Decoding the Genome Was Just the Beginning

the human genetic blueprint. The excitement and the hype was intense. President Clinton painted a tantalizing picture of the opening of a new scientific frontier. With this profound new knowledge, human kind is on the verge of gaining immense new power to heal. Genome science will have a real impact on all our lives, and even more on the lives of our children. It will revolutionize the diagnosis, prevention, and treatment

of most, if not all, human diseases. In coming years, doctors increasingly will be able to cure diseases like Alzheimer's, Parkinson's, diabetes, and cancer by attacking their genetic roots. It didn't work out that way at least not exactly. Welcome to Prognosis. I'm your host, Michelle fay Cortes. This week, we're going to tell you what happened after the press conference and how one of the greatest undertakings in medical history, the decoding of the human genome, was just the start of

an exhilarating, frustrating journey that's still far from over. Here's Bloomberg's Bob Langrath with the story. Sitting next to Clinton at the White House was Francis Collins. Cons is a geneticist, and he led the international team that worked on the genome project. Now he runs the National Institutes of Health. I was both excited about the way in which the world was going to find out that we had a draft of the human genome sequence, the instruction book for

human biology. But I had also just spoken at the funeral of my sister in law two days before, who died from cancer and for whom this particular advance hadn't come along soon enough. So I sort of put the whole thing into focus of what we had and how far we still needed to go for this to actually benefit people who are waiting for answers. Actually the genome

wasn't done. There was only a first draft. The unveiling was pushed out quickly, in part because the government was raising a private group at the press conference, the teams that only fully scanned about the genome. It would be three years before the final version was published, and even with the map, finding the causes of diseases in the genetic code was elusive. Instead of a few key genes driving common ailments like heart disease or diabetes, scientists found dozens,

if not hundreds. Human common disease is really complicated, more complicated than we thought it was going to be less than a decade ago. Despite the flood of new genome data, there was a sense that drugs were getting harder to discover. A two thousand and ten New York Times article called the goal of finding the genetic roots of disease elusive.

It said that, quote geneticists are almost back to square one and knowing where to look for the roots of common disease unquote, but behind the scenes, something important was happening. It took thirteen years and costs three billion dollars to decode the first genome, and fo million dollars of that

went just to the sequencing itself. According to Dr Collins, the sequencing machines that did most of the work for sequencing that first human genome or the size of phone booths, and it took a warehouse full of them to have the kind of throughtput you needed to achieve this. DNA sequencing needed to get faster, cheaper, and smaller. It needed a revolution. If you look over the history of science, the thing that has been profoundly game changing in a

scientific area is major technical innovations. You know, whether it was inventing the telescope, what it did to astronomy, inventing a microscope, what it did for microbiology and cell biology, and look at that first cat scan, what it did for radiology. That's Eric Greene, who is now director of

the National Human Genome Research Institute. He was an early genome research or at the ni H. I think we recognize that the technologies that were used for sequence in that first human genome were good enough, but we needed something far better. The trick was to take billions of letters in a person's DNA and process them all at the same time, like a computer circuit with billions of transistors all firing at once. As newer and faster machines

were introduced, costs sank rapidly. In two thousand and five, the cost of scanning a human genome ran to about ten million dollars. By two fifteen, raw scanning costs plummeted to below dollars. And in two thousand three, did I believe it was going to happen this quickly? Absolutely not. I'm sure any of us would have gotten it wrong, probably by toothfold. We probably would have said it would have taken, you know, thirty years to get down to

a thousand dollar human genome sequence. Room fulls of machines were no longer needed. Dr Collins says, now on the sequencing machines sit on the desktop, or in the most dramatic example, they're about the size of a cell phone that attaches directly to your laptop. That's when DNA sequencing went from being a research tool and became medicine. In two thousand and nine, doctors in Wisconsin were treating four year old Nicholas Voker for a mysterious disease that produced

holes and his intestine. In desperation, his doctor's convinced genesis at the Medical College of Wisconsin to sequence all his genes. Here's next doctor reaching out to the geneticist with an unprecedented request. Dear Howard, I hope you are well. I'm writing to get your thoughts on a patient of mine that might benefit from a high throughput sequencing of his genome. This is a unique situation. This patients is very ill and has been in the hospital since January. It worked.

