Saturday, October 11, 2014

The Superman Disorder?



When I was 13 years old I was diagnosed with Gilbert's Syndrome, a genetic disorder affecting the promoter of a gene for the enzyme glucuronyltransferase, which conjugates bilirubin. 5-10% of the population have GS, and it is benign, leading only to elevated levels of unconjugated bilirubin in blood tests and occasional slight jaundice, which friends of mine have sometimes remarked on.

What seems weird, though, is that in the last few years there has been a raft of statistical epidemiological studies suggesting that us GS guys have a huge, invisible health shield! Those of us with the disorder appear to be  protected, sometimes strongly,  against cancer, cardiovascular disease, respiratory disease and kidney disease, and have lower BMIs, reduced cholesterol, more elastic arteries, reduced inflammation status and all sorts of other yummy stuff. There was even an article published last year showing success in the bottom line: in a study of 25,000 people over 350,000 person-years the overall mortality  of us Gilbert's Grenadiers was only half that of normal people.

Why would this be? The suggestion (albeit disputed) is that protection arises at least in part because unconjugated bilirubin is a powerful antioxidant, and therefore protects against oxidative stress. That would then be a bit like having had your ration of five fruits and vegetables before you even get up in the morning.

I'm not buying it, of course. There has to be a catch somewhere, doesn't there? Hyperbilirubinemia in infants can lead to irreversible kernicterus, or brain damage. Also, drug toxicity would appear to be worse in some cases for us guys. So I'm waiting for the negative metabolic effects of GS to be elucidated using systems medicine approaches. But until that time, I'm formally in the superman club!

Tuesday, September 30, 2014

Copy Cats

So the continental passion for plagiarism finger-pointing would now appear to have finally reached the USA.

The recent  wave of appropriations appears to have started in Germany, with a number of high-profile politicians resigning after having been  inculpated for lifting sections of their doctoral theses. The first of these was  Karl-Theodor zu Guttenberg, the German Defence Minister (aka Baron Cut-and-Paste) in the Xeroxgate affair of 2011, and since there have several more, including the Education Minister Annette Schavan in 2013. There's even a website, Vroniplag, where theses can be virtuously scoured.

Now the plague of plagiarism seems to be overrunning US politicians and journalists as well.  While I remember Joe Biden purloining from Neil Kinnock in 1987,  there has been nothing like the density of recent episodes, including, to name but a few,  Fareed Zakaria, Rand Paul,  John Walsh and, in the last couple of days alone Mary Burke, the Gubernatorial candidate for Wisconsin and Gordon Ball, the challenger of Senator Lamar Alexander here in Tennessee. Each time the perpetrator is accused of vile cheating and resignation is demanded.

So what are we to make of all this? Well, for us scientists the rules are relatively simple: thou shalt not find out about someone else's original idea then claim thou hadst it first. And that's what makes the cases of the German politicians relatively cut and dried; they cheated, claiming originality of ideas,  in order to get their precious doctoral titles.

But in the recent US cases things seem to me to be  not always so clear. Certainly, when a politician states something in a powerful and original way, as did Kinnock in 1987 [Why am I the first Kinnock in a thousand generations to go to university? .... Is it because my ancestors were thick? ..... No, it's because they didn't have a platform to stand on]  then attribution is called for. But copying bland, unoriginal  prose into one's newspaper article or campaign website, while showing laziness or incapacity for original thought, does not imply the same level of theft. Stating that "a strong military is the basis of peace" should not require explicitly crediting the Darius the Great with having had the idea, should it?

Claiming original  ideas (or  novel, enlightening reformulations of old ones)  from others  is serious plagiarism.  The rest of the bleating is becoming rather trivial.







Wednesday, September 17, 2014

1707

"That the two Kingdoms of England and Scotland shall upon the First day of May which shall be in the year One Thousand Seven Hundred and Seven and for ever after be united into one Kingdom by the name of Great Britain And that the Ensigns Armorial of the said United Kingdom be such as Her Majesty shall appoint and the Crosses of St. George and St. Andrew be conjoyned in such manner as Her Majesty shall think fit and used in all Flags Banners Standards and Ensigns both at Sea and Land."

Saturday, September 6, 2014

The Age of Aerobatics


In the 1990s I lived with my family in Chateaufort-en-Yvelines, near Paris.

