A virus that kills cancer: the cure that's waiting in the cold

A virus that kills cancer: the cure that's waiting in the cold

• Posted by tatooke on September 1, 2012 at 11:12pm
  
• Send Message View Blog
  

Sitting in a refrigerator in a Swedish laboratory is
what promises to be a cheap and effective cancer treatment. So why are
the trials to bring it to market not going ahead?


On the snow-clotted plains of central Sweden
where Wotan and Thor, the clamorous gods of magic and death, once held
sway, a young, self-deprecating gene therapist has invented a virus that
eliminates the type of cancer that killed Steve Jobs.


'Not "eliminates"! Not "invented", no!'
interrupts Professor Magnus Essand, panicked, when I Skype him to ask
about this explosive achievement.


'Our results are only in the lab so far, not in
humans, and many treatments that work in the lab can turn out to be not
so effective in humans. However, adenovirus serotype 5 is a common
virus in which we have achieved transcriptional targeting by replacing
an endogenous viral promoter sequence by…'


It sounds too kindly of the gods to be true: a virus that eats cancer.


'I sometimes use the phrase "an assassin who kills all the bad guys",' Prof Essand agrees contentedly.

Cheap to produce, the virus is exquisitely precise, with only mild,
flu-like side-effects in humans. Photographs in research reports show
tumours in test mice melting away.

'It is amazing,' Prof Essand gleams in wonder. 'It's better than
anything else. Tumour cell lines that are resistant to every other drug,
it kills them in these animals.'

Yet as things stand, Ad5[CgA-E1A-miR122]PTD – to give it the full
gush of its most up-to-date scientific name – is never going to be
tested to see if it might also save humans. Since 2010 it has been kept
in a bedsit-sized mini freezer in a busy lobby outside Prof Essand's
office, gathering frost. ('Would you like to see?' He raises his laptop
computer and turns, so its camera picks out a table-top Electrolux next
to the lab's main corridor.)

Two hundred metres away is the Uppsala University Hospital, a
European Centre of Excellence in Neuroendocrine Tumours. Patients fly in
from all over the world to be seen here, especially from America, where
treatment for certain types of cancer lags five years behind Europe.
Yet even when these sufferers have nothing else to hope for, have only
months left to live, wave platinum credit cards and are prepared to sign
papers agreeing to try anything, to hell with the side-effects, the
oncologists are not permitted – would find themselves behind bars if
they tried – to race down the corridors and snatch the solution out of
Prof Essand's freezer.

I found out about Prof Magnus Essand by stalking him. Two and a half
years ago the friend who edits all my work – the biographer and genius
transformer of rotten sentences and misdirected ideas, Dido Davies – was
diagnosed with neuroendocrine tumours, the exact type of cancer that
Steve Jobs had. Every three weeks she would emerge from the hospital
after eight hours of chemotherapy infusion, as pale as ice but
nevertheless chortling and optimistic, whereas I (having spent the day
battling Dido's brutal edits to my work, among drip tubes) would stumble
back home, crack open whisky and cigarettes, and slump by the computer.
Although chemotherapy shrank the tumour, it did not cure it. There had
to be something better.

It was on one of those evenings that I came across a blog about a
quack in Mexico who had an idea about using sub-molecular particles –
nanotechnology. Quacks provide a very useful service to medical tyros
such as myself, because they read all the best journals the day they
appear and by the end of the week have turned the results into potions
and tinctures. It's like Tommy Lee Jones in Men in Black reading theNational Enquirer to
find out what aliens are up to, because that's the only paper trashy
enough to print the truth. Keep an eye on what the quacks are saying,
and you have an idea of what might be promising at the Wild West
frontier of medicine. This particular quack was in prison awaiting trial
for the manslaughter (by quackery) of one of his patients, but his
nanotechnology website led, via a chain of links, to a YouTube lecture
about an astounding new therapy for neuroendocrine cancer based on pig
microbes, which is currently being put through a variety of clinical
trials in America.

