“We have drunk Soma and become immortal; we have attained the light, the Gods discovered. Now what may foeman’s malice do to harm us? What, O Immortal, mortal man’s deception?”
Rigveda, 8.48.3
The Epic of Gilgamesh, considered the first great work of literature, is a collection of Mesopotamian poems that chronicles the journey of Gilgamesh, the king of Uruk.1 At the core of this journey is Gilgamesh’s search for immortality after the death of his brother Enkidu. Penned in the Third Dynasty of Ur (circa 2100 BC), it is one of mankind’s earliest surviving stories or epics.
The search for immortality occurs over and over again throughout history and throughout literature. As early as 475 BC, Chinese texts refer to various elixirs of immortality, and Emperor Jiajing (1521–67) is said to have died from mercury poisoning after consuming such an elixir. According to the Rigveda, a collection of ancient Vedic or Hindu hymns, amrita is a drink that bestows immortality. In Hinduism and other traditions, it is also referred to as “soma”. Indra, the god of the heavens, and Agni, the god of fire, drank amrita (or ambrosia) to attain immortality. In classical Greek mythology, the philosopher’s stone was not only able to turn lead into gold, but also grant immortality to the holder.
The technology of the Augmented Age may, for the first time in history, actually give mankind the tangible ability, not to attain immortality per se, but to significantly extend our lifespan and eliminate diseases that have plagued humanity for hundreds of years. The primary technology to watch over the next decade is that of genetic engineering—the ability to edit our DNA like computer code. At the heart of these advancements in bioengineering is the ability to understand the workings of our biology like never before, made possible largely through better measurement technology and computer processing power.
Some believe that this era will usher in a technology-led event or singularity that will give us the ability to live longer, if not indefinitely. The movement most often associated with the technology-based search for immortality is labelled the “transhumanist” movement. Unlike the historical efforts at finding the fountain of youth, the promise of increased longevity over the next couple of decades has some basis in fact as a result of the incredibly exciting technology improvements emerging in various fields associated with health care and medicine.
Transhumanism is a loosely defined movement that has developed gradually over the past two decades. It promotes an interdisciplinary approach to understanding and evaluating the opportunities for enhancing the human condition and the human organism opened up by the advancement of technology. Attention is given to both present technologies, like genetic engineering and information technology, and anticipated future ones, such as molecular nanotechnology and artificial intelligence.
Nick Bostrom, “Transhumanist Values,”
Journal of Value Inquiry 37, no. 4 (2003): 493–506.
This so-called post-human future focuses on two broad classes of human augmentation. The first is bioengineering and the second is technology-led augmentation, sometimes called cyborgification. Changing the way we live as humans and our overall health or condition is a key outcome of the Augmented Age. Over the next two chapters, we’re going to look at these two paths influencing humanity. This is not some fringe science-fiction consideration any more. Technology is fundamentally changing both our understanding of our biology and how we will actively manage our health and lifespan in the future.
In this chapter, we’ll consider how technology is helping us improve our own biology using genetics, personalised medicine and the principles that have emerged in the quantified self (QS) movement. In chapter 6, we’ll look at the use of technology to enhance our humanity more specifically.
To understand the potential impact of genetics and gene editing on the future of humanity, it is helpful to understand that huge strides have been made in the last few decades. In 1984, the first Human Genome Project (HGP) was proposed and funded by the US government, but the project really only got underway with international cooperation in 1990. It then took 13 years and collectively almost US$3 billion of public and private investment to complete the first human genome sequence of the approximately 20,500 genes and 150,000 base pairs present in the donor DNA samples.2 Today, companies like 23andMe can do a genotyping sequencing (comparing your DNA with other human baselines) for just US$100 in a few weeks. If you want a full, original genome sequence, it still costs around US$10,000, but that is expected to fall to under US$1,000 over the next few years thanks to Moore’s Law. Falling from US$3 billion to US$1,000 in just 25 years means that by 2025 it will likely cost less than US$10 to do an original sequencing of your DNA, and computer processing power will enable it within seconds.
Why is this important? There are dozens of diseases already identified that are genetic in nature3 such as autism, breast, prostate, skin and colon cancers, cystic fibrosis, haemophilia, Parkinson’s disease, sickle-cell anaemia and others. Many other diseases result from imbalances in the immune system or specific protein deficiencies that are likewise genetic. We’ll talk more about how gene editing will tackle these conditions later in the chapter.
It’s not just genetic engineering that is changing the way we manage our health. Significant costs are involved in treating diseases once diagnosed, and typically the later many conditions are diagnosed, the more expensive the treatment, and the lower probability of successful treatment. For many forms of cancer, early diagnosis makes you 90 per cent more likely to survive for at least five years after the diagnosis.4
Recent advances in imaging and detection techniques, along with chip-based diagnostics, are rapidly disrupting the fields of pathology and diagnosis. We’ll discuss a few of those technologies in a moment.
For now, a more immediate change to our health care and well-being has emerged through the application of technologies that measure our health and physical performance on an individual basis. This technology is collectively part of the QS movement. It is increasingly clear that the data we collect on how we use our time and money, how we consume food and water, how many steps we take or calories we burn, and how well we’re sleeping can be leveraged for a significant improvement in personal well-being.
If you’ve worn a fitness band like a Fitbit, or a smartwatch, you are already probably monitoring your steps or physical activity on a daily basis. While QS technology, standards and methodologies are still evolving, we can already see the broad areas in which it can be utilised to improve our lives.
There is growing evidence to support, for example, tracking your heart rate during exercise and beyond, as well as occasionally getting readings of your blood pressure, brain waves (while awake and asleep), body fat, weight and more. By tracking one or all of these measures, it allows you not only to improve your daily habits incrementally, but also allows medical and health professionals access to better data to give you personalised advice.
