On the "ethics" of germ line DNA editing

Edward Lanphier, Fyodor Urnov, Sarah Ehlen Haecker, Michael Werner and Joanna Smolenski have published a comment in Nature with a provocative headline "Don’t edit the human germ line. They are asking scientists to agree " not to modify the DNA of human reproductive cells." The idea is that editing the genome of sperm or egg cells produces changes that will be passed on to future generations and this poses certain dangers.

Physiologists fall for the Third Way

I looked forward to this "conversation" because I was already familiar with Denis Noble and his strange views of evolution [A physiologist thinks about evolution]. Noble reiterated his view of modern evolutionary theory at the meeting. He thinks that modern evolutionary theory (The Modern Synthesis or Neo-Darwinism) is all about random mutation and natural selection. He thinks it is based on the views of Richard Dawkins in The Selfish Gene. Neither he nor Michael Joyner (an anaethesiologist at the Mayo Clinic) have learned about random genetic drift or Neutral Theory and neither of them have much knowledge of population genetics. In other words, they are pretty ignorant about evolution even though they feel entitled to attack it.

The President and Vice-President arrive in Boston

There's a shuttle bus that runs between my hotel in Boston and the convention center where Experimental Biology takes place. I went down to the hotel lobby this morning to catch the shuttle bus. The first clue that something was amiss was the four policemen in their yellow jackets sitting in the lounge. Their big bikes were parked just outside. The second clue was a larger than normal number of people waiting for cabs and shuttle buses.

All of a sudden, the cops left and so did all the taxis and shuttles without any passengers. That was also a clue.

The hotel informed us that there would be no shuttles to the conference center this morning, no shuttles to the airport, and no taxis because the President of the United States and the Vice-President were arriving.¹ This requires shutting down I90 for several hours.

I decided to eat breakfast in the restaurant and wait out the disruption. (There wasn't anything interesting going on at the meeting this morning anyway.) I watched the motorcade go by on the Interstate. There were about a dozen cars lit up like Christmas trees, including an ambulance with lights flashing. Most of the lights were blue but there was a pretty mixture of yellow, red, orange, and green.

Judging by the number of angry people in the lobby, I can understand why the President and Vice-President need so much protection.

---

1. They are attending the opening of the Edward M. Kennedy Institute.

Interdisciplinary Research

I'm at the Experimental Biology meetings in Boston and yesterday I dropped into a session on "Training the Mind of an Interdisciplinary Scientist." There were talks on how to resolve disputes among member of the interdisciplinary team, and on how to choose a problem that your customers want solved (from an engineer). There are was also a talk from the University of Missouri-Kansas City about their graduate program. Every single graduate student has to choose an interdisciplinary problem for their thesis topic and they have to take a half dozen courses in each of two disciplines (at least).

The only experience I've had with being interdisciplinary is when I tried to understand what computer scientists were interested in and whether we could work together on some problems. We couldn't. The gap was too large. So biochemists have just adopted the tools and techniques of computational sciences and moved on.

Very few of my colleagues are doing interdisciplinary research and they seem to be getting along just fine. Is this whole "interdisciplinary" thing just a fad? Do you know anyone whose main area of investigation spans two distinct disciplines?

I got the distinct impression from the session that there's pressure from university administrations and granting agencies to become interdisciplinary. Is this true?

---

Plant biologists are confused about the meanings of junk DNA and genes

A recent issue of Nature contains a report on plant micro-RNAs (Lauressergues et al., 2015). The authors found that certain genes for plant micro-RNAs encoded short peptides in the micro-RNA precursors and those peptides seemed to have a biological function. What this means is that part of the longer precursor RNA that is cleaved to produce the final micro-RNA may have a function that wasn't recognized. If you thought that the part of the precursor that was thought to be discarded as useless junk was, in fact, junk, then you were wrong—at least for some genes.

This is not a big deal and the authors of the paper don't even mention junk DNA.

The paper was reviewed by Peter M. Waterhouse and Roger P. Hellens in the same issue (Waterhouse and Hellens, 2015). They think it's a big deal. Here's what they say,

Student essays about evolution

Students in my molecular evolution course have to write an essay. They can pick any topic they like as long as it's related to evolution and some controversy in the scientific literature. I have to approve the topic. The idea is that the students have to critically evaluate both sides of an issue and pick a side that they can defend.

The essays tell me a lot about what things are interesting in the course and how well the students understand the topics. Here are this year's topics.

