India, Novartis, and Australia’s new patent law…

April 1 and about the only thing on the internet that wasn’t a huge Poisson d’Avril was the “landmark” ruling that came from the Indian Supreme Court early on Monday. The result was delivered from a packed room, the two judges probably had to raise their voices to be heard. Poetry to the simple fact that their voices would be heard far and wide, as the story gets echoed through media outlets the world over. Landmark, in legal terms it was — in simple terms it wasn’t. What it really signified was a wake up call for Big Pharma — demonised for putting profits in front of patients (or rather patents in front of patients).

The case will begin a long overdue conversation on access to medicines. More and more we are coming to the conclusion that current models are broken. Or, if not broken, then shifted… biased.

“This is a huge relief for the millions of patients and doctors in developing countries who depend on affordable medicines from India, and for treatment providers like MSF,” said Dr. Unni Karunakara in a press release, MSF’s international president. “The Supreme Court’s decision now makes patents on the medicines that we desperately need less likely. This marks the strongest possible signal to Novartis and other multinational pharmaceutical companies that they should stop seeking to attack the Indian patent law.”

The drug is imatinib, commercially known as Gleevec. Novartis sought a patent for a new formulation — the beta crystalline form of Imatinib Mesylate. In the end, the final verdict was 112 pages long. With the last ten a nice comparison of the differences between the old and new formulations.

“In view of the findings that the patent product, the beta crystalline form of Imatinib Mesylate, fails in both the tests of invention and patentability as provided under clauses (j), (ja) of section 2(1) and section 3(d) respectively, the appeals filed by Novartis AG fail and are dismissed with cost.”

The end of Novartis’ seven year court battle. Indeed the ramifications for patients are important. The case is landmark but in no way unique.

In 2007, Thailand threw caution to the wind in a blatant affront to intellectual property rights and the considerations of pharmaceutical companies. Thailand announced that they would issue what is known as a compulsory licence to manufacture low-cost versions of already patented HIV and heart disease drugs from Sanofi Aventis, Abbott and Merck. A clear violation of international intellectual property rights. In that case, it was a technical legal grey area — exploiting a clause in the 1995 World Trade Organisation agreement on intellectual property that gives governments a large amount of freedom to bypass patents on drugs if they face any kind of health crisis. The question being what constitutes a national health crisis?

Big Pharma appealed, stating the act, although to the letter of the law, was not in the spirit of the law. Argentina and Philippines have already come under criticism for ignoring intellectual property rights. And with a global slowdown of the pharma industry, it is getting harder and harder for companies to chase profits. To put it another way — without the financial rewards that long-term patents offer there are less incentives to develop new medicines. The cost of creating that first pill is now estimated to be US$ 1 billion.

Some might dismiss the violation of intellectual property rights as the devil-may-care actions of rogue emerging states, but more and more the conversation is happening in other nations.

In October of 2012, Australia commissioned an expert panel to review the appropriateness of the extension arrangements for pharmaceutical patents. “In certain circumstances, pharmaceutical patents can be extended by up to five years beyond the normal patent term. These provisions were introduced back in 1998, and are due for review,” said Mark Dreyfus, Parliamentary Secretary for Industry and Innovation.

As a consequence, Australia’s intellectual property system has had its most comprehensive overhaul in two decades. The new law comes into full effect on 15 April 2013. Some call it a set of tough new laws that punish and privilege both sides of the equation — an attempt to “raise the bar.” The new law makes it increasingly difficult to obtain a valid patent, increasing the standards required to receive patent protection.

How the law plays out it still remains to be seen. Indeed, there seems to be a clear intention to curb the rise of “evergreening” by pharmaceutical companies — something that seems to stifle innovation and subsequent competition.

In the end there are no simple solutions in trying to balance profits on access to medicines. Big Pharma will always seek to make new drugs and market them to us. “Novartis most certainly will continue to seek patents for its innovative products in India,” said Ranjit Shahani, vice chairman and managing director of Novartis India. “We believe it is the legitimate way to go. Novartis will be cautious in investing in India especially with regard to introduction of innovative medicines.”

