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1953: The Discovery of the Structure of DNA

What is DNA?

DNA is a chemical inside your cells. It contains a list of
instructions that determines what you are like. One of the
instructions might give you red hair, another might make you tall.
Others might make you good at football. Others might make you
have Parkinson’s disease or Alzheimer’s, or another genetic
disease.

What is a genetic disease?

Many diseases are infectious e.g. smallpox, diphtheria, TB,
blood poisoning. On the whole, these have been conquered. The
process started with Pasteur making the link between germs and disease, and
reached its climax with the discovery and development of penicillin. The lives of
billions of people have been saved by these drugs.

Many other diseases are genetic, just like you get your hair colour and your height
and the size of your feet etc. from your parents and grandparents, so you can
inherit a tendency to get a disease from them. Alzheimer’s disease is probably
genetic, as is Parkinson’s disease. Some cancers can be genetic.


What happened in 1953?

Before 1953, people did not know what the structure of DNA was. Francis Crick
and James Watson, using the work of Linus Pauling and Rosalind Franklin, made
this discovery. Then, in the 1990s and the 2000s scientists mapped out the Human
Genome. This means that they worked out exactly what part of the DNA did what.
This made it possible to alter someone’s DNA.

What has this got to do with Medicine?

If you can alter someone’s DNA then you can alter what they are like.
You could give them a gene that makes them have brown hair, or a gene
that makes them smaller or a gene that stops them getting Parkinson’s disease, or
stops them getting Alzheimer’s.

So what?

The discovery of the structure of DNA and the mapping of the Human
Genome might lead to the conquest of inherited disease. This could
save millions of lives. But is there a downside....?

RW DNA NOTES                                                                        1
How and Who?

After the war, scientists across the world were trying to discover the structure of
DNA. There was a race on to see who could find it first. Some of the scientists
involved were Linus Pauling, Maurice Wilkins, Rosalind Franklin, Francis Crick and
James Watson.

Maurice Wilkins

   •   He worked at Kings College London.
   •   He was a physicist.
   •   He had been involved in the development of the
       atomic bomb during the war and felt guilty about
       this.
   •   He was the first person to use X ray diffraction to
       study the structure of DNA.


                         Crick and Watson

                            •    They worked at the Cavendish Laboratory in
                                 Cambridge.
                              • Watson was American, Crick was English. Watson
                                 was arrogant and brash but brilliant.
                              • They were the first to work out what the structure of
                                 DNA was. They announced their decision informally
                                 at the Eagle Pub in
                                 Cambridge.
                              • Officially they announced in
       a letter that they wrote in Nature Magazine. This was
       published on 25 April 1953.
   •   They were brilliant chemists who ‘sparked off’ each
       other. They were not methodical but instead had
       brilliant insights (hunches). They relied on the work
       of other people to test their insights: they worked out
       what the structure of DNA was without themselves
       doing any experiments. They relied heavily on the
       work of Wilkins and Franklin.
   •   How did they get hold of this work?




RW DNA NOTES                                                                        2
Rosalind Franklin

   •   She started working at Kings College London in 1951.
   •   She worked with Maurice Wilkins.
   •   She was an expert at using X ray diffraction to study the
       structure of chemicals, because throughout the 1940s
       she had used this method to study carbon.
   •   She was very methodical and thorough: if she had been
       less so then she might have discovered the structure of
       DNA before Crick and Watson.
   •   She improved Wilkins’ X ray diffraction techniques and
       produced some clear images of DNA: much clearer than any else had been
       able to achieve.
   •   One of these images, number 51, was shown by
       Wilkins to Watson, who was visiting King’s College
       London. It helped to confirm several hunches that he
       and Crick had.


                      Franklin’s photograph 51, taken in 1952
                      and later shown to Crick and Watson.



