Fashionable pharmaceuticals

The pharmaceuticals industry has an obsession with novelty. We want better drugs with fewer side-effects, but too often newness is correlated (wrongly) with an improvement in quality. One new drug that is twice as good at treating an illness as its predecessor is better than five drugs each offering a one per cent improvement on the first. ‘New’ drugs which appear on the market often seem to be derivatives of the well-tested substances which precede them and not genuinely novel drugs.

Consider escitalopram, a relatively new SSRI antidepressant. This is not a new drug in any meaningful way—rather, it is an enantiomerically pure form of the older, off-patent antidepressant citalopram. (In chemistry, a chemical’s connectivity—the order in which groups are bonded to one another—is referred to as its stereochemistry, and chemicals can have different forms or enantiomers as a result of these different ways of connecting the groups together.) Citalopram is a mixture of two enantiomers; isolate one and you’ve got escitalopram.

While escitalopram does seem to have better clinical efficacy at treating depression, it can’t really be said to be new in the way that, say, fluoxetine (Prozac) was when it hit the market in the late 1980s. Fluoxetine was seen as revolutionary when it was introduced, but its efficacy—and that of its more modern siblings—is still only barely better than placebo. Is it possible that nothing better has come along in more than twenty years?

A number of other drugs—amineptine, tianeptine, moclobemide and selegiline among them—have shown great promise in treating depression and, may indeed be suitable for general mood enhancement. Amineptine was withdrawn from the market because of its slight stimulant effects, never to be manufactured again. (Surely a substance which could genuinely and consistently improve one’s mood would be addictive by definition?)

The other three drugs have been shown to be promising antidepressants and mood enhancers but there seems little interest in comparing their efficacy with that of fluoxetine, the de facto treatment for depression in a number of countries. We are eager to test new drugs but no-one is willing to spend money testing ‘old’ drugs. Tianeptine isn’t even licenced for sale in the US, presumably because it is now off-patent and no company has any incentive to push for FDA approval.

Yohimbine is another interesting drug which languishes in scientific obscurity. Potentially quite a useful aphrodisiac and treatment for erectile dysfunction, this study into its effectiveness asks why so little data on it is available, concluding that its off-patent status is a serious disincentive for further investigation into its clinical efficacy:

Despite such a long history and encouraging activity, the drug has not yet been subjected to scientifically rigid human clinical trials. … Recent studies have been designed with a lack of insight and complete disregard of those fundamental studies. … Dose-response investigations are not available, alternative routes of administration have not been investigated… Synergistic activity with other drugs was last studied nearly four decades ago. Assessments of various populations were carried out in very limited cohorts and only in the most general terms. …

Yohimbine is an old drug. As such it does not enjoy patent protection or commercial viability. Until molecular/formulation changes can be brought about … serious investigation of the drug will remain in limbo.

If big pharma isn’t going to look into vintage pharmacotherapies, shouldn’t governments be willing to do so? If the purpose of bodies like NICE is to find the most effective treatment at the lowest cost, don’t they have an incentive to investigate other drugs; to scour the literature for candidate substances and fund studies of drugs which showed promise but were left languishing?

The immortality brigade

A fifty-seat room was never going to be big enough. People fill the aisles, sit on the ground and peer around the door. A man comes in a little late clutching a box bearing the LifeExtension ‘nutriceutical’ brand. Sunlight glints through the windows, dappling the trademark grey-speckled beard and ponytail of today’s speaker, the somewhat notorious Aubrey de Grey. For the next two hours, this room will house discussions of whole-brain emulation, ‘strong’ (self-improving) artificial intelligence and molecular medicine’s promise of immortality. For the moment, this was a room of Singularitarians.

The precise definition of the Singularity depends on who you ask, but popular variations usually involve the principle of exponentially accelerating returns in technology, invoking Moore’s law which states that transistor density, and hence computer speed, doubles every eighteen months. We quickly end up on the nearly vertical slope of the exponential curve, with colossal advances occurring near-instantaneously. At present, we can adapt to new technologies like the internet because they progress relatively slowly. If the scale and pace of modern research caused such advances came much more quickly, humans might have trouble keeping up with the cutting edge.

Consider what might happen if we were able to significantly augment human intelligence with machines. We would then be able to use our newfound intellect to build better machines, which would further improve us, allowing us to further improve on them… A point of explosive exponential increase.

