100 Greatest Discoveries (2004) s01e06 Episode Script
Genetics
A good priest to left his mark as a great scientist, like exploring the miracle of heredity A brilliant researcher, her work largely ignored by her male colleagues Until a revolutionary breakthrough.
A spell-binding journey to find the common thread of molecules That define the biology of life.
An unprecedented collaboration of scientific minds and real power dissolved the mysteries of what makes us human These are the greatest discoveries in history of genetics Nearly 50 years ago, this man discovered that I am his brother Bill, that sound wasn't a great discovery.
No, that's a joke.
Yes, it's a joke, jeez No.
not jeez.
Genes When we are conceived, we inherited the genetic characteristics of our parents But how are those characteristics transmitted from one generation to the next That's our first great discovery In the middle of the 19th century, an Augustine monk named Gregor Mendel Took up the question of biological inheritance with a series of experiments Mendel has a natural inquisitive mind and profound love of the nature His scientific interests range from research on plants to meteorology and the theories of evolution Working at a monastery in what is now the Czech Republic Mendel started by cross-breeding different strandsof garden peas Then observing the characteristics of their offspring Why choose peas He did he said for the fun of the thing Mendel noticed when he crossed a round peas with a wrinkled one.
The offspring were round, not the mix of the two characteristics as he had expected Yet when he bred the round pea offspring, that was the mix appeared And second generation has both round and wrinkled seeds He continued to experiment, trying to understand what kind of biological mechanism would cause certain characteristics to disappear in the first generation Only to reappear in the second Then one day, Mendel counted the number of the peas in the second generation that had the wrinkled characteristic Exactly one quarter of the peas were wrinkled What Mendel observed in his experiments Were the biological phenomena we now refer to as dominance and segregation.
Only Mendel did know it yet.
Still, his experiments produced a curious set of facts Which as he said forced themselves upon my noticed.
Is see no matter how he cross bred the various strains of peas The hidden characteristics showed up but only in one quarter of the second generation.
For Mendel, here was the breakthrough For the first time, he could demonstrate that the traits of successive generations were inherited in certain miraculous ratios.
In other words, there were fixed laws of that govern heredity.
With this insight, Mendel made the first great discovery in the science of genetics Each inherited characteristic must be decided by pair o what he called factors Each parent, he said, contribute one factor for each characteristic Certain factors are dominance, and others are recessive, depending on the combination of factors the offspring inherit Mendel's factors are called genes The term Mendelian trait is used to describe characteristic caused by a single gene that sometimes reappears on one quarter of the offspring's that characteristics can be innocuous, such as freckles or the ability to coil your tone.
But also can lead seriously illnesses like cystic fibrosis or Sachssdisease Imagine, all that from one man's work with the humble pea And the experiments with another humble species that produced our next great discovery.
Meet Drosophila melanogaster, a common fruit fly.
Its role in genetic research is as important today as it was over century ago Since the early nineteenth hundreds scientists began to reexamined Mendel's work on the inherited traits And in 1909, a Danish botanist named WL Johannsen called the term genes to describe Mendel's factors Among the researchers in the new field of genetics was Thomas Hunt Morgan An independent minded Columbia University embryologist In his early work, Morgan was critical of Mendel's conceptions of heredity And even skeptical of Darwin's theory of natural selection That's, until Morgan started working with Drosophila Joseph Gall is a cell biologist at the Carnegie institution in Baltimore Maryland Why did Morgan choose fruit flies What's going on Well, I think he chose fruit flies for several reasons.
The chief was the short generation time.
So that's very important.
The another important thing is that one female fly can give several hundred offspring So, to do genetics, first of all, you need a lot of data, You need a lot of flies, lot of individuals And you don't want to wait forever to get them.
And you can have many generations per year, a thousand and thousand of offspring The story goes at one day, Shortly after Morgan started breeding drosophila for his experiments A striking mutate appeared in his lab.
A fly with distinctive white eyes He decided to breed with the female fly that had ordinary red eyes Curious to see what the offspring would look like Two weeks later, he had his answer.
One by one, the first generation offspring appeared, all of them had red eyes Thinking that the white eyes might be a hidden characteristic, similar to what Mendel had observed Morgan waited to see what would happen in the second generation Short enough, the characteristics skipped the generation.
This time, some of the flies had red eyes, and some had white eyes.
But then, Morgan sought something else.
All of the flies with white eyes were male At the time, it was known that the gender of the species as determined by two of the rod shape structures found in the cell nucleus, the chromosomes For example, human females have two X chromosomes Human males have one X chromosome and one Y chromosome Morgan realized that the genes responsible for the white eyes must somehow be associated with the fact that male flies have only one X chromosome This meant that the females, the genes responsible for the red eyes on one of the X chromosome Might be overshadowing the genes for white eyes on the other.
To prove his point, Morgan bred thousands of fruit flies in studying their heritage Morgan's observations are absolutely fundamental to everything about genetics Because what Morgan in his studio shows was the genes are located in the linear order on the chromosomes Today, geneticists know that diseases like hemophilia and muscular dystrophy Are caused by defected genes on the X chromosome It's believed that other diseases like cancer may be linked to damaged or defected chromosomes For his discovery, Morgan was awarded the Nobel Prize for medicine in 1933 The first scientist to win in the field of genetics.
and Drosophila melanogaster, thanks the fruit flies contribution on Morgan's work Drosophila is enshrined one of the basic animal models in experimental science.
And its legacy led to our next great discovery One of the geneticists who studied fruit flies alongside Morgan was Georges Beadle Working in Paris in 1935, Beadle detected evidence that the inherited traits of eye color Drosophila Might be the result of genetically based chemical reactions.
Beadle pursued his investigation at Stanford University with colleagues Edward Taton For their experiments beadle and Taton selected another simple organism Neurosportcrusa bread mold They chose mold because it's easy to grow with simple nutritional meets Bread, air, and water Neurosport also has single set of chromosomes, which allows the researchers to observe the genetic changes easily.
Knowing that X-rays damaged the chromosomes, beadle and Taton eradiated the mold Which caused mutations in its genes of spores These mutated genes were unable to produce the nutrients necessary for the mole to grow.
