Exon 14

To paraphrase "GPs Behind Closed Doors", this post contains challenging medical issues.

Exon 14 sounds like a science fiction film. As little as ten years ago, it could well have been, but actually it is real.

I have something called the MET Exon 14 skipping mutation. It alters a specific gene, the MET gene (mesenchymal-epithelial transition) so that affected cells produce an abnormal protein which makes them grow uncontrollably.

The mutation causes lung tumours. It affects mainly smokers, but I put mine down to dirty Leeds in the nineteen-seventies when large numbers smoked, and offices, buses, cinemas, pubs and the shared houses I lived in reeked of a blue haze that stuck to your hair and clothes so much that you failed to notice. Leeds was also full of traffic fumes and pollution from coal fires and industries, and my accountancy job involved hours walking round warehouses, mills and factories where there were all kinds of dust and chemical vapours. The cause on my health record is "significant passive smoking". 

I was entirely symptomless until I had a seizure. Perhaps a routine chest X-ray might have detected it sooner and saved me a lot of trouble, but it was as good as impossible to get one during the covid lockdown, even if I had thought to request one.

Diagnosis begins with a CT-directed lung biopsy. You lie face-down in a CT scanner while a surgeon positions a thing metal tube into your back, through which they can then cut out and remove a small piece of tumour tissue for analysis and gene-sequencing. It is not a comfortable procedure. I wondered what was the cold liquid running into the back of my throat, which I had to spit out on to the scanner table. It was blood. We don't normally realise how cold the insides of our lungs get.

Gene sequencing is only the first part of the science fiction. There is a targeted therapy. The Merck drug company have licenced a chemical called Tepotinib (trade mane Tepmetko) in the form of a daily pill that blocks the abnormal protein, and slows down or stops the tumours from growing. It is a high cost treatment; I have heard a figure of £7,000 per month mentioned, but thanks to the NHS I do not have to pay.

Surprisingly, it is a relatively simple chemical - hydrochloride hydrate C₂₉H₂₈N₆O₂. I imagine that in some parts of the world they ignore the patent and make it themselves for a few pence per pill.

I have had other treatments too: chemotherapy which was awful, lung radiotherapy which was little trouble in my case, gamma knife radiotherapy which pinpoints and zaps small brain metastases, a brain op to drain the cyst that gamma knife left behind, which was scary. All over a year ago.

The side effects of Tepotinib are difficult, especially oedema (fluid retention). If you get cold it takes ages to get warm again because it is the equivalent of having 20 pounds (9 kg) of cold water bags strapped around your limbs and body, and, believe me, you would not want to have scrotal oedema (or vulval oedema I imagine, but don't know because I don't have that).

I am OK. It is but a scratch. I've had worse. None shall pass. I am still here.  

So, not only have we mapped the human genome to identify the 25,000 or so genes of our 23 chromosomes, we can gene-sequence malfunctioning cells to pick out a defective gene, understand its mechanisms, and construct a chemical to block its actions. To those of my generation, even the technologically literate, that really does sound like science fiction.

New things like this are coming along all the time. It should give hope to those who might become ill in the future.

Dirty Old Town

Every year, around this time, the asphalt surface of the school playground would be buried under a huge pile of coke. It was like lumps of gray cindery coal, but without much weight. Gradually, it disappeared into the school boiler room.

The coke was a by-product of the corporation gasworks, which manufactured coal gas supplied to our houses through a network of pipes. We had gas cookers, and gas taps beside the fireplace to which you could connect a free-standing gas fire through a rubber tube. I ran the Bunsen burner for my home chemistry set in the same way. Outside, there were gas lamps along the street, and a man with a long pole came to turn them on and off each evening and morning. My dad could remember the pre-electric days when houses had gas mantles for internal lighting.

Gas was produced by heating coal in the absence of air, with coke, tar, and chemicals as by-products. Coke burned hotter and cleaner than coal and could be used as fuel in specialized boilers. It was also used in industrial processes, but was no good for the home fireplace.

Dad’s Arthur Mee Encyclopedia (1927) has a series of pictures and diagrams showing how coal gas was made and the amount of plant and machinery needed. Here are the first three. 

The corporation gasworks were near the docks where they were supplied by canal with coal from the Yorkshire coal fields. In other towns, coal trains ran through the streets to the gasworks. The infrastructure was extensive: heavy engineering, railway lines, underground pipes. You could live in Gas Works Street, work at the gasworks, drink and be entertained at the Gas Club, and go on gasworks outings. Some of the structures are still around. 

