In 1990, the National Health Institute and U.S. Department of Energy laid out a proposal for a project that was expected to take fifteen years. The goal was to create a map of the complete human genome, then use the information to develop future DNA testing technologies and study the possibilities of genome sequencing.
Thirteen years and $2.7 billion later, the project was completed. All 3.2 billion base pairs of human DNA had been mapped out. Everything that characterizes a human being, from his intelligence and hair color, to his chance of getting cancer, to the likelihood of him cheating on his girlfriend, was electronically stored for the first time ever.
More than a quarter of the sequence was contributed by The Genome Institute, here at Washington University in St. Louis. The Genome Institute is one of three major NIH-funded sequencing centers in the United States, and is behind many research projects, from determining the DNA links among humans, animals, and plants, to sequencing a virus that has had a rapid outbreak across the country.
But what does this all mean for you? For example, if you have cancer, how can we help you with this new technology, in a way that we couldn’t in the past? What can DNA sequencing do that impacts you?
Well, let us take a look at the difficulties of cancer treatment. In the past, we knew much less about the nature of cancer. Questions such as which cells were targeted, which treatment would be best, and whether chemotherapy would help were difficult to answer. For example, while 75 percent of women who get breast cancer will receive chemotherapy after surgery, only 25 percent of them truly need it. The other 50 percent only receive the dangerous side effects – side effects that are expected and considered inevitable. We know that you have cancer, we know what type of cancer you have, but a solution that works on somebody with a seemingly identical condition will not necessarily work on you.
Dr. Elaine Mardis, the co-director of The Genome Institute, has worked for many years in the field of cancer genomics. “What we have always done with cancer, regardless of the type, is treat it with a combination of surgery for solid tumors, try to remove as much of the cancer as possible, and treat the patient with ‘broad-spectrum chemotherapy,’ ” Mardis explained. She notes that we have used a one-size-fits-all “broad spectrum” approach to chemotherapy because we had limited knowledge of how diseases target individuals.
But in medicine, one size does not fit all. The best methods used to treat severe illnesses vary from person to person, and for certain diseases, the ideal dose of medication has monumental variation. For example, the optimal dose of a blood thinning drug called Coumadin can vary 20-fold depending on your DNA. Genome sequencing has helped us make these predictions. By laying out the fundamental building blocks that make you who you are, we have improved our ability to understand how a disease affects you in particular, and how to properly fight it.
These discoveries lead into the idea of “personalized medicine”, where genetic information is used to make treatment decisions. The goal is the development of medical care that takes into account individual body types and identities. In simple terms, we want to be able to create a drug that understands you.
It is easy to get excited about this new field of medicine. Whereas the original genome project was very costly and took over a decade to complete, Mardis says that nowadays, an entire genome can be sequenced overnight on a single machine, for about $1000. Occasionally, eye-popping headlines will emerge, detailing how genetic testing has saved the life of a six-year-old boy with a severe intestinal disease or restored the health of a pair of California twins with a rare disease. In various TED talks, entrepreneurs have fantasized about people storing their genomes on their iPhones, or carrying around their DNA information on an ID card, which can be given to the pharmacy that will then prescribe the patient a side-effect free medication. There are companies like 23andme, which will compute many of your traits using only a saliva sample. And researchers at Washington University in St. Louis have been working to develop a personalized cancer vaccine.
But let’s slow down for a moment. Personalized medicine is still very young. And while it has helped us learn a lot about disease treatments, we still do not know everything. Mardis says that while some futuristic scenarios are “trendy notions,” there is still room for error at this stage. “Medicine is a slow thing to change,” Mardis said, mentioning that we need “hardcore data” to prove that this technology is accurate and valuable.
Peter Edelstein, the chief medical officer of academic publishing company Elsevier, told Frontiers that, while personalized medicine has performed miracles at times, we still have very little understanding of how the genome works. “When we say we sequence the genome, people falsely equate that to mean we understand the genome,” Edelstein said, adding that the biggest danger to this new scientific field is “thinking that we’ve figured this out, when we haven’t… It’s a very very complex system, and we need to be patient and recognize that we don’t know what the hell we’re talking about yet.”
When any new technology emerges, we can imagine that it will change everything. We can craft in our minds a world where we completely understand the human genome and use it to fight off any disease. “Everyday in the press, you see, ‘Cancer will be cured tomorrow!’ and then, of course, that fails,” Edelstein said, warning us not to gain unrealistic expectations. However, personalized medicine certainly has shown promise. Edelstein recalls the time he helped sequenced the genome of a man with cancer. While it was too late to save him, the information gathered was used to save the man’s 19-year old son from suffering the same fate.
From prediction cancer risk to determining the best drug therapy, and beyond, genomics is clearly changing medicine. “It truly is impacting people every day, even though we don’t understand everything about what we’re seeing genetically,” Edelstein said. Despite this, Edelstein maintains that only time will tell just how far this new technology will go.