Thursday, 9 September 2010

One thing which really is beginning to puss me off with Norway is something I thought I had become accustomed to long ago. Choice. Lack of it.

I used to shake my head at the lack of choice of wares in supermarkets compared to the UK, all from fruit to beers, but soon got used to it . Actually I rather like the quicker shop possible in the Kiwi Rema type set up, and get hacked off by Meny's high prices and variety. Bread at least here, is very fresh baked and usually in a perfusion of types in even a mid sized shop (read TINY if you are a Yank)


But then recently when I went to invest in a new mountain bike, at prices under 2000 usd/ 1200 Euro there were the chains' own brands: Knackeredmura, Merida and the cheekily stolen name "hard rock". Scotts were on offer from one chain, but as with the others the spec often left a lot to be desired: a good back derailuer coupled to some fairly crappy lower end drive chain, own label chain set and the compulsory cheap bouncy forks.

Cheap and nasty as it turns out, as my new steed flung me off on a mild load up and locked front wheel.What drew me into buying the bike was the Deore name and the 150€ "discount" but in fact this bike is definetly part of the great norsk marketing promotions con, which I will come back to.
.

What I mean to say out loud now is that the various channels want to sell you WHAT they want, not what you want. In bike shops and on the whole REMA 1000 principle ( which is a great idea for a country so logistically challenged with long distances, fjords and mountains as Norway is) they want to sell you a range where they can define the margins and hold stocking costs down.

That is to say, for the bike chains, pardon the pun, they want to buy fewer things from fewer suppliers and in bikes, reach back up the supply chain to those wry Taiwanese companies who did contract manufacture for the likes of Specialised and Saracen 20 years ago.

With production by virtual slave labour in China,the situation is that costs are lower while in addition, one layer of margin is taken out of the supply chain, which was previously owned by the big brands. Unfortunetly, there are only so many bikes a chain wants to product-manage, so in fact the choice is also taken out.

They want to make serious margin on mid priced bikes rather than stocking some
quality bikes at these price points and then making up on the cross sell to equipment and clothing. I have to admit though, that before Giant's entry to the EU market, bike suppliers had shops where they wanted them and shops pretty much well had to accept declinging margins on mid range bikes.

However as a consumer we didn't care back then in the 80s and 90s, because you could get a single group set bike to say 500€ (600 now I guess) which was good enough to get started in racing and then do as a trustworthy training bike for many years. No doubtful hidden components or poor part bins shifters. The unwritten franchise with the punter then was that the shop would enjoy your patronage for parts, upgrades, clothes and paraphinalia.

For the chainstores in Norway, in being limited in choice and blurring the quality of the product, they shoot themselves in the foot, because I am in no way shop loyal now: I will shop around and buy stuff on the internet. I take myself as just a consumer, a mere buyer. In other words the most important spot hire manager the company has when my wallet is needing emptied.

The same applies to cameras: Is there a death of independent, quality shops now as a whole on a western world basis? Due to lack of choice, dreradfully slow staff, poor basic personal service and lack of any true interest and expertise in cameras to be found in the chains here, I shop on the internet : there is one or two cameras max at each price point and they want to sell you the packages which they have bulk ordered to a higher margin.

They don't even have a good range of accessories: blow brushes, air cans, filters etc: they want to sell you a narrow choice of system and support only that with other non system peripherals being mediocre or over priced, worse both. Sytem peripherals themselves are
often over price at POS but luckily there are enough actors on the internet to make deals possible.

Now consumers will be drifting away completely from their franchise to previous sources of information; the shop! They will find the poor choice and service frustrating and rely on other consumers on the internet for advice on purchases and cheapest deals. The same is true of home electronics, where the POS info is so poor that you may as well use the internet. In future, as generation X moves into family modus, consumer electronics will be handled physically more by the Post Office here than the chain stores.


More seriously though, the same applies to the housing market unfortunetly. Developers get more margin by selling more individual units, or so goes the formula some business analysis from ten, fifteen years ago. So in Oslo there are masses of expensive, one bedroom housing and a total lack of affordable family "rekkehus" with three small bedrooms.

Here, it means that if you want any building activity and investment, then you have to follow the same model: small, "quality", expensive. And what has happened? We have a glutt of luxury flats which are not actual for families, while potential first family homes are too expensive and left for the local council to either buy or fund by renting for social clients.

