Chapter 11

To Infinity and Beyond

Gene patches are only part of how medicine will change in the next fifty years. If you think what I’ve described so far sounds like science-fiction, wait until I give you a peek at what else is possible. After all, it’s only been a bit more than forty years since we walked on the moon. Who would have thought that since then we would be able to hold a video conversation with friends or family on the other side of the world? Or that we could store the information from a set of encyclopedias on a hard drive the size of a pinhead? (That is still a lot bigger and a lot less information than is contained in the human genome!)

Over the next fifty years, medicine will change dramatically. Here are the top ten ways it will evolve:

10) More drugs will be delivered by inhalation.

I am a big proponent of aerosol delivery of drugs through the lungs and immediately into the bloodstream. In the past, inhaler devices have been relatively unsophisticated. But that is changing and soon, the first of many new systemic drugs should be approved for delivery by inhalation. Levadex, an anti-migraine drug developed by MAP Pharmaceuticals uses a more sophisticated inhaler device and has been used to deliver an old drug, dihydroergotamine, to those in the throes of a distressing migraine episode. But there are many more novel inhaler devices in development. The lungs have many built-in protections, specifically to prevent inhaled particles from getting into the body. We are getting cleverer at bypassing these defense mechanisms.

In another fifty years, more drugs that need to get into the bloodstream quickly (and avoid the liver which breaks most drugs down), will be delivered by one of the next generation of inhalers. They will completely surpass the old press-and-breath metered dose inhalers first introduced in the 1950s, that many patients with lung diseases still use today. The new devices will also deliver better medicines, faster and more effectively to those with lung disease. Until smoking is outlawed, that will always be a large number.

9) Implanted devices will include a slow-release drug that reduces the body’s attempts to attack the implant.

Many stents used today for opening up blocked arteries already carry these slow-release drugs. But the number and variety of implanted devices, often inserted in an acute situation to rapidly reverse a crisis and before long-term damage can be done, will greatly increase. This will require more regulatory flexibility than seen today as the effects of the therapy, both good and bad, may be shared by drug and device. Indeed, great changes within the regulatory framework for new medicines and devices will be necessary to ensure the Golden Age of Medicine is not hampered by outdated and obstructive bureaucracy.

8) Regenerative medicine will reduce the need to obtain replacements for failing organs from sudden death victims. Replacements will instead be grown in the laboratory.

Stem cells and regenerative medicine are on the verge of coming of age. It will be possible to repair damaged organs, even replace missing ones, by the insertion of stem cells with the potential to develop into specialized cells of the organ or body part. Already it is possible to grow some body parts outside of the body and then introduce them. New bladders are being created experimentally by the Wake Forest Institute for Regenerative Medicine in North Carolina. There, over two dozen children and young adults born with defective bladders have already had new laboratory-grown ones implanted. They have even built kidneys in the laboratory, that when implanted into animals, have produced urine. But the field will evolve rapidly with specialist companies developing the right growth factor supplements to help the stem cells develop into a new organ, a kidney, a liver or skin. So if you have a serious injury in a car crash, your damaged parts will be replaced using the power of regenerative medicine.

This will be important, because as our life expectancy increases (it’s already up by eleven years for men and twelve for women just in the last four decades), many more people will work into their seventies and eighties. As their organs, joints or tissues age, they may need replacements, and it will be much easier to get them in fifty years. This will help the aging population remain more mentally and physically active.

7) Fully portable electronic medical records will be commonplace.

The records will be initiated when you are born and will have information loaded on at every healthcare encounter with your doctor, your local hospital, the specialist hospital, your pharmacy, your dentist and your optician. Each will be able to enter new data and view existing data relevant to their practice. This will help you to receive faster and safer care. Maybe the information will be stored on a microchip worn as a locket or on a wrist strap. We may even have the option to keep these chips implanted under the skin as we do already with our pets. That is the surest way to keep you and your record united.

6) Small hospitals with community ties will replace the current huge university-based teaching centers.

