On BioScience and Life and Such

Posts Tagged ‘genetics’

I wish I wrote this

In Uncategorized on October 8, 2009 at 7:42 am

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An excellent excellent opinion piece in Nature by Bruce T. Lahn & Lanny Ebenstein. Since I cannot write as elegantly as they have, I’ll just urge anyone reading this to go and read the whole thing because it contains grains of gold like this on “biological egalitarianism”:

We believe that this position, although well-intentioned, is illogical and even dangerous, as it implies that if significant group diversity were established, discrimination might thereby be justified. We reject this position. Equality of opportunity and respect for human dignity should be humankind’s common aspirations, notwithstanding human differences no matter how big or small.

and this:

For now, to intentionally overlook the influence of group diversity on disease susceptibilities and treatment outcomes is to practise poor medicine.

followed by this:

….there is a much larger reason to embrace human diversity in all its forms, in our view. Humanity’s genetic diversity — small or large, within or among groups — is a resource for, rather than a detriment to, creating a more fulfilling and prosperous society. Just as people have come over time to cherish cultural diversity, so we hope that attitudes will warm towards genetic diversity.

topped off by this:

For example, although IQ is a useful metric of some aspects of intelligence and it is partly heritable, it is far from a complete measure of total mental capacity. Therefore, acceptance of human genetic diversity in its totality necessarily leads to the rejection of unidimensional rankings of the capacity of human individuals or groups. If anything, the study of genetics is taking us towards an ever greater appreciation of the multidimensional nature of human potential.

And summarized like this:

  • Promoting biological sameness in humans is illogical, even dangerous
  • To ignore the possibility of group diversity is to do poor science and poor medicine
  • A robust moral position is one that embraces this diversity as among humanity’s great assets

Beautiful reasoning. I hope it impacts like a large meteor.

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Find me a new term for “race”, please

In Uncategorized on February 5, 2009 at 9:02 am

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A single amino acid change causes hemoglobin t...
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Races doesn’t exist – well fine, but how do you want to label our genetic differences then. Stop using the “term” race because it leads to racism would be like treating a symptom while disregarding the disease.

Reading this post on Greg Laden’s blog we learn that using the term “race” in derogatory ways lead to racism. Well, duh, thank you captain obvious.

The discussion following the post adds some nuance to the subject, but still fails to adress the real problem: if you do not want to use “race”, which term would you want to use to describe groups who share a set of genetic traits ? Ethnicity maybe, a label of geographical location maybe, – what about “of Caucasian ancestry albeit with significant genetic differences to other Caucasians”.

Genetic traits can be grouped. In my work I need to do this when I do pharmacogenetics. Some of the genetic markers I need to test for are very common in Caucasians, some are very common in people of Asian ancestry and yet others are very common in people of African ancestry. Testing for all of them would be overwhelmingly many (and too expensive) so we need to make a selection of the ones that are most likely to be present in our patient population. And, we have to make this selection based on ethnicity, geographical loation of ancestry, or “race” if you will. I do this selection without any thought of other aspects of the word “race” . I do this to provide the best care I can to our patients.

One of the arguments in the above mentioned debate (and in the respective friendfeed entry) is that we do not need a label for these groups, – but I do ! To do my work in a proper manner I really do !

If anyone labels me a racist over having to do this, they are creating the problem rather than helping to solve it.

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A Christmas Reminder and ……duh !

In Uncategorized on December 23, 2008 at 11:02 am

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Father Christmas // Santa Claus // Père Noël
Image by Stéfan via Flickr

To those who read this post – a merry Christmas !

This appeared on several science news sites recently: “Genes may influence popularity“.

I’d like to point out a few things.

Firstly: ……………..duh………….Why is its news that anyone of your skills, your looks or your social behavior (you and your genes) makes you popular (or unpopular).

Secondly: For thousands and thousands of people Christmas is associated with loneliness. Christmas being a family and friends holiday, exacerbate their feeling of being left out, of being unpopular.  To those I’d like to point out that genes do not predestine you to unpopularity or loneliness. To be included in a community, to feel appreciated or even popular, you do not need a rule-breaking gene, a pretty face, athletic skills or extraordinary jolly christmassy outgoingness.

