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Evolutionary Biology: Technology for the 21st Century

Jim J. Bull

articlehighlights

Evolutionary biology is central to the development of:

  • drug/chemical compounds for medical use
  • methods for tracking pathogens, i.e., infectious diseases
  • biochemicals for medicine and other industrial use
  • data that reveals relationships among organisms

August 2000

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A child being immunized against polio. Photo: USAID Bangladesh

Evolutionary biology is misunderstood by some people.

Evolutionary biology has an image problem. Some people are threatened by it and thus oppose it. Many people — even many of its defenders — view evolutionary biology as irrelevant outside of academia. And in a few cases, even though evolution is perceived as relevant, some see it as responsible for death and misfortune, e.g., drug-resistance in medicine and pesticide-resistance in agriculture.

Examples of evolutionary biology

Its study is important to new medical technologies.

Most people are unaware of uses of evolutionary biology. Public non-appreciation of evolutionary biology may depend as much on its perceived irrelevance as anything else. Yet, evolution, especially microevolution, has been fundamental to some social improvements this century, and it promises to be profoundly important to biomedical technology in the next generation. For example:

Some agricultural methods depend on evolution.
  • Evolution underlies many improvements in agriculture (e.g., the artificial selection of crop strains and livestock breeds).
  • A less well-known fact is that evolutionary principles were used to produce many of our best vaccines and that evolution also causes problems with the use of some of those vaccines.
  • Some of the most promising areas for the future use of evolutionary biology lie in drug development and the biotechnology industry; patents worth vast amounts of money are based on ways of creating evolution (or avoiding evolution) in test tubes.
Evolution mechanisms made possible the polio vaccine.

Polio vaccine is an old example but it is a good one.

  • The vaccine now used to immunize against the disease poliomyelitis is a live poliovirus that we eat.
  • This live virus does not give us the disease (except to about 1-2 in a million people vaccinated) because it is genetically weakened so that our body can defeat it.
  • This process of weakening is called attenuation, and it is an evolutionary process. The attenuated vaccine strains came from wild, virulent strains of poliovirus, but they were evolved by Albert Sabin to become attenuated. Essentially, he grew the viruses outside of humans, and as the viruses became adapted to those non-human conditions, they lost their ability to cause disease in people.

This method of attenuation has been used to create many live vaccines. Evolution was the good guy here because it helped us make the vaccine. But the role of evolution and evolutionary biology does not end here — evolution becomes the bad guy too.

Evolution can also destroy the effects of vaccine.
  • When a person eats the attenuated virus, it infects his/her gut cells and starts doing what viruses do — making copies of itself.
  • These viral progeny infect other cells in your gut, those in turn make other viral progeny, and so on, until you have a population of poliovirus growing inside your gut.
  • Some of these viruses carry mutations, and some of those mutations (one or two in particular) restore most of the virulence to the virus.
  • In your gut, these restored viruses may have a selective advantage over the weakened viruses, and in the course of a week or so after eating the vaccine, you begin shedding virus with restored virulence. In short, an evolutionary process inside your gut undoes Albert Sabin’s attenuation of the virus.

These restored viruses do not hurt the person taking the vaccine because by the time restored viruses get to be abundant in the gut, the immune system has enough of a head start to keep the virus from getting into the central nervous system. Disease is caused only if the virus gets into the central nervous system.

Understanding evolution gives us clues on how to vaccinate effectively.
  • However, if we were to vaccinate just one person in a population of non-immunized people the restored viruses shed from this one person would infect other people and could start an epidemic of nasty poliovirus.

  • In fact, people have gotten the disease from people who were recently vaccinated.

  • Fortunately, this problem caused by evolution has an easy solution — when polio vaccine is first introduced to a community, we try to vaccinate everyone in the community at once.

  • This is what happened in the U.S. when the Sabin vaccine was first introduced in the U.S. in the 1950’s (vaccine “Sundays”), and it was done in other countries as well.

  • The WHO did all of China in 3 days, and vaccinated 90,000,000 people in India in one day.

  • Thus, understanding the evolution of poliovirus virulence allows us to use the vaccine without causing unnecessary disease.

The harm in misunderstanding evolution

The evolution of drug resistance in bacteria is one of the simplest examples of evolution that we have. It is extremely relevant to medicine. And since it is a case of microevolution, it is an example that should be widely embraced. Yet many people profoundly misunderstand drug resistance. Even news reports from the BBC have gotten it wrong.

