Those who do not remember the past are doomed to repeat it. And those who do not remember the sometimes irrational exuberance around past advances in biomedicine may be doomed to buy into the hype around today’s. From curing Alzheimer’s and Parkinson’s to eliminating cancer deaths, no goal has been too ambitious for the best minds in medicine to claim is within reach thanks to the latest scientific discovery.
Here is your genetic gut check.
This three-part series of documentary shorts, produced by Retro Report in partnership with STAT, looks back at the roots of three of today’s most promising genetic technologies: genetic testing to predict which diseases someone might develop, precision medicine to match people’s genes to the treatments most likely to work for them, and genome-editing via CRISPR to repair disease-causing genes. Watch and listen to experts explain how the 1980s and 1990s version of each was going to change medicine and save lives. It puts today’s promises in a whole new light.
PART 1
The race to sequence the human genome was also billed as a race to end disease. So what happened?
The $1.455 billion “All of Us” project that the National Institutes of Health is launching this spring stands on the shoulders of the $3 billion Human Genome Project, which was (mostly) completed in 2003. All of Us will collect DNA, health, lifestyle, and other data from 1 million Americans to, among other things, identify the genetic and environmental roots of disease and understand why different people respond differently to the same drug.
The genome project, which determined the sequence of most of the 3 billion biochemical “letters” that spell out human DNA, had similar goals. Some have been realized, others not. Its most sobering lesson was that very, very few diseases are caused by a single gene or even a handful of them; for common, complex diseases such as diabetes, scores of genes are involved. That dashed hopes of identifying disease genes that would lead to treatments and even prevention for the major killers.
The scientists behind All of Us, the most prominent part of the government’s precision medicine initiative, believe they can make the promise of the genome project a reality even as they are careful not to overpromise. “When something truly significant is discovered,” said NIH Director Francis Collins, a veteran of both projects, “its consequences are overestimated in the short term and underestimated in the long term.”
PART 2
Does the ability to more easily change the blueprint of life mean we’re on the path to repairing the broken bits in our genetic inheritance? Or have we tried this before and failed?
By now, you’ve probably heard of CRISPR. But maybe you didn’t know (or forgot) that the flashy genome-editing technique has a forebear: gene therapy. CRISPR repairs a disease-causing gene by replacing a misspelling in the A’s, T’s, C’s, and G’s that constitute DNA; gene therapy ferried in a whole new healthy gene, leaving the mutated one in place, and hoped for the best.
The best almost never happened: The first gene-therapy patient, who has an inherited metabolic disorder called ADA deficiency, saw the therapeutic benefits of receiving healthy genes decrease with time and was never able to stop taking the medication for her disease. The worst did happen, and the death of a young patient in a prominent gene therapy trial brought the field to a year-long halt.
“The expectations were crazy,” said a gene therapy pioneer. The early exuberance? “It’s very easy to get caught up in that.”
Should CRISPR’s proponents be worried?
PART 3
It’s now easier than ever to peer into your own genetic code. But are all of the new companies out there offering you information about yourself that you can believe?
Genetic testing has lived up to its promise better than anything else in the genome revolution. People can learn whether they inherited a disease-causing mutation and take steps to avert the disease, either through intense screening (for colon cancer, say) or prophylactic surgery (if they carry a gene for breast or ovarian cancer, for instance).
While detecting mutations is easy, understanding what mutations mean has proved to be anything but.
Yet here’s the thing about genetic testing – it’s moved out of the labs into the masses. New companies and new quackery are popping up everywhere, equating your personal genome to all manner of things beyond disease, from your wine tastes to even your dating preferences.
The question that must be answered now is: Even with your genome in hand, what can you believe?
Retro Report is a nonprofit media organization examining the history and context behind today’s news. To watch more from Retro Report subscribe to its newsletter or follow it on YouTube. You can also follow them on Twitter.
About the Author
Very informative. Please follow up with new developments in Stat!
Excellent and inspiring. I was born before genetic research was done.
Research at our Center for Integration of Science and Industry at Bentley University has examined the long lag between scientific discoveries, and the emergence of successful therapies based on these discoveries. Using data analytics and modeling, we have examined the time required to develop new medicines incorporating >200 different technologies, ranging from monoclonal antibodies and gene therapies, to novel drug targets discovered through genomics. We find that there is a consistent 25-30 year lag between the initiating discovery and the first successful therapeutic. McNamee, et al, (2017) “Timelines of translational science: From technology initiation to FDA approval.” PloSOne, e0177371. While the specific issues and advances are different for each technology, the pattern is consistent, and analysis shows that few, if any, biologic or targeted therapeutics have ever been successfully developed before the underlying technology reached a threshold of maturity. In the case of gene therapy, premature investments and clinical trials contributed not only to numerous failures, but may have actually delayed the emergence of today’s mature technologies. Ledley, et al. (2014) “Why commercialization of gene therapy stalled; examining the life cycles of gene therapy technologies.” Gene therapy 21, 188.
One key takeaway is that the basic science is solid, the clinical applications are promising, and that the charlatans are lurking. Thus it ever was…for all novel advances that affect vulnerable populations.