However, when they added the nutrients, some of the spores began to germinate For beadle and Taton, this was a breakthrough moment.
They realized that the radiated spores failed to produce the essential nutrients Because their genes were defective.
This was significant.
It meant that the genes were responsible for more than just passing inherited traits from one generation to the next.
They also directed the production of enzyme that the mold depended on for its survival Beadle and Taton's breakthrough is known as the one gene one enzyme hypothesize.
Lactose intolerance is an example of human metabolic condition caused by a single missing enzyme missing because some people 's inherited a gene that fail to produce lactose and unable to digest the sugar in dairy products.
This disorder can be easily treated by taking tablets containing the missing enzyme Thanks to beadle and Taton, we gained a fundamental understanding of what genes do And the stage was set for a new generation of remarkable genetic discoveries So far, we've seen how genes are transmitted, where their located and how they work But our next great discovery revealed a brand new surprise about what else genes can do.
And it came from a surprising source To learn more about McClintock, I paved a visit to David Kirk Professor of biology at Washington University in St.
Louis at Missouri.
There are many many things I want to ask you, let me start with Barbara McClintock She's a fabulous scientist, one of the world's best.
But she faced a lot of challenges right Oh, she sure did.
Partly because she was just too bright for most people And her mind went to fast.
But even though she is a member of academy She couldn't, she was never offered an academic position.
Primarily because she is a woman.
Also because she is somewhere brighter than any of her male colleagues.
Many people were afraid of her, afraid of her brain.
In 1942, disenchanted by her lack of career advancement in the male dominated field of genetics McClintock went to work at cold spring harbor lab in New York It was here that McClintock made history.
Working alone, she chose to search the genetic of mains.
Of special interest to her was the genetic mechanism underlying the unique mosaic of color kernels It was while studying these that McClintock began to notice a correlation between the color of kernels and the break that occurred in of its chromosomes The color of the corns correspond to where on the chromosome's break occurred A break in the chromosome occurred she said, when the gene went jump or transposed from one chromosome to another.
When this happened, it disrupted the activity of the other genes responsible for producing the pigment of the kernel Everybody at that time thought of chromosome in genes as being very stable things, just transmitted from one generation to another.
She found that certain genes she was trying to locate on the chromosome was being at different composition at different times In one corn plant, it will appear in one position of the chromosomes And in another corn plant, it goanna different position At the third plant might be a third position.
How could this be A single gene different location on different plants And she made the intuitive way that these genes were leaping, going from one place to another, which was totally unheard of at that time.
She was the first person who really saw the kind of detail of the presence of every chromosome Literally the first person She could look at the single kernel and corn and see the genes, see the chromosomes She could look like the chromosome and see the whole plant.
She was incredible.
Barbara McClintock's discovery of transposon was as evolutionary as it was revolutionary While some genetic mutations caused by transposon that linked to caner or other diseases Transposon may also be mechanism that causes genes to mutate and response to changes and environment and spur the evolution of species.
Today, we know the transposon existed in the genes of all living things Everything from algae to human beings So, my postdoctoral fellow whose name is Steve Miller came here specifically to try to find a transposon That could do what McClintock had shown the transposon to do.
He finally found one that he could control the jumping of And jumps well when he was interested in it, that he named after that basketball hero Michel Jordan.
So we always keep a big Michel Jordan on laboratory slam dunking with an algae.
Every basketball dream to dunk algae While Barbara McClintock never gained the fame of Michal Jordan.
She did she even own notoriety This experiment made her so bitter that she never gave another lecture there Though she continued working in the lab until her death in 1992 with the age of 89 She did live long enough to be vindicated 30 years after the pioneering discovery, McClintock was awarded the 1983 Nobel Prize for medicine DNA The cold spring harbor laboratory was the sitr of our next great discovery as well It happened here in 1952, Biologist Alfred Hershey and Martha chase was studying bacteria phage.
A virus known infected bacteria Through process called transformation, the virus takes over the bacteria's internal machinery And common reduce it to produce more viruses Bacteria phage consisted of two simple components, a protein shell and inside a mysterious substance scientists hadn't know about for decades called deoxyribonucleic acid or DNA Hershey and chase wanted to know whether the protein or the DNA that virus carried genetic information Using two radioactive chemicals they labeled the protein in one of the bacteria phages And the DNA in the other.
Then exposed the culture of E.
coli bacteria to these viruses After using a kitchen blender to separate the bacteria from the empty viral protein shells Hershey and chase saw the radioactive protein was not penetrating the bacterial wall But inside the bacteria, was the radioactive DNA It was the DNA, not the protein, that was able to directed the whole cell to make new viruses It was an extraordinary breakthrough Thanks to Hershey and chase and other scientists who also paved their way Suddenly we understood the true identity of the DNA Its' genetic material, the blueprint of life, and all came out of a blender like this Hershey was awarded Nobel Prize in 1969 for his work But Hershey and chasse's blender experiments were on to inspire a new era of genetic research Beginning with our next great discovery It's late of 1951, the chemical structure of DNA remained a tantalizing enigma At Cambridge university in England, biologist James Watson and physicist Francis Crick Had been working to unlock the secrets of the DNA molecule But they weren't alone.
Several other groups of competing scientists were hard at work, trying to solve the same puzzle Some important facts about DNA were already known For instance, scientists knew that DNA was composed of four bases Adenine, Cytosine, guanine and thymine They also had been able to infer some of its structure with the help of x-ray crystallography This technique involve passing an extra beam through a crystallized DNA molecule And capturing a vague shadow image of its internal structure on a photographic plate Under with this information, along with their own knowledge of chemical structure Watson and Crick began building a three dimensional model of DNA.
I want to arrange I had a biggest and small molecule and somehow you had to form link bounds Here's A and here's T.
And I want this hydrogen to point strikely this nitrogen.
So I had something like this So that went to link the pair And I want this hydrogen to point to this one and like this Today, you can buy a kid symbol structure that Watson and Crick put together But we are getting ahead of ourselves, Watson and crick needed more data.
With the help of physicist Maurice Wilkins, they gained access to an x-ray picture of DNA molecule that had been taken by his research partner.