Bacteria evolve quickly to resist antibiotics.

Bacterial resistance to antibiotics is an evolutionary phenomenon:

  • heavy use of antibiotics selects bacteria that are genetically resistant to the drug
  • with continued use of antibiotics, those resistant forms of the bacteria multiply and spread to other hosts
  • eventually, resistant bacteria replace the population of once-sensitive bacteria.

In the minds of some people, however, the problem with misuse of antibiotics is that it can lead to a physiological tolerance in the person taking the drugs, so that antibiotics are no longer effective in that person. That is, they think that drugs become ineffective because of the person, not the bacterium. This erroneous, non-evolutionary view has serious ramifications, because it can lead to an unwarranted complacency about antibiotic misuse. Because drug resistance is evolutionary, your neighbor’s misuse of antibiotics can injure or kill you. The unregulated use of antibiotics in, say, Europe can bring strains for which we have no defense to the U.S. and our hospitals. It is not simply a matter of the proper use of antibiotics in each of us individually; it is a matter of everyone’s proper use of antibiotics.

It is tempting to speculate that the common, though not universal, public failure to understand the evolutionary basis of drug resistance reflects a widespread ignorance of evolutionary principles, even principles professed to be uncontroversial. The fact that this misunderstanding is not confined to the western side of the Atlantic suggests that political opposition to the teaching of evolution is not the only cause.

Evolution helps us track pathogens and improve medications.

Modern applications of evolutionary biology

There are numerous ways to apply evolutionary biology to our needs today, among them:

  1. prolonging the life of drug/chemical resistant compounds
  2. constructing evolutionary trees
  3. pathogen tracking
  4. industrial production of biochemicals and other agents

1. Drug resistance and chemical resistance in microbes, plants, and animals. In the latter half of this century, industry has been exceptionally good at providing compounds to kill viruses, bacteria, insects that eat crops and weeds that grow in crop fields. We even have an abundance of chemotherapy drugs to kill rogue cancer cells. Yet virtually without exception, our attempts to kill these organisms cause them to evolve resistance against the chemicals used to kill them. For example:

AIDS is an example of a virus that evolves to thwart its destruction.
  • Isolates of the AIDS virus with up to 15 different drug-resistance mutations are known, and the latest drugs are becoming ineffective.

  • Some strains of bacteria are resistant to all available antibiotics.

  • For multi-drug resistant tuberculosis, surgery is the only cure because antibiotics don’t work and only 50% of those infected survive.

  • Chemotherapy for cancer often fails because drug-resistant cells evolve during treatment.

  • Pesticide resistance and herbicide resistance is so common now that the financial incentive to make new pesticides and herbicides is break-even or worse.

Evolutionary biology suggests how best to prolong the useful life of drugs/chemicals. The amounts of chemicals used, what combinations of chemicals to use, and when to apply them are all questions that can be assessed from the perspective of preventing or slowing the evolution of resistance. In some cases now, the companies marketing the compounds have a financial interest in maintaining the longevity of their product, and they are funding studies by evolutionary biologists to develop wise use protocols. In other cases, however, economic and emotional forces dictate policies that speed up the evolution of resistance (e.g., patients demand and physicians write prescriptions for antibiotics for viral infections; antibiotics are used in animal feed).

Evolutionary trees help scientists track pathogens that cause disease.

2. Evolutionary trees Perhaps the core of evolutionary theory is that all life forms are connected to each other through common ancestry. Molecular biology has reinforced this view to a far greater level than was deemed possible even 50 years ago. On a short time scale, of course, we observe that this is true — everything alive comes from something else that is both alive and similar. One of the big developments in evolutionary biology over the last 2 decades is a methodology to estimate the underlying patterns of ancestry among living things. These reconstructions of evolutionary history are known as phylogenies, or phylogenetic trees, because they are branched somewhat like trees when drawn from bottom to top. We can use molecular data to estimate the common ancestries of life as far back as we like — for example, between bacteria and our mitochondria (the energy-producing organelles in our cells). But we can also use these methods to estimate much more recent ancestries. And these methods have found many worthy uses in tracking infectious diseases.

