Recently, a valued friend and scientific colleague of mine (Jonathan Yewdell of the NIAID in Bethesda) made me aware of a netcast (http://www.twiv.tv/) and associated blog (http://www.virology.ws/) relating to virology. The originator of both is Vincent Racaniello, a well-known and highly regarded virologist and professor of microbiology at Columbia University. Dr. Racaniello currently happens to be curating a survey (http://www.virology.ws/are-viruses-alive/) asking people to answer the question: “Are viruses living?”
Earlier this month, I participated in the online survey (just once). In laying out his own position, Racaniello states (http://www.virology.ws/2004/06/09/are-viruses-living/) that “Viruses are not living things.” He uses the following definition, from a standard dictionary (Merriam-Webster; http://www.merriam-webster.com/dictionary/life), as his basis for reaching this conclusion: “life is “an organismic state characterized by capacity for metabolism, growth, reaction to stimuli, and reproduction.”” Presumably Racaniello’s thinking is that since viruses, at least as free virions, do not (for example) exhibit metabolism or reactions to stimuli, they are not alive.
My view of the status of viruses is somewhat at odds with Racaniello’s, so I initiated a correspondence. My perspective on the matter is delineated below:
A dictionary, any dictionary, is not an acceptable basis for selecting a definition for “life” if you are interested in having a serious discussion. Biology is the study of life, and lexicographers may experience life, but having life experience does not qualify one as a biologist, or virologist. If you require life to be defined by simultaneous possession of all four attributes (metabolism, growth, reaction to stimuli, and reproduction) cited in the Merriam-Webster definition, you will encounter problems of classification with such entities as bacterial spores (no growth for extremely extended periods), comatose patients (minimal reactivity of certain types), and frozen cells (no reproduction).
The following quote from Daniel Koshland [Science 295(5563):2215-2216] supports the preceding:
“What is the definition of life? I remember a conference of the scientific elite that sought to answer that question. Is an enzyme alive? Is a virus alive? Is a cell alive? After many hours of launching promising balloons that defined life in a sentence, followed by equally conclusive punctures of these balloons, a solution seemed at hand: “The ability to reproduce–that is the essential characteristic of life,” said one statesman of science. Everyone nodded in agreement that the essential of a life was the ability to reproduce, until one small voice was heard. “Then one rabbit is dead. Two rabbits–a male and female–are alive but either one alone is dead.” At that point, we all became convinced that although everyone knows what life is there is no simple definition of life.”
However, unlike Koshland, I would not assert that everyone knows what life is. There are many easy cases that anyone could properly assess, but the point is to agree on the more challenging cases, such as precisely when human life ends, a continuing focus of controversy. I agree with Koshland that there is probably no simple definition of life that will work uniformly well for all applications.
It is a common but fundamental mistake to attempt to use rigid categories, with absolute membership criteria, as in the Merriam-Webster definition of life, to group entities that are subject to evolution, such as organisms and viruses. The implicit assumption underlying classification based on such categories is that use of a label for a grouping implies homogeneity among the entities within the group with respect to key attributes. In biology and virology, labels are used routinely to group entities (e.g., HIV-1, E. coli, human IgG1) for which homogeneity of properties, even what may initially be viewed as critical properties, cannot generally be expected for the indefinite future. One could even argue that such dynamic heterogeneity is the essence of evolving, i.e. living, entities. In a 2009 blog post (evmedreview.com/?p=135) I addressed this issue and discussed some types of categories with membership criteria that are more suited to biology.
Racaniello emphasizes that viruses are passive. For example, they cannot actively seek out host cells to infect. While this point is true, it understates the extent to which viruses can exert control, in some sense, once they arrive at, enter, and begin to influence a susceptible host cell, even if they cannot employ intentional locomotion to find such cells. Virus-encoded molecules clearly do mediate many actions, including creating progeny virus by co-opting the functions of some host cell molecules and subverting the functions of others.
Even if the virus as a whole is regarded as ‘passive’, it strikes me as beside the point. I doubt that anyone suffering from infection with ebola virus, or even a circulating strain of seasonal influenza A virus, would be inclined to emphasize that the virus is “at the mercy of [its] environment,” as opposed to feeling that he or she is at the mercy of the virus (or, if you prefer, at the mercy of the virus-encoded molecules). However passive, viruses are awfully good at getting replicated given the environments in which they tend to find themselves.
Racaniello also argues that while the cells infected by viruses are alive, the virions are not alive. This perspective commits him to a rather unsatisfying serial resurrection model of the virus ‘life’ cycle.
I am not certain what view of this issue predominates among virologists. One of the most eminent virologists, David Baltimore, makes the following statement in an online ibioseminar (http://www.youtube.com/watch?v=d6fRICXrves) on viruses: “Viruses represent a separate kingdom of the living world.”
Meanwhile, in a new and widely-adopted textbook on evolutionary biology (Zimmer and Emlen, 2013) viruses are regarded as part of the living world. For example, on page three, the authors write: “While blue whales are the largest animals on Earth, the smallest living things are viruses.” So, my view is that viruses are alive in some key respects, although not all, but are better classified as part of the living world than as part of the non-living world if one is compelled to use a dichotomy. What may be a preferable perspective is simply to note that viruses exhibit only some of the properties routinely associated with living entities, and leave the matter there.
Alternatively, some individuals might be tempted to suggest that we formulate a new and precise boundary between the living and non-living states. For example, it might seem reasonable to suggest that the ability to undergo Darwinian (or neo-Darwinian) evolution is sufficient and necessary for the living state, but a few moments reflection should convince you that new problems inevitably arise. For instance, entities that only live in computers, or on computer screens, can be said to evolve in a fashion that looks extraordinarily similar to the evolution of genomes and organisms. Are these virtual entities alive?
My response to this apparently endless categorical fuzziness and complexity is what I refer to as the Principle of Radical Evolutionary Indifference. It postulates that evolutionary changes occur without the slightest regard to the pre-conceived categories of biologists and biomedical scientists. Related principles are the Principle of Mindless (or less provocatively, Insufficiently Reflective) Semantic Agglomeration (Upon finding that attributes A, B, and C occur together, a new entity is defined predicated on the unreliable assumption that A, B, and C must always occur together) and the Principle of (Nearly) Inevitable Semantic Disaggregation [When it is discovered that A and B can occur without C (or: A and C without B, B and C without A), the definition of the original entity is either revised or rendered unsatisfactory]. Until the implications of these principles are fully absorbed and digested, the conceptual revolution wrought by Charles Darwin will remain incompletely fulfilled.
Koshland DE Jr. Special essay. The seven pillars of life. Science. 2002 Mar 22;295(5563):2215-6. PubMed PMID: 11910092.
Greenspan N. Boundaries of categories, categories of boundaries, and evolution. evmedreview.com/?p=135
Baltimore D, (Cal Tech). Part 1: Introduction to Viruses and HIV. http://www.youtube.com/watch?v=d6fRICXrves
Zimmer C and Emlen DJ. Evolution: Making Sense of Life. Roberts and Company Publishers, Inc., Greenwood Village, CO, 2013, p. 3.