How to define evolution?

Do you think this video is helpful? [see "What Is Evolution?"] Is it important to know that evolution requires genetic changes and that it's populations that evolve? Is it important to have a definition of evolution that covers antibiotic resistance in bacteria and blood types in humans?

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Correcting the correction of a video about evolution

Charlie McDonnell is the author of a book called Fun Science: A Guide To Life, The Universe And Why Science Is So Awesome. He made a video on misconceptions about the theory of evolution (see below). Sally Le Page (below left) is an evolutionary biologist working on her Ph.D. at Oxford (UK). She noticed a few problems with the McDonnell video so she made one of her own to correct the misconception in the first video. Now it's my turn to correct the misconception in the video that corrects the first video!

Sally Le Page highlights six misconceptions in the McDonnell video. She points out that none of them are very important—they are "little niggles"—but she still thinks a comment is necessary. (I agree.)

What's in Your Genome? Chapter 4: Pervasive Transcription

I'm working (slowly) on a book called What's in Your Genome?: 90% of your genome is junk! The first chapter is an introduction to genomes and DNA [What's in Your Genome? Chapter 1: Introducing Genomes ]. Chapter 2 is an overview of the human genome. It's a summary of known functional sequences and known junk DNA [What's in Your Genome? Chapter 2: The Big Picture]. Chapter 3 defines "genes" and describes protein-coding genes and alternative splicing [What's in Your Genome? Chapter 3: What Is a Gene?].

Chapter 4 is all about pervasive transcription and genes for functional noncoding RNAs.

Chapter 4: Pervasive Transcription

• How much of the genome is transcribed?
• How do we know about pervasive transcription?
• Different kinds of noncoding RNAs
•         Box 4-1: Long noncoding RNAs (lncRNAs)
• Understanding transcription
•         Box 4-2: Revisiting the Central Dogma
• What the scientific papers don’t tell you
•         Box 4-3: John Mattick proves his hypothesis?
• On the origin of new genes
• The biggest blow to junk?
•         Box 4-4: How do you tell if it’s functional?
• Biochemistry is messy
• Evolution as a tinkerer
•         Box 4-5: Dealing with junk RNA
• Change your worldview

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What's in Your Genome? Chapter 3: What Is a Gene?

I'm working (slowly) on a book called What's in Your Genome?: 90% of your genome is junk! The first chapter is an introduction to genomes and DNA [What's in Your Genome? Chapter 1: Introducing Genomes ]. Chapter 2 is an overview of the human genome. It's a summary of known functional sequences and known junk DNA [What's in Your Genome? Chapter 2: The Big Picture]. Here's the TOC entry for Chapter 3: What Is a Gene?. The goal is to define "gene" and determine how many protein-coding genes are in the human genome. (Noncoding genes are described in the next chapter.)

Chapter 3: What Is a Gene?

• Defining a gene
•         Box 3-1: Philosophers and genes
• Counting Genes
• Misleading statements about the number of genes
• Introns and the evolution of split genes
• Introns are mostly junk
•         Box 3-2: Yeast loses its introns
• Alternative splicing
•         Box 3-2: Competing databases
• Alternative splicing and disease
•         Box 3-3: The false logic of the argument from         complexity
• Gene families
• The birth & death of genes
•         Box 3-4: Real orphans in the human genome
• Different kinds of pseudogenes
•         Box 3-5: Conserved pseudogenes and Ken Miller’s         argument against intelligent design
• Are they really pseudogenes?
• How accurate is the genome sequence?
• The Central Dogma of Molecular Biology
• ENCODE proposes a “new” definition of “gene”
• What is noncoding DNA?
• Dark matter

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What's in Your Genome? Chapter 2: The Big Picture

I'm working (slowly) on a book called What's in Your Genome?: 90% of your genome is junk! I thought I'd post the TOC for each chapter as I finish the first drafts. Here's chapter 2.

Chapter 2: The Big Picture

• How much of the genome has been sequenced?
• Whose genome was sequenced?
• How many genes?
• Pseudogenes
• Regulatory sequences
• Origins of replication
• Centromeres
• Telomeres
• Scaffold Attachment regions (SARs)
• Transposons
• Viruses
• Mitochondrial DNA (NumtS)
• How much of our genome is functional?

