Cities have long been considered part of the problem. They were supposed to be dirty and unnatural places to live, rife with violence and misery. In an age increasingly concerned with wellbeing and environment protection, cities seemed to epitomize the evil of human development. This perception in turn was translated into a series of famous 20^th-century antiurban policies: cheap gas, highway subsidies, tax incentives for home ownership, etc.

However, what’s the evidence for such antiurban bias? Not much. Indeed, researchers affiliated with the Santa Fe Institute argue that cities, far from being the evils long depicted, are actually the most efficient and productive way of organizing human population, inasmuch as they are characterized by superlinear scaling of socio-economic properties combined with sublinear scaling of resource use. This means that, if the population of a city is doubled, measures such as wages and patents produced per capita witness an average increase of around 15% (greater productivity), while at the same time its material infrastructure –such as the number of gas stations or the total length of its pipes, roads or electrical wires– is 15% lower than two cities of half the size (greater efficiency). As they get bigger, cities thus reduce their carbon footprint and generate disproportionate wealth.

Density is the key factor in explaining why cities use less energy. “There are clear environmental benefits in high density and in reducing urban sprawl by bringing spaces for living and working together within a single, compact footprint”, argues Norman Foster in a recent special report on cities for Scientific American. Moreover, urbanites rely less on personal cars, walk more and use public transports, resulting in an average much more energy-efficient mobility. This, combined with the fact that heavy industry is generally situated out of urban centres, explains why cities are characterized by the lowest carbon dioxide emission per capita.

Why Cities Are Smarter 

Although the “greater productivity” argument could as well be due to selection effects (richer and/or smarter people tend to go to cities) as to true value creation (concentrating people in cities indeed creates value), there is evidence that the latter effect is important. Indeed, average wage is more than five times higher in highly urbanized countries than in countries where the population still lives mostly in the countryside. Moreover, there seems to be evidence that the concentration of people in cities leads to a smarter aggregate, generating more inventions and creating more opportunities for economic growth.

This is mainly because the population density achieved by cities ensures an easy interchange of ideas leading to innovation. “Cities deliver the random exchanges of insight that generate new ideas for solving the most intransigent problems”, argues Edward Glaeser, Professor of economics at Harvard University. Such creative inspiration can result only from face-to-face contact with others. As Richard Florida, Professor in urban studies at the University of Toronto, puts it, “Great thinkers, artists, and entrepreneurs—what I call the creative class—rarely come out of nowhere. They cluster and thrive in places where the conversation and culture are the most stimulating.” He adds that all along the history of mankind, “cultural development and technological development have been closely linked to rising population density.”  The examples in history are not only famous but also numerous: from the Greek cities to the power of Rome, from the development of the modern economy in medieval cities of northern Europe to the development of Renaissance art in Italian Quatroccento metropolises. The first industrial revolution was also mainly driven by the rise of cities due to overpopulation in the rural areas.   

When population density increases and when an increasing share of the economy is knowledge-based, social skills –encompassing leadership, persuasion, team building and empathy– become one of the most important skill sets. In turn, this means that, as economic development continues, increased connectivity and highly developed sociability, not fear of chance encounters with strangers, will be driving cities ever more.

Wise Policy For Cities 

If a disproportionate share of wealth is created in cities, public authorities should favour policies that encourage people to live in the city while promoting the skills necessary to thrive in an urban environment. Although there hardly is a blueprint for urban success, which is highly intangible and very difficult to reproduce, the following high-level policies should help beget success.

• Attract people in the city

To attract people in the city, it is important to increase the supply of middle- and low-income apartments in city centres. Along with providing more housing space, raising gas taxes and putting in place congestion pricing around the city will help reduce significantly both pollution and waiting time. Finally, in order to increase the efficiency of urban structures (utilities, buildings and houses), public policies should incentivize retrofitting, i.e. the addition of new technology or features to existing structures (such as photovoltaic sheets on façades or waterworks leaks control).

• Endow them with the skills necessary to thrive

Improving structures is fine, but bringing more people to the city will fail to generate benefits if we are not providing them with the skills set that will enable them to be sufficiently productive/innovative so as to afford the high rents characterizing cities. Hence, public policies should ensure a strong support for education and foster the spirit of entrepreneurship. Indeed, “proxies for entrepreneurial energy, such as the share of employment in start-ups and the average firm size, correlate with successful urban reinvention”, says Edward Glaeser. Incentivizing entrepreneurship among university graduates is also key. “Active companies founded by MIT graduates generate annual revenues of about $2 trillion, roughly equal to the GDP of Brazil”, according to Michael Bloomberg, Mayor of New York City, in a recent guest article in the Scientific American. Entrepreneurship is also what most perfectly embodies the application of enhanced social skills –which we identified as one of the most important skills in cities of growing density.

The Rise Of The Cities 

Cities are bound to become important units of power and even of sovereignty in the future. In the course of the 20^th century, average city size has been multiplied by ten. Around 2008, for the first time in history, more people inhabited the world’s cities, which are expected to grow even bigger in the decades to come: two in three people born in the next 30 years will live in cities, and worldwide roughly one million people move to urban centres every week.

Moreover, cities may be inherently fitter to thrive in a globalized world and more democratically governable than whole nation states. Indeed, for instance there are signs that cities are in a better position to tackle global challenges such as climate change, as evidenced by the global alliance C40 –a network of the world’s largest cities “committed to implementing sustainable climate-related policies locally to help address concerns globally”.

