Ethical Issues in Science

 
One of the things I have to do this week is deal with the teaching of so-called "ethics" in genetics and biochemistry courses. Let me give you two examples in order to focus the debate: genetically modified foods, and a proper diet.

It's almost a requirement these days that introductory genetics courses include a section on genetically modified crops. This invariably leads to tutorials, or labs, or essays, about whether GM-foods are a good thing or not. These discussions are usually lots of fun and the students enjoy this part of the course. Professors are convinced they are teaching ethics and that it's a good thing to show students that ethics is an important part of science.

In introductory biochemistry courses we often have a section on fuel metabolism. That's the part of biochemistry that deals specifically with how your food is converted to energy. It's human biochemistry. In that section of the course the Professor often raises the question of proper diet. Is it okay to eat meat? Are trans fatty acids bad for you? Should you be eating carbohydrates? Our experience is that Professors who teach this section often have very strong opinions and their personal ethical stance is portrayed as scientific fact.

These are two different cases. In the first one, the question is whether the value of debating controversial "ethical" issues outweighs the disadvantages. The biggest downside, in my opinion, is the emphasis on technology as opposed to pure basic science. By giving prominence to "ethical" issues we are emphasizing the consequences of genetic knowledge as it relates to the human condition.

I prefer to spend my time trying to convince students that knowledge for its own sake is valuable. It's hard to do that if the fun part of the course has to do with the application of genetic technology in the creation of genetically modified foods.

The second case involves a different kind of ethics. Here, the students aren't debating whether you should eat trans fatty acids or not. They are being given an ethical perspective disguised as a scientific fact. I don't think this is a good idea. At the very least, the issue should be presented as controversial and students should be encouraged to read the medical literature; which, by the way, has very little to do with the biochemistry being taught in class.

Should students be discussing the benefits of the Atkins diet? Perhaps, but it should be a discussion and not a lecture, right? And does a focus on human eating behavior detract from the importance of basic scientific knowledge? I think it does.

Part of the problem arises from a desire to please the students. How often do we hear the complaint that students aren't interested in biochemistry and genetics? The students are bored by science so we have to add sections on genetically modified foods and genetic screening to our introductory genetics courses. Isn't this strange? Rather than concentrate on making the basic science as interesting and exciting as possible, we cater to the students by giving them the topics they think are interesting. That's no way to educate.

There's another problem; what is ethics? Sometimes it's hard to see the difference between simple controversy and ethics. Sometimes it's hard to define exactly what "ethics" is all about in spite of the fact that "bioethics" is one of the biggest growth industries in science. Here's where a philosopher or two could weigh in.

Plastic Duckies

 
On January 29, 1992 a 40-foot container fell off a ship in the middle of the Pacific Ocean. Inside the container were 29,000 "Floatees," small bathtub toys. There were blue turtles, yellow ducks, red beavers, and green frogs. Over the next few years, these toys washed up on shores all around the Pacific, especially in Indonesia, Australia, and South America [Friendly Floatees].

The story of these Floatees has been told many times. For years beachcombers around the world have been talking about Beachcombing Science from Bath Toys.

Thousands of the Floatees drifted north where they passed through the Bering Straight and became locked in the pack ice north of the Arctic Circle. The prediction was that they would emerge into the Atlantic in 2003 and, sure enough, Floatees started to turn up in New England and Great Britain. More are expected this year [Drake's other armada].

There's a picture of a plastic duckie on the cover of this month's Harpers magazine. The feature story is MOBY-DUCK: Or, the Synthetic Wilderness of Childhood by Donovan Holn. It's a wonderful read. Donaovan Holn has weaved together the story of the Floatees and his personal voyage of discovery. As you follow along you will learn about ocean currents, flotsam and jetsam, beachcombing, childhood, and so much more.

Astrobiology: A Null Set

 
Phil Plait of Bad Astronomy recently lost out to PZ Mierz of Pharyngula in the contest for best blog. His penalty for not getting enough astronomy enthusiasts to cast ballots is to write something about biology.

So naturally he chooses Astrobiology as his example— a discipline without a single living example. Typical astronomer, taking the easy way out.

As I tell my students, biology is much harder than physics and astronomy. Any biologist can handle physics with their eyes closed but physics students (and Professors) are afraid of biology. It's way too messy for them.

