Massive Database Planned To Crack The Secrets Of Aging

J. Craig Venter, PhD

Billionaire scientist J. Craig Venter has launched an ambitious and expensive commercial venture to amass and electronically analyze the medical, genomic, microbiomic, and metabolic data of 40,000 individuals every year. And eventually, 100,000 individuals a year. The goal? To identify biologically relevant patterns in these interconnected data—patterns that may eventually reveal different ways to block the complex interactions that trigger age-related diseases and even aging itself.

Revealing The Origins Of Disease And Death

J. Craig Venter, PhD, is best known as the biologist who, with just a fraction of the funding and in far less time, tied the United States government’s Human Genome Project in mapping the world’s first whole genome sequence in the early 2000s. More recently, he laid claim to creating what has been called the first self-replicating synthetic cell.

Thirteen years ago, Venter’s own genome was sequenced over a nine-month period at a cost of $100 million. But for the same total amount of money, it is now possible to map the genomes of 100,000 individuals. This astonishing accomplishment—getting the cost of a single genome down to the $1,000 price point—has been the Holy Grail of medical research, considered the tipping point in the pace of genetic discovery. Why?

Scientists realize that they will need to sequence hundreds of thousands, maybe even millions, of individuals to truly understand how genes influence disease and aging—so that more specifically targeted drugs, treatments, and preventive strategies can be developed. In order to make such massive sequencing studies financially feasible, $1,000 genomes are absolutely essential.

Venter’s new company, Human Longevity, Inc., is building the largest human genome-sequencing database in the world. By sequencing the genomes of people who are healthy, sick, young, and old, the database is expected to eventually offer insights into the aging process. But even at $1,000 a genome, that’s no easy task.

The reason is that in order to achieve this price point, you need a powerful DNA-scanning sequencer known as the HiSeq X. Each unit costs $1 million, and the company that makes them, Illumina, won’t sell you fewer than 10 of them.

So Human Longevity, Inc. bought 20.

To attain the $1,000 genome cost, you also need to keep these machines running constantly, which requires a constant volume of human samples to sequence. To that end, Venter has set up a collaborative program with the Moores Cancer Center. Soon, the genome of every single patient passing through the center—along with the genome of the patient’s tumor—will be sequenced at Human Longevity on an opt-out basis. The data will be stored and used to find new therapeutic targets, pathways, and biomarkers. Even this supply of data will only make a dent in the 40,000-genome annual capacity of Venter’s new enterprise, and he is actively seeking new individuals for genetic material.

Eventually, the project may be mapping the genomes of 100,000 people a year. How long can the secrets behind cancer’s origins continue to hide from this ongoing accumulation of DNA analyses?

Personalized Prevention Of The Diseases Of Aging

Human Longevity, Inc. considers cancer the most likely area of genomic research to deliver immediately actionable results.

“Today, people with cancer must wage war on two fronts, battling their disease and fighting for advanced treatments,” said Human Longevity co-founder and stem cell pioneer, Robert Hariri, MD, PhD, at a recent conference. “The oncology field is changing rapidly. Every tumor is different and every patient is different. Human Longevity believes the time is now to incorporate every individual’s genetic code as the starting point of care and therapeutic development.”

Cancer is just an initial focus. With preliminary funding of $70 million in hand, mostly from wealthy investors, Human Longevity plans to also concentrate on diabetes, heart disease, dementia, and liver disease, diseases that the company views as, “some of the most difficult to treat, let alone cure, [the] diseases affecting people as they age.”

To jump-start this lofty mission, Venter has hired a panel of scientific luminaries, a diverse crew of experts in genomics, stem cells, cancer, translational medicine, the microbiome, and emerging technologies. He plans to collaborate with companies in the genetics and stem cell arena, with large hospital systems and clinics that will utilize his firm’s services, with pharmaceutical companies that can discover and develop new therapeutics, and with academics.

This exciting genome-mapping venture seems extremely ambitious by itself. But it’s just one leg of Venter’s broader strategic plan.

