Dr Samuel Furse » 2013 » February

 Railway to Somewhere Thursday, Feb 14 2013 

Is £32bn enough to build a good railway?

We will have to hope so as that is the proposed budget for HS2, a new railway due to open in about 2033.  The long-awaited route was announced at the end of January 2013, raising a rather inevitable raft of concerns, including some about historical events and some that are more business-based.

There have been a variety of views expressed – generally either in favour of or against HS2.  Those in favour talk about increasing capacity and that trains will be faster, and presumably safer.  Opponents say it is not cost effective, that the evidence does not really support the reasoning proposed and that there are bigger priorities elsewhere, particularly regional railways in the north of England.  There is little doubt that such regional railways would undoubtedly join up that region better than the current system by increasing capacity and lowering journey times.

Increasing capacity on railways means, of course, improving infrastructure such that more people can travel between stations in a day.  I say stations, rather than cities or places, because that is what they seem to be called, inexplicably—either that or “station stops”.  It sounds like the rhetoric of an ignoramus or the result of a botched re-branding, but perhaps there is another possibility.  Perhaps they are just trying to be honest.

In the 19th century, it was often quite difficult for railway companies to cite stations and lines where they wanted them.  Just look at maps of places like Cambridge or Loughborough: the railway stations are barely in the place of the name they bear.  This sounds preposterous enough on its own, but the worst thing is that despite the century-and-a-half there has been to improve the situation, the railway station in Cambridge is still not near big roads, the airport, the centre of town or where most people live.  The same is true of a relatively new station ambitiously named “East Midlands Airport Parkway”.  Easily the nearest thing to that is a power station.  The station is five miles from the East Midlands airport.  No buses are scheduled to stop at the station, and you have to ring for a cab from the one firm advertised at the station; the hardware of a taxi rank is barely evident.  None of this poor planning and execution is helpful for passenger capacity, and thus usefulness of railway infrastructure, on anyone’s terms.  The transport minister in the Lords under the last Labour government summed this up from a different perspective when he said about the HS2 public consultation that “everyone wants the stations but nobody wants the line”.   We start to see why building new railways is difficult.

These points imply a history of a problem that would surely be put at the top of the list of building new railways: how to avoid compromising on the quality of the railway so the thing is useful once it is finished.  Usefulness is clearly the clear over-riding concern: no one embarks on major railway-building projects because they are bored.  Further, there is no doubt that a good railway will pay for itself on that basis alone, as Brunel’s railways have done, if the effort can be made in the first place.

It was therefore with bated breath that I awaited the proposed route of HS2.  They might finally be about to do something really good with this big project, I supposed that they might be about to join up some big places and allow branch lines and other building projects to develop after that.  I wondered if they might avoid the need for the closures of railways in the 1960s and 70s under Beeching, by ensuring that what was being proposed was useful in the long term.  The route published for HS2 was therefore rather disappointing.  Birmingham, and important hub in the West Midlands, appears to be a spur from the main line, rather than any kind of interchange.  It is therefore awkward to connect the northern stations with those in either the East or West Midlands by train.  A station is being built at a place called Toton, with the rather weak suggestion that this will serve “Both Nottingham and Derby”.  It is a good trick if you can do it, currently 20 minutes is a quick journey time by train between those two cities.

The truth is that this sort of thing represents a nasty compromise.  Making transport plans seem big and shiny will only become disappointingly empty if they are not backed up by joining up the planned infrastructure with other transport means and destinations in a coherent manner.  Put another way, there is no point in cutting journey times for distances of 150 miles by 45 minutes, if the 10 miles from the station to the final destination is not only required but then takes an hour because that station is in the arse end of nowhere on a line that is in the wrong place.

So, there is at least one thing that is wrong with HS2 (Birmingham spur) and another (Toton interchange) that is, at best, complicated.  On this basis, it seems likely that HS2 needs a re-think.  Despite these and other prescient concerns, it is quite difficult to be actively against HS2.  Are we are in a position to complain about funding of railway projects, especially when we need to invest in hardware to improve the economy?  The sad truth is that we will probably never be in a position to complain, even though much of the planning is dubious and does not fit with the priorities of what will be useful or workable.  This is why mainline stations get refurbished at a cost of millions, doubtless making their use marginally easier for a tiny number of passengers, but while several other places remain without a station at all.  That said, a refurbishment or a line that nearly goes somewhere useful is something, and something is more than nothing.

 Equal Marriage and Really Rubbish Debating Tuesday, Feb 5 2013 

Reform of the law about marriage is being debated and voted upon in the House of Commons today.  The debate has been going for a while, so a vote about now seems timely.   It will be between the ‘pro’ side, whose principle argument seems to be that same-sex couples should be allowed to get married if they want to, in the way that opposite-sex couple are, and the ‘anti’ side, whose principle argument seems to be that relationships and sex between two men (and by implication between two women) are forbade in religious texts and so should not be allowed to marry as this would lend credence to a sinful act.

