Finding the Code: The Race to Sequence the Human Genome and What It Means

ALEX DINH: I have a very aggressive type of cancer. It’s hard to treat.

ARCHIVAL (CBS NEWS, CBS THIS MORNING, 5-7-15):
GAYLE KING: Precision medicine…it’s being called the future of healthcare.

ARCHIVAL (CBS NEWS, 5-7-15):
DAVID AGUS: It means the right dose, of the right medicine for the right patient.

ARCHIVAL (NBC NIGHTLY NEWS, 10-24-17):
REHEMA ELLIS: A super targeted approach…

ARCHIVAL (ABC NEWS, 6-3-12):
DR. JENNIFER ASHTON: It’s really like a heat seeking missile.

NARRATION: Expectations are sky high for precision medicine, a new strategy that tailors treatment to individual patients.

ARCHIVAL (WHITE HOUSE, 1-30-15):
PRESIDENT BARACK OBAMA: You can match a blood transfusion to a blood type. What if matching a cancer cure to our genetic code was just as standard?

NARRATION: But we’ve heard these kinds of hopes before…during the race to sequence the human genome.

ARCHIVAL (NBC NEWS, 3-14-00):
JOHN COCHRAN: The race to crack the human genetic code…which could lead to life saving, revolutionary changes.

ARCHIVAL (CBS NEWS, 11-9-99):
FRANCIS COLLINS: Medicine will be transformed.

ARCHIVAL (ABC NEWS, 6-26-00):
CRAIG VENTER: There is at least the potential to reduce the number of cancer deaths to zero during our lifetimes.

TEXT ON SCREEN: RETRO REPORT & STAT PRESENT:

FINDING THE CODE
WITH SPECIAL CORRESPONDENT CARL ZIMMER

NARRATION: About 30 years ago, Marston Linehan began searching for a new way to help his patients with kidney cancer.

MARSTON LINEHAN (TO ALEX): Who else in your family has kidney cancer?

MARSTON LINEHAN: There were no effective forms of therapy, no drugs that worked. I lost every one of these patients who developed advanced disease. So we wanted to identify a gene for kidney cancer. And the hope was, if we could understand the gene that might provide the foundation for effective forms of therapy.

NARRATION: It was the start of the genome age, and scientists around the country were hunting for disease genes.

MARSTON LINEHAN: We had no idea what a mountain this was to climb. We set up a whole program. We analyzed DNA from over 4,000 patients. It took us nearly 10 years to find that gene.

NARRATION: Then, a group of government scientists had a big idea. Instead of searching for genes one by one, what if they could create a map that would locate and sequence every gene in our DNA?

ARCHIVAL (NBC, 1-1-97):
FRANCIS COLLINS: People are mostly hoping to see this have some payoff as far as human health.

NARRATION: Led by Francis Collins, the Human Genome Project was the most ambitious biological research program ever attempted. It started in 1990 with a 15-year timeline and $3 billion budget.

FRANCIS COLLINS (DIRECTOR, HUMAN GENOME PROJECT): So the motivation really was to enhance the ability to understand hereditary factors in all diseases as quickly as possible.

ARCHIVAL (ABC NEWS, 7-18-90):
ERIC LANDER (HUMAN GENOME PROJECT, LEAD INVESTIGATOR): The sorts of traits that affect the vast majority of the population - heart disease and diabetes, we know precious little about and those are really the frontiers of genetic research.

FRANCIS COLLINS: At the beginning, we didn’t have anything automated.

ARCHIVAL (NBC NEWS, 1-1-97):
FRANCIS COLLINS: This is Axon 5. This is a family.

FRANCIS COLLINS: Everything was done manually. We had to do all these chemical reactions one by one by one. There was radiation involved. You, like, had to wear protection. It was horrible.

NARRATION: The genome is made up of about 6 billion chemical letters. Collins knew without dramatically improved technology it would be impossible to read them all.

FRANCIS COLLINS: We were by 1998 finally where we could see this goal might be achievable. It was at that point that a separate effort was announced in the private sector.

ARCHIVAL (CBS NEWS, 11-9-99):
CRAIG VENTER: This is the largest DNA decoding lab in the world by far.

NARRATION: Former National Institutes of Health researcher, Craig Venter spent years trying to speed up gene discovery.

