Thursday, November 27, 2008

Investing in Biomedical Research

Given the current economic crisis, advocates of different causes are scrambling to defend the importance of boosting, and even retaining, public funding for their particular cause.

In these difficult times greater attention is given to the purported benefits of investing scarce funding in any particular area of policy. So on the bright side of things, during tight economic times we think more rationally about priorities. Ideally we would think this way in good economic times as well, as that would increase the likelihood of our staying in good economic times! But sometimes it takes a crisis to shake us from our intellectual slumber.

If the current economic crisis had occurred six years ago, for example, odds are the second Iraq war would not have happened (in which case the current economic crisis would probably have been avoided in the first place). And the current economic crisis will also dampen enthusiasm for trying to exert greater control over the global temperature. This was clearly illustrated in the recent Canadian election.

I am working on a longer post on why it is imperative that we do not lose focus on the importance of longevity science. But for now, here are a few comments from an editorial in the latest issue of Nature Biotechnology . It addresses the importance of investing in biomedical research more generally:

Scientists fear that the current economic woes will lead to substantial decreases in research funding. Yet government leaders would do well to consider the enormous economic benefit of biomedical research and to realize that boosting funding for such research could contribute to an economic turnaround.

Although it takes time for investments in research to deliver monetary returns, economists have estimated that public funding of biomedical research spurs economic growth. One study, for instance, reports a 28% rate of return on the original investment in research—far superior to any current savings account or mutual fund.

Government funding of biomedical research leads to the creation of jobs in both the public and private sectors. For example, in the US, a country with a long history of robust public biomedical research funding, there were more than 500,000 people working in the pharmaceutical industry in 2002.

Economic growth is also driven by sales of products and devices that have been developed with public funds for research. For example, economist Andrew A. Toole has estimated that a 10% increase in basic research funding leads to a 6.4% increase in the number of new compounds included in applications to the US Food and Drug Administration. The development of new pharmaceutical products or devices can bolster economic development when they are exported or licensed to other countries and can contribute to a favorable balance of trade.

There are direct and indirect economic benefits of investing in biomedical research. Healthcare improvements result in a more able-bodied workforce, leading to substantial improvements in productivity. Biomedical research also keeps healthcare spending down. Historically, these cost savings for the US health system have translated into a return of investment of three dollars for every dollar allocated to biomedical research.


Friday, November 21, 2008

Evolution, Explanations and Medicine

Over the past few months I have been reading chapters from this excellent book, and this has motivated me to write this post on evolution.

Consider the following events from a typical Monday morning.

(1) I wake up.
(2) My stomach grumbles with hunger.
(3) I walk downstairs to the kitchen.

Now if someone asks me to explain events (1), (2) and (3), I might say something like the following:

"I awoke because my alarm went off. I was hungry because I had not eaten for 8 hours. And I went downstairs to the kitchen because that is where my food is".

Now this kind of explanation makes perfect sense. It focuses on the immediate causes of (1), (2) and (3). And we structure, and make sense of, our world by piecing together information concerning different immediate or proximate causes.

But to return to (1), (2) and (3), we might ask: why do I sleep? Why do I feel hunger pains? And why do I have legs? These are more profound questions, ones that require us to adopt a "big picture" perspective that goes beyond the modes of query typical of making sense of our immediate day-to-day lives.

So when we frame the questions of (1) - (3) in this way we are not looking for a proximate explanation, but rather for "ultimate" or evolutionary explanations.

In Evolution in Health and Disease, the editors describe natural selection as a principle that must hold when certain conditions are present: variation in traits, variation in reproductive success, correlation of trait variation with reproductive success, and inheritance of trait variation.

They provide the useful example of water glasses in an inexpensive furnished apartment that has been repeatedly rented:

They can be explained by natural selection. Some collection of glasses came into the apartment. The fragile ones broke. The attractive ones left when renters departed. The nonfunctional ones with odd shapes were thrown out. What is left is what you find- a collection of sturdy, ugly, functional glasses. (8-9)

And the principle of natural selection provides us with an explanation of the events that unfold every morning of our lives. The events of my mundane Monday morning are in fact the result of endless trade-offs and adaptations that have taken place over millions of years.

