The Future of Almost Everything, page 10
Back in 1987, I said that developing a vaccine against HIV would be very difficult, because the virus keeps changing its outer surface, and escapes every vaccine trick we know. I predicted back then that it would be at least 15 years before a vaccine would be developed, and today there is still no likelihood of an effective, widely available vaccine by 2035.
Treatments have improved, as well as availability, and AIDS is becoming a chronic illness. But there is still no cure, treatments are toxic and are taken for life. We are discovering rare genes that provide partial or complete HIV protection, and which will lead us to gene-linked therapies.
Even if a cure is discovered tomorrow, it will take over 12 years for clinical trials to prove safety, and at least 25 years more to bring HIV under control. TB, for example, became curable in 1944, yet we still have the world’s largest pandemic today.
The good news is that prevention works, with falling or stable infection rates in many nations like Uganda where up to 30% of all sexually active men and women were infected at one time. However, complacency will be a constant challenge, in many nations among different parts of the community.
Spanish flu, SARS, bird flu, swine flu
Another mutant virus on the scale of HIV was the Spanish flu epidemic of 1918–19, which spread across the world in months, on foot, horses, donkeys, trains and ships, eventually killing over 30 million people, out of a world population of 2 billion. If a similar highly infectious and lethal pandemic begins tomorrow, it is likely to spread on international flights in days and weeks, not months, with no time for vaccine development or global distribution, and could kill 100 million people within a year. That is why the World Health Organisation keeps warning governments about these threats.
From swine flu to ebola
The genetic code of the Spanish flu virus is almost identical to that of swine flu. Therefore it was worrying when swine flu reappeared in Mexico in 2009. It spread globally in weeks and caused 14,000 deaths, despite mass-mobilisation of health resources, bans on travel, and almost instant lock-down of parts of Mexico.
SARS also appeared without warning in 2003. Over 8,600 people were infected with the virus within a few weeks, despite huge containment efforts, and 860 died. And 1% of carriers were so infectious that even touching a light switch 24 hours after they had done so could have been enough to kill you. SARS was only stopped by aggressive contact tracing and quarantine, in China, Canada and other nations. The outcome would have been very different if a single ‘super-spreader’ had travelled across Africa in a crowded plane, seeding clusters of infection in remote rural areas.
The 2014–15 ebola outbreak killed and orphaned many thousands, paralysed West African economies, stopped farming, closed markets, and caused widespread hunger and deaths from other treatable diseases, with constant threats of more outbreaks from infected animals in the bush.
How much more evidence do we need? Mutant viruses will be a major future threat, and we will see far greater investment into antiviral therapies, rapid vaccine development and epidemic monitoring as a result.
The ultimate nanotech robot
Around 28 years ago I predicted in The Truth about AIDS that doctors would one day use viruses as a therapy. Such an idea sounded very strange back then, but as I write this, I am chairman of a company that is doing just that, to destroy cancer cells.
Viruses are naturally occurring nanotech robots. They are not living, need no food, use no energy – just biological machines. Viruses have legs with sensors to detect what kind of cell they are touching. Once the legs latch onto the cells they are programmed to infect, the body of the virus fuses with the cell membrane, injecting a payload of genetic code.
Within minutes, the genes are read by the cell, and new proteins are being built. Every virus contains instructions to hijack each infected cell and turn it into a virus factory. The cell soon starts to fill with new virus particles until it explodes and dies, and the cycle of infection continues.
Scientists have redesigned different types of human viruses to target, infect and destroy cancer cells without damaging healthy tissue. At the same time, many of these viruses provoke an immune response against the cancer. Viruses can also be used to deliver extra genes, instructing cells to behave in certain ways as part of therapy.
Viruses will be used as weapons of war
These same techniques can be easily used to design viruses as weapons of war, perhaps with receptors that have an affinity to a particular race for example. But while bio-weapons undoubtedly exist in different nations, most will be very poorly targeted, with extremely high risks for those that deploy them.
Some fear that HIV and other dangerous viruses were created in bio-weapons labs, but HIV has been around for many decades and there is no evidence that any new dangerous virus has ever been created and released (yet). However, we do need to take great care to regulate the use of viruses, especially where properties have been altered.
And we also need to recognise that old viruses will inevitably be used as ‘low-tech’ weapons at some point – for example, to deliberately cause a huge outbreak of foot and mouth disease across farms of an enemy nation. Very easy to do – just one person driving a van for a day, dropping bits of infected meat near pigs on a few farms. And how could anyone prove which country was responsible? The cost of a single outbreak in the UK was more than $13bn.
Medical technology will change all our lives
Almost all the greatest medical advances will be from medical technology, pharma or biotech, or a combination. Medical technology alone will transform health care over the next 20 years. Here are just a few examples:
Endoscopy – rapid growth of tiny telescopes, keyhole surgery, shorter hospital stays. $75bn a year market by 2022.
3D imaging – ability to watch living tissue in astonishing resolutions, ‘travel’ inside blood vessels, see inside the heart, detect cancer cells during operations.
