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Monday, August 27, 2012

The Ethics of Genome Analysis

Lots of people are having their genomes sequenced or otherwise analyzed for specific alleles. Those people should get all the information that comes out of the analyses although, hopefully, it will be scientifically correct information and any medical relevance will be explained by experts.1

There's another group of people who submit their genomes for research purposes only and they usually sign consent forms indicating that their name will not be associated with the results. Under those circumstances, the researchers should never have access to the individual's name or any circumstances that are not relevant to the study.

Apparently that simple ethical rule is not always standard practice. Gina Kolatea writes about some ethical issues in the New York Times: Genes Now Tell Doctors Secrets They Can’t Utter.

Here's an example from her article ...
One of the first cases came a decade ago, just as the new age of genetics was beginning. A young woman with a strong family history of breast and ovarian cancer enrolled in a study trying to find cancer genes that, when mutated, greatly increase the risk of breast cancer. But the woman, terrified by her family history, also intended to have her breasts removed prophylactically.

Her consent form said she would not be contacted by the researchers. Consent forms are typically written this way because the purpose of such studies is not to provide medical care but to gain new insights. The researchers are not the patients’ doctors.

But in this case, the researchers happened to know about the woman’s plan, and they also knew that their study indicated that she did not have her family’s breast cancer gene. They were horrified.
This is a rather simple case of the researchers violating a standard protocol. They should not have known the identity of the patient and they should not have known what she intended to do.

Most of the "ethical problems" in the article are of this type. They involve researchers who are supposed to be concentrating on research and not on the treatment of individual patients. Those researchers have no idea whether the patients already know which alleles they carry or whether they are already undergoing medical treatment. That's just as it should be. If a DNA donor doesn't want to be contacted then it's ethically wrong for the researchers to violate that contract no matter how justified they think they are being. Furthermore, it should be impossible for them to find out the name and address of the donor so the issue should never come up.

John Hawks thinks this is an interesting ethical problem and he wants his students to discuss it in his classes [Grasping the genomic palantir].
That case is ethically straightforward compared to others, because the researchers could make a difference to an immediate medical decision. On the other hand, how many risk-free research participants went ahead with prophylactic mastectomies because researchers didn't know about their plans?

I think the article will be a good one for prompting student discussions in my courses, and I'll likely assign it widely. But I think the central ethical problem discussed in the article is temporary.
What will students learn from discussing issues like these? What controls are in place to make sure that students are informed about all the ethical issues? Will they be told that standard scientific protocols were violated once the researchers knew what the patient intended to do?


1. "Experts" do NOT include employees of any for-profit company that took money for sequencing the genome.

Thinking Critically About Graphs

Jeff Mahr is trying to teach his students how to think critically so he asked them a question about a graph. Check it out to see if you would pass his course: Clearly Critical Thinking?.

Wednesday, August 22, 2012

For All Those People Who Like to Take Pictures of Their Food Using Their iPhone

You know who you are!



Tomoko Ohta and Nearly Neutral Theory

There's an interview with Tomoko Ohta in the August 21, 2012 issue of Current Biology: Tomoko Ohta.

You should know who she is but in case you don't, here's part of the brief bio ...
In 1973, she presented her first major paper entitled ‘Slightly deleterious mutant substitutions in evolution’. This theory was an expansion of Kimura's ‘neutral theory’, which Ohta called the ‘nearly neutral theory’ of molecular evolution. Her theory emphasizes the importance of interaction of drift and weak selection, and hence the role of slightly deleterious mutations in molecular evolution. With the accumulation of genome data, some of the predictions of the nearly neutral theory have been verified. The theory also provides a mechanism for the evolution of complex systems. Her other subject is to clarify the mechanisms of evolution and variation of multigene families. She has received several honors, including the foreign membership of the National Academy of Sciences, USA and Person of Cultural Merit, Japan.
It's very important to understand the essence of Nearly Neutral Theory since it explains the relationship between fitness and population size. Everyone needs to understand that Ohta demonstrated how slightly deleterious alleles can be fixed in a population. Her work showed that an allele can become effectively neutral in small populations even though it may actually lower the fitness of an individual. It's a way of explaining the limits of natural selection and of extending the Neutral Theory of Kimura.

