It is estimated that over one billion people suffer from neurological illness. But despite increased awareness and decreased social stigma around neurological disease and mental illness, effective treatment options are often lacking. They can involve anything from basic lifestyle changes to going under the knife to electric shock therapy. But by far the most popular treatment is to medicate, medicate, medicate.

Each year, pharmaceutical companies spend billions of dollars on drug development for neurological disorders. The time and energy required to go from an initial “drug blueprint” to worldwide distribution can be immense. One of the most time-consuming steps in the process is testing and understanding the effects of a drug. Many other disciplines use model systems to test cause-and-effect relationships, so why don’t neurologists just pump drug prototypes into a mockup of the human brain? The answer: one doesn’t exist. Yet.

The “lab rat” of the human brain project — literally

In 2005, the Swiss Brain and Mind Institute (SBMI) began creating a complete model of the mammalian brain using lab rats. Dubbed the Blue Brain Project, they’ve made impressive headway: in 2006 they produced a man-made cortical column of 10,000 neurons—a brainy start, to say the least!

Although a rat brain is no substitute for a human brain, it has taught us a bunch about how mammalian brains work and how to get brain projects up and rolling. Unfortunately, scientists can’t run drug simulations on the rat brain model. This may seem surprising given that the rat and human genomes are very similar, but small genetic changes can have major impacts in drug response.

The Real Deal: The Human Brain Project

More recently, scientists have tried to model our own noggins. In the beginning of 2014, over 300 researchers assembled in Lausanne, Switzerland, and put their heads together and came up with a plan to map the entire human brain. This model is entirely computer-based, made up of a network of computers and servers that will be accessible online by researchers from around the world. Using everything from traditional MRI imaging and cadaver autopsies to more advanced computing and predictive modeling, the team hopes to have a complete working model of the human brain within two decades. Keep in mind that the Human Genome Project was forecasted to take half a century, but was completed in less than twenty-five years.

The project has, however, been running low on energy—it takes about 20 gigawatts of power to run the necessary equipment (about ten times the amount of energy needed to power New York City). To deal with these energy demands, the team is collaborating with IBM and Intel to create the first exascale computing machines, which should be ready by 2020—the estimated start-date of digital analysis. Additionally, cutting edge storage technologies are being examined, such as saving project data in the form of DNA—using the As, Ts, Gs, and Cs in the place of the binary “0s and 1s”. This effectively increases the “alphabet” of data, resulting in more stable and compact storage options. If anything, the Human Brain Project is stirring up interest in these emerging technologies.

What does this mean for us?

It’s still not known whether a human brain model will be accurate or sophisticated enough for drug testing. But there’s little doubt that the model will help in the primary treatment of neurological and psychological illnesses and speed up and reduce the cost of drug discovery. The model will allow researchers to find “biological signatures” — little quirks about neuron firing patterns — which will provide clues to the causes of many diseases. From there it’s only a matter of creating a drug that helps revert damaged areas, boost healthy brain activity, or a mix of the two.

What’s more, the creation of a simulated human brain could be transcribed and used as the foundation for the next generation of artificial intelligence. These so-called neuromorphic systems, although purely theoretical at present, are thought to be more efficient and intuitive than traditional artificial intelligence. Terminator-style self-awareness aside, the potential of using this technology for robots or back-end chips is enormous.

The Human Brain Project isn’t limited to medicine and science. Its completion could also result in an expansion of knowledge in the field of ethics. It might provide unprecedented insights into emotion, thought, personality, and memory. In fact, completion of the project could challenge our personal perceptions of freewill and identity.

Of course, there is strong possibility that this whole project will fail, becoming one big brain fart. The team could easily run into difficulties with funding or processing power, but that’s always a risk when doing “Big Science”. However, if the Human Brain Project does pull through, the findings will likely give us all something to think about.

Digging up bones for DNA
Although researchers cannot directly study deadly bacteria that existed thousands of years ago, they can unearth and study the remains of victims of age-old bacterial outbreaks. The scientists who do this type of work (called paleopathologists) are able to sequence the bacterial genes preserved within human bones and teeth. Analyses of ancient microbial DNA are providing crucial information about the origins and evolution of lethal human bacteria, and are changing our view of some of most devastating pandemics in history, such as the Black Death.