Cancer, as one of humanity’s greatest killer, is an important part of our civilisation. Indeed, the WHO identifies cancer as “a leading cause of death worldwide: it accounted for 7.9 million deaths (around 13% of all deaths) in 2007.” As such it ranks as the second cause of death in high-income countries. And Cancer’s casualties are projected to continue rising, reaching 12 million deaths by 2030. Crossing Cancer’s path long meant extremely rapid, degrading, painful and inexorable death. Indeed, history before modern medicine never provided any evidence of anyone ever breaking free from its chains.

How did this killer without par, after having been almost completely absent from much of humanity’s recorded history, come to grab the limelight in modern times? Is it because it is a “fundamentally modern” illness (whatever that means) as some have ventured to say? Is cancer a reaction to “modernity lifestyle”? Indeed it even seemed to actually bear the traits of modernity: cancer is an illness of excess (cells dividing out of control) and mobility (metastasis).

Well, no. It’s not due to some superficial affinity with modern lifestyle that Cancer developed into the number 1 public enemy and that the number of its victims started to shoot up. It’s because cancer is an age-related disease, that is, the risk of getting it increases with age. And as in most ancient societies people quickly succumbed to some other disease now mostly eradicated (at least in rich countries), they rarely managed to live long enough to get cancer. Therefore, the single most important reason for cancer's pre-eminence today is the progress in longevity and the fact that we already killed most of man's other killers.  

That such a ghastly murderer might be still walking free today, sowing blood and tears and imposing such an unbearable burden on humankind is just revolting. Fortunately, while Cancer steadily increased its number of victims during the 20^th century, men started to organize and develop a Resistance, called “Modern Medicine”. Since then it has been investigating and mobilizing resources to try to identify the elusive culprit and put him under arrest. However, whenever we thought we had finally laid our hands on him, he always managed to outsmart us and slip through our fingers. Nevertheless, thanks to our patient determination, we have been able to learn a lot about humanity’s most wanted enemy and we might just be getting closer to the tipping point where Cancer might start to lose the fight.

What follows is the story of Cancer’s profiling. A tale of human heroism, strategic war-planning and collaboration.

ANTIQUE CANCER: PRIMITIVE KNOWLEDGE OF CANCER AND HOW IT WAS DEMISED

Although Cancer has been most active since the last century, it doesn’t mean it didn’t exist before. Antique physicians already noticed its dirty crimes. The first real attempt at profiling Cancer –or attempt at a “theory of Cancer”– is due to the famous Roman physician Galen of Pergamon –in turn inspired by Hippocrates’ theory that the human body was composed of four fundamental “humours”: blood, yellow bile, phlegm, and black bile, whose combination and balance regulated the proper functioning of the human body. This theory, which back then and for a very long time reigned supreme, holds that any malady results from the excess or deficit of one of these humours (this is the basis for the famous therapeutic saignées operated by physicians until not such a distant past). Based on this framework, Galen advanced the theory that cancer was actually the effect of a dispersion of the black bile, pretty much like an internal overdose of black bile. It would thus spread out and then erupt in tumours. In this context, surgical intervention to extract tumours (which would seem natural for an uneducated person) was considered useless or foolish by established physicians. For them, there was nothing much to do but to let it bleed.

This situation, however, started changing when Vesalius came by in the 16^th century. He had this peculiar drive that has characterized many paradigm-shifts in history: he wanted to see with his own eyes –rather than readily accept the common wisdom. So he embarked on the task of mapping the human anatomy. Dissecting and cutting through viscera, pulling here, uncovering there, he slowly charted our vast internal territory. You might think that would be the most sensible thing to do for a physician but nobody before Vesalius ever bothered to do it… And after all his exploration, he could not find a single trace of that notorious black bile –that indefinite substance that supposedly throws people into melancholia. Nor did he stumble upon any humour wandering about. He did find blood in vessels indeed; and a pale watery fluid in the lymphatic system; and some yellow bile in the liver; – but the black bile was nowhere to be found. This threw in the first serious doubts that would start to shake Galen’s theory, which had been accepted for centuries.

Even when focusing autopsies on abnormal cadavers, stacked with tumours, Vesalius’ epigones could find no trace of the black bile. So the “divine Galen” was proven wrong after all. Fortunately, discarding this theory of the humours actually acted as a great catalyst and freed up many doctors that used to be entrenched in the straitjacket of this model. Now they had free license to find a new cure rather than simply bloodletting; now they could actually try to do something. Act.

SURGERY: A RAW FIREPOWER AGAINST CANCER

Of course the first natural thing to think of doing when faced with a tumour is to try to excise it. Indeed, since one of the main characteristics of cancer was to start local and only later going global, the natural deduction was to cut it off as soon as possible. Surgery was back in favour. However, back then surgery was still a very dangerous enterprise: it was painful and often lethal. What eventually made surgery possible on a large scale was the advent of the two greatest inventions the second part of the 19^th century gave to medicine: anaesthesia –the relief of the pain–, and antisepsis –the prevention of infection.

Antisepsis was conceived by Joseph Lister, a Scottish physician inspired by Pasteur’s work on the turbidity of meat. Pasteur had indeed shown that the degradation of meat was due to the growth of bacterial life. Hence Lister thought: what’s the difference between meat and wounded human flesh exposed to the air? In consequence, to avoid the risk of infecting the flesh when practicing surgery, he went out to look for some antibacterial process. And then one day, observing that sewage disposers used some liquid containing carbolic acid to cleanse their waste, he thought: why not apply this to post-surgery wounds? And it worked!