The Logic of Irreducible Complexity

 
Ross Thomas (HALFaCANUCK) uses predicate calculus to analyze whether the following argument,

the irreducibly complex nature of the eye proves God's existence

is logically correct. [Irreducible illogicality] The answer will surprise you.

P.S. Don't tell the IDiots about this one!

Alanis Morissette Doesn't Get Irony

 
Guy Kawasaki interviews Jon Winokur [Ten Questions with Jon Winokur: How to Heighten Your Sense of the Absurd]. In response to a question about what he's working on now (Q12) Winokur say he's writing a book called The Big Curmudgeon. Winokur then goes ont to say,

It drives me crazy when people say “ironic” when they mean “coincidental.” The classic example is Morissettian Irony, which I define in the book as “irony based on a misapprehension of irony, i.e., no irony at all.” It’s named for the pop singer Alanis Morissette, whose hit single, “Ironic” mislabels coincidence and inconvenience as irony.

In the song, situations purporting to be ironic are merely sad, random, or annoying (“It's a traffic jam when you're already late/It's a no-smoking sign on your cigarette break”). In other words, “Ironic” is an un-ironic song about irony. Which, of course, is ironic in itself. But wait, there’s more, a “bonus irony” if you will: “Ironic” has been cited as an example of how Americans don’t get irony, despite the fact that Alanis Morissette is Canadian!

I hate it when people don't get irony ... or sarcasm.

[To see the video, go to Alanis Morissette, click on "music" then on "ironic" at the bottom, third from the left.]

[Hat Tip: Jim Lippard]

[Photo Credit: Agência Brasil disponibiliza, gratuitamente, imagens e fotos. Para cumprir a legislação em vigor, solicitamos aos nossos usuários a gentileza de registrar os créditos como no exemplo: nome do fotógrafo—via Wikipedia.]

Basic Concepts: The Central Dogma of Molecular Biology

The demise of the Central Dogma of Molecular Biology is becoming an annual event. Most recently, it was killed by non-coding RNA (ncRNA) (Mattick, 2003; 2004). In previous years the suspects included alternative splicing, reverse transcriptase, introns, junk DNA, epigenetics, RNA viruses, trans-splicing, transposons, prions, epigenetics, and gene rearrangements. (I’m sure I’ve forgotten some.)

What’s going on? The Central Dogma sounds like the backbone of an entire discipline. If it’s really a “dogma” how come it gets refuted on a regular basis? If it’s really so “central” to the field of molecular biology then why hasn’t the field collapsed?

In order to answer these questions we need to understand what the Central Dogma actually means. It was first proposed by Francis Crick in a talk given in 1957 and published in1958 (Crick, 1958). In the original paper he described all possible directions of information flow between DNA, RNA, and protein. Crick concluded that once information was transferred from nucleic acid (DNA or RNA) to protein it could not flow back to nucleic acids. In other words, the final step in the flow of information from nucleic acids to proteins is irreversible.

Fig. 1. Information flow and the sequence hypothesis. These diagrams of potential information flow were used by Crick (1958) to illustrate all possible transfers of information (left) and those that are permitted (right). The sequence hypothesis refers to the idea that information encoded in the sequence of nucleotides specifies the sequence of amino acids in the protein.

Crick restated the Central Dogma of Molecular Biology in a famous paper published in 1970 at a time when the premature slaying of the Central Dogma by reverse transcriptase was being announced (Crick, 1970). According to Crick, the correct, concise version of the Central Dogma is ...

... 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)

Announcing the (Premature) Death of the Central Dogma
The central dogma of biology holds that genetic information normally flows from DNA to RNA to protein. As a consequence it has been generally assumed that genes generally code for proteins, and that proteins fulfil not only most structural and catalytic but also most regulatory functions, in all cells, from microbes to mammals. However, the latter may not be the case in complex organisms. A number of startling observations about the extent of non-protein coding RNA (ncRNA) transcription in the higher eukaryotes and the range of genetic and epigenetic phenomena that are RNA-directed suggests that the traditional view of genetic regulatory systems in animals and plants may be incorrect.

Mattick, J.S. (2003) Challenging the dogma: the hidden layer of non-protein-coding RNAs in complex organisms. BioEssays 25:930-939.

