004: Necessary Insertion

Last time I finished up saying: "Next time: Eminentia and Trade, else WTO and rules.."

Truth is, however, that to do so immediately would put me ahead of myself and clear exposition in relation to that topic.

I have Perjjo to thank for this realisation. For during the week he called to "wonder" whether my last blog (003) had reached into the souls of US pharmaceutical industry and/or marketing to an extent of 'eminence lacking!'. Today.

To explain this he had been reading an article which revealed Pfizer buying into Boston academia's "eminence". That is to say buying basic research collaborations. To my mind and knowing pharma's potential for such matters it had hitherto been not so much pharma executive requirement as investors' ace-holding directive. On consideration - checking dates and a few other relevant things - I decided no, any soul change was down to others. Still, within a week of that particular publication kind of says I was both close to the mindset and in need of this insertion.

So.. further to 003.. was a genuine lack of pharma R&D evident? If so, where lay a sustainable future for its players.?

If the first then surely Ledford@Nature would have an indicative answer.

If the second then credence is given another finding to hand. In the matter of innovation which framed my question on the topic, the Federal Drug Administration(FDA) approvals of Big Pharma drugs between 1997 and 2008. Importantly, two thirds [ 2/3 ] of those were classified as "follow-ons". Quite possibly approval-seeking to shelve patent or patent-ready stock for sustaining future marketshares. Cashflows. A case of old wine, new bottles...

At best then, only one third [1/3] truly new chemicals or molecules or like processes. To perhaps truly earn eminence by innovation. Likewise per its long tradition that innovation justifies this industry's patented price premia.

So what gives now—if a net third innovative then a larger market leverage shall be applied.? for whom? How? Waitta minute..!

Costs..?

Why yes, we cannot overlook this since the Financial Times in London has made pretty clear recently all the M&A has really been about cost cutting. Rationalizations..chopping jobs and old manufacturing plant including labs(Sandwich, Kent, anyone! NY out, Groton in!) Yet even FT say term's up for cost cutting. Show us the growth!

Enter Heidi Ledford(above) who opens — "The agreement is the latest sign of a growing trend in the pharmaceutical industry, which is trying to cut costs and improve efficiency by outsourcing the earliest phases of drug discovery."

Which in its way says it all. For her cited parties.

And Perjjo tells me how the later phases will run cheap (and mebbe nasty) among multitudes in third world clinics. Where ethics are somewhat slacker. BAU. Besides, some will always rely on homo sapiens being all-for-one, with one for all ;-)

The leverage.. see?

Yet I now wonder about this. From here I'd say there was a firm investors' sense of which costs Big Pharma must keep. And despite Merck's(qv) talk of its own previous collaborations.

For investors the innovation tag is pretty vital. Corporates legitimizing premia prices. With overall profitability tumbling even lowered pricing would give them no show against lower-priced and already major long-term generics competition.

But of course with but one third [1/3] of FDA approval drugs novel what ratio of these are In-house? Or owned? Could it be that already the external and/or independent twosomes and threesomes in molecular and nano science and biopharmaceuticals, along with novel agents in such processes have tipped the balance away from Big Pharma control over patent holders' monopoly pricing.?

Example for the small independents lies well in IT app-builder business opportunities. A several year software development and web/net beta testing can see very significant buyouts by deeper pockets dependent on 'viral' growth and product streams. Goose, gander stuff, I mean to say.

Then not beyond the bounds of reason are that these deals or research buyouts amount to pharma-wrap of such knowledge and future-makers in secrecy. Serving only insiders. Hey there's a lot at stake.!

Bottom line: Contention has a mind of its own. And its very own people. Conditioning chronic convergence. Hence the need of vigilance and watching this space..

003: Bigger Pictures

At lunchtime today I learned from Radio New Zealand's Midday Report segment WorldWatch that IBM - International Business Machines - was 100 years old.

Occasion to remind me of several visits to what the 1980s termed IBM House in a cityside property along Oxford Terrace, Christchurch. I was to learn there how IBM had arisen from "business mergers" and earned its 'big blue' reputation.. and .. wasn't there a computer that could beat any brain anywhere at chess!

Sandwiched between a tree-lined and pretty River Avon at its front and commercial warehousing construction at the rear. Inside, several offices per floor with then fashionable large single rooms divided by multi-partitions whose workstations revealed the firm to have shifted from typewriters, cash registers and office machinery to computers. For them desktop times had arrived.

But, it should be said, IBM was then already behind the times. Technology, and IT, times. Thenceforth they would not catch up, and so far as I know from the radio commentary's conclusion of a present "reinvention" arrived at in ruthless cutting-off-the-past style, this will be insufficient to regain the BAU lead. Kindly put, a phrase to aptly characterize them would be slow followers.