She describes what happened when she joined Kimura's group at Tokyo.
At that time, Kimura was thinking of combining the theory of stochastic population genetics, the field he had been working on, with biochemical data on the nature of the genetic material. He proposed his now famous ‘neutral theory of molecular evolution’ in 1968. The ‘neutral theory’ proposed that most evolutionary changes at the molecular level were caused by random genetic drift rather than by natural selection. Note that the neutral theory classifies new mutations as deleterious, neutral, and advantageous. Under this classification, the rate of mutant substitutions in evolution can be formulated by the stochastic theory of population genetics. Kimura's theory was simple and elegant, yet I was not quite satisfied with it, because I thought that natural selection was not as simple as the mutant classification the neutral theory indicated, and that there would be border-line mutations with very small effects between the classes. I thus went ahead and proposed the nearly neutral theory of molecular evolution in 1973. The theory was not simple, and much more complicated, but to me, more realistic, and I have been working on this problem ever since.
This has nothing to do with Darwinism even though it's a fundamental part of modern evolutionary theory. You can't have an intelligent discussion about genome evolution, adaptationism, molecular evolution, or junk DNA without a firm grasp of Nearly Neutral Theory.

It's a shame there's no Nobel Prize for evolution.


Tuesday, August 21, 2012

Designing a New Biochemistry Curriculum

I want to draw your attention to an article in the July/August 2012 issue of Biochemistry and Molecular Biology Education (BAMBED). The authors are Michael Klymkowski and Melanie Cooper and the title is "Now for the Hard Part: The Path to Curricular Design."
There is a growing acknowledgement that STEM education, at all levels, is not producing learners with a deep understanding of core disciplinary concepts [1]. A number of efforts in STEM education reform have focused on the development of ‘‘student-centered’’ active learning environments, which, while believed to be more effective, have yet to be widely adopted [2]. What has not been nearly as carefully considered, however, is the role of the curriculum itself as perhaps the most persistent obstacle to effective science education. It is now time to examine not only how we teach, but also what we teach and how it affects student learning.
This is an important point. Most of the science education reforms that are being proposed these days focus on style rather than substance.

In the long run, it really doesn't matter whether you are employing the very latest pedagogical techniques if what you are teaching is crap.

But we also need to recognize that there's a relationship between what we teach and how we teach it. If you want to teach scientific thinking—as opposed to memorizing pathways—then there may be superior ways to do it.
Recognizing how challenging it is to build scientific understanding requires that we recognize that scientific thinking, in and of itself, is by no means easy and is certainly not ‘‘natural.’’ We are programmed by survival based and eminently practical evolutionary processes to ‘‘think fast’’ [8]. In contrast, scientific thinking is slow, hard, and difficult to maintain. If students are not exposed to environments where they must practice and use the skills (both metacognitive and procedural) that they need to learn, they may fall back on fast, surface level answers, and fail to recognize what it is that they do not understand.
Scientific thinking (and critical thinking) have to be experienced and practiced. That means you have to make time for that in your course.


Klymkowsky, M.W. and Cooper, M.M. (2012) Now for the hard part: The path to coherent curricular design. Biochemistry and Molecular Biology Education 40:271–272. [doi: 10.1002/bmb.20614]

Origin Stories

Here's a podcast on the origin of life. Check out the website to see who's talking [Origin Stories].

For some strange reason the show begins with Greek mythology. Then it moves on to real science. There are three origin of life scenarios ...
  1. Darwin's warm little pond ... equivalent to primordial soup.
  2. Panspermia ... which doesn't solve anything.
  3. Hydrothermal vents ... which aren't explained
The moderator seems to think that primordial soup has problems and panspermia is a nonstarter but he doesn't explain the hydrothermal vent story and doesn't even mention Metabolism First.

The second half of the show features soundbites suggesting that the origin of complex organic molecules on Earth is a problem but they could form in interstellar space. But this is exactly the "problem" that Metabolism First tries to explain so it's puzzling that there was no advocate of this view on the show.

This is a complicated topic that is not compatible with the format of this show. How do you, dear readers, think it rates as science journalism? Is this a good way to get the general public interested in science?

The blurb on the website suggests that the series is highly rated by fellow journalists.
A show that explores the bigger questions. Winner of "Top New Artists" and "Most Licensed by Public Radio Remix" awards at PRX's 2011 Zeitfunk Awards.




Monday, August 20, 2012

Pseudogenes Are Pseudogenes and They Are Almost Always Junk

The IDiots have found a paper by Wen et al. (2012) with a very provocative title, "Pseudogenes are not pseudo any more."

