Nanopore Sequencing & the Problem With Patents

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Picture Credit: DNA | Public Domain Pictures

In 2003, researchers from all over the world achieved one of the greatest scientific endeavors of their time: identifying and mapping out the entire human genome. With over 20,000 genes analyzed, the scientific community reaped the benefits of the age of genomics, where scientists could identify the thousands of nucleotide base pairs involved with specific genetic diseases like Huntington’s and pinpoint the mutations that underlie different forms of cancer.

But now, a device from Oxford Nanopore Technologies could bring the same power of DNA sequencing from the laboratory into the palm of your hand. It’s called the MinION and it can sequence the DNA of any given sample in a matter of hours.

For decades, conventional DNA sequencing was widely regarded as a tedious, time-consuming process. In order to identify the genome of a particular sample, a researcher would have to create numerous identical copies of the DNA molecules, break each of those copies into tiny pieces for the machine to read, sequence each fragment individually and finally reassemble those pieces together again. It’s the equivalent to reading a book by shredding it to read each word separately and then taping the pages back together again. In addition, this cumbersome process involved expensive machines the size of refrigerators and took days or weeks to run.

Due to these practical limitations, many researchers have to rely on the products and services of large corporations to obtain the DNA sequence of their samples. Today, the one that currently dominates the sequencing market is Illumina, Inc., a corporate giant worth billions of dollars. At the moment, Illumina provides machines for almost every large sequencing center in the world and now has an almost complete monopoly in the industry. However, Oxford Nanopore Technologies intends to bring down this powerful behemoth with a revolutionary new way of reading DNA called nanopore sequencing, which identifies the nucleotide base pairs directly without breaking apart the DNA molecule.

The idea is rather brilliant. A nanopore is simply a very tiny hole, about 2.5 nanometers wide. Nanopore sequencing relies on the use of an incredibly thin synthetic membrane with numerous nanopores as well as nanopore sensors. When the membrane is submerged in liquid by itself and a current is ran through, a steady electrical pattern is measured as ions pass through the tiny holes.

These patterns change once a DNA sample is placed on the membrane. When the electrical current pulls a DNA molecule through a nanopore, the nucleotide bases block the pore and stop some of the ions from passing by. This blockage alters the current that the sensor is reading and ultimately causes the electrical pattern to dip. What makes this method so effective is that each nucleotide base of DNA blocks the pore in different ways and generates a unique and identifiable change in the current. In other words, one can identify the DNA sequence by simply reading the various spikes in the electrical pattern.

In addition to its speed, easy usage and portability, the MinION also boasts a 99.99 percent accuracy based on a performance of 90 percent without any false positives. Not only that, Oxford Nanopore Technologies set the price of their new, revolutionary sequencing gadget to a mere $1,000. When the MinION was first revealed to the world in 2012, one scientist tweeted: “I felt a great disturbance in the force, as if a million Illumina investors cried out in pain.”

The idea of genetically identifying any organic substance at any place and time has enormous implications. A DNA sequencer like MinION could not only be used in a lab but also in the field with little to no difficulties. During the Ebola outbreak in 2015, microbiologist Nick Loman used his newly-bought MinION to track the progress of the epidemic in real time while other scientists had to wait weeks for the results of their analysis to arrive.

For something as time-sensitive as a deadly epidemic, nanopore sequencing could save tens of thousands of lives. Not only that, Oxford Nanopore aims to make their product available to everyone everywhere. From NASA astronauts in space to high school students, the company envisions a future where DNA sequencing devices can become like telescopes, a formerly expensive scientific instrument that is now available to the everyday consumer.

Unsurprisingly, Illumina is trying everything in its power to stop MinION’s momentum. Last February, the sequencing industry monopolist filed several lawsuits against Oxford Nanopore Technologies claiming that the British company committed patent infringement by using bacteria-derived pores known as Mycobacterium smegmatis porin (Msp) to create their synthetic membrane.

At the moment, Illumina holds the patents for any system that use these Msp. Oxford Nanopore responded almost immediately, accusing the corporate giant of acting on unsubstantiated speculation to prevent the MinION from ever reaching the market all so that Illumina can maintain its monopoly.