We sleep because it aids the recovery of many different system levels (e.g. cellular and network), helps conserve energy, and helps with learning, etc. There are many theories concerning the functions of sleep, but the fact that sleeping is universal among animals suggests that it is very important to survival. Go 24 hours without sleep and you will soon realize how vital sleep is to your ability to function. The amount of sleep needed varies among species. A fruit fly, for example, can sleep up to 12 hours a day.

Why do we feel hunger pains? Well, it helps remind us that we need food, and when severe enough it will fixate our attention solely on the goal of "GETTING FOOD!". This is advantageous because it increases the likelihood that we receive a steady supply of the energy needed to survive and reproduce. A species that requires the diet needed to sustain human life would not survive long if it were not hardwired to satisfy our basic material needs.

And we have legs because they are beneficial for a creature (like us) that lives on land. If we lived in the ocean like clown fish then we wouldn't have legs (or be humans!). And if we shared the evolutionary history of birds we would have wings and feathers and be able to fly (though thanks the the magnificent human brain, we have created machines that now permit us to fly).

And so the trivial events of a regular Monday morning in fact reveal the incredible journey of evolution, and the development of the human species.

Why, you might ask, tell us this tale? Well, the emphasis we place on proximate explanations, well often very useful and appropriate, can also limit our understanding and perceptions of the challenges we face. For if my Monday morning was simply explained by the immediate causes of awakening from my sleep, being hungry and getting my breakfast, we would miss the incredible insights that evolutionary biology can contribute to our understanding of the world and our species. And these include important insights for medicine. In particular, to the aspiration to retard human aging.

To make the link from evolution to medicine, let me tell another story. The story is about Billy and his grandfather William. Billy is your typical 16 year-old boy. He is "girl crazy" and is trying to work up the courage to ask a girl from his class out on a date. Billy spends most of his free time chatting to his friends about girls, lifting weights so he can have more success with his efforts at romance, and he also spends a lot of time worrying about his clothes and hair.

Billy's grandfather, William, is 76 years-old. He has a variety of hobbies- he likes to paint and play chest, he volunteers and spends time with his grandchildren. But recently William has become increasingly more concerned about his limited mobility and chronic joint and muscle pain. Furthermore, he was recently diagnosed with high blood pressure and is at risk for a variety of other ailments. And thus his doctor has recommended he take a daily dose of medications to ease his pain and reduce the risks of more serious problems.

Billy and William are your typical 16 and 76 year-old. And yet there is an important link between Billy's obsession with girls and his grandfather's failing health. Evolutionary biology explains why Billy and his grandfather are in the situations they are in. The force of natural selection is set by the age at which reproduction first occurs in a population. And thus the surge in Billy's testosterone levels and overall gonadal function, and William's chronic health problems, reflect the trade offs that have been made between reproduction and survival. Historically, very few humans lived to the age of William, and thus investing in repairing damage late in life would not improve the success of reproduction. Furthermore, investing scarce resources in long-term repair would be inefficient and potentially wasteful. This is known as Kirkwood's "disposable soma" thesis- aging occurs because natural selection favors a strategy in which organisms invest fewer resources in the maintenance of somatic cells and tissues that are necessary for indefinite survival of the individual.

Rose describes it this way:

Henry Ford sent one of his engineers to a scrapyard to find out which parts of defunct Model T’s still had some usable life left. When the engineer reported back with a list of the durable parts, Ford instructed his engineers and suppliers not to make those parts so good that they outlasted the rest of the car. This strategy culminated in “planned obsolescence”, an ugly tradition in American manufacturing.... Evolution is regrettably similar. (91)

Should we treat the trade-off between survival and reproduction that happens to exist at this stage in the evolutionary history of humans with deference? A trade-off that has been shaped by natural selection and the extrinsic risks that once permeated the world, and yet one that will bring disease to an unprecedented number of humans living in this century? The answer is clearly “No”. We should search for safe and effective ways of modifying the biological processes of aging, so that people can expect to live more healthy lives. Utilizing the insights of evolutionary biology, biogerontologists are now searching for ways to modify the biological processes of aging. But many people fail to understand the importance of this research because they only understand the proximate, rather than ultimate, causes of disease. To fixate only on proximate causes limits our understanding of the things that cause disease. We only look at the immediate causes- like smoking, diet, particular genes, etc. But we must also aspire to grasp "the big picture", and Darwinian medicine helps us do this.