Naturally, lawyer Casey Luskin is all over this: Paper Rebuffs Assumption that Pseudogenes Are Genetic "Junk," Claims Function Is "Widespread". And just as naturally, the folks at Uncommon Descent (probably lawyer Barry Arrington) jump on the bandwagon: Junk DNA: Yes, paper admits, it WAS thought to be junk.

The authors of the paper, including Templeton Prize winner Francisco J Ayala, claim that pseduogenes exhibit two puzzling properties: (a) similar processed pseudogenes occur in mouse and humans suggesting that they are conserved, and (b) many pseudogenes are transcribed.

Processed pseudogenes arise when mRNA transcripts are reverse transcribed and inserted back into the genome. They usually come from genes that are highly expressed in germ line cells. Such genes tend to be highly conserved in related species. Mammals are closely related on the scale that were talking about. It's not surprising that a few new pseudogenes in such lineages are very similar in sequence. They're still pseudogenes. The vast majority of known pseudogenes are evolving at a rate that approximates the rate of mutation indicating that they are not constrained by negative selection.

Many pseudogenes are derived from gene duplications followed by mutations in one of the copies that make them incapable of producing a functional product. There's no reason to suspect that the first of these debilitating mutations will prevent transcription; therefore, one expects that many pseudogenes will be transcribed.

Some pseudogenes have been co-opted to provide a different function. There aren't very many examples but that doesn't stop the IDiots from making the fantastic leap from 0.0001% to 100%. (Pseudogenes represent about 1% of the genome [What's in Your Genome? ] so even if we assume that every single pseudogene is not a pseudogene, it hardly makes a dint in the amount of junk DNA.)

I discussed all this when I reviewed Jonathan Well's book The Myth of Junk DNA. The relevant chapter is Chapter 5 [Junk & Jonathan: Part 8—Chapter 5]. That review was posted in May 2011. It seems clear that the lawyers on the IDiot websites haven't read it.

Here's what one of them says on Uncommon Descent.
Darwin’s followers considered junk DNA powerful evidence for their theory, which is really a philosophy (often a cult), and that they often expressed that view, often triumphantly. Others insist it is true anyway.

The problem they hope to suppress is that if lots of junk in our DNA is such powerful evidence for their theory, then little junk throws it into doubt. That is, if it is such a good theory, why was it wrong on a point that was announced so triumphantly?

So it is a good thing that the science-minded public is reminded of the historical fact that Darwinism was supported by junk DNA. And it will be fun when the squirming editorials come out in science mags, warning people not to read too much into this, Darwin is still right.
I'm not even going to bother pointing out how stupid that is. If you're reading Sandwalk, chances are high that you could detect the lies1 with your eyes closed.


1. Yes, "lies." At this point there's no other explanation.

Wen, Y-Z., Zheng, L-L., Qu, L-H., Ayala, F.J., and Lun, Z-R. (2012) Pseudogenes are not pseudo any more. RNA Biology 9: 27 - 32. [doi: 10.4161/rna.9.1.18277]

Monday's Molecule #182

Last week's molecule was a ganglioside (GM2) that's associated with Tay-Sachs disease [Monday's Molecule #181].

This week's molecule is one of the most important enzymes in the known universe. What is it?

Post your answers as a comment. I'll hold off releasing any comments for 24 hours. The first one with the correct answer wins. I will only post mostly correct answers to avoid embarrassment. The winner will be treated to a free lunch.

There could be two winners. If the first correct answer isn't from an undergraduate student then I'll select a second winner from those undergraduates who post the correct answer. You will need to identify yourself as an undergraduate in order to win. (Put "undergraduate" at the bottom of your comment.)

Some past winners are from distant lands so their chances of taking up my offer of a free lunch are slim. (That's why I can afford to do this!)

In order to win you must post your correct name. Anonymous and pseudoanonymous commenters can't win the free lunch.

Winners will have to contact me by email to arrange a lunch date. Please try and beat the regular winners. Most of them live far away and I'll never get to take them to lunch. This makes me sad.

Comments are invisible for 24 hours. Comments are now open.

UPDATE: The molecule is complex III or ubiquinol:cytochrome c oxidoreductase, the enzyme responsible for the Q-cycle and the transport of proton across the plasma membrane of bacteria and the inner mitochondrial membrane in eukaryotes. This week's winner is Stephen Spiro.

