This year's winners occupies a sensitive area of health: gene therapy. Gene therapy, put simply, is when genes -- the instruction manual for how everything in an organism operates -- are manipulated to alter the way a cell -- the components of the organism -- works. It's called therapy because it has been developed to tackle disorders arising from human genes that have mutated or are defective.
This is a sensitive area for several reasons: gene therapy is as controversial as any area of study involving our genetic material. And the death of a patient in the U.S. in 1999 has cast a long cloud over researchers and investors. Which is partly why the first company to commercialize gene therapy for cancer is based in China: Shenzhen-based SiBiono GeneTech Co.
Gene therapy works like this: Genes contain the information necessary for cells to function and multiply. This genetic information is contained in DNA, long thin strands built from combinations of four sorts of bases.
When cells multiply by splitting, these combinations are passed on and checked by genes called regulators for errors, so that new cells are identical to the old cells.
But the process can sometimes go wrong, creating mutant cells. Or sometimes we are born with defective genes. Either way, gene therapy's approach is to replace the bad gene with a good one.
It sounds simple enough, but it's not. The first problem is to identify the healing, or therapeutic gene. Then, a way has to be found to deliver the corrected gene to the target cells, because a gene, unlike chemicals, cannot spontaneously enter cells.
This is usually done, perhaps illogically, by giving the patient a virus. A virus, it turns out, is a very good delivery system for this kind of thing since it's good at getting inside cells and then duplicating (the virus is modified so it is not pathogenic, or disease causing, and won't replicate once inside host cells.)
Once the gene is in the cell, it still has a long way to go. First it must find its way into the inner sanctum of the cell, the nucleus. From there it must be activated so that it can start issuing its payload to the cell.
In the case of cancer, gene therapy largely focuses on one small gene -- p53, so called because its expressed protein has a molecular weight of 53,000 daltons (a dalton is roughly the weight of a hydrogen atom).
The p53 gene is a very special, very complex gene, since it appears to act as a kind of guardian to the genome, or central directory of genes. The p53 is still only partially understood, but one thing is clear: it's intimately connected to at least half of all human cancers.
A group of special proteins constantly patrol the genome looking for faults in the DNA; if they find one they immediately report to the p53 gene, which in turn is released in packs of four to sort out the problem.
"DNA damage," David Lane, who discovered p53 in 1979, wrote in the New Scientist, "makes the genome unstable and prone to mutation and disintegration."
The problem is that DNA is constantly being multiplied as cells divide, so the damage needs to be resolved quickly before it spreads.
This is what p53 genes do, putting a halt on cell growth until repairs are done. If the cell is beyond repair, the p53 gene forces the cell to self-destruct, something called apoptosis.
But what happens if the p53 isn't working properly? This is what happens in many cancer cases. If the p53 gene is faulty, or has been bent out of shape by a virus, the patrolling proteins may report back on faults in the DNA chain, but the p53 gene does not function correctly.
In this case there is nothing to stop the cancerous cells from multiplying, and tumors to grow. "For a healthy person cells just divide regularly, via a regulator gene like p53," says Dr. Chiushi Fu, assistant to the founder and CEO of SiBiono, Dr. Zhaohui Peng. "But with a cancer patient the regulatory cell loses control so the cells divide without limit."
The secret, then, in combating cancer with gene therapy is to somehow ensure the p53 does its job. The most obvious way is to introduce "good" p53 genes into tumor cells, which is exactly what SiBiono GeneTech does by building a payload of a "healthy" p53 gene packed into a viral delivery mechanism called an adenoviral vector, containing a class of virus that would normally cause respiratory, intestinal and eye infections (including the common cold).
Once inside the nucleus the particles will unload their healthy p53 genes which, it is hoped, will then begin to do the job they're supposed to do -- halting the spread of cancerous cells.
SiBiono, under Dr. Peng, saw cancer as a natural focus for gene therapy. Unlike surgery, chemotherapy or radiotherapy, gene therapy went to the heart of the problem by tackling the genetic abnormality that causes the cancer in the first place.
The Gendicine therapy, the company's submission for the award says, "treats cancer from the very root of its initiation and development." That's not to say gene therapy can't be conducted in tandem with other therapies.
Indeed, SiBiono says that trials have thrown up some unexpected but positive findings in patients, including improved appetite, relief of cancerous pain and resistance to the side effects caused by radiotherapy or chemotherapy.
SiBiono has also been fortunate, if that's the right word, to step into a void left by setbacks in Europe and the U.S.
In 1999 an 18-year-old American man died from multiple organ failure four days after joining a gene-therapy trial, apparently reacting to the adenovirus carrier. And U.S. authorities in 2003 placed a temporary halt on some gene-therapy trials using a different viral-delivery mechanism after a French child developed leukemia-like conditions after gene therapy.
China, on the other hand, has been supportive of work in this field, including government investment from ministries and the local municipal government.
The company denies that processes are more lax, pointing out that China's regulatory body issued gene-therapy guidelines in 2003. Clinical costs are also lower in China, a fraction of the tens of thousands of dollars a U.S. company would have to pay per person.
Gendicine was approved by China's regulatory body in October 2003 and was officially launched six months later, the world's first commercially available gene-therapy product.
More than 4,000 patients from 26 countries have received treatment, without any reports of severe side effects, according to the company. SiBiono says sales of Gendicine reached 11.4 million renminbi ($1.4 million) in 2004 and it projects sales this year of nearly 19 million renminbi.
But that's not to say it has been a simple process to get this far. In the early years "it was a very difficult road," says Dr. Fu. "We put a lot of money in and at that time there was still risk."
Western competitors had more money, and trying to recruit patients in China was not easy. "We had to tell them what it is, they had no idea -- including the doctors," Dr. Fu recalls.
In the end, says Dr. Fu, the continued success of Gendicine will depend on whether it continues its initial promise. "The efficacy of the drug is the bottom line," he says. "Or I should call it the lifeline?"
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