The DNA papers

The DNA papers is a series of podcasts on the discovery that DNA is the source of genetic information. Each podcast is a discussion among experts on the history of molecular biology, including some who have been regularly featured on this blog. I draw your attention to episodes 6 and 15 where you can hear Matt Meselson one of the key figures in the 'phage group.

The key take-home lesson is that the importance of DNA was recognized by a small group of scientists who were paying attention to the scientific literature. By the time of Watson and Crick (1953) this small group was already convinced that DNA was the "stuff of life," which is why they realized that solving the structure was extremely important.

This is not unusual. There are many cases where a small group of knowledgeable experts are well in advance of the average scientist who often doesn't even realize that a revolution is under way.

• Episode 1 on Friedrich Miescher and the discovery of nuclein
• Episode 2 on Albrecht Kossel and the discovery of the building blocks of nuclein
• Episode 3 on Walter Sutton and the relation between chromosomes and heredity
• Episode 4 on Fred Griffith and the discovery of bacterial transformation/li>
• Episode 5 on Phoebus Levene, DNA chemistry and the tetranucleotide hypothesis
• Episode 6 on William Astbury, Florence Bell and the first X-ray pictures of DNA
• Episode 7 on Oswald Avery, Colin McLeod, and Maclyn McCarty and the chemical basis of bacterial transformation
• Episode 8 on Maclyn McCarty, Oswald Avery and the enzymatic evidence for DNA as the transforming substance
• Episode 9 on Erwin Chargaff and the evidence for non-uniformity of nucleotide base composition in DNA
• Episode 10 on Harriet Ephrussi-Taylor, Rollin Hotchkiss and the demonstration of bacterial transformation as a general phenomenon
• Episode 11 on Alfred Hershey, Martha Chase, and the conclusive evidence for the function of DNA as the material of heredity
• Episode 12 on Maurice Wilkins, Rosalind Franklin, their collaborators, and the data that supported the double helix model for DNA structure
• Episode 13 on James Watson, Francis Crick, and the DNA Double Helix
• Episode 14 on Matthew Meselson, Franklin Stahl, and semiconservative replication of DNA
• Episode 15 A conversation with Matthew Meselson and Franklin Stahl

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"Cancer Virus Hunters" by Gregory J. Morgan

That seven Nobel Prizes were awarded directly or indirectly for work in tumor virology illustrates the impact of the field on biomedical understanding. (p. 273)

We've entered a new era in the field of molecular biology. Almost all of the emphasis and excitement these days is based on studies of mammals, especially humans. Most of the big bucks are for studying some aspect of medicine so that even if you are interested in basic science you have to slant it toward curing some disease.

What really happened between Rosalind Franklin, James Watson, and Francis Crick?

That's part of the title of podcast by Kat Arney who interviews Matthew Cobb [Double helix double crossing? What really happened between Rosalind Franklin, James Watson and Francis Crick?].

Matthew Cobb is one of the world's leading experts on the history of molecular biology.

The way it’s usually told, Franklin was effectively ripped off and belittled by the Cambridge team, especially Watson, and has only recently been restored to her rightful place as one of the key discoverers of the double helix. It’s a dramatic narrative, with heroes, villains and a grand prize. But, as I found out when I sat down for a chat with Matthew Cobb, science author and Professor of Zoology at the University of Manchester, the real story is a lot more nuanced.

Photo 51 did not belong to Rosalind Franklin and it had (almost) nothing to do with solving the structure of DNA. Franklin and Wilkins would never have gotten the structure on their own. Crick and Watson did not "steal" any data. Whether they behaved ethically is debatable.

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Happy DNA day 2021!

It was 68 years ago today that the famous Watson and Crick paper was published in Nature along with papers by Franklin & Gosling and Wilkins, Stokes, & Wilson. Threre's a great deal of misinformation circulating about this discovery so I wrote up a brief history of the events based largely on Horace Freeland Judson's book The Eighth Day of Creation. Every biochemistry and molecular biology student must read this book or they don't qualify to be an informed scientist. However, if you are not a biochemistry student then you might enjoy my short version.