Thirdly: Please pay special attention to the word “may” in the news-headline. This gene may happen to be (mildly ?) associated with a specific behavior, but most certainly there are many other factors, genetic or social, that plays a role in complex behaviour leading to popularity (the actual paper isn’t out so it’s hard to thoroughly review the genetics). One should regard this research as one of many attempts to understand human behavior biology, another tiny step (forwards or backwards !) in a quest that will take many years, perhaps never to be completed.

Nature and nurture teams up and works against some of us sometimes, this becomes especially apparent during Christmas. But, if you want to help others feel popular this holiday ? Forget about genetics  – caring for, and paying attention to, others does the trick:

So what’s the “gene therapy” for those with genetic loneliness? Community service, social interaction, anything to get people out and to give them a sense that they are not alone in the world [says these researchers]. It gives them a sense that they belong. – Summer Johnson, PhD (taken from blog.bioethics.net)
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No I do not need a genetic scan to know my kids

In Uncategorized on October 31, 2008 at 10:40 am

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I have three children. I know them very well. Every parent should. I know that they have strengths, – some things they do very well (they know it too). I know that they struggle with other things (they are aware of this too). I tell them to tell me if I can help them learn something new or manage something they find complicated. I encourage them when I see that they are enjoying something they are good at. I tell them that it does not matter if there are things they do not master, – everyone can’t be good at everything I tell them. They accept that. We all do.

I can see if they are sick or are feeling unwell. I tell them to tell me if they feel sick or uncomfortable for some reason. I tell them I will do my best to make them well again. I comfort them and tell them that this will pass, and you’ll be fit as a fiddle again soon. I tell them to eat right, I tell them to stay active. We do this together. I tell them this is because we do not want to be permanently ill in the future.

I know my family, not only my kids. I know which diseases my father and mother have had, and their fathers and mothers too. I tell my kids to do things that will minimize the risk for similar ailments in the future. I try and minimize risk myself too, because that benefits me as well as my children.

When they grow up and can make informed medical decisions, I will tell them that they are free to scan their genetic sequence if they choose to.

I do not however, need a genetic scan to see what is good for them and what is not. I know them.

If you do not know your kids, – please start getting to know them now. To do that you do not need genetic testing, you need attentiveness and presence.

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Hammering nails in the “junk-DNA” coffin

In Uncategorized on October 28, 2008 at 2:12 pm

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A replica of the coffin used for Abraham Linco...

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Enough talk (see this previous post and links within), on to the peer-reviewed science. Below you will find a list of references that I hope will contribute to the fall of the term “junk-DNA“, – some of it may (currently) lack a known function, but it is not junk !!!

Disclaimer: This is a list of useful references when arguing against the common overestimation of the amount of “junk”-DNA. By listing these I am not claiming anything beyond what I have already posted on this blog or in a comment somewhere. Also and importantly, I have not myself  had the time to review these articles as thoroughly as I would have wanted to, – some have been read carefully, others lightly and yet others just skimmed through. Thus, you are more than welcome to comment on these references if you have opinions on any of them, or find them unsuited for this list.

The list will be continuously expanded, and if you have references you would like to add, please notify me with a comment to the post.

The references are unsorted. Feel free to copy, rearrange and use as desired…

Last updated 5/8-13:

  1. Alu elements as regulators of gene expression. Häsler J, Strub K, Nucleic Acids Res. 2006;34(19):5491-7. Epub 2006 Oct 4.
  2. RNA editing, DNA recoding and the evolution of human cognition
    Trends in Neurosciences, , Volume 31, Issue 5, May 2008, Pages 227-233
    John S. Mattick, Mark F. Mehler
  3. Evolution of the mammalian transcription factor binding repertoire via transposable elements, Bourque, Guillaume, Leong, Bernard, Vega, Vinsensius B., Chen, Xi, Lee, Yen Ling, Srinivasan, Kandhadayar G., Chew, Joon-Lin, Ruan, Yijun, Wei, Chia-Lin, Ng, Huck Hui, Liu, Edison T. Genome Res. 2008 0: gr.080663.108. DOI: 10.1101/gr.080663.108
  4. Lin L, Shen S, Tye A, Cai JJ, Jiang P, et al. 2008 Diverse Splicing Patterns of Exonized Alu Elements in Human Tissues. PLoS Genetics 4(10): e1000225 doi:10.1371/journal.pgen.1000225
  5. Dispensability of mammalian DNA. McLean C, Bejerano G., Genome Res. 2008 Oct 2. [Epub ahead of print]
  6. Functional Demarcation of Active and Silent Chromatin Domains in Human HOX Loci by Noncoding RNAs. John L. Rinn et al., Cell 129, 1311–1323, June 29, 2007
  7. A Strategy for Probing the Function of Noncoding RNAs Finds a Repressor of NFAT. A. T. Willingham, A. P. Orth, S. Batalov, E. C. Peters, B. G. Wen, P. Aza-Blanc, J. B. Hogenesch, and P. G. Schultz (2 September 2005). Science 309 (5740), 1570. [DOI: 10.1126/science.1115901]
  8. Dinger, M. E. et al. Long noncoding RNAs in mouse embryonic stem cell pluripotency and differentiation, Genome Res. doi: 10.1101/gr.078378.108
  9. Non-coding RNAs in the nervous system, Mark F. Mehler and John S. Mattick, J Physiol Volume 575, Number 2, 333-341, September 1, 2006 DOI: 10.1113/jphysiol.2006.113191
  10. Specific expression of long noncoding RNAs in the mouse brain, Tim R. Mercer* et al., PNAS  January 15, 2008   vol. 105  no. 2  716-721
  11. RNA Maps Reveal New RNA Classes and a Possible Function for Pervasive Transcription, Philipp Kapranov et al., Science 8 June 2007: Vol. 316. no. 5830, pp. 1484 – 1488 DOI: 10.1126/science.1138341
  12. Intergenic transcription is required to repress the Saccharomyces cerevisiae SER3 gene, Joseph A. Martens, Lisa Laprade and Fred Winston, Nature 429, 571-574 (3 June 2004) | doi:10.1038/nature02538
  13. Regulation of an intergenic transcript controls adjacent gene transcription in Saccharomyces cerevisiae, Joseph A. Martens, Pei-Yun Jenny Wu and Fred Winston, GENES & DEVELOPMENT 19:2695-2704, 2005
  14. Neuronal Untranslated BC1 RNA: Targeted Gene Elimination in Mice, Boris V. Skryabin et al., Molecular and Cellular Biology, September 2003, p. 6435-6441, Vol. 23, No. 18 0270-7306/03/$08.00+0 DOI: 10.1128/MCB.23.18.6435-6441.2003
  15. Pellionisz, A. (2008) The Principle of Recursive Genome Function. The Cerebellum (Springer), DOI 10.1007/s12311-008-0035-y
  16. Evolution of the mammalian transcription factor binding repertoire via transposable elements, Guillaume Bourque, Bernard Leong, Vinsensius B. Vega, et al.
    Genome Res. published online August 5, 2008; doi:10.1101/gr.080663.108