---

The central dogma, DNA makes RNA makes protein, has long been a staple of biology textbooks.... Technologies based on textbook biology will continue to generate opportunities in bioinformatics. However, more exciting prospects may come from new discoveries that extend or even violate the central dogma. Consider developmental biology. The central dogma says nothing about the differences between the cells in a human body, as each one has the same DNA. However, recent findings have begun to shed light on how these differences arise and are maintained, and the biochemical rules that govern these differences are only being worked out now. The emerging understanding of developmental inheritance follows a series of fundamental discoveries that have led to a realization that there is more to life than the central dogma.

Henikoff, S. (2002) Beyond the central dogma. Bioinformatics 18:223-225.

---

It will take years, perhaps decades, to construct a detailed theory that explains how DNA, RNA and the epigenetic machinery all fit into an interlocking, self- regulating system. But there is no longer any doubt that a new theory is needed to replace the central dogma that has been the foundation of molecular genetics and biotechnology since the 1950s.

The central dogma, as usually stated, is quite simple: DNA makes RNA, RNA makes protein, and proteins do almost all of the work of biology.

Gibbs. W.W. (2003) The unseen genome: gems among the junk. Sci. Am. 289:26-33.

Unfortunately, there’s a second version of the Central Dogma that’s very popular even though it’s historically incorrect. This version is the simplistic DNA → RNA → protein pathway that was published by Jim Watson in the first edition of The Molecular Biology of the Gene (Watson, 1965). Watson’s version differs from Crick’s because Watson describes the two-step (DNA → RNA and RNA → protein) pathway as the Central Dogma. It has long been known that these conflicting versions have caused confusion among students and scientists (Darden and Tabery, 2005; Thieffry, 1998). I argue that as teachers we should teach the correct version, or, at the very least, acknowledge that there are conflicting versions of the Central Dogma of Molecular Biology.

The pathway version of the Central Dogma is the one that continues to get all the attention. It’s the version that is copied by almost all textbooks of biochemistry and molecular biology. For example, the 2004 edition of the Voet & Voet biochemistry textbook says,

In 1958, Crick neatly encapsulated the broad outlines of this process in a flow scheme he called the central dogma of molecular biology: DNA directs its own replication and its transcription to yield RNA, which, in turn, directs its translation to form proteins. (Voet and Voet, 2004)

If the Watson pathway version of the Central Dogma really was the one true version then it would have been discarded or modified long ago. In his original description, Watson drew single arrows from DNA to RNA and from RNA to protein and stated ....

The arrow encircling DNA signifies that it is the template for its self-replication; the arrow between DNA and RNA indicates that all cellular RNA molecules are made on DNA templates. Most importantly, both these latter arrows are unidirectional, that is, RNA sequences are never copied on protein templates; likewise, RNA never acts as a template for DNA.

Fig. 2. Watson’s version of the Central Dogma. This figure is taken from the first edition of The Molecular Biology of the Gene (p. 298).

Watson's statement is clearly untrue, as the discovery of reverse transcriptase demonstrated only a few years after his book was published. Furthermore, there are now dozens of examples of information flow pathways that are more complex than the simple scheme shown in Watson’s 1965 book. (Not to mention the fact that many information flow pathways terminate with functional RNA’s and never produce protein.)

Watson’s version of the Central Dogma is the one scientists most often refer to when they claim that the Central Dogma is dead. The reason it refuses to die is because it is not the correct Central Dogma. The correct version has not been refuted.

Crick was well aware of the difference between his (correct) version and the Watson version. In his original 1958 paper, Crick referred to the standard information flow pathway as the sequence hypothesis. In his 1970 paper he listed several common misunderstandings of the Central Dogma including ....

It is not the same, as is commonly assumed, as the sequence hypothesis, which was clearly distinguished from it in the same article (Crick, 1958). In particular, the sequence hypothesis was a positive statement, saying that the (overall) transfer nucleic acid → protein did exist, whereas the central dogma was a negative statement saying that transfers from protein did not exist.

The Sequence Hypothesis and the Central Dogma in 1957
My own thinking (and that of many of my colleagues) is based on two general principles, which I shall call the Sequence Hypothesis and the Central Dogma. The direct evidence for both of them is negligible, but I have found them to be of great help in getting to grips with these very complex problems. I present them here in the hope that others can make similar use of them. Their speculative nature is emphasized by their names. It is an instructive exercise to attempt to build a useful theory without using them. One generally ends in the wilderness.