In saying this I'd like to reiterate a term I'd come up with back then yet whose currency in the relevance of a bigger pictures take on the pharmaceutical industry(PI) today in relation to westernized medicine, is a good match.

That term: EMINENTIA.

And taken to mean not what Gould's might give to an anatomical protuberance in the inner ear or a ridge of heart chamber tissue, but a condition arising from eminence. A condition arising despite the best and/or worst efforts of all PI players in westernized medicine, whose 'golden years' were said by a wiki topic as being in the 1990s. A condition which unless recognised  - IMO 1980s - and robustly dealt to as it arises would set forth a rigidity from which so very few would escape. Until too late.

That eminentia is well-and-truly set today for let's say the U.S. pharmaceutical industry is discernible in the context of a Standard & Poors Valuation and Risk Strategies research group report recently made. The PI - and yes largely US-led in this respect - has been embarked on very substantial merger and acquisition programs as it sought also to restate itself in the Health Care business..

Latest data shows how for all business some 828 M&A deals @ ~$93B have taken place. Compared to 2007 - 905 deals @ ~$172B - decline is apparent. Yes, the global Recession in part responsible.

Again all business, when it comes to choice we find Europe taking 45% in 2011(cf 50% 2010); whereas M&A  shot up 85% in target deals around Africa and the Middle East. Whilst for Latin America and the Caribbean the figures were somewhat less.

So much for context. Now for the sectors. Real and vital pointers. For Health Care:

Year-on-year(yoy) @ 2011 Health Care M&A dived. Minus 28%.

We could say how Pfizer's Wyeth 2009 buyout - reportedly the "biggest ever" at $68B - was writing on the wall. Surely?

Perhaps more significant, however, was the nature of that acquisition — cash, shares, loans essential to make the stake. What else might remain in circulation for such activity..? And besides, vigorous take-up in M&A terms does not plenteous opportunity make. But, OTOH, serious - unbuyable - contenders.

Contenders and contention then. Replacing competition..? If yes, eminentia rules. If no, no one rules. Another possibility is the PI remainder stuck and waiting for  upturn in M&A and the industry's so-called leaders pitching their immediate futures in biopharmaceuticals.

Which brings me back to a like theme of the intro. News of a BBC production about 20 vaccines for the future of.. patients or megalo-eminentia?

Next time: Eminentia and Trade, else WTO and rules..

Beginnings: 002

Post-WW1 they had resumed schooling together. She was early teens, he late. Attracted he was for sure. Nothing more fluid in form, style and balance existed in school athletics. Entered in the 150 yards dash, as their peers called it back then, she’d start out of the blocks in front and stay there all the way to the tape. The one to watch. Every audience’s hero in a race, his alone just everywhere else.

Aged 18 her symptoms started.. double vision.. fatigue.. Gotta see the eye man, was early advice. He hardly listened — hadn’t he seen it all before — here, try these prism glasses..  you’ll be fine.. opthalmologist-speak. Fatigue.. why wasn’t that all the running, training. Besides, you are a growing woman and shouldn’t be doing that stuff.. y’know what men do.

Things were beyond argument when her limbs went weak. Found a neurologist, her father soon declared, eminent isn’t the word for him. He has agreed to see you. Only one condition, that you are honest and tell him truly..

Which she did, right after his physical examination. Not hysterical, she told herself and reiterated: “My symptoms, that’s what I’m worried about.” Shown the door for her trouble she vowed henceforth avoid the patronizing patina of perfect fools. Wherever possible.

Worse, and worsening (euphemisms like ‘disease progression’ not allowed), even to the point of being unable turn over in bed, eat properly, likewise for speech. It was her fiancé, now a medical student who came home with a possible diagnosis. Myasthenia gravis.

He knew how this rendered her vulnerable. To a so-called wisdom of the times: No known treatment thus many things to try. - (Disabilities and How to Live With Them(1952). London: Lancet).

Gold injections, thyroid and suprarenal extracts, lecithin, glycine, ephedrine — among a you-name-it brigade — later, and so discharging his extended learning as much as her frustration at false hopes, there came a day she would never forget in 1935.

Living alone save her nurse companion she declared herself indifferent to another injection. A new substance her fiancé enthused. In minutes this changed to a strange feeling. As she was to put it, “ When I lifted my arms, exerting the effort to which I had become accustomed, they shot into the air ... every movement I attempted was grotesquely magnified until I learnt to make less effort... strange, wonderful, and at first very frightening ... we danced twice round the carpet. That was my first meeting with neostigmine, and we have never since been separated.”

