Decoding human history

From its first commercial scales in the early 20th century to recent cloud-based computing initiatives, IBM has been in the business of accessing and processing information. Some of the most complex information in the world is stored in the human genome, and IBM has been at the forefront of efforts to unlock it. In 2005, the company set out to help scientists understand the genome through two major undertakings: the Genographic Project in partnership with National Geographic, and the development of the DNA transistor.

The two efforts were closely related. The Genographic Project sought to trace the migration of prehistoric human populations from their origins in Africa to their present global distribution. Its goal was to create an accounting of movement during the millennia that preceded recorded history. To do so, IBM and its partners needed to improve the speed and efficiency of genomic sequencing dramatically — a goal that led to the development of the DNA transistor.

Together, these projects resolved a longstanding debate in anthropology: Researchers determined that humans migrated out of Africa through the Arabian Peninsula to India and then to Europe and Asia, rather than leaving Africa via Egypt as some scientists had previously speculated. In the process, IBM and its partners also revolutionized DNA sequencing technology, creating a modern environment in which ordinary people can learn their entire genetic ancestry by sending an inexpensive kit through the mail.

In spring 2005, IBM announced that it had partnered with the National Geographic Society to sequence hundreds of thousands of individual human genomes from populations around the world. The ultimate goal was to use this data to trace the path that humanity followed out of Africa.

Led by Spencer Wells, a National Geographic Explorer-in-Residence and American geneticist working at IBM, the Geographic Project was one of the most ambitious undertakings in human genomics up to that point. “We see this as the moon shot of anthropology, using genetics to fill in the gaps in our knowledge of human history,” Wells said at the project’s inception.

The effort comprised three core steps. The first was to establish a network of centers where scientists could gather and sequence genetic material from indigenous populations, whose genomes contain key markers that have remained unchanged for millennia. These markers acted as milestones in the effort to trace humanity’s path. By identifying them in other groups, researchers could determine when certain populations had passed through particular areas on their journeys.

The second step was to gather samples from human populations around the world. Volunteers purchased test kits for USD 99.95, which facilitated the collection of samples of genetic material for IBM to analyze. Researchers at IBM subjected these samples to the third step in the project: a massive, computer-assisted analysis of one of the largest bodies of human genetic material ever assembled. “Our challenge was whether it was even feasible to tease apart these [genetic] lineages to understand the commonalities,” IBM researcher Laxmi Parida said in 2011. “Through a determined approach of analytics and mathematical modeling, we undertook the intricate task of reconstructing the genetic history of a population.”

When the Human Genome Project, a collaboration among scientists at the National Institutes of Health and 20 universities and research centers around the world, completed the first functional sequencing of a human genome in 2003, the price tag came to USD 3 billion. If the Genographic Project was going to work, researchers would need to greatly reduce the cost of sequencing. At the time, the “thousand-dollar genome” was regarded as the holy grail of genetic sequencing technology: a goal most researchers considered possible but elusive.

In 2009, IBM announced a partnership with the biotechnology company Roche to develop what would become known as the DNA transistor, to expedite the process of scanning and sequencing human DNA molecules. The main challenge was to find a way to control throughput, the speed at which a strand of DNA passed through the reader. Such strands are approximately 100,000 times thinner than a human hair, making them extremely difficult to manipulate.

To address this problem, scientists from four fields — physics, biology, microelectronics and nanofabrication — came together to create a machine that could thread a DNA molecule through a 3-nanometer hole in a silicon chip. An electrical sensor “read” the DNA as it was ratcheted through the hole, one unit of DNA at a time.

Researchers discovered that they could control the throughput of the DNA using a multilayered metal and dielectric structure with voltage differences between the layers. These voltage differences created an electric field that could be manipulated to control the speed of the DNA’s passage. By solving the throughput problem, the DNA transistor had “the potential to revolutionize biomedical research and herald an era of personalized medicine,” as IBM Research scientist Gustavo Stolovitzky predicted at the time.

The development of the DNA transistor constituted a massive breakthrough in the efficiency of genomic sequencing, turning what had once been a multibillion-dollar process into something laboratories could perform at comparatively high speed and low cost. It helped complete the Genographic Project, and it provided the basis for a new industry in personalized DNA testing.

Today, individuals can have their genomes sequenced using home sample kits that retail for as little as USD 100, for applications ranging from medical diagnoses to the identification of long-lost relatives. If you go back far enough, we’re all related. Through the Genographic Project and the development of the DNA transistor, IBM helped discover how.