Her name was Rosaline Franklin Without her knowledge, Watson and Crick used the data from that x-ray image And successfully completed their model In the 1953 issue of natural magazine Watson and crick revealed their amazing discovery to the world Their model showed that he DNA molecules was a double helix The twin strands were compared of four known bases linked together by hydrogen bonds And the whole structure crotch screw like the spiral letter.
Which could easily pull apart in order to make copies of itself with the same encode genetic information.
Watson and crick had won the race.
The discovery of the structure of DNA sparked a scientific revolution It illuminated the molecular biochemical foundation of life in a whole new way It opened doors for areas of research in other great discovery that few ever imagine possible.
As for Watson and crick, their discovery of double helix along with Maurice Wilkins But whatever Wilkins's colleague Rosaline Franklin Despite her contribution to the discovery She wasn't considered for the 1962's Nobel Prize The rule state that it can only be awarded to living recipient.
Rosaline Franklin died in 1958 of ovarian cancer.
Most likely caused by exposure to x-rays Welcome to my world.
This is one of the trillion of cells that make up my body This material in the cell is called the cytoplasm Over here is the cell's nucleus Inside the fragile nucleus envelope are the long thin strands of DNA As we've seen, DNA contained genetic instruction that control the cell's metabolic functions and heredity Sounds simple enough But the process by which this genetic transfer occurs is sublime Is the story of our next great discovery Years before Watson and crick had found the structure of DNA.
Scientists knew that the DNA was responsible for making protein that resided inside of the cytoplasm But they were puzzled by how the DNA managed to transfer its genetic information for making proteins through the nucleus's wall The answer to the puzzle came to the collective work of several different scientists And like many discoveries, it began with an educated guess The production of protein in a cell is seen here in red Scientists found that cells with lots of protein production contain lot of this RNA, a chemical similar to DNA But with only one strand, not two This led scientists to wonder if RNA was somehow involved running the protein factory in the set of the cytoplasm To find out, once again, researchers tuned to the bacteria phage They detected that soon after the bacteria phage injected in the DNA into a bacteria, traces of viral RNA appeared in the host cell And the production of protein began to increase This was the moment of discovery Here was a special kind of RNA never seen before.
As it single strand enter one of it cell's protein factories It communicated the message for making new protein.
Scientists called it massager RNA.
Today, many scientists believed that massager RNA and other RNA molecules are descendents of the earth's most primitive chemical materials.
Part of the primordial soup that cooked up the first living organism As we've just seen, RNA translated structure form DNA for making proteins But what was the genetic code, The sequence of instructions that made this process possible In 1961, molecular biologist Marshall Warren Nirenberg and post doctorial fellow Heinrich Matthaei Carried out a series of experiments to see if it can synthesize proteins in the laboratory And in their experiments Nirenberg and Matthaei were working with RNA.
Like DNA, RNA is made of four chemical bases In the uearica moment of discovery, they found that when three of the bases allied in a specific sequence called a triplet.
The triplet code for a specific amino acid The order of the triplets is the blueprint for the production of proteins.
Today, Marshall Nirenberg is a research scientist at national institution of health So what is this mean to me as a citizen and tax-payer and voter What it meant to you is RNA is transcribed form DNA.
DNA is copied to RNA and RNA contains the information that determines this sequence of amino acids protein.
So what you inherited form your parents is the sequence of letters in DNA that determine how you synthesize How you make different kinds of proteins that needed for life.
That make me, yes, that make you.
Nirenberg and Matthaei's discovery was the first crack in the genetic code A peak in the secret vocabulary encrypted in each DNA molecule Enabling to instruct synthesize of proteins Over the next five years, Nirenberg successfully deciphered the 64 triplets that comprised the entire vocabulary of DNA The genetic code had been broken.
And in 1968, the discovery earned Marshall Nirenberg a share of Nobel Prize for physiology and medicine.
What was this like you made this discovery Well it was opening a door to a toy shop It means that we could do virtually everything we could decipher the genetic code.
Every living thing, has the same code Yes, the one code that used by every living thing on this planet.
And it's same, basically the same language that used And when we found that out, you know I knew all about Darwin.
I knew all about evolution.
But this broted homeand such immediate fashion All living things on this planet are related.
We are all derived from a common ancestor, and our bodies all speak the same language.
It had a very mark defect on me.
While we are watching Watson and crick structure of DNA Marshall Nirenberg and Matthaei uncovered the blueprint for how the structure worked The breakthrough that led to some of the discoveries since we've seen so far have never happen if not for this familiar organism Bacteria phage and our next discovery depended on it as well For decades it was believed that bacteria were completely vulnerable to invading bacteria phage Certain types of bacteria were in fact resisted to being infected by a bacteria phage.
How was that possible The first answer was provided in 1962 by microbiologist Werner Arber He found that some bacteria had enzyme that fought back against the virus by cutting its viral DNA into pieces This restricted the virus from taking over the bacteria.
So they were called restriction enzymes.
But how exactly did they work Among those hoping to unlock that secrets was microbiologist Hamilton smith.
When he noticed that the DNA of the virus was breaking down.
Smith acted quickly.
He purified the restriction enzyme They he identified the exactly was the restricted enzyme had severed the DAN.
Then came the moment of discovery Smith found that the enzyme were repeatedly cut the viral in the same place He had discovered the first site specific restriction enzyme With restriction enzymes, scientist now had molecular scissor They could used to cut the DNA molecules to virtually recreate nature.
This is significant Today, this ability to manipulate DNA is one of the basic tools in genetic engineering, what's called recombinant DNA research.
Since Hamilton smith's discovery, hundreds of restriction enzymes have been identified And scientist are using recombinant DNA for a world replication on which we depend Everything from the creation of more effective less expensive drugs To the production of human insulin for the millions of diabetics worldwide who rely on getting their daily doze.
With the discovery of massager RNA Scientists had found the process by which DNA communicate its instructions for making protein in the cytoplasm For decades, they believed this process are operated by one simple rule Instructions were coded form one gene in the DNA to one type of massager RNA.
