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One of my automated PubMed searches just brought up a paper that’s well outside the scope of my usual reading material. I’m glad I persevered with it, though, because this is a very important paper that highlights the dangers inherent in patents on gene sequences.
Thomas Kepler, Colin Crossman, and Robert Cook-Deegan from Duke University in North Carolina assessed the reach of a patent on the sequence of the human BRCA1 gene, a major susceptibility locus for breast and ovarian cancer. Women with a family history of these cancers are routinely referred for BRCA1 and BRCA2 mutation testing, and positive results have serious enough ramifications for the patient and her relatives that DIY testing would be an incredibly bad idea.
A company called Myriad Genetics currently holds patents relating to BRCA1 and BRCA2 testing, patents that technically prohibit any other entity from carrying out these important genetic tests (the Canadian Cancer Society have a synopsis of the current state of affairs on their website).
The paper by Kepler et al., cleverly titled “Metastasizing patent claims on BRCA1“¹, analyses the impact of one particular part of the patent claim, a claim that seemed “particularly broad”:

“The patent first makes claim 1, to “An isolated DNA coding for a BRCA1 polypeptide, said polypeptide having the amino acid sequence set forth in SEQ ID NO:2.” SEQ ID NO:2 is the 1863-residue amino acid sequence for the protein encoded by the BRCA1 gene. The patent further claims “5. An isolated DNA having at least 15 nucleotides of the DNA of claim 1.” Note that claim 1 is DNA coding for the polypeptide, not for any specific gene. There are, of course, many polynucleotides that would encode the BRCA1 polypeptide. Claim 5, then, is a claim on any 15-mer oligonucleotide found in any such sequence.”

The authors used some fancy-pants numbersmithin’ to assess the reach of this patent claim, and estimate that:

“the human genome contains over one million oligonucleotides covered by this claim, and that most human genes contain at least one and usually several oligonucleotides covered by the claim.”

The estimate appears to stand up after some fancy-pants samplin’ and other analyses.
Having sequenced my fair share of DNA as part of completely non-BRCA1-related projects, I’m probably in breach of this patent myself, and I’d be willing to bet that a fair percentage of the people reading this blog post are too. And interestingly, this very fact may represent grounds for ruling the patent invalid; the vast majority of gene sequences submitted to GenBank before the patent was filed contain the offending oligonucleotides. There goes that novelty claim, then…
This paper is a very creative (and hopefully effective) way to highlight the perils of patents on gene sequences, a practice that I personally have never understood and think should be decisively (and retroactively) banned. The BRCA patents are currently the subject of a lawsuit brought against Myriad Genetics by the American Civil Liberties Union and other entities, including scientific associations and patient advocacy groups. It goes without saying that the results of the lawsuit are of paramount importance, and very eagerly awaited…
1. The paper is currently an uncorrected proof in the journal Genomics. doi:10.1016/j.ygeno.2010.03.003

How do you feel about this poster?

How do you feel about it being posted right outside a major cancer clinic?
It was the title that caught my eye as I walked past said cancer clinic on my way to lunch earlier today. There’s an awful lot of this “I’m so thankful I got cancer because it made me realise what’s important in life” rhetoric around at the moment – on the internet, on TV, in the self-help section of bookstores, and anywhere else you care to look. And while I have no doubt that many people benefit greatly from this positive thinking approach, I’ve also heard that many cancer patients find it to be just one more source of anxiety and stress, and resent it being perpetually rammed down their throats.
Think about it: you’ve been told you have a very serious disease that could very well kill you. You’re undergoing some of the most toxic, side-effects-heavy treatment known to man. You feel like shit, you’re losing your hair, you’re extremely worried about yourself, your family, your romantic relationship, your finances, your career, you name it…
…and people keep telling you you’re supposed to feel grateful for all this?
When I got closer to the poster, I realised that most of the information below the title is the kind of common sense, harmless-as-long-as-it-complements-rather-than-replaces-conventional-treatment content that won’t hurt and might just help. Under a different title, and with the exception of the “beneficial nature of illness” line, I might not have given the poster a second thought. And I’m sure some people did find the information interesting and helpful.
However, I recently helped to develop a translational research project recruitment poster for display in the same cancer clinic, and encountered very strict guidelines about what information can and can not be posted in areas used by patients. I can’t say for sure, but based on my understanding of the guidelines, I don’t think the poster I saw today would have made the grade. For that reason, I’m not very happy about the way the poster and its title target (some might say ‘cynically’) the area’s high density of vulnerable people.
Mind you, I also get mad when I see parking wardens put tickets on patients’ cars, a sentiment that is definitely not shared by all of my colleagues. So maybe I’m just being overly sensitive again.
Blog comments are my teacher: have at it!