Developers have gone down the marketing high school path of "focusing on those higher value consumers who will provide higher ROI" . They know the demographics of the population as a whole, but they do so really want to make maximum margin on their units that they are blind to the overall saturation of these rather small niches. Yuppies, Dinkies, gay boys and rich pensioners are not in ever lasting supply or even a big enough group to be called a segment. Home owners want kids here.

This view on controlling the channels for large margin is fatally flawed: it leaves the punter pissed off. This makes the opportunity open for real entrepreneurs to come in with internet offering, or central shops in Oslo which can maybe grow to franchises eventually, offering true choice even just better value and service.

Housing is more pressing for us : the local authority is gagged and bagged : they more or less have to do what the developers say or there will be no development and the local trades people are a force to be reckoned with here.


The other big deal here which is the elephant in the living room, is false discounting. I am sure my bike is false discounted: on sale at full price only on paper for a matter of days, maybe just in the internet shop, and then when rolled out, hey presto, a massive 1500Kr off. The bike seems to be reasonable for the price but no way should it be a 5000 kr bike without a much better group set mix.

The same goes for training shoes: they want to sell you a 1000 krone set of shoes, and there is little choice at say 450 for the none idiot shopper who knows they cost $20 usd to make and
ship - max. So they tell you what a wonderful deal you are getting on a really, really high quality set of shoes. Now in shoes it is easy to get round the law by taking in an initial stocking and then punting them out as an also ran a while before actually actively selling them
at the desired margin/volume target: It is a steady up trade technique.

I feel squeezed out as a consumer. My last visits to camera shops have been met with uninterested staff, too busy with customers wanting prints and not being able to self service them. I mean I went in once with a credit card half way out the wallet and could have been sold round to a Nikon or Canon "thousand" range bin sale, even though I wanted an PEN EP1. But no, I got no service at all really.

Shops have to offer friendly, informed service and products are price-quality trade points which can match consumers needs. Also they need to be able to offer a range of products at the key price points from different manufacturers which each have something unique or offer slightly better value. The current Norwegian chain store model of "discounting" on sale-only wares ( products only in reality to be sold at the discounted price) will only drive consumers to seek better value and the one place this is going to happen more is on the internet.

Monday, 7 December 2009

Nano Nano the Panacea. What will be hidden in Pandoras Nanotech Box?

Nano Nano the Panacea. What will be hidden in Pandoras Nanotech Box?

I was watching a swedish/norwegian professor on TV who was estolling the virtues of the brave new nano world on friday. Nanotech will do everything apparently and alter how most anything manufactured interacts with our persons and personal bits. She meant the latter in a more formal medical way, but here in lies my take on nanotech.

Nanotech can be in some areas, the new marie curie playing with the "wonder stuff" which breifly radioactive material was.


My issue is that with many applications we will create carbon, silicon and metallic based nanoparticles which are not biodegradable and in their initial applications to products require no bio-safety testing.

Issues, which I will go into with explanations of my concerns later, include

  • Chronic Allergies
  • Subcell, cell-surface and perimembrane biological disruptions ( READ CANCER caused by nano technology)
  • Other issues with the non specific immune system reactions
  • Issues with how natural process in the body and environment clean up, transport or horde nanoparticles
  • In respect of the last, long term and unanticipated bio environmental dammage caused by nano particles

Why do I set such an alarmist tone?

Let's think about an area which you may call "micro" technology, or rather the seemingly wonderful technology which contained a pandoras box of issues eminating from the micrometer level.

Picture if you will, mid way through the last century and films promoting the wonder stuff which was fireproof and could be woven into pipe lagging or even fire proof suits for workers. You've got the picture: Asbestos.

The problem on a micro scale with asbestos was known about - roman slaves in their rock-wool mines died mysteriously young- some of what we now call asbestosis- the scarring of the lungs caused by massive exposure to the fibres as dust.

But asbestos held a far more worrying threat which casts it's shadow down to nanotechnology today. In theory just a single fibre of asbestos ( five microns long and less than three microns √ł) can cause a rare disease which in fact is the very one from which Cancer ( the crab) derives it's name. The insidious "mesothelioma". In advanced stages this manifests itself as inflamed, red strands of new tissue radiating from just below the rib cage through the ribs, a bit liek a king crab. The "new growth" is of course what we call generically cancerous tissue.

