47):
So genetically they look like the same thing.
Speaker 2 (16:49):
Powerful evidence for it. It really seemed to support that
idea one specific mutation, the twenty two Q eleven deletion
causing one disorder, even if it looked a bit different
in different people.
Speaker 1 (17:00):
But did everyone just say, Okay, it's one thing now.
Speaker 2 (17:04):
Not quite. This is where the social side of science
comes in. Unifying the genetic cause didn't automatically unify the
names or the communities built around them. Sprintson, for instance,
argued quite strongly that VCF syndrome was the more accurate
description the true syndrome caused by the deletion. Others preferred
the more neutral, genetically precise name twenty two Q eleven
(17:25):
point two deletion syndrome.
Speaker 1 (17:26):
Like the blind men and the elephant, different specialists focusing
on different aspects.
Speaker 2 (17:30):
That's a great analogy. Different specialists cardiologists, immunologists, speech pathologists,
geneticists were maybe emphasizing different features, and you had clinics,
research programs, family support groups all established around these separate names.
Speaker 1 (17:43):
Merging them wasn't simple, So even definitive genetic proof doesn't
always settle things neatly.
Speaker 2 (17:48):
Not always. And interestingly this contrast with Crater, Willy and
Angelman syndromes. They share the exact same deletion region on
chromosome fifteen that fifteen Q eleven thirteen area, but.
Speaker 1 (17:58):
They look completely different clinically right.
Speaker 2 (18:00):
Totally different due to genomic imprinting. Whether the deletion is
inherited from the mother or the father determines which syndrome
you get. So in that case, despite the identical deletion,
the distinct clinical pictures kept them firmly separate. Shows a complexity.
Sometimes the genetics unites, sometimes the clinic still divides.
Speaker 1 (18:17):
Fascinating. Okay, let's zeemat again. We've moved from blurry chromosomes
to specific bands and deletions. What happened when the Human
Genome Project came along in the raindeies.
Speaker 2 (18:27):
Ah, the HGP that really ushered in the era of
the molecular gaze a whole new level of seeing. While
fish probes let you look for one specific known deletion
like twenty two Q eleven the HGP aim for the
whole picture, all the DNA.
Speaker 1 (18:42):
Sequence, and how did they start to look at that
whole picture for variations beyond sequencing everything for everyone?
Speaker 2 (18:48):
Well, techniques emerged, like comparative genomic hybridization CGH, developed around
nineteen ninety two by people like Joe Gray and and
Ali Calioniumi. The idea was to compare a patient's entire
DNA load against a standard reference genome, looking for regions
where the patient had too much or too little DNA
gains or.
Speaker 1 (19:06):
Losses, so finding deletions or duplications genome wide, not just
at known spots exactly.
Speaker 2 (19:12):
And then came DNA chips or microarrays, pioneered by Edwin
Southern and commercialized by companies like a Fi Matrix around
nineteen ninety four. These could test thousands, eventually millions, of
tiny DNA spots simultaneously. This allowed for finding much smaller
gains and losses what we now call copy number variants cnbs,
things way too small to see even with high resolution banding.
Speaker 1 (19:33):
Right, But the raw output of the HGP, all those
a's tcs and gs wasn't exactly user friendly?
Speaker 2 (19:39):
Was it?
Speaker 1 (19:39):
Not?
Speaker 2 (19:39):
At all? Just a massive string of letters. That's where
genome browsers became absolutely essential. Things like the UCSC genome
Browser or ensemble that provided a visual interface way to
navigate this ocean of data. And crucially, what do they
use as the main organizing.
Speaker 1 (19:53):
Principle The chromosomes, those ideograms.
Speaker 2 (19:55):
Yes, they kept that familiar structure, the chromosome maps, the
banding patterns. They became the signposts as side of geneticist
Dorothy Warburton called them, the familiar neighborhood to orient yourself
within the molecular data. The visual chromosome map remained central
even in the molecular age.
Speaker 1 (20:13):
Okay, so this ability to see tiny CNV's genome wide
inevitably it moved towards prenatal testing.
Speaker 2 (20:20):
Right it did. Starting significantly in the two thousands, companies
like Signature Genomic Laboratories led by Lisa Schaeffer and Bessembajohnny
developed microarrays specifically for prenatal diagnosis. Initially they might target
known regions associated with intellectual disability, like their Signature chip,
but soon the technology allowed for whole genome backbone coverage.
(20:42):
The promise being, as Arthur Bode put it, the promise
was essentially to do every known for PIRSH test in
the world at once, plus find new things you weren't
even looking for. Catch everything.
Speaker 1 (20:50):
But that sounds like it could open a huge can
of worms, exactly.
Speaker 2 (20:54):
The peril the anxiety. Bioethicist Eveline Schuster wrote about this
in two thousand and seven, warning about a potential roadblock
for life. Her concern was this what happens when you
get a flood of information back from a prenatal micro array.
You might find the specific thing you were testing for,
but you might also find several CNVs of unknown clinical significance,
(21:15):
tiny bits of DNA missing or extra, but nobody knows
if they actually cause a problem or are just harmless variations.
Speaker 1 (21:22):
And parents facing a ticking clock on pregnancy decisions.
Speaker 2 (21:25):
Right they can be faced with terrifying uncertainty. Schuster worried
it could lead parents to terminate wanted, potentially healthy pregnancies
out of fear of the unknown, causing them to have
no baby at all.
Speaker 1 (21:35):
So who does benefit from seeing the whole picture prenatally,
It's still debated very much.
Speaker 2 (21:39):
So it's this constant balancing act. On one hand, discovering
new causes of disease. On the other the huge ethical
burden of interpreting uncertain results for anxious parents. Even when
the American College of Obstetricians and Gynecologists ACOG cautiously endorsed
micro array as a first tier test in some prenatal
cases in twenty thirteen, they stressed heavily the absolute need
(22:01):
for extensive genetic counseling beforehand and afterwards. The information is
powerful but potentially overwhelming.
Speaker 1 (22:08):
So wrapping this up, we've journeyed from doctors squinting at
physical traits, to peering through microscopes at chromosomes, adding stains
and bands, finding deletions, and now scanning the entire molecular code.
Speaker 2 (22:18):
Yeah, this whole complex infrastructure of the techniques, the classifications,
the maps, built piece by piece over decades has really
become this monumental edifice for prevention, as the book calls it.
Speaker 1 (22:28):
But that one mutation, one disorder idea, while powerful, hasn't
always been the full story, has it.
Speaker 2 (22:34):
No, As we saw with Peter Willy Engelman or the
did George vcf saga, the clinical picture how a condition
actually manifests, and even the social structures around diagnosis, they
still matter immensely in defining what a genetic identity means.
It's rarely just the DNA sequence.
Speaker 1 (22:50):
Ultimately, this deep dive really shows how the genomic gaze
lets us see ourselves genetically in incredible detail. The potential
for diagnosis, maybe even future treatment is huge, but it
forces these really profound questions on us.
Speaker 2 (23:04):
What information do we actually want, how do we handle uncertainty?
What choices do we make based on this incredibly detailed
but sometimes ambiguous blueprint.
Speaker 1 (23:13):
So for you the listener, maybe the takeaway thought is this,
as these technologies get ever more powerful, letting us see
our own unique genetic makeup in ever greater detail, how
might that change your personal understanding of what health or
disease even means? And what might that imply for the
kinds of choices you or society might face down the road.
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