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

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

Losing Our Last Resort: The Rise of Antibiotic-Resistant Bacteria

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Picture Credit: Bubonic Plague Bacteria | The National Library of Medicine

As we head into 2016, we have much to feel grateful for in this modern age. Technological marvels such as computers and high-speed Internet define an era of advancement that has exponentially sped up our society’s growth and capabilities. But amidst this impressive and fast-paced development, one crucial feature of humankind’s modern society is perilously close to collapsing. Of the many things we take for granted in the 21st century, protection against bacteria probably ranks the highest in terms of human impact. Of course, given our track record against such killer pathogens, this shouldn’t come as much of a surprise. Our species has lost repeatedly to plagues and disease since the start of human history. Pathogens such as bacteria, viruses, and other microorganisms are our oldest enemy.

When it comes to fatal illnesses, a large portion of human history was spent without an adequate solution. In Europe, terrors such as the Bubonic Plague brought death to every door and we had no way of fighting back. It wasn’t until 1796 that our first real counterattack came with the invention of vaccines by English physician Edward Jenner. About 120 years later, Scottish biologist Alexander Fleming discovered penicillin, a powerful antibiotic produced by the blue Penicillium fungi, cementing our defenses against the pathogens and saving millions of lives.

But the bad news is that we only thought we vanquished our invisible adversaries. In fact, they have only gotten stronger. You see, microorganisms like bacteria are not like fearsome monsters that disappear once you slay them. They’re much tinier, but there are so many of them that they are almost impossible to completely eradicate. And thanks to evolution, the ones that survive due to some bizarre mutation multiply uncontrollably until we’re faced with an upgraded version of our old foe. Every time this has happened in the past, scientists have responded with stronger, more toxic antibiotics, which deadly bacteria eventually thwart. Thus, advancements in antibiotics have always led to more resistant bacterial strains with new ways to survive, causing an endless microbiological arms race that’s becoming more tenacious with each cycle.

So, how long until our microbial enemies catch up to our highly sophisticated, advanced medicine? A hundred years? Two hundred? Actually, they already have. In a recent study conducted this year, a team of experts in China discovered strains of E.coli bacteria in livestock that could not be killed by antibiotics. Normal, right? Except the antibiotics in question were polymyxins, a class of antibiotics that have remained effective for the past sixty years since its discovery. These drugs represent the most potent of our arsenal against bacterial infections, our “last resort,” and they have proven to be useless against this new, impervious strand.

Upon further investigation, the team identified the gene responsible as MCR-1. Unfortunately, they also found this gene in 15% of the meat samples from food markets and 21% of livestock in Southern China over the span of four years. Even worse, the E.coli with this gene has already moved onto humans. Of the 1,322 samples from patients with bacterial infections, 16 of them had the MCR-1 gene.

According to Mark Woolhouse, a Professor of Infectious Disease Epidemiology at the University of Edinburgh, infections from antibiotic-resistant bacteria are already causing the deaths of tens of thousands of people every year. Taking the spread of the MCR-1 gene into consideration, that number will surely increase in the future. This could very well start an era of “pandrug-resistant” bacteria or, as some others have called it, the “antibiotic apocalypse.”

But how did this become such a widespread problem so quickly? It turns out that the MCR-1 gene is found on plasmids, a mobile form of DNA that can jump from one organism to another. Therefore, bacteria can easily spread this gene to other bacteria through a process called horizontal gene transfer, which is the primary reason why antibiotic resistance is a problem in the first place. This is an awfully serious development since bugs like E.coli are “the most common form of hospital-acquired infection.” Scientists worry that there may soon come a time when more patients become ill from bacterial infections and doctors won’t be able to do a thing about it.

To emphasize, this isn’t just some isolated, freak incident. A study from 2011 similarly found that the number of cases involving bacteria resistant to carbapenems, one of strongest type of antibiotics in our possession, has increased dramatically from just 3 cases in 2003 to 333 cases in 2010. That’s an increase of over 11,000% in just 7 years.

Experts have been worrying about this day since they realized bacteria could adapt to penicillin. Sure, scientists can just make a new, even stronger antibiotic, but unfortunately, we have long since passed the age of rapid antibiotic development — in fact, we’ve fallen several decades behind. In truth, our advancement in medicine has been steadily slowing down to a plateau, and bacteria have finally caught up and passed us.

It is rather ironic that this terrible news came in the middle of the first World Antibiotic Awareness Week. Just when this global campaign was trying to raise awareness and encourage strict regulations on antibiotics, this study further shows the urgency of the situation. But as much as this crisis seemed inevitable, it really wasn’t. Just as in any story with a moral, we essentially did this to ourselves. Almost every one of us contributed to this situation without even being aware of it. Because you see, the main reason why everything spiraled out of control was because of our love of meat.

It turns out that we have been using antibiotics beyond recklessly in the agriculture industry. According to reports, farmers around the world feed 63,000 tonnes of antibiotics to pigs, cattle, and chicken every year. That number is estimated to grow by 67% to 106,000 tonnes by 2030. That’s right: we have been feeding humanity’s most powerful antibiotics, our last resort against disease, into the mouths of livestock by the truckload. This is because people all over the world have been growing more prosperous in recent years, causing them to buy more meat products. According to the UN Food and Agriculture Organization (FAO), people in developing countries “now eat 50 per cent more meat per person, on average, than they did in 1983.” Livestock– including fish as well as eggs and dairy since they also come from livestock– has become a fast-growing market that we no longer can live without or get enough of.

Thanks to skyrocketing demand, quick and efficient factory farms have become the norm. In order to keep the animals alive and fat, these farms feed them high doses of antibiotics. A whopping 80% of antibiotics consumed in the United States go towards livestock and America is only in second place. On the list of excessive antibiotics use, China is the worst offender, consuming 50% more than the U.S. with a total of 15,000 tonnes per year, and that number is projected to double by 2030. India, Brazil, Indonesia, and Nigeria are all showing a worrisome upward trend in antibiotic use as well.

Even if countries started banning the use of antibiotics as growth promoters in livestock, it’s too late to preserve antibiotics that already exist. Epidemiologists compare that to “closing the barn door after the horse has bolted.” By the time resistant bacteria are multiplying in humans (which they are), the problem is way beyond the control of farmers.

There are other contributors to this problem besides livestock. Any unnecessary use of antibiotics only serves to further tip the scale in favor of deadly bacteria. Careless use of antibiotics to treat colds and the flu contribute to antibiotic resistance, since those sicknesses are caused solely by viruses, not bacteria. Overall, it seems lack of knowledge is the biggest factor in all this. A report by the World Health Organization (WHO) showed that 64% of everyday people who thought they knew about antibiotic resistance believed that antibiotics could be used for colds and the flu.

However, our doom isn’t quite sealed yet. Despite the grim forecast, experts still say that rigorously limiting the use of antibiotics could help greatly. The US Food and Drug Administration states that while banning antibiotics in animals may not stop all resistant strains, it can prevent bacterial infections like Salmonella, which sometimes infects meat, eggs, and dairy, from reaching the same danger levels. Additionally, the U.S. Centers for Disease Control and Prevention advise people to take their antibiotics exactly as the doctor prescribes them, to never share leftover antibiotics, and to not ask for antibiotics if the doctor doesn’t think they’re necessary.

While the situation does look bleak now, it still holds more hope than it did before the creation of vaccines and penicillin. Unlike before, we have weapons and defenses that stand a chance against one of the most powerful forces of nature. Under a united effort, humankind can still achieve a turnabout of miraculous proportions.

Originally published on January 28, 2016, in Boilerplate Magazine: Losing Our Last Resort

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