• Education: Misconceptions in Evolutionary Biology
• Are Transposable Elements Junk?
• RNA World Hypothesis
• Evolutionary Psychology and Biology: A Comparison
• The End for the Alternative Search for Complexity
• C-Value Paradox: Why Junk DNA Looks So Good
• Will Humans Ever Be Perfectly Evolved?
• Epigenetic Inheritance: A Turning Point in Evolution?
• Back to Basics (about evolutinary biology eduaction)
• The Relationship between Natural Selection and Artificial Selection
• Foreign Gene Incorporation in Agriculture and in the wild: Debunking Anti-GMO Rhetoric and the "Unnatural" Fallacy
• Enhancers: An Evo-Devo Perspective
• Will humans stop evolving?
• Genomic Screening: Currently Not Worth the Trouble
• The Decade Long Argument Over Junk
• What Is a Gene?
• Sex: Is It Really Advantageous?
• A Critical Analysis of Stephen Meyer's Darwin's Doubt; The Explosive origin of Animal Life and the Case for Intelligent Design
• The Role of Natural Selection in the Process of Biological Human Evolution
• The Struggle Between Humans and Bacterial Evolution
• Drifting Away: Perspectives on Modern Evolution
• The Continuing Struggle Against Junk DNA
• The Evolution of Influenza A: Antigenic Drift at Work?

---

Another successful prediction of Intelligent Design Creationism?

The genetic code is redundant. Many amino acids have multiple codons ranging from two to six. The different codons for the same amino acid are called "synonymous" codons.

As sequences of protein-coding genes began to accumulate in the 1980s, it became apparent that different synonymous codons were used preferentially in different species. The phenomenon became known as codon bias. By 1990 it was known that the frequency of codon usage was correlated with tRNA abundance. As a general rule, there is a different tRNA for each codon and if multiple codons exist for a given amino acid then insertion of that amino acid into protein will depend on different tRNAs carrying the same amino acid.

Quantifying the "central dogma"

There was a short article in a recent issue of Science that caught my eye. The title was "Statistics requantitates the central dogma."

As most Sandwalk readers know, The Central Dogma of Molecular Biology says,

... once (sequential) information has passed into protein it cannot get out again (F.H.C. Crick, 1958)

The central dogma of molecular biology deals with the detailed residue-by-residue transfer of sequential information. It states that such information cannot be transferred from protein to either protein or nucleic acid. (F.H.C. Crick, 1970)

You might wonder how you can quantify the idea that once information gets into protein it can't flow back to nucleic acids. You can't, of course.

The authors are referring to the standard scheme of information flow from DNA to RNA to protein. This is often mistakenly referred to as the Central Dogma by those scientists who haven't read the original papers. In this case, the authors of the Science article are asking whether the levels of protein in different cells are mostly controlled at the level of transcription, translation, mRNA degradation, or protein degradation.

Mary Lyon (1925 - 2014)

Mary Lyon died on Christmas day last December. She was 89 years old.

She was a famous mouse geneticist who spend most of her working career at the MRC labs in Harwell, United Kingdom (near Oxford). The labs are known as an international center for mouse genetics.

Mary Lyon is famous for discovering the phenomenon of X chromosome inactivation. This is when one the the X chromosomes of female mammals is selectively inactivated so that the products of the X chromosome genes are quantitatively similar to the dosage in males where there's only one X chromosome. The phenomenon used to be referred to as Lyonization.

I never met Mary Lyon but from what people say about her, I'm sure I would have liked her. Here's an excerpt from the obituary in Nature: Mary F. Lyon (1925 - 2014).

Lyon was a central figure in twentieth-century mouse genetics. She laid the intellectual foundations and developed the genetic tools for the use of mice as model organisms in molecular medicine, cell and developmental biology and in deciphering the function of the human genome. Lyon was editor of Mouse News Letter from 1956 to 1970, a publication that had a key role in establishing a mouse-focused research community in the pre-Internet age. She also helped to develop a common language for the field by chairing the Committee on Standardised Genetic Nomenclature for Mice from 1975 to 1990. Her pivotal contribution was recognized by the naming of the Mary Lyon Centre, an international facility for mouse-genetic resources, opened at Harwell in 2004, and by the creation of the Mary Lyon Medal by the UK Genetics Society in 2014.

Because everything Mary said was so carefully thought through, she could be difficult to talk to: on the phone, it was easy to think you had been cut off. She did not suffer fools gladly, but was a great supporter of the bright young scientist, often eschewing authorship of publications to enhance the profile of junior collaborators. She was intellectually rigorous but not dictatorial. When I began my PhD with her in 1977, she gave me a handful of papers, showed me the genetic tools — mice carrying the various mutations and chromosomal rearrangements — and said, “do something on X-inactivation”. That degree of academic freedom was exhilarating, coupled as it was with the safety net of robust critique.

... Her first love was mice, although she always had a cat — a tortoiseshell, of course.

X chromosome inactivation is one of the classic examples of epigenetics, sensu stricto. It was the subject of one of my most popular posts of all time: Calico cats. Calico cats almost always have to be female but there are very rare examples of male calico cats. Can anyone figure out why?