Winners
Nov. 2009: Jason Oakley, Alex Ling
Oct. 17: Bill Chaney, Roger Fan
Oct. 24: DK
Oct. 31: Joseph C. Somody
Nov. 7: Jason Oakley
Nov. 15: Thomas Ferraro, Vipulan Vigneswaran
Nov. 21: Vipulan Vigneswaran (honorary mention to Raul A. Félix de Sousa)
Nov. 28: Philip Rodger
Dec. 5: 凌嘉誠 (Alex Ling)
Dec. 12: Bill Chaney
Dec. 19: Joseph C. Somody
Jan. 9: Dima Klenchin
Jan. 23: David Schuller
Jan. 30: Peter Monaghan
Feb. 7: Thomas Ferraro, Charles Motraghi
Feb. 13: Joseph C. Somody
March 5: Albi Celaj
March 12: Bill Chaney, Raul A. Félix de Sousa
March 19: no winner
March 26: John Runnels, Raul A. Félix de Sousa
April 2: Sean Ridout
April 9: no winner
April 16: Raul A. Félix de Sousa
April 23: Dima Klenchin, Deena Allan
April 30: Sean Ridout
May 7: Matt McFarlane
May 14: no winner
May 21: no winner
May 29: Mike Hamilton, Dmitri Tchigvintsev
June 4: Bill Chaney, Matt McFarlane
June 18: Raul A. Félix de Sousa
June 25: Raul A. Félix de Sousa
July 2: Raul A. Félix de Sousa
July 16: Sean Ridout, William Grecia
July 23: Raul A. Félix de Sousa
July 30: Bill Chaney and Raul A. Félix de Sousa
Aug. 7: Raul A. Félix de Sousa
Aug. 13: Matt McFarlane
Aug. 20: Stephen Spiro


Sunday, August 19, 2012

Green T4 Bacteriophage Earrings

Ms. Sandwalk's birthday is coming up in a few weeks and I'm getting nervous. I always seem to choose the wrong present. Turns out that a telephoto lens for her camera isn't very romantic. Who knew?

This year it's a sure thing. I worked on bacteriophage T4 as a graduate student and she helped me type my thesis. It's the perfect gift. [NEW - Green T4 Bacteriophage Earrings]

Right?


A Question for Anthropologists

This year's special issue of Scientific American is "Beyond the Limits of Science." One of the articles is about human evolution. The title is Super Humanity in the print issue but the online title is Aspiration Makes Us Human.

The author is Robert M. Sapolsky, a professor of biology and neurology at Stanford University in California (USA). Stanford is a pretty good school so he probably knows his stuff.

Here's how Sapolsky starts off ...
Sit down with an anthropologist to talk about the nature of humans, and you are likely to hear this chestnut: “Well, you have to remember that 99 percent of human history was spent on the open savanna in small hunter-gatherer bands.” It's a classic cliché of science, and it's true. Indeed, those millions of ancestral years produced many of our hallmark traits—upright walking and big brains, for instance.
This doesn't make sense.

Let's assume that our ancestors left Africa only 50,000 years ago. If that represents 1% of our evolutionary history then it means that our species and it's immediate direct ancestors lived on the African open savannah for 4,950,000 years.

Could that possibly be true even if you only count the main line of descent? What is the evidence that supports these claims? How much of the early history of Homo sapiens was influenced by adaptation to open savannah? Does anyone have a scientific answer to this question?

Setting aside the "main line," we now have good evidence that modern Homo sapiens acquired alleles from Neanderthals, Denisovans, and, perhaps more ancient Homo erectus. All three spent substantial time evolving in places that looked nothing like the open savannah in Africa. The proportion of the "invading" alleles may be only 10% or less but that's still significant.

Do we know for sure that all of the important features of modern humans came from alleles that were fixed by adaptation on the savannah? What if some of the more important behavioral alleles came from Neanderthals and became fixed because they were so much fitter than the savannah alleles?

Take the alleles that make women like to shop, for example. Maybe they arose in the Denisovans because they have access to better trade routes in central China? Maybe the women on the savannah preferred to store their cash in elephant tusks?

The evolutionary psychologists have developed awesome explanations for human behavior based on their detailed understanding of the social structure of hunter-gatherer groups living on the savannah for millions of years. What if our genetic ancestors lived elsewhere? The bad news is that all those just-so stories will be wrong. The good news is that they can publish a completely different set of stories and get twice as many publications.


Saturday, August 18, 2012

Atheists Have to Address the Social and Emotional Needs of People (or the Church Wins)

I stole this title from the Friendly Atheist, Hemant Mehta [Atheists Have to Address the Social and Emotional Needs of People (or the Church Wins)].