Huge mega hospitals that treat thousands of patients in big, often university-based, teaching centers will become a thing of the past. Imagine a world where Seattle Grace, of Grey’s Anatomy, is replaced by the much smaller medical facilities of Private Practice. There will be smaller units built with much closer links to community-based healthcare teams. There will be smaller mobile, or fixed, operating “rooms.” These units will be able to operate at a much higher efficiency than today’s operating room and will be open 18, or even 24 hours a day, at a fraction of today’s costs, with support staff preparing patients.

5) Surgery will be performed remotely on a routine basis – and most surgery will be microsurgery and use a microscope.

Surgery will routinely be performed by surgeons who are remote from the operating table using sophisticated, microscopic video cameras and minute tools worked robotically over the internet. This is already possible and has been done, though it hasn’t been widely publicized. Let’s say the best hand surgeon in the world is in France and you are in Chicago. You will be able to get her to work on you in Chicago without leaving her home in Paris. This will have many benefits, including democratizing health care so that everyone has access to top surgeons.

In-person surgery will still be performed, but there will be a stronger focus on microsurgery. And the operations will be much less invasive, so the post-operative recovery will be much faster with many more patients able to return home on the same day, and back to work within a few days.

4) A spit swab for genome sequencing will replace the heel prick that is done when a baby is born today.

Since a blood test at birth is far less revealing than genetic testing, insurance companies will cover the cost of this test. The outlay will be a fraction of today’s prices, due to increasing automation and competition. The insurance companies will have embraced the need to provide coverage for diseases that are identified and will help you, through your doctor, avoid many of the triggers and adverse behaviors that contribute to illness today.

With more in-depth information about the genetic risks of various ailments, health, and how to sustain it, will be taught better in school. The result will be that our children and grandchildren will make better lifestyle choices for themselves than today’s overweight, unhealthy population.

3) Blood tests will disappear.

A whole new series of disease monitoring devices and measurements will be available. Many diseases currently untreatable, or other diseases where the monitoring of the disease’s effects are crude, will have new biomarkers identified. These new methods will be more sensitive, more predictive and more specific than those available today. In addition they will be less invasive. Today’s blood tests will be replaced by collecting a urine sample, breathing into an analyzer, or taking a hair sample. The machines needed to monitor these biomarkers will be small, portable and easy to operate, so that management of many more diseases will be overseen by your primary care practitioner, or internist, in your own neighborhood. The need for regular checkups, even for the few diseases where effective therapy may still be lacking, will involve less travel, upheaval, stress and cost for you and your family.

2) New bugs will be stopped dead in their tracks.

Infectious diseases will be tackled on a much faster basis.

In the last century we have made remarkable progress already against communicable disease. But there are still some microbial enemies pitted against us that have yet to be beaten back. Oligomers will play an important but marginal role in this battle. The oligomers will be too expensive for everyday use, but they will be ideal for rare, lethal diseases or the emergence of multi-drug resistant strains.

Big hospitals heretofore have been a major breeding ground for new bugs. The small number that will remain to undertake heroic surgery or care for desperately ill patients with all the sophisticated life support systems will be linked to special laboratories. When a new infection is discovered, almost on an individual patient level, samples of the infection will be examined, the bug identified and the sequence of its RNA determined. Oligomers against that bug will be rapidly developed and the bug will literally be stopped dead in its tracks. Lethal hospital acquired infections and outbreaks of fatal pandemics will be contained and defeated within a few days with the use of fast response teams aided by scrupulous quarantine and impeccable logistical support.

1) Gene patch therapy will be superseded by gene replacement therapy.

The healing powers of oligomers will only be a start. The miraculous results they get will only whet researchers’ appetites so that a Band-Aid will no longer be enough. Scientists will want to be able to provide a full cure. And the only full cure that will truly work for an untreatable rare disease will be replacing the faulty gene that created it. As societies, we will struggle with the ethics of inserting new genes and removing less favorable ones. There will be a tremendous fear of designer babies. And certain countries where boy babies are preferred may go through some upheaval, as too many baby boys will lead to a lot of lonely old men.