  17. Natural selection on gene function drives the evolution of LTR retrotransposon families in the rice genome. Regina S. Baucom et al. Genome Res. Published in Advance November 24, 2008, doi: 10.1101/gr.083360.108
  18. Bekpen C, Marques-Bonet T, Alkan C, Antonacci F, Leogrande MB, et al. (2009) Death and Resurrection of the Human IRGM Gene. PLoS Genet 5(3): e1000403. doi:10.1371/journal.pgen.1000403.
  19. Local DNA Topography Correlates with Functional Noncoding Regions of the Human Genome. Stephen C. J. Parker, Loren Hansen, Hatice Ozel Abaan, Thomas D. Tullius, Elliott H. Margulies. Published Online March 12, 2009. Science DOI: 10.1126/science.1169050.
  20. A Functional Role for Transposases in a Large Eukaryotic Genome.
    Mariusz Nowacki, Brian P. Higgins, Genevieve M. Maquilan, Estienne C. Swart, Thomas G. Doak, Laura F. Landweber. Science 15 May 2009: Vol. 324. no. 5929, pp. 935 – 938 DOI: 10.1126/science.1170023.
  21. Unstable Tandem Repeats in Promoters Confer Transcriptional Evolvability. Marcelo D. Vinces, Matthieu Legendre, Marina Caldara, Masaki Hagihara, Kevin J. Verstrepen. Science 29 May 2009: Vol. 324. no. 5931, pp. 1213 – 1216. DOI: 10.1126/science.1170097.
  22. The regulated retrotransposon transcriptome of mammalian cells. Geoffrey J Faulkner1, Yasumasa Kimura2, Carsten O Daub2, Shivangi Wani1, Charles Plessy2, Katharine M Irvine3, Kate Schroder3, Nicole Cloonan1, Anita L Steptoe1, Timo Lassmann2, Kazunori Waki2, Nadine Hornig4,5, Takahiro Arakawa2, Hazuki Takahashi2, Jun Kawai2, Alistair R R Forrest2,6, Harukazu Suzuki2, Yoshihide Hayashizaki2, David A Hume7, Valerio Orlando4,5, Sean M Grimmond1 & Piero Carninci2. Nature Genetics 41, 563 – 571 (2009)
  23. Distributions of selectively constrained sites and deleterious mutation rates in the hominid and murid genomes. Eory L, Halligan DL, Keightley PD. Mol Biol Evol.2009; 0: msp219v1-msp219
  24. Characterization of viral and human RNAs smaller than canonical microRNAs. Zhihua Li, Sang Woo Kim, Yuefeng Lin, Patrick S. Moore, Yuan Chang, and Bino John. J. Virol. doi:10.1128/JVI.01325-09.
  25. SVA retrotransposons: Evolution and genetic instability. Dustin C. Hancksa and Haig H. Kazazian Jr. Seminars in Cancer Biology, doi:10.1016/j.semcancer.2010.04.001
  26. High-throughput sequencing reveals extensive variation in human-specific L1 content in individual human genomes. Adam D Ewing and Haig H Kazazian. Genome Res.  gr.106419.110; Published in Advance May 20, 2010, doi:10.1101/gr.106419.110
  27. A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Laura Poliseno, Leonardo Salmena, Jiangwen Zhang, Brett Carver, William J. Haveman & Pier Paolo Pandolfi. Nature Volume:465, Pages: 1033–1038. Date published: (24 June 2010). doi:10.1038/nature09144
  28. Orchestrated Intron Retention Regulates Normal Granulocyte Differentiation. Justin J.-L. Wong1, William Ritchie, Olivia A. Ebner, Matthias Selbach, Jason W.H. Wong, Yizhou Huang, Dadi Gao, Natalia Pinello, Maria Gonzalez, Kinsha Baidya, Annora Thoeng, Teh-Liane Khoo, Charles G. Bailey, Jeff Holst, John E.J. Rasko. Cell, Volume 154, Issue 3, 1 August 2013, Pages 583–595
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After whole genome sequencing comes PCR