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What's in Your Genome? Chapter 1: Introducing Genomes

I'm working (slowly) on a book called What's in Your Genome?: 90% of your genome is junk! I thought I'd post the TOC for each chapter as I finish the first drafts. Here's chapter 1.

Chapter 1: Introducing Genomes

• The genome war
• What is DNA?
• Chromatin
• How big is your genome?
• Active genes?
• What do you need to know?

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Another physicist teaches us about evolution

Michio Kaku is a theoretical physicist at the City College of New York. Like many physicists, he thinks he's smart enough to know everything about everything so he doesn't hesitate to lecture people about evolution.

In this case. He's telling us that humans have reached perfection in all adaptive traits so there can't be any more selection for things like bigger brains. He tells us that human evolution has stopped because no animals are chasing us in the forest any more. He also let's us know that there are no more isolated populations because of jet planes. Watch the video to see how little he understands.



Is there something peculiar about physicists? Does anyone know of any biologists who make YouTube videos about quantum mechanics or black holes? If not, is that because biologists are too stupid ... or too smart?

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Sloppiness in translation initiation

There are two competing worldviews in the fields of biochemistry and molecular biology. The distinction was captured a few years ago by Laurence Hurst commenting on pervasive transcription when he said, "So there are two models; one, the world is messy and we're forever making transcripts we don't want. Or two, the genome is like the most exquisitely designed Swiss watch and we don't understand its working. We don't know the answer—which is what makes genomics so interesting." (Hopkins, 2009).

I refer to these two world views as the Swiss watch analogy and the Rube Goldberg analogy.

The distinction is important because, depending on your worldview, you will interpret things very differently. We see it in the debate over junk DNA where those in the Swiss watch category have trouble accepting that we could have a genome full of junk. Those in the Rube Goldberg category (I am one) tend to dismiss a lot of data as just noise or sloppiness.

Did Rosalind Franklin produce the first X-ray diffraction images of DNA?

There's an interesting video of ten famous women scientists at Interesting S_Word: [Top 10 Female Scientists of History]. The image of Rosalind Franklin caught my eye (see right).

Perhaps I'm nitpicking but fake news is all the rage these days so I think we'd better be extra careful to present real facts rather than alternative facts. In that spirit, I'll mention two things.

Dan Graur explains junk DNA

If you want to be a serious participant in the debate over junk DNA then you should watch this video. Dan Graur presents the standard arguments for junk DNA—most of which have been around for decades. He also destroys the main arguments against junk DNA. You are entitled to choose sides in this debate but you are not entitled to pose as an authority unless you know the best arguments from BOTH sides. It is not sufficient to just quote evidence for function as support for your bias. You must also refute the evidence for junk. You have to show why it is wrong or misleading.

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Hat Tip: PZ Myers

ENCODE workshop discusses function in 2015

A reader directed me to a 2015 ENCODE workshop with online videos of all the presentations [From Genome Function to Biomedical Insight: ENCODE and Beyond]. The workshop was sponsored by the National Human Genome Research Institute in Bethesda, Md (USA). The purpose of the workshop was ...

1. Discuss the scientific questions and opportunities for better understanding genome function and applying that knowledge to basic biological questions and disease studies through large-scale genomics studies.
2. Consider options for future NHGRI projects that would address these questions and opportunities.

The main controversy concerning the human genome is how much of it is junk DNA with no function. Since the purpose of ENCODE is to understand genome function, I expected a lively discussion about how to distinguish between functional elements and spurious nonfunctional elements.

Darwin Day 2017

Today is Darwin Day but I'm too busy with other things to write a new post in his honor. So here's a post from 2007 (slightly updated) to help you enjoy the day.

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Today is the birthday of the greatest scientist who ever lived. When you visit Darwin's home (Down House) you get a sense of what he must have been like. One of the things that's obvious is the number of bedrooms for the children. The house must have been alive with the activities of young children. It's no wonder that Darwin needed some peace and quiet from time to time.

Gwen Raverat was Darwin's granddaughter (daughter of George Darwin). She described Down House as she knew it in the years shortly after Darwin died.

Of all places at Down, the Sandwalk seemed most to belong to my grandfather. It was a path running round a little wood which he had planted himself; and it always seemed to be a very long way from the house. You went right to the furthest end of the kitchen garden, and then through a wooden door in the high hedge, which quite cut you off from human society. Here a fenced path ran along between two great lonely meadows, till you came to the wood. The path ran straight down the outside of the wood--the Light Side--till it came to a summer-house at the far end; it was very lonely there; to this day you cannot see a single building anywhere, only woods and valleys.