This move by Illumina illustrates just one of numerous legal issues that stand in the way of scientific progress. The scientific community is often plagued by patent aggregators, people or companies who enforce patent rights to make a profit or keep such patents away from those who may pose a threat against them. Despite not using their patents for research or manufacturing purposes, these entities prey on smaller companies to force them out of business. Never having proven their ability to produce their own nanopore sequencer, Illumina could very well be yet another patent aggregator trying to neutralize the incoming threat to their business.

Even if the MinION does not contain Msp pores, Illumina could still utilize the doctrine of equivalents. This aspect of patent law claims that Oxford Nanopore Technologies could still be liable for patent infringement as long as the product in question performs the same function as the patented invention in the same way. Originally created to cover the difficulty in describing the invention exactly, the doctrine can now be used to back companies like Oxford Nanopore into a corner.

Depending on the outcome of this legal battle, the entire course of scientific progress can be altered. With such great scientific advancements at risk due to capitalistic greed, it’s time to take another look at our patent system to prevent other innovations from becoming similarly obstructed. Overhauling the patent system is essential to taking money and special interests out of scientific research and thereby crafting an atmosphere more conducive to intellectual cohabitation and progress.

According to phylogenomics researcher Joe Parker, nanopore sequencing can bring about a second age of genomics. If that future can never come to fruition, then the same bleak stasis will certainly sabotage other shining opportunities for society as well.

Originally published on May 4, 2016, in The Miscellany NewsNanopore sequencing research should be encouraged

A Bright, Eco-Friendly Future: Bioluminescence as Our Next Light Source

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Picture Credit: Lit by Bioluminescence | Glowee

Imagine a world where the streets glow with a dreamlike shade of blue as if you’re walking in the presence of ethereal spirits wandering the city. While that image sounds too mythical to be real, one start-up company is working to create this otherworldly environment for the future. Glowee, a French company planning on harnessing the power of bioluminescent bacteria, has officially debuted after successfully crowd-funding in May 2015. Their goal: to replace the electric street lamps of France with blue microbial lamps.

Bioluminescence is an organism’s ability to generate light in the dark. This is different from fluorescence, which involves absorbing light from an external source and immediately re-emitting a modified version of that light. While fluorescence is a physical process, bioluminescence is a chemical one that occurs due to an enzyme, luciferase. In the biochemical reaction, luciferase catalyzes the light-emitting pigment luciferin with oxygen in order to create light. For humans, bioluminescence has the potential to be­come a valuable source of renewable energy.

Consider the latest global push towards reduc­ing CO2 emissions and fighting climate change. At the 2015 UN Climate Change Conference, world leaders came to an agreement that everyone must do everything they can to cut down our energy consumption. While politicians can promise to limit emissions, real progress cannot occur with­out a viable green energy solution. Rather than an immediate transition to green energy, what if we tackled the problem one chunk at a time? This is where inspirations from nature and the creativity of science mesh together. For instance, biolumi­nescence doesn’t require any electricity to pro­duce light. Given this fact, researchers are investi­gating engineered bioluminescence as a possible alternative to regular street lighting.

Replacing electric lamps with bioluminescent ones may seem almost trivial in the face of cut­ting global energy consumption, but reducing the number of public street lamps is a very necessary first step. In truth, lighting up the streets every night is an incredibly expensive task. According to the U.S. Energy Information Administration, the U.S. spent a total of $11 billion on outdoor lighting in 2012, 30 percent of which went to waste in areas that didn’t use or need that light. Furthermore, a recent research study determined that there are currently about 300 million total streetlights around the world and that num­ber will grow to 340 million by 2025. With such severe drawbacks that come with electrical lighting, the use of bioluminescent light is a way to alleviate some if not most of that cost.

Today, the race to find the best form of engi­neered bioluminescence continues to bring us various creative inventions and solutions. At Syr­acuse University, a small team of scientists led by Rabeka Alam discovered a way to chemically at­tach genetically-altered luciferase enzymes from fireflies directly onto the surface of nanorods to make them glow. In a process they called Bioluminescence Resonance Energy Transfer (BRET), the nanorod produces a bright light whenever the luciferase enzyme interacts with the fuel source and can produce different colors depending on the size of the rod. According to one scientist on the team, “It’s conceivable that someday firefly-coated nanorods could be in­serted into LED-type lights that you don’t have to plug in.”