In Uncategorized on October 23, 2008 at 8:56 am

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I attended an Applied Biosystems SOLiD seminar the other day. Let me tell you this: the SOLiD system packs some serious sequencing power (as does it’s competitors like Illumina, -and possibly others). Only imagination sets limits to the potential uses for such whole genome (and whole transcriptome !) sequencing. Thus, I found myself continuously drifting off, dream-designing new projects we could set up. But, at the same time I couldn’t keep from thinking that in terms of diagnostics, this a massive overkill. Too much information is not always a good thing when it comes to disease and disease predisposition. If one particular genetic variation is relevant to the symptoms presented, then there’s hardly necessary to return the whole genome or transcriptome. You would end up giving the patient information on a whole range of diseases, – the patient may not want/need to know this. Especially since we know that (currently) there is considerable uncertainty surrounding the future disease-risk associated with most genetic markers. Besides, once you know the relevant genetic regions it would probably be sufficient to run a couple of million markers to determine any predisposition.

Early model of a Polymerase Chain Reaction mac...

Good (?, and really) old PCR.

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Thus, all of these projects ended with good old PCR, which is kind of strange since sequencing one would think, is the superior of the two technologies. Here’s how I figured my (would be) whole genome sequencing projects would go:

  1. Pick species/subspecies/individual trait or disease group
  2. Sequence everything you can get your hands on
  3. Characterize genetic differences be it SNPs, indels, repeats, CNV or any other
  4. And then, …..design PCR/real-time PCR assays for diagnostics/further research and such.

Because, obviously, once everything is sequenced, there’s no need to keep sequencing. My prediction is that at that point (real-time) PCR (and quite possibly Sanger sequencing capillary electrophoresis) will regain it’s lost status as preferred tools for molecular biologists.

So, as a comfort to all those who are unable to jump on the whole genome sequencing train: Not to worry ! We’re just going through a phase. This too shall pass.

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It’s not all about the genes, well it’s not all about the environment either

In Uncategorized on October 16, 2008 at 8:23 pm

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When having a good debate on a given topic, there will usually be arguments ranging from one extreme to the other (and anywhere in between). The true answer you will find, is never those extremes.

The middle ground is sometimes hard to maintain in discussions and debates because the extremes keep hitting each other in the head, making impenetrable noise as they do so. Examples I have been involved in lately are debates on race, IVF, abortion, junk-DNA and open access publishing. Arguably, this mechanism is present for almost any discussion.  So also for the the debate on how much of human nature is shaped by genes and how much by the surrounding environment, -the nature vs. nurture discussion.

Reassuringly though, as most debates mature, they do tend to move towards the golden mean. Most people are confident now that human biology (behavior) is a result of a combination of our genes and the environment in which we live and grow. I am confident about this too, but I see research giving support to this notion far to seldom. First example I remember, was this article on domestic violence and genetics:

A functional polymorphism in the gene encoding the neurotransmitter-metabolizing enzyme monoamine oxidase A (MAOA) was found to moderate the effect of maltreatment. Maltreated children with a genotype conferring high levels of MAOA expression were less likely to develop antisocial problems. These findings may partly explain why not all victims of maltreatment grow up to victimize others, and they provide epidemiological evidence that genotypes can moderate children’s sensitivity to environmental insults. – Caspi A et al. Role of genotype in the cycle of violence in maltreated children.Science. 2002 Aug 2;297(5582):851-4.

I remember reading it and thinking, – yes !! Finally some evidence proving what we all thought we already knew . And I’ve kept waiting for other reports to similarly illustrate this gene/environment interplay so clearly (for the record, I know that the MAOA-results have not been unequivocally reproduced). Now, I have seen sporadic reports on other gene/environment interactions, but the mountain of evidence I had been expecting since 2002 just has not appeared.

That’s why when I read this review on ADHD the other day, which was exemplary in referencing and discussing gene/environment interactions, I was pleased and reassured that this field is far from forgotten about. Here are some descriptive quotes:

The neurobiology of psychiatric disorders is not about inevitability but is instead about vulnerability and propensity; it is only in certain environments that the disease is likely to emerge.


One of the explanations why results of genetic studies of ADHD have been contradictory is that not all individuals carrying a vulnerable genotype develop the disorder as the genetic effect may only become apparent among the subgroup of individuals exposed to a certain environmental risk. Thus, the importance of studying gene–environment interactions in behavioral disorders lies in the hypothesis that some genes show effects only in groups of individuals subjected to specific environmental stressors. – Kieling C at al. Neurobiology of attention deficit hyperactivity disorder.Child Adolesc Psychiatr Clin N Am. 2008 Apr;17(2):285-307, viii.