Tracking heart rate was traditionally accomplished through an expensive, clinic-based ECG machine that required you to be hooked up via ten different sensors with long wires connected to a desktop machine. If you wanted portability in your heart rate monitor, in the past it required a user to wear a cumbersome chest band, which was uncomfortable for many. Today, you can now wear a wristband heart rate monitor, such as the Mio5 or the Apple Watch. Once you have a wearable monitor, you will be able to start using a variety of apps that utilise heart rate, mostly for fitness, but also for some very strange things, including whether you are allergic to specific foods6 or how comfortable, stressed or emotional you feel about the people you spend time with.7 All of this is possible because of the response our heart shows to a wide variety of activities.
Fitness apps are starting to track more and more data, as part of programs that include dozens of measures. One typical way for people to dip their toe (or legs) into the QS pool is to start using a treadmill. Once you start walking on a treadmill, you can gradually increase the speed to that of jogging and then to running. (One definition of running used in gyms is the 10-minute mile pace or faster, or 6 miles per hour and above.) Once you start running, you can increase the pace gradually. Here’s a treadmill readout that Alex photographed after a milestone run, and the comments he posted to his friends on Facebook:
Just spending US$84 or so on a Vivofit8 or another such device that tracks steps can result in a person doing many more steps or much more of whatever good behaviour is being tracked. Here is an example of a personal achievement. Alex walked 55,848 steps in one day to decisively win the weekly Step Challenge for people who use Vivofit.
Alex recounts his experience from that week:
“It was raining, but to make sure that I didn’t fall behind, I walked up and down the halls of my hotel while reading books. I even walked up and down the aisles of the plane as my fellow passengers slept, just to get in a few thousand extra steps. Look at the calories burned on that particular day—4,065…from just walking. That’s more than a pound’s worth of calories (3,500) torched while I walked on my treadmill desk, and everywhere else I could.”
Gamification through peer-group competition or comparison can be a very powerful motivator, as can competing against yourself to improve. This is a core element of the quantified self that we now recognise as a powerful behavioural imperative.
Most people are shocked to discover how often their sleep is interrupted during a typical night’s slumber. Tens of millions of people around the world have been introduced to this concept via the weight loss television reality show The Biggest Loser. It’s not unusual for contestants, all of whom start off obese, to find that they have sleep apnea and stop breathing many times a night. This condition wakes people up over and over, sometimes hundreds of times a night, and keeps them from the most refreshing and mentally renewing levels of sleep, including rapid eye movement (REM) sleep and deep wave sleep (DWS).
In fact, sleep difficulties like obstructive sleep apnea can cause high blood pressure, heart problems, weight gain, type 2 diabetes, asthma, acid reflux and lapses in concentration. People with sleep apnea are five times more likely to have traffic accidents than normal snoozers.9
The QS related to deep waves has become somewhat like a holy grail, with researchers such as Dr Giovanni Santostasi switching his professional focus from astrophysics (which makes use of the analysis of wave forms to find and precisely describe stars and other objects in outer space) to DWS research by studying electroencephalograms (EEGs), readings of the brain’s electrical activity which appear in distinctive wave patterns.
To quote Dr Santostasi, neuroscientist at Northwestern University Feinberg School of Medicine:
“Sleep in general, and a specific stage of sleep called slow wave sleep (SWS) in particular, is of paramount importance for cognitive and bodily health. SWS facilitates long-term memory storage and has been found to have significant effects on metabolism, cardiovascular health and proper functioning of the immune system. Failing to get enough SWS promotes obesity and diabetes, negatively impacts cardiovascular health and impairs the functioning of the immune system, in addition to negatively impacting cognitive functioning and long-term memory retrieval. Furthermore, the quality of SWS decreases dramatically with age and this leads to significant age-related cognitive impairment.”
Dr Santostasi and his colleagues have developed a system that utilises acoustic stimulation of the brain to increase the duration and intensity of slow wave activity (SWA) so as to stabilise and increase the quality of sleep. It does this by synchronising the electrical activity of the brain regions responsible for facilitating SWA during SWS to the degree with which they would be naturally synchronised in a young and healthy individual, in such a way as to externally control the quality (i.e. duration and intensity) of SWA during SWS.
The QS idea is that facilitating this synchronisation via sound instead of electricity brings the power to enhance SWS into the hands and heads of consumers. Up to now, using electricity to effect this synchronisation (i.e. via transcranial direct current stimulation) has required the expertise of trained technicians in order to be safe and effective.
“The new quantified self system utilises feedback algorithms that measure the duration and intensity of SWS as it is naturally occurring in the user’s brain and modifies the amount with which SWA is enhanced in proportion to how much it is lacking, which is much more effective than increasing the duration and intensity of SWA by some unchanging baseline degree. This allows the system to adapt in accordance with the degree with which a user’s SWS is impaired.”10
Soon, you’ll be able to put on headphones to go to sleep and enter an SWS state that will improve your brain, ability to learn, memory and ability to get to and/or maintain a healthy weight. By using this method, you may also need less sleep each night. Imagine what you could do with 2 or 3 hours of less sleep each night, but still wake up in better shape than you do today?
A new device launched recently on a Kickstarter campaign gives you the ability to scan food in front of you and get an estimate of the number of calories you are about to consume.
The portable scanner harnesses the power of physics and chemistry to figure out everything from the sugar content of a given apple to whether or not that drink you left on the bar has been drugged. The device, called “SCiO”, uses spectroscopy, a technology similar to the one that helps astronomers figure out the make-up of the stars.
SCiO detects the molecular “signature” of your food and then sends the details to your smartphone through its Bluetooth connection. SCiO’s database translates that signature into nutritional content including typical calorie counts, properties of the food, etc.
Figure 5.3: The SCiO spectrometer works with your smartphone to tell you the chemical make-up of food. (Credit: SCiO)
While this technology is still in its infancy, we can anticipate in the near future a smartphone that tells you how many calories and carbs are in the meal you just instagrammed to your friends. Once individuals are armed with such knowledge, what impact will this have on the obesity epidemic globally? Imagine your smartphone telling you that if you eat that last doughnut, your chances of a heart attack in 14.6 years will increase by 7.5 per cent. How would you react?