The exact biological mechanism is known and for further reading, but to summarise the small fibre is picked up by a type of roving immune cell which tries to engulf and destroy it, only to be empaled upon a two ended spear, then itself becoming a dangerous chemical bomb filled with free radicals and enzymes otherwise threatening to normal lung cells. It soon impales a lung cell and seeds a cancer.

Okay, this exact mechanism is maybe unlikely from nanoparticles which are very much smaller. BUT it shows how an inert, non biological particle eliceted a disease which would still today be unanticipated if it were a new substance.

Cellular machinery is biochemical I hear you say, not prone to mechanical interuption. Well that is not the case. Intracellular machinery utilses biochemicals ( primerily ATP) as a fuel to effect many mechanical operations, and I believe most of these remain un-illuciated today.

In ways analogous to those which we see when asbestos fibres interupt a biological, primary immune mechanism so could some nanoparticles do the following:

  • Block up cell membrane mechanisms- receptors, transport channels, formation of new cells- distuptions to all of which are linked to cancer.
  • Interfere with intercellular mechanisms: mecahnical 'substrates' cells grow along- causing defects in foetuses- or disrupting the immune system in this way.
  • Illiciting or interfering directly with antibody mediated immune response; antibodies interact at the nano and pico / √•mstrong levels. People of course have allergies to fairly inert substances like copper, cobalt, chromium. This happens at the nano level.

Will nano-techies not design us out of this issue, or will the particles not be contained or washed off easily?
Nanotechnologies, which are not a food or medical device, require no biological safety testing. In any case there may be new problems which are not currently screened for in tests, or cancers, cell damage or unborn defects may take longer to show than current cell based assay and animal testing would detect.

We can choose not to buy nano, just like GMO, right?

WRONG inert, non degradable nano particles will start to build up in our environment and bodies after it is widely employed in paints, cleaning substances, coatings and in of course clothing or medical devices ( laterly will get some level of saftey, but that is not gauiranteed if deiseases take years to incubate or accumlation occurs by unknown processes)

So what do I recommend: At the moment there should be a biohazard due dilligence for any nanotechnology which is

  • not proven compeletly biodegraded, by a safe mechanism to safe residues
  • non encapsulated, non covalently bound to a larger substrate - ie potentially airborne
  • anything to be used in proximity to the skin, airways etc MUST be trialled at least by ADMETOX.
  • An immediate moritorium on production of paints, coatings etc where the above are not satisfied.

Tuesday, 3 November 2009

A Brief History of the Technologies of Life!

I had the occiasion to be at a dinner with a then senior manager at Invitrogen corp, Charles Golightly, who is no longer with the company.

Being a former mol biologist ( coming in handy once in a while) I was encaptivated by his fortelling of a remarkable set of entrepreneurial escapades.

From his verbal reconaissance, having often dealt with GIBCO and invitrogen reps, and some sources on the web I have been able to put together a bit of a history which is unofficial and uncomfirmed.


Now I write this for the very irony that the name "life technologies" was far too good to go away. It's back and saying the same thing it did before, moving to do stuff for our own life quality, understanding of biology, and improvement of health . In fact this "near to patient" is hardly new to the corporation, which has either ditched or pulled out of several 'close to patient' routes before. It seems that "mol biol tools" scientists, business men and product/programme managers are a little shy of the FDA and all the paper work which comes with it.

In Two Years Time Biotech is 60

It all probably began with Helen A's cervical cancer -tumour cells in 1951 ( look it up on google) She was an anonymised afrocaribean US citizen whose cancer cells were found to be not only growing in culture outside the body, but seemingly "immortalised". Wikipedia cite them being from an specific woman, and as now in many countries the cells where taken and utilised without consent or rights to commercial uses. Strains of her cells are saving lives today and widely used in advanced research and production of diverse proteins for research purposes. This was most likely the start of the 'consumer need' to have media in which to grow cells in vitro

A decade later and two biologists, Bob and Earline Ferguson, inherited their parents farm on the Grand Island - on the river near Buffalo, NY state. Amongst the live stock were some goats and they found they could tap the blood and extract a serum useful for growing various cell types in. They soon found a market and founded, in true ACME style, the Grand Island Biological Company : GIBCO. Incorporated by 1963.

Gibco grew quietly and diversified around their core media and nutrients media for cell culture. The farm house apparently stood in the midst of GIBCOs large production facility which dominates the island today, right into the 1990s when it became a bit of a liability.