CRAIG VENTER (FOUNDER AND PRESIDENT, CELERA GENOMICS): I was the first to make the transition from the old manual way. My lab had the very first automated DNA sequencer.

NARRATION: His announcement, that his company – Celera Genomics – would sequence the genome before the government shook the scientific world.

ARCHIVAL (CBS NEWS, 11-9-99):
CRAIG VENTER: It’s going to be years if not a decade faster.

NARRATION: He was using a new approach, called shotgun sequencing, where the genome is broken up, sequenced and quickly reassembled by a computer.

CRAIG VENTER: It’s like a jigsaw puzzle with 25,000 pieces. But we knew how to put the pieces together.

NARRATION: Suddenly, it was a competition. Venter suggested that Collins’ team sequence the mouse genome… leaving humans to him.

Collins refused, and said Venter’s untested approach was likely to produce a genome full of gaps or mistakes.

ARCHIVAL (NBC, 3-14-00):
JOHN COCHRANE: It’s not just about science, but also about the race for vast sums of money…

NARRATION: Collins also attacked Celera’s plan to sell genome information…and to patent genes, which could make it harder for medical researchers to work on them.

ARCHIVAL (CBS, 11-9-99):
FRANCIS COLLINS: Somebody else who has a great idea about what that gene might do and a way to turn that into a product for public benefit may be discouraged from doing so.

NARRATION: The tension soon made headlines.

ARCHIVAL (CBS NEWS, 11-9-99):
WYATT ANDREWS: Are you going to win?
CRAIG VENTER: We’re not going to lose.

CRAIG VENTER: Everybody likes a good competition. It’s not often that a small group takes on the whole federal government.

FRANCIS COLLINS: It actually made this effort to sequence the human genome something that people had heard about.

ARCHIVAL (CBS NEWS, 11-9-99):
WYATT ANDREWS: It’s the greatest human science project ever.

FRANCIS COLLINS: Once it’s on the front page of The New York Times that there’s a competition going on then everybody is like, what’s going on there?

ARCHIVAL (CBS NEWS, 11-9-99):
WYATT ANDREWS: Every day, it’s robot v. robot, public computer v. private computer.

ARISTIDES PATRINOS (HUMAN GENOME PROJECT, DEPARTMENT OF ENERGY): Both the public program and Celera were in a frantic race of sequencing. It became clear that the acrimony was only going to grow. I was starting to become concerned that this was turning into a mud wrestling match. And, it was damaging both of them, and of course damaging to our program as well.

NARRATION: One of the Genome Project’s original architects, Department of Energy scientist Aristedes Patrinos, arranged months of secret meetings between Venter and Collins, hoping to make peace…..And on June 26, 2000…

ARCHIVAL (WHITE HOUSE, 6-26-00):
FRANCIS COLLINS: I’m happy that today the only race we are talking about is the human race.

NARRATION: …they presented the genome to the world…together.

ARCHIVAL (WHITE HOUSE, 6-26-00):
PRESIDENT BILL CLINTON: In coming years, doctors increasingly will be able to cure diseases like Alzheimer’s, Parkinson’s, diabetes and cancer by attacking their genetic roots.

NARRATION: For researchers like Marston Linehan, hoping to use genes to find cures, it was like striking gold.

MARSTON LINEHAN: The Genome Project gave us the map. All of a sudden then we knew the sequence of every gene. We didn’t have to spend years and years finding them. That was a huge advantage for us.

NARRATION: But it also made things more complicated. After finding one kidney cancer gene, he kept finding more and more.

MARSTON LINEHAN: We now know of 16 different genes that cause kidney cancer. We thought kidney cancer was a single disease. It’s not a single disease. It’s a number of different types of cancer that just happen to occur in the kidney.

NARRATION: Alex Dinh was only 34 when he got kidney cancer.

AKEX DINH (TALKING TO HIS CHILDREN): This is when I first came to America.

ALEX DINH: I was born in Vietnam. My parents always wanted to give me a better life….The week that I was diagnosed, we just found out that we were expecting our-our third kid, so it was, you know, this week of rollercoaster emotion. I had my left kidney removed. Then it started to spread to the other side of my abdomen. So, then we said surgery’s not an option anymore.

NARRATION: Alex and his wife are doctors. Wondering why he got cancer so young, they went for genetic testing.

ALEX DINH: They tested the entire genome and found that I had this one specific mutation. A rare gene, kidney cancer’s rare, I get them both.

