Thursday, February 11, 2016

Unbreak My Heart: A Short History Of The Defibrillator and CPR

“Hearts cannot be broken, they're small squishy things
They don't break like glass but they bruise easily” – The Judybats

While hearts can’t be broken, their rhythmic beating can go awry – a condition we call arrhythmia. Many people don’t think of the heart as a muscle, but that’s what it is - a muscle that pumps blood around the body through a series of regular contractions. When the ventricles contract, oxygenated blood gets pumped out into circulation; when they relax, they fill back up with blood. Disruption of this routine delays delivery of blood to tissues and organs, including the brain.

Ventricular fibrillation is caused when a heart disorder leads to a problem with the electrical impulses running the cardiac muscles, which makes them quiver instead of contracting. A defibrillator basically sends an electric shock through the heart, stopping it in hopes that it starts back up with its normal rhythm restored. A remarkable feat that has saved tens of millions of lives, but how did we learn to do this?

Ventricular fibrillation usually occurs as a consequence of previous cardiac damage, such as a heart attack. But what about the pain that we feel when someone “breaks” our heart? Believe it or not, stress-induced cardiomyopathy, also known as “broken heart syndrome” is a real thing!
For centuries, it was believed that muscles used air or liquid to inflate. In the 1780s, Luigi Galvani “popped” this so-called “balloonist” theory by applying a newly discovered power called electricity to the leg muscles of a dead frog. In his experiments, Galvani stimulated limb muscles with heat, lancets, or chemical irritants…but only an electrified rod prompted those muscles to contract. This was a profound discovery that opened up a whole new field in medicine that studies the role of electricity in physiology (electrophysiology). And it raised an exciting question:  can electricity be used to reanimate life?   

Long ago, people used to believe muscles expanded and contracted because of air or fluid inside them. This was referred to as the “balloonist” theory.
Galvani’s nephew, Giovanni Aldini, set out to address that haunting question by performing what scientists were calling “Galvanic experiments”. In 1803, he freaked out a lot of people with a public demonstration involving the corpse of a freshly executed criminal and a pair of conducting rods hooked up to a battery. Aldini proceeded to touch the corpse at his mouth, ear, and, of course, his rectum. An eyewitness account documented the creepy results: “On the first application of the process to the face, the jaws of the deceased criminal began to quiver, and the adjoining muscles were horribly contorted, and one eye was actually opened. In the subsequent part of the process the right hand was raised and clenched, and the legs and thighs were set in motion.” (from the Newgate Calendar, January 18, 1803).

You might be wondering if Galvani or Aldini’s experiments inspired Mary Shelley’s 1818 classic, Frankenstein: or, The Modern Prometheus. While Shelley was aware of their work, electricity was not mentioned in her novel as the means by which Dr. Frankenstein’s creature was brought to life…that specific idea was incorporated later on when the story was made into a movie.
As dramatic as the “shocking” experiment was, the lesson was that electricity would not reanimate a corpse. So it wasn’t until 1930 that this sort of work was resurrected with simpler objectives:  using electric currents to kickstart a heart. Enter William Kouwenhoven, who invented the heart defibrillator, a device that essentially “restarts” the cardiac engine*. His experiments did not get off to a promising start. In 1928, high voltage shocks from electrodes placed on the head and one limb of a rat only resulted in a dead rat. But by 1933, he was able to restore normal heartbeats to dogs. However, this required direct contact with the dog’s heart muscle to work. This method of “open chest heart defibrillation” was practiced on patients until 1957, when Kouwenhoven built a device capable of delivering the electrical pulses from outside the body.

One of the first defibrillators by Kouwenhoven compared to what they look like today.
Kouwenhoven’s defibrillation studies also led to the development of cardiopulmonary resuscitation (CPR) as a critical life-saving technique. One fine Saturday – because all good scientists work through the weekends – a graduate student named Guy Knickerbocker noted a brief rise in blood pressure when he pressed those heavy copper defibrillator paddles onto the dog’s chest. This gave rise to the idea that by forcefully pressing on the chest, one could help circulate blood through the body until the heart started beating again.

