Isegoria

Many primeval forests aren’t in fact primeval but the result of recent accidental rewilding:

In the Americas — North, Meso and South — the first Europeans to arrive in the 15th and 16th centuries reported dense settlement and large-scale farming. Some of them were simply not believed. Spaniards such as the explorer Francisco de Orellana and the missionary Brother Gaspar de Carvajal, who travelled the length of the Amazon river in 1542, claimed that they had seen walled cities in which many thousands of people lived, raised highways and extensive farming along its banks. When later expeditions visited the river, they found no trace of them, just dense forest to the water’s edge and small scattered bands of hunter-gatherers. Orellana and Carvajal’s reports were dismissed as the ravings of fantasists, seeking to boost commercial interest in the lands they had explored.

It was not until the late 20th century that investigations by archaeologists such as Anna Roosevelt at the University of Illinois at Chicago and Michael Heckenberger at the University of Florida suggested that Orellana and Carvajal’s accounts were probably accurate. In parts of the Americas previously believed to have been scarcely inhabited, Heckenberger and his colleagues found evidence of garden cities surrounded by major earthworks and wooden palisades, built on grids and transected by broad avenues. In some places they unearthed causeways, bridges and canals. The towns were connected to their satellite villages by road networks that were planned and extensive. These were advanced agricultural civilisations, maintaining fish farms as well as arable fields and orchards. As in Slovenia, what appeared to be primordial forest had grown over the traces of a vanished population.

It appears that European diseases such as smallpox, measles, diphtheria, the common cold were brought to the Caribbean coast of South America by explorers and early colonists and then passed down indigenous trade routes into the heart of the continent, where they raged through densely peopled settlements before any Europeans reached them. So feracious is the vegetation of the Amazon that it would have obliterated all visible traces of the civilisations built by its people within a few years of their dissolution. The great várzea (floodplain) forests, whose monstrous trees inspired such wonder among 18th and 19th century expeditions, were probably not the primordial ecosystems the explorers imagined them to be.

Gruesome events — some accidental, others deliberately genocidal — wiped out the great majority of the hemisphere’s people and the rich and remarkable societies that they’d created. In many parts of the Americas, the only humans who remained were — like the survivors in a post-holocaust novel — hunter-gatherers. Some belonged to tribes that had long practised that art, others were forced to re-acquire lost skills as a result of civilisational collapse. Imported disease made cities lethal: only dispersed populations had a chance of avoiding epidemics. Dispersal into small bands of hunter-gatherers made economic complexity impossible. The forests blotted out memories of what had gone before. Humanity’s loss was nature’s gain.

The impacts of the American genocides might have been felt throughout the northern hemisphere. Dennis Bird and Richard Nevle, earth scientists at Stanford University, have speculated that the recovering forests drew so much carbon dioxide out of the atmosphere — about 10 parts per million — that they could have helped to trigger the cooling between the 16th and 19th centuries known as the Little Ice Age. The short summers and long cold winters, the ice fairs on the Thames and the deep cold depicted by Pieter Breugel might have been caused partly as a result of the extermination of the Native Americans.

(I don’t recall ever seeing the word feracious before. As you might infer, it means fruitful or fertile.)

Ordinary people have three kinds of cones in their eyes, attuned to red, green, and blue, but a few people, mostly women, are tetrachromats, with four kinds of cones:

For years, researchers weren’t sure tetrachromacy existed. If it did, they stipulated, it could only be found in people with two X chromosomes. This is because of the genes behind color vision. People who have regular color vision have three cones, tuned to the wavelengths of red, green, and blue. These are connected to the X chromosome — most men have only one, but most women have two. Mutations in the X chromosome cause a person to perceive more or less color, which is why men more commonly have congenital colorblindness than women (if their one X chromosome has a mutation). But the theory stood that if a person received two mutated X chromosomes, she could have four cones instead of the usual three.

Note the use of most in that paragraph:

The original story stated that all men have one X and one Y chromosome and that all women have two X chromosomes. This statement neglected to include those with Klinefelter Syndrome and transgender individuals. We regret the error.

(Hat tip to T. Greer.)

Why are so few blockbuster drugs invented today?

On Sept. 25, 1990, James D. Watson, the Nobel Prize-winning co-discoverer of the double-helix structure of DNA, and at the time the director of the National Center for Human Genome Research, wrote a letter to this paper making a prediction: “The ability to sequence DNA quickly and cheaply will also provide the technological basis for a new era in drug development.”

At that moment, the idea that the human genome would lead to a multitude of cures for diseases seemed inevitable and irresistible. DNA is, after all, nature’s instruction booklet for building living things; open that book and read its instructions, the thinking ran, and the botched instructions that result in diseases would be revealed. From there, a logical series of steps would arrive at a cure. Once a malfunctioning gene was isolated, scientists would find the protein coded by that gene. Then they’d use that protein as a target. Finally, they’d run tests of tens of thousands of unique chemical entities that drug companies have stockpiled over the years, to find one that fit the target like a key in a lock, to correct its function.

But this golden road to pharmaceutical riches, known as target-based drug discovery, has often proved to be more of a garden path. The first disappointment has been that most diseases affecting large numbers of people are not caused by a handful of mutations that can be unearthed as easily as digging potatoes in a field. Geneticists have called this the problem of “missing heritability,” because despite what they promised in the 1990s, they have found no single genetic variants that are necessary and sufficient to cause most forms of widespread diseases like diabetes, heart disease, Alzheimer’s or cancer.

The second disappointment is that even when a genetic variation can be plainly linked to a disease, the process for figuring out what to do about it rarely works as efficiently as advertised. Compounds that appear to hit a designated target right between the eyes still often fail to be safe and effective in animal and human studies. Biology is just way too complicated.

“If you read them now, the claims made for genomics in the 1990s sound a bit like predictions made in the 1950s for flying cars and anti-gravity devices,” Jack Scannell, an industry analyst, told me. But rather than speeding drug development, genomics may have slowed it down. So far it has produced fewer returns on greater investments. Scannell and Brian Warrington, who worked for 40 years inventing drugs for pharmaceutical companies, published a grim paper in 2012 that showed the plummeting efficiency of the pharmaceutical industry. They found that for every billion dollars spent on research and development since 1950, the number of new drugs approved has fallen by half roughly every nine years, meaning a total decline by a factor of 80. They called this Eroom’s Law, because it resembled an inversion of Moore’s Law (the observation, first made by the Intel co-founder Gorden E. Moore in 1965, that the number of transistors in an integrated circuit doubles approximately about every two years).

[...]

So far, most drug companies have continued to devote a vast majority of their funding to target-based research, even as more traditional methods of drug discovery have proved more productive. A study published last year by David Swinney found that only 17 of 50 novel drugs approved by the F.D.A. between 1999 and 2008 came from target-based research, compared with 28 from what Swinney calls “phenotypic” discovery, made by studying living cells in Petri dishes, animals and humans. Many of the drugs in this latter category — Alamast for allergies, Amitiza for constipation, Abreva for herpes cold sores, Ranexa for angina, Veregen for genital warts and Keppra, Excegran and Inovelon for seizures — were discovered by chemists who didn’t set out knowing what the drugs’ targets were, or even how they worked. In one now well known case of nontargeted research, scientists developed a drug for angina and found that while it wasn’t effective for relieving chest pain, it did cause erections in the study’s male volunteers. The researchers changed course, and Viagra was born.