A long time ago, on a blog platform far, far away, Richard Grant blogged about his delirious experience with some hard-core drugs given to him by some shady Dutch-Canadian drug dealer Eva Amsen. In the comments, Austin Elliott suggested that Richard may be one of the 10% of Caucasians with deficient CYP2D6 enzyme activity, leading to long lived high levels of dextromethorphan that may result in the transformation of an innocent cough and cold remedy into a dissociative psychedelic drug. Network-wide genetic testing was suggested.
This episode reminded me of a dilemma experienced by a Former Colleague (FC). FC had just read a paper¹ reporting that a promoter length polymorphism in the 5-HTT gene is associated with the development of depression in response to stressful situations. FC had developed depression during a time of stress some years before, and wondered whether this polymorphism might be to blame. Finding their thoughts returning again and again to this question, FC considered whether it was a) possible and b) advisable to run a surreptitious test on their own DNA.
Possible? Sure. FC’s lab did lots of DNA extractions and even more PCR. No-one checked the primer sequences FC ordered to ensure that they matched project-related sequences. Adding an extracurricular extraction, amplification and electrophoresis gel lane would in all likelihood have gone completely unnoticed.
Advisable?
Well, let’s leave aside the obviously, objectively, unethical use of grant-funded lab supplies and equipment for personal genetic tests. Yes, it would have been wrong, but the unethical spending would have represented an essentially negligible fraction of the lab’s overall budget… and anyway, other aspects of the dilemma are much more interesting.
What really gave FC pause was the psychological effect of knowing their genotype, even though they understood full well that the association between the variant 5-HTT allele and stress-triggered depression is not absolute, and some uncertainty would remain. Would it change the way they thought about their depression to know that it was quite possibly caused by a single polymorphism? Might it help to mitigate the stigma of poor mental health, and possibly even relieve some of the symptoms? Conversely, if the PCR results ruled out the polymorphism, might FC’s depression worsen? How might the result affect their future deliberations about whether to have children?
In the end, after much thought and discussion among friends, FC decided not to run the test. Not for nothing do genetic counsellors undergo so much training, and going it alone just felt like too much of a minefield.
With the advent of next generation sequencing, more and more of these genotype-phenotype correlations will become apparent. And in labs around the world, anyone with access to a PCR machine could find themselves wondering if the latest finding might just apply to them. Without the usual checks and balances in place that regulate the translation of genetic tests into clinical practice, students, postdocs, and other lab staff are vulnerable to the temptation to tack one extra lane onto their next experiment in order to delve into their own genome.
Would it really matter if lab workers could test themselves to confirm that NeoCitran makes them delirious because of a CYP2D6 deficiency? Well, only if they intend to use that knowledge to obtain a cheap, over-the-counter high. But when the results might change the way someone thinks about their mental health, the stakes are raised and we have a very real dilemma on our hands.
The other issue is that personal genetic testing performed in secret by lab workers potentially leaves the lab open to litigation and other costs. My undergrad department used to get students to extract and stain their own chromosomes in a second year cytogenetics lab, but stopped a couple of years before I started the course when one student was found to have a balanced translocation that suddenly shed light on her sister’s recent miscarriage. The university department ended up paying for her entire family’s genetic counselling costs. I could also imagine a scenario in which someone in a similar situation to FC uses their lab’s equipment and supplies to run a test on their own DNA, is distressed by the results, and sues because they were never told that this is something that you shouldn’t do…
Have any readers ever tested their own DNA, either with or without their superiors’ knowledge and permission? Has anyone received any formal training or advice on this issue? I think it’s going to be a growing problem, and I wouldn’t be surprised to see it appearing in some research institutes’ employee handbooks and training / orientation sessions in the near future.
1) Caspi et al, “Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene”. Science 2003, 301:386-9