*Kouwenhoven’s research stemmed from earlier findings, most notably those made by Jean-Louis Prevost and Frederic Batelli. In 1899, they observed that electrical shocks could induce ventricular fibrillation in dogs, but even larger shocks could restart their hearts.

Contributed by:  Bill Sullivan

Bresadola, M. (1998). Medicine and science in the life of Luigi Galvani (1737–1798) Brain Research Bulletin, 46 (5), 367-380 DOI: 10.1016/S0361-9230(98)00023-9

Wednesday, February 3, 2016

Where Do “New” Viruses Come From?

Every year there seems to be a new virus that just popped up out of nowhere to cause us a great deal of pain and suffering. Is it the work of a mad scientist vying for global domination? Are these viruses coming back to life after being frozen for millennia? Are they hitching a ride to Earth via meteorites?

The truth is many of these viruses are not so new – but we are creating new opportunities for them to infect us. Many viruses jump from other animals into people – a process known as “zoonotic transmission” – and some of our actions roll out the red carpet for the virus. Let’s take a closer look at where some of these “new” viruses may have originated and how they spiral out of control.


Microcephaly is a term used to describe babies born with much smaller head size than normal, which is indicative of incomplete brain development. In Brazil, this birth defect occurs about 150 times per year. However, in the past 4 months, nearly 4,000 babies have been born with microcephaly - a dramatic spike that has set off alarm bells.

Photo of a child born with microcephaly, which has been linked to the Zika virus.
While evidence is still circumstantial, the primary culprit is a previously obscure virus called Zika, named after the forest in Uganda where it was first identified in a rhesus monkey back in 1947. Zika is transmitted through mosquitoes, which basically operate like flying dirty syringes. If they fed on an infected person, they can transmit the virus to the next person they bite.

Global warming and increased travel have conspired to create excellent opportunities for viruses like Zika to spread. It only takes one infected person to attend a major spectacle (for example, the 2014 FIFA World Cup in Brazil) to start a chain reaction of viral transmission. Viruses need no passports and can jet set around the world in unprecedented time. Global warming is an issue because it has allowed the species of mosquito that carries these viruses to thrive in areas that used to be too cold. Even El Niño has been catching some of the blame for helping to spread Zika.


While Zika jumped to humans from other primates, the African filovirus Ebola is thought to have originated in fruit bats. Bats can transmit a number of other deadly viruses, including rabies. Bats happen to be a source of food in several of the areas where Ebola outbreaks have occurred, consistent with the idea that bats are the culprits. Once Ebola infects a human, it can spread quite easily to other people through bodily fluids.

Bats like this one are now considered to be a major carrier capable of spreading the Ebola virus to people.
Ebola first appeared in humans in 1976 in the Sudan and the Democratic Republic of Congo. The initial outbreak killed an estimated 600 people, but the latest outbreak that began in 2014 in West Africa has been the worst in history, killing over 11,000 people. This wasn’t due to an enormous fruit bat invasion, but rather human-to-human transmission. Genetic studies indicated that the entire epidemic likely stemmed from just a single infected child in Guinea, the so-called “Patient Zero”. A catastrophic mix of poor health facilities and unsanitary practices ignited to spread the virus like wildfire.

The 2014 Ebola outbreak started with a toddler who fell sick in Meliandou village in Guinea. Source.
Credit: Live Science

MERS, Middle East Respiratory Syndrome, first made headlines in 2012. This life-threatening respiratory virus reared its ugly head in Saudi Arabia first, but has since been reported in 25 other countries, including those not in the Middle East (due to unwitting travelers carrying more than their luggage). MERS is caused by a coronavirus, so the causative agent is typically referred to as MERS-CoV. Like many other respiratory viruses, coughing in close proximity can spread MERS-CoV between people.

But how did MERS-CoV get into people in the first place? According to the World Health Organization:  “It is believed that humans can be infected through direct or indirect contact with infected dromedary camels in the Middle East. Strains of MERS-CoV have been identified in camels in several countries, including Egypt, Oman, Qatar and Saudi Arabia.”