I became interested in Darwin's children about fifteen years ago when I first began to appreciate the influence they had on his life. We all know the story of Annie's death when she was ten years old and how this led to Darwin's rejection of religion. There were other tragedies but Charles and Emma turned out to be very good parents.

Here's a short biography of each of Darwin's children from AboutDarwin.com

William Erasmus Darwin
The first of Darwin's children was born on December 27, 1839. He was a graduate of Christ’s College at Cambridge University, and was a banker in Southampton. He married Sara Ashburner from New York, but they had no children. William died in 1914.

Anne Elizabeth Darwin
Born on March 2 1841, and died at the age of ten of tuberculosis on April 22, 1851. It was the death of Annie that radically altered Darwin’s belief in Christianity.

Mary Eleanor Darwin
Born on September 23, 1842 but died a few weeks later on October 16th.

Henrietta Emma Darwin ("Etty")
Born on September 25, 1843 and married Richard Buckley Litchfield in August of 1871. She lived 86 years and edited Emma's (her mother) personal letters and had them published in 1904. She had no children.

George Howard Darwin
Born on July 9, 1845. He was an astronomer and mathematician, and became a Fellow of the Royal Society ... in 1879. In 1883 he became the Plumian Professor of Astronomy and Experimental Philosophy at Cambridge University, and was a Barrister-at-Law. He studied the evolution and origins of the solar system. George married Martha (Maud) du Puy from Philadelphia. They had two sons, and two daughters. He died in 1912.

Elizabeth Darwin
Born on July 8, 1847 and died in 1926. She never married and had no children.

Francis Darwin
Born on August 16, 1848. He became a botanist specializing in plant physiology. He helped his father with his experiments on plants and was of great influence in Darwin's writing of "The Power of Movement in Plants" (1880). He was made a Fellow of the Royal Society in 1879, and taught at Cambridge University from 1884, as a Professor of Botany, until 1904. He edited many of Darwin's correspondence and published "Life and Letters of Charles Darwin" in 1887, and "More Letters of Charles Darwin" in 1903. He also edited and published Darwin’s Autobiography. He married Amy Ruck but she died when their first child, Bernard, was born in September of 1876. He then married Ellen Crofts in September of 1883, and they had one daughter, Frances in 1886. Francis was knighted in 1913, and died in 1925.

Leonard Darwin
Born on January 15, 1850. He became a soldier in the Royal Engineers in 1871, and was a Major from 1890 onwards. He taught at the School of Military Engineering at Chatham from 1877 to 1882, and served in the Ministry of War, Intelligence Division, from 1885-90. He later became a liberal-unionist MP for the town of Lichfield in Staffordshire 1892-95, and was president of the Royal Geological Society 1908-11. Leonard married Elizabeth Fraser in July of 1882. He married a second time, but had no children and died in 1943.

Horace Darwin
Born on May 13, 1851. He was a graduate of Trinity College, Cambridge, and became an engineer and a builder of scientific instruments. In 1885 he founded the Cambridge Scientific Instrument Company. He was the Mayor of Cambridge from 1896-97, and was made a Fellow of the Royal Society in 1903. Horace married Emma Farrer in January of 1880 and they had three children. He died in 1928.

Charles Waring Darwin
Born on December 6, 1856 but died on June 28 1858.

This is something I wrote about my visit to Westminster Abby 17 years ago.

Eventually we wind around the Monastery and finally enter the Nave. Ignoring the monument to Winston Churchill (1874-1965) and hardly bothering to look up and admire the high ceiling, I head for the front of the church where I can see the statue of Isaac Newton (1643-1727). This is the same statue that plays such an important role in the Da Vinci Code but today I’m not interested in Newton or his orb. I takes me only a few seconds to find the marked stone on the floor. I’m standing on the grave of Charles Robert Darwin.

I can picture the scene on Wednesday, April 26, 1882—a grand funeral attended by all of London’s high society and the leading intellectuals of the most powerful nation in the world. Darwin would not have been pleased. He wanted to be buried quietly in the Downe cemetery with his brother Erasmus and two of his children. Darwin's family was persuaded by his friends Galton, Hooker, Huxley and the President of the Royal Society, William Spottiswoode, that, for the sake of England, Darwin should be laid to rest in Westminster Abbey. As Janet Browne writes in her biography of Charles Darwin, "Dying was the most political thing Darwin could have done."

