IMA_Conservation_Science_Lab

by Emily Low
figures by Daniel Utter 

Discovery in science does not follow a straightforward path. Scientific research is conducted using models that are still being developed, in the context of dozens of unanswered questions, and using techniques and approaches no one else in the world has used before. According to the Association of American Medical Colleges (AAMC), basic science “provides the foundation of knowledge for the applied science that follows.” In the biomedical sciences, the phrase “basic science” often refers to research using model organisms to obtain the background knowledge necessary for technological and drug development. In basic science, scientists utilize many simple organisms, like fruit flies and worms, because they are easy to study and manipulate, yet share many molecular and biological processes with humans. Results of these basic studies contribute to our understanding in fields such as genetics, biochemistry, stem cell research, and neurobiology. However, the connection between this kind of research and general human welfare can be unclear, even to the most knowledgeable expert. How can we know whether or not the things scientists study will be useful in the future? Do we need to know the future application of a project for it to be valuable?

A case study: the discovery of restriction enzymes

In 1978, the Nobel Prize in Physiology or Medicine was awarded to Werner Arber, Daniel Nathans, and Hamilton O. Smith “for the discovery of restriction enzymes and their application to problems of molecular genetics.” Restriction enzymes, or protein “scissors” found in bacteria that can cut DNA, are critical tools for today’s molecular biologists, and can be found in almost every biological laboratory. Restriction enzymes contributed to the sequencing of the human genome, as well as the creation of the first synthetic cell.

However, the scientists who discovered restriction enzymes were not originally hunting for ways to manipulate DNA. As Arber described it, “I did not of course imagine that this sidetrack would keep my interest for many years. Otherwise I might not have felt justified to engage in this work because of its lack of direct relevance to [my initial] research.” Arber was initially studying how radiation damages genetic material and how this damage is fixed. The first step he took was to create a set of tools. He needed to find out how to introduce foreign genetic material into radiation-sensitive types, or strains, of E. coli bacteria, and to do this, he selected a type of virus called bacteriophage. Bacteriophage specifically infect bacteria, injecting their genetic material into the bacteria to provide information for the synthesis of new viruses. These viruses are small and fast-growing, and so make experiments efficient and easy to perform. However, different strains of bacteria were known to be resistant to infection by certain strains of bacteriophage. As Arber was determining how to facilitate the transfer of bacteriophage DNA into E. coli, he realized that the reason his strain of E. coli was resistant to infection by his bacteriophage was because the bacteria must have some kind of protective modification. Curious to discover the nature of this modification, Arber and the scientists in his lab found that phage DNA was being chopped up by miniature bacterial scissors—restriction enzymes. The characterization and isolation of these restriction enzymes by Arber, Nathans, Smith, and others allowed for the development of restriction enzymes as everyday tools. Restriction enzymes are now widely used in molecular cloning, the process by which scientists can cut and paste DNA into bacteria to make copies of genes. This technique is critical for determining sequences in a person’s DNA, as well as for disrupting genes in model organisms to determine how they function in models of disease. Furthermore, restriction enzymes and molecular cloning have contributed to the sustainability of the modern food industry. Much of the produce found in grocery stores today are from crops that are genetically engineered for properties like greater resistance to pests and herbicides, while animals like cows and sheep have been genetically modified for protection against disease.

Figure 1. The discovery of restriction enzymes. Scientists had observed that some strains of E. coli bacteria were resistant to infection by certain strains of bacteriophage, and that some were not. They discovered that resistance occurred when the bacteria (grey ovals) possessed restriction enzymes (orange scissors), which recognize bacteriophage DNA (red) and cut it up. When bacteriophage DNA is intact, it provides instructions for the production of new bacteriophages (right side, unsuccessful defense). When the DNA is cut up, bacteria are not infected (left side, successful defense).
Figure 1: The discovery of restriction enzymes. Scientists had observed that some strains of E. coli bacteria were resistant to infection by certain strains of bacteriophage, and that some were not. They discovered that resistance occurred when the bacteria (grey ovals) possessed restriction enzymes (orange scissors), which recognize bacteriophage DNA (red) and cut it up. When bacteriophage DNA is intact, it provides instructions for the production of new bacteriophages (right side, unsuccessful defense). When the DNA is cut up, bacteria are not infected (left side, successful defense).

In hindsight, bacteriophage research was important for the discovery of restriction enzymes, as well as solving many other questions in molecular biology. But imagine that you didn’t know that this would happen. If you were considering whether to fund bacteriophage research at the time, would you have done it?

Choosing which research to fund can be a little bit like swinging at a piñata while blindfolded—you don’t know which direction to swing to hit the prize. Choosing to swing in just one direction every time could be fruitless. However, if you swing in a different direction each time, you increase your chances of hitting the piñata. In the same way, the more avenues of scientific research we decide to fund, the more likely we are to come across new answers.

Is scientific effort ever wasted?

