On BioScience and Life and Such

Archive for June, 2008|Monthly archive page

A good science blog is:

In Uncategorized on June 26, 2008 at 9:29 pm

A response to some points made on Friendfeed and Twitter (@biotecher) –

In addition to posting news, a science blog should serve to make science more accessible by being less formal in its presentation. By blogging a personal (and political) viewpoint a scientist can express thoughts he would otherwise be unable to in a scientific journal/publication. A good science blog serve as a discussion hub for scientists and I am pretty sure that blogs in this way will continue to be important information channels both between scientists and out to the public.

Which blog is the best I think is irrelevant, – we need a lot of them. Twitter and Friendfeed are just a bit to shallow for proper scientific arguments to be made, but like blogs serve  as an extension to journals, they serve as extensions to blogs.


Was it all in vain ? The scientific method tale

In Uncategorized on June 23, 2008 at 9:34 am

post to news.thinkgene.com

I did my PhD on one of the most studied enzyme-systems of all time, the cAMP-dependent protein kinase (PKA). One would think that the tools we used were accurate when the enzyme was as thoroughly characterized as it was. But alas!, now we learn they had major flaws. The endless kinase assay’s lasting until the wee hours, were they all in vain ?

“….nonspecific effects are
widespread; they include actions on other protein kinases and signaling
molecules and also on basic cellular functions, such as transcription.”

We had two teams in my group, one was the gene characterizing team – we did cloning, sequencing, expression and transcription analyzes mostly. The other was the protein activity and interaction team who did a lot of enzyme activity (kinase) assays, protein-protein interaction and immunoblots. Members frequently crossed team borders to learn the necessary methods. I was in the gene-group, but I did my occasional kinase assay and cell-culture experiment as well. As a rule, the kinase assays (as well as cell culture assays) always included inhibitors of the kinase and very often those inhibitors were H89 and/or  KT5720. These inhibitors were thought to be specific so that any decrease in enzyme activity one would see upon adding them, was attributed too a loss of PKA activity.

A recent review by Andrew J. Murray in Science puts a serious dent in that assumption. These inhibitors seems to act on a range  of other signaling systems. Their targets seems to be very diverse indeed. Specific they most certainly are not. That means that a lot of the inhibition we would see and base our conclusions on, was wrong.

“…a substantial
body of evidence has now accumulated
that indicates that both H89 and KT 5720
can have effects independent of PKA inhibition.
These actions are extremely varied;
some of the most worrisome actions are the
substantial effects on the MAPK and calcium
signaling pathways, which interact with
the PKA pathway and mediate multiple
cellular functions.”

and even more worrying:

“Furthermore, many of
these non–PKA-based actions of H89 and
KT 5720 occur at concentrations that have
been widely used to investigate PKA function.”

The final conclusions and the cellular mechanisms we unraveled, one can only hope were not wrong, which would be fortunate for me and others with a history in the field. But, one can never be sure and reevaluation may be in place for some of the past studies

“the molecular bases of some
cellular processes attributed to PKA solely
through the use of these compounds may
have to be reevaluated.”

Any experiment with H89 in the future needs to take this new information into account. And in the review, the author outlines a number of alternative approaches to inhibit PKA activity in a specific manner.

The above outlined studies indicate that neither
KT 5720 nor H89 should be used alone
to study the function of PKA. As these compounds
are so commonly used, it will therefore
be necessary to devise strategies that
can overcome their shortcomings.

Although annoying and possibly detrimental to papers I have published in the past, I cannot help having this proud feeling. Because, this is the beauty of the scientific method: not only do we admit we’re wrong (and publish it in high impact journals), we have efficient methods to prevent the wrongdoings from continuing. Any responsible and updated reviewer will now dispute all conclusions based on experiments involving these inhibitors. Then scientific results in the field will become more accurate. In addition, new conclusions and insight may come from this increased understanding of the limitations on previous results.

Science involves unrestricted sharing, regardless of the nature of the information. Add peer-review and you have  the scientific method working at its best.

Genetic counseling as a patient right, not as a progress killer

In Uncategorized on June 20, 2008 at 12:57 pm

Genetic future had a thorough and balanced post on Direct To Consumer genetic testing. The following discussion between Daniel, Deepak and Dr. Murphy shed further light on the issues surrounding this topic.