Which then produced one protein But in the nineteen eighties, this theory was challenged when scientists began detecting something new.
Genes that coded multiple massager RNAs, which then produced multiple proteins It were taking the combined efforts several scientist to find out how this was possible.
But finally they had their answer.
Through a process called alternative splicing.
Some genes are able to code For more than one protein The discovery of alternative splicing was important Because it gives scientist valuable insight into the role that RNA plays in the production of proteins And that insight helped researchers make advances in the whole range of biomedical applications For example, scientist have used their knowledge of alternative splicing to create more effective pain-killers Some medicine are designed to block the production of specific alternative splicing proteins enzymes which regulate pain in the nervous system London, 1985, a boy arrives by plane from the Africa nation of Ghana.
The purpose of this visit to be reunited with his mother But custom spectators are suspicious the boy's passport appears to be a forgery.
And there is no prove that the woman he is meeting is really his mother.
The British government decides to deport the boy Desperate, the woman tunes to detective for help.
His name is Alec Jeffries Not a real detective, but a geneticist at Leicester University Before we learn the rest of the story, a little background By the nineteen eighties, scientist had become aware of the genetic variation among individuals is very common And they begun to link the presence of this so-called DNA variance to the presence of the disease causing genes in large families For example, Huntington s disease, and that bring this back to Alec Jeffries In 1984, Jeffries found something never see before, It was a DNA variant formed by short identical sequences of DNA that were repeated over and over Jeffries called this repeated sequence minisatellite DNA Then came the breakthrough discovery What we detected were lots of beats of DNA and in human's they have clearly variable, very variable In fact, what we got first was very murky DNA fingerprints and that point is penny drops Jeffries's discovery made history When he was asked to help solve the mystery of the boy from Ghana For the first time, DNA fingerprinting was put to the test Jeffries compared the DNA of the boy with the DNA of his supposed mother.
The result showed a striking similarity in the minisatellite DNA, proving beyond the doubt that the boy was her son.
So that when she was told the DNA evidence has been accepted your boy is coming back.
He's permanent with you and it was the vrouw in that lady's was magic and this is, I mean the first time that had ever done this, the first time that DNA was in molecular genetics and she have been used to go on an nonclinical contest that straightly help someone.
It has been over fifty years since Watson and crick's great discovery of DNA's double helix structure Since then, scientist have probed and revealed many of the genome secrets.
But not without some surprises In 1997, scientist Andrew Fire and Craig Mello were conducting a series of experiments To better understand the functions of specific genes The injected synthetic RNA made up of two stands into the cell of a round worm, then watched What happened next was astonishing.
A mechanism within the worm cell destroyed the double stands RNA As well as some of its own massager RNA In fact, the genes were responsible for coding the production of proteins in the cell was tuned off Fire and Mello has discovered what came to be known as RNA interference Today, Andrew Fire is a geneticist at Stanford University We sort of kemipound the experiments where we were injecting RNA and hoping that things would happen that very specific things Things with a little Things with a little needle, right into a worm arcais Although similar experiments we done in systems And if you see the a situation where the RNA goes in there Not only is it shuttle off, which is not surprise you don't know what happen then It also shedding off one of it cell genes, then you have surprising situation, that was really surprise that came here in 1990 The discovery of RNA interference was a milestone It gives scientist a potentially powerful new technology What is the RNA interference really mean for the future What is the applications of this The first one is really understanding the new biological mechanism Whatever make genes silence, Whatever make genes silence turn it off The second is being able to do this general screen of what genes do.
Be able to look at gene's function, just using the mechanism tool And the third thing is sort of, I would say the Holy Grail on the field Is can we use RNA as therapeutic Cure disease, RNA interference, can we cure disease with this And the model there, the idea is you take disease where the people are sick because there is a gene mad out of control It's a genetic disease.
Genetic disease which includes virus, includes tumor, includes certain genetic disease as well And the question is can we shut that gene off This holy grail of therapeutic use in humans is still just out of reach But Fire's discovery of RNA interference opened the door to a new generation of life saving breakthroughs The mystery of what makes us human was partially solved with the cracking of the genetic code But the rest of the answer lay on our next great discovery The sequencing of our complete genetic blueprint called the genome The effort have been called the largest collaboration in history By 1990, the team had joined in forces Craig Venter was one of the team's leaders How did you get started on this thing What make you want to sequence the human genome Well, my experimental career was looking for one gene, gene for the adrenalin receptor for the brain, the heart and the choice was trying to look the entire human genome which we had sensuously no knowledge of only a few hundred genes at the time so here's the most important information to our humanity and we knew sensuously nothing about it we are announcing today for the first time our species can read the chemical letters of genetic code so what did you find so fist, the most simple thing we found was that we have only a tiny fraction of genes that some people were predicting that a set of three hundred of thousand, we found twenty thousand then we found that the variation between humans is remarkably low or almost virtually identical to each other and by sequence in the genome of other mammals of sequence my standard of poodle shadow with the dog genome, the mouth genome, the rat genome we are not doing the monkey rhesus genome here we found out that all mammals share most of the genes on the same order or the same sets of genes and its just move around from one chromosome to another so where is this all the sequencing taken us oh, whatever you found in the beginning was this laid a whole new foundation for science that people were respecting miracle cures there was lots of over high this one you first started out.
.
That's right Now, any scientist, any studio in the world that has access in the internet And most human genes without yet even functions about them So we are studying a new foundation having this information to have the structure of the genes.
they can study their function and this change our view of evolution or similar with mammal's genome, even were plants and bacteria's genome its compatible medicine already with new diagnostics understanding the complexity of genes in search with human traits that's can be a huge challenge for the future So, how did you feel when your group sequence finished, did it, hold it up When we finished it, finished witting the paper describing for the first time It was published in one of the most famous that I have ever have in my life And it was just a fantastic period of satisfaction with whatever our team did and tried to contribute to the history of humanity It's hard to believe but from Gregor Mendel s great discovery of the laws of heredity to the complete sequencing of the human genome, has been a mere a hundred and fifty years But thanks to some of the greatest discoveries in the history of science It has been entire of us to understand some of the life's deep secrets And to understand the genetic ties that bind all living organism that include your brother.