There are many questions that science seeks to answer. How do we prevent global warming? How do we cure cancer? How do humans adapt to their environment? In the face of limited resources and time, answering such complex questions is difficult. It can be tempting to funnel funds for scientific research towards expensive, cutting edge technologies that aim to answer these questions, ignoring questions that seem less important and approaches that are slow or old-fashioned. However, by investing only in research that focuses specifically on climate change or human health, we lose the opportunity to obtain knowledge we didn’t even know existed. The unexpected discoveries made in the context of basic research are important for solving scientific problems, making all of the work and money worthwhile.

The case for funding basic science

To a scientist, one of the most compelling reasons to perform basic research is because the research is inherently interesting. Something can be exciting because it is novel—never before observed or described by any other person. Or, something can be intriguing because it is central to many different biological processes, and has the potential to impact many different fields of research. A line of research may be thought-provoking because it seems counterintuitive or illogical, and we want to know why a certain phenomenon exists. The theme that all of these points share is the drive to understand new things and put them in the context of everything else we know about how the world works. But if there is no clear relationship to human welfare, what makes all of these individual studies useful?

Many problems that arise in human health and welfare, from disease to climate change, cannot be solved without understanding the important context basic research provides. For example, the Zika virus has only been recognized as a human pathogen within the past few years, but decades of research elucidating how these kinds of viruses work and how human immune systems fight off pathogens have been crucial to the extremely rapid development of vaccines that have been successful in mice and monkeys. If basic research is underway, we can approach new problems with knowledge gained from work that has already been performed.

The need for context is especially relevant when trying to find treatments for diseases like autoimmune disorders and mental disorders, where we still do not understand what causes these diseases to manifest. To know which cellular processes we need to target to treat a disease, we must first have a working knowledge of how they work and all of the ways that they can go wrong. For example, the discovery of cisplatin as a compound to treat cancer came from observations that cisplatin stopped cell division from occurring. At the time, scientists knew quite a bit about how cells divide, and had learned that tumors grow rapidly because cancer cells divide very quickly. They realized that stopping cell division might stop the growth of a tumor, and proceeded to test cisplatin on tumors, which led to cisplatin becoming a top-selling cancer drug. Without understanding what a tumor is and what causes it to grow, we would not have realized the value of cisplatin as an anti-cancer compound.

One delightful aspect of scientific research is that many discoveries are serendipitous. The discovery of the polio vaccine, restriction enzymes, and even viruses occurred when observant scientists realized that something unexpected was happening in their experiments, and took the time to depart from their original research question to pursue the more interesting sidetrack. There are few indicators by which we can know whether scientific projects will lead to the most applicable conclusions, but the most useful tools gained from science have often arisen by chance.

Figure 2: A timeline of discoveries from basic biomedical research and their applications. The characterization of viruses in the 1890s and the knowledge used to purify antibodies for vaccines against measles in 1944 were critical to the quick development of the Zika vaccines currently being tested in animals. Similarily, the discovery of restriction enzymes in the 1960s made it possible to sequence the human genome in the early 2000s and to create the first synthetic cell in 2010. Cisplatin was discovered as a compound that could halt cell division in 1961, and adopted as a drug to prevent the division of cancer cells in tumors in 1979.
Figure 2: A timeline of discoveries from basic biomedical research and their applications. The characterization of viruses in the 1890s and the knowledge used to purify antibodies for vaccines against measles in 1944 were critical to the quick development of the Zika vaccines currently being tested in animals. Similarily, the discovery of restriction enzymes in the 1960s made it possible to sequence the human genome in the early 2000s and to create the first synthetic cell in 2010. Cisplatin was discovered as a compound that could halt cell division in 1961, and adopted as a drug to prevent the division of cancer cells in tumors in 1979.

Is there any guarantee that a scientific pursuit will benefit the public good?

This question lies at the heart of deciding what kinds of scientific research should be funded. If we define the public good as a cure for cancer, or a treatment for Alzheimer’s, or the solution to global warming, it is difficult to know which lines of research will be beneficial. However, if we define the public good as a wealth of knowledge that we can apply to solving the world’s issues, then scientific research, including basic research, is guaranteed to contribute.

Emily Low is a Ph.D. Candidate in the Biological and Biomedical Sciences Program at Harvard Medical School.

This article is part of our Special Edition: Dear Madam/Mister President.

For more information:

Restriction Enzymes.” Scitable, Nature Education.

What is Basic Research?” National Science Foundation, Third Annual Report.

The Myth of Basic Science.” Matt Ridley, The Wall Street Journal.

Basic Science Can’t Survive Without Government Funding.” Nathan Myhrvold, Scientific American.

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One thought on “Basic Research: Understanding The Way Things Work and Why It Matters

  1. It would be helpful to know how to donate to fund basic research. I would far rather do that than contribute to an organization that ostensibly funds research into a particular disease. Universities and federal agencies such as NIH and the VA do research, but how does one designate that the donated funds are to be used for basic research and not, for instance, for construction or other purpose?

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