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15 million mobile phones used to track malaria…

We all know that mosquitoes spread malaria. What we never quite realise is that humans also spread malaria — and quite significantly. In some places, the spread of malaria is directly linked to the mass movements of human populations. The movements of infected humans seem to increase the dispersal of parasites beyond what would be possible by mosquitoes alone.

Fifty years ago, when we first tried to eradicate malaria, it failed — and among the main culprits (along with drug resistance and unsustainable funding) was listed movements of human populations. Historically, movements of infected people from areas where malaria was still endemic to areas where the disease had been eradicated led to a resurgence of the disease. As people and populations move, they can increase their risk for acquiring the disease, or increase the risk of transmitting it.

As always wars and civil unrest tend to favour disease transmission, and malaria is no different. During the 1980s in Angola, 15 years of continuous war had displaced hundreds of thousands of people. As a direct result, malaria moved from sixth to first place as the leading cause of mortality. This, simply because the capital city Luanda underwent an unprecedented population increase — and the malaria endemicity rose along with it. In a population that wasn’t ready for it.

The relationship between malaria transmission and population movement is undoubtedly complex. Population movements that either place people at risk for malaria or cause them to pose a risk to others cannot be stopped. But it seems now they can be tracked and we can mitigate for it.

In June of 2008, the movements of approximately 15 million people in Kenya were tracked using their mobile phones. Tracked, not by governments or refugee aid organisations, but tracked by researchers from the Harvard School of Public Health. During a 12 month period, every call or text made by each individual to one of 11,920 cell towers located within the boundaries of 692 settlements was logged and recorded.

Surveillance is a term that loses more and more of its meaning with every single advance in technology. Usually we picture more nefarious intents and purposes for tracking citizens. Within that year in Kenya, starting points and destinations of all 15 million individuals were tracked — giving each person a primary settlement to call home and mapping their movements in relation to malaria prevalence. Researchers determined where each person spent most of their time based on the location of the majority of their call and text records — this was their home base.

Mapping that onto malaria prevalence for the entire country allowed researchers to estimate and infer an individual’s probability of being infected and the probability that visitors to the settlement will become infected. Researchers built up what was essentially a parasite movement network.

There was some directionality to the net movements of people and parasites between settlements. Settlements can either be characterised as “source” or a “sink” — net emitters of people and parasites are sources and net receivers are sinks. As the capital city, Nairobi and its immediate surroundings, become a major destination for both humans and parasites. And from there, two sources of importation of malaria parasites exist. First, individuals visiting endemic areas may become infected during their stay, depending on the malaria endemicity of the destination, and may carry parasites back to their primary settlement. And secondly, infected individuals can carry parasites with them towards other settlements.

In analysing the movements of people within Kenya, researchers discovered that returning residents contribute to some movements of parasites between regions within Lake Victoria and coastal areas. Nairobi imports the largest proportion of infections from returning residents — those infected coming back from journeys to the coast and central Kenya.

It turns out that the structures of the networks of parasite and people movements were remarkably stable over the course of the year. Meaning that elimination efforts can also be robust.

Spatial analysis using maps to associate geographic information with disease can be traced as far back as the 17th century. In this day and age we are able to gather vast amounts of data with relative ease. GPS systems mean it is possible to integrate highly accurate geographic location with virtually any measurable observation — in real time and across multiple measurable observations.

The ease of gathering this much human health-related data points to the question of ownership and confidentiality. Essentially, big data problems.

The idea is that with those vast amounts of data collected, mitigation will be easier — early warnings and detections, hazard preparedness and the like. It is a somewhat new concept in the way we approach global health. Taking into consideration the universal and trying to capture the entire picture. Of course, every intervention is local… but this time it starts out at the global.

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The beat the mosquito’s heart didn’t skip…

It pulsed continuously without stopping. Then it repeated, as it had done many times before. Then, without delay, almost without skipping a beat, it changed direction. The action was as old as man himself, yet this time, completely and uniquely different — the perfect heartbeat. The perfect mosquito heartbeat.