Thanks bill No no thank you for taking the timeĀ thanks bill no, it's i who must thank you for taking time
A spell-binding journey to find the common thread of molecules That define the biology of life.
An unprecedented collaboration of scientific minds and real power dissolved the mysteries of what makes us human These are the greatest discoveries in history of genetics Nearly 50 years ago, this man discovered that I am his brother Bill, that sound wasn't a great discovery.
No, that's a joke.
Yes, it's a joke, jeez No.
not jeez.
Genes When we are conceived, we inherited the genetic characteristics of our parents But how are those characteristics transmitted from one generation to the next That's our first great discovery In the middle of the 19th century, an Augustine monk named Gregor Mendel Took up the question of biological inheritance with a series of experiments Mendel has a natural inquisitive mind and profound love of the nature His scientific interests range from research on plants to meteorology and the theories of evolution Working at a monastery in what is now the Czech Republic Mendel started by cross-breeding different strandsof garden peas Then observing the characteristics of their offspring Why choose peas He did he said for the fun of the thing Mendel noticed when he crossed a round peas with a wrinkled one.
The offspring were round, not the mix of the two characteristics as he had expected Yet when he bred the round pea offspring, that was the mix appeared And second generation has both round and wrinkled seeds He continued to experiment, trying to understand what kind of biological mechanism would cause certain characteristics to disappear in the first generation Only to reappear in the second Then one day, Mendel counted the number of the peas in the second generation that had the wrinkled characteristic Exactly one quarter of the peas were wrinkled What Mendel observed in his experiments Were the biological phenomena we now refer to as dominance and segregation.
Only Mendel did know it yet.
Still, his experiments produced a curious set of facts Which as he said forced themselves upon my noticed.
Is see no matter how he cross bred the various strains of peas The hidden characteristics showed up but only in one quarter of the second generation.
For Mendel, here was the breakthrough For the first time, he could demonstrate that the traits of successive generations were inherited in certain miraculous ratios.
In other words, there were fixed laws of that govern heredity.
With this insight, Mendel made the first great discovery in the science of genetics Each inherited characteristic must be decided by pair o what he called factors Each parent, he said, contribute one factor for each characteristic Certain factors are dominance, and others are recessive, depending on the combination of factors the offspring inherit Mendel's factors are called genes The term Mendelian trait is used to describe characteristic caused by a single gene that sometimes reappears on one quarter of the offspring's that characteristics can be innocuous, such as freckles or the ability to coil your tone.
But also can lead seriously illnesses like cystic fibrosis or Sachssdisease Imagine, all that from one man's work with the humble pea And the experiments with another humble species that produced our next great discovery.
Meet Drosophila melanogaster, a common fruit fly.
Its role in genetic research is as important today as it was over century ago Since the early nineteenth hundreds scientists began to reexamined Mendel's work on the inherited traits And in 1909, a Danish botanist named WL Johannsen called the term genes to describe Mendel's factors Among the researchers in the new field of genetics was Thomas Hunt Morgan An independent minded Columbia University embryologist In his early work, Morgan was critical of Mendel's conceptions of heredity And even skeptical of Darwin's theory of natural selection That's, until Morgan started working with Drosophila Joseph Gall is a cell biologist at the Carnegie institution in Baltimore Maryland Why did Morgan choose fruit flies What's going on Well, I think he chose fruit flies for several reasons.
The chief was the short generation time.
So that's very important.
The another important thing is that one female fly can give several hundred offspring So, to do genetics, first of all, you need a lot of data, You need a lot of flies, lot of individuals And you don't want to wait forever to get them.
And you can have many generations per year, a thousand and thousand of offspring The story goes at one day, Shortly after Morgan started breeding drosophila for his experiments A striking mutate appeared in his lab.
A fly with distinctive white eyes He decided to breed with the female fly that had ordinary red eyes Curious to see what the offspring would look like Two weeks later, he had his answer.
One by one, the first generation offspring appeared, all of them had red eyes Thinking that the white eyes might be a hidden characteristic, similar to what Mendel had observed Morgan waited to see what would happen in the second generation Short enough, the characteristics skipped the generation.
This time, some of the flies had red eyes, and some had white eyes.
But then, Morgan sought something else.
All of the flies with white eyes were male At the time, it was known that the gender of the species as determined by two of the rod shape structures found in the cell nucleus, the chromosomes For example, human females have two X chromosomes Human males have one X chromosome and one Y chromosome Morgan realized that the genes responsible for the white eyes must somehow be associated with the fact that male flies have only one X chromosome This meant that the females, the genes responsible for the red eyes on one of the X chromosome Might be overshadowing the genes for white eyes on the other.
To prove his point, Morgan bred thousands of fruit flies in studying their heritage Morgan's observations are absolutely fundamental to everything about genetics Because what Morgan in his studio shows was the genes are located in the linear order on the chromosomes Today, geneticists know that diseases like hemophilia and muscular dystrophy Are caused by defected genes on the X chromosome It's believed that other diseases like cancer may be linked to damaged or defected chromosomes For his discovery, Morgan was awarded the Nobel Prize for medicine in 1933 The first scientist to win in the field of genetics.
and Drosophila melanogaster, thanks the fruit flies contribution on Morgan's work Drosophila is enshrined one of the basic animal models in experimental science.
And its legacy led to our next great discovery One of the geneticists who studied fruit flies alongside Morgan was Georges Beadle Working in Paris in 1935, Beadle detected evidence that the inherited traits of eye color Drosophila Might be the result of genetically based chemical reactions.
Beadle pursued his investigation at Stanford University with colleagues Edward Taton For their experiments beadle and Taton selected another simple organism Neurosportcrusa bread mold They chose mold because it's easy to grow with simple nutritional meets Bread, air, and water Neurosport also has single set of chromosomes, which allows the researchers to observe the genetic changes easily.
Knowing that X-rays damaged the chromosomes, beadle and Taton eradiated the mold Which caused mutations in its genes of spores These mutated genes were unable to produce the nutrients necessary for the mole to grow.
However, when they added the nutrients, some of the spores began to germinate For beadle and Taton, this was a breakthrough moment.