---

On the handedness of DNA

Double-stranded DNA forms a helical structure where the two strands are twisted into a helical shape. If you think of the base pairs forming a ladder then imagine that the entire ladder could be distorted by rotating the ends relative to each other. The result would be the helical shape of DNA. The twisting results mainly from the attraction between the planar base pairs (rungs of the ladder.) They are "happier" when they are stacked close together right on top of each other. (The "force" is called "stacking interactions.")

This is not how DNA is actually built since there's never a time inside the cell when the DNA forms a ladder-like structure that's not helical, but you get the picture. [The Three-Dimensional Structure of DNA]

The final form of double-stranded DNA on the right is a cartoon used to illustrate certain features. I've deliberately drawn it with about 10-11 base pairs per turn so you can see the shape of the helix.

Conrad Black attacks the shabby, shallow world of the militant, atheist

Conrad Black, also known as Baron Black of Crossharbour, KSG, was stimulated by a conversation with Christian apologist, and physicist, John Lennox. Black decided to write a column for the National Post (Toronto, Canada): Conrad Black: The shabby, shallow world of the militant atheist.

Richard Dawkins tweeted ...

Conrad Black seems to be at large again. Spot the factual errors, illogicalities and failures to understand.

Good advice. I wonder how many can be packed into a brief diatribe?

Keep in mind that no matter how many strawmen are erected, the important issue is whether gods exist. If you are a Christian, and you are going to attack the "shabby, shallow world" of atheists then the very least you can do is present your strongest case for the existence of gods.

Check out Conrad's Black's evidence for the existence of gods. (Warning: you will have to ignore all the rhetoric about the benefits of religion because it isn't relevant. On the other hand, there's a certain enjoyable irony in reading about how Christians are more moral than atheists.)

---

How the genome lost its junk according to John Parrington

I really hate it when publishers start to hype a book several months before we can read it, especially when the topic is controversial. In this case, it's Oxford University Press and the book is "The Deeper Genome" Why there is more to the human genome than meets the eye." The author is John Parrington.

The title of the promotion blurb is: How the Genome Lost its Junk on the Canadian version of the Oxford University Press website. It looks like this book is going to be an attack on junk DNA.

We won't know for sure until June or July when the book is published. Until then, the author and the publisher will have free reign to sell their ideas without serious opposition or push back.

Here's the prepublication hype. I'm going to buy this book and read it as soon as it becomes available. Stay tuned for a review.

Junk DNA comments in the New York Times Magazine

It's always fun to be quoted in The New York Times Magazine but there's a more serious issue to discuss. I'm referring to a brief article about online comments after Carl Zimmer published a piece on "Is Most of Our DNA Garbage?" a few weeks ago. If you read the comments under that article you'll discover that we have a lot of work to do if we are going to convince the general public that our genome is full of junk.

Richard Lenski answers questions about the long-term evolution experiment (LTEE)

Richard Lenski has a blog called Telliamed Revisited. He's been answering questions about his long-term evolution experiment and the latest answers are at: Questions from Jeremy Fox about the LTEE, part 2.

"Did the LTEE have any hypotheses initially, and if so, how were you going to test them?

Short answer: Yes, the LTEE had many hypotheses, some pretty clear and explicit, some less so. (What, did you think I was swimming completely naked?)"

Well worth reading ....

---

Economist Stephen Moore explains why we should mistrust science.

Stephen Moore is an conservative economist who writes for the Wall Street Journal. Here's a quote from the Wikipedia article ...

In a February 2, 2011 appearance on HBO's Real Time with Bill Maher, Moore stated "I say the Reagan tax cuts were the greatest economic policy of the last 50 years" and added "the lowest income people had the biggest gains" during the 1980s. Politifact.com found Moore's assertion to be false.

Moore thinks he's in a position to explain why scientists should not be trusted [The myth of ‘settled science’].

The magazine [National Geographic] is incredulous that so many skeptics "believe that climate activists are using the threat of global warming to attack the free market and industrial society generally."

Wait. Climate change activists are using the issue as a means of attacking free-market capitalism. This past summer major environmental groups gathered in Venezuela to solve leading environmental problems like global warming, concluding: “The structural causes of climate change are linked to the current capitalist hegemonic system.”

How is it paranoia to believe that the climate change industry wants to shut down capitalism when the movement plainly states that this is its objective? And how can a movement be driven by science when its very agenda violates basic laws of economics? I am no scientist, but I’m highly skeptical of a movement whose first advice is to steer the U.S. economy off a cliff toward financial ruin.

Well, there you have it. According to Stephen "I am no scientist" Moore, science can't be trusted because it violates the basic laws of economics, like those laws that Ronald Reagan must have obeyed when he instituted the greatest economic policy of the last 50 years.

QED

---