One of the most interesting uses of QS information is to allow you to see trade-offs in each of the things you do or don’t do, and how this—on average—seems to statistically influence your life expectancy. You can start to make powerful positive trade-offs by changing just a few bad habits as illustrated in figure 5.4:
The first 20 minutes of cardio exercise gives you back an HOUR of extra life?! Why didn’t someone tell Alex that, oh, 33 years ago when he was about to stop running for the next 28 years? And the next 30 minutes is almost break-even? That’s a pretty good deal. The best deal? Having fruit with coffee in the morning and vegetables with wine at night. Total banked for a day with an hour of running and that meal plan? An extra 4.5 hours added to your lifespan!
Let’s dive deeper into this concept of adding years to our lives and life to our years, and building our brains while we are at it, before looking at how to activate the protection against linear decay, and upgrading ourselves.
QS products started off as separate products and, by 2013, had reached over US$200 million a year in sales, primarily for devices that counted steps and calculated calories based on height, age and weight input by the user. Several apps have duplicated or emulated this functionality in iOS and Androids. Such an app functionality became part of the Apple iOS in 2015, in large part to increase the functionality and usefulness of the Apple Watch. Apple calls this particular app HealthKit.
As you can see from the screen shot of Apple’s HealthKit app in figure 5.5, there are seven major categories (body measurements, fitness, me, nutrition, results, sleep and vitals) and 67 separate categories under All, ranging from active calories through to zinc levels.
Undoubtedly, each new major version of the operating system (iOS or Android) will likely add additional categories in the years to come. This data is going to be essential for future treatment, as you will soon see.
Technologically, society’s mania for measurement has created multiple US$100 billion valuation companies, including Intel (whose chips we buy because of their increasing MHz of processing power), Cisco (whose routers enable us to reduce milliseconds of latency), Facebook (whose measures of Friends, Likes and Comments are all enumerated so that we can see them) and Google (whose searches save us a reported 20 minutes on average as opposed to carrying out the same search using paper sources). With all of the measures and the capability of having ready online access to tens of thousands of baselines, which ones actually count?
How long we live influences everything, in part because of dependencies. A number of futurists use, either explicitly or implicitly, models like DSTEP, which was devised by Frank Feather. Demographic changes lead to social changes lead to technological changes lead to economic changes lead to political changes.
In Feather’s methodology, everything that happens in the world happens because of changes in demographics. In the recent past, the most significant demographic change has occurred because lifespan is getting measurably longer. On average, our life expectancy gets approximately five hours longer every day due to medical advancements and science.11 As Thomas Kirkwood explained in a special issue of Scientific American:
“It is often said that our ancestors had an easier relationship with death, if only because they saw it so much more often. Just 100 years ago life expectancy was shorter by around 25 years in the West. This literal fact of life resulted because so many children and young adults perished prematurely from a variety of causes. A quarter of children died of infection before their fifth birthday; young women frequently succumbed to complications of childbirth; and even a young gardener, scratching his hand on a thorn, might be lost to fatal blood poisoning.
Over the course of the past century sanitation and medical care so dramatically reduced death rates in the early and middle years of life that most people now pass away much later, and the population as a whole is older than ever before. Life expectancy is still increasing worldwide. In the richer countries around the world it lengthens five hours or more every day, and in many developing countries that are catching up, the rate quickens still faster.”
Ultimately, though, if you want to live longer, you have to look out for your own health. You have to find your own way of embracing things that are good for you, and rejecting things that are bad for you.
This is where those 67 categories in the iOS health app suddenly become useful. You can go through and start tracking a specific measure, and keep working on it until you have reached a plateau. Then choose another measure and repeat the process. Alternatively, you can start multiple ways of improving that are synergistic whereby time, money or effort invested in one area will be useful in many other areas. It used to be very hard, or nigh on impossible, to keep track of this data, but the cost of doing so is coming down dramatically.
Although men generally have more muscle mass than women, both sexes reach their physical peak as young adults in their late 20s to early 30s, according to Human Development: A Life-Span View by Robert Kail and John Cavanaugh. After this point, your physical strength will slowly decline throughout the remaining years of your life. Sensory abilities peak in your early 20s. Depending on the individual, vision typically begins to deteriorate in your 40s and 50s. However, hearing starts to decline as early as your late 20s. The ability to taste, smell, balance and feel pain or changes in temperature remains the same until your later years.
There are five areas in which we decline by roughly 1 per cent annually after we reach our peak. We call them “linear decay factors” because they are roughly linear, either on normal graph paper or if put on a logarithmic scale. We call the process of doing everything it takes to neutralise these linear decay factors, or even start getting improvement again, the “Activated Self”. It is what we will logically do in the future with all that data we’re collecting and interpreting about our health.
Telomeres are the end caps on our chromosomes, which are made of the tightly wrapped double helix of our DNA. They are sometimes compared with aglets, the little pieces of plastic at the ends of your shoelaces.
We have 15,000 units of telomeres at conception. Each time our cells divide, we lose telomeres. Our cells divide so many times while we are in the womb that by the time we are born, we have only 10,000 remaining units. A typical human who dies of natural causes in old age will have around 5,000 units or so. In the absence of special treatment (which animals such as Turritopsis nutricula, a type of jellyfish, can perform to rejuvenate their cells), after a certain number of divisions, our cells hit the Hayflick limit and cannot divide any more.
One of the causes of ageing is that telomere, or DNA, damage occurs and is not repaired before the cell divides. Think of it like an aglet that frays at the end of your shoelace. When it is gone, the shoelace continues to fray and unwind its thread until it is useless or needs to be replaced.
A 2013 study established that people who suffer from anxiety have shorter telomeres. In the study, researchers at the University of California, San Francisco, and the Preventive Medicine Research Institute found that better lifestyle management could help lengthen telomeres over time which, in turn, could extend lifespan. For the study, researchers followed 35 men for over five years. The participants had early stage prostate cancer. About ten men in this group were asked to adopt a healthier lifestyle such as eating nutritious food, exercising for 30 minutes a day and taking up meditation to reduce stress levels.