   •   Rosalind Franklin shared more of her discoveries about DNA with the British
       Medical Research Council, who were paying for her work. She did this on
       the understanding that her results would be confidential. They would not be
                      circulated. One of the men who sat on the Medical Research
                      council was Max Perutz. He worked at the Cavendish
                      Laboratory in Cambridge
                   • He shared some of Franklin’s findings about DNA with Crick
                      and Watson. This helped to confirm some more of their
                      hunches. This enabled them to work out the structure of
                      DNA, and announce and publish their findings.
                   • Franklin, according to Crick and Watson, was very close to
                      discovering the structure of DNA — about one month behind
                      them.
                   • Would Crick and Watson have succeeded without Franklin’s
       work?
   •   Could Franklin have succeeded without Crick and Watson’s work?
   •   Rosalind Franklin did valuable work on polio before dying of ovarian cancer
       at the age of 38.
   •   Max Perutz won the Nobel Prize for Chemistry in 1962 for his X ray work on
       blood.




RW DNA NOTES                                                                     3
What next?

In 1962 Crick and Watson and Wilkins were awarded the Nobel Prize for their work
on DNA; Franklin could not be awarded it since she was dead and the award could
not be given posthumously.
In his book about the discovery of the structure of DNA Watson made some
disparaging remarks about Franklin.
The discovery of the structure of DNA enabled the mapping of the human genome.
This has the potential to have a huge effect on medicine and on all our lives.


Summary

Maurice Wilkins was the first person to use X ray diffraction to study the Structure
of DNA.
Rosalind Franklin perfected these techniques and provided essential information
about the structure of DNA.
Crick and Watson got hold of Wilkins’ and Franklin’s information and used it to
confirm their brilliant hunches.
Crick and Watson discovered the structure of DNA first. They and Wilkins were
awarded the Nobel Prize in 1962. Franklin could not receive it because she had
died.




The importance of the discovery of DNA

DNA has been called the most important scientific discovery of the 20th century.
Understanding of the structure of DNA enabled other scientists to work on the
individual elements of the DNA spiral. The biggest research project is The Human
Genome Project (HUGO)

This is a project to identify all 100,000 genes and all 3,000 million base pairs in
DNA molecules. By contrast with the individual research of Crick and Watson, this
is a huge, international, multi-million dollar project. 18 countries are taking part,
mainly the USA, Britain, Japan, France and Canada. It was set up in 1986 and was
completed in 2003.

There are a huge range of products flowing from this research. Some have medical
implications, some go beyond medicine and several are very controversial.
Several diseases and disabilities are caused by a single problem gene. Most
notable are cystic fibrosis and Huntington’s chorea. Gene therapy (theoretically
possible, but not yet) - would involve putting normal genes into body, this might

RW DNA NOTES                                                                        4
help these conditions. Other gene based conditions may be treatable eventually,
such as sickle-cell anaemia, Alzheimer’s disease, muscular dystrophy.
Screening for certain disease or disability-causing disease either in the womb or
soon after birth is already used as part of preventive medicine
Drugs could be designed to deal with particular problems “custom drugs” which
would avoid some of the haphazardness of drug research.
Genetic engineering. Living things plants, even animals, (e.g. Dolly the sheep)
can be created to have certain characteristics. GM (genetically modified) crops
could thus be disease-resistant, long living etc.
DNA “fingerprinting” has been used in crime
detection, rape cases and paternity suits.
There is media discussion of parents being able to
“design” their children: not only their gender, but their
appearance, physique, intellectual ability. However,
scientists are sceptical about whether this could
come about.

       Dolly the sheep (1996-2003) was the first
       mammal to be cloned from a single adult cell,
       proving it was possible to clone a whole
       mammal.


In the 1990s the Human Genome Project began working out the exact contents of
the DNA in the human body - finding out exactly what each part of the DNA does.
The information contained in one person would fill 160,000 books like this! That’s
why it took ten years for scientists — working as a huge team across eighteen
countries and using the latest computers — to finish the project.