The Sequence Hypothesis. This has already been referred to a number of times. In its simplest form it assumes that the specificity of a piece of nucleic acid is expressed solely by the sequence of its bases, and that this sequence is a (simple) code for the amino acid sequence of a particular protein.

This hypothesis appears to be rather widely held. Its virtue is that it unites several remarkable pairs of generalizations: the central biochemical importance of proteins and the dominating role of genes, and in particular of their nucleic acid; the linearity of protein molecules (considered covalently) and the genetic linearity within the functional gene, as shown by the work of Benzer and Pontecorvo; the simplicity of the composition of protein molecules and the simplicity of nucleic acids. Work is actively proceeding in several laboratories, including our own, in an attempt to provide more direct evidence for this hypothesis.

The Central Dogma. This states that once “information” has passed into protein it cannot get out again. In more detail, the transfer of information from nucleic acid to nucleic acid, or from nucleic acid to protein may be possible, but transfer from protein to protein, or from protein to nucleic acid is impossible. Information means here the precise determination of sequence, either of bases in the nucleic acid or of amino acid residues in the protein.

Crick, F.H.C. (1958) On protein synthesis. Symp. Soc. Exp. Biol. XII:138-163 quoted in Judson, H.F. The Eight Day of Creation, Expanded Edition (1979, 1996) p. 332.

So, how do we explain the current state of the Central Dogma? The Watson version is the one presented in almost every textbook, even though it is not the correct version according to Francis Crick. The Watson version has become the favorite whipping boy of any scientist who lays claim to a revolutionary discovery, even though a tiny bit of research would uncover the real meaning of the Central Dogma of Molecular Biology. The Watson version has been repeatedly refuted or shown to be incomplete, and yet it continues to be promoted as the true Central Dogma. This is very strange.

The Crick version is correct—it has never been seriously challenged—but few textbooks refer to it. One exception is Lewin’s GENES VIII (Lewin, 2004) (and earlier editions). Lewin defines the Central Dogma of Molecular Biology as,

The central dogma states that information in nucleic acid can be perpetuated or transferred but the transfer of information into protein is irreversible. (B. Lewin, 2004)

I recommend that all biochemistry and molecular biology teachers adopt this definition—or something very similar—and teach it in their classrooms.

Crick, F.H.C. (1958) On protein synthesis. Symp. Soc. Exp. Biol. XII:138-163. [PDF]

Crick, F. (1970) Central Dogma of Molecular Biology. Nature 227, 561-563. [PDF file]

Darden, L. and Tabery, J. (2005) Molecular Biology

Lewin, B. (2004) GENES VIII Pearson/Prentice Hall

Mattick, J.S. (2003) Challenging the dogma: the hidden layer of non-protein-coding RNAs in complex organisms. BioEssays 25:930-939

Mattick, J.S. (2004) The hidden genetic program of complex organisms. Sci. Am. 291:60-67.

Thieffry, D. (1998) Forty years under the central dogma. Trends Biochem. 23:312-316.

Watson, J.D. (1965) The Molecular Biology of the Gene. W.A. Benjamin. Inc. New York

Chapel Hill, North Carolina

I'm going to Chapel Hill next weekend. It's one of my favorite places in the world. My daughter lives there. (Hi Jane, are you ready?)

I'm going to meet some bloggers.

Monday's Molecule #9

 
Name this molecule. You must be specific. We need the exact chemical name and the common name. The common name will be much more familiar to you. We'll discuss how this molecule works after you've been given a chance to identify it.

Comments will be blocked for 24 hours. Comments are now open.

Even at a conference, you've got to eat!

 
Even at a conference, you've got to eat! I'm going to Mama Dip's for Bar-B-Que on Saturday night. Are you going too?