Armed with these two technological advances, surgeons, long perceived as mere butchers, found a new legitimacy and kind of became the stars of the show. Bolstered by early successes, they quickly discovered that cancer was a moving disease, sowing tumours here and there, and that one was never sure whether the seed had been taken off altogether or whether it had been left behind to start growing again. So surgeons entered a cat-and-mouse play with cancer, cutting here and there, and getting ever more radical by the day. In particular, in the case of breast cancer, they got nearly fanatical in their desire to extract the evil from women’s breasts, and ended up inventing the “radical mastectomy”, which basically consisted in cutting to the bone, to ensure no evil seed was left.

Such radical surgery actually evolved into a collective obsession of the physician profession and a kind of religious fervour started to ensconce the practice. Based on the idea that cancer somehow spread centrifugally from its locus of origin, the principle was to cut its progress short as radically as anatomy could permit. In a macabre sadomasochistic dance, surgeons had a kind of guru status and patients were eager to anatomically eradicate the evil within: assuming more cuts meant greater security against relapse, they were willing to undergo radical mastectomy, even though the underlying theory was never actually put to test. As a result, countless women were horribly disfigured for, it turned out, nothing. Indeed, it took scrupulously controlled trials in the 1950s to establish that more surgery did not lead to more cures.

THE HUMAN BODY AS A SUM OF CELLS AND WHAT IT MEANS FOR CANCER

Meanwhile, at the interface between 19^th and 20^th century, the conception of the human body, with the help of increasingly powerful microscopes, evolved into that of a sum of molecules and of cells, which grow, multiply and get renewed. Within this new paradigm, if there was a problem, it was first framed as a molecular-level problem. Such change in perspective could lead to powerful discoveries. For instance, all we knew about leukaemia at the time was the basic symptom of a sudden burst of pus –but with no stigmata or infection. When it was found out that this “spontaneous suppuration” was actually due to the overproduction of white blood cells, which were created in factories situated in the bone marrow and the spleen, there was a shift in how scientists approached cancer. The key to understanding cancer seemed to lie in how cells behave, grow and multiply. So people started to classify the evolution of cells and in particular distinguished between hypertrophy (growth of the size of a single cell) and hyperplasia (growth of the number of cells). Leukaemia was thus pathological hyperplasia of white blood cells.

More generally, whatever Cancer’s actual impersonation (blood cancer, breast cancer, uterus cancer, and so on), the principle stays the same: Cancer is a sorcerer throwing a spell on a certain type of cell, which drives them to pathological hyperplasia. 

Endowed with this new knowledge, scientists could, among other things, start to better appreciate why Marie Curie was losing her nails, hair and skin after her life-long proximity with X-rays-emitting material. Knowing that X-rays attack DNA molecules by hacking their division, they also found that they primarily target rapidly dividing cells. That’s why Madame Curie had her nails bitten –because nails grow fast. This discovery did not let people sit idle as everybody was quick to grasp the application for a potential new cure for cancer, typically characterised by the growth of rapidly dividing cancer cells. It was not long before X-ray shotguns targeted at cancer saw the day. After the scalpel, this was the second weapon devised to counter-attack the fearsome enemy. 

However, whatever the early successes and medical capability of these weapons, cancer always ended up reappearing. For a few months the surgical or radiant treatment seemed to have worked wonders, but then patients always eventually relapsed and Cancer was back –often with a vengeance. How did he always manage to escape?

The trouble is, while cancer starts concentrated in one place, it quickly spreads about through furious cell division, gaining ability to travel around and adapt to other places in the body. Indeed, cancer is fundamentally a systemic illness. From the time it is diagnosed, it has already irreversibly spread out (“metastasized”). No local treatment can definitely cure it –except for really early diagnoses.

CURING A SYSTEMIC DISEASE: THE RISE OF CHEMOTHERAPY 

If cancer is a systemic disease, what about systemic treatments? In the wake of the pursuit of a systemic treatment, yet another great –perhaps the greatest– discovery of medicine grabs the centre of the stage: specific affinity. This is the idea that a chemical does not necessarily interact indiscriminately with any molecule to be found in the body, but only with those with which it has “affinity” –and such an affinity is often an affinity of form. Picture these molecules as a vast mix of keys and locks and biology as great mix-and-match game. Sometimes keys and locks “bind” together, and the molecules “click”. Among other things, such bindings may “de-activate” the molecules.

This discovery is the result of the convergence of two trends at the dawn of the 20^th century: the multiplication of the number of synthetic chemicals when the Industrial Revolution reached the dyeing industry, and the idea that organic chemicals and inorganic chemicals were essentially the same (i.e., biology is chemistry), which was in the air at least since Wöhler’s synthesis of urea in 1828. The explosion in the variety of forms and structures in synthetic chemicals was bound to lead to the discovery of useful new properties: there lay a vast number of keys that may find locks in our bodies. The rise of synthetic chemistry and the realization that biological processes were actually chemical processes suddenly led entrepreneurs and scientists to embark on a race to find synthetic chemicals with a useful action on biological entities –what is today commonly referred to as “drugs”. This in a nutshell was the basis for today’s multibillion-dollar pharma business.