Looking around I can see the tomb of Joseph Hooker and a memorial to Alfred Wallace, two of the scientists who were Darwin’s pallbearers. (Another pallbearer, Thomas Henry Huxley, is buried elsewhere.) Nearby are the final resting places of a host of famous scientists; Kelvin, Joule, Clerk-Maxwell, Faraday, Herschell, and Sir Charles Lyell. Lyell was Darwin’s hero and mentor. We are told that Darwin’s wife Emma wished he were buried closer to Lyell.

I am not overly sentimental but this visit has a powerful effect. I think Charles Darwin is the greatest scientist who ever lived—yes, even greater than Sir Isaac Newton whose huge statue overshadows Darwin’s humble marker in the floor. Natural selection is one of the greatest scientific ideas of all time. Darwin discovered it and he deserves most of the credit. But Charles Darwin died on April 19 in 1882 and that was a long time ago.

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What did ENCODE researchers say on Reddit?

ENCODE researchers answered a bunch of question on Reddit a few days ago. I asked them to give their opinion on how much junk DNA is in our genome but they declined to answer that question. However, I think we can get some idea about the current thinking in the leading labs by looking at the questions they did choose to answer. I don't think the picture is very encouraging. It's been almost five years since the ENCODE publicity disaster of September 2012. You'd think the researchers might have learned a thing or two about junk DNA since that fiasco.

The question and answer session on Reddit was prompted by award of a new grant to ENCODE. They just received 31.5 million dollars to continue their search for functional regions in the human genome. You might have guessed that Dan Graur would have a few words to say about giving ENCODE even more money [Proof that 100% of the Human Genome is Functional & that It Was Created by a Very Intelligent Designer @ENCODE_NIH].

NIH and UCSF ENCODE researchers are on Reddit right now!

Check out Science AMA Series: We’re Drs. Michael Keefer and James Kobie, infectious .... (Thanks to Paul Nelson for alerting me to the discussion.)

Here's part of the introduction ...

Yesterday NIH announced its latest round of ENCODE funding, which includes support for five new collaborative centers focused on using cutting edge techniques to characterize the candidate functional elements in healthy and diseased human cells. For example, when and where does an element function, and what exactly does it do.

UCSF is host to two of these five new centers, where researchers are using CRISPR gene editing, embryonic stem cells, and other new tools that let us rapidly screen hundreds of thousands of genome sequences in many different cell types at a time to learn which sequences are biologically relevant — and in what contexts they matter.

Today’s AMA brings together the leaders of NIH’s ENCODE project and the leaders of UCSF’s partner research centers.

Your hosts today are:

Nadav Ahituv, UCSF professor in the department of bioengineering and therapeutic sciences. Interested in gene regulation and how its alteration leads to morphological differences between organisms and human disease. Loves science and juggling.
Elise Feingold: Lead Program Director, Functional Genomics Program, NHGRI. I’ve been part of the ENCODE Project Management team since its start in 2003. I came up with the project’s name, ENCODE!
Dan Gilchrist, Program Director, Computational Genomics and Data Science, NHGRI. I joined the ENCODE Project Management team in 2014. Interests include mechanisms of gene regulation, using informatics to address biological questions, surf fishing.
Mike Pazin, Program Director, Functional Genomics Program, NHGRI. I’ve been part of the ENCODE Project Management team since 2011. My background is in chromatin structure and gene regulation. I love science, learning about how things work, and playing music.
Yin Shen: Assistant Professor in Neurology and Institute for Human Genetics, UCSF. I am interested in how genetics and epigenetics contribute to human health and diseases, especial for the human brain and complex neurological diseases. If I am not doing science, I like experimenting in the kitchen.

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A philosopher tells us how to think clearly about evolutionary causes ... avoid adaptationism

I think philosophy has lost its way. The discipline gives credence to religious philosophers who write about god(s) and to other philosophers who reject determinism and think the mind-body problem is still an open question. Philosophers still debate the validity of the ontological argument. Philosophers of science have not even settled the question of what is science, let alone come up with a valid answer of how to do it. There are few other disciplines that are still respected after several hundred years of trying, and failing, to answer the most fundamental questions in their field. Many academic philosophy department are hotbeds of political correctness and just plain politics.