They realized that the radiated spores failed to produce the essential nutrients Because their genes were defective.
This was significant.
It meant that the genes were responsible for more than just passing inherited traits from one generation to the next.
They also directed the production of enzyme that the mold depended on for its survival Beadle and Taton's breakthrough is known as the one gene one enzyme hypothesize.
Lactose intolerance is an example of human metabolic condition caused by a single missing enzyme missing because some people 's inherited a gene that fail to produce lactose and unable to digest the sugar in dairy products.
This disorder can be easily treated by taking tablets containing the missing enzyme Thanks to beadle and Taton, we gained a fundamental understanding of what genes do And the stage was set for a new generation of remarkable genetic discoveries So far, we've seen how genes are transmitted, where their located and how they work But our next great discovery revealed a brand new surprise about what else genes can do.
And it came from a surprising source To learn more about McClintock, I paved a visit to David Kirk Professor of biology at Washington University in St.
Louis at Missouri.
There are many many things I want to ask you, let me start with Barbara McClintock She's a fabulous scientist, one of the world's best.
But she faced a lot of challenges right Oh, she sure did.
Partly because she was just too bright for most people And her mind went to fast.
But even though she is a member of academy She couldn't, she was never offered an academic position.
Primarily because she is a woman.
Also because she is somewhere brighter than any of her male colleagues.
Many people were afraid of her, afraid of her brain.
In 1942, disenchanted by her lack of career advancement in the male dominated field of genetics McClintock went to work at cold spring harbor lab in New York It was here that McClintock made history.
Working alone, she chose to search the genetic of mains.
Of special interest to her was the genetic mechanism underlying the unique mosaic of color kernels It was while studying these that McClintock began to notice a correlation between the color of kernels and the break that occurred in of its chromosomes The color of the corns correspond to where on the chromosome's break occurred A break in the chromosome occurred she said, when the gene went jump or transposed from one chromosome to another.
When this happened, it disrupted the activity of the other genes responsible for producing the pigment of the kernel Everybody at that time thought of chromosome in genes as being very stable things, just transmitted from one generation to another.
She found that certain genes she was trying to locate on the chromosome was being at different composition at different times In one corn plant, it will appear in one position of the chromosomes And in another corn plant, it goanna different position At the third plant might be a third position.
How could this be A single gene different location on different plants And she made the intuitive way that these genes were leaping, going from one place to another, which was totally unheard of at that time.
She was the first person who really saw the kind of detail of the presence of every chromosome Literally the first person She could look at the single kernel and corn and see the genes, see the chromosomes She could look like the chromosome and see the whole plant.
She was incredible.
Barbara McClintock's discovery of transposon was as evolutionary as it was revolutionary While some genetic mutations caused by transposon that linked to caner or other diseases Transposon may also be mechanism that causes genes to mutate and response to changes and environment and spur the evolution of species.
Today, we know the transposon existed in the genes of all living things Everything from algae to human beings So, my postdoctoral fellow whose name is Steve Miller came here specifically to try to find a transposon That could do what McClintock had shown the transposon to do.
He finally found one that he could control the jumping of And jumps well when he was interested in it, that he named after that basketball hero Michel Jordan.
So we always keep a big Michel Jordan on laboratory slam dunking with an algae.
Every basketball dream to dunk algae While Barbara McClintock never gained the fame of Michal Jordan.
She did she even own notoriety This experiment made her so bitter that she never gave another lecture there Though she continued working in the lab until her death in 1992 with the age of 89 She did live long enough to be vindicated 30 years after the pioneering discovery, McClintock was awarded the 1983 Nobel Prize for medicine DNA The cold spring harbor laboratory was the sitr of our next great discovery as well It happened here in 1952, Biologist Alfred Hershey and Martha chase was studying bacteria phage.
A virus known infected bacteria Through process called transformation, the virus takes over the bacteria's internal machinery And common reduce it to produce more viruses Bacteria phage consisted of two simple components, a protein shell and inside a mysterious substance scientists hadn't know about for decades called deoxyribonucleic acid or DNA Hershey and chase wanted to know whether the protein or the DNA that virus carried genetic information Using two radioactive chemicals they labeled the protein in one of the bacteria phages And the DNA in the other.
Then exposed the culture of E.
coli bacteria to these viruses After using a kitchen blender to separate the bacteria from the empty viral protein shells Hershey and chase saw the radioactive protein was not penetrating the bacterial wall But inside the bacteria, was the radioactive DNA It was the DNA, not the protein, that was able to directed the whole cell to make new viruses It was an extraordinary breakthrough Thanks to Hershey and chase and other scientists who also paved their way Suddenly we understood the true identity of the DNA Its' genetic material, the blueprint of life, and all came out of a blender like this Hershey was awarded Nobel Prize in 1969 for his work But Hershey and chasse's blender experiments were on to inspire a new era of genetic research Beginning with our next great discovery It's late of 1951, the chemical structure of DNA remained a tantalizing enigma At Cambridge university in England, biologist James Watson and physicist Francis Crick Had been working to unlock the secrets of the DNA molecule But they weren't alone.
Several other groups of competing scientists were hard at work, trying to solve the same puzzle Some important facts about DNA were already known For instance, scientists knew that DNA was composed of four bases Adenine, Cytosine, guanine and thymine They also had been able to infer some of its structure with the help of x-ray crystallography This technique involve passing an extra beam through a crystallized DNA molecule And capturing a vague shadow image of its internal structure on a photographic plate Under with this information, along with their own knowledge of chemical structure Watson and Crick began building a three dimensional model of DNA.
I want to arrange I had a biggest and small molecule and somehow you had to form link bounds Here's A and here's T.
And I want this hydrogen to point strikely this nitrogen.
So I had something like this So that went to link the pair And I want this hydrogen to point to this one and like this Today, you can buy a kid symbol structure that Watson and Crick put together But we are getting ahead of ourselves, Watson and crick needed more data.
With the help of physicist Maurice Wilkins, they gained access to an x-ray picture of DNA molecule that had been taken by his research partner.