Some practising scientists might also enjoy refreshing their memories so they have an accurate view of what happened in case their students ask questions.

The Story of DNA (Part 1)

Where Rosalind Franklin teaches Jim and Francis something about basic chemistry.

The Story of DNA (Part 2)

Where Jim and Francis discover the secret of life.

Here are some other posts that might interest you on DNA Day.

• Rosalind Franklin Announces the Death of the Helix
• Sixty Years Ago Today: April 25, 1953
• Rosalind Franklin's Birthday
• Did Rosalind Franklin produce the first X-ray diffraction images of DNA?
• The Wilkins, Stokes and Wilson Nature paper (1953)
• The Franklin & Gosling Nature paper (1953)
• The Watson & Crick Nature Paper (1953)

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My father on D-Day: 75 years ago

Today is the 75th anniversary of D-Day—the day British, Canadian, and American troops landed on the beaches of Normandy.¹

For us baby boomers it always meant a day of special significance for our parents. In my case, it was my father who took part in the invasions. That's him on the right as he looked in 1944. He was an RAF pilot flying rocket-firing typhoons in close support of the ground troops. His missions were limited to quick strikes and reconnaissance during the first few days of the invasion because Normandy was at the limit of their range from southern England. During the second week of the invasion (June 14th) his squadron landed in Crepon, Normandy and things became very hectic from then on with several close support missions every day [see Hawker Hurricanes and Typhoons in World War II].

The history of DNA sequencing

This year marks the 40th anniversary of DNA sequencing technology (Gilbert and Maxam, 1977; Sanger et al., 1977)¹ The Sanger technique soon took over and by the 1990s it was the only technique used to sequence DNA. The development of reliable sequencing machines meant the end of those large polyacrylamide gels that we all hated.

Pyrosequencing was developed in the mid 1990's and by the year 2000 massive parallel sequencing using this technique was becoming quite common. This "NextGen" sequencing technique was behind the massive explosion in sequences in the early part of the 21st century.²

Even newer techniques are available today and there's a debate about whether they should be called Third Generation Sequencing (Heather and Chain, 2015).

Nature has published a nice review of the history of DNA sequencing (Shendure et al., 2017). I recommend it to anyone who's interested in the subject. The figure above is taken from that article.

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1. Many labs were using the technology in 1976 before the papers were published.

2. New software and enhanced computer power played an important, and underappreciated, role.

Heather, J.M., and Chain, B. (2015) The sequence of sequencers: The history of sequencing DNA. Genomics, 107:1-8. [doi: 10.1016/j.ygeno.2015.11.003]

Maxam, A.M., and Gilbert, W. (1980) Sequencing end-labeled DNA with base-specific chemical cleavages. Methods in enzymology, 65:499-560. [doi: 10.1016/S0076-6879(80)65059-9]

Sanger, F., Nicklen, S., and Coulson, A.R. (1977) DNA sequencing with chain-terminating inhibitors. Proceedings of the National Academy of Sciences, 74:5463-5467. [PDF]

Shendure, J., Balasubramanian, S., Church, G.M., Gilbert, W., Rogers, J., Schloss, J.A., and Waterston, R.H. (2017) DNA sequencing at 40: past, present and future. Nature, 550:345-353. [doi: 10.1038/nature24286]

Bastille Day 2017

Today is the Fête Nationale in France known also as "le quatorze juillet" or Bastille Day.

This is the day in 1789 when French citizens stormed and captured the Bastille—a Royalist fortress in Paris. It marks the symbolic beginning of the French revolution although the real beginning is when the Third Estate transformed itself into the National Assembly on June 17, 1789 [Tennis Court Oath].

Ms. Sandwalk and I visited the site of the Bastille (Place de la Bastille) when we were in Paris in 2008. There's nothing left of the former castle but the site still resonates with meaning and history.

One of my wife's ancestors is William Playfair, the inventor of pie charts and bar graphs [Bar Graphs, Pie Charts, and Darwin]. His work attracted the attention of the French King so he moved to Paris in 1787 to set up an engineering business. He is said to have participated in the storming of the Bastille but he has a history of exaggeration and untruths so it's more likely that he just witnessed the event. He definitely lived nearby and was in Paris on the day in question. (His son, my wife's ancestor, was born in Paris in 1790.)