Such drugs are “systemic” in the sense that, wherever one injects them, they will travel around the body and only interact with specific molecules or cells. That’s where the name “chemotherapy” comes from: it simply means “curing with chemicals”, and it is the third great firepower against cancer, after surgery and X-rays.

The discovery of the first chemotherapeutic drugs against cancer was surrounded with serendipity. During First World War, toxic gases were used by Germans as a weapon –so-called “mustard gas” (because it smelled like mustard)– in the trenches. Subsequent studies on wounded soldiers to understand how these gases affected health showed that the mustard gas primarily attacks white blood cells and the bone marrow –the factory of white blood cells, known to reproduce themselves fairly rapidly. Later on, when other researchers would consult these war-time studies, they thought: if the mustard gas selectively kills white blood cells and since leukaemia is death from overproduction of white blood cells, then why not distil in reasonable doses that mustard gas or a similar drug? That’s the principle of chemotherapy: to pump poisons into the body in order to kill cancer cells. As we can see, the powerful idea of discrimination that is behind chemical medicine (the fact that different molecules –different “keys”– get different locks) does not only operate on form but also on other properties of cells –for instance, their rate of division. Just like X-rays actually. This, of course, is very fortunate, as it would be impossible to discriminate between normal cells and cancerous cells solely on the basis of form, inasmuch as one major trait of cancer is that it consists in normal cells being high-jacked. Cancer cells’ Achilles’ heel, however, is their rapid growth rate.

Nevertheless, once again, pretty much like for surgery and radiation, no matter how promising or how effective the chemical treatment proved to be at first, there eventually always were relapses. It seemed like Cancer ultimately always got around the drug and managed to outsmart it. Was chemotherapy equally powerless in front of Cancer?

What if, doctors reasoned, we inject multiple drugs at once? That way, they gambled, Cancer, overwhelmed by the surge in the army of drugs, would not have time to adapt. And indeed they were spot on: results showed that the greater the number of different poisons pumped into the body, the better the responses. Moreover, doctors also found that each round of chemotherapeutic drug kills a fixed percentage of cancer cells (this percentage varies in function of the drug used and increases with the number of drugs used simultaneously) –like the half-life of a radioactive element. This means that one needs multiples rounds to really eradicate the disease, that is, to get this number down to zero. So even if all signs of Cancer’s presence had vanished, one had to continue to pump the poison in, because the number of cancer cells was still not zero: Cancer was just hibernating, hidden inside the body, keeping a low profile –but ready to burst again when times are more favourable.

The leap of faith physicians had made by increasing the number of drugs and prolonging their use paid off handsomely, beyond any expectation actually. Results were spectacular: although the leukemic kids were initially nearly poisoned to death by the chemicals, plunging all doctors into extreme tension, after a while there was complete remission of all the kids treated. All cancer associations were ecstatic. Did we finally lay our hands on the long-awaited anti-leukaemia treatment?

But Cancer had yet to unveil his most devilish trick. Almost cornered, Cancer in his leukemic impersonation went out of his way to find the ultimate retreat: he went to hide inside the brain, where the poisonous drugs could not reach. As Siddharta Mukerjee explains, “It was a consequence of the body’s own defense system subverting cancer treatment. The brain and spinal cord are insulated by a tight cellular seal called the blood-brain barrier that prevents foreign chemicals from easily getting into the brain. It is an ancient biological system that has evolved to keep poisons from reaching the brain." But the same system also kept the chemotherapeutic drugs out of the brain, creating a natural "sanctuary" for cancer in the body's most intimate refuge. The consequence was that the kids eventually all died one after the other.

This revolting scheme by Cancer prompted some to declare total war on cancer: the treatment duration lengthened, the number of drugs used increased, and the brain was washed with high-dose radiation. Undeterred, some practitioners even resorted to injecting drugs right inside the skull to work around the blood-brain barrier. There was a rush to pump ever more drugs into patients. This perseverance actually paid off: certain types of leukaemia seemed curable after all. But at what price… Nonetheless, the same technique of multidrug chemotherapy was successfully applied to a few other types of cancer, such as Hodgkin’s disease.

Of course, the limit to chemotherapy is the dose of toxicity that the patient's body is capable of enduring. At some point toxicity becomes too deadly, a ceiling is hit and more doses do not lead to more cures. In particular, the ceiling seemed to lie in the marrow, as marrow cells were the first cells to undergo extinction. So intrepid doctors set out to lift this ceiling by simultaneously transplanting allogeneic or autologous bone marrow into the patient. This allowed them to multiply doses tenfold (“megadose chemo”). However, the procedure carried considerable risk, only a few survived and this was mainly used on refractory leukaemias, and then on breast cancers.

TOWARD A MORE SUBTLE APPROACH TO CURE: CANCER AS A GENETIC DISEASE

However, one can’t keep throwing chemicals and cross one’s fingers that it’ll work. No fundamental knowledge underpinned Medicine’s offensives on cancer. The process pretty much consisted in cooking up some new chemical cocktail, inject it in mice and see what happens; if it works, let’s apply it to humans. Our civilization had rushed into a cure frenzy without pausing for deeply understanding the disease. In 1986, the first ever statistical appraisal of the global progress of the war on cancer by John Bailar and Elaine Smith indeed strikingly showed that nearly no progress had been made over the last 40 years. All that money… This was not merely due to the poor effectiveness of the cures so far developed, but, importantly, it was also due to the rise of new cancers in the population (the most prominent being lung cancer, whose rise followed the spread of smoking habits). It was definitely time to back up a little and grow a more fundamental knowledge of the disease. Back to basic biology of cell functioning. Don’t rush to a cure. First know your enemy. Let scientists do their job. Cancer thenceforth was considered less as a foe on which to wage war and more as a puzzle, a scientific puzzle.