3. Molecular epidemiology — pathogen tracking To an epidemiologist studying infectious diseases, it is very useful to know how or where a person became infected with the disease. This information is perhaps the most basic fact we can use in preventing the further spread of a disease. For over a decade now, epidemiologists have been using DNA sequences of viruses to make phylogenetic trees and thereby track the sources of infections. Some of these examples are spectacular.

Law: A case of intentional HIV injection?
In a highly publicized case in Lafayette, Louisiana in 1998, a woman claimed that her ex-lover (a physician) deliberately injected her with HIV-tainted blood (HIV is the virus that causes AIDS). There were no records of her injection and no witnesses. So how could her story be tested? Evolutionary trees provide the best scientific evidence in a case like this.

A woman’s claim to how she was infected with AIDS was supported by evolution.
  • HIV picks up mutations very fast — even within a single individual.

  • If one person gives the virus to another, there are few differences between the virus in the donor and the virus in the recipient.

  • As the virus goes from person to person, it keeps changing and gets more and more different over time.

  • Thus, the HIV sequences in two individuals who got the virus from two different people will be very different.

  • Thus, if the woman’s story were true, her virus should be very similar to the virus in the person whose blood was drawn but should be very different from viruses taken from other people in Lafayette.

  • That was exactly what the evolutionary trees showed; her virus appeared to have come from the patient’s virus but was unlike the virus taken from other people in town.

  • Since there was no way to explain how she would have gotten that patient’s virus on her own, the evolutionary analysis supported her story. (Incidentally, this case was the first use of phylogenetics in U.S. criminal court.)

Other cases Evolutionary trees have been used in many other cases of infectious disease transmission:

  • the transmission of the AIDS virus by a dentist to his patients
  • deer mice as the source of hantavirus infections in the Four-Corners area
  • the source of rabies viruses in human cases, leading to the discovery of a case in which rabies virus took at least 7 years to kill a person
  • whether recent cases of polio in North America were relict strains from the New World, were vaccine strains, or were introduced from Asia

4. Industrial production of biochemicals and other agents “Directed evolution”, i.e. artificially-induced evolution, has become part of the jargon in biotechnology:

Biotechnology allows us to give direction to evolution.
  • Artificially evolved enzymes and other proteins are soon to become part of household and medical technologies.
  • We will have protein-based drugs that, unlike the proteins inside our bodies, degrade slowly so that we don’t need to take so much of them.
  • Enzymes are being evolved to work in detergents (which they don’t normally do).
  • And as the stuff of futuristic novels, molecules are being developed to bind anthrax spores, ricin molecules, and other potential bioterrorism agents.

All of these developments take advantage of one or more forms of test-tube evolution. Armed with a knowledge of how natural selection works and combined with the right kinds of laboratory technology, people can create molecules to perform seemingly any kind of function. In some of the more spectacular cases, these test tube evolution methods have created enzymes from purely random pools of DNA (or RNA) sequences. Even 10 years ago, it was thought that a DNA enzyme was impossible, yet armed with only an understanding of how to apply test tube evolution, a DNA enzyme can now be created in days.

Conclusion: The public needs education about evolution to understand what is going on in biotechnology.

In conclusion

The pace of evolutionary biology and its ramifications has outstripped public awareness as well as expanded beyond the knowledge base of most classical evolutionary biologists. Even the textbooks have not kept up. It is thus difficult but important to recognize that evolutionary biology has implications to a new century of medicine, agriculture, biotechnology, and even law. Students educated with this knowledge will have an edge in the competitive job markets of the future, but at least in some areas of medicine, a basic public understanding of evolutionary principles may be essential in successfully waging the ongoing war with infectious diseases.

Editor’s Note: The paper “Applied evolution” by J.J. Bull and H.A. Wichman in Annu. Rev. Evol. Syst. 2001, 32:183-217, provides a recent examination of this topic.

Jim J. Bull, Ph.D., is the J. F. Miescher Regents Professor of Molecular Biology at the University of Texas in Austin. He works on problems of genetics and evolution, especially as they pertain to disease. He uses experiments to understand how viruses evolve in the presence of inhibitors, how they might be engineered to make safe vaccines, and whether bacterial viruses (phages) can be used to treat bacterial infections.
http://www.icmb.utexas.edu/directory/details.asp?id=18

Evolutionary Biology: Technology for the 21st Century

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Understanding Evolution

Your one-stop source for information on evolution. Learn the facts in Evolution 101, browse the resource library, read about evolution in the news, or discover a wealth of materials to help educate others about evolution and related concepts—it’s all right here! http://evolution.berkeley.edu