I stopped the video and took a snapshot of the poster behind the
lecturer's podium listing useful research company addresses; on the
website of one of these organisations was a reference to a scholarly
article that, when I checked through the footnotes, led, via a doctoral
thesis, to a Skype address – which I dialled.

'Hey! Hey!' Prof Magnus Essand answered.

To geneticists, the science makes perfect sense. It is a fact of
human biology that healthy cells are programmed to die when they become
infected by a virus, because this prevents the virus spreading to other
parts of the body. But a cancerous cell is immortal; through its
mutations it has somehow managed to turn off the bits of its genetic
programme that enforce cell suicide. This means that, if a suitable
virus infects a cancer cell, it could continue to replicate inside it
uncontrollably, and causes the cell to 'lyse' – or, in non-technical
language, tear apart. The progeny viruses then spread to cancer cells
nearby and repeat the process. A virus becomes, in effect, a cancer of
cancer. In Prof Essand's laboratory studies his virus surges through the
bloodstreams of test animals, rupturing cancerous cells with Viking
rapacity.

The Uppsala virus isn't unique. Since the 1880s, doctors have known
that viral infections can cause dramatic reductions in tumours. In 1890
an Italian clinician discovered that prostitutes with cervical cancer
went into remission when they were vaccinated against rabies, and for
several years he wandered the Tuscan countryside injecting women with
dog saliva. In another, 20th-century, case, a 14-year-old boy with
lymphatic leukaemia caught chickenpox: within a few days his grotesquely
enlarged liver and spleen had returned to ordinary size; his explosive
white blood cell count had shrunk nearly 50-fold, back to normal.

But it wasn't until the 1990s, and the boom in understanding of
genetics, that scientists finally learnt how to harness and enhance this
effect. Two decades later, the first results are starting to be
discussed in cancer journals.

So why is Magnus – did he mind if I called him 'Magnus'? – about to stop his work?

A reticent, gently doleful-looking man, he has a Swedish chirrup that
makes him sound jolly whatever his actual mood. On the web, the first
links to him proclaim the Essand Band, his rock group. 'Money,' he said.
'Lack of.'

'Lack of how much money? Give me a figure,' I pressed. 'What sort of
price are we talking about to get this virus out of your freezer and
give these people a chance of life?'

Magnus has light brown hair that, like his voice, refuses to
cooperate. No matter how much he ruffles it, it looks politely combed.
He wriggled his fingers through it now, raised his eyes and squinted in
calculation, then looked back into his laptop camera. 'About a million
pounds?'

More people have full-blown neuroendocrine tumours (known as NETs or
carcinoids) than stomach, pancreas, oesophagus or liver cancer. And the
incidence is growing: there has been a five-fold increase in the number
of people diagnosed in the last 30 years.

In medical school, students are taught 'when you hear hoof beats,
think horses not zebras' – don't diagnose a rare disease when there's a
more prob-able explanation. It leads to frequent misdiagnoses: until the
death of Steve Jobs, NETs were considered the zebras of cancer, and
dismissed as irritable bowel syndrome, flu or the patient getting in a
tizz. But doctors are now realising that NETs are much more prevalent
than previously thought. In a recent set of post-mortem investigations,
scientists cut open more than 30,000 bodies, and ran their hands down
the intestines of the dead as if they were squeezing out sausage skins.
One in every 100 of them had the distinctive gritty bumps of NETs.
That's two people in every rush-hour tube carriage on your way home from
work, or scaled up, 700,000 people in Britain, or roughly twice the
population of the city of Manchester. The majority of these tumours are
benign; but a small percentage of them, for reasons that no one
understands, burst into malignancy.

Many other cancers, if they spread, acquire certain features of
neuroendocrine tumours. The first person to own a successful
anti-neuroendocrine cancer drug – it doesn't even have to cure the
disease, just slow its progress as anti-retrovirals have done with Aids –
will be not only healthy but also Steve Jobs-rich. Last year the
pharmaceuticals giant Amgen bought a cancer-assassinating version of the
herpes virus for $1 billion. That Magnus's virus could be held up by a
minuscule £1 million dumbfounded me.