They found an unexpected mutation and it pointed to a treatment, a bone marrow transplant. The case exploded into the headlines with the Milwaukee, Wisconsin Journal Sentinel wrote a Pulitzer Prize winning series about the success. Around the same time, researcher Stephen Kingsmore helped perform a highly detailed genome of a

Korean person. The medical potential was becoming clearer. We kind of as a team had a Eureka moment when we said, ah ha, there's a huge amount of information in here that's of practical usefulness to people, and this really changed the trajectory of my career. Maybe want to go from a basic research institute back into a hospital environment where we could start to apply this and understand what it

might mean for the future of medicine. By two thousan twelve, Dr Kingsmore was testing out a new ultra fast sequencing machine on sick babies. We started to use it in our neonatal intensive care unit, where decisions had to be made within minutes or ours. There was no time to lose in making it diagnosis, and so we published a paper in October twelve saying that we could decode a baby's genome in forty eight hours and return those results back to the ne anatologists and showed that it would

change the management. That was truly a breakthrough. Dr Kingsmore is now at the forefront of using genome testing to diagnose and treat infants with unknown genetic diseases at the RADI Children's Institute for Genomic Medicine in San Diego. It turns out to be an ideal application for genome sequencing. Tens of thousands of babies are born each year with

unknown genetic diseases. There are ten thousand genetic diseases, and no physician on planet Earth has ever seen them all, so picking which of those to test for is incredibly difficult. The second thing is that in newborns, the genetic diseases really don't look like their textbook description. When you put those two reasons together, it means that without the ability to just survey the entire genome and examine all ten thows and genetic diseases at once, the likelihood of a

physician making the correct diagnosis is almost zero. His lab has three of the top of the line geno i'm scanning machines from a company called a Lumina. The machines are roughly the size of a washing machine. In urgent situations, his team can decode a baby genome in about two days.

We receive blood samples and medical records from about fifteen children's hospitals all around North America, and so they will contact us and let us know that they have a kid who they believe they might need a genome sequence on,

and the following morning the sample will arrive. Will then put that into our batch for the day, and our goal is to deliver a diagnostic result as quickly as as humanly possible back to that physician, with a goal obviously of giving treatment guidance that will either save a child's life or prevent complications of that disease. In three years at Rady, Dr Kingsmore's team is the code of the genomes of hundreds of sick babies, and it is making a difference. So one and two or one in three,

we will make a diagnosis. A figure that's completely consistent is that of those diagnoses will resultant changes in how the baby is managed in the intensive care unit. And then about one and four has a change in outcome. Sometimes it has life saving There are some extraordinary saves. There are some children who undoubtedly would die, and we make a phone call with a diagnosis. There's a treatment that's given promptly, and the child does well, faster, cheaper.

DNA toton was beginning to revolutionize medical care by two Then in two two things happened, one in Washington and the other in Hollywood. The Supreme Court said that jeans couldn't be someone's intellectual property, and one of the world's biggest movie stars made a start medical choice based on

her DNA. A few years ago, a blood test revealed that Angeline had carried a mutation of the b r c A one gene, giving her an estimated eighty seven percent risk of breast cancer of fifty risk of ovarian cancer. So in she had both brushed removed and underwent reconstructive surgery, emerging as a beacon of hope for women when she told the world, I feel wonderful. I'm very, very grateful. Ellen Mattlof at the time was a cancer genetic counselor

at Yeah University. She helped patients and their families understand their risk, what are the correct tests, and interpret complex DNA results. When I was the director of the cancer Genetic Counseling program at Yale, I saw several things shifting, and they were seismic shifts. First, Angelina Jolie came out with her New York Times editorial that she was a b r C A one carrier, and overnight our referrals increased by fort and they never returned to baseline. There

was a huge change. Then a few weeks later, the Supreme Court issued its ruling that meant companies, including the one that had a monopoly in the test Angelina Jolie used, couldn't own the patents on Jeanes Here's Dr Collins again.

