Thursday, November 23, 2006

Still talking

The voters have spoken... and less than 1 in 150 agree with my preference. No seat in Parliament for EénNL. Should I emigrate? Note to myself: stay with science, don't go into politics ;-)

Sunday, November 19, 2006

Talking and lying

On 22 November 2006, elections will be held for the Dutch House of Representatives or Parliament (‘Tweede Kamer’). Although realising the shortcomings of politics, as illustrated by the derivation of the word parliament from the French ‘parlez’ (talking) and ‘mentir’ (lying), I consider it a citizen’s duty to vote. I’d planned to orient myself on my vote a bit earlier, but unfortunate circumstances in my family have priority.

Lately, voting is becoming more difficult. It isn't that my preferences evolve like the saying (sometimes wrongly attributed to Winston Churchill) “If you are not leftist when young, you have no heart; but if you remain leftist when growing older, you have no brain”. Voting is made harder by the similarities between politicians and cars. Modern cars, shaped by wind tunnels into optimal fuel efficiency, are hard to distinguish from each other. Likewise, polls and focus groups have moulded most politicians, especially those from the big established parties, into almost identical creatures. One must take care not to succumb to sympathy for religious fundamentalist, racist, or otherwise distasteful politicians just because they seem authentic compared to the wind tunnel models.

The Dutch political system offers the choice between several parties, and allows for creation of new parties in a relatively easy way. This is a clear benefit over systems that are essentially two-party, particularly those that seem to evolve into an almost ridiculous 50-50 split of the population (why vote? Just toss a coin). In contrast we Dutch must avoid the paralysis of choice: 25 parties have registered, 18 of them participating country-wide, of which 12 are expected to win seats in Parliament. I lack the time and the endurance to watch the circus of political debate that is unfolding on Dutch television; moreover, this will mostly involve wind tunnel candidates and is expected to be rather boring. In that sense, the late Pim Fortuyn is clearly missed. Not being wind tunnel shaped he enlivened the debate; sadly, he inspired the first political murder in the Netherlands in about four hundred years.

One of the most peculiar newcomers is the Animal Party (Partij voor de Dieren). It’s not like, decennia after giving women the right to vote, we’ve done the same for animals. Rather, apparently some people think that humans are so well off in The Netherlands, it’s time to give priority to animals. In the short novel Gen’esis I introduced the fictional activist group NatureFirst, whose members plan to commit suicide after having murdered as many people as possible, arguing that nature is best served by extinction of the human race. Within a year following publication, Pim Fortuyn was murdered by an animal activist. I guess his murderer Volkert van der Graaf will be made a honorary member of the Partij voor de Dieren.

Talking about voting rights, the Calvinist Staatkundig Gereformeerde Partij has for a long time been against voting rights for women (they probably still are – I wanted to check their website, but that is closed on Sundays. How this brings back memories from boring forced-inactive Sundays from my youth…). I’ve understood that in order not to lose half of their potential votes, they allow Calvinist women to vote for the party chosen by their husbands.

To go back to my choosing problem, wind tunnel shaping of politicians appears to diminish their charisma, so I can’t use this criterion. Fortunately, information technology is there to help. Two websites have been created to assist the indecisive voter. The first and oldest one is It starts with the question whether the Dutch should be allowed to directly choose their prime minister. In the current system, after the election the executive branch of government is formed, the biggest party delivering the PM. In contrast, many feel that the international representative of the Netherlands should be directly chosen. I wonder whether Harry Potter would have made it. As a related matter, it is a pity that the political parties, certainly the major ones, avoid addressing the future role of the Dutch royalty, whose hereditary position is an anachronism in today’s meritocratic society.

As befits the tolerant attitude of the Dutch, the query contains a question about legalisation of soft drugs. Have a joint!

Although the 30 questions cover only part of the programmes of the political parties they provide an interesting perspective, especially because the answers of the parties are also shown. Strikingly, the CDDP answers the first question affirmative, and says ‘maybe’ to the 29 others. No, they are not aiming to achieve the Guinness record for single-issue parties; according to their website they have set up a system of ‘continuous direct democracy’ (that’s the CDD) by allowing voters to select other political parties as 'leaders' on certain issues. The CDDP politicians (if elected) will then follow the 'leader' parties’ votes on these issues. An innovative idea; let’s see how it works out. Not with my vote.

Reassuringly, the Stemwijzer matches my profile close to a party I’ve voted for in the past, the VVD ('party for freedom and democracy'). However, the party leader has indicated his preference for continuing his coalition with the Christian Democrats, and I prefer to keep religion and politics separate. Moreover, the newcomer EénNL gives a better match.

The second site is After answering a list of questions, my place in the political spectrum is shown in a two-dimensional graph as right from the middle (still got some brains it appears), and neither progressive nor conservative. Closest parties in the graph, with equal distance, are again the VVD and EénNL.

Some consider a vote for a small party a lost vote, because small parties mostly don’t participate in governing. I disagree. First, opposition seats are important as well. Second, the internet tools that enable easy comparison of individual preferences with the programmes of all political parties greatly enhance the exposure of small parties to voters, so maybe after the elections they won’t be small anymore.

