Fast, Low-Cost Human Genomes Will Transform Our Lives

The human genome stores the information needed to replicate our bodies. It is stored on 23 chromosome pairs and consists of just over 3 billion DNA base pairs. This information could be stored in a computer in the form of a 725-megabyte data file.

The idea of determining the sequence and mapping the human genome can be traced back to 1953, when James Watson and Francis Crick deduced the molecular structure of DNA. However, it wasnt until the mid-1980s that a serious commitment was made toward that effort. It was called the Human Genome Project.

Thousands of scientists, working in more than 100 laboratories in nine different countries, contributed to the project. In 2001, a draft of the complete human genome was published. The total estimated cost was over $3 billion.

Many may wonder what benefit there is to having this information; what, if anything, can be done with it? The answer lies in the understanding it brings about what the different genes do, how they affect human health, and how the genes that do not encode proteins act as switches to enable gene expression.

Its worth noting that for all the variation between human beings, the DNA sequence differs from one person to another by only one-tenth of one percent. But, it is these differences that determine how each person looks, and to which diseases one is susceptible.

Statistics reveal just how important it can be to leverage genetic information:1

? 60 percent of all people will, at some time in their lifetimes, be affected by a gene mutation. ? 71 percent of admissions to a major U.S. pediatric hospital have an underlying genetic basis. ? Only 1 percent of genetic disorders are diagnosed at birth.

This difference between the high number of pediatric admissions and the lower rate of diagnoses at birth reveals the potential that genome sequencing offers for early detection. But it is no small task. There are approximately 2,200 disorders for which we have identified an underlying causal gene. For example, Cystic Fibrosis is linked to the mutation of a particular gene, which is known to mutate in 1,300 different ways.

Unfortunately, the exorbitant cost of sequencing has made producing a full human genome map for every person out of the realm of possibility ? until now.

While some technologies have brought the cost of sequencing an individuals human genome down into the $5,000 to $20,000 range, that is still far from affordable as a routine procedure. One company, however, is pioneering a different approach that is closing in on the promise of providing a human genome for less than $1,000. On top of that, it will also be much quicker than the conventional sequencing approach.

The company is Ion Torrent and its technology is called the Personal Genome Machine, a piece of equipment that is already able to identify mutations that are present in the genome of patients with cancer. According to Ion Torrents CEO, Jonathan Rothberg, by late 2012 his company will be sequencing human genomes as quickly and cheaply as it can sequence much smaller bacterial genomes, which currently takes about two hours.2

The breakthrough that is enabling Ion Torrents technology to work faster than other technologies is that it uses semiconductors to sequence DNA, rather than relying on conventional wet chemistry.3

Other advanced technologies sequence DNA using fluorescently tagged molecules that are scanned by a microscope. Ion Torrents machine detects DNA sequences electronically with sequencing chips. This offers cost savings since it does not rely on expensive lasers and cameras.

Instead, these sequencing chips come from the same semiconductor plants as do computer microprocessors. Similarly, as the production volume of these sequencing chips continues to increase, the costs per chip will continue to drop. Since Ion Torrent began selling its machine a year ago, the cost of the sequencing chips has already dropped from $250 to $99.

At the same time, researchers at Ion Torrent have increased the chips sequencing capacity to 100 million base pairs. Thats a ten-fold increase from when the technology was first launched. According to Rothberg, their third-generation chip, which will be available next year, will once again demonstrate a ten-fold jump, with a capacity to sequence one billion bases.

Although the technology in the Personal Genome Machine has not yet reached the industry goal of "a full human genome for $1,000," it is already delivering some very impressive results in sequencing smaller genomes.

As Rothberg explains, "We are not the cheapest machine for a human genome, but we are the cheapest if you want to look at 200 genes or a pathogen behind an outbreak."

This past June, the Ion Torrent technology did just that. A new strain of E. coli had killed more than 20 people in Europe, and the Personal Genome Machine was used to identify the microbes drug-resistant genes.4

In other uses, Yemi Adesokan, cofounder of the genomics startup Pathogenica, has developed a test for human papilloma virus in Pap smear samples that leverages Ion Torrents technology. Adesokan is able to gain an advantage over existing tests because the Personal Genome Machine can detect infection with multiple strains of the virus. This is significant because a positive test can be linked to an increased risk of cancer.

Additionally, researchers around the world are using Ion Torrent machines to sequence genes involved in cancer and other diseases. Armed with this ability, scientists are now able to track the precise genetic changes that are responsible for individual cases of cancer, gaining insight into how tumor cells originate and evolve.