33 is a nice friendly, symmetrical number; can I stop here, please?
To celebrate, I am launching my big 2010 fundraising campaign!
In June, I’m going to spend a weekend cycling from Vancouver to Seattle to raise money for the BC Cancer Foundation as part of the Ride to Conquer Cancer. The final route is still TBD, but will be something like 250 km / 150 miles over two days. Oh, and did I mention I only have a hybrid, rather than a road bike? (Yes I am crazy). The longest ride I’ve ever done was 60 km in one day, for the MS Society; I did that without any training at all, but this is a different beast altogether and I will be putting in some serious clicks between now and June!
FULL DISCLOSURE:
I work for the BC Cancer Agency, who will be the ultimate recipients of the money raised. The money is all going to support our research efforts rather than our publicly-funded treatment centres.
A couple of years ago I wrote about the difference in culture between the BCCA, where many of the staff and trainees raise money to support the institute, and my PhD institute in Scotland, where people were more than happy to donate to, say, a cancer hospice, but were reluctant to raise money for their employer.
So, what convinced me that my Canadian colleagues have it right?
Well, my PhD and postdoc projects were almost completely divorced from any clinical impact. But my new colleagues’ research is very, very different. I work with people doing some simply amazing work in cancer genomics, and I’m involved in some other outstanding translational and clinical research projects. (I wish I could tell you about some of the other awesomeness emanating from our labs and clinics, but until it’s published, that’s just not possible). For the first time in my career, I have more contact with cancer patients than just seeing them in the canteen when I pop into the clinical building to grab some lunch, and I have a much better understanding of how my colleagues’ work can and will result in better diagnostic and treatment options.
In the last couple of years I’ve also seen several relatives, friends, and colleagues (and their kids) diagnosed with cancer, and a few of them have either died or have incurable metastases.
HOW YOU CAN HELP:
In order to take part in the ride, I need to raise at least $2,500. This is almost as daunting as the length of the ride, and hence I am asking my awesome blog readers to help out!
Now, I’m not just asking for money, and I’m not expecting people to give without receiving anything in return. Please click through to my other blog for full details of how you can help, and how I might thank you!
“You can view my personal page and make donations here”:http://www.conquercancer.ca/site/TR/Events/Vancouver2010?px=2353200&pg=personal&fr_id=1331&fl=en_US&et=KQIeQZCxXhjxqwCz8GyLSQ..&s_tafId=158451.
This will be the only time this year or next year that I ask for donations. 2012 and onwards… well, it depends on how my legs feel when we get to Seattle!
Thank you in advance for your donations, advice, link love, and good luck vibes!
Right, I’m off to work and then to the Canada-Norway hockey game. Let’s hope Team Canada can give me a win for my birthday! If anyone’s watching on TV, I’ll be the one in the red shirt.
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I am publicising this event and asking for donations with pre-arranged permission from Nature Network management. Thank you so much, guys! Keep up the good work.

The opening ceremony of the 2010 Vancouver-Whistler Winter Olympics is a mere 49 hours away, and (except for the trifling matter of a shortage of snow at some venues and the developing hula-hoop crisis), we are ready! Let The Games Begin!
The Olympics coincide with the usual February frenzy of CIHR operating grant deadlines. These grants are the life blood of Canadian biological sciences research, the equivalent of the US NIH R01 awards.
Grant wranglers such as myself were delighted to hear that the CIHR has updated their procedures for this round, meaning that original signatures are no longer required. All we need are the original or scanned signatures of all co-applicants – the principal applicant and institution are now deemed to have signed when they hit their respective “submit” buttons. Hallelujah!
This news is especially good for off-campus researchers, like “my” PIs; in the past I’ve spent whole days at the unfamiliar and confusing UBC campus, juggling maps and lists of guidelines to make sure the signatures were obtained from the right people, in the right offices, in the right order.
However, my delight was soon tempered by the realisation that the internal forms (three different kinds, each requiring multiple signatures, in the right order) had not kept pace with the CIHR’s updates. I resigned myself to fighting the crazy Olympic traffic and the crowds coming and going from the ice hockey venue on the UBC campus.
BUT!
“Due to the Olympics”, we have a) been permitted to use scanned signatures on the internal forms, and b) been granted an extension to the internal signature deadlines!
The former is something that’s been discussed for years. Let’s hope that this unexpected Olympic benefit becomes one of the much-vaunted Legacy Projects.
The latter is just gravy.
Thank you, CIHR and UBC!

My sister-in-law got me a puzzle of the day desk calendar for Christmas. She apologised for not giving me something “better” (i.e. more expensive), but in all honesty it was one of the best presents I got this year.
The puzzles from January 29-31 consist of (vaguely) science-related anagrams. In each case, you have to fill in the blanks with two words that are anagrams of each other. The first few were ridiculously easy, but a couple of them proved tricky enough that I had to write the letters of some likely words down in random order to play with.
Who wants to play?!
Only one answer per commenter per hour, please, to give people in other time zones a chance to take part! No need to go in the right order though. I’ll do my best to add answers and bragging rights credit as the comments come in!
1) DNA AND RNA are blueprints for making proteins (Elizabeth)
2) Of all the elements, NONE is as useful for making brightly lit signs as NEON (Alyssa)
3) The coral REEF was FREE of pollution (Kristi. Oh, if only this was true)
4) Because the telescope was out of focus, the astronomer was UNABLE to see the NEBULA clearly (Graham. For shame, Alyssa, for shame!)
5) The brilliant BRAINY scientist could count in BINARY as well as decimal (Ken)
6) When doctors DILATE a patient’s eyes, they see more DETAIL in the retina (Kristi)
7) The computer used a fast ALGORITHM to compute the LOGARITHM of a number (Joanna)
8) You can turn a TRIANGLE into a square by ALTERING the number of sides (Kristi)
9) The doctor had to CALIBRATE his tools to look for a BACTERIAL infection (Stephen)
Have fun!