Results showed that the men who changed their lifestyle had longer telomere length, about 10 per cent longer than the other participants. In contrast, the men who didn’t adopt healthy behaviour had shorter telomeres by the end of the study.
One of the most promising aspects of longevity research is the ability to liberate telomerase (the enzyme that repairs telomeres) and rejuvenate telomeres, thereby extending cell life almost indefinitely. Telomere length is considered one of the primary ageing “clocks” in the human body but our bodies currently do not have the unaided capacity to lengthen telomeres. Expect to hear a lot more about telomeres in the science of longevity activation.
VO2 maximisation (or simply VO2 max) is a measure of maximum ventilatory capacity, measured in millilitres of oxygen per kilogramme of (your) body weight per minute. We lose 1 to 0.1 point of VO2 max a year starting from the age of 28 until death, an average of about 0.4 more if a person sits for hours each day or is overweight.
The highest human VO2 max recorded was 97.5 for a cyclist taken in 2012. Most Olympic marathoners are in the mid- to high-70s. The highest VO2 max for a domesticated animal is 150 for race horses, and for a mammal in the wild, up to 300 for a cheetah, which can run 60 to 70 miles an hour but only for about two minutes.
The best way to boost your VO2 maximisation is to repeatedly run 1 mile as fast as you can. VO2 is the greatest open secret of good runners and cyclists. The more oxygen you inhale, all other things being equal, the better and more clearly you can think, the farther you can run and the more you can stay alert and energised. Your brain consumes 20 to 25 per cent of your oxygen supply, so it makes sense to maximise your ability to ventilate every cell with oxygen. Aiming to boost and keep VO2 max as high as possible for as long as possible is one of the major keys to keeping mentally alert in your golden, or senior, years.
Sarcopenia is the Greek term for “muscle poverty” or “muscle wasting”. From the age of 30, we lose 1 per cent of our lean muscle mass each year. Skeletal muscle can be divided into fast twitch and slow twitch. In chickens, the fast twitch is typically the white meat and the slow twitch is the dark meat. In humans, fast twitch muscles decay faster than slow twitch, creating the problem of the elderly stumbling and being unable to catch themselves, and then falling down, or the problem of being unable to get up out of chairs.
Researchers have already shown that when older people eat, they cannot make muscle as fast as the young. Now they’ve found that the suppression of muscle breakdown is blunted with age. This may explain the ongoing loss of muscle in older people—when they eat, they don’t build enough muscle and, in addition, their insulin fails to shut down the muscle breakdown that rises between meals and overnight.
A 2009 research study by the American Journal of Clinical Nutrition showed that three weight-training sessions per week over 20 weeks could rejuvenate blood flow in the extremities to the level of someone in their late 20s.
Osteopenia is the Latin medical term for “bone loss, poverty or wasting”. From the age of 30, women and most men lose about 1 per cent of bone mass a year. From age 40, however, osteopenia accelerates in women and, on average, they lose 2.5 per cent and more of bone mass from their spines and hips, making them often grow shorter and more prone to breaking a hip if they stumble and fall from sarcopenia. Breaking a hip is terrible for the elderly. In recent years, the mortality rate from breaking a hip after the age of 70 was a shocking 30 per cent within the first year and 50 per cent within 18 months of the fall.
Resistance training can combat this effect because as you put more tension on your muscles, the tension puts more pressure on your bones, which then respond by continuously creating fresh, new bone. In addition, as you build more muscle, and make the muscle that you already have stronger, you also put more constant pressure on your bones.
Of all the linear decay factors, brain poverty or brain wasting is the scariest. From the age of 26 (or earlier), the average person will lose 1 to 2 grammes12 of brain mass a year, increasing gradually, so that within 15 years (age 45) that person is losing at least 2 to 3 grammes a year. This increases to 3 to 4 grammes a year from age 60, 4 to 5 grammes a year from 75 and 5 to 6 grammes a year from 90.
A team of researchers from the University of California, Los Angeles (UCLA), discovered that obese, elderly individuals had 8 per cent lower brain mass than older people of normal weight. Additionally, people who were simply overweight had 4 per cent less brain volume than their slimmer counterparts. In addition, being anxious, depressed, paranoid, suffering from trauma, divorce, violent crime or sustained emotional distress will further accelerate loss of brain mass. Blindness, deafness and lose of other senses, as well as loss of mobility, can also cause loss of brain mass.
Dr Daniel Amen, who claims to have reviewed over 75,000 SPECT (blood flow) brain scans in his medical research clinics, asserts that being overweight or obese will cause the loss of 4 to 8 per cent of brain mass. Amen notes that research from the University of Pittsburgh also found that the brains of overweight people—with body mass index (BMI) scores between 25 and 30—had 4 per cent less volume than brains of people with lower BMIs. In addition, brains of overweight subjects looked eight years older than those of healthy subjects. People who were obese—with BMI scores over 30—had 8 per cent less brain volume, and their brains looked 16 years older than those of healthy people.
“We found that changing the brain also changed the body,” Amen says. “Significantly, we also found that as weight goes up, brainpower goes down. The size and function of the brain diminishes as BMI goes up. This information should make everyone concerned about [his or her] weight... Fat can produce inflammatory chemicals that damage your brain. We found that the larger people were, the smaller their frontal lobes were, and that’s a disaster because the frontal lobes run your life!”
Dr Daniel Amen, University of Pittsburgh
The average human brain weighs 1,300 to 1,500 grammes (approximately 2.9 to 3.3 pounds). Although the brain accounts for only about 2 to 3 per cent of the total body weight of an adult, it consumes about 20 to 25 per cent of the body’s oxygen supply. Interestingly, 60 per cent of a newborn’s oxygen supply is consumed by the brain because the brain is doing huge equivalents of Bayesian analysis and other statistical/stochastic comparisons and learning to fully engage and interpret the data from their eyes, ears, nose, tongue, fingers, skin, etc.