The Human Genome Project has 5% of its budget set aside to deal with the
massive ethical, legal and social issues involved. Some of these are:

Access to genetic information, perhaps about pre-disposition to certain diseases.
How does this affect: insurance, adoption, schools, courts, employers?
The psychological impact of knowing about your own genetic make-up.
What is “normal”? Is “disability” a disease?
Who should have access to genetic treatments? Who will pay?
Who should make a profit out of genetic therapy, genetic engineering?
Who owns DNA? Can you patent a gene?




RW DNA NOTES                                                                        5
Rosalind Franklin: The Dark Lady of DNA

In April 1953, James Watson, Francis Crick and Maurice Wilkins identified the
substance of life, the structure of DNA.
They later shared a Nobel Prize. Their discovery depended heavily on the work of
a woman, chemist Rosalind Franklin, whose research was used without her
knowledge or permission. Watson’s memoir of the discovery dismisses Franklin as
frumpy, hostile and unimaginative. A later work by a friend casts Franklin as a
feminist icon, cheated of recognition.

Now, a new book enters the fray. Rosalind Franklin: The Dark Lady of DNA, by
Brenda Maddox. The book strikes something of a middle ground: Franklin was
instrumental in discovering the structure of DNA, but she wasn’t altogether ignored.
It was Franklin’s photograph of the DNA molecule that sparked a scientific
revolution. Wilkins showed Watson the photo, and, Watson said, “My jaw fell open
and my pulse began to race.” The photo showed, for the first time, the essential
structure of DNA, the double-helix shape, which also indicated its method of
replication.

It was Franklin’s photographic skills that made the discovery possible, says
Maddox. “She could take photographs of crystals and interpret the patterns. ”She
had “a particular genius at aligning hand and mind.”

She did not know the other men were using her research upon which to base the
article that appeared in the journal Nature. She didn’t complain either. This may be
thanks to her upbringing, says Maddox. Franklin “didn’t do anything that would
invite criticism. . . (this was) bred into her.”

She wouldn’t share in the Nobel Prize either. Maddox says this not because
Franklin was overlooked, but because she was dead. The award is not given out
posthumously. Franklin was diagnosed with ovarian cancer in 1956 at age 36, and
died two years later, without an award, but not without recognition eventually.