Neostigmine is an anticholinesterase drug. Its use is also diagnostic for myasthenia gravis, dramatic relief of weakness and fatigue confirming this disease.

Implicit to its use is knowledge of the biochemical balancing act a body performs by way of the central nervous system(CNS)—motot neuronal—muscle set ups. Body release of acetylcholine makes it the primary driver of nerve ending/muscle action.

This is not of permanent duration in and of itself, being reduced - hence controlled - by cholinestrase. Too much cholinesterase makes for too little muscle action via acetylcholine. The weakness, fatigue and loss of muscular function MG’s attendant and consequential symptoms.

So.. rebalance cholinesterase with anticholinesterase administration and.. and retrain muscles for more normal movement.. and voila!

I smiled, thought: the bigger bolt..  to eliminate slack in those rehaped lopper blade holes.. well not quite but pretty darn good.

He was looking away from me, out the window into the rear garden darkness. Can’t say why yet I sensed his mind upon a small plaque set beneath a tree there. After a long pause he spoke.

“The doctor was her locknut. Drug titrations, watching, always watchful. I mean complementary atropine to keep a check on her CNS’s buddy the autonomic.. and then those too much (cholinergic crisis) times including ats knocking up the rebalancer..”

“You were her doctor,” I said slowly, quizzically.

“No, no, I did surgery. But you know that. Her doctor was.. is a friend of ours.. I mean mine.. Look, if you’ve time tomorrow we could mebbe go over there.. drop in.”

He eyed me kindly, his look saying the subject was over, and the tone of his voice tellingly so. “You er.. you don’t happen to play chess do you.. like to help me with an opening I screwed up!”

Next time - 003 - bigger pictures.. contexts.. for trade, industry, jobs, government...

Beginnings: 001

Tom's critical "surmise" was a surprise. Stinging. Yet also, and I am pretty sure he had no idea what he had set in train, taking me back to the safety of constructive effect. In experience.

Which I will now relate. In the interests of telling exactly where I am coming from. And how.

I'd been to a conference, given a talk, and next day promised myself a visit to a former surgeon who had retired in the vicinity.

On arrival I found him sitting on a wooden step beside the cottage's sunny front garden. Beside him a couple of hand tools, a stripped down pair of hedge loppers and a very worn, very dark greasy bolt and nut.

"No, no, you finish up," I said when he stood to wipe his hands and grasp mine in welcome. "Besides, I'm curious to know how you do this. Worn out surely—you are fixing them?"

"Sure thing," said he fossicking among glass jars in a wooden box. "Ream or rasp them out .. those holes.. then a bigger bolt with good thread and two nuts and—"

"Two nuts?" I smiled, shaking my head in misgivings at the rudeness.

Evenly he said, "You'll see, go on indoors, make us a cuppa.."

Fifteen minutes later, coffees on a tray, and I saw. He had cleaned out the lopper blades' holes and filed them larger, rounder, with a metal rasp. Then fitted a larger bolt with a washer and nut to hold those blades together, operating via the tool's meter length tube handles.

"Now this," he explained as he fitted another nut, spinning it into place with his index finger, "nut two. When one won't do you make it two. One was why this tool  wore out and I never knew. So.. number one tightens the blades for open-and-shut cutting, number two locks it down. Lock-nut. Least for me, here and now, that's the theory. Here, give 'em a try for me.. put theory to work.."

Worked, showered, dined and conversation after a wonderful dinner in the quiet enclosure of late evening there I was to ask him where the fix it idea came from.

"Wherever did I get it from? The lock-nut idea? Hey, that will take me back. Lemme see now..."

I waited. I'd known about such things from hobby DIY mechanics days , but that was then, now was planned obsolescence, replace the whole tool and keep a workforce in jobs.

Still seeking a firmer line with which to answer he began, "Actually, and thanks again for helping with the hedge, that other pair I was using was new at the weekend. Looked the same, newer but.. same kind of mechanism and.. well, I figured it would probably be a shorter time to the same stuffed lopping as the old pair.. yeah, I can tell from your nod you agree tools aren't made to last.."

"Well you've changed that all right," I said, "a sharpen here and there and the oldies are forever." With a learner's gratitude adding, "At least two of everything makes for twice as long."

My reward was hearty laughter. Throwing his head back to show a muscular tanned neck and firm torso. Reveal how fitness and figure had made his retirement good.

Yet in no wise hinting at anything else about him. Like what followed.. and served to graduate me in what I became skilled at..

Tomorrow: a heartenening story .. untreatable chronic disease and the medical student..