On the other side of the world, Dutch designer Daan Roosegaarde has been working to­gether with the tech company Bioglow to create bioluminescent trees to light up the streets. Incorporating important re­search from the University of Cambridge, Roose­gaarde and his team spliced DNA containing the light-emitting properties from bioluminescent organisms into the chloroplasts of plants. As a re­sult, those plants can produce both luciferase and luciferin that allows them to glow at night.

For Glowee, the plan is to harness biolumines­cence by using Aliivibrio fischeri, a species of bioluminescent bacteria found in certain marine animals like the Hawaiian bobtail squid. They first produce a gel containing the bioluminescent bac­teria along with various nutrients that keep the bacteria alive. Then, the gel is used to fill small, transparent containers, allowing the light to glow through. This method not only makes the light source wireless but also customizable depending on its purpose and design. These bioluminescent lamps would certainly appeal to shop owners in France, especially since the French government recently passed a law that forces all businesses to turn off their lights at 1 a.m. to fight light pollution.

Unfortunately, despite countless efforts towards perfecting engineered bioluminescence, it may still be a long while before our streets are lit by genetically-altered plants or bacteria. The two main obstacles in this endeavor are the rel­atively dim nature of the lights as well as their short lifespan. Even with Glowee’s bio-lights, the company’s current prototype can only produce light up to three days. Some argue that the cost and production of these bioluminescent products greatly overshadow their benefits, saying that such eco-friendly alternatives can never catch up to electrical lighting. While there may be lim­itations, all these projects by businesses and in­stitutions signify the public’s growing desire for real change.

A lot of these projects were funded not by the government but by Kickstarter and other funding platforms. Perhaps many of the backers were just mesmerized by the aesthetic appeal, but the public nevertheless recognizes the potential behind engineered bioluminescence. With continuous effort and scientific innovation, a town or a neighbor­hood powered by living organisms instead of electricity can be a reality. By following the ghost­ly blue light ahead, we would take a tremendous first step towards a world where humans and na­ture can truly coexist.

Originally published on March 30, 2016, in The Miscellany News: Scientists note perks of bioluminescence

Precision Medicine: It’s Best Not to Get Hopes Up

Picture Credit: President Obama | 2016 | whitehouse.gov

In an ideal world, every person must receive a custom healthcare treatment that matches their biological makeup. We may not live in an ideal world today, but the latest efforts in preci­sion medicine plan on coming as close to it as possible. Despite enthusiasm for this movement, similarly grand ambitions in the past have shown that the results often come up short of the prom­ises made. Personalized medicine is a mode of healthcare where every practice and treatment is tailored specifically to each patient. The idea was to collect genetic information from all indi­viduals to create an all-encompassing database. However, personalized medicine has undergone some changes over the years and has recently re­defined itself as “precision medicine.”

Rather than creating drugs or medical devic­es that are unique to a single patient, precision medicine classifies individuals into small groups based on their susceptibility to a particular dis­ease or their response to a specific treatment. These small groups allow physicians to know what sort of care a patient needs depending on what sub-group the patient is in.

Don’t let the definition change fool you. The name change mainly aims to allow the movement to start afresh. By rebranding itself as precision medicine, the practice gains a second chance af­ter failing previously. Even with this fresh start, precision medicine is still liable to obstacles that personalized medicine stumbled over in the past. For instance, electronically recording the genome of every individual remains expensive. Collecting all that information and acquiring the technology to store it is not something to take lightly.

There are also fears regarding patient privacy concerns and legal liability. This sharing of pa­tient data can easily end badly for both the doctor and the patient. However, precision medicine has only gotten more popular since its re-branding. What makes precision medicine so revolutionary is its focus on individuals rather than on a demographic. Instead of using a one-size-fits-all approach, it takes into account individual differences from genetic makeup to personal lifestyles. The hope is that precision medicine can accelerate the creation of tailored treatments for diseas­es like cancer.