Seeing this discussion from the outside I have the following thoughts to share (the text underneath is also a comment on the above mentioned blog post):

I can tell you that I live in a country where genetic testing is regulated extensively: any pre-diagnostic or pre-symptomatic test can only be done by a few authorized (public) medical genetics centers, and must be followed by genetic counseling both before and after testing. These strict test-definitions actually include “innocent” tests like cyp-testing for pharmacogenetics. I can promise you that you do not want a situation like this. Over-regulation hinders progress and takes away personal freedom. While I am sure that some regulation should be in place (like lab-analyzes quality control and restrictions to avoid overselling of tests and/or test-results), medical counsel is not really that essential. This point is underscored by the fact that patients seems to largely ignore the potential impact of even the most damning of genetic test-results (Huntington’s, see my previous posts (1, 2, 3) on genetic counseling). That said, patients that feel insecure when faced with their own genetics (which is probably a lot of them) should most certainly have the opportunity to consult a physician knowledgeable in genetics. This however, should be implemented as a patient-right rather than industry-prohibition.

And the discussion goes on

Quote of the month June 08

In Uncategorized on June 19, 2008 at 11:06 am


So that’s it: to me, DNA represents the Next Great Hack — maybe the Last Great Hack; who knows what the world — what humanity — will look like on the other side of the biotech boom?

Thomas of Aminopop, when asked what DNA means to him by Dr. Hsien-Hsien Lei at Eye on DNA.

Publication phusis, Call for help

In Uncategorized on June 16, 2008 at 11:10 am

I have had many thoughts on how to present scientific data, and will have many more. SciPhu is, so far, the compilation of some of those, and blogging is the adverse event from trying to realize them. I have however come as far as I can on my own and need help to carry this project through.

This is what I have been planning: SciPhu is supposed to develop into a certification site for scientific thoughts, ideas and data. It is supposed to gather a large community of competent reviewers from virtually any scientific field. These reviewers are supposed to provide thorough peer-reviews of any scientific presentation as requested for evaluation on SciPhu.com. A successful review is supposed to give the author(s) a stamp to put on their presentation as a guarantee for scientific quality and credibility.

Through a FriendFeed discussion (original post by Bill Hooker) I came across this commentary on the problems of evaluating online publications. The author, Gary A. Olson, presents some solutions that are very similar to the principles I’ve worked out for Sciphu.

Clearly, the scholarly community needs to devise a way to introduce dependability into the world of electronic scholarship. We need a process to certify sites so that we all can distinguish between one that contains reliable material and one that may have been slapped together by a dilettante. We need to be able to ascertain if we can rely on a site for our own scholarship and whether we should give credit toward a colleague’s tenure and promotion for a given site.

And he proposes to establish certification bodies to achieve these goals.

The major professional and scholarly organizations in each discipline should (devise a certification process in which a site owner can apply to have a site reviewed and recognized, perhaps for a nominal processing fee. The site would be subjected to a formal and rigorous review by peers in the disciplinary area covered by the site.

Which is a very good description of what I wanted SciPhu to be like (except for maybe the fee, which should be for commercial users only). I have taken the liberty to replace with SciPhu in relevant places in the rest of these bullet points (the original text in brackets):

  • Only those sites meeting the highest standards should be awarded certification.
  • Once a site wins certification from SciPhu (the national scholarly society), it should be permitted to display that stamp of approval prominently.
  • The certification should remain in effect for a specific and limited amount of time (since a site can change rapidly and without notice). The site should regularly seek renewal of its certification.
  • SciPhu (Each disciplinary organization) should issue a resolution recommending that departments construe certification of a site as indicating that it has met the highest standards of scholarship.
  • SciPhu (Each organization) should maintain an online registry of certified sites.

A central site accessible to all is much more efficient than local evaluation bodies. Also the potential to gather a large collection of qualified referees is present only on a truly international site. Such a broad site would also be able to satisfy the open-access requirements in our Web/Science 2.0 future.

The SciPhu blog was set up as a starting point to gather a community of peer-reviewers. Making the blog successful is going to take a long time however, and given this commentary as well as the current interest in different publishing models, it seems wise to try and speed up.

To do this I need help. I need help setting up a good site, – a wiki perhaps. I also need help advertising this to the broader Scientific community and recruit referees. Even with help, achieving success is not going to be a stroll in the park. But without help it is going to be near impossible.

The end result may not end up as originally planned: names, concepts and strategies may/will change on the way, but I strongly believe that this is a path worth traveling.

I also think that Gary A. Olson is to narrowminded when it comes to requirements and scope of such a certification. Doing this online with a large community of referees makes it possible to get peer-review very quickly because reviewers would be accessible around the world 24-7. And there is no reason to limit such reviews to scientific publications. Any news-piece, advertisement or company information with scientific content could get reviewing through a SciPhu-like site. Extending reviewing to non-scientific publication forums is also the commercial opportunity, or business model if you will.