At the same time, focus also shifted from cure to prevention, a path down which there seemed to be large benefits to grab. Prevention encompassed finding out the causal agents triggering cancer (“carcinogens”) and protecting people against them. The epic battle to establish the link between tobacco and lung cancer epitomized this new approach. But it was hardly the only carcinogen found: many other discoveries followed, such as the link between exposure to asbestos and scrotal cancer.

Carcinogens were not only chemicals. It was further found that infectious agents (viruses and bacteria) could be vectors of cancer as well. They all had the same consequences: cell mitosis gone berserk, throwing cells in hyperplasia. How could one reconcile such tremendous diversity in carcinogens with the quest for a unique cancer-causing mechanism?

The big question then became: how does a carcinogen trigger cancer? What is the true nature of a carcinogen? At this point came an important discovery by American biochemist Bruce Ames, who established that a carcinogen is nothing but a sort of mutagen, i.e. a chemical having the property of enhancing the rate of mutations within biological cells. As he used to study mutagens and rank those by effectiveness, when he happened to notice that the most powerful mutagens also tended to be carcinogens, he implied that somehow the capacity to alter genes is linked to the ability to induce cancer. Now did that mean that carcinogens had the ability to influence mutation directly or rather that they changed the genes, which in turn upset cell growth? Did our enemy actually lay in our genes?

To answer that question, we have to turn toward Rous Sarcoma Virus (RSV), the first cancer-causing virus discovered. RSV also has the peculiarity of being a retrovirus. Unlike traditional viruses, which storm into a cell, use their host to copy themselves then head off without altering their host’s genetic makeup, a retrovirus is able to transcribe its RNA back into DNA and attach its genome to its host’s. It is only after such an operation that the infected cell started to go nuts. So could it be that cancer results from the activation of a “viral gene” inducing the infected cell to proliferate?

The RSV is made up of four genes. One of them in particular was isolated as the one causing all the turmoil: without it, no cell proliferation. Because of its cancer-causing property, this gene was called an “oncogene”. The protein it encodes is a kinase, a kind of protein which has the property of activating other proteins by attaching to them a phosphate group, thereby acting as a “switch”. However, the problem with our oncogene is that it transcribes a kinase on steroids, turning on whatever protein it finds, eventually impinging on the proteins controlling cell division.

If a gene bore by a virus could cause cancer once expressed, is it possible that a normal, non-infected genome naturally bears potentially cancer-causing genes that only wait for the helping hand of a mutagen to turn themselves evil?

That’s precisely what researchers Varmus and Bishop found: there exists a gene (which they fondly baptized “src”), similar to RSV’s oncogene, and which is present in the genome of nearly all animal species. So the RSV is not at all the cause of cancer, but merely an accidental vector. During its endless cycle of reverse transcription, the retrovirus just happened to pick up the oncogene and spread it.

Following this lead, researchers made additional discoveries. They distinguished between “positive” and “negative” oncogenes: while the former causes cells to proliferate (like src), the latter prevents cell proliferation. In the first case, it is the presence of the gene which is to be feared; but in the second case, it is its absence that leads to cancer (which is why it is called an “anti-oncogene”). Therefore, cancer can result from either “jammed accelerators” or “missing brakes”, as Siddhartha Mukherjee puts it. Moreover, while the positive oncogene required but a single mutation to activate (its presence on one strand of chromosome is enough), the negative oncogene needs two hits to shut down (it must be defective in both arms of the chromosome). 

It so happens that oncogenes are central in the genomic network. Any biological event is said to be “six degrees away” from the action of an oncogene (named after the sociological six degrees of separation), because they are the ones influencing cell growth/division, which is a phenomenon so important in how living beings are designed to function. And as the business of a gene is to produce a protein, an oncogene's protein is also key in a cell's grand ballet of proteins.  

Have we finally zeroed in on the chief villain?

BIOTECH: A NEW ARMY ON THE MARCH

While these discoveries empowered us with new means to hunt down our culprit, at the same time the world witnessed the rise of biotech companies, which would make the most out of these discoveries by converting them into viable business models to produce drugs for large-scale cure campaigns. The story of Genentech exemplifies the advent of biotech companies. Genentech was founded following the development of the recombinant DNA technology, which enables to inject part of a genome into another one, taking genes from a given living being and putting them into another one’s cells to let it produce its proteins there. So cells could be used as bioreactors to produce the most difficult chemicals to produce, i.e. proteins. 

The underlying logic stays the same as that of chemotherapy: the goal is to find chemicals that, by binding to the cancerous agent, will be able to terminate it. But now we know that this agent is the kinasic protein produced by oncogenes. As proteins are small and complex chemicals, the traditional way of producing drugs was powerless to find a match to bind these proteins. Hence the importance of the biotechnology revolution, which rather than using industrial reactors uses Nature's reactors instead to produce its synthetics. For instance, Genentech developed a drug that managed to bind to the protein transcribed by an oncogene involved in severe breast cancer and thereby inactivate its kinasik activity. It's good old "specific affinity" at molecular level: binding to a very specific element in cellular division's algorithm rather than to a whole cell. This wouldn't have been possible without the fine-grained knowledge painstakingly accumulated by fundamental research.