In honor of the French national day I invite you to sing the French national anthem, La Marseillaise. An English translation is provided so you can see that La Marseillaise is truly a revolutionary call to arms. (A much better translation can be found here.)¹

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1. I wonder if President Trump sang La Marseillaise while he was at the ceremonies today?

Check out Uncertain Principles for another version of La Marseillaise—this is the famous scene in Casablanca.

Reposted and modified from 2016.

June 6, 1944

Today is anniversary of D-Day—the day British, Canadian, and American troops landed on the beaches of Normandy.¹

For baby boomers it means a day of special significance for our parents. In my case, it was my father who took part in the invasions. That's him on the right as he looked in 1944. He was an RAF pilot flying rocket firing typhoons in close support of the ground troops. During the initial days his missions were limited to quick strikes and reconnaissance since Normandy was at the limit of their range from southern England. During the second week of the invasion (June 14th) his squadron landed in Crepon, Normandy and things became very hectic from then on with several close support missions every day.

Vimy Ridge

Today marks the 100th anniversary of the beginning of the Battle of Vimy Ridge. The battle invovled four divisions of the Canadian Corps and it has become a symbol for Canada of the sacrifices made during World War I. The symbol is remarkable for the beautiful Canadian National Vimy Ridge Memorial designed by Walter Seymour Allward. He intended it to be a "sermon against the futility of war."

It is remarkably successful as such a symbol since, among other things, it contains the names of more than 11,000 Canadians who died in World War I and whose bodies were never recovered. We visited the memorial in 2011 with my granddaughter Zoë [Canadian National Vimy Memorial] and found the name of Lance Corporal Robert Alexander Hood, a cousin of Leslie's grandfather and Zoë's great-great-grandfather.

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Bastille Day

Today is the Fête Nationale in France known also as "le quatorze juillet" or Bastille Day.

This is the day in 1789 when French citizens stormed and captured the Bastille—a Royalist fortress in Paris. It marks the symbolic beginning of the French revolution although the real beginning is when the Third Estate transformed itself into the National Assembly on June 17, 1789 [Tennis Court Oath].

Ms. Sandwalk and I visited the site of the Bastille (Place de la Bastille) when we were in Paris in 2008. There's nothing left of the former castle but the site still resonates with meaning and history.

One of Ms Sandwalk's ancestors, William Playfair witnessed the storming of the Bastille.

In honor of the French national day I invite you to sing the French national anthem, La Marseillaise. An English translation is provided so you can see that La Marseillaise is truly a revolutionary call to arms. (A much better translation can be found here.)

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Check out Uncertain Principles for another version of La Marseillaise—this is the famous scene in Casablanca.

Reposted from 2009.

Nature publishes a misleading history of the discovery of DNA repair

The history of DNA repair is well-known. Here's a quote from "Early days of DNA repair: discovery of nucleotide excision repair and homology-dependent recombinational repair" by W.D. Rupp in 2013 (Rupp, 2013).

This article describes events related to the first papers published in the 1960s describing nucleotide excision repair (NER) and homology-dependent recombinational repair.

Here's are the relevant papers.

Setlow, R.B., and Carrier, W.L. (1964) The disappearance of thymine dimers from DNA: An error-correcting mechanism. Proc. Natl. Acad. Sci. (USA) 51:226–231. [Full Text]

Boyce, R.P., Howard-Flanders, P. (1964) Release of ultraviolet light-induced thymine dimers from DNA in E. coli K-12. Proc. Natl. Acad. Sci. (USA) 51:293–300. [Full Text]

Pettijohn, D, and Hanawalt, P. (1964) Evidence for repair-replication of ultraviolet damaged DNA in bacteria. J. Mol. Biol. 9:395–410. [PubMed]

The Burghers of Calais at the Metropolitan Museum of Art in New York

There are 13 casts of the famous sculpture by Rodin [The Burghers of Calais]. I've seen four of them (Paris, Washington, Los Angeles, New York). I took this photo today at the Metropolitan Museum of Art in New York.