The National Institute of Health studies of Dr Henrietta van Praag and her colleagues, as popularised by the writing of Harvard’s John Ratey,13 instruct us that if we run for at least 45 minutes at a pace which raises our heart rate to at least 75 per cent of its maximum, we will create new neural stem cells, primarily in the hippocampus. These new cells will last for about 21 days. In order for them to “wire” with other neurons and last longer, we would need to learn something new. “Neurons that fire together, wire together” is the neuroscientist’s way of summarising this process.
One of the more exciting discoveries about exercise-induced neurogenesis is that the brain loses brain cells more rapidly in some areas than others. Amazingly and fortuitously, the areas that lose brain cells the soonest and fastest are also the areas that add brain cells back again at an accelerated rate. Over a dozen independent researchers have reported this effect.14
By doing specific exercises more regularly and maintaining a stricter diet, you can dramatically change your general health and your lifespan. The quantified self is just the start of a whole range of tools that we’ll use in the future to improve our quality and length of life.
Today, one of the more contentious areas of health care is the very nature around the treatment of conditions and symptoms. Rather than remove the cause of many health issues, a great deal of energy in pharmaceuticals and medicine goes into combating the symptoms of a condition or disease. Part of this is based on the fact that we’re not very good at removing these conditions permanently, and also partially due to the fact that drug companies tend to make more money out of ongoing treatment regimens rather than from something that eliminates the need for treatment.
Let’s take cancer as an example.
At the beginning of the twentieth century, one person in twenty would get cancer. In the 1940s, it was one out of every sixteen people. In the 1970s, when President Nixon declared “War on Cancer”, it was one person out of ten. Today, one person out of every two or three people gets cancer in the course of their life.15 Yes, you read that right. The incidence of cancer in society has exploded in the last 100 years. Is that just better diagnosis?16 No, it appears that more and more people are getting cancer.
To be fair, we have improved survivability of many types of cancer significantly, and that is expected to continue to improve. Based on growth and ageing of the US population, however, medical expenditures for cancer in the year 2020 are projected to reach at least US$180 billion, an increase of 27 per cent over 2010. If newly developed tools for cancer diagnosis, treatment and follow-up continue to be more expensive, medical expenditures for cancer could reach as high as US$207 billion.17 There were an estimated 14.1 million cancer cases around the world in 2012; of these 7.4 million cases were in men and 6.7 million in women. This number is expected to increase to 24 million by 2035, so we need to find a cure for cancer. How will we get there?
Figure 5.6: Microfluidic devices like this are just the start of a range of non-invasive chipbased diagnostic tools that replace traditional testing labs.
As we mentioned earlier in the chapter, early diagnosis is probably the primary thing we can do to impact cancer survival rates over any other short-term strategy. To that end, technology has a significant role to play. A Harvard student may have just developed a technique that is a great example of this possible future.
In November 2015, 18-year-old Neil Davey won the silver medal in the undergraduate section of the National Inventors Hall of Fame’s Collegiate Inventors Competition for his research project, “Early Cancer Diagnosis by the Detection of Circulating Tumor Cells using Drop-based Microfluidics”. This non-invasive cancer detection method is representative of a whole slew of new technologies that come with enhanced computer power, chip-based diagnosis and improved sensor technologies.
The Harvard student utilised an emerging technique that involves injecting a tiny amount of blood into a microfluidic device to encapsulate single cells from the blood stream in individual drops. Some of these devices can use sample sizes as small as 100 nanometres. Davey then utilised a polymerase chain reaction (PCR), a common technique in molecular biology, to target and amplify fragments of cancer DNA within the microfluidic drops. By shining a laser onto the droplets, he was able to detect and quantify the brightness of the samples, indicating the presence (or not) of cancer DNA in a circulating tumour cell.
“The advantage of this technology is that it is ultra-sensitive, so I can detect as few as one cancer cell from a billion normal cells in the blood… The process is also very specific. One can uniquely detect a wide range of cancers using this DNA amplification technology.”
Neil Davey, undergraduate student at John A. Paulson
School of Engineering and Applied Sciences18
Previously, a biopsy of a tumour was the only way to properly and accurately diagnose the type of cancer, and this was extremely invasive, often requiring surgery. Microfluidics is safer, faster and a fraction of the cost of typical testing procedures that are in place today.
Microfluidics is going to radically change the way we think about health care and diagnosis. Think about pretty much any condition you might need to be tested for today—high cholesterol, diabetes, kidney or liver problems, iron deficiency, heart problems, sexually transmitted infections, anaemia, hepatitis, HIV and various viruses—and they are typically tested for either via blood being drawn or via urinalysis. With blood tests, it typically involves drawing a significant amount of blood to get accurate tests. Here is where technology advancements will dramatically change these tests.
While facing some controversy recently, the Silicon Valley start-up Theranos was one of the first to really tackle this problem. Theranos has developed blood tests that can help detect dozens of medical conditions based on just a drop or two of blood drawn with a pinprick from your finger. At Walgreens pharmacies across the United States, you simply show a pharmacist your ID and a doctor’s note, and you can have your blood drawn right there. From that one sample, several tests can be run often at a fraction of the cost of a typical pathology test. A typical lab test for cholesterol, for example, can cost $50 or more in the United States. The same Theranos test at Walgreens costs around US$3.
But why do we need to go to a place, such as a pharmacy or a doctor’s surgery, at all? The winner of the 2014 Tricorder XPrize, created by Peter Diamandis and sponsored by the likes of Nokia and Qualcomm, was an eight-year-old company that has received grants and support from NASA, the National Institutes of Health, the Bill and Melinda Gates Foundation and many others. DNA Medical Institute (DMI) is the creator of a device called rHEALTH (short for Robot or Remote Health).
The rHEALTH diagnostic system requires a patient to provide just a single drop of blood. This drop of blood is dropped into a small receptacle, where nanostrips and reagents react to the blood’s contents. The whole cocktail then goes through a spiral micro-mixer and is streamed past lasers that use variations in light intensity and scattering to come up with a diagnosis. You can then get the results delivered to your smartphone via Bluetooth.