There is the definite possibility that I may not have paid enough attention and contrary to what I believe, one can find a mountain of publications on gene/environment interactions. If not (and I’m right), the reason there aren’t that many publications on this topic may be that research into this field is really hard to do. And that of course, is a good excuse.

But, regardless of the presence of this mountain or not: in order to use genetic research with any confidence in medical practice (and future research), the exact contributions from genes and environment needs to be worked out for as many traits as possible. And that (I hope) is our inevitable future – knowing our genes and what they will do to/for you given your surroundings. Subsequently, being able to manipulate these two factors will transform both nature and nurture. Potentially, we’ll reach the golden mean.

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On race and genetics

In Uncategorized on February 12, 2008 at 3:10 pm

In the previous post “A refreshing view on James Watson“, I referred to the website HonestThinking. The background was a post on this website pointing out the lack of scientific evidence for the unison discreditation of Watson. This has spurred a debate in some (local) newspapers about the validity of the term “race”. Race it is argued, is a social construct used to stigmatize groups. In addition there are claims that there isn’t any biological/genetic evidence to indicate that we are more different between races than within a race. Race is clearly then, a controversial term.

HonestThinking has replied to, and rejected, these arguments elegantly and has referred to the brilliant website Edge. Edge has a piece written by Mark Pagel on this issue which is very worth reading (see quote below).

As a reminder that knowledge is key to avoid prejudice, enlightened biologists do not view race as controversial. We are familiar with genetic diversity. We know that there are significant differences between ethnic groups. Our community does not associate these genetic differences with political or racist issues. James Watson on the other hand, did, – and that was hopefully, the real reason for his job-suspension. Our challenge is to communicate the scientific truth in a manner exactly opposite to Dr. Watson’s.

The scientific truth is that there are genetic differences with biological implications. These differences are larger than we previously thought. Not only are there differences in protein encoding regions of DNA, there are also differences leading to differential gene expression and in addition, there are differences in genetic insertions/deletions in the human genome. Add to this a variation in gene copy number and the multitude of ways we can be different at the genetic level becomes apparent. Altogether the 99,9 % genetic similarity we thought existed between humans is probably much lower.

On top of the genetic differences there are epigenetic differences that can contribute to phenotype variation (difference in appearance). Thus, we are all substantially different, but that does not mean we are of unequal value. It just means we’re not the same, – let’s be thankful and appreciative of that. I know I am.

Ending quote from Mark Pagel in Edge’s “The World Question Center”:

What this all means is that, like it or not, there may be many genetic differences among human populations — including differences that may even correspond to old categories of ‘race’ — that are real differences in the sense of making one group better than another at responding to some particular environmental problem. This in no way says one group is in general ‘superior’ to another, or that one group should be preferred over another. But it warns us that we must be prepared to discuss genetic differences among human populations.”

A refreshing view on James Watson

In Uncategorized on January 23, 2008 at 12:23 pm

On the Honest Thinking website there is a post that comments on the unison negative response to James Watson’s remarks on race when interviewed by The Independent.

As many will remember the interview created a general outrage and Watson was suspended from his job. There is no doubt that his phrasing was not very delicate, to put it mildly. The subsequent reactions from the politically correct masses were perhaps justified since traces of racism could be found between the lines in his remarks (as well as in previous public comments by Watson).

But, what is the science behind it all ? This popular article shows us that there’s more than one side to this story. It seems that there is solid scientific evidence to support the alleged IQ-difference between blacks and whites. Importantly though, the reasons for this difference is currently not well understood. And even more importantly, genetics is probably only partly to blame.

The way such data is presented is crucial to how it is interpreted and used in a political world. Matters of race awakens strong emotions in us. To avoid misuse of scientific data, it is important to carefully present results concerning race as unbiased and delicately as possible. The motto taken from Honest Thinking: “…….being truthful about whatever one publishes, …….. uncompromising dedication never to suppress relevant data, even when data collides with dearly held prejudices.” is commendable, but fails to account for the presentation itself. The presentation was in this case, equally or even more important than the data, – a lesson hopefully learned by Professor Watson.