Monday, 15 February 2016

Article on dealing with floods published in the Irish Daily Mail, 9 January, 2016


There's no magic wand to solve our flooding woes, which have been with us since time began. Instead, this writer argues, we have to retreat from flood plains.


By Gerry Byrne

‘Bandon is destroyed,’ declared the tall Garda rather theatrically as he sent us miles further inland from our planned itinerary from Cork to Schull for a New Year's break little more than a week ago.  And not just Bandon was destroyed. We passed through mile after mile of flooded fields, homes and roads and faced even more diversions until we finally and circuitously reached our goal, via Bantry, no less.

But the earlier part of the journey, from Dublin to Cork City had already convinced us that something apocalyptic had indeed happened to the landscape. Flooding was visible everywhere. As yet more inundated properties loomed into view I gave quiet thanks that I live on the east of the island, on the side of a hill, miles from a big river, and in an area with the second lowest rainfall in the country.

The car radio crackled that day with phone-ins peppered with calls for ‘Enda to come and see this...’ as though he possessed some magic bucket which would drain the land in minutes. The truth is that, apart from re-engineering the entire island overnight, there was very little that even Enda could do. The nation was experiencing a national disaster. Kansas gets whirlwinds, Nepal earthquakes, other countries have volcanic eruptions or droughts but we get lots of rain and flooding.

Indeed, in scientific terms we could not be worse placed to receive the Atlantic storms which nature hurls at us. In an ideal world Enda the Wizard would shift the entire island several hundred miles to the south and safely out of the way of the salvo of depressions that the Atlantic launches at us every year.

Last month it was easy to lose track of the storms, there were so many. But the weather statistics told their own tale. Many places experienced three and half times more rain than the average month of December and it often fell in a matter of hours, not days or weeks. A total of 300 mm on average poured on our heads from above.

Let me try to place that in perspective. Pretend that, overnight, Ireland became completely flat with a big wall around it preventing last month's rainwater from escaping to the sea. The entire island, every inch of it, would then be flooded to a depth of 300 mm, or one foot. That's nearly up to the top of your wellies, everywhere in the country. It would seep into every house.

Now, let us magically remove the big wall and instantly grow back the hills and mountains and force all that water to drain away. On the east coast of the country relatively short, fast flowing downhill rivers like the Boyne, the Liffey, the Dodder, the Dargle and the Slaney would quickly deal with the wellie-deep water in their catchments and funnel it to the Irish sea without too much flooding.  

In the Midlands and the hilly country further to the south, things are very different. Geography, which favours drainage on the East Coast, works against it elsewhere. More than a third of the rainfall falling on the Republic can only go one way, into the long river Shannon which meanders though a flat plain, draining some or all of 17 counties with a fall of only a few metres between Carrick-on-Shannon and Killaloe, 170 km driving distance apart.

Drop a tennis ball in the upper reaches of a flooded River Liffey and it could be in the sea within 24 hours. A tennis ball dropped off the bridge at Carrick-on-Shannon could take weeks to reach the sea, so slowly does the current move. While a flood dramatically accelerates the flow of the Liffey, on the Shannon it simply causes it to develop the watery equivalent of middle-aged spread as it spreads out across the landscape, flooding the central plains like it has done for millennia.

In the south, especially in West Cork, rivers are funnelled through valleys running largely towards the east which occasionally reach rock-bound bottlenecks causing the water to pile up, as it does in the centre of luckless Bandon. Bear also in mind that hilly country, as in West Cork, usually attracts heavier rainfall which drains rapidly into these valleys contributing to a form of flash flooding.

Many locals have blamed the Shannon flooding on the multiplicity of government and local agencies which administer the river and their alleged failure to co-operate, but a recent consultancy study carried out on behalf of the Office of Public Works' CFRAM project has declared the actions of those agencies has made little difference one way or the other. If anything, their policies mostly tend to reduce, not exacerbate, flooding.

Still, practically every flood news report brings further criticism of local and national authorities but while Bandon, in the words of the policeman, was ‘destroyed’ twice last month, it couldn't be blamed on any lack of effort on the part of Cork County Council which, following similar flooding in 2009, commissioned flood defences. Work was due to commence earlier last year but was delayed (and still is) following legal action by a disgruntled contractor who is contesting the legality of the tendering system.