An interesting quirk of nature is how remarkably constant the number of heartbeats exist within a lifetime. An interesting quirk, more a function of the metabolic demands of the animal in question rather than any underlying feature of the heart itself. Humans, mice, insects all have the same number of total heartbeats. The human heart, from life to death, will beat roughly 3 billion times. A mouse will use up its heartbeats in about two years. An elephant, with a much slower heartbeat, will last for much longer. The mosquito’s heart beats at a rate of just over one beat every second (1.3 Hz). In one minute it will beat 82 times, of which, some of that will be in the other direction.

The heartbeat is nothing unique to humans and has been around long before us, but we have romanticised it and given it a meaning more than its basic function. For researchers at Vanderbilt University, Nashville, Tennesee, this is also the case for the mosquito’s heart, where function and meaning is more than its basic, simple architecture.

Dr Julian Hillyer, the lab’s director, and his team have offered the most comprehensive visualisation to date of how the mosquito’s heart beats. They filmed live restrained female Anophelese mosquitoes — the same species of mosquito responsible for life threatening malaria — through a microscope connected to a very sophisticated camera.

The beatings of thirty mosquitoes were collected and analysed frame-by-frame to arrive at a comprehensive structure of the heart. They painstakingly dissected individual mosquitoes, injecting infinitesimally small amounts of fluorescent fluid into them, allowing them to describe the mechanics, directionality and flow involved when the insects blood (hemolymph) is propelled through the heart.

A mosquito’s heart is very different — without veins or arteries, it pumps a clear liquid called hemolymph. The hemolymph flows from the heart into the abdominal cavity and eventually cycles back through the heart. The heart runs along the insects body as an unbranched tube, no thicker than three tenths of a millimeter. Helical twists of muscle fibres support the central tube. Their sequential contractions makes the heart in a wave-like peristaltic action. A peristaltic action that has the ability to run in both directions.

Another set of muscles anchors the heart where ever there is a valve, at intervals, along the mosquito’s body – just underneath its cuticle shell. All of this was visualised in fluorescent detail, using different coloured flourescent dyes to highlight different structures inside the insect’s body. Winning the lab’s images the Nikon Small World photomicrography competition in 2010.

As stunning as the images were, it was the functionality gained from the study that provided the most insight. Following and tracking tiny microscopic particles (microspheres) showed how the insect’s hemolymph entered and was expelled from the heart, and, most importantly, how the heart reverses direction.

Most of the time, the heart pumps the mosquito’s clear hemolymph blood towards the mosquito’s head, but occasionally it reverses direction and pump fluid to the last segment of its abdomen. The direction in which the heart contracts reverses roughly 5 times every minute.

Heartbeat reversal is not unique to the mosquito — a phenomenon that has been observed in other orders of insects. You would think that something that small would have no need for such an elaborate beating system, but perhaps it is the only way the heart can regulate the different hemolymph pressure and volumes entering it. Thus far, a conclusive “why” has eluded researchers.

An insect group that carries malaria, the virus that causes dengue fever, West Nile virus and the lymphatic filariasis causing nematode roundworm Brugia malayi. Mosquitoes represent the most significant pests and disease vectors that transmit deadly human and animal pathogens.

The insect heart is the gateway to the insect’s circulatory system and to understanding the interaction between the insect and its pathogens. Dr Julian Hillyer and his team have turned their efforts to the mosquito’s immune system, hoping to understand the process in which pathogens migrate through the mosquito’s body cavity and the mosquito’s own immune system response against them during their journey to their mouthparts — the point of entry relevant to human disease.

Certainly, a better understanding of its biology will be needed to contribute to the development of novel pest and disease control strategies as diminishing efficacy of current control methods continue to cause problems. A increasing realisation that tackling the disease before it gets into man is a worthwhile effort and becoming more and more a viable option.