It was a wonderful day, indeed, when the Supreme Court, in a nine to nothing decision, came out with their conclusion that gene patenting ought not to be a ouabol that it didn't fit with the original goals of the patent system, and I think that has opened up diagnostics in a much broader way, which has been a very good thing for the whole field and has accelerated the possibilities of many of us having that kind of information

now or in the future. For years, one company had the patent on b r C A one and b r C A two, the most common causes of hereditary breast cancer. That meant that hospitals and companies not holding the patent couldn't combine them into broader tests. Gene patenting was a serious threat on the view of many of us to progress in this field, and yet it continued for quite a few years after that. At the time of the Supreme Court ruling, BRCA testing costs as much

as four thousand dollars. Within days of the decision, new companies that have been barred from the market started offering their own tests. Cost plummeted. Ellen matt Loff, who now runs a startup called My Gene Council, was a plaint different the Supreme Court case. She saw the impact on patients firsthand. And today we have some testing companies that have offered b r C A one and two testing from time to time for a hundred or two hundred dollars,

so it's changed dramatically. Of course, cost isn't the only problem that geneticists were grappling with, and the easy diagnoses and freely flowing data envisioned years ago haven't quite come to pass. I can remember fifteen years ago when the genome was sequenced that everyone was saying that first of all, you would carry around your genome like a flash drive

and it would be a piece of cake. You just bring it to your doctor's office, plug it in, and that every doctor would be so educated on genomics that they would be able to interpret it. None of that has been as simple as it sounded. But where the failure has come is helping consumers and healthcare providers under stand and use the data. Also, as genetic tests become more common, the risk of misinterpretation by doctors untrained in the complex world of genetics is growing. This is especially

true in the high stakes area of cancer. We're ordering the wrong tests or misinterpreting the result can lead to a fatal illness or unnecessary surgery. It's a problem that some say is getting worse, we're finding that genetic test results are being misinterpreted more often now than ever before, and the reason for that is that fewer patients are seeing certified genetic counselors to order their tests and to interpret them after. And also the tests have grown in complexity,

so it's easier to misinterpret them now. In terms of drugs, Dr Collins says cancer is one area that seen a direct impact from the Genome project. Cancer is fundamentally genetic disease, and understanding gene abnormalities and patient tumors has led to powerful new treatments for leukemia, certain types of lung cancer, and breast cancer. If you want to take an area we're having access to genome sequence has been revolutionary, it's cancer.

If I had cancer today, or if anybody I know had cancer today, I would want their tumor to undergo a complete DNA sequencing in order to identify what mutations have happened in that cancer to cause those good cells to go bad. Increasingly, cancer centers are scanning patients DNA to match them to the treatment most likely to work for them, and biotech companies are working on developing a liquid biopsy that which detect signs of cancer in the blood.

So far this year, there have been about a dozen new cancer drugs approved by the FDA, and so the list of targeted drug treatments for cancer is growing almost daily. Nevertheless, many tumors have turned out to have a complicated array of mutations and we don't always know how to arget them. But there may be another reason why there aren't more

gene based drugs. Louise am All, who studies complex systems at Northwestern University That's found that risk averse researchers have been concentrating most of their attention on genes that have been known for years. They are ignoring unknown genes, some of which could lead to medical breakthroughs. One of the numbers that I think is important is this idea that five of the genes are accounting for about fifty of the publications. Very little attention is really being given to

a very large fraction of the of the genes. In fact, in the five years between twous and eleven and two fifteen, Dr Amroll and as research partner Thomas Stutgart found only a handful of new genes broke out from obscurity to become objects of intensive scientific research. Everybody is becoming more and more conservative, which means that the way in which we are exploring the known is less and less efficient.

