October 22, 2012
A tale of two scientists
Two British Heart Foundation scientists
explain what Nobel Prize winners John Gurdon and Shinya Yamanaka’s
stem cell work means for their research, and reveal what their
school reports said about them…
'Doesn't pay enough attention
Chris Denning works out of a lab at the University of
Nottingham, where he and his team are using innovative stem cell
techniques to test the effectiveness of approved drugs on patients
with long QT syndrome – a type of arrhythmia.
The syndrome is usually treated with
beta-blockers, which can have some inconvenient side effects.
As always, new treatments are needed - but the
process of clinical trials to find those new drugs is often
long and involved.
Chris is helping narrow down the list of potential treatments, but
in an unusual way. Instead of asking people to take pills or have
injections, he’s taking their skin cells away to the lab.
What teacher said
According to Chris, his childhood beginnings didn’t show much
Frequently brought up for not paying attention in class, and
told off for his poor English, the boy who ‘could be good at this –
if he tried harder’ didn’t seem cut out for a career in
Thanks to Nobel Prize winner Shinya Yamanaka’s
those skin cells can then be turned into stem cells. The process is
already so refined that it can take just 3 to 4 weeks to get those
stem cells, and after a month or so to make sure everything is
fine, they’re then given the boost that turns them into
cardiomyocytes – heart cells.
Chris says, “For decades we scientists struggled with massively
complex ways of turning one type of cell into another, usually
starting with egg cells like the frogspawn John Gurdon created, and
moving slowly forward into other areas with the technology that
created medical marvels like Dolly the Sheep. But for every step
forward there was another setback, and the ethical considerations
“Without Yamanaka’s major
discovery and the work of those who came before him, what we’re
doing now would simply not be possible. In particular Jamie
Thompson in the United States’ work on embryonic stem cells meant
we started well ahead of the game.
“Yamanaka transformed the way we
think about stem cells. Who would have thought that it only
four genes to
turn more or less any type of cell into a stem cell?”
And once they have stem cells, how do they
turn them into heart cells? Chris says “We give them the same kind
of signals Mother Nature gives us in the womb.”
It can take up to six months to generate
enough heart muscle cells, but when they’re ready Professor Denning
and his team can test all sorts of drugs with the potential to help
patients with long QT right there in the lab.
“Finding out that we could take ordinary skin
cells from someone with long QT, turn them into stem cells and then
heart cells, and they still behaved the way they would for someone
with the syndrome was a real breakthrough.
“Being able to test drugs on heart cells in a dish has made the
process of discovering treatments so much more efficient.”
Luckily for us here at the British Heart
Foundation – and probably Chris too – at 13 his ideas were turned
around by a particularly inspiring biology teacher. So Mr Linburn,
this is for you.
'I have to thank John Gurdon'
Dr Andreia Bernardo is working hard to
learn more about how an embryo’s heart develops in the womb. In the
future she hopes this will help lead to new treatments and
techniques for diagnosing congenital heart disease.
But without access to stem cells, this kind of
research would be almost impossible.
“With stem cells we can mimic the development
of the heart and study what happens when, say, a particular protein
isn’t present. We’re looking at a protein that appears to be key to
ensuring the early heart develops properly,” explains Dr
"My love of science was nurtured at
“At the age of 14 I had one really inspiring
teacher who propelled me into science. I have a lot to thank her
for – she recognised my interest and encouraged it."
Andreia divides her time between labs at the National Institute for
Medical Research in London and the University of Cambridge, home of
Nobel Prize winner John Gurdon whose pioneering research was the
foundation for stem cell studies like hers.
“I have to thank him – his work completely
changed the field of developmental biology and ultimately paved the
way to deriving human embryonic stem cells without having to use
"John Gurdon proved that specialised adult
cells still contain the genetic information needed to become other
types of adult cells. He created a whole new frog from a single
adult cell taken from a frog’s intestine.”
Being at Cambridge with
John Gurdon and hearing him speak is a tremendous honour for Dr
Bernardo – he still attends lab meetings, even on the day he won
the Nobel Prize.
Shinya Yamanaka, who shares the Nobel Prize
with Gurdon, was also an inspiration at a key point in Andreia’s
scientific career. Yamanaka took Gurdon’s discovery further – he
found a way to turn cells that couldn’t change into ones that
could, - known as induced pluripotent stem (iPS) cells - without
needing an egg cell.
“I was just finishing my PhD when he made his
key stem cell discovery. In 2007, I went to one of his first talks
after the research on human iPS cells was published. It was a
really exciting time and I was fortunate enough to meet him –
despite the magnitude of his findings, he was incredibly
“I’m now able to use stem cells as a tool to
study questions about how the heart develops. Ultimately I hope
this work will contribute to our understanding of congenital heart
disease and contribute to new ways to treat it.”
We know who Andreia would thank if she wins a
Nobel Prize one day. In the meantime we hope to see how her
research progresses so that in the future, it can help babies born
with heart defects.