The rHEALTH mobile unit is currently a desktop unit, but DMI is working on getting it down to the size of a tricorder that you could carry in the palm of your hand.
For other basic biomonitoring, the theme of the Star Trek Tricorder keeps coming up in developmental technology. The Scanadu Scout Tricorder is a device that also links to your smartphone and can give you even more comprehensive “live” information than the likes of your fitness heart rate monitor.
The Scanadu Scout is a non-invasive biomonitoring system that measures physiological parameters such as temperature, heart rate, pulse oximetry and blood pressure. It does this by just touching a small portable device to your head, and sends the data to an app for analysis.
Scanadu’s mission statement says everything about how technology is tackling the challenge of personal diagnosis:
“To be the last generation to know so little about our health.”
Today, there are already devices like the Illumina MiSeqDx, which is a desktop DNA sequencer. Ultimately within the next 20 years, each individual will be able to have access to a device that instantly sequences their DNA and compares it with known conditions, and can diagnose almost any health condition they might currently have due to a virus or other illness. If you have cancer, not only will that handheld device be able to diagnose the type of cancer with better accuracy than a doctor today, but it will also be able to sequence the genes of your specific cancer cells in real time and then send that data to a lab somewhere on the other side of the world to manufacture a specific, targeted, personalised medicine.
Researchers at Washington University in St. Louis recently used gene sequencing19 to compare healthy tissue to diseased tissue among three patients with advanced melanoma. By pinpointing each patient’s unique protein mutations, the researchers were able to craft vaccines that increased the strength of the patients’ cancer-killing T-cells.
Figure 5.10: Seven different gene sequences of common prostate cancer (Credit: Nature 470, no. 7332, February 2011)
Research in personalised medicine today focuses on analysing a patient’s genome, but additionally on environmental, social, biometrical and religious influences, and then tailoring a treatment for each individual based on that data. The science is fundamentally about moving from a one-size-fits-all approach to where we design targeted medicines that are based on your DNA, body chemistry and how you are likely to respond to different chemicals or levels of treatment.
One possibility is figuring out the proper dose and strength of drugs for patients suffering with depression. Currently, treatment is somewhat hit and miss and requires physicians to try different doses of different medicines, monitoring the patient over a period of days or weeks, and then continuing to adjust the dosage until they get it right.
Gene-based information will help doctors prescribe much more effective, accurate doses sequenced to DNA. So instead of using a drug like a selective serotonin reuptake inhibitor (SSRI) which attempts to control the way the body uses serotonin, personalised medicine would be able to stimulate the body to produce or reduce serotonin levels (and other neurotransmitters) to norms for your genotype. We expect to see similar advancements in painkillers, infectious disease therapies and drugs for neurological disorders such as epilepsy.
With improved genetic sequencing capability, we’re realising that identifying a type of cancer, like prostate cancer, is not enough to accurately determine a form of treatment. Recent studies have shown that each individual patient with the same type of cancer may have very different genetic traits within their cancer. So personalised medicine is going to be a necessity for effective treatment in the future.
However, genomics is one small part of the ability to create personalised or precision medicine that works. Your big “health” data such as quantified self data, previous medical history, family history and lineage, locations you’ve lived, environmental influences you are regularly exposed to, previous blood tests, previous responses to different medicines and other such information are all going to be critical to the ability to target specific conditions or ailments with targeted, precision medicine. Indeed, the success of personalised medicine will likely hinge on improved, centralised access to electronic health records.
If you have concerns about sharing your data on your health, location history, previous medical treatments and so forth, be aware that this is going to radically restrict your ability for treatments in the future—the future of health care is about genes, sensors and data.
If you want to understand gene therapy and augmenting our biology, it is helpful to think of our genetic code in a similar way to software. Within our DNA are specific instructions that produce the essential humanity of who we are. If our parents or ancestors had encoded in their DNA a deficiency of a certain protein, had genes that trigger specific conditions or were missing genes that prevent other conditions, then that “code” will produce either a specific mutation or result in a high probability of you contracting a disease. If we can learn to “edit” that code and reinsert it into our DNA in the proper sequence, we can fill required gaps, or simply remove errors.
In 1987, biologists noted that bacteria possess a natural defence mechanism that recognises invading viruses. Then in 2000 to 2002, scientists recognised that bacteria not only responded to but also reacted by processing and dissembling the attacking virus DNA. They dubbed the process CRISPR, an acronym for “clustered regularly interspaced short palindromic repeats”.
Between 2009 and 2012, CRISPR techniques were explored to optimise the cutting of DNA in virus candidates by examining the proteins that bacteria cells used in their immune defence. A protein called CRISPR associated protein 9 (Cas9) was discovered. Cas9 is no ordinary protein, it is a nuclease, an enzyme specialised for slicing DNA strands. It has two active cutting sites (HNH and RuvC), one for each strand of the DNA. By 2012, it was proposed that Cas9 could be used as a genome editing or engineering tool in human cell culture to possibly single out and destroy genes responsible for diseases like Parkinson’s, Alzheimer’s, diabetes, inherited cancers like breast cancer, immune deficiencies and so on. Right now, gene therapy is focused on monogenic diseases, or diseases that involve a single gene.
CRISPR/Cas9 not only makes cuts in DNA but also allows for new genetic sequences to be inserted. Scientists can then introduce an engineered virus or DNA plasmid with the required DNA sequence. A project spearheaded by researchers at the University of California, San Francisco, used CRISPR/Cas9 to edit HIV out of human T-cells. When HIV infects the body, it modifies the body’s own immune system by changing the DNA of T-cells. With innovations in the Cas9 process, researchers were able to successfully edit the CXCR4- and PD-1-infected genes in the T-cells, replacing them with healthy cells. Modified T-Cells from healthy patients have been introduced via stem cell therapy before, boosting the immune system’s response, but this was the first time that researchers were able to edit the HIV virus out of an existing patient’s cells. In Philadelphia, researchers were able to make HIV patients resistant to the virus by removing the CCR-5 protein from white blood cells through gene therapy.