That, for me, describes 1950s Britain (and earlier): asphalt playgrounds, school boiler rooms, gas lights, gas works, coal trains pulled by steam engines, and coke before it had any other meanings. I have no idea why it came to me in the middle of the night. 

It became obsolete when we changed over to North Sea Gas in the early 1970s. Millions of household appliances had to be converted to burn natural rather than coal gas. The gas storage tanks at the gas works continued in use for many years, until condemned as unnecessary. Many have since been dismantled. We have hardly any gas storage in Britain now; just a few days’ supply, as compared with a few months’ supply in Germany.

I found my love by the gasworks croft
Dreamed a dream by the old canal
Kissed my girl by the factory wall
Dirty old town, dirty old town

I heard a siren from the docks
Saw a train set the night on fire
Smelled the spring on the smoky wind
Dirty old town, dirty old town

Clouds are floating across the sky
Cats are prowling upon their beat
Spring’s a girl in the streets at night
Dirty old town, dirty old town

I’m going to make a good sharp axe
Shining steel tempered in the fire
We'll chop you down like an old dead tree
Dirty old town, dirty old town

https://musescore.com/user/5060416/scores/4832062

Don't Tell 'Em

All the talk of babies on blogs made me think back to when our daughter was born.

We arranged for our son to stay overnight with friend Barbara if needed. She was needed. When the hospital said to make our way in, I took him to her house and she tucked him up in bed top-to-tail with her two-year-old.

We drove to the hospital, but things seemed to come to a stop and there was some discussion as to whether we should return home. A lavender bath got things moving again, and our daughter was born at half-past-one in the morning.

I returned home to get some sleep. I phoned Barbara in the morning and asked to speak to our son as it seemed only right he should be the first to know. She gave him the phone, and I told him he had a baby sister.

"Oh! Right! I'm going to finish my breakfast now." That was all he said. He hung up.

I returned to the hospital and brought wife and daughter home. In the meantime, Barbara had taken our son to nursery school from where our child minder picked him up later in the day.

I went to collect him. The child minder was still very much in the dark. She was desperate to know what had happened. What did we have?

"He won't tell us," she said. "He hasn't said a word all day. He wouldn't tell Barbara, either. He has refused to say anything at all."

I gave her our good news.

Son would now claim he was practising the levels of discretion and confidentiality required in the professional capacity in which he now works. He was four at the time.

A chip off the old block. When we got married, I didn't tell anyone at the computer company where I worked. They thought I was just going on holiday. They only found out when the company received notification that my tax code had changed to reflect my new marital status. The payroll administrator did not  practice the levels of discretion and confidentiality required.

A Visit From The Police

... who told my parents I went in pubs

New Month Old Post: first posted 19th April, 2019.

My generation was not as open with our parents as our children are with us, at least not in my part of the North of England, or maybe it was just me. I never told my parents I went in pubs. Not even when old enough. The police told them. It was Easter Sunday, 11th April, 1971.

It was the day after I had been with three friends to The Green Bottle in the curiously named Spawd Bone Lane, Knottingley. The pub was packed with noisy, holiday-weekend drinkers, and we took little notice of a short-haired man in a suit sitting alone at a table in the middle of the room until he asked us one by one to go over to have a few words with him. He was a detective investigating a vicious attack on an elderly lady the previous afternoon*, although we did not know that until later. 

I can still remember some of what he asked – name, age, address, where I been between 4.30 and 6.30 the previous afternoon, and where I worked. I told him I was an accountants’ clerk with Goodwill and Ledger in Leeds, to which he said, “Oh! Do you know Mr. Black?” I said no, there was no Mr. Black where I worked, to which he replied that he worked at the Huddersfield office. It so happened that we did have an office in Huddersfield, and being naïve and trusting, thinking it a genuine question, I said I wasn’t sure but thought I might have seen that name on the letterheads, and that Mr. Black might be a partner at the Huddersfield office. It seemed to arouse the detective’s interest. I had never been grilled by the police before, and found it unsettling, although I tried hard not to show it.

The detective moved on to my friends, one of whom was in the middle of a Fine Art degree, with a contrary “art student” attitude, full of the deep and mysterious philosophies to which such beings are prone. He was going through a phase of answering questions with enigmatic answers, that’s if he could be bothered to answer at all. When approached on a train in the Midlands by a woman carrying out a travel survey, he told her he was on his way to Johannesburg. No matter who was asking, or how serious the situation, he took the same line. It was also the case, coincidentally, that he had the same surname as me, which drew the obvious follow-up from the detective.

“Oh! Are you related?”

“I suppose we must be.” 