More generally, kinase-coding genes are all potentially oncogenes due to their centrality in molecular physiology and their role as monitors of cell division. There are about 500 kinases, each targeting a specific subset of proteins. The key strategy for biotech companies aiming at developing anti-cancer drugs is thus to act on kinases, i.e. to produce kinase-inhibitors to control a cell's master-switches. 

CANCER: THE LAST BARRIER BEFORE IMMORTALITY

For all the astounding scientific and technological breakthroughs of the two last decades, there are still plenty of gray areas left. In particular, two hallmarks of the cancer syndrome are still lacking an explanation: the fact that a cancer is not a sudden appearance but a progressive development, and the fact that cancer cells metastasize throughout the body. Indeed, the enemy follows some well-defined procedure in its killings. Systematic steps. Patterns. He acquires new capabilities, enabling him to change places, haunt new territories. How does he do that? Like any other animal subject to Darwin’s algorithm of evolution, a cancer cell goes through a cycle of mutation, selection and survival, endowing it with new properties, like resistance to death signals, motility, inducement of blood vessel growth, etc. It can also mutate in such a way as to change the structure of a kinase, thereby escaping the effect of the drug.

Are we battling endlessly against an infinitely shrewd enemy? We found out who Cancer is and how he comes into existence. However, it’s still unclear how he operates to propagate inside a body before knocking his victim out. This is the latest focus of the battle against cancer, which is still in progress and far from over.

Our cells are our self. Our very existence depends on a sustained renewal of our stock of cells. This is a fine-tuned machine. Cancer cells differ from "normal cells" in that they are immortal and have a greater drive to self-replicate. But what is normalcy? In the coming era where living to be 100 years old will be common, cancer is likely to be even more all over the place than it is today. What will "normal" be then? In a civilization running frantically toward achieving immortality, Cancer is likely to be the greatest and perhaps insuperable built-in obstacle to our endeavours. He is so much entrenched within ourselves that getting rid of him could well mean getting rid of our most indispensable physiological processes: regeneration, healing, growth. It is as if our enemy was growing within, trying to take control of us to impose a new life-form, immortal and ever-increasing. His seed seems eternal. Always potentially present. Like a ghost of our selves. They call it a “malady” –actually it’s much more than that: it really is a living being within ourselves. 

Sources:

S. Mukherjee, “The Emperor of all maladies – A biography of cancer”, 2010

Scientific American, “Untangling the roots of cancer”, 2003

S. Arrison, “100 plus – How the coming age of longevity will change everything, from careers and relationships to family and faith”, 2011

A. Park, "The stem cell hope - How stem cell medicine can change our lives", 2011

who.org

“Even so I yearn day after day, longing to reach home, and see the hour of my return. And if some god should strike me, out on the wine-dark sea, I will endure it, owning a heart within inured to suffering. For I have suffered much, and laboured much, in war and on the seas: add this then to the sum.” (Odysseus).

Why would Homer use such a bizarre colour epithet as “wine-dark sea”? Anyone can see that the sea is not “wine-dark”. Was he blind? Was he biologically incapable of discerning colours? Or is it just poetic license? Well, why then does he in other parts of his work use the same word to describe totally different colours? And why does he, for a same object, frequently use different colour epithets? Why, more generally, is Homer’s colour palette so poor?

This colour puzzle raises a more general question about the language of perception: should we expect every language on earth to partition the colour spectrum with the same focus points and the same number of divisions? In other words, could it be that Homer really saw the sea as “wine-dark”?

Research tells us that, although the progressive refinement of our colour vision, from the crude perception of degrees of brightness to a full-fledged colour palette, has some natural/universal basis (such as the opposition between bright and dark as a primary basis for colour perception, or the red colour as one of the first colours to be perceived, for obvious evolutionary reasons), this evolution has been strongly linked to the appearance of artificial colour (in dyes or jewellery) or to the emergence of evolutionary needs (like being able to distinguish yellow fruits over a green background). Indeed, everyday dealings with artificial colour educate the eye, and thus culture can influence how we perceive colours.

For instance, it has been shown that people perceive two colours, separated by the same objective “distance”, as further apart if that distance crosses a “mental” boundary in their culture’s partitioning of the colour spectrum, than if that distance had not crossed any mental boundary. Russians, who have a greater nuance for blues than other cultures, would see two blues as further apart as a blue and a green, such as perceived by an Englishman, for instance.

This story about colour is important because it shows us that culture can influence the division of concepts, and that this influence of culture is greater whenever nature shows some fuzziness in how it carves out things. With cats and dogs, or physical objects in general, it is unlikely that there are any significant difference at all between different languages in how these objects are chiselled from the perception continuum. That is, it’s unlikely that a language would have a word for “front half of a dog” and another one for the other half, although one is likelier to find two language with two different ways of slicing the colour spectrum, which is a fuzzier concept. So in general, whenever we enter a more abstract lexical field, we may expect greater variation in the dissection of the world.

Now how could language actually influence thought? Surely not as some delusional linguists suggested in the beginning of the 20th century, arguing that the limits of one’s language are also the limits of one’s world. For instance, verbs in the Hopi language are tenseless –does it mean they don’t have any notion of time? And what about the Nootka language, which has the peculiarity of not distinguishing between verbs and nouns? Should this fact lead one to think Nootka speakers are unable to distinguish between action and thing?