In a democracy, this seems like a fairly ordinary debate in many ways—two groups of people debate/argue over a certain thing and whichever is the biggest group by the end, at least in parliament, wins.  It is how virtually every other decision is made in a western democracy.  But I do find myself wanting more.  What the arguments in the debate boil down to is that one side wants it because they think they should have it, and the other side thinks they should not.  Based on that you might say there is not much difference, one might easily think that any kind of objective decision was basically impossible.  It could be met with the attitude ‘Let it go to the majority, there’s no shame in that.’   I am not so sure, and for two reasons.

First is the obvious unfairness of one group of people (e.g. devout Christians) telling another group of people (gayers) how they should build their relationships.  This notion that it is not allowed according to the bible becomes preposterous with even the most superficial analysis: if the law were changed to allow pairs of men and pairs of women to get married, it would not change what Christians or other religionists do or have to do with respect to marriage.  So why should the religious argument about what is written in religious texts be relevant?  It almost makes basing marriage laws on the bible look tantamount to religious persecution.

The second argument is a bigger one.  It also goes right to the heart of our legal system.  It is an argument about equitability.

Historians tell us that the signing of Magna carta in 1215 was the first step towards an equitable legal system in England.  It was the initial move towards all people being treated equally in the eyes of the law.  Obviously we continue to make exception for those who are too young to make the decisions knowingly, or too ill or infirm to do so, but in general being 18 or 80, male or female, rich or poor, justice is the priority in decision making.  This, I think, is universally agreed as a good plan.  So, if we aspire to an equitable legal system, in which all consenting adults have equal legal value, why would we not let any two of them get married?  Despite the length of the debate, that argument does not seem to have surfaced.

I suspect marriage reform will take place, and in case my inflammatory tone has hidden it too well, I strongly support the move.  I think there are too many people who do support the move for it to be voted down and it is too much of a vote-winner not to go through.  It just seems a shame that we will probably get the right thing but for the wrong reasons.

 Edelfosine: A Lipid with Applications in Cancer Friday, Feb 1 2013 


The uncontrolled growth of cells in a body is the traditional definition of cancer, and it remains relevant. The difficulty with tackling this disease in a clinical setting is being selective; we want to be able to kill off only the cancerous cells, and not healthy ones. Although there have been many successes in drug–based cancer treatment (cis-platin, taxol, etc), this remains one of the biggest challenges. With this in mind, several approaches are being researched, including semi-physical studies of the surfaces of cancer cells.

Czyz et al. [1] have shown that the introduction of a man-made lipid (known as ‘non-endogenous’) into living systems has several chemical, and presumably physical, effects. One claim they make is that one such non-endogenous lipid, edelfosine (see Figure), accumulates in the cellular and endoplasmic reticulum membranes. This is evidenced by the reorganisation of these parts of the cells. There is the suggestion that this reorganisation also occurs on a much more local scale, with particularly high concentrations of edelfosine in so called ‘lipid rafts’. However, with the theory of lipid rafts still being controversial (at least in living systems) it is unclear what foundation there is for that assertion.

Figure. The molecular structure of edelfosine.  Note the head group similarity to phosphatidylcholine and the hydrolyisis-resisting ether-linked fatty alkyl chain.

Figure. The molecular structure of edelfosine. Note the head group similarity to phosphatidylcholine and the hydrolyisis-resisting ether-linked fatty alkyl chain.

What is clear, is the chemical influence of this lipid. Through the use of a protein, called pHluorin, and shining light at the cells, the pH of the liquid medium inside the cells (called cytosol) could be determined [2]. The colour and intensity of the light re-emitted by this protein are a function of the concentration of hydrogen ions present. With appropriate calibration, this gives a good insight into the ionic environment inside the cell. What Czyz et al. found was that the intracellular environment becomes much more acidic soon after the lipid had been administered, which immediately begs the question of how this occurs on a molecular level. The suggestion is that the presence of edelfosine has a direct knock-on effect on the cellular machinery that controls the internal environment. This in turn leads to proteins being transported to the wrong parts of the cell, reducing its ability to control pH and prevent the system becoming acidic.

This impressive action of this lipid provides a useful entry into a cancer therapy because it is needed only in small amounts. Edelfosine disrupts an important cellular control mechanism, the falling apart of which leads ultimately to apoptosis.

Although it is not clear what side-effects there may be, or how good a cancer drug therapy this particular lipid will make clinically, the therapeutic approach of using a non-endogenous lipid that accumulates in and interrupts the biochemistry of the target cells, is a tantalizing one that is currently only in the early stages of research.

References

[1] O. Czyz, T. Bitew, A. Cuesta-Marbán, C. R. McMaster, F. Mollinedo, V. Zaremberg. Journal of Biological Chemistry, 2013, DOI: 10.1074/jbc.M112.425744.

[2] R. Orij, J. Postmus, A. Ter Beek, S. Brul, G. J. Smits, Microbiology, 2009, 155, 268-278.