The burghers thought they were sacrificing their lives to save the inhabitants of Calais, which was being starved into submission by Edward III of England in 1347. Their lives were spared after Queen Philippa convinced her husband to be lenient.

One of my ancestors is Paon de Roet. He was a knight in Queen Phillippa's retinue and was one of two knights assigned to protect the burghers of Calais. I descend from Paon de Roet's daughter, Katherine. Her sister, Philippa (named after the Queen), married a poet named Geoffrey Chaucer [My Connection to Geoffrey Chaucer and Medieval Science].

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On this day in 1945

At 8:15 AM on August 6, 1945 an atomic bomb was detonated over Hiroshima, Japan. Approximately 78,000 civilians were killed on that day. Six months later the death toll had risen to about 140,000 people.

There are many arguments in favor of dropping the bomb, just as there are many arguments against it. What's clear is that in the context of 2015 we are not in a good position to judge the actions of countries that had been at war for many years.

The most important lesson of Hiroshima is that war is hell and many innocent people die. It's all very well to enter into a war with the best of intentions—as the Japanese did on December 7, 1941—but it's foolish to pretend that when you start a war there won't be any suffering. When you do that, you can really say that the victims of Hiroshima will have died in vain.

The killing and maiming of civilians is an inevitable outcome of war, no matter how hard you might try to restrict your targets to military objectives. Before going to war you need to take the consequences into account and decide whether the cost is worth it.

Hiroshima was not a glorious victory. It was ugly, heartbreaking, and avoidable. War is not an end in itself, it is the failure of peace. War is not an instrument of foreign policy—it is an admission that you don't have a foreign policy.

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[The top photograph shows the mushroom cloud over Hiroshima on the morning of August 6, 1945 (Photo from Encyclopedia Britanica: Hiroshima: mushroom cloud over Hiroshima, 1945. [Photograph]. Retrieved August 7, 2007, from Encyclopædia Britannica Online.

The bottom image is taken from a Japanese postcard (Horoshima and Nagassaki 1945). It shows victims of the attack on Hiroshima.]

Sunday, June 18, 1815

Today is the 200th anniversary of the Battle of Waterloo.

The diagram on the right shows the initial disposition of the Anglo-Dutch army under Wellington (red) and the French Army under Napoleon (blue). You can see how they got there by reading my earlier posts [Thursday, June 15, 1815 , Friday, June 16, 1815 , and Saturday, June 17, 1815 ].

There are many detailed descriptions of the battle online so I'm not going to bother with details. The French armies had to eliminate the fortified positions at Hougoumont, La Haye Sainte, and Papelotte. They succeeded at La Haye Saint and Papelotte but the British held on to Hougoumont. This is one of the decisive skirmishes of the battle. The French committed far too many troops to the attack on Hougomount and wasted far too much time.

The diagram on the left shows the situation late in the day when the Imperial Guard is attacking Wellington's center. That attack was driven back and the retreat of the elite Imperial Guard triggered a general retreat of all French forces. Wellington signaled a general advance that didn't stop until the allies reached Paris.

Note the Prussians attacking from the East (right) the French corps under Grouchy had not prevented Blücher from carrying out his promise to support Wellington. The French were doomed as long as Wellington held out until the end of the day and that's what happened.

I've been to the battlefield twice. Here's a photo from 2010 when I went with my daughter, son-in-law, and newly born granddaughter. The big hill behind them was made for tourists so they could get an overview of the battlefield from the top. Most people think it ruined the site.

There are monuments to various military leaders all over the battlefield. Most of the thousands of men who died that day have no monuments to mark where they fell. One of Ms. Sandwalk's distant cousins, Isabella Hood, was married to John Whyte of the British Dragoons. He died at Waterloo. His wife moved to Canada.

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Saturday, June 17, 1815

After the defeat at Ligny, the Prussians retreated in good order to Wavre and by Saturday, June 17th a large part of the Prussian army had reached that town.

Meanwhile, Wellington had massed his forces on the ridge south of Mont St. Jean and he was fortifying the farm at Hougoumont on his right and the village of Papelotte on his left. In addition, he placed a garrison in La Haye Sainte, a farm right in front of his center on the main road to Brussels. As usual, most of Wellington's troops were posted on the reverse slope of the ridge where they could not be easily seen by the advancing French army and they were partially protected from cannon fire.