By expanding genetically-based patient trials, scientists and doctors will have much more infor­mation to work with when leading research and providing treatment. A nationwide database of patient genetic and medical information can help guide treatment and reduce uncertainty. Preci­sion medicine also attempts to ensure that drug companies spend time developing treatments for specific groups of patients. Most firms currently try to optimize profits by producing drugs that can benefit large groups of people.

While beneficial to many, this ignores the plights of those with rare medical conditions who must go extreme lengths to get proper care. Precision medicine aims to promote the creation of treatments for a wide range of diseases, common and rare.

There are countless reasons to push for preci­sion medicine. However, I am suspicious at the growing hype over precision as the next great landmark achievement in healthcare. Even with the aforementioned risks, the re-branding has succeeded spectacularly. Precision medicine has entered the forefront of national discussion and the public often views it as the bringer of a new age of healthcare.

In his final State of the Union address, President Obama announced the Precision Medicine Initiative (PMI) to push for the nation to adopt this movement, asserting, “My hope is that this becomes the foundation, the architecture, whereby 10 years from now we can look back and say we’ve revolutionized medicine.” The President asked Congress for $215 million to support the initiative. Thanks to Obama’s support, the PMI Cohort program plans on amassing a record of one million U.S. volunteers.

Despite the optimistic outlook on the issue, precision medicine is far from ideal. In addition to the costs and legal issues, there are concerns as to whether a database on genetic information would even be significantly useful. Back in 2003, scientists discovered that even after mapping out the human genome, a person’s genetic code remains as perplexedly complex as ever.

There are too many risks involved in interpreting genetic information. In one case, a woman underwent extreme surgery and had her uterus removed due to an incorrect reading of her ge­netic-test results. Unfortunately, these accidents are not uncommon. There are also problems outside of the scope of the medical field. Once an all-encompassing patient database is established, countless issues involving ethics arise. Say that the ideal scenario of establishing precision medicine comes to fruition. Who would claim ownership for this data? How do we make sure this information isn’t abused and used to deny insurance coverage or jobs? What is to stop insurance companies from raising premium prices once the person’s genetic information is available?

These are all valid points to consider that come with an issue as complicated as this. This leads to concerns about security. Hospitals and other havens of digital, medical information are easy targets for cyber-attacks. Just recently, a string of hospitals in California, Kentucky, and Maryland became victims of information technology breaches and were forced to pay a ransom to convince the hackers to return the databases to normal. If something similar happened to the precision medicine patient database, the consequences could be catastrophic.

The most important message is that we should always carefully consider all the possibilities before launching headfirst into what seems like a great idea. The extreme hype over precision medicine as some great benchmark in health­care will only blind us to the possible pitfalls that might appear. Sure, the likelihood of disaster may be small, but if it does happen, there will sufficient blame-tossing to go around.

Precision medicine makes great promises to dramatically improve the quality of life with one simple end goal. However, one must not get dragged away by the illusions of grandeur. For now, it’s best to approach the issue with caution.

Originally published on April 13, 2016, in The Miscellany NewsRisks of precision medicine need review

The Contagious Nature of Cancer

 

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Picture Credit: Richard Harris | Soft-Shell Clams | 2015 | KERA News

 

If there is one word that strikes fear into peo­ple’s hearts and conveys a haunting image of sickness and death, it’s cancer. According to the Union for International Cancer Control (UICC) and the International Agency for Re­search on Cancer (IARC), this disease is a glob­al epidemic that kills 7.6 million people every year, 4 million of whom are below the age of 69. Even worse, experts predict that the death toll is projected to increase to 6 million lives per year by 2025. Scientists are continuing to pursue different fields of research that can shed new light on the nature of this deadly disease. Recently, experts have come across a horrifying discovery: cancer may be contagious.

