Finding the right rhythm

The Nobel Prize in Chemistry 2019 recognizes the creation of a rechargeable world that paved the way for pacemakers.

The Nobel Prize in Chemistry 2019 was awarded jointly to John B. Goodenough, M. Stanley Whittingham and Akira Yoshino “for the development of lithium-ion batteries.” Their lightweight, rechargeable and powerful battery is used in mobile phones, laptops and electric vehicles, and it can store significant amounts of energy from solar and wind power. Lithium-ion batteries have also paved the way for pacemakers, one of the medtech industry’s greatest innovations.

A lightweight hardwearing battery

The development of the lithium-ion battery began during the oil crisis in the 1970s, when methods that could lead to fossil fuel-free energy technologies were developed, describe the Royal Swedish Academy of Sciences. Whittingham discovered an extremely energy-rich material and he created a cathode in a lithium battery. The cathode was made from titanium, disulfide which at a molecular level has spaces that can house (intercalate) lithium ions. The battery’s anode was made from metallic lithium, which has a strong drive to release electrons. His battery had great potential but the drawback was that lithium is reactive and this made it too explosive.

The Nobel Laureates in Chemistry 2019, John Goodenough, Stanley Whittingham and Akira Yoshino. Illustration: Niklas Elmehed/Nobel Media AB

Goodenough then demonstrated in 1980 that cobalt oxide with intercalated lithium ions could produce as much as four volts, resulting in much more powerful batteries.

Then Yoshino created the first commercially viable lithium-ion battery in 1985. He used petroleum coke, a carbon material that can intercalate lithium-ions. A lightweight hardwearing battery that could be charged hundreds of times before it deteriorates was born, described the Royal Swedish Academy of Sciences in their press release about the Nobel announcement.

Maintaining heart rhythms

The pacemaker has saved millions of lives and its history is a fascinating one, and it also includes several scientists, engineers and clinicians, all around the world. Already in the 1800s it was discovered that the heart possesses electrical activity, but it was not until 1932 that the first device, an artificial pacemaker, was built (by the American physiologist Albert Hyman). His pacemaker was only tested in animals and at that time artificial heart stimulation was a controversial subject.

The first cardiac pacemaker was invented in 1952 by Paul Zoll, among others. It had the size of a small cathode ray tube television. When smaller batteries and more reliable transistors were developed the device became smaller in size and at the end of the 1950s it could be worn around the neck. Another hurdle along the way to developing the pacemaker was how to prevent water in the body affecting the pacemaker’s electronics. This problem was solved by using hermetically sealed titanium cases. Other scientists, engineers and clinicians who have contributed to the development of the pacemaker include Mark Lidwell, Wilfred Bigelow, John Callaghan, John Hopps, Aubrey Leatham, Geoffrey Davies, Earl Bakken, C. Walton Lillehei, and many more.

The first implantable pacemaker

The first fully implantable cardiac pacemaker was actually developed and inserted for the first time in a patient in Sweden. It was invented by physician and engineer Rune Elmqvist together with surgeon Åke Senning, and was inserted into the first patient, Arne Larsson, in 1958. Larsson was suffering from heart rhythm disturbances called Strokes-Adams syndrome. His symptoms made him faint up to 20 to 30 times a day. On October 8th 1958 he became world famous when he became the first person in the world to have a pacemaker operated into his body. The pacemaker had the same size as a matchbox. Time was short for Larsson and Elmqvist had to mold the components of his device in a simple plastic cup with synthetic resin, according to the Siemens Healthineers MedMuseum. It was a successful operation, but after only three hours the pacemaker stopped. Another copy of the device was operated in the next morning and this second one lasted for weeks.

Rune Elmqvist is adjusting a galvanometer at the University of Lund, Sweden. Copyright: Håkan Elmqvist

All in all, Arne Larsson had 26 different pacemakers in his body over the 43 years following the first implantation. He died in 2001, aged 86, not from his heart problem or his pacemaker but from other causes. The pacemaker had given Larsson quality of life, like the ability to swim and ride a bicycle, and he could work and travel by plane. Today over three million people have a pacemaker.

The Elmqvist pacemaker was developed by his company Elema-Schönander AB, but shortly after the first operation the company was acquired by Siemens and in 1972 Siemens-Elema AB was founded. In 1994 the pacemaker division of the company was sold to the US company Pacesetter, which is and was a part of St. Jude Medical.

“The pacemaker had given Larsson quality of life, like the ability to swim and ride a bicycle, and he could work and travel by plane.”

”In 1994 when Pacesetter and its owner, St. Jude Medical, acquired the pacemaker division from the company that Rune Elmqvist founded, this spurred innovation and patenting work. Over a period of ten years Groth & Co both wrote and applied around 50 patents originating from the company’s facility in Järfälla that related to the pacemaker. These patents concerned improvements within most of the pacemaker’s functions. Patent filings were perhaps primarily within the detection of deviating heart rhythms, but also to some degree concerned the battery and its capacity, status and process of replacement,” says Mathias Loqvist, Head Patent Department, Groth & Co.

In 2011, the pacemaker left Sweden when St. Jude Medical moved their manufacturing of pacemakers and electrodes to facilities in Malaysia and Puerto Rico and shifted R&D focus. Around 450 out of 600 employees lost their jobs. Today the remaining staff are focusing on developing products and services built on communication with pacemakers, which nowadays have a small radio antenna. For example, the new developments can be technology to monitor health and analyze how the information can be used in a new way.