But the potential to fully heal the millions of people with rare diseases will be so powerful that it will overcome the issues that stem from this new technology.

As to what will be the more traditional procedure, the gene patch, it will live up to its full potential. Tomorrow’s gene patches will be highly targeted drugs that will bind to up to thirty letters or so of our messenger RNA as it peels off the three billion letters of our genome.

The variety of chemistries being used and the number of companies developing these gene patches will have dramatically increased. The growth of this industry will accelerate as the first few gene patches are approved and the regulators become more familiar with the technology and its strengths and weaknesses. Blockbuster drugs will slowly decline in number and a large number of far more personalized drugs will be manufactured. This will be true of drugs in general, not just the wave of RNA targeting oligomers. They will all be much more targeted to you and your disease.

Your own doctor will be far more involved in delivering the oligomers to you than with previous medicines, and monitoring your continued wellness throughout your life. The oligomers will be tracked even down to the individual vial with replacement supplies being generated by the manufacturers on an individual patient basis. Careful follow up of these gene patches, and larger, longer, more detailed safety follow up of all drugs, not just oligomers, will be rigorously enforced.

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One final note: To make things easier to understand, I have simplified the truth about rare diseases and how they can be treated by gene patch medicine. Unfortunately, the story is a lot more complex than I have suggested. I’d like to take the last few paragraphs of this book to give you a fuller picture of how things work.

Not everyone with even the same rare disease has the same genetic makeup. Duchenne muscular dystrophy for instance. It has many different genetic variations that lead to the lack of the vital dystrophin in the muscles. Only about 85% of DMD patients have a genetic mutation that can be treated by skipping an exon, and even for those, there are twenty or more different exon targets, one or more of which may need to be skipped to restore the RNA reading frame.

If your son is diagnosed with DMD, you will need to know exactly which one of the hundreds of different genetic mutations he has, and therefore which of the numerous gene patches he should be given. Some patients may need more than one patch! Research is already under way on that topic.

The companies developing the DMD oligomers believe their oligomers generate new, functioning dystrophin for the most common form of DMD. Both companies, Prosensa and Sarepta have other oligomers currently in development personalized to skip other exons for different genetic variants of DMD. The exact genetic profile of the individual must be very carefully characterized to ensure that the new gene patches work and apply themselves, like a Band-Aid, to exactly the right bit of the molecular message, the mRNA.

More recently both companies have reported clinical benefit from their initial exon 51 skipping programs, demonstrated by an improvement in walking, albeit over just six minutes.

But will the new dystrophin now being detected in the early clinical studies replace the missing protein in all muscles, and at the same rate?

DMD affects all muscles, limbs, breathing muscles of the chest, back muscles supporting the spine, and even the heart muscle. It also has adverse consequences on the development and functioning of the brain. We still do not know if the missing dystrophin in the chest or heart muscles can be replaced, and the breathing and heart functions preserved. And we don’t know for sure whether the brain will also benefit too from the functional, but shortened dystrophin generated by these new oligomers.

And then there’s the question of timing. Will the gene patch work on all these organs if it is given to the growing fetus during pregnancy for the full benefits to accrue?

There is still much work to be done as we learn about these new gene patch medicines. As we answer one question, three more pop up. Today’s exciting scientific breakthroughs will seem mundane as we delve more deeply into the genome to try to better design and target the next generation of gene patches.

Personalized medicine is here to stay, in your doctor’s office, at your local hospital, at the regional, national and university centers as well as on some bigger pharmacy shelves. With this new focus, comes an ability to better diagnose, monitor and treat disease effectively and safely. We will also be able to predict and prevent future ill health and promote well-being.

How quickly society grasps these new paradigms remains to be seen, but many are ready and willing now, not least those patients and their families with rare diseases for whom RNA targeting oligomers brings hope of effective management, if not a “cure” for their disease. In comparison to the advances over the last five thousand years, the advances likely in the next fifty have the potential to transform our society like nothing before. We are entering a Golden Age of Medicine. One day soon you will be able to Defy Your DNA.