Those who embrace the aging "status quo" must square this with other elements on the "evolutionary status quo". Take our immune system. Do we favor the immunity "status quo"? No. For if we did, we should abandon immunizations and return to the high rate of child-mortality that existed in the past. But should we not strive to also reduce late-life morbidity and mortality? The aged do not deserve disease or death. Indeed, we already aspire to aid the aged, which is why we fund cancer research, AD research, etc. So why not fund research that might permit us to delay all age-related afflictions?

And lastly, think about human emotions, and happiness. Should we accept our evolved natures, with all their virtues and vices? The editors of Evolution in Health and Disease make this excellent point:

We did not evolve to be happy: rather we evolved to be happy, sad, miserable, angry, anxious, and depressed, as the mood takes us. We evolved to love and to hate, and to care and be callous. Our emotions are the carrots and sticks that our genes use to persuade us to achieve their ends. But their ends need not be our ends. Goodness and happiness may be goals attainable only by hoodwinking our genes. (13)

So evolution offers many profound insights that have important implications for medicine, as well as moral and political philosophy. Once we give attention to both the proximate and ultimate causes of morbidity and mortality, our aging blinders will be discarded. Our perception of the greatest challenges facing humanity this century will change. And the things we perceive to be obstacles to promoting public health will also change. Ignorance and irrationality are among the greatest threats to public health this century. And so we should think of strategies for reducing their prevalence.


Thursday, November 20, 2008

Some Reflections on World Philosophy Day

Today is “World Philosophy Day”, a celebration of philosophy. In that spirit I offer the following brief reflections on the state of contemporary political (and moral) philosophy.

(1) Philosophy means “love of wisdom”.

(2) The current currency of trade in contemporary moral and political philosophy is “moral intuitions”. The merits of a principle or theory are largely assessed by how well they cohere with our moral sensibilities when isolated in the abstract (e.g. Trolley type examples, hypothetical two-person worlds, etc.). This is what Rawls called the process of “reflective equilibrium”, and for over 30 years philosophers have had many spirited debates- between consequentialists and deontologists, egalitarians and libertarians, egalitarians and prioritarians, egalitarians against other kinds of egalitarians, etc.- to see whose intuitions were the most “intuitive”.

How much wisdom has this “battle of intuitions in the abstract” yielded? My own opinion is, very little. At a minimum, the benefits have not been proportionate to the large investment made. But I think it is actually worse than this. By fixating our attention on the wrong kinds of questions, we have generated new dogmas that impair, rather than enhance, our deliberations concerning how to live our individual and collective lives. It is almost akin to the fixation once given to the question: how many angels can dance on the head of a pin? To what extent have debates concerning luck egalitarianism, for example, helped us grasp a better understanding of the basic principles that should be guiding our collective action? I have posted my thoughts on this before (see here). The failure of luck egalitarianism, like many a political theory, is its failure to place concerns of responsibility in their proper context, and to see the other relevant considerations that play a much greater role in influencing our life prospects (see this post, for example).

Or consider the much debated Trolley cases. As noted before, Schmidtz does a great job of showing how such abstract examples miss important nuances in our views about trust and justice. They nuances are either bracketed or discarded. Schmidtz asks us to consider the following two examples:

Trolley: A trolley is rolling down the track on its way to killing five people. Switching the trolley to another track on which there is only one person would save five and kill one.

Hospital: Five patients are dying from lack of suitable organ donors. A UPs delivery person walks into the hospital. She is a suitable donor for all five patients. Kidnapping her and harvesting her organs would save five and kill one.

Most people say you ought to switch tracks and kill one to save five but you cannot kidnap and murder one to save five. Why not? Trolley, argues Schmidtz, "tells us that numbers sometimes matter. Hospital tells us that sometimes what matters is being able to trust others to respect us as separate persons". Unlike the contrived thought experiments philosophers often concoct, the real world does not stipulate that there is no other way. And when people object to Hospital their objection is often premised on the belief that there must be another way.