Quite what a post-Singularity world will look like is impossible to say, but the potential payoffs are large: the end of ageing, the ability to augment, back up and restore one’s brain, collective consciousness and a life of leisure enabled by the advent of strong AI are a few of the benefits touted by advocates.

Most striking is the apparent inevitability the advance of computing technology: since its inception in 1965, Moore’s law has held unwaveringly. It presumably has some physical limit above which further improvements are not possible. Some predict that it may not last more than five or ten years more. Of course, such prophesies have been made for the last thirty years, and still processing power grows apparently unabated.

It’s de Grey’s turn to speak. His appearance is no less striking than his talk: he wears a loose, lime-green check shirt, sleeves rolled up, and sports a ponytail and bushy beard that comes down practically to his navel. He resembles a biblical prophet working dress-down Friday at an internet startup. de Grey’s organisation—Strategies for Engineered Negligible Senescence, or SENS—promotes the development of techniques that can maintain and repair the ageing body.

“When this does become a possibility,” de Grey explains, “no government will fail to deliver this technology universally as the cost of maintaining an ageing population is so vast. And when the prospect of immortality is on the cards for all of us, perhaps we’ll take other existential risks—climate change among them—more seriously.”

Strikingly, de Grey presents a model showing that the quality of molecular medicine need only double once every forty-two years to allow those alive today to live forever with sufficient regenerative treatments. “For fuck’s sake,” he exclaims, “that’s the time it took to go from the Hindenberg to Concorde.” Murmurs of approval from the audience, though his talk contains a dispiriting vacuum of information on how sophisticated our abilities currently are or whether any projects in the pipeline are keeping us on track for the goal of immortality within our lifetime.

The debate in the room quickly turns intense, with a gamut of views expressed and discussed. Unsurprisingly, a meeting such as this tends to involve detailed discourse on the vagaries of developing AI or of whole-brain emulation, rather than on the basic feasibility of the Singularity. de Grey expressed his own, rather serious, doubts: a key necessity is the ability for an artificially intelligent machine to recursively improve upon its own intelligence, but de Grey suggested that there might be a mathematical upper limit to the rate of this improvement. Beyond this, though, there is little more than superficial discussion of how likely the Singularity is to come to pass, which for a field as apparently fantastical and potentially revolutionary as this is disappointing.

Even de Grey’s speech on ending ageing went mostly unchallenged, despite the implications his work could have. Many contemporary philosophers, transhumanist Nick Bostrom among them, have opined on the ways in which engineered immortality would radically change the way society operates, but de Grey himself is oddly silent on the matter. This seems surprising—public opinion of Singularitarians seems to be generally apathetic or negative, with the Singularity painted as a ‘geek religion’ of sorts, and views on ending ageing are even less accepting, so those espousing post-human viewpoints need to make the moral case for their convictions. In this room in Birkbeck, though, de Grey is probably preaching to the converted.

The term ‘Singularity’ is likely to see frequent use among technojournalists in search of an impressive but baseless story in the years between now and whenever the Singularity actually comes to pass. An important point is that some of the technological advances promised are very feasible and almost inevitably are right outside the door. Public discussion of the ethical quandries invented along with smart drugs or personal genome sequencing is important if we are to avoid these innovations causing damage rather than good due to imprudent or unscrupulous use.

After a brief adjournment to the Marlborough Arms, the Singularitarians disperse into Bloomsbury. de Grey cycles off to get a train back to Cambridge, beard flowing behind him. For a man who plans to live forever, it’s a little surprising he doesn’t wear a helmet.

First published in a ‘science in London’ feature in Pi Newspaper, November 2009.

Thinking of the children

I was given the task of writing a piece on the primary school science club I help run which is to appear in UCL’s Volunteering Services Unit (VSU) annual review as a showcase of the work the Unit funds. This is what I came up with—comments and suggestions are much appreciated.

The scant paragraph in the VSU’s weekly email asked simply for ‘two or three enthusiastic scientists to assist with running a school science club’. Not wanting to turn down an opportunity to affirm our scientific prowess, four volunteers-to-be enlisted and met for coffees in the Bloomsbury Café opposite the monolithic facade of the Chemistry building.

Under the wing of Dr Andrea Sella, UCL Chemistry lecturer and demonstrator extraordinaire, we set about planning a series of hour-long sessions suitable for the seven- to eleven-year-olds we would eventually be working with. Never short of innovation, UCL’s online learning environment became the electronic home of the Gillespie Science Club as we worked to collaborate on designing sessions and assemble a rota for the four of us, scheduling two people per session while ensuring that everyone was worked evenly as their respective schedules allowed.

