The Telegraph, Alexander Masters, 31 Aug 2012
Professor
Magnus Essand and Dr Justyna Leja look at an image of oncolytic viruses
bursting cancer cells (Photo: Di Yu)
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.
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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 the National 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
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