“What does that mean?”

“Are we not all related in some way?”

The detective was suspicious. Did he think I had given him a false name, that of my art student friend? We had a bit of a laugh about it afterwards.

When you consider the gravity of the situation, it was not really funny at all, but we were still at that stage of youthful innocence which takes little seriously. Without really being part of it, we liked to imagine we followed the trendy, counterculture of underground bands and magazines such as Oz which was about to face an obscenity trial. You don’t realise now when you see old clips of bands such as Black Sabbath, just how excitingly anti-establishment they seemed, even in name. The police were joked about: you would see “Screw the Pigs” scrawled in four-foot letters on garage doors. This pushing of the limits, I would now say, was only possible because England, on the whole, was a much safer and law-abiding place than it is today, which makes the attack on the old lady all the more shocking.  And of course, we did not yet know the awful details of the incident. 

The following day, being Easter Sunday, I was at home, going through the pointless motions of revising for my accountancy exams. Dad called me down to the front room where two more short-haired men in suits wanted to see me. 

“These two gentlemen are police officers, and would like to ask you some questions.”

Being the sort of person who feels guilty even if not (you know, when the teacher asks who made that silly noise and you go red, terrified she thinks it was you, even though it was someone else), it really scared me. I had to explain about the pub in Knottingley and about being questioned, and the two detectives went off satisfied, but it felt very awkward.

And that’s how my parents found out I went in pubs, although, they probably knew already.

There is now no sign The Green Bottle ever existed. It closed for good and was boarded up by 2009, burnt out in 2010, demolished, and is now the site of a care home. 

*From newspaper archives, I can see that the elderly lady was 88 year-old Mrs. Dorothy Leeman. She had been beaten around the head, bound, gagged and robbed of £80 on Good Friday in her roadside shop at Hilltop, Knottingley, Yorkshire. She never properly recovered and died less than six months later. It was an appalling attack and I don’t believe anyone was ever caught.

A Family History Mystery

The mystery of John Price, and our part in its solution.  

Neil Price: Dickens’s Favourite
Blacking Factory (The Conrad Press, 2023)  

 

I have mentioned before that my wife is descended from Henry Francis Lockwood, the architect of Bradford Town Hall and the mill and town of Saltaire. Much of her family history was pieced together by her father trawling through archives in the 1950s and 1960s, then a painstaking and laborious task demanding patience and perseverance.  

After retirement I filled in more details. It was much more interesting than my own family history, and I spent months on it like a full-time job, placing a lot of information on genealogy web sites.

One of Henry Francis Lockwood’s uncles was Charles Day, the boot blacking manufacturer, who made the kind of fortune that would easily place him alongside today’s richest rock stars. When he died in 1836, one estimate valued him at £450,000, the RPI equivalent of £40-£50 million today. But in terms of property price inflation, the value of his holdings in London and elsewhere would now be astronomical.

It was widely believed that Charles Day had just one daughter, Caroline, with his wife, Rebecca Peake. However, at the very end of his life, he added a codicil to his will:

    “I Charles Day of Edgware and Harley House being of sound mind so desire that the three Post Obit Bonds for £5000 cash which will be presented at my decease may be doubled that is made £10000 cash and that the same may be invested for the benefit of my three natural sons ...”

That was quite a revelation. Wills are public documents and the existence of three, secret, illegitimate sons would have been a real scandal. He left them each the equivalent of around £1 million today, producing incomes of perhaps £45,000 per year.

I tried hard to identify who these three natural sons might be, without success, but left a summary of the will and other details in various places online. This turned out to be crucial.

Around the same time as my father-in-law was busy with his research, a certain Hugh Price was struggling with his own family history. One could fancy them together in Somerset House (then the genealogical archives), two gentlemen, strangers, each unaware of the other’s connection, brief nods of acknowledgement, departing their separate ways, never again their paths to cross.

Hugh had long been troubled by his great-grandfather, John Price. He knew that John had had three boys with Sarah Peake, and that their names had been Henry, Alfred and Edmund Price; Alfred being his grandfather. But otherwise John remained a mystery. Indeed, some records named him as Charles Price rather than John. 

Hugh died in 1986 and the quest was taken up by Hugh’s son, Neil, who had been intrigued by the problem since boyhood. Like me, he soon had the immense power of the internet at his disposal, but this only added further questions. It revealed that the three brothers had lived quietly but very comfortably at the best addresses in London and Edinburgh, without ever having worked or followed any profession other than “fundholder”. Where had these funds come from? And John/Charles Price remained elusive as ever.