If you are interested in starting a broad and open-minded collaboration on this (and I really hope you are), please leave a comment, send me a mail or even better, join and use The Life Scientists room on FriendFeed for further discussions.

Duh !

In Uncategorized on June 10, 2008 at 10:32 am

“No shit sherlock” and/or “Thank you captain obvious”:

The ACCORD results may encourage doctors to recommend lifestyle interventions – such as weight loss and exercise – as other options besides medication, Krumholz says.

From a Nature News piece on diabetes treatment

The 2008 bullet points of the year award goes to…

In Uncategorized on June 9, 2008 at 8:13 am

…..Nassim Nicholas Taleb

From a TimesOnline piece by

1 Scepticism is effortful and costly. It is better to be sceptical about matters of large consequences, and be imperfect, foolish and human in the small and the aesthetic.

2 Go to parties. You can’t even start to know what you may find on the envelope of serendipity. If you suffer from agoraphobia, send colleagues.

3 It’s not a good idea to take a forecast from someone wearing a tie. If possible, tease people who take themselves and their knowledge too seriously.

4 Wear your best for your execution and stand dignified. Your last recourse against randomness is how you act — if you can’t control outcomes, you can control the elegance of your behaviour. You will always have the last word.

5 Don’t disturb complicated systems that have been around for a very long time. We don’t understand their logic. Don’t pollute the planet. Leave it the way we found it, regardless of scientific ‘evidence’.

6 Learn to fail with pride — and do so fast and cleanly. Maximise trial and error — by mastering the error part.

7 Avoid losers. If you hear someone use the words ‘impossible’, ‘never’, ‘too difficult’ too often, drop him or her from your social network. Never take ‘no’ for an answer (conversely, take most ‘yeses’ as ‘most probably’).

8 Don’t read newspapers for the news (just for the gossip and, of course, profiles of authors). The best filter to know if the news matters is if you hear it in cafes, restaurants… or (again) parties.

9 Hard work will get you a professorship or a BMW. You need both work and luck for a Booker, a Nobel or a private jet.

10 Answer e-mails from junior people before more senior ones. Junior people have further to go and tend to remember who slighted them.

Nassim Nicholas Taleb

Update: Why don’t they make a birth control pill for men

In Uncategorized on June 5, 2008 at 11:10 am

post to news.thinkgene.com

But they have………, and like the female pill, it’s based on hormones, – mainly testosterone. According to a review by John K Amory et al., Testosterone mixed with second agents like Progestogens and GnRH-antagonists is able to suppress spermatogenesis to zero in 80-90 % of men and give near completion suppression in the rest.

Thus, the more relevant question must be: why aren’t men taking their birth control pill ?

Well one reason can be that men could be facing an injection rather than a pill, – and needles are psychological barriers to many, – men and women alike.

Another reason is men being hormonal (sic)…..mixed with a fear of possible side effects. But then again, side effects may not be a major issue since, in gym’s and athletes arena’s around the world, many men are taking these hormones, exactly because of the side effects to infertility – improved athletic performance and muscle mass. Thus, one would think that these side effects were desirable for a lot of men.

For men, it looks as though the purpose of infertility just doesn’t quite cut it as reason good enough for taking your pill, even if the side effects have a positive spin or are minimized. Men are simply shying away from hormonal treatment to stop spermatogenesis, for whatever reason.

Aternatives then, are needed since according to MaleContraceptives.org contrary to what can be concluded from the perspectives mentioned above, there is an expressed will amongst men to use pharmaceutical contraceptives. They list projects for improved hormonal therapies as well as non-hormonal alternatives already in existence or in development. They even list a number of places where clinical trials are happening. Trials you could join presumably, if interested.

A company that is not listed on their site (yet) is Spermatech which is a (the only ?) company working on a non-hormonal pharmaceutical contraceptive. Their drug target is a sperm specific protein that is crucial for sperm motility. If you knock out the activity of this protein, you also knock down the sperms ability to swim and hence it’s ability to fertilize the egg. And it all should happen without effects in the rest of the body since the protein is sperm specific, – or so the theory goes. Because, It is a long way from drug target to approved pharmaceutical. So far though it’s all looking very promising.

No matter which drug or treatment reaches the market, it’s about time we as men, share the burden of pharmaceutical contraception with our women. Possibly, we could even save some lives since todays female birth control pill is not risk free.

More blogging on this issue can be found by searching the phrase “Why don’t they make a birth control pill for men” at ScienceBlogs.

Original post here.

Disclaimer: I own shares in Spermatech AS. Their patents were issued based on scientific publications where I was lead author.