Ultra-resolution microscopy – able to observe things going on inside an individual cell in real time, watch a photon of light excite a retinal cell, a drug molecule attach to a receptor.
Digitised patient records – instant availability in the Cloud of all tests, scan images and other medical records. The US Veterans Health Administration has Big Data on 20 million patients, 2 billion text entries, 16 million X-ray images and 1.5 billion prescriptions.
Computer-aided diagnosis – let robots treat the sick, using Big Data to predict what will happen. Such tools will transform what doctors need to remember, and how they are trained. Computer-assisted diagnosis will be universal in some countries for some types of conditions by 2025, with doctors forced to use it not by law but by insurance companies.
Telemonitoring, telemedicine and home diagnostics – huge growth in virtual medicine and home monitoring devices, where doctors and specialist nurses make decisions in a faraway location. However, we will not see many surgeons controlling robots many thousands of miles away, because speed of light is too slow, with delays from surgeon, to robot, to image, to surgeon, as well as risks when things go badly wrong that no one locally can sort out.
Growth of Do-It-Yourself health care – web-based diagnostics and mobile apps with a wide range of biosensors, so that many patients know more than their doctors about their own condition.
Social media and sharing health experience – scoring carers, rating doctors and hospitals.
Replacement of reading glasses by a tiny implant into the cornea, made of hydrogel, to change the curvature of the eye.
Low cost gene readers – (see p. 93)
Future of dentistry
Dentistry will also change rapidly over the next three decades, mainly as a result of medical technology. More people will be able to afford cosmetic dentistry, and the governments of emerging nations will provide more access to free dental care.
Treatment will be transformed by huge advances in diagnostics, instant 3D imaging, local 3D manufacturing and printing, plus advances in new tooth-filling materials and ‘invisible’ braces to correct poorly aligned teeth, with near-perfect results.
Next-generation tooth cleaning will encourage daily repairs of microscopic defects. However the greatest transformation globally will be because of far wider consumption of fluoride, in emerging nations, strengthening teeth of children. And fluoride will go on protecting the teeth of that generation as it gets old, so dentistry will change beyond recognition over the next 50 years, from repair to cosmetic work.
Future of pharma
If you want to know the future of medicines, take a look at the list of drugs that are in clinical trials today, on pharma websites. The global list of potential new therapies is short, unexciting, and stuffed full of ‘more of the same’ – more anti-blood pressure tablets, and so on. I qualified as a physician over 30 years ago, and the sad truth is that most drugs used today are ones we learned about at medical school, or slight variations of them.
Big Pharma finds real innovation difficult, slow and expensive. The largest five companies have a combined research and development budget of $32bn, while the 50 largest have a combined budget of around $100bn, which is larger than the GDP of the world’s poorest 35 nations. Despite all this activity, Big Pharma is likely to generate less than 40% of the world’s new drugs over the next 25 years.
Most breakthroughs in the next 25 years will take place in over 20,000 smaller biotech companies, most of which do not yet exist, often partnered with university teams. These companies will typically aim to sell promising drugs to pharma companies at some point before, or during, early clinical trials. Biotech products already account for 21% of the $750bn a year of pharma sales, and are likely to grow by around 7% a year over the next decade, compared to only 4% for small-molecule drugs.
$1.3 billion for a new drug to market
Over the next two decades, the total cost of bringing a new drug to market will rise by at least 4% a year. It already costs over $1.3bn to bring a drug to market in the 15-year process from discovery to early development, through animal studies and full clinical trials. Of these, 80–90% of new drugs do not make it, and all pharma/biotech will remain a high-risk business. In the past 5 years, more than $240bn has been spent by pharma on drugs that failed in final clinical trials.
Since patent life is likely in most cases to continue to be restricted to only 25 years, of which 15 are usually lost in development, pharma companies will have to make a good return in less than a decade of sales.
Pharma companies will see lower sales than were typical in the past for many new specialist drugs, especially those with toxic side effects such as cancer chemotherapy, as gene profiling is used more widely to select precisely the right treatment for each person (pharmacogenomics). That means a reduction in ‘hope for the best’ prescribing.
The price of drugs will fall rapidly over the next 10–15 years, as almost all patents expire on drugs sold today. We are talking about billions of dollars of lost revenue over a decade (and corresponding savings to governments and insurers).
A course of patent-protected drug therapy that costs $100 today will typically cost less than $5 as a ‘generic’ by 2030. Of course, doctors will be offered a range of equally expensive new therapies by then. But most will be incremental changes, tinkering slightly with existing drugs to extend patent life and sales.
To make matters worse for the pharma companies, if a drug shows huge benefits for a disease like malaria in the poorest nations, the company will be under huge pressure to give it away ‘at cost’ for ethical reasons.
Some large pharma companies could lose up to 35% of revenues almost overnight if forced to withdraw one or more well-accepted ‘blockbuster’ drugs because of unexpected health risks.
