The primary goal of basic, or fundamental, research is to gain knowledge. Questioning how things actually work is a part of human nature. For instance, wondering why the Earth is round. Or what is heat? What is life? This curiosity is in each of us, and science provides a systematic way of answering those questions. However, is it justified to invest tax money or even the lives of animals in order to satisfy this scientific curiosity? Shouldn’t this price only be paid for research with more concrete applications? On this page, we explain that basic research indeed has its practical uses and should be conducted for pragmatic reasons.

• Why do we need basic research?
• Hard facts about the benefits of basic research
• Is there research that will never have a benefit?
  • Hot Bacteria: Taq Polymerase
  • How Do Flies Develop? The Hedgehog Signaling Pathway
  • Shedding Light on Algae: Optogenetics
  • Can Bacteria Get Colds? Restriction Enzymes
  • Electrical Conduction in Gas: X-Rays
  • The Physics of Bubbles: Surfactant
  • Oxygen in Urine: Tissue Respiration
  • The Twitching Frog Leg: Bioelectricity
• Conclusion

Why do we need basic research?

Every aspect of applied research – be it the development of drugs, machines or any other methods – is based on the knowledge of basic underlying principles. In order to invent light bulbs, we first needed to understand the physical principles of electricity. In order to develop antibiotics, we first had to understand the metabolic pathways present in bacteria, and also how bacteria could cause infectious diseases! Applied research projects grow like tree branches from the trunk of basic knowledge.

Basic research is like a tree trunk, from where applied research projects can grow

Since the earliest days of science, researchers have said that all new knowledge and its applications can only be built upon prior knowledge. As an example, consider one of the great geniuses of the modern era, Sir Isaac Newton (1643-1727). Newton described the laws of motion, the law of gravity and developed calculus – all before his 26^th birthday! He himself said that his scientific advances were only possible because he stood “on the shoulders of the giants.” With this, he was referring to the knowledge gained by previous researchers that he could build upon.

Scientists stand “on the shoulders of giants.”

The legendary neuroscientist Santiago F. Ramón y Cajal (1852-1934) expressed a similar idea. Ramón y Cajal wrote that knowledge has to accumulate over a long time period, until finally, “several truths can be combined into a useful whole,” i.e. into an application. We have translated the timeless text on basic science by Ramón y Cajal from Spanish into English here.

Hard facts about the benefits of basic research

In 1975, Julius H. Comroe and Robert D. Dripps systematically examined the relationship between basic research and applications. For this they asked cardiologists and pulmonologists which medical developments were most important in their field in the last 30 years. They compiled a list of ten applications, topped by open-heart surgery (e.g. procedures on the heart valves), vascular surgery (e.g. bypass surgery), and hypertension medication. For each point on the list, the authors identified hundreds of sources of underlying knowledge (e.g. of anesthesia, blood typing and electrocardiography (ECG)). Then, they identified 2,500 scientific papers that were of essential importance for one of these areas and examined a portion of them in greater detail. Comroe and Dripps found that 61.5% of the scientific work was basic research. That is, most of the research to which we owe the 10 most important advances of cardiac and pulmonary medicine until 1975, was carried out before the far-reaching benefits were foreseen. A heart surgery would not be possible if electricity had not been discovered (e.g. work from Charles du Fay, Benjamin Franklin), followed by the discovery that animals conduct electricity in their organs (Luigi Galvani, Alessandro Volta), such as the heart (Carlo Matteucci). Additionally, with the development of ECG we were able to measure and monitor the heart’s electrical activity (Augustus D. Waller, Willem Einthoven). Comroe and Dripps compared medical progress to the climbing of a summit growing with each generation. While no single person could reach the summit by starting all the way in the valley, they do not have to because each generation starts at an ever-higher point, climbing further than ever reached before.

