[NIH] money well spent.”
Potential cures, or at least treatments that offer a significant life extension are stuck in the chasm between the bench and the doctor’s office: or what has been called the valley of death.
The problem starts in the lab, at the bench, and continues through the entire system. The entire system is broken!
The NIH and academia is structured to reward and fund basic discoveries; like identifying a gene for cancer! It doesn’t reward the translational grunt work that turns such breakthroughs into drugs. “Colleagues tell me they’re very successful getting NIH grants because their experiments are elegant and likely to yield fundamental discoveries, even if they have no prospect of producing something that helps human diseases,” says cancer biologist Raymond Hohl of the University of Iowa. In 2000, for instance, scientists at four separate labs discovered a gene called ABCC6, which, when mutated, causes PXE (pseudoxanthoma elasticum), a rare genetic disease in which the skin, eyes, heart, and other soft tissue become calcified—rock hard. By 2005, scientists had genetically engineered lab mice to develop the disease. The next step would be what’s called screening, in which scientists would laboriously test one molecule after another to see which had any effect on ABCC6. But “academic scientists aren’t capable of creating assays [test systems] to do that,” says Sharon Terry, CEO of the Genetic Alliance, which supports research on rare genetic diseases (her children have PXE). “It’s time-consuming drudgery and takes an expertise that hasn’t trickled down to the typical academic scientist.” Ten years later, there is still no cure for PXE!
If a researcher does discover a molecule that cures a disease in a lab rat, the reasonable next step is to test its toxicity and its efficacy in more lab animals. Until this underlying research has been completed, it is very unlikely a private company would be interested in purchasing the rights to the potential drug. “A company wants to know, how specific and toxic is the molecule?” says Kenneth Chahine, an expert in patent law at the University of Utah. “It might work great in a mouse, but will it make a rat keel over?
Our system does not reward this type of basic research and so, often, it doesn’t happen. It isn’t fun and it more importantly; the research will have a hard time getting funded. Our system wants and funds creative, slick, innovative research, not boring inelegant research. So, we never find out how much of a compound will it take to kill and does it show efficacy in other animals. Instead the discovery falls in to ‘valley of death’ and its potential is lost to the future!
All researchers are always worried about where the next grant will come from, so they want only to be involved in high profile, career boosting projects. I don’t blame them, I do blame the system.
If we are serious about really seeing translational research, actual influence in the doctor’s office, we will have to made fundamental changes to our systems. Until we honestly re-evaluate and change the system we should not expect things to get better. We should not expect to see drugs that will provide long term survival and we should not expect to see cures.
Among the needed changes includes forcing cooperation among turf-guarding academics. “There are thousands of researchers working on exactly the same thing,” says Bruce Bloom, whose Partnership for Cures foundation supports research on new uses for existing drugs. “Under the current system they cannot and will not collaborate for fear that it will jeopardize funding, patent protection, and publication. Look at the progress open-source software has made in IT. Imagine the progress open-source research could make in biomedicine.”
We also need to encourage and fund answers to the question ‘How can I get funding to turn this discovery into something?’ Some universities have begun to create drug-development groups, a good step in this direction.
Daria Mochly-Rosen of Stanford University has pointed out that the NIH has increased support for research intended to help patients. However, “there is still very little funding for steps such as testing a compound’s toxicity in several species of lab animals, synthesizing the molecule, and scaling up that synthesis. “What we lack in academia is an understanding that these steps can be intellectually interesting, too,” said Mochly-Rosen. Responding to this concern and giving us a potential new model, she founded Spark. It evaluates the discoveries from Stanford scientists that have not been licensed to a company and, with industry input, identifies 20 per year that have promise. The inventor is taught the basics of drug development and gets funding support to carry out the “drudgery.”
In the health care reform act passed this March there is a program called ‘Cures Ac-celeration Network.’. ‘Cures Ac-celeration Network’ will give grants ($500 million is authorized this year) to biotech companies, academic researchers, and advocacy groups to help promising discoveries cross the valley of death.
There have been changes, but too little and too late. We need to evaluate our current funding systems to make translation research more prestigious and more fundable. It is nice to discover a new gene, but it is great to save a life and cure a person.
Inspired by an Article in Newsweek – May 15, 2010
Joel T Nowak, MA, MSW