Abstraction often impairs, rather than enhances, our understanding of practical wisdom. The examples philosophers should consider are ones that contain such complexities, rather than ones that bracket or ignore them. The latter is preferred, however, because many academic philosophers value precision over proportionality (see this post ). And the cost of this academic obsession is, unfortunately, often wisdom. But Philosophy department’s do not grant tenure and promotion by “how much wisdom” you have generated; and thus there is little incentive for academic philosophers to concern themselves with this. Indeed, many philosophers look down on applied or interdisciplinary philosophy, as if it were “Philosophy-Lite”. I believe this is unfortunate.

One complaint that political philosophers often make against taking real-world constraints (like scarcity, our biology, etc.) more seriously is that it suffers from a form of “status quo” bias. But what these same philosophers fail to realize is that by investing so much in “the battle of intuitions” they are in fact appealing to their own “status quo” bias. Namely, the emotions and intuitions we happen to have at this stage in our evolutionary history, and living in the particular societies we happen to be living in at the time we happen to be living (and typically those they share with their supervisors, and others in the field).

But there is a wealth of empirical studies, from psychology and economics to law, which document many different limitations, biases and fallacies which humans are susceptible to when making various decisions and judgments. And so the choice is not between a “status quo” bias and no “status quo” bias. Rather it is between different frameworks, some of which are better protected against some biases than others. A framework premised on abstraction and idealization is particularly dangerous because the theorist is often unaware of the biases they are invoking.

So today, World Philosophy Day, is a day for philosophers to critically reflect upon the wisdom of placing a high premium on intuition and abstraction.

It is fitting to give Bertram Russell the final word today... [CLICK]


Wednesday, November 19, 2008

The Brain and Our Extended Childhood

Most humans reach their maximal height by age 18. Many other species, including mammals like mice and dogs, would have long died before reaching 18 years old. And yet we humans take so long to reach our full physical maturity. What, one might wonder, is the evolutionary payoff of such a prolonged childhood?

The answer is in our head, literally. It is our big brain, the most incredible of organs. Your brain weighs only around 3lbs, which might not sound that big. But when you compare the size of the human brain to that of much larger mammals, like the elephant and whale, you realize how large our brain is relative to our overall body size.

Growing large brains requires a lot of energy. Humans could not have grown such large brains without spending such a long time in childhood and adolescence. Rather than rush to attain our full adult height, we invest more of our energies into growing our complex brains first. The latest Science podcast has a fascinating discussion of the evolution of childhood, and the paper is here. Here is a sample from the podcast:

Interviewer– Robert Frederick
So, with all that evidence, over what time period did our species evolve – from one that lived fast and died young, to one that lived slow and died old?

Interviewee – Ann Gibbons
Well, they’re closing in on the time and place. It looks like Homo erectus was living a much slower life. It’s interesting, Homo erectus looks like us– it’s tall, strapping, beginning to get a bigger brain at 1.8 million years, 1.5 million years– but it’s growing up like a chimpanzee. So, that means it had a very different family and social structure. It was reproducing more around age twelve, thirteen, rather than around nineteen. So, Homo erectus was not fully in place in a modern way; it was beginning to transition to a longer childhood though. And, then, we know that by the time our species appeared, 200,000 years ago in Africa, that the fully modern pattern was in place 180,000 years ago. So, the window of time has been narrowed to sometime between about 1.2, 1.5 million years ago and 200,000 years ago – when this strategy evolved in our ancestors. So, researchers are teasing that out, not just with fossil teeth but also reconstructions of the brain size – that’s an indirect measure because a large brain, while it doesn’t drive the long childhood, there has to be a long childhood for it to get so big.

Interviewer – Robert Frederick
Interviewee – Ann Gibbons
Because the brain actually – it’s very interesting. This is kind of complex, but it’s fascinating. Brains grow up very rapidly; however, to be able to handle the energetic burden for that brain to get so big, the body is small – it stays small in humans until we have that adolescent growth spurt. We stay small much longer. Partly, the thinking is to be able to balance this whole energy budget – you can’t be growing everything up at the same time – it’s just too expensive for the mother, it requires too many calories – she’s not able to support that, nor is the baby able to get that any calories. So, the brain goes up first, then the body has to catch up – and then, of course, there’s integration of the forebrain and other kinds of complex stuff that’s happening in the brain, later. So, it seems that the brain took advantage of this life history strategy – that we evolved a long life history strategy first for reproductive reasons, and that just set a nice template upon which the brain was able to get larger.