Imagine No Religion 7 (Toronto, June 2-4, 2017)

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Ricky Gervais explains atheism

Watch Ricky Gervais explain atheism to Stephen Colbert. I like his explanation of the difference between science and religion. In fact, I like it so much I'm going to embellish it a bit and present it here ...

Imagine what would happen after a giant meteor strike that wipes out everyone except for a small native tribe in the Andes that had no contact with other people before the apocalypse. All books and all knowledge will be destroyed.

Ten thousand years later there will be science books and they'll be pretty much the same as the ones we have now because people will simply rediscover the basic truths of nature. There might be religious books but they won't be anything like the holy books we have now because the people will have invented entirely new gods. That's the difference between science and religion.

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Why is life the way it is?

Nick Lane is very good at explaining complex biology and biochemistry. He is the winner of the Royal Society's Michael Faraday Prize for 2016. Here's his lecture. It's worth watching if you want to understand the latest informed (naturalistic) speculations on the origin of life.

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Trying to educate a creationist (Otangelo Grasso)

Otangelo Grasso is a creationist who's convinced he can learn to understand biochemistry by reading what's on the internet and copy-pasting it into his website. He then takes that limited knowledge and concludes that evolution is impossible. He often poses "gotcha" questions based on his flawed understanding.

His behavior isn't very different from most other creationists who suffer from Dunning-Kruger Disease but he happens to be someone who I thought could be educated.

I was wrong.

Over the years I've tried to correct a number of errors he's made so we could have an intelligent discussion about evolution. You can't have such a discussion if one side ignores facts and refuses to learn. Here's an example of a previous attempt: Fun and games with Otangelo Grasso about photosynthesis. Here's a post from yesterday showing that I wasted my time: Otangelo Grasso on photosynthesi.

Discovery Institute publishes another anti-evolution book

It's not Saturday morning but you can enjoy this cartoon anyway.

Tom Bethell ... writes like a dream.
                      —Fred Barnes

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Scientists confused about photosynthesis - press release makes it worse

Photosynthesis is the series of reactions that capture light energy and use it to make ATP and sometimes reducing equivalents (e.g NADPH). There are many different versions of photosynthesis. One of the simplest is found in purple bacteria where the process results in formation of a proton gradient that's used to drive ATP synthesis.

The evolution of the citric acid cycle

I just realized that I don't have a post devoted to the evolution of the citric acid cycle. This need to be remedied since I often talk about it. It's a good example of how an apparently irreducibly complex pathway can arise by evolution. It's also a good example to get students to think outside of the box. Undergraduate biochemistry courses usually concentrate on human physiology and too often students transfer that bias to all other species. They assume that what happens in humans is what happens in plants, fungi, protozoa, and bacteria.¹

Here's what the standard citric acid cycle looks like (Moran et al., 2011 p. 393).

Once again, the IDiots don't understand evolution

This is so frustrating. I've been debating creationists for almost 30 years. My colleagues and I have tried time and time again over those three decades to educate them about real evolutionary theory. We've also tried to teach them about the difference between evolution and the history of life. In order to explain the history of life on Earth you need to account for mass extinctions and other chance events that have nothing to do with evolution. They refuse to listen.

The latest evidence is a recent post by David Klinghoffer [Theory of Evolution? Call It a "Narrative" Instead]. He says,

The theory of evolution by natural selection operating on random mutations, as a sweeping explanation for life and how it got there, is a "narrative." It presents a very smooth story, persuasive to most scientists. The facts may all be true, but the conclusion: BS.

No knowledgeable scientist thinks that natural selection is the only mechanism of evolution so no knowledgeable scientist thinks that mutation + selection explains the history of life. That's just BS. Not only are scientists aware of what modern evolutionary theory actually says but they're also aware of other factors that determined the history of life.

Now you know why we call them IDiots. What is it that makes them so resistant to learning about the ideas they so adamantly oppose? They can still oppose correct ideas if they want. Isn't that better than fighting strawmen?

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Why does the human population carry an allele that increases the risk of Alzheimer's?

The human apolipoprotein E gene (ApoE) has several alleles segregating in the human population. One of them, E4, is associated with increased risk of Alzheimer's. Ed Yong, writing for The Atlantic, asks "Why Do Humans Still Have a Gene That Increases the Risk of Alzheimer's?