But if we keep having at attitudes we are never I mean, it's going to be you know, a new gene understood per per year, and at that rate it would only take about another fifteen thousand years to understand

every single gene in the human geno. One method that has proven useful for finding new drugs has been looking for people with certain genetic abnormalities, but instead of hurting them, their mutations help and a robust constructor in Texas with super low cholesterol had a rare mutation in a gene called PCSK nine. That discovery has led to two powerful new cholesterol lowering medications into US and fifteen here's Dr Collins again finding individuals who are rare examples where they're

protected against disease. You could call them superhumans. Um is very much part of what anybody who thinks about genetics would hope to find, and that's what we found with PCSK nine. It's one of those really amazing success stories of the last decade. To help find more vision treatments, the NAH set up a giant new research program that will track the health information of one million American residents,

eventually sequencing the genomes of all of them. That all of us project will cost one point five billion over ten years. If we really want to understand how effectively to apply precision medicine to the average person in this country, we need a very large pilot study to find out how that works. This will be the largest, most powerful research database ever contemplated in this country, and it will teach us whether such things as knowing your genome sequence

is going to make you healthier. So what's next? George Church, the genetics professor at Harvard Medical School, thinks the state of DNA testing and scanning it's like the Internet in the early nineties. So I was using computer network type of things around, which is about the time that the Internet started, and it was pretty sleepy until around when suddenly everybody saw that there was a web browser, and then within a year there was millions of web pages.

From almost a standstill, we have all the infrastructure in place to sequence millions of human genos possibly billions, with a little effort, but people are not aware of it. They don't realize that the killer apps are already some of them are already there. In October, the Food and Drug Administration approved the first direct to consumer tests to spot genetic variations and how people's bodies interact with different medicines, but warned that people shouldn't use it to make medical

decisions by themselves. But while most people don't need it, the potential for greater use of genetic testing is enormous. Here's Dr Collins again. We now know that probably two or three percent of us are walking around with significant DNA mistakes that would be actionable right now if we knew about it that we have one of those misspelled things that places us at risk maybe for heart disease or cancer, or some clotting problem or some neurologic difficulty.

Two or three percent, well goodness six If they're three million people just in this country, we're talking about somewhere between six to nine million people right now that if they had that information, their medical care would change for their benefit. George Church thinks that genome scanning could directly help at least one percent of people and more are walking around with genetic variants and might put their children

at risk. But that would be my guess is ten years from now, we could have everybody who has any reasonable health care plan, maybe a billion people sequenced, and then five of those that are at risk for having children that have a severe genet disease will avoid that. The key, he says, is getting people to do it. I think it's analogous to seat belts, where the seat belts were free, but people still didn't use them and you had to had to have some public health strategy.

We've come a long way. Francis Collins's career shows how much the technology has advanced. When he and other scientists were trying to find the gene for cystic fibrosis in the nineteen eighties, it was agonizingly slow going. It was horrendously difficult. There was no genome project. There was very little knowledge about anything about the DNA of the human except little tiny islands that people had worked on. It took years, but now, thanks to their groundwork, there finally

our treatments today. If you gave me DNA samples from a few families with cystic fibrosis and a DNA sequencer, a decent graduate student would have this answer in about two days. That's the way it's happened. That's the that's a great example of just what it has meant to cross into this new territory where these technologies are so

powerful and so widely available. So if anybody tries to say, well, you know, general Mix was sort of a fizzle that didn't get us anywhere, boy, just look at what's now feasible. And that's it for this week's prognosis. Thanks for listening. Do you have a story about healthcare in the US or around the world. We want to hear from you. You can email me m Cortes at Bloomberg dot net or find me on Twitter at the Cortes. If you are a fan of this episode, please take a moment

to rate and review us. It helps new listeners find the show. This episode was produced by Liz Smith. Our story editor was Tim and Ette. Thanks also that Drew Armstrong Francesco Levie is head of Bloomberg Podcasts. We'll see you next week.