But new flood defences for Fermoy convincingly saved the town from a bad drenching last month showing that someone is finally getting things right. Defences also appear to have spared Athlone from suffering Bandon's fate.

Saving large centres from the worst flooding has got to get priority and it's interesting to note that Cork City, whose turn to be destroyed came in 2009, escaped a repeat ducking last month, despite rainfall of biblical proportions in the Lee catchment during December.

It's smaller, rural settlements, or single one-off homes, often farmhouses, that need to worry as the cost per head of protecting them is enormous, compared to preventing flooding in larger towns and cities. 

And the question has to be asked: Is it better for those homes and farms to be abandoned to their fate and their occupants re-homed like abandoned puppies on higher ground, or in larger towns where flood defences are more effective? The answer is probably yes. Indeed, Enda Kenny has already suggested as much and he deserves some credit for having the political courage to say it.

Many of these properties are on flood plains of one form or another and they are flooding more, not less often because, not only are we losing the battle against nature, we are contributing to our own defeat. Shannon flooding comes courtesy of, let’s call it, the Law of Unintended Agricultural Consequences.

To explain, let me wind back a few hundred years when large areas of the Midlands were covered with peat bogs. In periods of high rainfall, these acted like a giant sponge, holding back some of the excess water which was then released slowly into the rivers. Many of those bogs have since been either drained for agriculture, or for turf cutting, thus reducing their sponge-like properties. The result is that more and more water is flooding immediately into the rivers instead of trickling in more slowly.

It's not just the bogs. Farmers have always drained land to make it more productive but the availability of efficient machinery and, in many cases, government grants, accelerated the process exponentially in recent years. But that soggy land played a vital role in storing excess water in the landscape, not in the river.  We need to minimise that land drainage.

AS TV weathermen never tire of telling us, flooding is more likely when the soil is saturated with water after a long period of rain. Because of that saturation additional rain simply runs directly into watercourses but our taming of the land may be accelerating this process. Heavy stocking of cattle compacts the soil, reducing its water carrying properties and giant farm machines contribute their share.

Clearing scrubland and felling trees doesn't help either and the concept of set-aside may need revisiting in a more innovative light. There's evidence that healthy vegetation contributes significantly to the water-holding capacity of the soil, because of the penetration of roots and the way leaves evaporate moisture back into the air.

It's impossible to tell how much earlier flood protection schemes are contributing to the flooding of the Shannon. These usually involved the dredging and draining of tributary rivers and streams to prevent local flooding of farms but all they often achieved was to cause water to reach the river even quicker and flood all the sooner. Sometimes it just flooded back up the tributary as the main river burst its banks even more rapidly and spread out over the plain, a further example of that law of Unintended Agricultural Consequences.

Flood defence engineers will have to be careful not to repeat the same mistakes again. Mrs Byrne, say, outside Athlone may be lucky in persuading the authorities to build a giant Dutch-style dyke all around her farm but the acres of waist-high water displaced by that dyke will simply move down the river a bit and flood someone else's land which has never flooded before. Then that owner will bellow on the airwaves for a dyke or some other flood prevention solution and someone else's land then gets flooded in a pattern that gets repeated ad infinitum all along the river.

I'm not ruling out the possibility that engineers might come up with some wizard wheeze that fixes the Shannon problem, perhaps involving a neat combination of calculus and trigonometry and lots of pumps, but neither am I rushing to the bookies to put bets on it.

I don't believe drainage is the answer but rather the opposite. We need to find more ways of slowing down the accelerating rush of water into the river, and in the meantime, to admit defeat and abandon attempts to prevent flooding in areas where it traditionally floods.

I'm quite happy for the Shannon flood plain to be used for agriculture, but when it rains too much, we should allow the old lady of the skies to spread her skirts on the land as she has done for thousands of years, while we respectfully retreat to higher ground.

*Gerry Byrne is the winner of three science journalism awards in Ireland and the USA.