King, J., & Hillyer, J. (2012). Infection-Induced Interaction between the Mosquito Circulatory and Immune Systems PLoS Pathogens, 8 (11) DOI: 10.1371/journal.ppat.1003058

Andereck JW, King JG, & Hillyer JF (2010). Contraction of the ventral abdomen potentiates extracardiac retrograde hemolymph propulsion in the mosquito hemocoel. PloS one, 5 (9) PMID: 20886066

Not all clicks are created equally…

The other week I did a guest blog post over at Scientific American. It was essentially about my thoughts on how to write to your own particular brand of sensibilities — your niche. The day of being a generalist science writer has probably already come and gone. And besides, the way science communication has evolved, we shall see more and more experts take to the proverbial airwaves — not only as advocates for their science but as genuine great science communicators.

“The internet has been the great democratiser of just about everything we can think of. But perhaps news, journalism, and writing were the ones to fall furthest and from the greatest height when the playing field was levelled. In this information age, we are now forced to become digital natives. Everything has to be framed for the Internet—search engine optimization, 140 characters, and all. While in the “good old days” of print, journalists and writers competed for the frontpage, now they compete for clicks. The more eyeballs, the better. In order to adequately communicate science online, one must acknowledge this situation before attempting to do something about it.”

And thanks to Khalil over at SciAm’s Incubator Blog.

The Contagion of Violence…

When Professor Plum killed Dr Black, in the library, with the candlestick it was for no other reason than murder is a disease. Murder is infectious and the contagion of violence is everywhere.

Violence begets violence.Violence within nations and cultures. It occurs within families and between partners. It increases the risk of violence directed at children and increases the risk of the children behaving violently themselves. Violence within a community perpetuates and spreads. Children catch it from their parents, and parents can catch it from their children. Violence is highly contagious in all respects it seems.

It was a 2012 essay by L. Rowell Huesmann that sparked off a study, appearing in Justice Quarterly. A study with a simple premise and question; if homicide is infectious, it should diffuse through communities, infecting those susceptible, and that diffusion should be detectable. Much in the same way we can track the flu from year to year, we can track the spread of murder as an epidemic. It offers an interesting way of looking at murder and homicide.

Welcome to Newark, New Jersey. A city that houses roughly 277,000 people has a homicide and murder rate over three times greater than that of anywhere else in the US. There were 104 murders and 504 shooting victims in 2006 alone. Firearms were used in 71% of the 380 reported murders in 2011. Suffice it to say, Newark is not a safe place.

The study took a look at how murders and homicides moved and behaved over a 26-year period (1982 to 2008) across the city. Firearms and gangs were the infectious agents; spreading from within the centre of the city and spreading south-westerly over the course of nearly three decades.

Their main argument is that the way murders move across a community is not random. The elements required for disease to propagate itself may be relevant and can be applied to the movement of homicide. And if this is so, then it can be predicted and controlled.

If you take a look at a map of Newark it is hard to see a pattern. Homicides occurred in all parts of the city. Almost the entire city appears to be a hot spot for murder. But analysis over the decades suggest that there was expansion of overall homicides between 1982 and 2008 with a dip in 1997 and a sharp rise in 2000. And highlighted an area of the city (North and East) that seemed largely immune to the spread of homicide. Indeed, murder was on the move.

The criminal justice system seeks to prevent murder, but only after the fact — by deterring those that do it with the penalty that awaits them after the fact (jail and criminal prosecution). Indeed, police forces already have an eye out for certain hotspots within a location. Areas where violence is known to spark and ignite at any given moment. What they don’t know is where it will go next. The authors of the study model homicide as an infectious disease as simply a way to offer instructive understanding of how homicide works. The most telling application of this non-literal model is the fact that for homicide to spread as a disease, a population susceptible to transmission must be present. Just like every other infectious agent, except this time poverty and social inequality replace a population with no herd immunity.

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Zeoli, A., Pizarro, J., Grady, S., & Melde, C. (2012). Homicide as Infectious Disease: Using Public Health Methods to Investigate the Diffusion of Homicide Justice Quarterly, 1-24 DOI: 10.1080/07418825.2012.732100