NARRATION: Through a friend, Alex heard about Dr. Linehan, whose lab was using genes to develop treatments for kidney cancer.

MARSTON LINEHAN: Once you discover a cancer gene we take tumors from patients and study how the cancer gene works. Then we work on the development of drugs.

NARRATION: In this case drugs for the type of tumor Alex has.

MARSTON LINEHAN: And if they look good then we go to clinical trials in patients.

NARRATION: Four years ago, Alex joined one of those trials – for his specific cancer… one of a small, but growing number of cancers that can be treated with this type of targeted drug.

ALEX DINH: I’m still able to take care of my family. I’m still able to work. Meaning without it I know I wouldn’t be here still.

MARSTON LINEHAN: It’s all you might call personalized medicine, targeting that specific gene mutation instead of just trying this drug and that drug and this drug.

NARRATION: But critics, like epidemiologist Nigel Paneth, point out few patients are likely to be as fortunate as Alex.

NIGEL PANETH (EPIDEMIOLOGIST, MICHIGAN STATE UNIVERSITY): We haven’t yet found very many examples of drug interventions that depend upon genes…there are one or two here. The last 60 or 70 years we’ve added about ten or 11 years of life expectancy in the US. None of that is due to genetic discovery.

NARRATION: That’s because, after years of research, it turns out the relationship between genes and most serious health conditions is more complicated than expected.

FRANCIS COLLINS: Heart disease, schizophrenia, some of the common cancers. There was a hope that while those would not be the result of a single gene they’d be influenced by a short list of genes…Maybe for diabetes there would be, you know, four or five genes. We’re up to 82, each one of which has a very modest effect. And we didn’t know that until we looked.

NARRATION: Francis Collins, whose own lab works on diabetes, still wants to find out what role genes play in most common diseases. As head of the National Institutes of Health he’s helped start a massive new federal effort…. called the Precision Medicine Initiative.

ARCHIVAL (WHITE HOUSE 1-30-15):
PRESIDENT BARACK OBAMA: The time is right to unleash a new wave of advances in this area, in precision medicine.

NARRATION: It will employ dramatic advances in sequencing…

ARCHIVAL (WHITE HOUSE 1-30-15):
PRESIDENT BARACK OBAMA: The year Dr. Collins helped sequence the first human genome, it cost about $100 million dollars, and today it costs less than $2,000.

NARRATION: …And supercomputers to sift through the genomes and health records of about a million people…searching for the links between genes, the environment and our health.

FRANCIS COLLINS: There are genes and there are environment and they somehow come together in a way that causes somebody to become ill or not. So if we really wanted to get a complete understanding of what causes diabetes or the common cancers or Alzheimer’s disease or mental illness, you’ve got to look at both of those things.

NARRATION: But Collins and the government still have competition.

CRAIG VENTER: We’re processing on average a complete human genome every 15 minutes. We set a target goal of trying to get a million genomes by 2020.

NARRATION: Craig Venter now runs Human Longevity, one of several private companies also analyzing genomes and health data, hoping to pick up where the original genome sequence left off.

CRAIG VENTER: It’s just not a direct linear line of the genome was sequenced, we found this gene and now “X.” What we’re discovering now are the things that occur maybe once in the human population out of 10,000 or 20,000. It’s the rare combinations of things that determine our human traits.

NARRATION: But it’s hard to know how much impact those discoveries might have.

NIGEL PANETH: Huge amounts of data don’t guarantee that you will find the things that matter. In fact, they increase the chances that you will find tiny things…tiny things that don’t matter very much. It won’t be a solution to diabetes, hypertension, heart disease, lung cancer, breast cancer. Because those are not largely determined by the genetic inheritance we get.

NARRATION: For those who’ve been part of the genomic revolution…

ALEX DINH: Without these medicines, I’m sure I wouldn’t be alive today.

NARRATION: … there is not question but to push forward.

CRAIG VENTER: It’s like we’re coming out of the Dark Ages. Medicine’s been based on rough symptomology and a little bit of hocus-pocus without knowing the true molecular nature of what’s going on.

FRANCIS COLLINS: You know there’s the famous first law of technology, which is when something truly significant is discovered its consequences are always overestimated in the short run and underestimated in the long run. I think that’s absolutely true for the human genome.

(END)