The ultimate goal is to be able to determine the best treatment for each patient through a quick, affordable test. Today, a large number of patients receive chemotherapy which will either not work or will cause catastrophic side-effects because of the individuals specific genetic makeup. Once personal genomes can be quickly and cheaply sequenced, it will change the way cancer and other diseases are treated.

An example from the fall of 2008 provides a glimpse into where genome sequencing is going, and how Ion Torrent technology will speed the process.5

A patient had adenocarcinoma of the tongue, a rare type of cancer that had metastasized to his lungs. Traditional chemotherapy offered little chance of success. The only hope was to use a targeted therapy that attacks genetic dysfunctions of the cancer. Unfortunately, none had been developed for this particular type of cancer, so one would have to be created.

The hunt was on for clues that would give the researchers insight into how to treat the cancer. Taking a sample of the patients tumor, they isolated the DNA and processed it in their sequencing machines; this was a three-week, around-the-clock effort.

Adding the genetic mistakes identified in the sequenced DNA to their knowledge of the molecular pathways associated with this cancer, the researchers created a model of what might have gone wrong. Based on this, they concluded that the patient had a genetic defect that increased the activity of a molecular pathway that has been linked to the growth of cancer cells.

The patient was treated with a drug that inhibits the activity of the defective gene, and within a month the results were dramatic. Whereas the cancer had grown by 20 percent in the six weeks prior to treatment, after the treatment it had shrunk by 20 percent. It then stabilized for six months and began growing again.

Treated with a second set of drugs, again based on the genome model, the cancer was again stabilized, this time for four months. However, it then began to spread rapidly. Because this is a fast-growing cancer, waiting another three weeks for another sequencing was not an option. So, the patient died while doctors attempted, once again, to arrest the growth through chemotherapy.

This example highlights why physicians mostly run genomic tests that entail only tens or hundreds of genes today. But as is often the case, they need faster and broader results. The several weeks it took for each sequencing of DNA in this scenario is typical for most machines and technologies.

With the Ion Torrent machine, researchers can now gain a huge advantage: speed. Sequencing time is slashed to only a couple of hours.

Based on this trend, we submit the following three forecasts for your consideration:

First, if this technology continues to improve at its current pace, scientists will soon have a powerful tool for deciphering the factors at play across a patients entire genome.

As a result, better diagnostic tests and more accurate prognoses will be available, enabling doctors to better target therapies and determine which patients would benefit from which treatments.

Second, the benefits of genomics will accrue over a number of years as we come to understand the code fully.

Knowing a persons DNA sequence is just one part of the actionable knowledge we need for truly personalized medicine. The next step will be to understand the correlation between the 3 billion base pairs and specific outcomes. Getting to that point will take at least 10 years of sequencing and mapping so that we understand each of the many individual variations. Considering there are perhaps millions of genetic mutations that are related just to various cancers, its likely to be 20 years before we see a combination of medicines and other therapies truly tailored for each individual. In our fast-paced world, waiting 20 years for a cure seems like a distant dream. However, compared to the millennia in which diseases have afflicted mankind, this will be like "a blink of the eye."

Third, with everyones complete genome readily available, new ethical issues will need to be addressed.

For example, debates will rage over the conflict between privacy of information and a companys desire to know about any physical predispositions that could affect job performance. Some employers will claim the right to use a persons genome when considering that person for a position. A marker for heart disease, it could be argued, should exclude a person from a physically taxing job, such as firefighter or warehouse worker. Similarly, health insurance providers will have a strong interest in using a persons genome to assess risks and set premiums, or even deny coverage. With detailed information of genetic dispositions, actuary tables may become a thing of the past, since it will be possible to base ratings on specific genetic markers, rather than averages based on factors like age and gender.

References List :
1. To access the document “Project Roadmap 2010-2012,” visit The Human Variome Project website at: http://www.humanvariomeproject.org 2. MIT Technology Review, November 20, 2011, “$1,000 Genome in Two Hours by 2012, says CEO of Ion Torrent,” by Christopher Mims. ⓒ Copyright 2011 by Technology Review. All rights reserved. http://www.technologyreview.com 3. MIT Technology Review, July 21, 2011, “A Semiconductor DNA Sequencer,” by Emily Singer. ⓒ Copyright 2011 by Technology Review. All rights reserved. http://technologyreview.com 4. Ibid. 5. MIT Technology Review, January/February 2011, “Cancers Genome,” by Emily Singer. ⓒ Copyright 2011 by Technology Review. All rights reserved. http://www.technologyreview.com