She was by far the world’s most famous sheep. When scientists from Edinburgh’s Roslin Institute announced in early 1997 that they had, using nuclear transfer, cloned the first mammal from an adult cell, the world went mad for Dolly. There were Dolly the sheep postcards, stuffed animals (dressed, of course, in red tartan dresses), T-shirts, children’s books and baseball caps. Everything the ewe (named in honour of Dolly Parton, because she was cloned from a mammary cell) did – from the birth of her four offspring to the sad announcement in 2003 that she would have to be put to sleep because she was suffering from a progressive lung disease – made headlines across the globe.
Because of her early death, many critics of cloning argued that her health (she suffered from a form of arthritis usually found in older animals) was affected, and that there could be health risks associated with premature ageing of clones. Dolly’s legacy has been not only to put the institute on the map, but to also bring the debate over the ethics of cloning forward.
What the Roslin Institute did for groundbreaking research on cloning is what biotech company Geron Corporation, which bought the Roslin Institute’s commercial arm, Roslin Bio-Med in 1999, believes it can do for stem cell and cancer research.
“Embryonic stem cells are going to revolutionise medicine [and] there is no question that we are the dominant player in the world in that field,” says Geron Corporation CEO Dr Thomas Okarma. “And we will be the first across the goal line.”
Based in Menlo Park, California, the company was founded in 1990 with the original aim of studying the biology of the human ageing process and extending the lifespan by slowing that process down. “It was an attractive way to raise money, but hard to actually put into practice, so what quickly happened was the scientists moved from looking at the ageing of humans to the ageing of human cells, which is very biologically and molecular-based,” says Mr Okarma.
The research of those early scientists – which included the Nobel Prize for Physiology or Medicine 2009 winners Elizabeth H Blackburn and Carol W Greider – uncovered the importance of telomerase biology, which has become the core competence of the company for their three product portfolios.
What Geron has found is that telomeres, located at the end of chromosomes, are key genetic elements involved in regulating the cellular ageing process. Each time a cell divides, telomeres shorten, so that once they reach a certain short length, cell division halts. This means that telomeres work as a molecular clock for cellular ageing. When the telomerase enzyme is introduced into normal cells it helps restore telomere length, which, says Mr Okarma, resets the clock and increases the functional lifespan of cells without changing the cell’s biology or causing them to become cancerous.
“The discovery of normal cells that express telomeres was what led to our embryonic stem cell programme,” says Mr Okarma. “That is how we became the leader because we started the field; we got all the licences and developed our own technology and patents that put us way far ahead of everyone particularly during the [George W] Bush years when there was no funding for our academic colleagues.”
Geron focuses its business on therapeutic products for the treatment of cancer that inhibits telomerase; pharmaceuticals that trigger telomerase in tissues affected by cell ageing, injury or degenerative diseases; and the treatment of several chronic diseases from cell-based therapies created from human embryonic stem cells.
Imetelstat, Geron’s anti-cancer drug that is the world’s only specific telomerase inhibitor, has demonstrated successfully in phase one trials that it not only kills the bulk of mature cancer cells, but is the only drug that hits the cancer stem cell; phase two clinical trials in patients should begin later this year. “Imetelstat will be Geron’s first demonstration to the world that what we have invented here is a breakthrough [for] cancer,” says Mr Okarma.
Geron’s stem cell research is also potentially groundbreaking; the company was the first in the world to gain approval from the US’s Food and Drug Administration (FDA) to do clinical trials on humans after a 22,000-page report (the longest the FDA has ever received) was submitted. Despite the FDA putting the trials on hold last September because of some concerns over an animal trial, Mr Okarma is confident the issue will be resolved and the human trials can begin.
“What we are talking about is a whole new value paradigm for medical therapeutics,” he says. “Going from taking a pill or gene therapy that transiently alleviates symptoms to a single intervention of living cells that permanently restores structure and function to the tissue that is damaged by an injury or an illness – that is incredible.”
Mr Okarma says that for now Geron, which also has a majority stake in Hong Kong’s TA Therapeutics, has no plans for expansion. “We have a lot on our plate that we have to deliver on,” he says. “My concern is raising enough money to distribute to people working on all these projects, whether in the UK, Hong Kong or Menlo Park, so it is really our duty as a publicly held company to deliver clinical value on these projects.” Mr Okarma rankles when asked about running the company on a loss. “Most biotech companies operate at a loss and that is sort of the game,” he says.
“When the Geron story is written, I think the interesting chapter will be how frugal we have been.
We have raised and spent $500m since inception to develop what we now have on the table – now compare that to big pharmas that will spend a billion dollars on a single drug.” Mr Okarma admits that they have yet to go through all the stages of clinical trials and do not yet have any products available – but he believes it is only a matter of time.
“We have a very rich balance sheet and nearly $200m in cash, no debt and we have lots of good analysts and investors – both individual and institutional – because they see incredible value in what we are doing. My job is to maintain that interest to make sure we make tangible progress month after month.”
Menlo Park, CaliforniaFounded
Geron Bio-Med Limited (Edinburgh, Scotland); TA Therapeutics Limited (Hong Kong)CEO