Well, let this kind of considerations to cocktail-dinner conversations, and consider the following: rather than what a language allows its speakers to think (as in Orwell’s 1984), the influence of language over thought has to be sought in what a language accustoms its speakers to think, due to its grammar rules. Grammar is the set of rules laying out what must be expressed in a language. Language is not a prison preventing us from seeing or thinking about some things. It is merely a lens. However, a lens can have an influence on one’s thoughts.

For instance, an English sentence does not necessarily specify gender, contrarily to French or German, which necessarily do. And studies have shown that a “genderized” language (such as French or German) influences our perception in that, for a same reality, speakers of languages describing it with a feminine noun will tend to associate that reality with “feminine” values, while speakers of languages describing it with a masculine noun will tend to associate that reality with more manly connotations.

Does this back up the theory that languages can differ in what they can express? Not at all. Take the Matses, a small tribe in the Amazonian forest, who have a language that compels its speakers to specify the degree of pastness (recent past, distant past, or remote past) and the degree of evidentiality whenever they use a verb. Their evidentiality requirements means Matses always have to specify, whenever they make an assertion, how they came to know about the facts they are reporting (direct reporting, inference, or hearsay). This grammatical system is highly sophisticated. Can you thus imagine how little a putative Matses ethnologist would think of the imprecision of indo-European languages? However, even though “Western” languages do not compel to provide all this information systematically, nothing prevents us from specifying that information –showing how silly it is to assume that a language’s grammar is its prison.

An additional intriguing linguistic case comes from the Guugu Yimithirr language, an Australian aboriginal language, and the way it treats spatial relations. Speakers of that language have to describe spatial relations in absolute (or geographic) coordinates, whatever the scale. We Westerners also use absolute coordinates (north-south-east-west) but only at a large scale. It would never occur to you to say: “Would you be so kind as to pass me the salt at the south-west of your plate?” or “The sock you’re looking for is just north of your eastern foot”. Similarly, if someone on the street asks you his way, you will spontaneously answer in “egocentric” coordinates: “first, turn left, then when you reach the end of the road, turn right; the building you’re looking for will be just in front of you”.

Well, a Guugu Yimithirr person would never talk like that. Should you put them in a dark cellar, they still would be able to talk in fixed cardinal directions, thanks to the extensive training they got since they were born. They actually do not understand egocentric coordinates. And what’s even more puzzling is that even their memories of things past are also in absolute coordinates. For instance, someone recollecting of his boat overturning in the sea on its eastern flank, will in illustration spontaneously wave his hands in a different manner according to his spatial position when he tells the story, so as to always show east.

Yet does this mindset influence thought? It seems so. Let a Guugu Yimithirr person enter some room, in which there is table in some corner; on the table, there are two objects with a specific arrangement: object B at the right of object A. Now let’s have this same person enter another room, perfectly identical to the former, but with the sole difference that the room is in opposite orientation. Now if on the table you only had object A and if you asked the Guugu Yimithirr person to place object B as it was placed in the first room, while you would put it back at the right of object A, he instead would put it on the left. This solution, absurd in terms of egocentric coordinates, makes however perfect sense in geographic coordinates. Therefore, space is perceived in a different way by speakers of Guugu Yimithirr.

What’s the lesson from all this? That linguists should be humbler in their claims and that, like for any science, it is only through this kind of little and rigorously controlled experiments that one can come up with confident conclusions regarding such fashionable philosophical quests as the influence of language on thought, rather than through grandiloquent assertions based on little else than fantasies.

Sources:
G. Deutscher, “Through the language glass – Why the world looks different in other languages”, Metropolitan Books, 2010.
L. Boroditsky, “How language shapes thought”, Scientific American, 2011.

A recent publication in Nature suggests jaws and teeth were initially developed in primitive fishes (placoderms, the ultimate ancestors of humans) to raise their odds of copulating with a female fish. “Jaws may have originally evolved to help male fish grab ahold of females and stabilize them during mating, only later taking on the role of food processing.” Hear that, girls?

Today, some species still have pretty direct behavioural connections to that original functionality. Indeed, some male sharks, with a view of courting the opposite sex, bite them in the back, neck and pectoral fin –thereby helping them later to better hold onto their partner while copulating. Hey, that’s worth pondering.

Before placoderms, sexual reproduction among fishes consisted in spawning –females spread their eggs all around the ocean, then males come and magnanimously fertilize them and embryos are just left over in the open. Yet that was arguably not a powerful enough strategy for spreading one’s genes on to the next generation, as most embryos just ended up being food for other fishes.

Therefore males and females started spawning still closer to each other and while males developed ever more functional pelvic fins (ancestor of the penis) to better target the eggs, placoderms eventually thought: ‘Hey, why not directly fertilize the eggs inside that beautiful lady? That way, I’m pretty sure my offspring is going to carry on my genes.’

And thus was sex invented.

So let’s express our heartfelt gratitude to our jaws and teeth and bitings, for internal fertilization has been one of the major efficiency improvements in the story of life, drawing what is called the arthrodire radiation – “the first big species radiation of any jawed animal in the fossil record”, all thanks to the invention of sex. Species that stuck to spawning now have much, much fewer descendants –and much, much less fun.

Sources:
J. A. Long et al., "Devonian arthrodire embryos and the origin of internal fertilization in vertebrates", Nature, 2009.
J.A. Long, "Dawn of the deed", Scientific American, 2011.

Inspired by David Willetts’ The Pinch.

