How uncovering DNA’s secrets changed, well, everything

In 1953, a group of scientists found a critical piece of a biological puzzle. 
 
The scientific community already knew that deoxyribonucleic acid, or DNA, carried instructions for the traits found in living things. They also understood the chemical makeup of DNA molecules.  
 
These scientists identified DNA’s structure: the double helix. Two long backbone strands spiral around each other, creating what looks like the sides of a twisting ladder. Organic bases pair up between the two strands, creating a scaffolding that looks like rungs. The work explained how DNA molecules are organized and suggested how DNA might be able to copy itself to pass along traits.  
 
This was Nobel Prize-winning work, and it acted as a forerunner to the Human Genome Project. Launched in 1990, this ambitious, international effort aimed to map and sequence the entire human genome — the complete set of DNA found in a human. While the double-helix discovery showed the blueprint of DNA, the Human Genome Project would provide the key to reading and understanding it. Along with human DNA, the endeavor also mapped the genomes of a few other forms of life, including a yeast, a fruit fly, a mouse, and a plant from the mustard family.  
 
National DNA Day, held April 25, commemorates the discovery of DNA’s double helix in 1953 and, in 2003, the Human Genome Project’s successful completion. 
  
The insights from these discoveries have since influenced the world in many ways — agriculture, ancestry, and forensics, to name a few. They also changed how we deal with rare genetic diseases and cancer, unraveling how inheritance works and examining diseases at the molecular level. 
  

Two decades of progress 

In just over 20 years since the completion of the Human Genome Project, scientists have used those insights to make rapid, life-changing advances. 

Exact Sciences is celebrating milestones in 2024 for three major parts of its business that utilize DNA and ribonucleic acid, RNA, to serve patients:  

• The 20-year anniversary of PreventionGenetics, an Exact Sciences subsidiary specializing in rare disease testing  
• The 20-year anniversary of the Oncotype DX Breast Recurrence Score® test, which provides individualized information about whether a patient’s cancer is likely to recur or how well it may respond to chemotherapy  
• The 10-year anniversary of the Cologuard® noninvasive colorectal cancer screening test, which detects cancer-indicating DNA in patients’ stool    

Many of Exact Sciences’ tests use insights gained through the Human Genome Project and the discovery of the double helix, so much so that the Exact Sciences corporate logo nods to DNA’s structure. 
 
Tony Krentz is a molecular biologist and geneticist and serves as vice president of laboratory operations at PreventionGenetics. He says that the Human Genome Project provided a foundational piece necessary to Exact Sciences’ work.  
  
“We needed to know what the genome looked like,” he says. “We needed to be able to map specific genes to areas of the genome and then map specific conditions to genes. So, for example, if a child has cystic fibrosis, we now know we can find genetic defects in the CFTR gene. The Human Genome Project made that possible.” 
 
PreventionGenetics started small in 2004, with just two tests in its Marshfield, Wisconsin, lab. The tests investigated inherited instances of cerebral cavernous malformations (clusters of blood vessels that can form brain lesions) and malignant hyperthermia, which is a severe reaction to drugs used in anesthesia. 
 
Today, the company offers tests for nearly all clinically relevant genes. Technological advances have created remarkable efficiencies, Krentz says. 
 
“In 2003, we sequenced the human genome at a cost of around $2.7 billion, and it took about 15 years to complete,” he says. “Today at PreventionGenetics, we can sequence hundreds of genomes per day at a small fraction of the cost.” 
 
That translates to a vastly improved ability to serve patients and the professionals who provide their health care, Krentz says. 
 
“The goal of precision medicine is to provide personalized treatment, and we can do that through genetic testing,” he says. “Historically, if I were sick, medicine would treat me with what worked best for an average human. That’s generalized health care. We’re now moving into precision medicine, where we’re going to treat you in the way that’s best for you as an individual, based on your specific genetic makeup. The goal is to have very focused treatment options.” 
 

Precision oncology and cancer screening 

The Human Genome Project looked different from other biomedical research in a few ways.  
 
For one, it was a global collaborative effort, with research happening in different labs around the world instead of with a small team in a single place.  
 
And two, instead of first formulating a hypothesis and then exploring it — the traditional approach to research — the researchers simply intended to investigate an unknown part of their field.  
 
Biologist Ariane Kemkes is director of clinical curation at Exact Sciences’ lab in Phoenix, Arizona. Watching the Human Genome Project unfold excited her as a scientist, she says.   
 