Thursday, November 13, 2008

Canada's Growing Health Care Costs

The CIHI reports that spending on health care in Canada will reach $5,170 per Canadian in 2008. This figure represents 10.7% of the Canadian GDP, the highest share ever recorded. This topic raises many important and interesting issues that, unfortunately, few politicians ever bring up let alone intelligently debate. For example, the balance between public- and private-sector spending and spending on people in different life-stages. Here is a sample from the press release:

Since 1997, the public- and private-sector shares of total health expenditure have remained relatively stable, with governments accounting for 70% of total spending and the private sector (including privately insured and out-of-pocket expenses) for 30%. In 2008, public-sector health care spending is expected to reach $120.3 billion (70.0% of total spending), compared to $51.6 billion spent by the private sector (30.0% of total spending).

Prescribed drugs and dental care account for the largest shares of private health care spending, while hospitals and physicians represent the largest shares for the public sector.

....In 2006, the latest year available for age-specific data, per capita health care spending by provincial and territorial governments was highest for infants younger than 1 ($7,891) and people 65 and older ($9,967). In contrast, health care spending on Canadians between the ages of 1 and 64 averaged $1,832 per person.

Among seniors, there was also great variation. For those age 65 to 69, the average per capita spending was $5,369 in 2006. For those age 85 to 89, per person spending reached an average of $21,209.

This last point adds further weight to the importance of retarding human aging. Keeping people healthier longer would not only benefit aged persons, it would also benefit other people who rely on health care services and other social programs. So everyone would be better off living in a society with decelerated aging.


Wednesday, November 12, 2008

Ten Things You Probably Didn’t Know (But Should) About Aging

Why, you might wonder, would a philosopher and political theorist spend so much time worrying about aging (see here, here and here)?

Well, because I believe aging is the most important neglected issue of our time! If you don't believe me, consider the following ten facts about aging you probably didn't know:

1. The inborn aging process is now the major risk factor for disease and death after around age 28 in the developed countries and limits average life expectancy at birth to approximately 85 years (source).

2. Why do we age? Aging occurs because natural selection favors a strategy in which organisms invest fewer resources in the maintenance of somatic cells and tissues that are necessary for indefinite survival of the individual. (source)

3. Aging is not immutable. The lifespan of organisms such as worms, flies, and mice can be extended by restricting food intake. And experiments with the fruit fly Drosophila melanogaster have demonstrated that their lifespan can be doubled by delaying reproduction over generations. (source) Castration of salmon (source) and humans (source) can also extend lifespan.

4. Approximately 1 in 10 000 Americans are centenarians (source). Having a centenarian sibling increases one’s chances of survival to very old age. (source). The FOXO3A genotype is strongly associated with human longevity (source).

5. The first human clinical trials for an anti-aging molecule began this year. (sources here and here)

6. If you live to 95, you actually stop aging! (but have a very high risk of mortality) (source)

7. In the two hundred years from 1800 - 2000, life expectancy at birth in the world increased from below 30 to 67. (source).

8. There are approximately 600 million persons aged 60 years and over; this total will double by 2025 and will reach virtually two billion by 2050 - the vast majority of them in the developing world. (source) October 1st is the International Day of Older Persons.

9. Despite the fact that the vast majority of the world's 6.5+ population will die from age-related causes, aging research is underfunded. In the year 2006, the National Institutes of Health was funded at $28 billion and yet less than 0.1% of that funding was spent on understanding the biology of aging. (source)

10. Even a modest deceleration in human aging could be this century’s most important medical intervention. Furthermore, there is a sound scientific basis for believing this could be achieved. We are closer to this goal than we are to eliminating cancer or heart disease. Furthermore, age retardation could yield health dividends far greater than those that would be achieved by the elimination of any specific disease of aging. This is the case because of the fact of co-morbidity. This means that eliminating all cancers would only add a few years to life expectancy as one of the other afflictions of senescence would soon ravage an aged person (e.g. heart disease, stroke, diabetes, AD, etc.). So delaying all these afflictions is much more important than eliminating just a couple of them.