'That's a banker's bonus,' I said. 'Less than a rock star's gold
toilet seat. It's the best bargain going. If I found someone to give you
this money, would you start the clinical trials?'

'Of course,' replied Magnus. 'Shall I ask the Swedish Cancer Board how soon we can begin?'

I do not have a million pounds. But for £68 I flew to Uppsala. I
wanted to pester Prof Essand about his work, face to face, and see this
virus, face to petri dish. I wanted to slip some into my mittens,
smuggle it back to England in an ice pack and jab it into Dido.

Magnus's work is already funded by the Swedish Cancer Society and the
Swedish Children Cancer Society (neuroblastoma, the most common cancer
in infants, is a type of neuroendocrine tumour). A virus that he
previously developed (against prostate cancer) is about to enter human
trials in Rotterdam, supported by a European Union grant.

The difficulty with Magnus's virus is not that it is outré, but that
it is not outré enough. It is a modified version of an adenovirus, which
is known to be safe in humans. It originates from humans, occurring
naturally in the adenoids. The disadvantage is that it is too safe: the
immune system has had thousands of years to learn how to dispatch such
viruses the moment they stray out of the adenoids. It is not the fact
that Magnus is using a virus to deal with cancer that makes his
investigation potentially so valuable, but the novel way he has devised
to get round this problem of instant elimination by the immune system,
and enable the virus to spread through tumours in other parts of the
body.

The closer you get to manipulating the cellular forces of human
existence, the more you sound like a schoolboy babbling about his model
aeroplane. Everything in the modern genetics lab is done with kits.
There are no fizzing computer lights or fractionating columns dribbling
out coagulations of genetic soup in Magnus's lab; not a single Bunsen
burner. Each narrow laboratory room has pale, uncluttered melamine
worktops running down both sides, wall units above and small blue
cardboard cartons dotted everywhere. Even in their genetics labs, Swedes
enjoy an air of flatpack-ness. The most advanced medical lab in the
world, and it looks like a half-fitted kitchen.

To make and test their virus, Magnus buys cell lines pre-fab
(including 'human foreskin fibro-blast') for $50-100 from a company in
California; DNA and 'enzyme mix' arrive in $179 packets from Indiana;
protein concentrations are tested 'according to the manufacturer's
instructions' with a DIY kit ($117) from Illinois; and for $79, a parcel
from Santa Cruz contains (I haven't made this up) 'horseradish
peroxidase conjugated donkey anti-goat antibody'.

In a room next to Magnus's office, a chatty woman with a ponytail is
putting DNA inside bacteria. This God-like operation of primal delicacy
involves taking a test tube with a yellow top from a $146 Qiagen kit,
squirting in a bit of liquid with a pipette and putting the result in a
box similar to a microwave: 'turn the dial to 25 kilovolts and oophlah!
The bacteria, they get scared, they let the DNA in. All done,' the woman
says. As the bacteria divide, the desirable viral fragments increase.

What costs the £1 million (less than two per cent of the price of Francis Bacon's Triptych 1976)
that Magnus needs to bring this medicine to patients is not the
production, but the health-and-safety paperwork to get the trials
started. Trials come in three phases. What Magnus was suggesting for his
trifling £1 million (two Mont Blanc diamond-encrusted pens) was not
just a phase I trial, but also a phase II, which, all being well, would
bring the virus right to the point where a big pharmaceuticals company
would pay 10 or 100 times as much to take it over and organise the phase
III trial required by law to presage full-scale drug development.

'So, if Calvin Klein or Elton John or… Paris Hilton stumped up a million, could they have the virus named after them?'

'Why not?' Magnus nodded, showing me the bacteria incubator, which
looks like an industrial clothes washer, only less complicated. 'We can
make an even better one for two million.'