It is easy to understand the respect and admiration one can have for a noble creature like the camel. But getting a little too intimate with a camel may literally leave you breathless.
So stay away from coughing camels! In some areas, camels are butchered for food and their milk and urine (yes, urine) is consumed. These practices provide additional avenues for possible transmission of MERS-CoV to humans.

UPDATE (3/1/16): A new study suggests that we have bats to thank once again for spreading MERS-CoV to camels.


Human Immunodeficiency Virus (HIV), which causes AIDS, wasn’t on anyone’s radar until an unusually large number of people starting suffering from rare diseases with strange names like Kaposi’s sarcoma, toxoplasmosis, and pneumocystis. These diseases are hardly ever seen in people with normal, healthy immune systems. Turns out they were secondary infections – the primary infection was HIV, which was destroying the very immune cells that are needed to keep those other illnesses at bay.

Historical records have placed the earliest cases of HIV infection to the 1950s, which suggests it has been moving through humans slowly through the decades prior to its explosion in the early 1980s. An increase in international travel, unsafe sexual practices, and intravenous drug use are all factors that have contributed to accelerating the epidemic.

HIV (yellow particles) is a cunning foe that destroys the immune cells (blue) designed to protect us from foreign invaders.
We still don’t know how HIV leapt into the fabric of human DNA, but the evidence is very strong that it came from other primates. SIV, or simian immunodeficiency virus, has been found in African primates and is highly similar to HIV; it is easy to imagine that blood from infected primates, some of which are butchered for food or kept as pets, found its way into a person's open wound. Once in humans SIV evolved into HIV, transmissible to others through bodily fluids. HIV likely spread around Africa in its early days through the use of shared needles in impoverished hospitals.

It’s a virus world after all

As you can see from these examples, many “new” viruses were actually pre-existing in other animals and just made a “species jump” into humans. But how did these viruses get into the other animals in the first place? That question is a lot harder to answer.

Viruses are little more than a fragment of DNA or RNA, perhaps rogue genes that escaped a cell and became independent, infecting other cells in order to replicate and spread. Richard Dawkins coined the term, “the selfish gene”, and that is a very accurate description of viral DNA/RNA. What we do know is that viruses have been around a long, long time, perhaps before the dawn of life itself. There are even viruses that infect bacteria.

Once inside host cells, viruses replicate quickly, which means they are very adaptable. Their ability to evolve quickly is likely to be a key factor explaining why these selfish genes can make a reproductive factory out of a wide variety of different hosts…and why “new” viruses can appear to spring out of nowhere.

While viruses are a nuisance to us now, they may have been important drivers of evolutionary change in the past. It has been proposed that RNA viruses may have led to the formation of DNA and DNA replication mechanisms, without which we would not even be here to complain about them!

Contributed by:  Bill Sullivan, Ph.D.

Simpson, D. (1964). Zika virus infection in man Transactions of the Royal Society of Tropical Medicine and Hygiene, 58 (4), 339-348 DOI: 10.1016/0035-9203(64)90201-9

Forterre P (2006). The origin of viruses and their possible roles in major evolutionary transitions. Virus research, 117 (1), 5-16 PMID: 16476498

Koonin EV, Senkevich TG, & Dolja VV (2006). The ancient Virus World and evolution of cells. Biology direct, 1 PMID: 16984643

Baize, S., Pannetier, D., Oestereich, L., Rieger, T., Koivogui, L., Magassouba, N., Soropogui, B., Sow, M., Keïta, S., De Clerck, H., Tiffany, A., Dominguez, G., Loua, M., Traoré, A., Kolié, M., Malano, E., Heleze, E., Bocquin, A., Mély, S., Raoul, H., Caro, V., Cadar, D., Gabriel, M., Pahlmann, M., Tappe, D., Schmidt-Chanasit, J., Impouma, B., Diallo, A., Formenty, P., Van Herp, M., & Günther, S. (2014). Emergence of Zaire Ebola Virus Disease in Guinea New England Journal of Medicine, 371 (15), 1418-1425 DOI: 10.1056/NEJMoa1404505