Rather quaint eh? Bunch of goat farming proto hippies becoming the biggest biotech company of the 1970s. They were in the area of fairly simple blood extracts, vitamins, sugar/protein block solutions and so on. I guess few even in Buffalo knew what they did, and with the fetal bovine serum being a major money maker, it wasn't for the squemish I guess! Still big, high margin business today, FDA approved! However in the field of molecular biology- enzymes as tools, there was little activity before the advent of BRL on the scene.

Later in the 70s some time, Bathesda Research Laboratories was founded in a GARAGE and a back room of a real estates agent rented through someones wife or husband. They set about making the new and highly useful "restriction enzymes" which cut DNA up at usually specific sequence, and they brewed up bacteria, macrophages and other cells to harvest these from in small bioreactors. The simple business model was scalable in repeating these reactors on a small, hand to mouth expansion model and also in offering many new products from the "home brew" extraction process. When I was a geneticist, BRL restriction enzymes were worth many times the value of gold by weight! I seem to remember 500 GBP for like maybe a microgramm.

As they expanded, they were loathed to move their bioreactors for fear they might upset the bugs and lower yields, but by 1982 VC were well on board and the now large concern with large problems.

The First Big Biotech -Founded in 1983 by Merger

Although you wouldn't maybe glean this from and VC history of what they know as Biotechnology- whacky new drugs and the supply chain in that area - the merger of these companies above would create the first major biotech company, before most VC were out of nappies. Life Technologies was founded in 1983 by the merger of Bethesda Research Laboratories, Inc. and GIBCO Corp., a subsidiary of Dexter Corp. GIBCO was an amalgam of some 40 businesses acquired over a 15-year period by North American Mogul Products Co., a firm incorporated in 1915 that changed its name to Mogul Corp. in 1968 and was acquired by Dexter in 1977. GIBCO had sales of $77.3 million and net income of $4.5 million in 1982.


Remember DEXTER!

Bethesda Research, by contrast, at that time coudl be described was a struggling private company that, according to its chairman, Frederick Adler, was within a week to ten days from filing for bankruptcy in 1982. ( source, new york times) Adler, described in a Barron's news story as a "flamboyant venture capitalist and turnaround artist," laid off about half of the company's 500 employees and lopped off marginal research and unprofitable product lines. According to Adler, Bethesda Research was on the verge of launching an initial public offering of its own when it merged with GIBCO. It became profitable during the last quarter of 1983.

Dexter took a 64 percent stake in newly formed Life Technologies. The first chairman was Adler and the first president was M. James Barrett, a microbiologist who Adler had lured to Bethesda Research from SmithKline. The firm originally had headquarters at GIBCO's old offices in Chagrin Falls, Ohio. Net sales came to $91.4 million and net income to $3.7 million in 1983.

In 1985 Life Technologies was producing and selling more than 3,000 products used in scientific and medical research, human health diagnostics and treatment, biotechnology, and industrial applications. Among its units, the Invenex Laboratories division, located in Orlando Florida, was specializing in the production and sale of small-volume parenteral solutions such as nutritional supplements, electrolytes, antihistamines, antibiotics, diluents, anticholinergics, and generic diuretics. This division was sold to LyphoMed Inc. in 1985 for $39.5 million in cash and notes.

In 1986, the year it went public with an offering of about seven percent of its outstanding common stock, Life Technologies believed itself to be the leading supplier of sera and other cell-growth media. It was also a leading supplier of enzymes and other biological products necessary for recombinant-DNA procedures. In December of that year the company completed the sale of its Sensititre product line to Radiometer A/S, a Danish instrumentation company. By then the company had moved its headquarters to Gaithersburg, Maryland. In 1987 the company signed a technology transfer and licensing agreement with Toray Industries of Tokyo. This agreement conferred on Toray exclusive marketing rights in Japan, Korea, and Taiwan for products based on Life Technologies' nonisotopic DNA technology for detecting hepatitis B and human papillomavirus (HPV), with the company receiving a sum of $2 million over three years.


Invitrogen Corp was founded by the charismatic californian, Lyle Turner with partner Joe Fernandez, around 97 and inc. 1989. 11 years later they would be in the lear jet set and even some of their warehouse guys were millionaires on their share options.