Watch the video. Hemant makes the point that large churches in the USA provide a number of social services that, apparently, aren't available anywhere else. He points out that asking someone to give up their religion is asking them to give up all kinds of other things like volunteer groups, daycare, and support groups. Hemant thinks that atheists need to create "churches" that will fill these needs.

This is the same argument made by another prominent American atheist, Dan Dennett [What Should Replace Religion?].

I don't get it. Why should atheists have to form their own "churches"? In Canada these services are provided by local community centres—there are four within a short drive of were I live. The one within walking distance is called South Common Community Centre. It has a swimming pool (see photo above), a public library, many gyms and exercise rooms, and meeting rooms. There's daycare and classes of various sorts, dozens of volunteer organizations and support groups, swimming lessons for adults and children and lots more. The community centres are funded by civic government and paid for by taxes. They are open to everybody.

Some of them rent out space for church services on Sundays but they are definitely secular. They are not atheist centres.

The best way to provide the services that people need has already been invented. It's called socialism. It's wrong to assume that the only solution is competing services supplied by various religious churches plus one non-religious church.

Is it impossible to work in America toward the goal of secular social services for all? Is that why the only solution seems to be for atheists/humanists to form their own competing religion to provide those services for nonbelievers?



Friday, August 17, 2012

What Would Disprove Jerry Coyne's Version of Evolution?

Jerry Coyne has a particular view of evolution—one that conflates fact, theory, and history [What would disprove evolution?].

Based on his version of evolution, he then offers some examples of what it would take to disprove evolution.

I was tempted last month to challenge his views but I kept putting it off. Now, Ryan Gregory has done the job, and it's an admirable job.

I agree with everything Gregory says at: An example of why it is important to distinguish evolution as fact, theory, and path.

Please leave comments on Ryan's site.


Disproving Evolution

Elsewhere on the internet there's a discussion about whether evolution can be disproved by simply finding a fossil out of order.

Here's what I said on Facebook ...
The statement is untrue. If we discover that a given species is older than we thought then we will just revise our view of the history of life on Earth. It will not disprove the fact of evolution and it will have no effect on evolutionary theory. It is a mistake to link the truth of evolution to our current understanding of the history of life. That history can be easily changed without threatening evolution.


Thursday, August 16, 2012

R. Elsiabeth Cornwell Talks About Social Networks

R. Elisabeth Cornwell is Executive Director of the Richard Dawkins Foundation (US). She has a Ph.D. in psychology and her day job is Professor at the University of Colorado at Colorado Springs.

Here's Cornwell giving a talk at TAM2012. It makes me cringe but is it just me? Apparently not if you read the comments at YouTube.


She talks a lot about bullies and their presumed psychiatric problems but she doesn't give any examples. Who is she thinking about? Jonathan Wells? PZ Myers? Margaret Thatcher? Rush Limaugh? Stephen Jay Gould? Jerry Falwell? Ken Miller? Ann Coulter? Christopher Hitchens? Thomas Huxley? Rachel Maddow? Richard Dawkins?

It would have been nice to see the difference between pre-internet "bullies" and those on the internet. Are there any example of people who were "civilized" before they got on the internet but became bullies once they started a blog?


Stipends for Graduate Students

Here's what we pay our slaves graduate students while they are working toward their degrees. How does it compare with other biochemistry departments?

Biochemistry Graduate Student Stipends for 2012-2013

M.Sc. students

Domestic Students
$17,000 living allowance plus tuition ($7,160.00) and incidental fees ($1,241.52) = $25,401.52

International Students
$17,000 living allowance plus tuition ($16,886.00) and incidental fees ($1,241.52) AND UHIP ($684.00) = $35,811.52

Ph.D. students

Domestic Students
$19,000 living allowance plus tuition ($7,160.00) and incidental fees ($1,241.52) = $27,401.52

International Students
$19,000 living allowance plus tuition ($16,886.00) and incidental fees ($1,241.52) AND UHIP ($684.00) = $37,811.52

(UHIP is the University Health Insurance Plan)

My graduate student stipend in 1968 was $3000, which is $19,500 in 2012 dollars. I don't remember how much tuition and the health plan cost. We lived in subsidized housing, The rent was $56 per month.

We have about 140 graduate students in our department. Many of them are in the photo along with several much older "students" who earn a lot more money.