A breakthrough is like climbing a mountain – one step at a time

It is often not clear whether a research project is basic or applied because the transition area is very large. Thus, the Basel Declaration recommends against a conceptual distinction. Somebody who investigates physiological principles might be said to work towards a medical improvement just as much as somebody developing a specific drug. In their recent work, Robert S. Williams and colleagues traced the development of important new drugs against cystic fibrosis (Ivacaftor) and cancer immunotherapy (Ipilimumab). They found that the development of Ivacaftor dates back to the work of 2,900 scientists across 2,500 institutes over 60 years. The development of Ipilimumab required the work of 7,000 scientists across 5,700 institutions over 100 years. The authors concluded that a broad knowledge base was necessary for the development of both drugs. In their opinion, a limited focus of all research efforts on the treatment of cystic fibrosis and cancer would not have been successful due to lacking the necessary knowledge base.

Is there research that will never have a benefit?

No, below you will find a number of examples where seemingly useless research has done an irreplaceable service to humanity.

Hot Bacteria: Taq Polymerase

In the 1960s, researchers examined bacteria that live in hot geysers. They wanted to know how these bacteria could sustain temperatures typically hostile to life. Useless curiosity research, right?

Hot Spring in Yellowstone Park (Photo Source: Wikipedia)

This work led to the discovery that the bacterium Thermus aquaticus has a particularly heat-stable version of a vital enzyme called DNA polymerase, responsible for assembling DNA molecules from nucleotides. In 1988, the DNA polymerase from Thermus aquaticus (Taq polymerase) became the crucial ingredient for an applicable polymerase chain reaction (PCR). PCR has since become a standard method for DNA analysis. Without this tool, the current progress in genetic research would be unthinkable. PCR is an integral part of HIV testing, identification of genetic fingerprints, paternity testing and the diagnosis of various genetic diseases.

How Do Flies Develop? The Hedgehog Signaling Pathway

In the late 1970s, scientists began to investigate how fly eggs develop into full-fledged flies. Well, that’s interesting, and perhaps even a bit disgusting, but what’s the use?

Fruit Fly Pupae (Photo Source Wikipedia)

This research was essential for our understanding of developmental biology. Many of the genetic mechanisms discovered in flies are also found in humans. Amongst others, the discovery of the Hedgehog signaling pathway in fly embryos formed the basis for the skin cancer drug Vismodegib.

Shedding Light on Algae: Optogenetics

Since the beginning of the 20th century scientists have been researching how a type of unicellular algae always manages to swim to the light in their ponds. This information cannot seriously have a practical use, right?

Puddle with Algae (Photo Source: Wikipedia)

Actually, this research led to the identification of channelrhodopsin, a photosensitive ion channel protein that is encoded by a single gene. This protein was a key component in the development of optogenetics. Optogenetics works by introducing a photosensitive channel protein into cell membranes (mostly nerve cells) via genetic manipulation. These cells can then be activated by light. Depending on the type of channel introduced to the cell, the light will selectively activate or silence certain neurons. The introduction of optogenetics about ten years ago led to an enormous acceleration of neuroscience research. Medical applications of optogenetics, which are currently being developed, aim to return eyesight to the blind, return paralytic bladder control and optimize deep brain stimulation for Parkinson’s and other diseases.

Can Bacteria Get Colds? Restriction Enzymes

Like us, bacteria can become infected by viruses. We defend ourselves with our complex immune system, but what about bacteria? Do they also have an immune system? Unique, useless curiosity research! Or do they want to cure bacteria of colds?

Viruses Infect a Bacterium (Photo Source: Wikipedia)

Research of the bacterial immune system in the 1960s and ’70s led to the discovery of restriction enzymes. It was only through these enzymes that we were able to specifically modify genes. Through this discovery we can, for example, use bacteria to produce life-saving insulin for diabetics, instead of having to isolate it from cows or pigs, vaccines, medical antibodies, hormones and many other drugs. Further, exploration of the bacterial immune system has recently led to the discovery of CRISPR/Cas9, an even simpler way of modifying genes. This method accelerates biological research enormously and raises great hopes for the development of effective gene therapy.

Electrical Conduction in Gas: X-Rays

A Crookes tube is a cathode ray tube that, in response to high voltages, produces a weak light through electron streams. One caveat of cathode ray tubes is that they require a lot of power. This is obviously not the future substitute for light bulbs, so why continue researching cathode ray tubes?