Three things you didn't know about Chateaufort:

- On 19 August 1913 Adolphe Pegoud  parachuted out of a plane from the Chateaufort airstrip. While descending, as he said, 'comfortably', he noticed his empty plane performing weird arabesques in the sky before crashing. This gave him the idea to fly a plane upside down, which he then did,  thus inventing aerobatics.

- Chateaufort has a little hill, which, though nothing like l'Alpe d'Huez, is still celebrated, as the last hill on the Tour de France.  We watched the Tour there in 1994. Arriving an hour before the riders were due, we waited three hours for their arrival, during which two storms passed over. After an inexorable parade of cars, they flew by, bunched, in a confusing flash.  I looked for the yellow jersey - there were five of them. In 1989 they erected a bronze stele at the top of the hill for Jacques Anquetil, the first cyclist to win the Tour five times. It was quickly stolen, presumably for the metal, and replaced with a less valuable version.

- Chateaufort has a restaurant called La Belle Epoque, which was one of the snootiest in the region when we lived there. When my ex-advisor, Martin Karplus at Harvard, asked where I lived, I replied that it was very small and he wouldn't have heard of it. He persisted, and when I told him he said "Wait a minute! Doesn't that have a nice restaurant?"

Friday, September 5, 2014

Why Elect judges?

One thing I never really understood about the USA is this need to elect judges. In Europe, where I come from, judges are by and large appointed according to how good they are for the job, rather than for political reasons. In other words, what counts is how well any prospective judge knows the law.  The politicians make the laws, and the judges simply decide whether these laws are being followed, don't they? Having elected judges certainly makes them accountable to the public, but how is there public to know who is a good or bad judge? Moreover,  candidate judges  have to bend to popular undercurrents and special interests.  A weird procedure. Hey, why not elect doctors and professors as well?

Tuesday, August 12, 2014

Wull Oi Dort Know 'Bout Tha' Rum Ole "Accent Reduction" Do

Oi see ORNL huz cancelled 'as "Suthern Accent Reduct'n" clarse.
Wull, Oi come frum Nawfolk in the UK, 'an um 'av'n fun 'ere tryun ter wroite  loike how Oi use ter speak over thar.

If yew can't picter ut 'ere's a video link ter 'ow 'ar Nawfolk Dumplin accent go.
Ass a sawng whut sold more 'an the Beatles or the Rolling Stones down our way..

Ar go'a say Oi wu'nt a gart no-where if Oi'd a kept that accent, so I s'pose I sor'a did a bit a accent reduc'n moiself - dort know zakly when, tho. Prob'ly at Leeds Uni, coz they sure as hell couldn't understand a good ole Nawfolk Dumplin dialect even there. So I s'pose the Suthen Accent Reduct'n thang at ORNL moite a bin a good thang - did summon loike 'ut moiself, yew see.

Saturday, July 19, 2014

A Special Pill Just for You





One of the many significant acts of my former advisor, Martin Karplus, was to help set up, in 1989, Vertex Pharmaceuticals -  one of the first companies to use a design strategy based on "rational", structure-based approaches.  Now, Kalydeco, designed by Vertex, is a glimpse into the future of personalized medicine. It is the first cystic fibrosis drug to treat the underlying cause of the disease, and works for those ~4% of patients with a certain mutation of an ion channel, which is potentiated by the drug. 4% amounts to about 2,000 patients, for whom this a wonder drug.  However, Vertex has slapped a $300,000+  yearly price tag on this drug, making it one of the most expensive in existence, and this has led to an understandable outcry from various sources, including some scientists involved in the development of the drug itself. In retort, Vertex point out that they have spent $6.5 billion on R&D that needs to be recouped and that it has only two drugs on the market.

Given that personalized medicine is aimed at ever smaller numbers of patients,  many fear that this approach will lead to ever more expensive drugs. But the one facet few seem to be talking about in this context is the origin of that  $6.5 billion number above. Most of that outlay will have been researching failures. Many of us are now trying to develop fast and efficient ways of finding drug candidates that are more likely than before to have high efficacy and safety.  This will get more personalized medicines to market quicker, with less R&D outlay. It stands to reason that if Vertex had discovered Kalydeco earlier, when its total R&D outlay had been only, say, $1 billion, then the price tag would have been lower.

It's not written in stone that personalized medicines will have to break the bank.