RW DNA NOTES                                                                       6

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The Discovery of DNA

  • 1. 1953: The Discovery of the Structure of DNA What is DNA? DNA is a chemical inside your cells. It contains a list of instructions that determines what you are like. One of the instructions might give you red hair, another might make you tall. Others might make you good at football. Others might make you have Parkinson’s disease or Alzheimer’s, or another genetic disease. What is a genetic disease? Many diseases are infectious e.g. smallpox, diphtheria, TB, blood poisoning. On the whole, these have been conquered. The process started with Pasteur making the link between germs and disease, and reached its climax with the discovery and development of penicillin. The lives of billions of people have been saved by these drugs. Many other diseases are genetic, just like you get your hair colour and your height and the size of your feet etc. from your parents and grandparents, so you can inherit a tendency to get a disease from them. Alzheimer’s disease is probably genetic, as is Parkinson’s disease. Some cancers can be genetic. What happened in 1953? Before 1953, people did not know what the structure of DNA was. Francis Crick and James Watson, using the work of Linus Pauling and Rosalind Franklin, made this discovery. Then, in the 1990s and the 2000s scientists mapped out the Human Genome. This means that they worked out exactly what part of the DNA did what. This made it possible to alter someone’s DNA. What has this got to do with Medicine? If you can alter someone’s DNA then you can alter what they are like. You could give them a gene that makes them have brown hair, or a gene that makes them smaller or a gene that stops them getting Parkinson’s disease, or stops them getting Alzheimer’s. So what? The discovery of the structure of DNA and the mapping of the Human Genome might lead to the conquest of inherited disease. This could save millions of lives. But is there a downside....? RW DNA NOTES 1
  • 2. How and Who? After the war, scientists across the world were trying to discover the structure of DNA. There was a race on to see who could find it first. Some of the scientists involved were Linus Pauling, Maurice Wilkins, Rosalind Franklin, Francis Crick and James Watson. Maurice Wilkins • He worked at Kings College London. • He was a physicist. • He had been involved in the development of the atomic bomb during the war and felt guilty about this. • He was the first person to use X ray diffraction to study the structure of DNA. Crick and Watson • They worked at the Cavendish Laboratory in Cambridge. • Watson was American, Crick was English. Watson was arrogant and brash but brilliant. • They were the first to work out what the structure of DNA was. They announced their decision informally at the Eagle Pub in Cambridge. • Officially they announced in a letter that they wrote in Nature Magazine. This was published on 25 April 1953. • They were brilliant chemists who ‘sparked off’ each other. They were not methodical but instead had brilliant insights (hunches). They relied on the work of other people to test their insights: they worked out what the structure of DNA was without themselves doing any experiments. They relied heavily on the work of Wilkins and Franklin. • How did they get hold of this work? RW DNA NOTES 2
  • 3. Rosalind Franklin • She started working at Kings College London in 1951. • She worked with Maurice Wilkins. • She was an expert at using X ray diffraction to study the structure of chemicals, because throughout the 1940s she had used this method to study carbon. • She was very methodical and thorough: if she had been less so then she might have discovered the structure of DNA before Crick and Watson. • She improved Wilkins’ X ray diffraction techniques and produced some clear images of DNA: much clearer than any else had been able to achieve. • One of these images, number 51, was shown by Wilkins to Watson, who was visiting King’s College London. It helped to confirm several hunches that he and Crick had. Franklin’s photograph 51, taken in 1952 and later shown to Crick and Watson. • Rosalind Franklin shared more of her discoveries about DNA with the British Medical Research Council, who were paying for her work. She did this on the understanding that her results would be confidential. They would not be circulated. One of the men who sat on the Medical Research council was Max Perutz. He worked at the Cavendish Laboratory in Cambridge • He shared some of Franklin’s findings about DNA with Crick and Watson. This helped to confirm some more of their hunches. This enabled them to work out the structure of DNA, and announce and publish their findings. • Franklin, according to Crick and Watson, was very close to discovering the structure of DNA — about one month behind them. • Would Crick and Watson have succeeded without Franklin’s work? • Could Franklin have succeeded without Crick and Watson’s work? • Rosalind Franklin did valuable work on polio before dying of ovarian cancer at the age of 38. • Max Perutz won the Nobel Prize for Chemistry in 1962 for his X ray work on blood. RW DNA NOTES 3
