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In Search of Enlightenment
A political philosopher's reflections on politics, philosophy, science and medicine.
"Enlightenment is man's emergence from his self-incurred immaturity" (Immanuel Kant, 1784).
Wednesday, October 13, 2010
Stratified Medicine: The Dawn of a New Era in Medicine
For the most part, medicine has been deployed on a "one type fits all" mentality to prevent/treat disease. There are of course exceptions and provisos to this. The age or relative health of a patient is often taken into consideration when deciding which course of treatment will be the most safe and effective for a particular patient. A person's medical history (e.g. adverse reactions to a particular treatment, allergies) or lifestyle (e.g. smoker) is also relevant to determining which specific treatment is best for a patient. But beyond those kinds of considerations, prescribing X to treat person Y was based on the evidence that X has proven to be an effective treatment for other people suffering the same thing that afflicts person Y.
But the genetic revolution has opened up a new door of "personalized medicine" that permits doctors to tailor treatments to their patients based on knowledge about their specific biology. And so X might be prescribed for person Y because it has proven to be a safe and effective treatment for a group of people who share the same specific genetic mutations that person Y has. This could increase the safety and efficacy of medical treatment.
Nature@news has this interesting story about how the UK unveiled plans this week to utilize broad genetic testing for selected cancer patients. As the story notes, "this form of 'stratified medicine' uses genetic information to group patients according to their likely response to a particular treatment". A sample from the story:
....The tests, which will look for several dozen mutations in about a dozen genes linked to cancer, will be carried out on people with lung, breast, colorectal, prostate or ovarian cancers, or metastatic melanoma, who are being treated at six NHS hospitals. Therapies that target specific tumour-causing mutations have already been approved, or are on the verge of approval, for most of these conditions, says Peach.
....Peach hopes that the first phase of the cancer programme will pave the way for expanding genetic testing to more patients and other conditions, such as diabetes, AIDS and even psychiatric disorders. Cancer offers a good testing ground for personalized medicine, because numerous targeted therapies already exist, but "there's no reason why this should be restricted to cancer", says Peach.
First Clinical Trial of Human Embryonic Stem Cell-Based Therapy
This news release, from Geron, marks an important and bold step forward for the medical sciences. The first clinical trial of human embryonic stem cell-based therapy is now underway and, as a phase 1 trial, will assess the safety and tolerability of the therapy.
I look forward to seeing how things progress with this trial.
The story of humanity is a fascinating and inspiring one.
Despite the great adversity our species has, and continues to, face, we are capable of great compassion, imagination and inspiration. Indeed, it is perhaps these human traits that have helped us overcome the almost insurmountable obstacles we have faced in our species' evolutionary history.
What we are today reflects the challenges we have had to overcome in the past. From our two eyes and two hands, to our emotions like love, hope and fear, we are a complex history of biological and, more recently, cultural evolution. The inhospitable and unpredictable environments in which our species lived has given us aggression and compassion, emotion and reason, fear and happiness.
To help us overcome starvation we developed tools for hunting and farming. To help us overcome infectious disease we created the sanitation revolution and vaccinations. Our ability overcome diverse and complex forms of adversity is admirable.
The history of humanity is thus one of struggle (with all of its accompanying tragedy) but also one of hope (with all of its accompanying inspiration). Hope for a better state of affairs. One where humans have more opportunities to enjoy health, love and happiness. This aspiration to make things better is, I believe, what makes us truly human. And it is an aspiration that links us to our distant ancestors.
The title of this post is "David vs Goliath". Humanity is David, and Goliath represents all the things that have, and continue to, challenge the health and welfare of humans. The specific form of Goliath alters over time. Reflecting on the causes of death in the 20th Century, for example, we see that Goliath was warfare (including two World Wars), totalitarianism, and, most importantly, infectious disease. The Flu pandemic of 1918, for example, killed an estimated 50 000 000 people, which is more than 3 times the estimated number of deaths caused by four years of “Great War” in 1914-18. And small pox is estimated to have killed between 300 and 500 million people in just the 20th century.
In the 21st century, Goliath is CHRONIC DISEASE (e.g. cancer, heart disease, stroke, etc.). Just 1 year of chronic disease today kills as many people as 300 years of the Black Plague.
In the decade from 2005 and 2015, the World Health Organization estimates that 220 million people will die from chronic illness, 144 million of these deaths will be in lower middle income countries like China and India.
To slay the Goliath of today humanity must be more compassionate, more imaginative, and more inspiring than it has been in the past. Slaying Goliath in the 21st century will require, I believe, an aggressive effort to understand the biology of aging, and then the development of interventions that modulate the rate of aging, so that humans can enjoy more disease-free life and a compression of morbidity at the end of life.
Why we age, and become frail and diseased, is a legacy of our evolutionary history. In short, because life in the state of nature was "nasty, brutish and short" the force of natural selection does not apply to the post-reproductive period of the human lifespan. So most disease and death today are caused by evolutionary neglect. And given the size of today's aged populations, unprecedented numbers of humans will suffer the ravages of chronic disease.
The vision of David battling Goliath came to me today as I happened across the following video this morning and was deeply moved by it. It is an interview with J.M. Smith, an evolutionary biologist who died in 2004. While a student Smith studied fruit fly genetics with J.B. Haldane.