Matching Genomes, Metabolomes, And Microbiomes To Disease

In addition to sequencing the genomes of an anticipated 40,000 individuals a year, Human Longevity will use mass spectrometry to document individuals’ metabolomes—the constantly changing array of small molecules of biochemicals and lipids circulating throughout participants’ bodies.

While genome sequencing can reveal information about inherited risk of disease or hint at how long a person will live, metabolic data can clarify how environment, diet, and other factors affect an individual’s health and life span. Metabolic data also help researchers interpret genomic information. Pinpointing a particular gene as important in a disease or a normal cellular process does not, in itself, clarify what that gene actually does. But if a particular metabolite is found to correlate with a particular genetic signal, then researchers can zero-in on the function of the gene. The relevance of blood biochemistry is underscored by the fact these metabolites change as we age—to such an extent that an analysis of blood metabolites can reveal a person’s specific age.

However, aging and human cell behavior changes are not the only cause of changes in blood metabolites. The microbes in our bodies—which outnumber human cells 10 to one—generate metabolites that can be detected in the blood.

For this reason, Human Longevity will also be mapping at least some participants’ microbiomes—the complete makeup of the trillions of bacteria, viruses, and fungi living in each individual’s gut, mouth, and other body sites, as well as on the skin.

With aging and disease, the microbiome is believed to alter its composition, leading to changes in what molecules are produced. For instance, an August 2014 online study by Cancer Prevention Research found that analysis of the gut microbiome allowed scientists to distinguish between healthy participants and those with precancerous polyps or invasive colorectal cancer.* By better understanding how each person’s microbiome interrelates with his overall genetic and metabolic map, the company hopes to develop better probiotics—as well as better diagnostics and drugs to improve health and wellness.

Bringing hard relevance to these complex genetic, metabolic, and microbiomic data sets, Human Longevity will also collect the clinical medical history of every individual whose genome it sequences. Each participant’s complex data can be intricately compared with critical medical information.

Imagine the engineering feat involved in incorporating each participant’s clinical records with the rest of his or her amassed, personal data at the planned rate of over 100 human genome sequences a day. But Venter is looking beyond this technological challenge: He has his eye on nothing less than changing the face of medicine and human biological decline.

Will 100 Be The New 60?

First, Venter plans to deliver predictive and preventive medicine on a revolutionary scale by discovering the very earliest warning signs for susceptibility to chronic illnesses such as cancer, Alzheimer’s, and heart disease. Second, he envisions blocking the interconnected pathways of these diseases with specific, new interventions tailored to each individual’s distinct profile.

Just one way Venter aspires to accomplish this is by translating a web of personalized data into stem cell therapies. He expects to use techniques developed at his existing company, Synthetic Genomics, to rewrite the genetic code of stem cells to correct errors and use stem cell therapy as one of the key adjuvants to changing long-term health and aging outcomes. It’s an example of how his mission seems to be based on a granite-like conviction that a host of emerging and complementary fields are ready to mature at once.

While the upfront costs and complexities may seem overwhelming, Venter says, “[Human Longevity] is going to change the way medicine is practiced by helping to shift to a more preventive, genomic-based medicine model, which we believe will lower healthcare costs.”

When people reach 100 years of age, they are often suffering from multiple diseases and cannot care for themselves. Venter wants these people to reach 100 years for the simple reason that they remain in good health and are therefore, self-sufficient.

Extending the number of healthy years will require focusing, not on individual diseases, but on aging. Why aging?

“The easiest answer is that aging is a central component of every disease that we want to address therapeutically,” said Hariri. “We believe that many of the processes at the cellular and the genomic level that we call aging are related and connected.”

The sheer volume and diversity of the data being assembled virtually guarantees that this project will yield revolutionary new clues to the mysteries of aging and disease. Optimistically, Dr. Venter and his team expect a lot more. As Human Longevity co-founder and vice-chairman, Peter Diamandis, summarized it:

“Our goal is to make 100 years old the new 60.”

*Available at: http://cancerprevention-research.aacrjournals.org/content/early/2014/08/06/1940-6207.capr-14-0129.abstract. Accessed August 21, 2014.

For more information about Human Longevity, Inc., visit www.humanlongevity.com.

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