In March 2015, Chinese scientists announced that they had successfully used CRISPR techniques to modify the gene responsible for β-thalassaemia, a potentially fatal blood disorder, in non-viable human embryos. The Chinese team injected 86 embryos and then waited 48 hours. This allowed enough time for the CRISPR/Cas9 system and the molecules that replace the missing DNA to act, as well as for the embryos to grow to about eight cells each. Of the 71 embryos that survived, 54 were genetically tested. The testing revealed that just 28 were successfully spliced, and that only a fraction of those contained the replacement genetic material.
This not only raises fundamental ethical issues but also identifies the biggest criticism of CRISPR technology, in that it is still an inexact science. For gene therapy to be successful, it needs to be highly targeted, and to avoid any genetic contamination. This outcome may slowly become a possibility as researchers have recently devised a way to reduce off-target DNA binding of a class of gene editing proteins known as transcription activator-like effector nucleases (TALENs). This method allows scientists to evolve the proteins freely, which in turn makes them more specific and targeted over time.
Whichever technique leads to the breakthroughs scientists are working towards, it is likely that gene editing will dramatically improve over the next decade and become a standard method of treatment for any inherited disease or condition. We will no longer look to treat the symptoms of diseases but simply eliminate those conditions entirely.
The applications for gene therapy are nothing short of stunning and completely revolutionary. This field is accelerating so rapidly that each week major new research announcements are made. At the time of printing, significant progress has been made using gene therapy in getting closer to treating or potentially curing the following conditions, to name but a few:
1. Hearing: deafness, hearing loss, tinnitus, Meniere’s disease
2. Sight: congenital and degenerative blindness such as Leber’s congenital amaurosis, retinal gene therapy, choroideremia
3. Hereditary, genetic and autoimmune diseases: neuromuscular disorders such as muscular dystrophy, amyotrophic lateral sclerosis (ALS), limb-girdle myasthenia (caused by the defective DOK 7 gene), Emery-Dreifuss muscular dystrophy, spinal muscular atrophy and myotubular myopathy; diseases such as Parkinson’s (by restoring delivery of glutamic acid decarboxylase), Alzheimer’s and Friedreich’s ataxia; even depression could be treated by restoring P11 brain proteins
4. Cancer and blood disorders: leukaemia, acute myeloid leukaemia, gliomas, pancreatic cancer, liver cancer, haemophilia, sickle-cell anaemia
5. HIV: Studies have shown that patients become resistant to HIV following the removal of the CCR-5 receptor protein in white blood cells.
6. Heart and lung diseases: celladon heart failure, calcium upregulation, congestive heart failure and peripheral arterial disease, cystic fibrosis, α1-antitrypsin deficiency, asthma, acute respiratory distress syndrome (ARDS), pulmonary edema
With gene therapy, we will be able to correct errors in our DNA as well as remove diseases, deficiencies and hereditary conditions. That is an astounding possibility, and it is most definitely within reach of the sciences. If you combine gene therapy, stem cell therapy, sensor-based monitoring and other augmentation that will be available, the fact is that we will have more control over disease and its treatment than ever before. In fact, it is likely that we will make more progress curing disease over the next two decades than in the last one hundred years of medical science. By 2030, access to advance medical techniques and gene therapy will have potentially added another 20 to 30 years to the life expectancy of those living in developed nations.
Once gene editing has been perfected, the next likely consideration is enhancing our biology by inserting improvements into our DNA. Transgenics is a field in which human-animal hybrid genetic research is already developing some promising traction. While the ethics of inserting animal DNA into humans is obvious, the use of human DNA in animals doesn’t have the same restrictions today.
The first successful transgenic animal was a mouse. Bred in 1982, this “supermouse” was created by inserting human growth hormone genes into fertilised mice embryos. Transgenic rabbits, pigs, goats, sheep, fish, cattle and, more recently, primates followed. The underlying principle in the production of transgenic animals is the introduction of a foreign gene or genes into an animal (the inserted genes are called transgenes). The foreign genes “must be transmitted through the germ line, so that every cell, including germ cells, of the animal contain the same modified genetic material.”20
Take the following examples. Transgenic fish include salmon that grow about ten to eleven times faster than normal fish due to growth hormones and genetically modified freshwater zebrafish that carry a fluorescent protein gene from jellyfish which allows them to glow. Transgenic mice include those with amyloid precursor genes that exhibit the same brain conditions as patients with Alzheimer’s and those biologically engineered to overexpress the NR2B receptor in their synaptic pathways, making them learn faster their entire life. Pigs genetically engineered today with at least five different human genes can conceivably grow organs for human transplant with low rejection rates, including hearts, lungs, kidneys and so forth. Transgenic cows that produce human lactoferrin and interferons in their milk are effectively a bovine/human milk hybrid while prion-free cows have been genetically engineered to be resistant to mad cow disease. Transgenic goats have been engineered that express spider silk in their milk.
The use of transgenics in crops is expected to have huge benefits to food security, as genetically modified crops increase yield, provide robust protection against disease and address food scarcity driven by climate change.
“Transgenic technologies—which enable the transfer of genes from one plant species to another to produce a plant with new or improved traits—hold the most promise for achieving food security in the next 15–20 years.”
National Intelligence Council, Global Trends 2030:
Alternative Worlds, 2012
Transgenic technologies, which allow for the genetic intermingling of human and animal characteristics, could eventually lead to an almost endless array of human-animal hybrids. There is plenty to be envious about with regard to our non-human friends. Dogs hear and smell much better than we do, cats can see in the dark, some primates have better memorisation skills than us21 and birds have remarkably strong vision. Looking ahead to the day when we can apply transgenic modifications to ourselves, many would-be transhumans would probably like to acquire, for instance, the eyes of a hawk, the scales of a lizard, the ability to swim like a dolphin or hold their breath like a crocodile.