In this interview Smith discusses the illness and death of his teacher, who died of cancer. This brief video moved me in many ways. It captures the human ability to display humour and determination in the face of adversity, as well as love and friendship. It captures humanity's most redeemable qualities, as told by one the greatest scientists of the 20th century.
It is only fitting to quote a passage from Haldane's famous poem on cancer:
I wish I had the voice of Homer To sing of rectal carcinoma Which kills a lot more chaps in fact, Than were bumped off when Troy was sacked
To slay Goliath this century we must build on the work of great minds like Haldane and Smith. We must transcend the "disease model" approach to the medical sciences, and develop Darwinian medicine.
And aging research is at the frontier of this more robust and ambitious vision of medicine. Modifying the biological clocks we have inherited from our Darwinian past would be this century's most important advance in public health. For age retardation would help protect the 2 billion people who will be over the age of 60 by 2050 from the chronic diseases that currently ravage unprecedented numbers of aged people in the world today. In order for this biological revolution to occur we must also undergo a cultural revolution. We need a rational and humane culture. We need more compassion, more imagination and more (new sources of) inspiration.
And we all have a moral responsibility to help spur on this cultural revolution and become 21st century humanists.
This year's Noble prize in medicine has been awarded to Robert Edwards for the development of IVF. Here is an excerpt from the press release:
Robert Edwards is awarded the 2010 Nobel Prize for the development of human in vitro fertilization (IVF) therapy. His achievements have made it possible to treat infertility, a medical condition afflicting a large proportion of humanity including more than 10% of all couples worldwide.
As early as the 1950s, Edwards had the vision that IVF could be useful as a treatment for infertility. He worked systematically to realize his goal, discovered important principles for human fertilization, and succeeded in accomplishing fertilization of human egg cells in test tubes (or more precisely, cell culture dishes). His efforts were finally crowned by success on 25 July, 1978, when the world's first "test tube baby" was born. During the following years, Edwards and his co-workers refined IVF technology and shared it with colleagues around the world.
Approximately four million individuals have so far been born following IVF. Many of them are now adult and some have already become parents. A new field of medicine has emerged, with Robert Edwards leading the process all the way from the fundamental discoveries to the current, successful IVF therapy. His contributions represent a milestone in the development of modern medicine.
The Sept issue of Scientific American is a special issue on "the end". It includes this fascinating article by one of the leading experts on aging. Here are a few excerpts:
IF YOU WERE GIVEN a free hand to plan how your life will end—your last weeks, days, hours and minutes—what would you choose? Would you, for example, want to remain in great shape right up until the last minute and then go quickly? Many people say they would choose that option, but I see an important catch. If you are feeling fine one moment, the very last thing you would want is to drop dead the next. And for your loving family and friends, who would suffer instant bereavement, your sudden death would be a cruel loss. On the other hand, coping with a long, drawn-out terminal illness is not great either, nor is the nightmare of losing a loved one into the dark wastes of dementia.
We all prefer to avoid thinking about the end of life. Yet it is healthy to ask such questions, at least sometimes, for ourselves and to correctly define the goals of medical policy and research. It is also important to ask just how far science can help in efforts to cheat death.
....By far the majority of natural organisms die at relatively young ages because of accidents, predation, infection or starvation. Wild mice, for example, are at the mercy of a very dangerous environment. They are killed rather quickly—it is rare for a wild mouse to see its first birthday. Bats on the other hand are safer because they can fly.
Meanwhile maintenance of the body is expensive, and resources are usually limited. Out of the daily intake of energy, some might go to growth, some to physical work and movement, some to reproduction.
....Here is where the disposable soma theory comes in. The theory posits that, like the human manufacturer of an everyday product—a car or a coat, for example—evolving species have to make trade-offs. It does not pay to invest in allowing indefinite survival if the environment is likely to bring death within a fairly predictable time frame. For the species to survive, a genome basically needs to keep an organism in good shape and enable it to reproduce successfully within that time span.
....Using the science of aging to improve the end of life represents a challenge, perhaps the greatest yet to face medical science. Solutions will not come easily, despite the claims made by the merchants of immortality who assert that caloric restriction or dietary supplements, such as resveratrol, may allow us to live longer. The greatest human ingenuity will be needed to meet this challenge. I believe we can and will develop treatments targeted at easing our final years. But when the end arrives, each of us—alone—will need to come to terms with our own mortality. All the more reason then to focus on living—on making the most of the time of our lives, because no magic elixir will save us.
NatureNewshas the scoop on a new global survey of scientific literacy. A sample from the story:
Science, it is often said, is an international language. But how international are attitudes towards science and scientists? Nature and our affiliated publication Scientific American set out to learn how the views of the scientifically literate public vary around the world. Our web-based survey of more than 21,000 readers of Scientific American and its translated editions in 18 countries revealed that although these science enthusiasts read the same publication and share many attitudes in their perception of science, they seem to diverge on some of the hottest-button issues.
The differences are most striking between east Asia and the rest of the world. For example, a startling 35% of the Japanese and 49% of the Chinese respondents agreed that there is "reason for doubt" about evolutionary theory's ability to explain the variety of species on Earth. In contrast, the numbers for the rest of the world fluctuated around 10%. Japanese and Chinese respondents were also less likely than others to say that they trust scientific explanations of the origins of the Universe. And almost one-third of scientifically literate Chinese people say that scientists should not get involved in politics, compared with around 10% of respondents in most of the rest of the world.
