Healthcare Revolution — Part I: Living Longer

In 1901, average life expectancy in USA was 49 years, and in India 23 years. Fast forward a century, in 2001 Americans lived for an average 77 years and Indians 62 years. The global population increased from 1.6 billion to 6.1 billion! We have learned to live longer. We have even changed how we die: a massive shift from infectious diseases (Pneumonia, Tuberculosis, Gastrointestinal infections etc.) to Non-Communicable Diseases (Heart Disease, Cancer, Noninfectious Airway diseases etc.) as the most common causes of death has been recorded in the United States.

Top 10 Causes of Death: 1900 vs. 2010. From N Engl J Med 366;25.

This story recounts the crucial innovations that drove this radical change in human lives. It then reflects on the lessons learned from these innovations and sets the stage for the second part of this series where those lessons will be used to predict how the next decade is likely to evolve. The second part will end with a visualization of how our health might look like in 2030.

Looking into the past, five major themes drove the healthcare revolution during the period from 1900 through 2000. These are Diagnostics, Medicines, Devices, Surgical techniques and Public Health. The first four of these are large global industries now, contributing significantly to the global healthcare market, which in 2018 was $8.4 trillion.

The Diagnostics journey began in 1896 with the discovery of X-rays by Roentgen. Soon, these images started guiding doctors in managing bone fractures and chest diseases like Tuberculosis. It took several decades for the 'plane' X-ray images to convert to more high-resolution cross-sectional images of the human body through the invention of Computerized Tomography (CT scans) by Godfrey Hounsfield in 1972. A new modality called Magnetic Resonance Imaging (MRI) which does not involve radiation, but rather uses very powerful magnetic fields to extract imaging information from body structures was invented and deployed by late-eighties. These MRI images now form the mainstay of body imaging and thousands of systems have been deployed in hospitals and imaging centers around the world. In fact, so central is imaging to modern medicine that very few surgeries can be performed today without using some form of imaging to inform the surgeons of the underlying abnormalities.

Another important form of diagnostics emerged from the microscopic and chemical examination of blood and other body fluids or tissues. While the microscope was invented in the 17th century, it was left to Louis Pasteur (1822–1895) and Robert Koch (1843–1910) to develop microbiology and the currently accepted 'germ theory of disease'. By 1901, a famous medical text listed Hemoglobin estimation, Blood culture, isolation of typhoid bacilli from urine and a handful of other similar lab tests. Today, a well-known laboratory testing vocabulary (LOINC) codes nearly 78,000 tests that can be carried out on the human body!

Medicines, or more formally Pharmaceuticals started becoming main-stream in the 19th century through humble origins as botanical extracts — for example morphine and quinine. In 1897, chemical synthesis of epinephrine was accomplished, and Parke-Davis marketed epinephrine under the brand name Adrenaline which proved to be quite useful for asthmatic attacks and other allergic reactions. In 1903, barbiturates were discovered, and Bayer started marketing Phenobarbital which proved quite useful as a sedative and an anti-epileptic. In 1920s, Banting and Best isolated insulin from pancreatic extracts and Eli Lilly and Company started marketing Insulin for diabetics.

A real shift in pharmaceuticals and humans' fight against infections started in 1928 with the discovery of penicillin by Alexander Fleming, but its mass production had to await other improvements in industrial techniques. Finally, large scale penicillin was produced in time (2.3 million doses) for the Normandy invasion during the spring of 1944. By 1945, hundreds of billions of doses of Penicillin were being manufactured and marketed. The aftermath of World War II saw an explosion in the discovery of new classes of antibiotics including cephalosporins, streptomycin, the tetracyclines and erythromycin. During the years 1940–1955, the rate of decline in US death rate accelerated from 2% per year to 8% per year, and then returned to the historical rate of 2% per year. The dramatic decline in the immediate post-war years has been attributed to the rapid development of new treatments and vaccines for infectious diseases that occurred during those years. Beyond antibiotics, the discovery and population scale deployment of vaccines including TB (1921), Diphtheria (1923), Tetanus (1924), Pertussis (1926), Polio (1952), Measles (1963), Mumps (1967), Rubella (1970), Meningitis (1978) and Rotavirus (1998) played a huge role in eradicating or controlling several infectious diseases.

Prior to 1940s, approximately 23% of all deaths among persons over age of 50 were attributed to hypertension. In 1952, researchers at Ciba discovered the first orally available vasodilator — hydralazine. A bit later in the same decade, scientists at Merck discovered chlorthiazide, which remains one of the most widely used anti-hypertensives even today. In ensuing years other classes of antihypertensive drugs were developed including loop diuretics (Hoechst), beta-blockers (ICI Pharma), ACE inhibitors and angiotensin receptor blockers.