Friday, 2 January 2015

Virtual Pharma

One-time stock market highflier Merrion
Pharmaceuticals has slimmed down
to the boss — and nobody else.

 Dr John Fox, Merrion's CEO, and only employee.

GERRY BYRNE reports on the
challenges of drug development

Published in Business Plus Magazine, December 2014 Edition

Daily injections of insulin are
tiresome for diabetic adults, and a
nightmare for untold millions of
children. So much so that when
an Irish bioscience company offers to
replace daily injections with a simple
tablet, you’d imagine that, like the
inventor of the proverbial perfect
mousetrap, potential investors are
beating a path to its door.
You’d think. Truth is that Merrion
Pharmaceuticals (which is offering such
a panacea) runs the real risk of running
out of cash before its promising
product, which could potentially be
worth billions, can reach the market.
Merrion is a former campus
company which in 2004 acquired
GIPET, a promising drug delivery
platform technology, from the rump
of the former Elan, which itself had
developed over its history several
promising alternative methods of
drug delivery, most notably the
medicinal patch.
Some drugs are so complicated that
they are unable to pass through the
wall of the stomach or intestines into
the bloodstream and, like insulin, must
be injected. But Merrion’s GIPET does
exactly what its synonym stands for
(Gastrointestinal Permeability
Enhancing Technology) and it renders
complex molecules soluble so they can
be taken in tablet form.
Merrion did well when it launched
an IPO priced at 405c a share in 2007,
rapidly achieving a market valuation
of €67m. In March 2009, the share
peaked at 515c on some good news
about a research partnership with
Danish insulin market leader Novo
Nordisk that was valued at upwards of
€100m, especially if viable products
were brought to market.
At the time Merrion had an
interesting pipeline of seven products,
only two of which were diabetes
related. The rest ranged from
treatments for breast and bone cancer,
osteoporosis drugs and a medication
to deal with deep vein thrombosis and
other blood clotting issues. At the time
of its 2007 IPO the Merrion
prospectus warned that the sums
raised would be insufficient to see its
library of patents through the full
spectrum of clinical trials. And at the
time diabetic treatments were further
down the list of Merrion’s priorities.
Instead its meteoric shining star
then was a GIPET version of an
existing osteoporosis treatment,
Fossamax. Yet the slings and arrows of
pharmaceutical fortune are such that
the osteoporosis remedy now sits
forlornly on a shelf awaiting funds to
take it into further trials, while
Merrion’s version of two insulin
treatments have leapfrogged ahead
and look set to enter further clinical
trials in the coming year.
The reason for the turnaround in
relative drug fortunes is because
Nova Nordisk smiled favourably
on Merrion’s versions of its
injectibles, while another company
which had shown great interest in the
osteoporosis treatment decided not to
proceed with it, and later sold the
drug in question, Fossamax, to a
South African company.
Merrion is a good example of how
smaller biotech companies have
benefited as the structure of drug
research and development has
changed dramatically over the past 20
years or so. Drug majors once
maintained large R&D departments
which invented new drugs and
prepared new products for market.
Now they have largely abandoned inhouse
research and development.
“Pharmaceutical giants have
downsized R&D and now tend to
search and develop, not research and
develop,” explains Mary Shire, Vice-
President for Research at the
University of Limerick. “They find that
buying promising candidates with
good data is more cost-effective than
investing in their own R&D and this
explains Novo Nordisk’s’ partnership
with Merrion.”
An analogy with the mining, oil and
gas sectors is not entirely misplaced.
Natural resource giants for years have
done very little of their own
exploration, relying instead on a
myriad of independent prospectors
which sniff out promising leads. If they
hit the jackpot, the territory gets sold
to a major mining or petrochemical
giant. If there’s a dry hole, or a lean
horizon, the prospector (and its
investors) takes a hit. It’s why investing
in exploration vehicles is like buying a
lottery ticket: you have a chance of
great riches but an even larger chance
of losing your investment.
Merrion is pharma’s equivalent of an
exploration company. That it has
come up with pay dirt is beyond
dispute, but time, and the structure of
the pharmaceutical market, has not
been on its side.
Nova Nordisk, while showing a keen