Chicken with Ribs
pork ribs and choice of fried or bar-b-que chicken
Chopped Bar-B-Que Pork with Chicken
choice of fried or bar-b-que chicken
Brunswick Stew & Chopped Bar-B-Que
served with coleslaw and cornbread only
Bar-B-Que Pork Ribs & Chopped Bar-B-Que Pork
for the true connoisseur
Chicken & Dumplings
broiled chicken seasoned and cooked with rolled dumplings
Chittlins
really "down home" served plain or pan fried
Chicken & Gravy
our 1/4 fried chicken smothered in gravy, white or dark meat
Salmon Biscuit
fried salmon patty sandwiched between a sliced buttermilk biscuit
Country Ham Biscuit
country ham sandwiched between a sliced buttermilk biscuit
Sausage Biscuit
pork sausage sandwiched between a sliced buttermilk biscuit
Chicken Tender Biscuit
chicken tenders smothered in gravy sandwiched between a sliced buttermilk biscuit
Sweet Potato Biscuit
Mama Dip's sweet potato biscuits served hot with butter

Safer than LSD and 'Shrooms

 
Would you take this drug if it made you dream you were climbing in the Himalayas with a duck, an ape, and a turtle? Kevin Beck would.

The duck wasn't a very good climber but it was turtles all the way up.

There's Some Kinda Test Going ON

 
The BBC reports that South Africa close in on victory. Here's an excerpt from the article,

Nazir was dropped by Pollock before the break off the luckless Ntini and could have been run out twice before thrashing the seamer over mid-wicket for six and seeing his stumps re-arranged attempting a repeat.

Naved, who survived a strong caught behind appeal off Pollock in the first over after tea, and Kaneria took over to launch a succession of meaty blows.

Three fours came in one over from Ntini and a startled Pollock was thrashed over long-off and mid-wicket for huge maximums.

Harris saw off Kaneria to bring the carnage to an end but the momentum had shifted back towards Pakistan.

Hmmm ... it looks like English but .....

Does anyone want to explain to this ignorant Canadian what's happening?

A Professor's Worst Nighmare

 
Has this ever happened to you? Read what happens when a Professor doesn't look in the mirror after putting on his pants [A classic professorial moment].

Time-shifting "Studio 60 on the Sunset Strip"

 
Freakonomics reports that my favorite TV show, Studio 60 on the Sunset Strip, is the show that people are most likely to record and watch at some other time [“Studio 60″: Tops in Time-Shifting]. I thought this might reflect the sophistication of the Studio 60 audience but then I read the rest of the top ten time-shifted shows .....

Massacre in Canada

 
The results of the latest grant competition in Canada are leaking out and the news is bad. Canadian health science research is being gutted.

The main funds for health science research come from the Canadian Institutes of Health Research (CIHR). This is the agency that funds basic science in biochemistry, molecular biology, immunology, human genetics etc. CIHR grants are the backbone of research in my department (Biochemistry) and many others.

The word from CIHR is that only 15% of the September applicants will be funded. Many of my colleagues have already received notice that they are below the cutoff. Their grants will be terminated.

These colleagues are not incompetent scientists. Many of them publish 3-5 papers a year in high quality journals. In most cases they have had continuous funding since they were first hired 10-20 years ago. Their groups consist of research assistants (lab technicians), several post-docs, and several graduate students. The lab techs and the post-docs will be terminated and the graduate students may not be able to finish their degrees.

This is a disaster. You cannot sustain high quality research if your chances of getting a grant are only 15%. What's happening is that excellent scientists are being kicked out of the system due to lack of funds at CIHR. This has got to change. The Conservative Government of Stephen Harper is ruining careers.

Already there's talk of a moratorium on hiring new faculty members. Why should we bring in new scientists if their chances of success are so small? (The funding rate for new grants is even lower than 15%.)

Stay tuned.

Birth-and-Death Evolution in Mammalian Gene Families

Once we recognize the accidental nature of evolution as described in birth-and-death evolution of gene families [The Evolution of Gene Families] we are better prepared to appreciate the significance of other studies.

In an earlier posting [Mammalian Gene Families: Humans and Chimps Differ by 6%] I described the results of Demuth et al. (2006) who looked at global expansion and contraction of gene families. They published this diagram to show the extent of gene loss and gain in mammalian lineages.

Figure 1. Distribution of gene gain and loss among mammalian lineages.

Creative Commons Attribution License

The Creationists made a big deal about this when the paper first came out but we can now see that the expansion and contraction of gene families is just part of the normal, ongoing, process of birth-and-death evolution.