Her name was Rosaline Franklin Without her knowledge, Watson and Crick used the data from that x-ray image And successfully completed their model In the 1953 issue of natural magazine Watson and crick revealed their amazing discovery to the world Their model showed that he DNA molecules was a double helix The twin strands were compared of four known bases linked together by hydrogen bonds And the whole structure crotch screw like the spiral letter.
Which could easily pull apart in order to make copies of itself with the same encode genetic information.
Watson and crick had won the race.
The discovery of the structure of DNA sparked a scientific revolution It illuminated the molecular biochemical foundation of life in a whole new way It opened doors for areas of research in other great discovery that few ever imagine possible.
As for Watson and crick, their discovery of double helix along with Maurice Wilkins But whatever Wilkins's colleague Rosaline Franklin Despite her contribution to the discovery She wasn't considered for the 1962's Nobel Prize The rule state that it can only be awarded to living recipient.
Rosaline Franklin died in 1958 of ovarian cancer.
Most likely caused by exposure to x-rays Welcome to my world.
This is one of the trillion of cells that make up my body This material in the cell is called the cytoplasm Over here is the cell's nucleus Inside the fragile nucleus envelope are the long thin strands of DNA As we've seen, DNA contained genetic instruction that control the cell's metabolic functions and heredity Sounds simple enough But the process by which this genetic transfer occurs is sublime Is the story of our next great discovery Years before Watson and crick had found the structure of DNA.
Scientists knew that the DNA was responsible for making protein that resided inside of the cytoplasm But they were puzzled by how the DNA managed to transfer its genetic information for making proteins through the nucleus's wall The answer to the puzzle came to the collective work of several different scientists And like many discoveries, it began with an educated guess The production of protein in a cell is seen here in red Scientists found that cells with lots of protein production contain lot of this RNA, a chemical similar to DNA But with only one strand, not two This led scientists to wonder if RNA was somehow involved running the protein factory in the set of the cytoplasm To find out, once again, researchers tuned to the bacteria phage They detected that soon after the bacteria phage injected in the DNA into a bacteria, traces of viral RNA appeared in the host cell And the production of protein began to increase This was the moment of discovery Here was a special kind of RNA never seen before.
As it single strand enter one of it cell's protein factories It communicated the message for making new protein.
Scientists called it massager RNA.
Today, many scientists believed that massager RNA and other RNA molecules are descendents of the earth's most primitive chemical materials.
Part of the primordial soup that cooked up the first living organism As we've just seen, RNA translated structure form DNA for making proteins But what was the genetic code, The sequence of instructions that made this process possible In 1961, molecular biologist Marshall Warren Nirenberg and post doctorial fellow Heinrich Matthaei Carried out a series of experiments to see if it can synthesize proteins in the laboratory And in their experiments Nirenberg and Matthaei were working with RNA.
Like DNA, RNA is made of four chemical bases In the uearica moment of discovery, they found that when three of the bases allied in a specific sequence called a triplet.
The triplet code for a specific amino acid The order of the triplets is the blueprint for the production of proteins.
Today, Marshall Nirenberg is a research scientist at national institution of health So what is this mean to me as a citizen and tax-payer and voter What it meant to you is RNA is transcribed form DNA.
DNA is copied to RNA and RNA contains the information that determines this sequence of amino acids protein.
So what you inherited form your parents is the sequence of letters in DNA that determine how you synthesize How you make different kinds of proteins that needed for life.
That make me, yes, that make you.
Nirenberg and Matthaei's discovery was the first crack in the genetic code A peak in the secret vocabulary encrypted in each DNA molecule Enabling to instruct synthesize of proteins Over the next five years, Nirenberg successfully deciphered the 64 triplets that comprised the entire vocabulary of DNA The genetic code had been broken.
And in 1968, the discovery earned Marshall Nirenberg a share of Nobel Prize for physiology and medicine.
What was this like you made this discovery Well it was opening a door to a toy shop It means that we could do virtually everything we could decipher the genetic code.
Every living thing, has the same code Yes, the one code that used by every living thing on this planet.
And it's same, basically the same language that used And when we found that out, you know I knew all about Darwin.
I knew all about evolution.
But this broted homeand such immediate fashion All living things on this planet are related.
We are all derived from a common ancestor, and our bodies all speak the same language.
It had a very mark defect on me.
While we are watching Watson and crick structure of DNA Marshall Nirenberg and Matthaei uncovered the blueprint for how the structure worked The breakthrough that led to some of the discoveries since we've seen so far have never happen if not for this familiar organism Bacteria phage and our next discovery depended on it as well For decades it was believed that bacteria were completely vulnerable to invading bacteria phage Certain types of bacteria were in fact resisted to being infected by a bacteria phage.
How was that possible The first answer was provided in 1962 by microbiologist Werner Arber He found that some bacteria had enzyme that fought back against the virus by cutting its viral DNA into pieces This restricted the virus from taking over the bacteria.
So they were called restriction enzymes.
But how exactly did they work Among those hoping to unlock that secrets was microbiologist Hamilton smith.
When he noticed that the DNA of the virus was breaking down.
Smith acted quickly.
He purified the restriction enzyme They he identified the exactly was the restricted enzyme had severed the DAN.
Then came the moment of discovery Smith found that the enzyme were repeatedly cut the viral in the same place He had discovered the first site specific restriction enzyme With restriction enzymes, scientist now had molecular scissor They could used to cut the DNA molecules to virtually recreate nature.
This is significant Today, this ability to manipulate DNA is one of the basic tools in genetic engineering, what's called recombinant DNA research.
Since Hamilton smith's discovery, hundreds of restriction enzymes have been identified And scientist are using recombinant DNA for a world replication on which we depend Everything from the creation of more effective less expensive drugs To the production of human insulin for the millions of diabetics worldwide who rely on getting their daily doze.
With the discovery of massager RNA Scientists had found the process by which DNA communicate its instructions for making protein in the cytoplasm For decades, they believed this process are operated by one simple rule Instructions were coded form one gene in the DNA to one type of massager RNA.
Which then produced one protein But in the nineteen eighties, this theory was challenged when scientists began detecting something new.
Genes that coded multiple massager RNAs, which then produced multiple proteins It were taking the combined efforts several scientist to find out how this was possible.
