Harnessing the human genome is the future of healthcare—and Johnson & Johnson is helping lead the way

DNA was first identified in 1869 by Friedrich Miescher, a Swiss physician and biologist who called it “nuclein.” The next most notable DNA discovery: Four UK-based researchers figure out that DNA is comprised of a double helix structure.

Why was this such a breakthrough? Because this unique shape suggested how DNA might be replicated when cells divide. It also marked the beginning of the biotechnology industry. Without knowledge of DNA’s structure, scientific techniques including DNA sequencing, genetic engineering and functional genomics would not exist.

The DNA double helix looks like a twisted ladder. Each “rung” is comprised of two nucleotides, the building blocks of DNA that form base pairs. DNA sequencing, also called genome sequencing, determines the exact order of these base pairs in a living organism. Humans have about 3 billion base pairs, which explains why the earliest attempts at genomic sequencing undertaken later in the 20th century were so costly and time-consuming.

In 1977, Fred Sanger, an English scientist, pioneers the Chain Termination Method of sequencing, aka the Sanger Sequencing. He and his team sequence the first full genome, not of a human but a virus. (All living things have a unique genome, including viruses.)

In the mid-1980s, Canadian scientist Lap-Chee Tsui and his team begin looking for the gene associated with cystic fibrosis, and in 1989 they pinpoint a gene called CFTR. It is the first time anyone has discovered a disease-causing gene.

Although the search for CFTR took years, scientists today could use modern gene sequencing to make a similar finding in just a few hours.

The Human Genome Project was launched in 1990, and 13 years later results in the first-ever sequence of the human genome—or 92% of it, which was as far as scientists could get with the technology available at the time. There have been numerous refinements since then, and the most complete version was released in 2022 by scientists at the National Institutes of Health’s National Human Genome Research Institute. Humans have 20,000 to 25,000 genes, and this latest reference genome is a map against which individual genomes can be compared.

Since the first human genome sequence, scientists around the world have been sequencing individual genomes and comparing them against the reference standards to identify disease-causing variants. By 2013, scientists had identified hundreds of variants linked to disease that could be treated if they are detected and acted upon with medical strategies.

The Human Genome Project helps jump-start the development of new diagnostic tools and treatments. The most growth has occurred in the oncology field, where scientists have developed targeted treatments that are effective in patients whose tumors express a particular genetic variant or biomarker.

After 22 years of development, a Janssen drug developed to treat aggressive bladder cancer hits the market. This novel therapy is effective in patients whose tumor has a specific abnormal gene.

Around the same time, the company deepens its commitment to developing precision medicine strategies and bringing the innovations to patients. In 2021, a Janssen medicine became the first targeted therapy approved by the U.S. Food and Drug Administration (FDA) for advanced non-small cell lung cancer in patients with a specific genetic mutation. In 2023, a Janssen therapeutic was FDA-approved for use as a first-line targeted treatment for prostate cancer patients who carry a certain mutation and for whom chemotherapy is not clinically indicated.

The company is currently pursuing precision treatments for a variety of conditions, including those related to the cardiovascular, immune and neurological systems.

Johnson & Johnson joins forces with the UK’s national funding agency investing in science and research, the Wellcome Trust (a global charitable science foundation) and three other pharmaceutical companies to support whole genome sequencing of all UK Biobank participants.

Set up almost 20 years ago, UK Biobank recruited half a million altruistic volunteers to create the world’s most comprehensive source of health data. It is available to approved researchers worldwide via a protected database containing only de-identified data (e.g. name, address, date of birth and more stripped out), and drives scientific discoveries that improve human health. The rich database is regularly augmented with additional data from the half a million volunteers on lifestyle, whole body imaging scans, health information and proteins found in the blood.

This collaboration, facilitated through the London-based Johnson & Johnson Innovation team, produces the world’s largest repository of WGS data.

“Nowhere in the world had anyone attempted human whole genome sequencing at this scale, but we could see the potential it had to generate novel, highly relevant human disease targets—and with targeted therapeutics, greatly improve the potential for clinical trial success,” says Nerida Scott, Ph.D., Regional Head, Johnson & Johnson Innovation for Europe, the Middle East and Africa. “In addition, we believed it could give us the opportunity to screen all our internal programs and external partnering opportunities to confirm human target relevance and help increase the chance of successfully delivering products that transform human health.”

Johnson & Johnson and the other partners were committed to whole genome sequencing rather than whole exome sequencing (WES), which covers only 2-3% of the genome. WGS is a major enhancement on WES.

“WGS captures the entire genome, enabling detection of coding and noncoding genetic variation, structural variants and variation in complex regions that are technically challenging to genotype,” says Shuwei Li, Ph.D., Director, Population Analytics & Insights, R&D Data Science & Digital Health, Johnson & Johnson Innovative Medicine. “When you do whole exome sequencing, you’re only looking at the coding region; it’s like one thin slice of an apple.”

For years scientists referred to noncoding DNA as “junk DNA.” But it’s become clear that some noncoding sequences regulate gene expression and protein formation. “We want to characterize the whole genomic landscape and integrate WGS into the human multi-omic framework built by the Population Analytics team to support target identification, prioritization, precision strategies and clinical trials,” says Li.

On November 30, after a period of exclusive access for Johnson & Johnson and the three industry WGS partners, UK Biobank announces that the sequenced genomes of all 500,000 participants are available to approved researchers across the globe.

Scientists can now apply to use this huge data set, which has over 10,000 variables for each participant, to combine information about several gene variants and more accurately predict disease risk, says Howe. That’s key, because very few diseases directly stem from a single gene mutation. Most common illnesses—like heart disease, diabetes, depression and cancer—likely result from the interaction of several genes, as well as environmental factors.

This addition to UK Biobank’s database also promises to streamline clinical development of new therapies by helping match patients to the best treatment for them, says Scott. Two people with rheumatoid arthritis, for instance, might show nearly identical symptoms, yet the biology of what’s driving the underlying disease and how to best treat it might be drastically different.

The availability of the sequenced genomes could help expedite the development of novel drugs. “It will enhance precision strategies by making research more effective and yielding better, more precise treatments for patients around the world,” she adds.