Lyle was supposedly the guy who was a researcher and sick of pippetting, titrating and so on just to get the right qauntities of REs, buffers, acids and so on and struck on the business idea of launching new mol biol products as kits, with small vials of reagents enough for a defined amount of reactions. Now this was a stroke of genius, because everyone was used to buying in bulk ( 500ml is often way "Bulk" quantity when used for a 50 ul reaction) to get a reasonable deal per gramm or ml, or just because chemical companies like sigma didn't bother making small vials for limited reactions. As I remember pre IVGN, there was always hydration of powders and contamination of liquids and lots of people using out of date 500ml bottles of this and that or having labs full of home brewed bottles made up to starndard solutions from powder, used for a month and then "just kept handy". Science was shit back then BTW. Real lab rat conditions.

The company initially found success with its kits for molecular cloning— notably, The Librarian, a kit for making cDNA libraries, and the FastTrack Kit for mRNA isolation from biological samples.


Now they grew, and had pot on the table at board meetings, and probably golfed from their lear jet eventually. In 1999 though, there was a lot of economic turmoil and DEXTER corporation was open for stock market raids by the nasty capitalists. However someone advising or acting with Lyle and Joe, spotted the weakness of the WHOLE dexter company on the "street" and the opportunity to use Invitrogen's cash positive and high share value to lever enough to 'eat the bigger fish". Which they did- they got life technologies out of dexter in 2000.

Lyle soon realised no doubt that the tail could not wag the dog- Life Tech had loads of personnel, world wide, and a heavy sales and support organisation. Ivgn was small, fast acting, big on the branding front with funky advertising and the use of DM over shoe leather sales forces.

Life tech had 'gateway' vectors and many tipped this to be synonymous with Windows, just for CLoning. Lyle and Joe wanted gateway , maybe for a while, but probably got it too late.


Any idea that they would get a 'fusion synergy' by inhereting the Life Tech sales force would soon evapourate in the first of many take over clashes. Life tech sold some pretty basic stuff, and all the best sellers sold on volume of GIBCO products- My opinion is that they couldn't sell gateway, weren't maybe incentivisced to do so, and missed the biggest window of opportunity at companies like AMGEN who were validating second generation vectors for volume proiduction already.

Their reps and managers were a mixed bunch but not very up on mol biol- many had been with the company for years, some got in with "biology degrees " ( i knew a PM who had probably never used a micropippetor) and it seems others were not even biology majors. I know- I have met many of them and spoken to their sales managers in the 90s as I thought about workign in sales there. Life tech reps were rather dull types with 'foot on throat' sales managers - I often met them at conferences, the managers that is, and they were a strange bunch to be working selling to scientists. DOuble glazing sales management seemed to be better suited to some of their aggressiveness. All opinion from meeting a spectre of them.

SO the IVGN tail could not wag the dog, and any other small company like Probes which came on board and tried, would be eaten up eventually. Invitrogen kept the "life technologies" label as a strap-name under all their stuff, for a while at least. By this take over, and integration of all those mol biol products from IVGN, the beast changed nature in how consumers (scientists) viewed the company. All the big deals they could get on the GIBCO end were done or could be done, by the old gaurd team there, who stacked genetic institutes, warehouses and probably garages with gibco product all on pull forward sales and large discounts way back when.

Rather than this , very soon into the 200os , invitrogen became percieved as the wallmart of biotech research tools. Management still believed they had a raft of new cutting edge products and ever higher margins, and that innovation, platform solutions and high technical service was essential. Consumers however put up with the odd thawed product because it was easy to order, and the catalogue was cool to shop from over coffee in the departmental library. It took Greg Lucier about three years to understand that the corporation was good at logistics and shop front, consumer business on a micro- granular scale, and not at big deals and near patient stuff.

Thereafter new companies were assimilated as are brands sold on the shelf under their own makers name at wallmart to some extent, with packaging being at least standardised to mother invitrogen branding. "life tehcnologies" was dropped around 2003 I think. Too much clutter.

Now we have come full circle - Life Technologies Corp. and the company is still tilting at the windmills of near patient care, whilst gene-therapy never really takes off and many of the big medical protein production deals are validated and locked in. Almost thirty years ago GIBCO BRL sold off nearly all their 'near patient' therapeutic divisions and earlier acquisitions. There is a big old doggy in their and it sure as hell isn't letting the tail wag it of the hearth rug o f mol biol research IMHO.