The map on the right (above) shows the positions of the armies on each day. As you can see, the Prussians were well-positioned to come to the aid of Wellington by advancing troops from Wavre toward the battlefield at Mont St. Jean (Waterloo). Wellington and Blücher were in touch during this day of preparation and Blücher promised to attack the French right on the following day.

The map on the right (above) shows Grouchy marching off to the East but this is not accurate. Grouchy did keep in touch with the Prussians retreating down the road to Wavre and there was a battle at Wavre the next day. However, Grouchy did not press the Prussians as hard as he should have and he did nothing to prevent them from coming to the aid of Wellington the next day. All historians agree that this failure on the part of Grouchy played a major role in Napoleon's defeat. The second map is a bit better.

Napoleon joined Ney at Quatre-Bras and pursued the Anglo-Dutch army down the road to Brussels. The French were not able to bring up their forces very quickly so they were not in position to attack on the 17th.

By that evening the French had amassed 48,000 infantry, 14,000 cavalry, and 250 guns. Wellington's force consisted of 50,000 infantry, 11,000 cavalry, and 150 guns. The Prussians committed 48,000 men out of a force twice that size.

There was a heavy rain that evening. The men huddled in their tents knew that the decisive battle would be fought the next day and thousands of them would never live to see another night.

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Friday, June 16, 1815

Napoleon's Army of the North had crossed the Belgian frontier and was advancing toward Brussels. Napoleon had surprised the allied armies with his rapid advance and now they choose the risky strategy of a forward concentration in the face of an enemy attack. The Prussians had an easier task since they choose to concentrate their army at Ligny covering their supply lines to the East. The forward outposts fall back to Ligny under pressure from the French right under Grouchy. [see Battle of Waterloo]

On Thursday evening Wellington attended a ball given by the Duchess of Richmond in Brussels and it wasn't until the early hours of Friday the 16th that he gave orders to concentrate the Anglo-Dutch army at Quatre-Bras. Prince Orange was ordered to hold Quatre-Bras until the rest of the army arrived.

Wellington's strategy was to stay in contact with the Prussians at Ligny where the combined armies could defeat Napoleon. Napoleon's goal was to prevent the allied armies from supporting each other and crush one of them with overwhelming superiority of numbers. As it turned out, neither strategy succeeded on Friday, June 16th.

Ney held the Anglo-Dutch troops at bay around Quatre-Bras in a tough battle with heavy losses. He eventually took the crossroads at Quatre-Bras only to be driven back when Wellington arrived with fresh troops. Meanwhile, Napoloeon attacked the Prussians at Ligny with Grouchy's corps and the reserve that had been under his personal command. The Prussians were defeated but not destroyed [Battle of Ligny].

The map (left) shows the positions on Friday evening as the Prussian center collapses. It also shows the wandering of D'Erlon's corps that never got into either battle. It it had attacked the flank of the Prussian army Napoleon might have gained a decisive victory and if it had supported Ney it could have prevented Wellington's army from using the crossroads at Quatre-Bras. [see Waterloo: Myth and Reality]

Now comes one of the decisive moments of the Waterloo campaign. Blücher's Prussians retreated in orderly fashion on Wavre where he could remain in touch with Wellington who was forced to fall back to Wavre after the position at Quatre-Bras became untenable. Grouchy was ordered to pursue Blücher and prevent the Prussians from supporting the Anglo-Dutch army. Grouchy failed to do this because his corps did not move quickly and was confused about the direction of the Prussian retreat. As we shall see, Grouchy's failure is blamed for the defeat at Waterloo two days later.

Meanwhile, Wellington was able to fall back to a defensive position at Waterloo where he waited for the French army.

"Ligny by Ernest Crofts (1875). This representation of the battle shows Napoleon surrounded by his staff surveying the battlefield while columns of infantry advance to the front. The windmill at Brye on a hill, north west from Ligny, was a good vantage point and Blücher made it his headquarters during the battle, hence in this context it is an iconic symbol of Napoleon's victory." [Battle of Ligny]

Summoned to Waterloo: Brussels, dawn of June 16, 1815 by Robert Alexander Hillingford. Officers leaving the Duchess of Richmond's ball.