From mercury to lithium-iodine cells

Another very important innovator behind the pacemaker was the electrical engineer Wilson Greatbatch. He was working on an oscillator to aid in the recording of tachycardias at the University of Buffalo, USA, in 1960 when he accidentally discovered a way to make an implantable pacemaker (Aquilina, Images Paediatr Cardiol, 2006). The oscillator required a 10 KΩ resistor at the transistor base, but Greatbatch misread the color coding on his resistor box and got a 1 MΩ resistor by mistake. When he plugged in the resistor the circuit started to “squeg” with a 1.8 millisecond pulse followed by a 1 second interval during which the transistor was cut off and drew practically no current. He realized that this small device could drive a human heart. In 1959, he patented his pacemaker, and William Chardack, Chief of Surgery at Buffalo’s Veteran’s Hospital, reported the first success in a human with this unit in 1960.

Wilson Greatbatch. Photo: University of Buffalo

It was also Wilson Greatbatch who convinced the industry to change from mercury to lithium-iodine cells. Early pacemaker batteries had short, unreliable lifetimes until he developed the long-life lithium-battery in the 1970s. The first pacemaker using a lithium-ion battery was introduced and implanted in a patient in 1972 (source: The Central Intelligence Agency). Greatbatch’s battery soon became used in more than 90 percent of the world’s pacemakers. His innovation gave the pacemaker reliability and the long lifetime needed for it to become standard in cardiac care. With Greatbatch’s battery a patient could expect to only have one pacemaker inserted during his or her lifetime.

In addition to longevity, lithium-ion batteries have another advantage in pacemakers. When the battery is getting closer to the end of its life, the voltage begins to decrease, and due to the decreasing voltage electrical designers can design an end of life indicator for the pacemaker that allows the device to inform the doctor that a new battery is needed. It can then be changed safely before it discharges completely.

“Early pacemaker batteries had short, unreliable lifetimes until Wilson Greatbatch developed the long-life lithium battery.”

Lithium-ion batteries can also be used for other medical applications, such as neuro-stimulation and in insulin pumps for diabetics. The pacemaker has paved the way for the development of implantable defibrillators, diabetes insulin pumps, hip replacements and artificial limbs.

An ongoing development

During the first decades after the pacemaker was invented, it could only emit one steady pulse. Several refinements have been made since then, for example the titanium casing (replacing the epoxy resin and silicone rubber), non-invasively programmable pacemakers, dual-chamber pacemakers, steroid-eluting leads, rate-responsive pacemakers, microprocessor-driven pacemakers, and bi-ventricular pacing for heart failure (Aquilina, Images Paediatr Cardiol, 2006).

“Today’s pacemakers are as small as a coin and weigh only 13 to 40 grams.”

Today the pacemaker can adjust itself to the patient’s individual heart rhythm, at any level of physical activity. It can also synchronize the right and the left chambers during congestive heart failure and via a computer it can communicate wirelessly with healthcare professionals 24 hours a day. Today’s pacemakers are as small as a coin and weigh only 13 to 40 grams. They are operated under the skin at the collar-bone and the stimulating electrode is inserted into the heart through a vein. The operation is performed through local anesthesia and takes less than one hour. In a typically modern pacemaker the battery’s capacity is similar to a cell phone’s battery, but it can last up to ten years.

In recent year there have also been several improvements when it comes to pacemaker technologies. Dave Fornell at Diagnostic and Interventional Cardiology (February 2018) has listed the most important of these. One of the greatest advancements has been the FDA cleared MRI-conditional models. These models allow patients to undergo MR imaging exams without harm to the device or changes to the device settings. Other improvements involve tracking device data and patient health through wireless remote monitoring systems, new data recording functionality to provide more information on patient health and device status, the introduction of single-chamber transcatheter-delivered, leadless pacemaker systems, and longer battery life and technology to help reduce pacing requirements to conserve battery power.

For future pacemakers micro turbines developed by scientists in Switzerland could also play an important role. The micro turbines can be placed in blood vessels and with the help of the blood circulation they could generate electricity. The idea is to provide the pacemaker with energy without using batteries. However, today the technique can cause blood clots and it has to be developed further.

Lithium-ion battery: Akira Yoshino developed the first commercially viable lithium-ion battery. He used Goodenoughs lithium-cobaly oxide in the cathode and in the anode he used a carbon material, petroleum coke, which can also intercalate lithium ions. The batterys functionality is not based upon any damaging chemical reactions. Instead, the lithium ions flow back and forth between the electrodes, which gives the battery a long life. Illustration: Johan Jarnestad/The Royal Swedish Academy of Sciences

The pacemaker – how it works

In a healthy heart a collection of nerve cells in the right atria of the heart (known as the Sinoatrial node) emits impulses to the heart muscle so that it contracts itself and relaxes at a regular rate. If the Sinoatrial node is damaged and not working as it should the heart beats too slowly, irregularly, or in the worst case, not at all.

Pacemakers use electrical impulses to regulate the beating of the heart. The device is battery-operated and consists of two parts; a generator and wires. The generator is a small battery-powered unit that produces the electrical impulses that stimulate the heart to beat. It may be implanted under the skin through a small incision, and it is connected to the heart through tiny wires that are implanted at the same time. The impulses flow through these leads to the heart and are timed to flow at regular intervals, just as impulses from your heart’s natural pacemaker would.

Pacemakers treat disorders making the heart’s rhythm too slow, fast or irregular.