So with some hesitation because I haven’t seen much from their leader on television, and apart from what’s written in their programme I don’t know their intentions, I conclude EénNL may be my best choice for these elections. Congratulations Mr. Pastors. Use my vote wisely, please.

Thursday, October 12, 2006

Nobel reflections

“In science we trust”. Not because it is perfect, or the only way to truth. But as a way forward for humankind, it is hard to beat. Most importantly, in its quest for knowledge and truth, it has developed extraordinary strong mechanisms to constantly check and improve itself. It is a strong driver of human progress. As I wrote earlier this year in the old fashioned way, on paper: "science and courage have shown us the way out of the cave".

Earlier this week I learned that the 2006 Nobel Prize for medicine or physiology was awarded for the discovery of gene silencing by RNA interference, which was discovered in 1998 by Fire and Mellow, and this brought back memories from my first postdoc position.

In the early nineties, as an ambitious but somewhat insecure young scientist who felt lucky to have obtained a postdoc job as a molecular biologist after having done a cell biology PhD, I cloned a cDNA fragment that yielded a Northern blot signal that took me some time to decipher. It was cloned by differential screening and named “255” because that was the number of the clone. The picture shows two lanes of RNA. The left lane contains RNA isolated from undifferentiated HT29-D4 colon carcinoma cells, the right lane contains RNA from differentiated cells. The blotted RNA was hybridised with the radiolabelled cDNA probe 255. It appears that a single species of RNA (just above the 5S RNA band) is more intense in the differentiated cells, whereas the ‘smear’ is more intense in undifferentiated cells.

Subsequent experiments yielded similar but not identical clones, e.g. DD-24 (isolated by differential display). The small RNA just above 5S appears to be the same as in 255, but the ‘smear’ hybridisation is less intense as compared to the small RNA. The signal in the third lane (HeLa cells) is the same as in the undifferentiated HT29-D4 cells.

After some thought, I concluded that the pattern could be explained by assuming that the small RNA that became more intense with differentiation represents an RNA whose expression suppressed that of many other genes (the ‘smear’ in the picture). I reckoned these genes were detected because they shared a homologous region with the ‘suppressor’ RNA, which was involved in the putative mechanism of suppression.

When I discussed this hypothesis with the senior group leader who was appointed as advisor of my project (by his and my boss, the MD/PhD department head who lacked expertise in molecular biology), he remarked with just a little hint of unbelief and disapproval “This could be the Nobel Prize, but it is more likely to be an artefact and a distraction from your project”. The concept of RNA interference was unknown at that time. He had much more experience in molecular biology than I had, so I took his advice and did not further explore these findings, focusing instead on cDNA clones that looked like real mRNAs. Alas, I never published the findings mentioned above.

To check the advisor’s qualities as a prophet, upon learning the news of the 2006 Nobel Prize I dug out the data from this project. At the time of cloning, the DNA sequences of 255 and DD-24 were unknown. Checking again now the human genome project is finished, significant similarities with published sequences were found. Clone 255 turned out to be part of the coding sequence of TMEM50B, a human transmembrane protein. Clone DD-24 partially matches a human BAC clone, however, the sequence annotation did not mention specific features in this region.

So for me the intriguing question remains: was I indeed looking at an artefact, or was my hypothesis correct and was this an early finding of interfering RNA? I have left this project since 1994, and molecular biology since 1998, so any clues from readers are welcome.

As you may imagine, this little story features large on my list of potentially missed opportunities (trumping the glimpse of EGF receptor heterodimerisation during my PhD work, well before EGFR2-4 were discovered). I wonder what would have happened if I would have disregarded the advice, and pushed forward investigating these unexpected findings. It might have ended in disaster (especially the EGFR project, which could have jeopardised completion of my PhD work). Apart from my personal failings to pursue these research findings, I wonder about the influence on both my advisors and myself of the Dutch system of research funding that was operating at the time. To me the system seemed largely risk-averse, favouring scientists who slowly but solidly built their little piece of the temple of knowledge over those who tried to speed up by experimenting with novel building materials and designs. So be it. When in 1998 - a few years too late, as I realised later - I shut the university doors behind me for a position in industry, the relief was greater than the regret.

Still with me? Thank you! I’m impressed. Apologies if I got too technical above. Future postings may see more mundane topics like the upcoming Dutch elections, and the lack of real choice as I perceive it now (I’ll study this more deeply when we are closer to election time). I may dwell on the joys of living in the ‘ever closer’ European Union, especially when living in one member state and working in another, having to deal with regulations and taxes in both - not to mention the daily 203 km commute :-(. Science and politics of GMO (Genetically Modified Organisms or Greenpeace Membership Operation, whatever you prefer) also interest me. Perhaps I will introduce you to my favourite author, Nicholas van Damme. I’ll try to avoid the topic of religion, but may not always succeed; it seems the scars of my Calvinist childhood are not yet completely healed.

All the best,