The first oral contraceptive, Enovid, was developed by ED Searle & Co and approved by FDA in 1960. By 1965, 6.5 million American women were on the 'pill'. On another front, Mustard gas was deployed as a weapon in World War I and autopsies of its victims revealed severe bone marrow depression. This led to the discovery of Mustine (a prototype of Nitrogen Mustard) by Goodman and Gilman which was deployed for the treatment of Non-Hodgkins lymphoma in 1946. Soon thereafter, a new class of anti-cancer drugs called antifolates was discovered and in 1947, Major League Baseball Hall of Famer Babe Ruth became one of the first humans to receive this treatment for nasopharyngeal carcinoma. He improved for several months but died the following year. In 1965, a major breakthrough in cancer therapy occurred when the idea of combining different drugs with varying mechanisms of action was proposed. The first regimen called POMP was later extended to the MOPP regime [(M)ustard Nitrogen, (O)ncovin, (P)rocarbazine & (P)rednisolone] by Vincent DeVita et al and this was shown to cure Hodgkin's lymphoma and some forms of Non-Hodgkin's lymphomas in a reliable and consistent manner. The still incomplete journey of conquering cancer had begun its first steps. Currently, nearly all successful cancer chemotherapy regimens use this paradigm of multiple drugs given simultaneously, called combination chemotherapy.

Moving to our third theme of medical devices, implantable orthopedic implants (plates, screws and rods) started appearing by 1920s due to the availability of X-ray images which enabled surgeons to see the bone damage prior to surgery. Stainless steel was the first material used (c. 1926), followed by Tantalum in 1936 and finally Titanium & its alloys from 1947 onwards. Titanium forms the mainstay of most orthopedic implants even today because it is MRI compatible. Around September 1940, Dr Austin Moore implanted the first metallic hip implant into a patient at Columbia Hospital in South Carolina. The first heart pacemaker was invented in 1950, but it was the size of a cart! By 1958, thanks to development of silicon transistors which allowed miniaturization, the first wearable, external, transistorized pacemaker was used in a patient. Around the same time, development of biocompatible silicone elastomer allowed the invention of hydrocephalus shunts for diverting excess fluid in the brain into the abdomen. Knee replacement implants started by 1970s and now nearly 600,000 knee replacements are performed in the United States every year. The technique of inserting catheters and injecting radio-opaque dyes to image the anatomy of the blood vessels in patients (angiography) had started to become mainstream after the WW II, and the first coronary angioplasty was performed by Dr Gruentzig at University Hospital, Zurich in 1977. Stents are tubular devices that serve as scaffoldings to keep the blood vessels open after the plaques have been removed by angioplasty, and the first stents were implanted in coronary arteries of patients in 1986. This technique has exploded in its usefulness and application around the world and around 1.8 million stents are now implanted in United States alone per year.

All the above themes (i.e., Diagnostics, Pharmaceuticals & Devices) contributed to the development and advancement of surgical techniques, most of which form the mainstay of modern medicine. While surgical procedures have a long history (early evidence of surgery has been seen in Egyptian mummies and ancient Indian texts describe techniques like rhinoplasty in some detail), the two World Wars in the 20th century led to a huge increase in surgical techniques to deal with injuries. Antibiotics and better anesthesia techniques made it safer to open the living human body and fix it structurally from inside. Surgical procedures on every part of the human body developed during the second half of the 20th century culminating in transplantation of entire organs including the kidney (1950), lungs (1963), pancreas (1966), liver (1967) and heart (1967). Millions of surgeries are now performed around the world with tremendous safety and success and this is testament to the power of modern medicine which has been built on these four pillars.

Finally, the theme of Public Health has been working in the background to enable the above themes to be much more effective. Improvements in sanitation systems in cities and water supply have had a major contribution towards preventing diseases (e.g., cholera and typhoid) and enabling humans to live longer lives. Ironically, failures in public health like the current nutritional crisis (leading an explosion of obesity and diabetes) and the continuing tobacco and drugs crisis have started becoming obstacles for health rather than enablers.

So, what have we learned about healthcare innovation from this dramatic century? First, innovations in other seemingly unrelated fields (e.g., chemistry, metallurgy, electronics, quantum physics etc.) are often major contributors to healthcare advances — many times more so than internal improvements. Therefore, for predicting future of healthcare, one will have to watch the relevant non-healthcare trends very carefully. Secondly, innovations in healthcare have much slower ramp up curves than in other industries like manufacturing and technology. New techniques and technologies need to be understood by the doctors, tried carefully and then adopted. Typically, it takes 15–20 years for a new innovation to become mainstream in modern medicine. Thirdly, while serendipity sometimes plays a role in innovation (e.g., Fleming noticing effect of penicillin), more often it is intense curiosity and determined effort made by hundreds of people over long periods of time which lead to significant advances in healthcare.

In summary, we have made more gains in our health during the 20th century than the preceding 20,000 years. This has been made possible due to overall advance in our knowledge across various fields and mastery over the materials. These changes are accelerating, not slowing down and we now have 8 billion people connected via the internet and mobile telephony systems generating large quantities of data that can be analyzed by huge data server farms running sophisticated artificial intelligence algorithms. These trends are reviewed in the next essay in this series, Healthcare Revolution Part II: 5 Ways We Will be Living Better By 2030.