I can think of several answers off the top of my head. The most important one is that Alzheimer's has very little effect on your ability to have children. The disease may not even have developed in most of our ancestors who tended to die younger. In order to be subject to negative selection the allele has to affect adults before they reproduce.

The second reason is that the slight deleterious effect, if there is one from an evolution perspective, may not have been significant enough in small populations. I know, and I hope my students know, that neutral and deleterious alleles can reach significant frequency in a population by chance. The general public doesn't know this.

Check out Ed Yong's article to see his explanation.

“It doesn’t make sense,” says Ben Trumble, from Arizona State University. “You’d have thought that natural selection would have weeded out ApoE4 a long time ago. The fact that we have it at all is a little bizarre.”

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The pervasive transcription controversy: 2002

I'm working on a chapter about pervasive transcription and how it relates to the junk DNA debate. I found a short review in Nature from 2002 so I decided to see how much progress we've made in the past 15 years.

Most of our genome is transcribed at some time or another in some tissue. That's a fact we've known about since the late 1960s (King and Jukes, 1969). We didn't know it back then, but it turns out that a lot of that transcription is introns. In fact, the observation of abundant transcription led to the discovery of introns. We have about 20,000 protein-coding genes and the average gene is 37.2 kb in length. Thus, the total amount of the genome devoted to these genes is about 23%. That's the amount that's transcribed to produce primary transcripts and mRNA. There are about 5000 noncoding genes that contribute another 2% so genes occupy about 25% of our genome.

Pyruvate dehydrogenase astonishes Ann Gauger

Ann Gauger was reading a cell paper the other day [Digging Deep in Biology: "Things Get Even More Complicated When You Look Closer"]. The subject was the localization of citric acid cycle enzymes and pyruvate dehydrogenase (PDH). She did a little digging and this is what astonished her ...

... so I looked up pyruvate dehydrogenase and found to my astonishment that it is not one enzyme but an enormous complex of three different enzymatic activities clustered together on a cube-shaped core of 24 units, or alternatively a dodecahedral core of 60 units. The enzymes work together to turn pyruvate into acetyl CoA in a three-step process, handing off to each other as the reaction proceeds.

Why are most biologists adaptationists?

I enjoyed listening to Michael Lynch's talk on Friday. Much of what he said has been covered in Sandwalk over the past few years. His main point was that nothing in biology makes sense except in the light of population genetics. He laments the fact that most biologists, and even most evolutionary biologists, don't have a firm grasp of population genetics and the importance of random genetic drift.

I asked him why he thought this was true. He said he didn't know why. I think he was being polite. If you read his book, "The Origins of Genome Architecture," you'll see that he attributes this phenomeon to ignorance of modern evolutionary theory.

The dynamic duo tell us about five problems with evolution

Here's a link to a remarkable radio interview with Stephen Meyer and Doug Axe. The subject is the Royal Society meeting last November on New trends in evolutionary biology: biological, philosophical and social science perspectives. The theme is not Intelligent Design Creationism, instead it's all about so-called problems with evolutionary theory. That's really what ID is all about in spite of what the IDiots may claim. [see A Royal Pain: Stephen Meyer and Douglas Axe on Five Problems for Evolution.]

Here are the five problems according to IDiots.

1. Fossil record (Cambrian explosion)
2. The origin of information (no known natural source of information)
3. The necessity of early mutations (you can't mutate regulatory genes that act early in development because all mutations in those genes are lethal)
4. Epigenetic information (you can't evolve new body plans by mutating DNA because development is controlled by non-DNA epigenetic information)
5. The universal design intuition that we all have (everybody thinks that people are created by a god-like designer, even atheists, so it must be true)

What the heck is epigenetics?

"Epigenetics" is the (relatively) new buzzword. Old-fashioned genetics is boring so if you want to convince people (and grant agencies) that you're on the frontlines of research you have to say you're working on epigenetics. Even better, you can tell them that you are on the verge of overthrowing Darwinism and bringing back Jean-Baptiste Lamarck.

But you need to be careful if you adopt this strategy. Don't let anyone pin you down by defining "epigenetics." It's best to leave it as ambiguous as possible so you can adopt the Humpty-Dumpty strategy.¹ Sarah C.P. Williams made that mistake a few years ago and incurred the wrath of Mark Ptashne [Core Misconcept: Epigenetics].