“Microbes: What They Do & How Antibiotics Change Them”

On our site, Maura Meade-Callahan explains the evolutionary process of antibiotic resistance.
http://www.actionbioscience.org/evolution/meade_callahan.html

“Evolution: Fact and Theory”

Richard Lenski provides an excellent summary of evolution.
http://www.actionbioscience.org/evolution/lenski.html

Science in the 21st century

Hear the interview “A Brave New World” conducted on 12/11/98 by Lateline (Australian Broadcasting Corp.) with three great scientific minds about what we can expect from science in the 21st century: Sir John Maddox, author, “What Remains to be Discovered”; Professor Paul Davies, author, “The Fifth Miracle” and Professor Michio Kaku, author, “Visions”.
http://www.abc.net.au/lateline/stories/s17000.htm

Evolutionary biology

This extensive document, prepared by delegates of several professional scientific societies, describes the current and potential accomplishments of evolutionary biology and its importance in educational curricula.
http://www.rci.rutgers.edu/~ecolevol/evolution.html

The future of biology

Read chapter 4 of “The Third Culture: Beyond the Scientific Revolution” by Brian Goodwin, biology professor, reprinted online to consider the author’s view on the future of biology.
http://www.edge.org/documents/ThirdCulture/k-Ch.4.html

Learn about biotechnology online

“Guide to Biotechnology” from the Biotechnology Industry Organization provides an overview about biotechnology. No science background is required. Chapters cover history, technologies and their applications, and ethics.
http://www.bio.org/speeches/pubs/er/

AIBS Online Presentation

View the PowerPoint presentation “When Humans Create Rapid Evolution by Changing the Environment by Stephen Palumbi, presented at the 2005 evolution symposium “Evolution and the Environment.”
http://www.aibs.org/events/special-symposia/resources/NABT_Palumbi_2005.pdf

Read a book

  • »Gene Future: The Promise and Perils of the New Biology by Thomas F. Lee is an examination of where we are going, where we should go, and where we dare not to go with the knowledge revealed by the “New Biology” (Perseus Press, 1993).
  • »Scanning the Future by Yorick Blumenfeld (Editor). Twenty articles by distinguished writers and thinkers, including physicists Murray Gell-Mann and Steven Weinberg, biologist Edward Wilson, and statesman Nelson Mandela have been selected to show what can be done to build a better future. The anthology presents challenging perspectives and stirs the imagination with ideas on the good society, technology and progress, genetics and evolution, and the environment. It shows that we can improve the world through an inventive use of knowledge and that the individual can make a difference (Thames and Hudson, 1999).

Campus Freethought Alliance (CFA)

CFA is an organization dedicated to the advancement of “reason, science, and freedom of inquiry.” Resources include teaching guides for educators and a list of speakers that can be invited to address students.
http://www.campusfreethought.org/

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Teaching Resources from the Northwest Association for Biomedical Research (NWABR)

The Northwest Association for Biomedical Research (NWABR) strengthens public trust in research through education and dialogue. Its diverse membership spans academic, industry, non-profit research institutes, health care, and voluntary health organizations. Through membership and extensive education programs, it fosters a shared commitment to the ethical conduct of research and ensures the vitality of the life sciences community.

HIV Vaccines
Our HIV Vaccine Curriculum Unit focuses on engaging students in considering the elements of a vaccine trial. Students explore the life cycle and structure of HIV, different vaccine types, ethical issues related to research studies with human participants, and global contexts of vaccine trials.
http://www.nwabr.org/curriculum/hiv-vaccines

ActionBioscience.org original lesson

This lesson has been written by a science educator to specifically accompany the above article. It includes article content and extension questions, as well as activity handouts for different grade levels.

Lesson Title: Applied Evolution: How Will We Get There from Here?
Levels: high school - undergraduate
Summary: This lesson examines evolution in light of recent biology breakthroughs and future possibilities. Students can perform a simulated natural selection activity with candy, prepare a mock HIV court case, imagine Earth in the future, track a Hantavirus outbreak, conduct “Marty the Mutating Marcescens” experiment, brainstorm a potential detergent enzyme… and more!

Download/view lesson.
(To open the lesson’s PDF file, you need Adobe Acrobat Reader free software.)

Useful links for educators

Useful links for student research

In addition to the links in the “learn more” section above:

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