Quatre Bras (Black Watch at Bay) by William Barnes Wollen

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Thursday, June 15, 1815

It was 200 years ago today that Napoleon's army crossed the Belgian border at Charleroi and advanced on Quatre-Bras in order to split the Prussian and British armies. By occupying the central position, Napoleon hoped to defeat each army separately and occupy Brussels and the channel ports.

Neither Blücher nor Wellington were expecting such a rapid advance so Napoleon gained the element of surprise in the opening days of the campaign [Battle of Waterloo].

The Prussian outposts were quickly overrun and the army was ordered to assemble at Ligny. Napoleon's right, under Marshal Grouchy, pursued the retreating Prussians while the left, under Marshal Ney, marched on Quatre Bras in order to prevent the British army from uniting with the Prussians.

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James Hutton and John Playfair and a genealogical connection

I'm reading Eternal Ephemera by Niles Eldredge and learning about the early history of evolution and geology. Eldredge describes the work of James Hutton who is known as the father of modern geology. Here's the Wikipedia description of his work ...

He originated the theory of uniformitarianism—a fundamental principle of geology—which explains the features of the Earth's crust by means of natural processes over geologic time. Hutton's work established geology as a proper science, and thus he is often referred to as the "Father of Modern Geology".[2][3]

Through observation and carefully reasoned geological arguments, Hutton came to believe that the Earth was perpetually being formed; he recognised that the history of the Earth could be determined by understanding how processes such as erosion and sedimentation work in the present day. His theories of geology and geologic time,[4] also called deep time,[5] came to be included in theories which were called plutonism and uniformitarianism.

Why did they bury Darwin in Westminster Abbey?

I'm gradually starting to work on my book about evolution by accident. The first chapter is "Darwin Died in 1882." The point I'm making is that evolutionary biology is a 21st century discipline not one that's stuck in the nineteenth century.

I was re-reading an old article from the 2006 issue of Skeptical Inquirer with the title¹ I picked for this blog post. The author is W.G. Weyant, an historian at the University of Calgary (Calgary, Alberta, Canada). He says,

Why, then, did they bury Darwin in Westminster Abbey? The brief answer is "because he was dead," but that, while true, clearly is not the whole story."

The whole story is interesting because it reflects the attitudes of late Victorian society in England. This was a time when scientists were honored even if, or especially because, their ideas were upsetting. It appears to be an age when smart, rational, people were admired.

I don't know if this is still true in Europe but it's not true in Canada and it's certainly not true in the USA. Actors and singers are admired, but not intellectuals. I wonder what late Victorian society would have thought on seeing the memorial services for Francis Crick and Michael Jackson? I wonder what they would have thought of Ted Cruz?

Weyant also writes,

Approximately a decade after publication of the "Origin of Species" in 1859, most educated Englishmen, including many of the clergy, had accepted the fact of evolution. More that a few of them were uneasy about where the evidence and their reason were taking them, but they went nevertheless.

That's an interesting way of putting it. Today, we see many people who are faced with the same uneasiness but the response is quite different. When the choice is faith or facts, they choose not to follow the path of reason.

I think we're finally beginning to realize that science and religion are not compatible, confirming the worst fears of educated Victorians back in 1882. Jerry Coyne's new book is likely going to start a serious debate, one that has been largely ignored in the interests of accommodationism.

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1. I wasn't the first to do this; see Why did they bury Darwin in Westminster Abbey?

Happy 10th birthday to YouTube!

The first video was posted to YouTube on April 23, 2005 [see YouTube]. I took this photo (right) a few years ago near my daughter's place in Playa Vista, California. It's a production facility, YouTube Space LA, on the site of the former Howard Hughes airport.

The main purpose of this post is to give me an excuse to post one of my granddaughter's favorite YouTube videos (below top). She's a big fan of YouTube and so is my two year old grandson—he likes videos of rocket launches (below bottom).

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