Very late one night in 2015, Neil was following up links to his great-great grandmother’s Peake family. You may have noted that the surname of Charles Day’s wife was also Peake. Neil had been tipped off that a family member had been extremely wealthy, and wondered whether this could be the source of the brothers’ funds. He came across my summary of Charles Day’s will:

    “After about 20 further minutes of scratching about and fumbling for more information as to how John Price fitted into all this (if at all), the penny suddenly dropped. It was about 1am and my shriek of recognition certainly woke [my wife] and probably some of the neighbours! The “Three natural sons” – it was too much of a coincidence – they had to be Henry, Alfred and Edmund Price! But how?”

Indeed they were. John/Charles Price and Charles Day were one and the same. The reason for the deception was that Day’s wife knew nothing of the boys’ existence, and even more explosive, their mother was her cousin, Sarah Peake. Furthermore, Day’s assistant and confidente in all of this was none other than his wife’s sister. The boys may later have known their father’s identity, and that they were illegitimate, but they maintained the secrecy and kept it from their own children. Illegitimacy was seen as a shameful stain on the character until very recent times.  

Their identities emerged only because the will was subject to lengthy litigation, in which Henry, Alfred and Edmund Price of Regent’s Park are sometimes named among the many respondents. Along with several other possibilities, I had even wondered whether they might be the three natural sons, but they were almost impossible to trace. Price is a very common name, and where I did seem to find them they appeared to be associated with Peakes rather than Days. You would have to be an unusually obsessive genealogist to delve into an ancestor’s brother’s wife’s cousins.

When Neil contacted me, I said he needed to look at the court papers at the National Archives. I had only seen newspaper reports. The initial case concerned an unscrupulous attorney who had attempted to write himself into the will as co-Executor on highly favourable terms, but this was ruled invalid. He contested the ruling, resulting in the boys being named, but their mother’s identity was never revealed. The ramifications went on for decades and the case became celebrated for its length and complexity. Dickens used it as the model for the case of Jarndyce v Jarndyce in ‘Bleak House’, in which he pokes fun at the Court of Chancery, its lawyers and the enormous costs involved.  

The Court papers provide a window into the lives of Day and his family, and how the three boys were hidden from Day’s wife, the rest of the family, the prying public, and the shame of illegitimacy. This, and how the firm of Day and Martin built up their business and became so successful, is a tale of Regency London, ruthless competition, inspired marketing, shameless counterfeiting, an eligible heiress and a vacuous playboy, and no end of other fascinating and entertaining detail.  

One uncanny coincidence was this. For his last two decades, Charles Day was blind. You can see this in the portrait on the cover of Neil’s book. One of Day’s many acts as a benefactor was to found a charity called The Blind Man’s Friend. Eventually, the charity and the portrait passed to the Clothworkers’ Company. Neil Price, during his working life, sat through many meetings in the Clothworkers’ Hall, never aware that, there, all the time, on the wall above, the portrait of his mysterious great-great grandfather, John Price, i.e. Charles Day, had been watching over him.  

If anyone is interested in Neil's book I can pass on his contact details if you email me via my profile page. 

Didlum

In answering the question on Yorkshire Pudding's blog: "How much money have you got stashed away in your house and where exactly do you keep it?", I said none because my wife puts it in the didlum. Did anyone know what I was talking about? It's all right. I'm used to it.

When I was little, my mother paid each week into Nanna Fenwick's didlum. Nanna Fenwick (that's Fenwick with a voiced W) was a fearsome but trustworthy woman who lived across the back lane. Her didlum started each year around the beginning of February, and if you paid in, say, ten shillings a week, you would have about £20 when it paid out in time for Christmas. You only got back what you paid in, without interest, but it was safe from the temptation of a tin on the mantlepiece. I don't know how many people paid into her didlum, but I suppose Nanna Fenwick put it all in the Post Office and got a bit of interest herself for running it, not that there was much interest to be had anywhere then.

I guess they are too posh to have any didlums in Sheffield.

Hello, Cheeky!

Do you ever wake up in the night giggling uncontrollably about something remembered from long ago?

What set me off last night was a story from someone I worked with soon after leaving school.

At his junior school they had a class budgerigar. Its name was written on a sign on the front of its cage. It was easily detached. 

It was in the days when nearly all children walked to and from school, as did their teachers because they all lived locally. Not all cars then. The teacher used to leave her outdoor coat over the back of her chair in the classroom.

One day, she walked home with a sign saying, “My name is Cheeky”, fixed to the back of her coat.

That middle of the night giggling got me a thump in the ribs.