“In a research collaboration like this, you had researchers all over the planet. Scientists from all walks of life were contributing,” Kemkes says. “All of a sudden you have this huge pile of data, and how do you really make sense of it all? It propelled this notion of sharing data and ideas. Often researchers are worried about giving out new ideas, and they want to protect their research or save it for publication. The Human Genome Project made that all available just for the common good. It allowed everybody to participate and share.”  
 
So many ideas emerged from the project, with different groups carrying them forward in different ways. Some researchers pursued solutions for diagnosing diseases. Others imagined ways to use genomes for therapy selection, using a patient’s DNA and RNA to tailor their cancer treatment approach. That’s when the Oncotype DX Breast Recurrence Score test emerged, Kemkes says. 
  
The Exact Sciences-acquired company that developed the Breast Recurrence Score® test created “an incredibly useful product for women with breast cancer,” she says. “It spared some patients from chemotherapy and let them confidently choose a different route that was best for them.” 
 
In the years since, Exact Sciences’ precision oncology portfolio has expanded to address other cancers and stages, including the OncoExTra® therapy selection test for patients with advanced or metastatic cancer. The OncoExTra test helps physicians understand changes to a patient’s genomic profile, which can aid them in making informed choices when designing a cancer treatment plan. 
 
Kemkes reflects on how much progress has been made in a short time within tight parameters. 
 
“I think the important thing to note is that about 99.5% of our genome is identical in humans,” she says. “What separates us are minute changes.”  
 
The entire field of precision medicine has emerged within that small sliver of the human genome that gives each person a one-of-a-kind genetic makeup, she says. 
 
“It’s an amazing feat of biology to have created this type of complexity in an almost identical genome,” Kemkes says. “We are so closely related overall, and yet it’s a planet of individuals. We each are unique organisms with unique features.” 
 
Jerry Machado, an Exact Sciences laboratory geneticist and senior clinical laboratory medical director in Madison, Wisconsin, credits the Human Genome Project for changing the future of cancer by helping us understand the biology of the disease.  
 
In addition to precision oncology, which helps patients make informed decisions after a cancer diagnosis, scientists also apply genomic insights to cancer screening, in tests such as Cologuard. 
 
Learnings “allowed cancer diagnostic companies like Exact Sciences to go through the human genome and develop screening tests for cancer by focusing on cancer-related genes,” Machado says. “So we can develop a test like Cologuard that can detect signs of colorectal cancer earlier when it’s more treatable or even preventable.” 
 
Harnessing the vast amounts of data found in DNA — 3 billion nucleotides in the human genome alone — has enabled so much advancement in the field, Machado says. 
 
“Genetics has really sprung forward, with new, exciting stuff happening in only the past couple of decades,” he says. “The Human Genome Project built today’s landscape for genetics-based testing. It has changed people’s lives.” 
 

What is DNA?  

Deoxyribonucleic acid, or DNA, is the molecule that contains genetic information in all living cells. DNA features two long strands that coil around each other. Each strand is made of smaller units called nucleotides, which have one of four bases: adenine (A), thymine (T), cytosine (C), or guanine (G). The bases on one strand pair with the bases on the other strand, creating a twisting, ladder-like structure — the double helix. The order of the bases provides instructions for making proteins. Proteins are the building blocks of life, and they carry out different functions in the cell and the organism. 
  

DNA’s early history 

1866

A botanist studying pea plants publishes work that will go on to provide the mathematical foundation of genetics. 
 

1869

A biochemist first isolates nuclein, now known as DNA. He believes that nuclein plays a role in heredity but concludes that the simple molecule alone could not possibly create nature’s vast diversity.  
 

1944

A team of scientists shows that heredity happens through DNA. 
  

1953

Scientists determine that DNA’s structure consists of a double helix, a spiral of two DNA strands winding around each other.  
 

1966

A team of scientists cracks the genetic code. Their work shows how the four nucleic acids — adenine (A), cytosine (C), guanine (G), and thymine (T) — combine to spell out three-letter “codons.” Codons are units of genetic information that instruct cells on how to create protein chains in DNA. 
 

1977

A group of scientists develops a method for mapping the order of nucleotides in DNA. Sanger sequencing, a widely adopted DNA sequencing technique, takes its name from English biochemist Frederick Sanger, who worked on this project. 
 

1983

The first human disease gene is mapped using DNA markers. The gene is for Huntington’s disease, a rare condition that causes nerve cells in the brain to break down. 
 

1990

The Human Genome Project begins, with scientists all over the world collaborating to generate the first sequence of the full human genome, which is the entire set of DNA instructions found in a human cell.  
 

2003

The project is completed, with the international team delivering a finished version of the human genome sequence.