Sunday, Sep 7, 2008
In just a few years, doctors will know everyone's genetic identity. This knowledge will be a blessing -- and a curse.
Nov 28, 2005 | It's the not-too-distant future, say 2016. You have been diagnosed with Stage III melanoma. Cancer has metastasized throughout your body. Just 10 years ago, in 2006, the choice of treatment would have been based on the type of primary cancer, the size and location of the metastasis, your age, your general health and your treatment history. Your prognosis would have been gloomy. But that was back in 2006, before we entered the era of nanomedicine.
In 2016, your doctor will be capable of scanning your entire genome in a few minutes. She will do this because every cell has a different gene expression pattern or profile. When a cell becomes cancerous, this profile changes. Your Stage III melanoma has a unique, schizoid genetic signature reflecting both a skin cell heritage and a newly acquired outlaw metabolism. Your doctor will explain that while your cancer has a great deal in common with other Stage III melanomas, it is not exactly like any other. Your doctor knows this because for the past few years DNA from virtually every melanoma patient in the U.S. healthcare system has been routinely extracted, scanned and deposited in a national database. This population of sequences, fully analyzed and with a user-friendly graphic interface, is available in real time. Searching this database for any specific cancer sequence will be about as difficult in 2016 as finding Madonna's birthday on Google is today.
The exam room of 2016 reflects a rainbow of nanomedicine paraphernalia. Diaphanous pink microtubes sit in bubble packs like sets of false nails. Red motorized pipettes hang in translucent blue plastic racks like designer tool kits from the Starship Enterprise. Shelves are filled with what appear to be airline-size single-serving cereal boxes with very slick, stunningly bright labeling. These boxes contain individually packaged, ready-to-use diagnostic kits with exciting brand names -- DNA Warrior, Mighty Clone or Gene Catcher. An invisibly small drop of your body's fluid is injected into the DNA Warrior, which is a cylindrical cassette the size of a pinhead. This cassette is slotted into the Sherlock Genomes molecular diagnostics system.
From the outside, this "system" appears considerably less complex than your current cellular telephone. Inside, a single melanoma cell is purified from your blood via solid-phase fluorescent immunoaffinity chromatography, a technique in which a single cancer cell is "hooked" from amid millions of its healthy companions using a synthetic antibody molecule and "reeled in" on the beam of light produced when the two unite. Twenty years ago this technique required a million-dollar instrument the size of a 767 cockpit and a dedicated operator. Now it is little more than routine blood work.
Once purified, the renegade cell is moved via electroosmotic microfluidic channels to a lab chip that, in another venue, could pass for a credit card. Electroosmosis uses the charged molecules on the surface of the channel itself to cause a solution to flow in a specific direction. This will only work when a tube or channel is extremely small. Microfluidics use pipes the size of a human hair to create plumbing systems that empty into reaction chambers much smaller than the head of a pin. This enormous volume is dictated by the dimensions of your humanity -- any smaller and a living cell wouldn't fit inside. On the lab chip, a purified cancer cell relinquishes its cache of chromosomes and within seconds your entire genome has been sequenced. That bears repeating. In a few years single-molecule DNA sequencing will be a reality. The 2.91 billion bits of biological data that bestow your unique genetic identity will be available virtually anytime for the cost of a routine blood test. Sound far-fetched? Two weeks ago J. Craig Venter, the genomics entrepreneur who paced the U.S. government to the completion of the Human Genome Project, announced that he hopes to offer $10 million as a prize (he originally pledged $500,000) for automated DNA sequencing technology that can decode a human genome for $1,000. At that same conference, a commercial instrument capable of sequencing 1 billion bases, or chemical groups, of DNA per day was unveiled.
A machine that "shreds" a billion bases of DNA a day could burn through the human genome in 72 hours. Yet we fully expect that this phenomenal accomplishment will be eclipsed within a few years by nanoengineering. Around the world, research teams are closing in on single-molecule DNA sequencing technology. One group has published a design for an instrument that could place a million single-molecule sequencers on a device the size of a postage stamp. To accomplish this, each sequencer will have an operating volume of one zeptoliter -- much less than one billionth of one billionth of a liter! There can be no doubt that within a few years, most individuals will have their genome sequenced and encoded as part of their medical record. And this is just the beginning.
No equation can represent the astonishing technological trajectory we are on. The trek from Olduvai Gorge to Mesopotamia -- from Homo habilis to the wheel -- took 1.5 million years. A mere 5,500 years took us from the wheel to the double helix. Then 50 years to the human genome. Nanotechnology, our ability to build molecular devices with atomic precision, is the transcendent culmination of our co-evolution with tools. With the advent of nanomedicine, we will turn these tools inward.
The National Cancer Institute's fact sheet on nanotechnology and cancer says, "Most animal cells are 10,000 to 20,000 nanometers in diameter. This means that nanoscale devices (having at least one dimension less than 100 nanometers) can enter cells to interact with DNA and proteins. Tools developed through nanotechnology may be able to detect disease in a very small amount of cells or tissue. They may also be able to enter and monitor cells within a living body."
According to the National Institutes of Health, nanotechnology could create devices capable of reporting the onset of cancer at the exact moment of molecular metamorphosis, long before today's tests are effective. The key, as with DNA sequencing, is single-molecule sensitivity. One approach will use individual carbon nanotubes (molecular rods about half the diameter of the DNA molecule itself) to literally trace the physical shape of a single DNA molecule the way a phonograph needle traces a vinyl record. Another early-detection strategy will use the quantum dots (Q-dots) described in a previous article. Latex beads filled with these crystals will be designed to bind to specific DNA sequences. When the crystals are stimulated by a flash of light, they emit colors that light up the sequences of interest. By combining different-sized quantum dots in a single bead, scientists will create probes that release a spectral bar code specific for each type of cancer mutation.
Nanotechnology will also create tools to eradicate cancer cells without harming healthy cells. In therapy applications, as in detection, single-molecule recognition is the key. Each magic nanobullet will home in on a specific, targeted molecular structure. In fact, the goal is to treat cancer like an infectious disease. We will be vaccinated with nanoparticles that continuously circulate through the body. This cancer vaccine -- really a primitive cancer-killing nanobot -- will detect molecular changes, assist with imaging, release a therapeutic agent and then monitor the effectiveness of the intervention.
How close are we to cancer-killing nanobots? The NIH Web site talks about nanoshells -- minuscule beads coated with gold. By manipulating the thickness of the layers constituting the nanoshells, scientists will design them to absorb specific wavelengths of light. The most useful nanoshells are those that absorb near-infrared light, which can easily penetrate into the body. Absorption of light by the nanoshells generates a lethal dose of heat. Researchers can already link nanoshells to antibodies that recognize cancer cells. In a "magic bullet" scenario, nanoshells will seek out their cancerous targets. Once they have docked, they will be zapped with near-infrared light. In laboratory cultures, the heat produced by light-absorbing nanoshells killed tumor cells while leaving neighboring cells intact. Experts believe quantum dots, nanopores and other devices may be available for clinical use in five to 15 years. Therapeutic agents are expected to be available within a similar time frame. Devices that integrate detection and therapy could arrive in the clinic in about 15 to 20 years, which means a cure for your Stage III melanoma and other forms of cancer could arrive within your lifetime.
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