In the Mars trilogy by Kim Stanley Robinson, the author proposed splicing animal genes into the DNA of the Mars colonists as part of a regular process of getting longevity treatments (which in themselves were corrective gene therapy editing out replication errors in genetic code and restoring telomeres). One of the characters added a cat-derived “purr” to her biology. Another trend theorised was the addition of crocodile haemoglobin to grant CO2 tolerance for a partially terraformed red planet that was still poor in oxygen.
Advances in synthetic biology will likely result in production facilities making novel treatments and diagnostics agents. Advances in regenerative medicine almost certainly will parallel these developments in diagnostic and treatment protocols. For example, replacement organs, such as kidneys and livers, could be developed by 2030.
As discussed in chapter 2, 3D printers have the potential for some incredible applications in the way we manufacture products, even at home, in the future. However, one specific application of 3D printing that holds huge promise in the field of medicine is bioprinting. Bioprinting in its simplest form is using a 3D printer to “print” an organ, bone or muscle tissue to replace damaged parts of your body. One of the more exciting applications is being applied to regenerative medicine to address the need for tissues and organs suitable for transplantation. 3D printing has already been used widely in facial reconstruction surgery.
Figure 5.11: 3D-printed “bone” is commonly used in facial reconstruction surgery. (Credit: Osteofab)
Compared with non-biological printing, 3D bioprinting involves additional complexities, such as the choice of materials, cell types, growth and differentiation factors, and technical challenges related to the sensitivities of living cells and tissue and vasculature construction.
Addressing these complexities requires the integration of technologies from the fields of engineering, biomaterials science, cell biology, physics and medicine. 3D bioprinting has already been used for the generation and transplantation of several tissues, including multilayered skin, bone, vascular grafts, tracheal splints, heart tissue and cartilaginous structures. Other applications include developing high-throughput 3D-bioprinted tissue models for research, drug discovery and toxicology.
3D printing has already been used in numerous medical procedures. For example, in 2012, physicians at the University of Michigan successfully utilised 3D printing to construct a synthetic trachea for three-month-old Kaiba Gionfriddo, who suffered from recurrent airway collapses.22 Other successes include printing bone to replace one patient’s jaw and part of the skull in another patient. As a developing industry, 3D printed body parts generated over US$500 million in revenue for companies globally in 2014, and that is expected to double by 2016.
In 2006, Wake Forest University’s Dr Anthony Atala was successful in using inkjet printers to “grow” replacement bladders. The process for growing each patient’s organ began with a biopsy to get samples of muscle cells and the cells that line the bladder walls. These cells were grown in a culture in the laboratory until there were enough cells to place onto a specially constructed biodegradable mould, or scaffold, shaped like a bladder. The scaffold was designed to degrade as the bladder tissue integrated with the body. Testing showed that the engineered bladders functioned as well as bladders that are repaired with intestine tissue, but with none of the side effects. Today, the patients are all still doing well.
Other candidates for regenerative medicine and 3D-printed organ replacement are organs like the thyroid, kidney and liver. Atala was able to create mini “hearts”, about 0.25 millimetres in size, by reprogramming human skin cells into heart cells, which were then clumped together in a cell culture. A 3D printer was then used to give them the desired shape and size. Furthermore, in March 2015, the Russian bioprinting company Skolkovo successfully 3D printed a thyroid gland for a mouse and transplanted it. The company has said it is on track to print a human kidney by 2018.
With all of these potential bio-enhancements, we will be able to literally engineer a near-perfect human specimen in the next 30 to 40 years. Many humans will likely be genetically error free, with the ability to live much longer lifespans, while the medical community will be able to attack cancers or disease on an individual genome basis, along with correcting degraded cellular or organ health through organs built to your own unique specification. This all sounds like science fiction, but many of these technologies are already within our grasp.
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1 The ruins of Uruk are situated in modern-day Iraq.
2 There were various donors for the HGP, both male and female. Much of the sequence (> 70 per cent) of the reference genome produced by the public HGP came from a single anonymous male donor from Buffalo, New York (code name RP11).
3 See https://www.genome.gov/ for the National Human Genome Research Institute database which lists all currently known genetically inherited conditions.
4 http://www.cancerresearchuk.org/
6 https://itunes.apple.com/us/app/sweetbeat/id492588712?mt=8
8 http://www.amazon.com/Garmin-Vivofit-Fitness-Band-Blue/dp/B00HFPOX9W/ref=sr_1_7?ie=UTF8&qid=1415520287&sr=8-7&keywords=garmin%20vivofit
9 See WebMD.
10 Author’s interview with Dr Giovanni Santostasi
11 Thomas Kirkwood, “Why Can’t We Live Forever?” Scientific American, Sept 2010, p. 14, http://www.scientificamerican.com/magazine/special-editions/2015/03-01/.
12 1 gramme is the equivalent of 0.028 ounces. An eighth of an ounce is commonly accepted as a flat 3.5 grammes while 6 grammes is about half a tablespoon in imperial measurements.
13 http://www.amazon.com/Spark-Revolutionary-Science-Exercise-Brain/dp/0316113514
14 See Shaun Clark’s research for more information.
15 Cancer Research UK
16 In his final State of the Union, President Obama announced a “moon shot” to cure cancer and appointed Vice-President Biden to lead the charge.
17 National Cancer Institute
18 Harvard University, John A. Paulson School of Engineering and Applied Sciences
19 Beatriz M. Carreno et al., “A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells,” Science 348, no. 6236 (15 May 2015): 803–808.
20 “Transgenic Animals” from the Canadian Council on Animal Care
21 http://www.baxterbulletin.com/viewart/20120625/NEWS01/306250010/Apes-monkeys-more-social-smarter-than-previously-thought
22 David A. Zopf et al., “Bioresorbable Airway Splint Created with a Three-Dimensional Printer,” New England Journal of Medicine 368, no. 21 (2013): 2043–2045.