There are reasons to be cautious. A recent investigation by Amgen
found that 47 of 53 papers (on all medical subjects, not just viruses)
by academics in top peer-reviewed science journals contained results
that couldn't be reproduced, even though company scientists repeated the
experiments up to 50 times. 'That's why we have to have such a careful
peer-review process,' Dr Tim Meyer, Dido's energetic, soft-spoken
oncologist, warns. 'Everybody thinks that their new treatment for cancer
is worth funding, but everybody is also keen that only good-quality
research is funded.' Similar to Prof Essand in youth but less polite of
hair, Dr Meyer is the co-director of the Experimental Cancer Medicine
Centre at University College London. Beside his office, banks of
white-coated researchers are bent over desks, busy with pipettes and
microscopes. His team pursues an exciting brew of new anti-cancer ideas:
antibody-targeted therapy, vascular therapy, DNA binding agents and
photodynamic therapy. Each of these shows remarkable promise. But even
for such a brilliant and innovative team as this, money is not flowing.

Everyone in cancer science is fighting for ever-decreasing small
pools of cash, especially now the government has started tiptoeing into
charities at night and rifling the collection boxes. It is big news that
Dr Meyer and the UCL team won a grant of £2.5 million, spread out over
the next five years, to continue his institute's cutting-edge
investigations into cancers that kill off thousands of us every week:
leukaemia; melanoma; gynaecological, gastrointestinal and prostate
cancers. Without this money, he would have had to sack 13 members of
staff. The sum of £2.5 million is roughly what Madonna earns in 10 days.

He peers at Magnus's pairs of photographs of splayed rodents with
glowing tumours in one shot that have vanished in the next. He knows the
Uppsala neuroendocrine team well and has great respect for them. 'It
may be good,' he agrees. But until Magnus's findings are tested in a
clinical trial, nobody knows how good the work is. Astonishing results
in animals are often disappointing in humans. 'We all need to be subject
to the same rules of competitive grant funding and peer review in order
to use scarce resources in the most effective manner.'

Back at home with whisky and fags, I nursed my entrepreneurialism.
There are currently about half a dozen cancer research institutes in
Europe developing adenoviruses to treat cancer – all of them
pathetically short of cash. Enter the Vanity Virus Initiative. Pop a
couple of million over to Uppsala University, and you will go down in
medical books as the kind heart who relieved Ad5[CgA-E1A-miR122]PTD of
its hideous hump of a moniker, and gave it the glamour of your own name.
What's the worst that can happen? Even if Magnus's innovations don't
work in clinical trials the negative results will be invaluable for the
next generation of viruses. For the rest of time, your name will pop up
in the reference sections of medical papers as the (insert your name
here) virus that enabled researchers to find the cure for cancer by
avoiding Magnus's error.

On my third glass of whisky, I wrote an email to Dr Meyer suggesting
that he issue a shopping list each year at the time that bankers receive
their bonuses, which could be circulated in the City. The list would
itemise the therapies that his Experimental Cancer Medicine Centre have
selected for support, and quantify how much would be needed in each case
to cover all outstanding funds and ensure that the work is branded with
your name.

The corridors connecting the different research departments of the
Uppsala medical campus are built underground, in order to protect the
staff from death during the Swedish winters. Professors and lab
technicians zip back and forth along these enormous rectangular tunnels
on scooters, occasionally scratching their heads at the tangled
intersections where three or four passageways meet at once, then pushing
off again, gowns flying, one leg pounding the concrete floor like a
piston, until they find the right door, drop the scooter and rise back
upstairs by lift. Suspended from the ceiling of these corridors is a
vacuum tube that schluuuuups up tissue samples at top speed, and
delivers them to the appropriate investigative team. Magnus led me along
these tunnels to the Uppsala University Hospital, to visit the chief
oncologist, Kjell (pronounced 'Shell') Oberg – the man who will run the
trial once the money is in place.

'The trouble with Magnus's virus is Magnus is Swedish,' he says, wincing and clutching the air with frustration.