Crookes Tube Turned On and Off (Photo Source: Wikipedia)

In 1895, Wilhelm C. Röntgen experimented with Crookes tubes. He came across a strange phenomenon – a new type of radiation that can penetrate objects where light cannot. He quickly realized that one could take pictures from inside the body using this X-radiation – an invaluable step forward for medicine. Radiography using X-rays are used to this day in every hospital to diagnose and evaluate patients.

The Physics of Bubbles: Surfactant

In the 1950s E.J. Radford tried to determine the surface area of the lungs. Do we really need to know the exact dimensions? In addition, there were already estimates due to microscopic measurements. Wasted effort, right?

Giant Bubble (Photo Source: Wikipedia)

Radford used the surface tension of the lung tissue for his measurements. This method gave rise to an estimate of the lung surface 10 times smaller than previous ones – unless his assumption that the surface tension of lung tissue was equal to other tissues was wrong. This was exactly what was investigated by John A. Clements, who found that a film on the alveoli greatly reduces the surface tension, similar to soap bubbles. In his investigation, Clements was able to pull up basic research from 1805 to understand the surface tension of bubbles. Subsequent work found that this film “surfactant” is missing in premature infants. This is in fact the cause of respiratory distress syndrome, the leading cause of death in premature infants. We owe our ability to treat this syndrome to basic research. For now we can use preventive drugs for lung maturation or manually apply surfactant in acute cases. Thanks to the advances of genetic engineering we no longer need to isolate surfactant from animals, but can produce it microbiologically.

Oxygen in Urine: Tissue Respiration

In the 1870s, Edward F. W. Pflüger measured the content of oxygen and other gases in all kinds of bodily fluids, including blood, urine, lymph and bile. Was that really a wise investment of research funds?

Urine (Photo Source: Wikipedia)

Pflüger’s research has been of fundamental importance to our understanding that oxygen is absorbed through the lungs, transported to bodily tissue via the bloodstream and consumed there. He refuted the idea that the consumption of oxygen occurs in blood or the lungs and proved that respiration takes place in bodily tissue. This knowledge has been a prerequisite for numerous medical applications, including the development of the heart-lung machine.

The Twitching Frog Leg: Bioelectricity

Luigi Galvani discovered in 1780 that applying voltage to a frog’s leg will cause it to twitch. He investigated this phenomenon for many years and inspired many other researchers to do so too. Macabre! Do you want to bring the dead back to life now? Or could there be some other useful application?

Galvani’s Experimental Set-Up  (Photo: Public Domain)

The work of Galvani laid the foundation for our current understanding of the workings of muscles and nerves. The realization that these bodily functions are due to electrical processes resulted in countless medical applications. Some examples include deep brain stimulation in Parkinson’s, the measurement of cardiac activity by means electrocardiography, treatment of life-threatening ventricular defibrillation, pacemakers, or the diagnosis of epilepsy and other disorders using electroencephalography.

Conclusion

As long as an experiment answers a scientific question it is useful. Considering again the studies by Comroe and Dripps or by Williams and colleagues, we can see that  contributions from basic science were essential for applied medical science. But what is more, taking their approach is limited to only seeing the direct links of the final product of basic science to application, which invariably masks most indirect contributions. For instance, what contribution did scientists who tried to refute a theory make at the  time? Their work was important if it helped to systematically eliminate weaknesses of the theory. In a famous experiment, Albert A. Michelson and Edward W. Morley wanted to prove for good the existence of luminiferous aether, the hypothetical medium in which light waves supposedly moved. They failed. In spite of their very precise measurements, they could not find the predicted movement of the aether relative to the earth. Their hypothesis was wrong, and they drew the wrong conclusions from their results. But the measurements were correct. Their experiment is now considered one of the most important in the history of physics. It motivated a number of other studies and considerations that led to the development of Albert Einstein’s theory of relativity. Einstein once said about basic research, “the most important thing is to never stop asking questions. Curiosity has its own raison d’être.”