Monday, November 10, 2008

What Worry About Aging? (Part 3)

I am in the midst of writing a longer blog post (and new academic paper) on evolution and medicine that deals with the distinction between the proximate and ultimate causes of behaviour and disease.

When preparing that post I came up with the following short story (which in many ways parallels some of the points made in this excellent paper) which I thought it might be prudent to ponder:

Monday morning at 9am Bob left his house for work as he did every weekday. However, he noticed he had a flat tire, caused by a two-inch slash to his front tire. Slightly frazzled, Bob quickly replaced the tire with the spare he had in the trunk of his car. And off he went to work, arriving an hour late.

Tuesday morning at 9am Bob was leaving for work when he noticed that he had a flat tire again! And just like yesterday, a two-inch slash caused the flat. Extremely frazzled, Bob called a tow truck to take his car to the service station. While waiting to get a new tire Bob noticed his neighbour, Jim, was also getting his tire replaced. After a few minutes they realized that Jim’s story was identical to Bob’s. Two flat tires; with two equally sized slashes.

Puzzled by these occurrences they compared notes on where they had driven. Perhaps there was a construction zone close to their street that had lots of nails? But a nail wouldn’t make such a large slash to a tire. Unable to solve the mystery, they went on their separate ways once their tires had been repaired. Bob arrived at work 3hours late.

Wednesday morning Bob was leaving for work when he noticed that he had a flat tire yet again! And so did his neighbour Jim, and all the other cars on his street! The only person who did not have a flat tire was Ted, who lived across from Bob. Bob asked Ted if he knew what caused the two-inch slashes to everyone’s tires but his. Ted suggested it was probably his large pocket knife, which he always used when slashing his neighbour’s tires. "Aha!", thought Bob. That was it. Now he knew what was causing the flat tires.

That evening all the neighbours met at Bob’s house where he revealed the answer to the ongoing mystery. “The flat tires were caused by Ted’s pocket knife!” Bob proudly explained.

“Now what?” wondered Jim.

“I have a plan” replied Bob. And he filled everyone in on his plan to remedy the problem.

Thursday morning Bob awoke extra early. He opened his garage which was now filled with brand new tires. He removed one of these tires and stood by his car.

“Morning Bob” said Ted, as he approached Bob's car with his pocket knife drawn.

“Morning” replied Bob.

Ted then proceeded to slash Bob's tire before casually moving on to the next house. Bob’s neighbour Jim was also waiting for Ted, with spare tire in hand, to quickly change the tire.

“Lucky we bought all these extra tires” remarked Jim as he walked over to Bob.

“That’s right” replied Bob. “Now we will be less inconvenienced by Ted’s pocket knife, the object responsible for all these flat tires”.

And then they went into their respective homes to enjoy breakfast. They were a little tired, and a little more cash-strapped than usual, but not as bad-off as they could have been if they didn’t purchase all those extra spare tires!

The moral of the story: an exclusive fixation on the proximate, rather than ultimate, cause severely limits our opportunities for living flourishing lives. To develop effective strategies that would prevent the massive onslaught of chronic illness humanity is set to experience this century we must devise strategies that seek to redress the ultimate, and not just proximate, causes of disease.

Evolution provides new insights that could help the biomedical sciences devise more effective strategies for promoting our opportunities for health. Rather than prepare by having extra spare tires ready, we should seek to prevent flat tires from occurring by confronting Ted ourselves, or reporting his actions to the police. The knowledge that his pocket knife caused the slash is really of secondary concern (perhaps most useful as evidence in the criminal case against Ted), for it is Ted’s *actions* that are the true cause of the problem. And the solution lies in altering Ted’s behaviour, not in trying to arrange our lives around the inconveniences he causes. Ted is senescence.

While it is not possible to eliminate all the risks of vandalism (or senescence), we ought to at least consider strategies that would minimize the likelihood of these harms being inflicted (like prohibiting vandalism). It is irrational and short-sighted of the neighbours to just accept and live with such harms when there is good reason to believe that other actions would dramatically improve the situation. The current approach to the diseases of aging is like the neighbourhood’s actions. We often fixate on the proximate causes of disease, thus ignoring the evolutionary causes of health and disease. This constrained perspective must be overcome if we hope to meet the challenges facing humanity this century.


Wednesday, November 05, 2008

Main Menu (November 2008)