  • 4. What next? In 1962 Crick and Watson and Wilkins were awarded the Nobel Prize for their work on DNA; Franklin could not be awarded it since she was dead and the award could not be given posthumously. In his book about the discovery of the structure of DNA Watson made some disparaging remarks about Franklin. The discovery of the structure of DNA enabled the mapping of the human genome. This has the potential to have a huge effect on medicine and on all our lives. Summary Maurice Wilkins was the first person to use X ray diffraction to study the Structure of DNA. Rosalind Franklin perfected these techniques and provided essential information about the structure of DNA. Crick and Watson got hold of Wilkins’ and Franklin’s information and used it to confirm their brilliant hunches. Crick and Watson discovered the structure of DNA first. They and Wilkins were awarded the Nobel Prize in 1962. Franklin could not receive it because she had died. The importance of the discovery of DNA DNA has been called the most important scientific discovery of the 20th century. Understanding of the structure of DNA enabled other scientists to work on the individual elements of the DNA spiral. The biggest research project is The Human Genome Project (HUGO) This is a project to identify all 100,000 genes and all 3,000 million base pairs in DNA molecules. By contrast with the individual research of Crick and Watson, this is a huge, international, multi-million dollar project. 18 countries are taking part, mainly the USA, Britain, Japan, France and Canada. It was set up in 1986 and was completed in 2003. There are a huge range of products flowing from this research. Some have medical implications, some go beyond medicine and several are very controversial. Several diseases and disabilities are caused by a single problem gene. Most notable are cystic fibrosis and Huntington’s chorea. Gene therapy (theoretically possible, but not yet) - would involve putting normal genes into body, this might RW DNA NOTES 4
  • 5. help these conditions. Other gene based conditions may be treatable eventually, such as sickle-cell anaemia, Alzheimer’s disease, muscular dystrophy. Screening for certain disease or disability-causing disease either in the womb or soon after birth is already used as part of preventive medicine Drugs could be designed to deal with particular problems “custom drugs” which would avoid some of the haphazardness of drug research. Genetic engineering. Living things plants, even animals, (e.g. Dolly the sheep) can be created to have certain characteristics. GM (genetically modified) crops could thus be disease-resistant, long living etc. DNA “fingerprinting” has been used in crime detection, rape cases and paternity suits. There is media discussion of parents being able to “design” their children: not only their gender, but their appearance, physique, intellectual ability. However, scientists are sceptical about whether this could come about. Dolly the sheep (1996-2003) was the first mammal to be cloned from a single adult cell, proving it was possible to clone a whole mammal. In the 1990s the Human Genome Project began working out the exact contents of the DNA in the human body - finding out exactly what each part of the DNA does. The information contained in one person would fill 160,000 books like this! That’s why it took ten years for scientists — working as a huge team across eighteen countries and using the latest computers — to finish the project. The Human Genome Project has 5% of its budget set aside to deal with the massive ethical, legal and social issues involved. Some of these are: Access to genetic information, perhaps about pre-disposition to certain diseases. How does this affect: insurance, adoption, schools, courts, employers? The psychological impact of knowing about your own genetic make-up. What is “normal”? Is “disability” a disease? Who should have access to genetic treatments? Who will pay? Who should make a profit out of genetic therapy, genetic engineering? Who owns DNA? Can you patent a gene? RW DNA NOTES 5
  • 6. Rosalind Franklin: The Dark Lady of DNA In April 1953, James Watson, Francis Crick and Maurice Wilkins identified the substance of life, the structure of DNA. They later shared a Nobel Prize. Their discovery depended heavily on the work of a woman, chemist Rosalind Franklin, whose research was used without her knowledge or permission. Watson’s memoir of the discovery dismisses Franklin as frumpy, hostile and unimaginative. A later work by a friend casts Franklin as a feminist icon, cheated of recognition. Now, a new book enters the fray. Rosalind Franklin: The Dark Lady of DNA, by Brenda Maddox. The book strikes something of a middle ground: Franklin was instrumental in discovering the structure of DNA, but she wasn’t altogether ignored. It was Franklin’s photograph of the DNA molecule that sparked a scientific revolution. Wilkins showed Watson the photo, and, Watson said, “My jaw fell open and my pulse began to race.” The photo showed, for the first time, the essential structure of DNA, the double-helix shape, which also indicated its method of replication. It was Franklin’s photographic skills that made the discovery possible, says Maddox. “She could take photographs of crystals and interpret the patterns. ”She had “a particular genius at aligning hand and mind.” She did not know the other men were using her research upon which to base the article that appeared in the journal Nature. She didn’t complain either. This may be thanks to her upbringing, says Maddox. Franklin “didn’t do anything that would invite criticism. . . (this was) bred into her.” She wouldn’t share in the Nobel Prize either. Maddox says this not because Franklin was overlooked, but because she was dead. The award is not given out posthumously. Franklin was diagnosed with ovarian cancer in 1956 at age 36, and died two years later, without an award, but not without recognition eventually. RW DNA NOTES 6