But finally they had their answer.
Through a process called alternative splicing.
Some genes are able to code For more than one protein The discovery of alternative splicing was important Because it gives scientist valuable insight into the role that RNA plays in the production of proteins And that insight helped researchers make advances in the whole range of biomedical applications For example, scientist have used their knowledge of alternative splicing to create more effective pain-killers Some medicine are designed to block the production of specific alternative splicing proteins enzymes which regulate pain in the nervous system London, 1985, a boy arrives by plane from the Africa nation of Ghana.
The purpose of this visit to be reunited with his mother But custom spectators are suspicious the boy's passport appears to be a forgery.
And there is no prove that the woman he is meeting is really his mother.
The British government decides to deport the boy Desperate, the woman tunes to detective for help.
His name is Alec Jeffries Not a real detective, but a geneticist at Leicester University Before we learn the rest of the story, a little background By the nineteen eighties, scientist had become aware of the genetic variation among individuals is very common And they begun to link the presence of this so-called DNA variance to the presence of the disease causing genes in large families For example, Huntington s disease, and that bring this back to Alec Jeffries In 1984, Jeffries found something never see before, It was a DNA variant formed by short identical sequences of DNA that were repeated over and over Jeffries called this repeated sequence minisatellite DNA Then came the breakthrough discovery What we detected were lots of beats of DNA and in human's they have clearly variable, very variable In fact, what we got first was very murky DNA fingerprints and that point is penny drops Jeffries's discovery made history When he was asked to help solve the mystery of the boy from Ghana For the first time, DNA fingerprinting was put to the test Jeffries compared the DNA of the boy with the DNA of his supposed mother.
The result showed a striking similarity in the minisatellite DNA, proving beyond the doubt that the boy was her son.
So that when she was told the DNA evidence has been accepted your boy is coming back.
He's permanent with you and it was the vrouw in that lady's was magic and this is, I mean the first time that had ever done this, the first time that DNA was in molecular genetics and she have been used to go on an nonclinical contest that straightly help someone.
It has been over fifty years since Watson and crick's great discovery of DNA's double helix structure Since then, scientist have probed and revealed many of the genome secrets.
But not without some surprises In 1997, scientist Andrew Fire and Craig Mello were conducting a series of experiments To better understand the functions of specific genes The injected synthetic RNA made up of two stands into the cell of a round worm, then watched What happened next was astonishing.
A mechanism within the worm cell destroyed the double stands RNA As well as some of its own massager RNA In fact, the genes were responsible for coding the production of proteins in the cell was tuned off Fire and Mello has discovered what came to be known as RNA interference Today, Andrew Fire is a geneticist at Stanford University We sort of kemipound the experiments where we were injecting RNA and hoping that things would happen that very specific things Things with a little Things with a little needle, right into a worm arcais Although similar experiments we done in systems And if you see the a situation where the RNA goes in there Not only is it shuttle off, which is not surprise you don't know what happen then It also shedding off one of it cell genes, then you have surprising situation, that was really surprise that came here in 1990 The discovery of RNA interference was a milestone It gives scientist a potentially powerful new technology What is the RNA interference really mean for the future What is the applications of this The first one is really understanding the new biological mechanism Whatever make genes silence, Whatever make genes silence turn it off The second is being able to do this general screen of what genes do.
Be able to look at gene's function, just using the mechanism tool And the third thing is sort of, I would say the Holy Grail on the field Is can we use RNA as therapeutic Cure disease, RNA interference, can we cure disease with this And the model there, the idea is you take disease where the people are sick because there is a gene mad out of control It's a genetic disease.
Genetic disease which includes virus, includes tumor, includes certain genetic disease as well And the question is can we shut that gene off This holy grail of therapeutic use in humans is still just out of reach But Fire's discovery of RNA interference opened the door to a new generation of life saving breakthroughs The mystery of what makes us human was partially solved with the cracking of the genetic code But the rest of the answer lay on our next great discovery The sequencing of our complete genetic blueprint called the genome The effort have been called the largest collaboration in history By 1990, the team had joined in forces Craig Venter was one of the team's leaders How did you get started on this thing What make you want to sequence the human genome Well, my experimental career was looking for one gene, gene for the adrenalin receptor for the brain, the heart and the choice was trying to look the entire human genome which we had sensuously no knowledge of only a few hundred genes at the time so here's the most important information to our humanity and we knew sensuously nothing about it we are announcing today for the first time our species can read the chemical letters of genetic code so what did you find so fist, the most simple thing we found was that we have only a tiny fraction of genes that some people were predicting that a set of three hundred of thousand, we found twenty thousand then we found that the variation between humans is remarkably low or almost virtually identical to each other and by sequence in the genome of other mammals of sequence my standard of poodle shadow with the dog genome, the mouth genome, the rat genome we are not doing the monkey rhesus genome here we found out that all mammals share most of the genes on the same order or the same sets of genes and its just move around from one chromosome to another so where is this all the sequencing taken us oh, whatever you found in the beginning was this laid a whole new foundation for science that people were respecting miracle cures there was lots of over high this one you first started out.
.
That's right Now, any scientist, any studio in the world that has access in the internet And most human genes without yet even functions about them So we are studying a new foundation having this information to have the structure of the genes.
they can study their function and this change our view of evolution or similar with mammal's genome, even were plants and bacteria's genome its compatible medicine already with new diagnostics understanding the complexity of genes in search with human traits that's can be a huge challenge for the future So, how did you feel when your group sequence finished, did it, hold it up When we finished it, finished witting the paper describing for the first time It was published in one of the most famous that I have ever have in my life And it was just a fantastic period of satisfaction with whatever our team did and tried to contribute to the history of humanity It's hard to believe but from Gregor Mendel s great discovery of the laws of heredity to the complete sequencing of the human genome, has been a mere a hundred and fifty years But thanks to some of the greatest discoveries in the history of science It has been entire of us to understand some of the life's deep secrets And to understand the genetic ties that bind all living organism that include your brother.
Thanks bill No no thank you for taking the timeĀ thanks bill no, it's i who must thank you for taking time