'It is so,' Magnus agrees sorrowfully. Swedishly uninterested in
profiteering, devoted only to the purity of science, Magnus and his
co-workers on this virus have already published the details of their
experiments in leading journals around the world, which means that the
modified virus as it stands can no longer be patented. And without a
patent to make the virus commercial, no one will invest. Even if I could
raise the £2 million (I want only the best version) to get the therapy
to the end of phase II trials, no organisation is going to step forward
to run the phase III trial that is necessary to make the therapy public.

'Is that because pharmaceuticals companies are run by ruthless
plutocrats who tuck into roast baby with cranberry sauce for lunch and
laugh at the sick?' I ask sneerily.

'It is because,' Kjell corrects me, 'only if there's a big profit can
such companies ensure that everyone involved earns enough to pay their
mortgage.'

There is no ready source of public funds, either. For reasons
understood only by Wotan and Thor, the Swedish government refuses to
finance clinical trials in humans, even when the results could
potentially slash the country's health bill by billions of kronor.

All is not lost, however. Kjell does not have to wait until the end
of the trials – which could take as much as 10 years – for the full,
three-phase process before being able to inject Magnus's virus into his
patients, because as soon as the test samples are approved and ready for
use, he can by European law start offering the medicine, on an
individual basis, to patients who sign a waiver confirming that they're
prepared to risk experimental treatments. Within 18 months he could be
starting his human case-studies.

At several moments during my research into this cancer-delaying virus
from the forests of Scandinavia I have felt as though there were
someone schlocky from Hollywood operating behind the scenes. The
serendipitous discovery of it on the internet; the appalling frustration
of being able to see the new therapy, to stand with my hand against the
freezer door knowing that it is three inches away, not well-guarded,
and that it might work even in its crude current state, but that I may
not use it; the thrill of Kjell Oberg's powerful
support; the
despair over the lack of such a silly, artificial thing as a patent.
Now, Dr Leja steps into the narrative: she is the virologist whose
brilliant doctoral thesis first put me on to the
cancer-eating-virus-left-in-a-freezer, and whose name heads all the
subsequent breakthrough research papers about this therapy. She turns
out to be 29, to look like Scarlett Johansson and to wear voluptuous red
lipstick.

Justyna Leja slinks up from her chair, shakes my hand and immediately
sets off into a baffling technical discussion with Magnus about a good
way to get the patent back for the virus, by a subtle manipulation that
involves something called a 'new backbone'. She also has in mind a small
extra tweak to the new-backboned microbe's outer coat, which will mean
that the virus not only bursts the cancer cells it infects, but also
provokes the immune system to attack tumours directly. It will be easy
to see if it works in animals – but is it worth lumbering the current
virus with it for use in humans, who tend to be less responsive? The
extra preparatory work could delay the phase I and II trials for a
further year.

Back at his lab, Magnus opened up the infamous freezer. I took a step
towards the plastic flasks of virus: he nipped the door shut with an
appreciative smile.

'What would you do,' I asked bitterly, returning my hand to my
pocket, 'if it were your wife who had the disease, or one of your sons
whose photograph I saw on your desk?'

He glanced back at the freezer. Although his lab samples are not made
to pharmaceutical grade, they would be only marginally less trustworthy
than a fully-sanctioned, health-and-safety certified product that is
between 1,000 and 10,000 times more expensive.

'I don't know,' he groaned, tugging his hair in despair at the thought. 'I don't know.'

To donate money to Professor Magnus Essand's research on viral
treatments for neuroendocrine cancer, send contributions to Uppsala
University, The Oncolytic Virus Fund, Box 256, SE-751 05 Uppsala,
Sweden, or visit www.uu.se/en/support/oncolytic.
Contributions will be acknowledged in scientific publications and in
association with the clinical trial. A donation of £1 million will
ensure the virus is named in your honour

http://www.telegraph.co.uk/science/9508895/A-virus-that-kills-cance...


Thanks to: http://extraterrestrials.ning.com