interest in Merrion’s tablet versions of
two of the Danish firm’s insulin
formulations, is not yet ready to fully
step up to the plate. The company has
signed a development agreement
which is worth €58m in phased
payments to Merrion to assist it to
nurse its products through the
minefield of clinical trials which can
easily cost tens of millions. Merrion
received €2m of payments in the past
year.While this gives Nova Nordisk an
option on Merrion’s patents, it doesn’t
commit it to doing a licensing deal.
Despite being based on existing
approved drugs, Merrion’s diabetes
products face a tough and very
expensive series of clinical trials to
satisfy the US Food and Drug
Administration that they are both safe
and effective. Like most of Merrion’s
drug prospects, they have already
succeeded in Phase One trials, where
the reformulated medication employing
GIPET has been successfully tried out
on a small sample of patients.
Phase Two requires a much larger
patient sample, upwards of 300
patients, but a further Phase Three
must then be trialled, where thousands
of patients are tested over a longer
period of time. Even at this stage
Merrion will not be out of the woods
because the drug’s performance must
be sampled over a further period,
Phase Four, to ensure no harmful side effects
occur with time.
Elan’s famed Tysabri, which is used
to treat Multiple Sclerosis, despite
passing successfully through Phase
Three trials, had to be temporarily
withdrawn in 2005 after Phase Four
monitoring revealed that two patients
were struck by a rare brain infection.
The FDA subsequently decided that
the benefits of the drug outweighed
the risks and it was allowed back on
the market.
A successful drug is doing well if it
reaches full market availability within
eight years. But the statistics for
drug success and failure are not
encouraging. For every 1,000
promising compounds identified, only
a handful are likely to reach the market
within a reasonable period of time. And
90% will fail during clinical trials.
An analysis by Forbes last year
estimated the cost to a US drug major
of launching a new drug in excess of
$5 billion, after adding on the price of
those that had failed. On a standalone
basis, the average new drug still costs
in excess of $1 billion to develop.
Merrion has the advantage of using
already approved drug molecules in its
GIPET-based compounds and
therefore is unlikely to need hundreds
of millions to get them over the line.
Chief executive Dr John Fox, a clinical
research veteran of pharmaceutical
giant Shire and Merrion’s former
director of research, still reckons he
would need more than €40m to
conduct clinical trials on its most
complicated formulation, a GIPETbased
treatment for post-menopausal
women recovering from breast cancer.
“We still have a couple of other
interesting projects but we don’t have
the cash to exploit them without
someone else coming in,” says Fox.
“However, we have a tremendous
industry validation with Nova Nordisk
and they are now entering the pointy
end of the development. This is where
it is starting to get serious and they
believe that it is going to get under the
market, and they have a huge
investment in taking this forward.”
Despite the promise held out by the
Nova Nordisk collaboration,Merrion
itself couldn’t be in worse shape. All of
its staff have been let go and its lab
equipment sold. Its Citywest HQ is on
the market at a valuation of some
€200,000 less than previous book
value. Income, apart from anticipated
further stage payments for the
development of the two insulin
compounds, has dried up and the
company had little more than
€300,000 in cash when it last reported.
Merrion’s sole objective is now
protecting its intellectual
properties, continuing its
collaboration with Nova Nordisk and
attempting further licensing deals for
the GIPET patents. “We really are a
virtual organisation now and you are
talking to the only salaried employee,”
quips Fox.
As if things couldn’t get much worse,
the company’s main debt, a €5m loan
from the investment vehicle of the
family of the late Tony Ryan, is due for
repayment. Following the intervention
of Declan Ryan, who is also a major
Merrion shareholder, repayment has
been stayed until September 2015.
Interest continues to be paid on the
loan although Fox admits its looming
deadline poses a concern.
Fox recently did a deal with
Portuguese pharmaceutical synthesiser
Hovione to produce under contract the
drug materials he will need for the
forthcoming insulin clinical trials.
“This allows the technologies to be
developed and marketed even though
Merrion does not have its own
business development team anymore,”
Fox explains.