Demography matters. After the Second World War, between 1945 and 1965, Western countries experienced two baby booms, for a variety of more or less obvious reasons. When reaching the job market, the baby boomers (i.e., our parents), contemplating the prospect of having to compete against a lot of fellows, adapted by delaying marriage, having fewer children and putting women at work, thereby maintaining household living standards.

This generation was meant to be one of the luckiest but also one of the most egoistical –and here is why.

Over the last 30 years, our parents have benefited from an extraordinary ‘demographic bonus’. Contrarily to conventional wisdom, belonging to a crowded generation does not lead to a tougher life as one can expect competition at every corner; instead, a youthful and growing population increases aggregate demand, stimulating the full use of available resources. Moreover, the baby boom generation has benefited from an extraordinary ‘demographic sweet spot’: a bulge of workers, catering to the needs of rather few dependants, as there were few pensioners (not many people were born in the 1930s, as the Great Depression did not exactly put people in the mood for love) and low birth rates.

Actually, no other generation in human history ever had it so good. They entered an “age of plenty and experiment”, full of disdain for the confined and conventional lives led by their parents.

However, this unprecedented appearance of one generation much larger than the preceding and following ones has started off a huge shift in the intergenerational balance of economic power. Indeed, during the last decades, while the median age of production can be said to have been quite stable at around 40, the median age of consumption, from around 45 in the mid-1980s, has steadily increased and is still on the way up –witnessing a transfer of resources towards the baby boomers as they age. While the pensioners’ income that our parents have been financing has stagnated in the last 20 years, the baby boomers’ earnings have altogether shot up. At the same time, young people have witnessed a marked decline in their earnings compared to all working people. In the mid-1970s, young people earned a lot compared to the older generations; today they earn much less than older generations. Moreover, today’s youngsters (i.e., us, the children of the baby boomers) face globalisation, which tends to curb pay rises or even to drive wages down, which not only has the effect of preventing a shift of resources to us, but also of increasing returns on capital –owned –surprise!– by the baby boomers.

On the asset front, it is but normal that the older you are the wealthier, since one accumulates wealth and property throughout life (in the form of house, pension and financial assets). Yet, the question is whether there have been changes in the relative wealth of the generations during the last decades. And indeed there were. The house price boom of the past 15 years has resulted in a huge transfer of wealth to the baby boomers. What is more, when the baby boomers were young and packing up debt (in the 1970s and 1980s), they went through a period of very high inflation (around 10%, quite through-the-roof for developed countries standards), which, as you may know, has the remarkable virtue of de facto reducing the value of their debt (and, by the way, wiping out the savings of the then pensioners). Of course, since then, central banks have gained independence and have thus become experts at curbing inflation: nowadays, we can be pretty sure of not seeing our debt inflated away for the foreseeable future (yippee!). Here again, our parents are on the comfortable side of the equation –having since then written off their debt and being today’s savers.

Regarding pensions, generous pension schemes (where you receive a percentage of your last salary until you die) designed for baby boomers by baby boomers in the ages of plenty, are now being closed off for younger workers (whose work nevertheless still funds these very pension schemes) to be replaced by defined contribution pensions. In addition, since the time these generous pension schemes were set up, life expectancy of the beneficiaries has considerably improved, proportionally perking up their value.

Housing, pensions, and financial assets –all have evolved in indecent favour of our parents and in detriment to all other generations.

But the scandal does not end up here. As our parents felt increasingly richer, they did not deem it necessary to save anymore. They could just as well eat their houses, i.e. borrow against the increase in their value and spend the money away. For all practical purposes, they basically took an asset bubble for savings, thereby relieving them from the need of putting aside real savings. Accordingly savings fell to historic lows, unprecedented in human history, with even negative savings in some countries. What is worse, today’s young generation starting on the housing ladder (i.e., us) consequently has to face these sky-high house prices –and with very little help from mom and dad (since they have no nest egg left).

If one considers that the level of saving and investment is a measure of a society’s commitment to the future, one cannot but acknowledge that, to some extent, the ‘contract between the generations’ has been broken, and that in the course of the second half of the 20th century, vertical ties across the generations have weakened and been replaced by stronger horizontal ties with contemporaries and friends –in other words, an era of hyper-individualism.

But what now that the baby boomers are starting to head toward retirement? The new working generation (i.e., us) will have to bleed to maintain a greater population of pensioners. The funny part is that retired baby boomers will not even need to use their larger voting power to claim their due. Indeed, if the welfare state follows a balanced-budget rule (which it does), this means that public spending follows demand: when many kids, prop up education spending; when many pensioners, increase health spending. However, such an apparently sensible rule can lead to great injustice (inevitable given the long time horizons involved and the tendency for short-sightedness among politicians). As a result of that very rule, age-related public spending is forecasted to increase at a 5% annual rate for the coming decade. Yet this increased spending has to be made by a less sizeable generation (i.e., us), therefore mechanically augmenting the levy per capita. Once again, yippee!

But that is not all. To crown it all, even though our parents benefited from the welfare state more than any other generation, public debt has been inexorably piling up while they were in charge, meaning that they were not even taxed enough to pay for a relatively low level of public spending. Instead, they decided to shift that burden onto their children’s shoulders. That is the icing on the cake!

(We will not even tackle here the issue of the adjustment cost to environmental change.)

In conclusion, the coming 20-30 years promise to be rather challenging for us fellows.

Oh, and, –I almost forgot– Mom, Dad, –Thank You.