How old is the plague?
In the past two thousand years there have been three well-documented outbreaks of the bubonic plague: the Plague of Justinian (6th century), the Black Death (14th century), and the so-called “third plague pandemic” (19th and 20th centuries). Yersinia pestis is the causative agent – the bacterial bad guy – in all three of these pandemics, but there’s been some debate as to whether or not the Justinian Plague and the Black Death came from the same strain of Y. pestis. In other words, are they different pests or the same pestis?

Researchers recently studied two 1,500-year old skeletons in Germany, from a cemetery that is home to victims of the Plague of Justinian. Y. pestis DNA was sequenced from the skeletons and the analysis showed that the strain of the bacterium present in the 6th century (during the Plague of Justinian) differs from the strain that caused the Black Death. The fact that different strains caused these two pandemics, suggests that new deadly strains could emerge in the future.

Despite a long and sordid history of killing large numbers of people, Y. pestis is neither the oldest nor the most deadly human pathogen; that award just might belong to Mycobacterium tuberculosis, which, as the name implies, causes tuberculosis.

Is tuberculosis our oldest enemy?
Tuberculosis, which is caused by M. tuberculosis, is a disease that primarily affects the lungs, although other parts of the body can also be infected. Despite the potential to be fatal, most infections are asymptomatic, resulting in a latent form of tuberculosis. Of these infections, about 10% will eventually progress into an active, and potentially deadly form of the disease.

In 2008, paleopathologists studied 9,000-year old skeletons exhumed from an abandoned village in Israel. The researchers were amazed to see signs of tuberculosis on the skeletons (lesions on the bones) and were ultimately able to identify tuberculosis DNA within the remains. This indicates that tuberculosis has been active for 9,000 years – and it continues to infect new individuals daily. But does that mean it is the oldest human-specific pathogen? Although nine millennia is a long run for any disease, the bacteria that cause leprosy (Mycobacterium leprae and Mycobacterium lepromatosis) may be even older.

What is leprosy?
Leprosy causes a loss of feeling on the surface of your skin, the severity of which varies depending on the number of M. leprae or M. lepromatosis bacteria in the body. Feeling no pain may not sound too bad, but it can lead to reoccurring accidental injuries – burning, cutting, bruising, etc. – eventually causing permanent disfigurement. Today, the majority of the world’s population is immune to leprosy, but the disease was highly prevalent in Europe up until the 16th century, when infection rates suddenly dropped. Although M. leprae and M. lepromatosis were not discovered until 1873 and 2008, respectively, there have been accounts of the disease over the millennia. Most historical documentation shows a stigmatization of leprosy, with lepers being ostracized and isolated from the general population.

The age of leprosy
The age of an organism is often difficult to determine, but new research managed to identify the DNA of skeletons and used genetic techniques to figure out additional information. By studying the genes of leprosy-causing bacteria trapped in human remains, scientists estimate that a leprosy-causing ancestor existed as far back as 20 million years ago, and the DNA hasn’t significantly changed in comparison to modern strains. Unlike tuberculosis, where evidence only dates back 9,000 years, leprosy was infecting the early ancestors of modern humans, making it the oldest infection discovered thus far. But why did the leprosy rates suddenly decline in the 16th century?

How we adapted to beat leprosy
Humans – their genome and immune system – change over time. In the present day population, 95% of people are immune to leprosy and numerous changes in our DNA have resulted in genes that contribute resistance to leprosy. The burden of this disease over the years has induced mutations on the human race, and it’s likely that this genetic selection is what accounts for the sudden drop in leprosy rates in Europe. With leprosy-resistant mutations on our side, most people in the world will never have to worry about getting hauled off to a leper colony anytime soon.

With the looming age of antibiotic-resistant bacteria and other infections, it’s easy to understand why we fear these ancient microbes. Many concerning reports have recently surfaced about the Ebola virus, MERS in the Middle East, and MRSA in our hospitals, but we don’t hear often enough about the victories on the microbiological battlefield. The World Health Organization is committed to increasing access to medication. Hygienic practices are being improved and regulated on a larger scale. It’s no longer common to see rodents infesting urban streets. Although there are many dangers out there, we have made so many advances that our oldest parasites – causing the plague, tuberculosis, and leprosy – might just have to find some other hosts.

Tirthankar Ray is a third-year undergraduate in Biology and Microbiology and Immunology at Western University. He attended the 2013/14 fall-semester biology seminar series as a science communications project with Dr. David Smith from the Biology Department. David Smith is an assistant professor in the Biology Department at Western University. You can find him online at www.arrogantgenome.com and @arrogantgenome.