US giant Illumina, which is building a new R & D hothouse at Granta Park in Cambridge, has formed a new company branded GRAIL to enable cancer screening from a simple blood test.

It is being powered by Illumina sequencing technology based on Cambridge IP dating back to the mid 1990s. The venture is backed by Bill Gates among others.

GRAIL aims to develop a pan-cancer screening test by directly measuring circulating nucleic acids in blood.

Detecting cancer at the earliest stages dramatically increases long-term survival, so successful development of a pan-cancer screening test for asymptomatic individuals would make the first major dent in global cancer mortality, Illumina believes.

GRAIL, which is currently headhunting a CEO, has been formed as a separate company, majority owned by Illumina. It is initially funded by over $100 million in Series A financing from Illumina and ARCH Venture Partners, with participating investments from Bezos Expeditions, Bill Gates and Sutter Hill Ventures.

GRAIL’s unique relationship with Illumina provides the ability to economically sequence at the high depths necessary to create a screening test with the required sensitivity and a hoped for level of specificity never before achievable for cancer screening.

The story begins in the labs of Cambridge University and specifically in blue skies research conducted at the chemistry department which evolved into the revolutionary sequencing by synthesis (SBS) technology that is the foundation of Illumina sequencing instruments.

In the mid-1990s, Cambridge scientists Shankar Balasubramanian (pictured above) and David Klenerman were using fluorescently labelled nucleotides to observe the motion of a polymerase at the single molecule level as it synthesised DNA immobilised to a surface.

The contributions of Cambridge scientists to the first draft of the human genome and the University’s rich history of DNA research by Alexander Todd, James Watson, Francis Crick, and Fred Sanger, inspired Drs. Balasubramanian and Klenerman to theorise how this approach might be used to sequence DNA.

A series of creative discussions in the lab and at a local pub during the summer of 1997 sparked ideas surrounding the use of clonal arrays and massively parallel sequencing of short reads using solid phase sequencing by reversible terminators; the SBS methodology became the basis of a new DNA sequencing approach and in 1998 Solexa was formed.

Work continued in the lab but VC money allowed the founders to set up corporate facilities in 2000 at Chesterford Research Park.
In 2001, the team’s research progress attracted £12 million in Series A funding, enabling it to build its management team. Three years later, Solexa acquired Manteia’s molecular clustering technology.

The amplification of single DNA molecules into clusters enhanced the fidelity and accuracy of gene calling, while reducing the cost of the system optics through generation of a stronger signal.

A year later, the team sequenced the complete genome of bacteriophage phiX-174, the same genome Sanger first sequenced using the method. However, the SBS technology generated significantly more sequence data, delivering over three million bases from a single run.
In 2005, Solexa acquired instrumentation company Lynx Therapeutics in a reverse merger, becoming an international public company on the uS technology exchange, NASDAQ, with offices in Cambridge UK and Hayward, California.

Engineering and software production teams based in Hayward immediately went to work transforming the successful Solexa prototype into a commercial sequencing instrument and in 2006 the first Solexa sequencer– the Genome Analyzer – launched. It gave scientists the power to sequence a gigabase  of data in a single run.

Solexa was acquired by Illumina in early 2007. In the intervening years, the technology and instrumentation have sequenced hundreds of microbial, plant, and animal genomes. Next-generation sequencing (NGS) data output has increased at a rate that outpaces Moore’s law – more than doubling each year.

Fast forward to 2016 and today’s potentially transformational development, which will be progressed both sides of the Atlantic.
Jay Flatley, Illumina CEO and chairman of GRAIL, said: “We hope today is a turning point in the war on cancer. By enabling the early detection of cancer in asymptomatic individuals through a simple blood screen we aim to massively decrease cancer mortality by detecting the disease at a curable stage.”

GRAIL says it has secured the counsel of a world-class set of industry and cancer experts for its advisory board.

Dr Richard Klausner, formerly Illumina chief medical officer and NCI director, and a director of GRAIL, said: “The holy grail in oncology has been the search for biomarkers that could reliably signal the presence of cancer at an early stage.

“Illumina’s sequencing technology now allows the detection of circulating nucleic acids originating in the cancer cells themselves, a superior approach that provides a direct rather than surrogate measurement.”