With every new insight bringing us closer to putting an end to cancer, this finding proves to be a terrifying yet valuable piece of infor­mation. This discovery originated in the 1970s when scientists were puzzled by the outbreak of leukemia in soft-shell clams along the east coast of North America. They found that this type of cancer could be spread to healthy clams by injecting them with the blood of cancer-stricken clams. For decades, research­ers concluded that a virus was transmitting the cancer. It wasn’t until 2015 that a team of experts lead by Stephen Goff from Columbia University finally pinpointed the answer: the cancer itself was spreading to other clams. This meant that the clam leukemia originated from a single host and somehow gained the ability to survive and thrive in other hosts.

As the second leading cause of death in the U.S., a top cause worldwide, cancer was thought to have a single saving grace: its non-infectious nature. While a tumor may outwit all attempts to stop its growth in a patient, the cancer ul­timately dies with its host, unable to infect another victim. However, the idea of cancer being transferred to new hosts is nothing new. In 1964, researchers at the National Cancer In­stitute performed an experiment where they harvested cancer cells in hamsters and injected them into healthy hamsters to encourage the cancer’s evolution. After numerous cy­cles, the tumor developed into a “super tumor” that could spread from hamster to hamster, without a needle, through social contact.

Regarding human cases, there have been a handful of documented cases where doctors, surgeons, and laboratory work­ers accidentally pricked themselves with a sur­gical instrument infected with cancer cells and had tumors proliferate in the wounded area. In almost all these cases, the infected person had to undergo emergency surgery before the tumor grew out of control.

However, these examples were extremely rare, freak incidents caused by accidents and human tampering. Cancer isn’t known for spreading naturally. It may be triggered by a carcinogenic chemical, bacteria or a virus, but the actual cancer cells shouldn’t be able to move from host to host like a pathogen. Yet, with the discovery of the clam leukemia’s contagious nature, the number of known exceptions to this commonly-held belief has increased to three.

The other two exceptions belong to dogs and Tasmanian devils, an aggressive species of marsupial found in Australia. For dogs, the tumor cells are physically transmitted during sexual contact where the tearing of genital tissues provide a bridge for the cancer . This condition, called Canine Transmissible Venereal Tumor (CTVT), originated 11,000 years ago from a single dog and has been circulating ever since. With Tasmanian devils, a cancer known as Devil facial tumor (DFT) disease has been spreading as they fight and bite each other’s faces. Having emerged from a single source, this contagious cancer has been completely ravaging the Tas­manian devil population and has ultimately put them on the endangered-species list.

What makes the clam leukemia worrying is that, unlike dogs or Tasmanian devils, this type of cancer is not spread through physical con­tact. Instead, it’s speculated that the clams are drawing in floating cancer cells as they sieve food from the water. It may not be a quick or efficient way for cancer cells to transmit themselves to other hosts, but it’s bound to happen eventually. Goff and his team are already in search of other species that are affected by cancer spread in a similar man­ner. They have already found similar instances in other mollusks in European waters as well as a contagious cancer that affects cockles.

It is terrifying to imagine cancer evolving into a transmissible contagion, especially one that can get into our water supply and cause tumors through contaminated drinking water. However, scientists have relieved fears, stating that no case of cancer naturally transferring to humans has been observed and that transmissible cancers still remain very rare. In addition, natural immunity in humans prevents hu­man-to-human cancer transmissions.

However, what’s worrying is that this scientific revela­tion is just one addition to a growing trend of cases on contagious cancer. In 2013, a man from Medellin, Colombia was diagnosed with can­cer thanks to the spread of cancer cells from a cancer-ridden tapeworm inhabiting the man’s body. On November 2015, scientists study­ing DFT disease found a second type of con­tagious cancer in the Tasmanian devils, mark­ing the discovery of two transmissible cancers within just 30 years.

Whether or not cancer is truly contagious to humans, it’s important to keep track of the progress being made in this field of research. Any development may cause huge shock-waves in the scientific community and prepare us for a grim future ahead. Even if cancer can’t be spread from person to person, researching how tumors are spread in animals can provide more insights on its mechanism and prevention. Whichever direction this research takes, the scientific community should bring more focus on this issue and expand its efforts in finding answers. The idea of contagious cancer may be frightening, but more extensive study could ultimately yield new insights and perhaps even the eternally sought-after cure.

Originally published on March 2, 2016, in The Miscellany NewsResearch reveals implications of clam cancer