The sessions themselves had a central theme—demonstrating the properties of dry ice, making glow-in-the-dark jelly, simulating a scale meteor strike; the usual—and involved giving a brief presentation on what we would be doing and then moving our aspiring young seekers of knowledge to a demo area where we performed our experiment, either a demonstration if dangerous substances were involved or in small groups in which they could each have a go.

The first few sessions went fairly smoothly, though for most of us it was the first time we’d worked with children and our charges’ capacity for belligerence (of the most endearing and inquisitive kind) did, at times, seem unending. After a time, however, something remarkable happened: we started to get comments from parents, some of whom had never before heard of the science club, expressing their admiration for our work. We had, it seemed, gained a reputation as bringers of empiricism—and of fun.

We had not only become men and women of some repute in the primary school community (with Dr Sella, the man behind the scenes, being nothing short of a celebrity) but we gradually learned how best to capture the attention of the students and keep them engaged while developing in them the skills needed of future scientists, and indeed of future non-scientists if they are to fully understand the world around them. Long-winded presentations were a no-no, but any opportunity for the kids to show off their knowledge was lapped up. Some children were louder than others, but with some effort we worked to ensure the quieter ones were heard.

One thing that every one of us noticed and was astounded by was the children’s curiosity. Almost all of our tutees asked lots of questions, some of them very astute, and we did our best to encourage it. Most people, it seems, learn to suppress this curiosity for one reason or another. With luck, there will be ten boys and girls out there who continue to ask questions of their teachers and superiors, and never stop doing so. See if you can spot them.

Pharmacotherapy

I like to think I’m quite good at picking birthday presents. A loaded Oyster card for an aspiring Londoner, a copy of Gray’s Anatomy for a soon-to-be medic, and those trinkets, of little monetary value and which without context would be meaningless but, given to the right person, invoke a fond memory—mementoes of events shared.

For some years I’ve been interested in the writings of David Pearce, a philosopher who describes in lucid detail his vision for eliminating suffering from sentient life. His chef d’œuvre, The Hedonistic Imperative, is a philosophical manifesto proselytising and elaborating upon the moral urgency of this goal and how it might technically be achieved and is as much a philosophical text as a scientific and literary one. He combines mellifluous prose with a solid understanding of the bioscience needed for ‘paradise-engineering’: genetics, molecular biology, nanotechnology and what he lyrically calls “the biochemistry of bliss.” It’s an undoubtedly provocative read.

What better gift, then, for a blossoming polymath?

HI is not yet mainstream, and it’s not available in book form at all. Unafraid of intellectually challenging birthday presents, I set about binding my own copy of the treatise.

The method is not exact, but after looking at as many DIY bookbinding tutorials as I could bear I settled on what I thought was the best and most efficient way of making a hardy, hand-bound book. Typeset in nicely-kerned Helvetica and Univers 45, the book was printed on A4 paper, two-to-a-side, four-to-a-page in eight-sheet signatures (the industry term for a single ‘fold’ of sheets. Have a look at the spine of a commercial book; you’ll see them). Each signature had four holes put through its centre, and with the folded signatures stacked on top of each other they were sewn one to the second, the second to the third and so on; a kettle-stitch.

The book-block assembled, a simple card cover was cut and glued to the spine. A day of drying later and a contrasting navy slip case assembled to protect the book, it was ready for the finishing touch: a decal symbolic of Pearce’s message.

It’s highly stylised, but it’s there: the molecular structure of MDMA, the so-called ‘penicillin of the soul’ the empathogenic-entactogenic effects of which provide perhaps a glimpse of a possible world which Pearce believes, someday, we may inhabit.

For my favourite pharmacologist.

Hello, world.

So, here it is. The very first in what will hopefully become a long line of posts.

Ultimately, I want this to become a corner of the internet I can call my own—part stream of consciousness, part formal essays. The idea that this domain has been unused for years surprises me a little when I think of it, as I classically enjoyed tinkering with my website and showing off my work. Some frisson of self-consciousness must have brought an end to that as it has most of my online projects, but here I am again, come full circle, with a website once more—hopefully a little more refined than the hand-codings of a thirteen-year-old—and with it a new-found online presence.

In a few hours’ time this post will be indexed and cached by Google and the Internet Archive, a fossilised carbon copy of this tract. To some that immortality might be reason alone to publish; to me it’s a reason not to. But then, everyone is afraid of sucking. And everyone is afraid of starting. So let’s begin.