Orphan diseases will get special treatment
Yet in spite of the above, our world needs a profitable pharma industry able to take risks to develop next-generation therapies. That is why we can also expect more concessions by regulators, seeking to balance patient safety with the need to accelerate new drug development, particularly for people who are otherwise certain to die soon.
Governments will expand lists of so-called orphan diseases, where numbers of sufferers are too few to attract much pharma interest. Orphan diseases will attract special subsidies, tax incentives, fast-track approval, better pricing and longer patents.
Expect new models for drug development where knowledge and patents are owned by the public, with work funded by the taxpayer, while production and distribution are carried out by pharma companies – as seen in AIDS research. Expect big changes also in medical publishing. More public bodies that fund research will insist that published results are freely available to all. Expect new patterns of collaboration: co-opetition, crowd-sourcing, open innovation, crowd-funding. Super-wealthy patrons will also fund many biotech innovations, as social enterprises.
Many new pharma blockbusters
While many pharma leaders have claimed that the days of new blockbuster drugs are over, the truth is that from time to time we will see gigantic sales and profits from key breakthroughs. Just imagine the sales from a new drug proven to delay the onset of Alzheimer’s by 3 years. Other examples will include breakthroughs in rheumatoid arthritis, asthma and diabetes, and drugs that make people ‘feel’ much younger. As I say, many of these new therapies will probably have started out as a concept in a biotech company or a university lab.
Future of biotech – altering the basis of life itself
We are without doubt living in the age of the gene. This will take us way beyond biotech discoveries to sell on to pharma companies. It is hard to comprehend the gigantic steps that humankind is now taking to redesign the very basis of life itself.
Every form of life on earth is programmed in the same biotech language of DNA and RNA. We share almost all our genes with amoeba, insects, earthworms, rats, rabbits, and horses. We can cut and paste sections of genetic code very easily, without needing to know in advance what the results might be. Human genes have been added to mice, cows, sheep, rabbits, rats and fish, to name just a few.
Large numbers of designer animals have been born. Several million mutants are made in European laboratories every year, each of which is a unique mix of two, three or more different species, for example, transgenic sheep programmed to produce human hormones or other complex molecules in their milk. Scientists have also created a goat with genes from a spider, so that spider web proteins are excreted into the milk. These proteins can be extracted to create a kind of textile fibre which is highly elastic and almost as strong as Kevlar.
Expect humanised cows to produce low-fat milk. Another goal will be cows that produce human breast milk. Biotech farming raises new animal welfare issues – for example, in the case of cows that are programmed, or driven by hormone injections, to produce many times their natural daily yield of milk.
Ability to read your genetic code (genome)
By 2025, doctors will be able to read an individual’s genetic code in less than 2 hours for less than $3500, enabling us to predict our medical future with far greater accuracy – using Big Data, Cloud Computing, combining tens of thousands of genomes, medical records, lifestyle data.
It took $3bn and 15 years of work to decode a single genome. Expect costs to fall towards $500 by 2035, using nanopore sequencing and other techniques. Expect gene readers on devices as small as today’s USB sticks by 2040, taking 30 minutes to decode each strip of genetic code.
Big Data has already identified genes associated with speech, memory, murder, addiction, excessive risk-taking, shyness, obesity, faithfulness and happiness, among other things. And once a gene is located and a test devised, the test can be used to select early dividing embryos before implantation after IVF, raising a host of new ethical issues. It is one thing to decide not to implant embryos that carry genes which guarantee a very serious, lifelong illness, but quite another to select embryos for some enhanced characteristic.
Researchers have already found that a high proportion of murderers on death row in the US share a common gene or genes, raising profound questions about responsibility or therapy. Having the ‘wrong genes’ has been cited in mitigation against sentence of execution in America over 50 times since 1994. Men with XYY chromosomes are more likely to commit murder, while the gene affecting production of monoamine-oxidase-A in the brain is called the Warrior Gene, because it is linked to very aggressive behaviour.
Ability to alter your own genes
Once you find a rogue gene in your own genome, which is almost certain to make you very sick one day, why not try to correct the defect? This is the basis of gene therapy, and as we have seen, a relatively simple method is to use human viruses.
Humans will experiment with different ways to enhance the genes they have naturally. Some athletes are already pushing their bodies even harder with injected gene fragments, which have short-term effects and are very hard to detect. Bio-doping will be a major problem in the Olympics, and is already beginning to raise questions about the validity of every new sporting record.
Who owns a species?
The world will soon have to face more big questions about ownership of gene-mutated animals. Is it right for a company to own an entire species? Is it right to create a species which by its genes is guaranteed to suffer? Both questions were raised by the creation of the first type of oncomouse, designed to develop fatal cancer 90 days after birth. The oncomouse was created in America for the testing of cancer treatments and is commercially owned, protected by patent.
Patents on human genes
Is it right for companies to own human genes? A man in the US developed cancer and gave cells for research. The genes were used to develop a diagnostic test and the process was patented. He was furious. ‘I own my own genes,’ he said. He challenged the company and fought them all the way to the Supreme Court, but lost his case. As a result, humans do not have the right to own their own genes in America.
