Wednesday, February 23, 2011

Euphenics, Algeny, and Orthobiosis

Posted by Nathaniel Comfort on 02/23 at 04:52 PM

“Recent years have seen breath-taking advances in the molecular foundations of biology,” wrote the bacterial geneticist Joshua Lederberg in 1963.  Indeed, the secrets of heredity seemed to have at last been laid bare. In 1960, François Jacob and Jacques Monod had described the full machinery of a bacterial gene, a suite of components they named the “operon.” The next year, Marshall Nirenberg and Heinrich Matthaei at NIH had begun to crack the genetic code. The newspapers were full of the new genetics and the secret of life in 1961-62, and in October, 1962, Watson, Crick, and Wilkins won the Nobel Prize for the double helix. At a CIBA Symposium on “The future of man” the next month, Lederberg gave a lecture, which Nature published the following May.

With the genetic code and the machinery of protein synthesis, it seemed, all of biology was united by a single fundamental set of mechanisms. The old problems of physiology, development, and evolution were emerging as epiphenomena of genetics and biochemistry.

Such thoughts turned Lederberg’s mind to eugenics. “Like other noble aims,” he wrote, eugenics had been horribly abused, which unfortunately hindered the development of its more honorable and constructive applications. Like most biologists before or since, he thought that the use of genetic knowledge for human improvement was not only permissible but morally imperative. The hard part was knowing when, how, and how fast to proceed.

Lederberg speculated that researchers might some day “diagnose, then specify, the actual DNA composition of the ideal man.” He retained a troublingly naive but all too common Platonic view of human nature. Such rationalistic blindness to the challenges of consensus is what led to the genetic horrors of the Holocaust in the first place. In short, although Lederberg was circumspect about when to undertake eugenic efforts, he still believed there was a more or less indisputable “ideal man” to aim for.

Still, Lederberg’s point here was that eugenics remained too far-fetched, and that its pursuit distracted from more immediate and constructive applications of molecular biology to the human good. “To dramatize the antinomy,” he wrote, “I propose the term ‘euphenics’ as the counterpart of ‘eugenics,’ in the same sense that ‘phenotype’ is opposed to ‘genotype’.” Long before one could reliably control human evolution, it would be possible to control individual human development. Mankind was entering an era of “developmental engineering,” in which brain size, immune function, and physical characteristics of the body would all be controllable. Diseases would be preventable. Everyone would be above normal.

Three years later, he elaborated. Some biologists, he said, were getting carried away with fantasies of “chemical control of genotype.” He called this “genetic alchemy, or algeny.” Algeny was “diversionary,” he wrote, not because it wouldn’t one day come, but because it distracted us from more immediately available euphenic methods of genetic amelioration. In 1970, he offered a further refinement, introducing yet another neologism, “orthobiosis,” to denote the correction or perfection of life and of man, which may but need not be genetically based.

The brilliance of euphenics is that it permits eugenic progress—in the original sense of general genetic improvement—by focusing on individuals rather than populations. This then avoids many of the morally suspect requirements of an organized eugenic program, enabling medical practice to work toward eugenic ends. Not only is there no conflict between medicine and eugenics, as early eugenicists often feared, but pursuit of the one leads to the other.

Much of what Lederberg placed under euphenics we would call genetic medicine. Since before 1950, medical genetics had been moving toward a more individualized approach to genetic disease. Medical geneticists—many of whom proudly considered themselves eugenicists—understood that the way to treat the population was one individual at a time. Often, that had meant reducing the odds of disease or defect by preventing marriage or birth—both methods that often required persuasion if not coercion. But by the sixties that was beginning to change.

Molecular studies of development and especially metabolism, broadly construed, were shifting attention from “genetic diseases”, which followed a simple pattern on a pedigree, to studies of constitution. Biochemical genetics was blurring the difference between the normal and the pathological. Increasingly, the molecular approach to disease meant looking not for diseases that were genetic, but for the genetic component of any disease. Susan Lindee has noted the rise of the notion that all disease is genetic, although I have encountered it as early as 1951, well before what she has called the structural revolution of the 1960s.  At any rate, it has been a long, gradual process and almost all twentieth-century biology is really pre-history to the richly developed constitutional medicine of the genome age.

The legacy of Lederberg’s euphenics can be found in contemporary biomedical themes such as pharmacogenomics and personalized medicine, branches of research and treatment that claim to treat the individual—and to seek out the molecular and therefore hereditary basis of all health and illness.

In contrast, “algeny” has continued under the banner of genetic engineering and gene therapy. In 1997, French Anderson, the fallen hero of gene therapy, explicitly linked them historically—an act of refreshing candor.  For Anderson, as for Lederberg, eugenics was a good idea with a dirty history. But the gene therapists ignored Lederberg’s word of caution.

Twenty years of gene therapy trials have proven Lederberg right about algeny. After numerous, tragic failures and scant, modest successes, the gene cowboys are humbler now. Review articles no longer trumpet the end of all disease at the hands of genetic surgeons; instead, they assert earnestly that there really is a role for gene therapy in certain cases, provided we push forward cautiously.

Ironically, the term “algeny” itself was turned against the biomedical researchers. In 1989, the professional activist Jeremy Rifkin borrowed it for the title of a book critical of the new biotechnological medicine. Lederberg intended no derogatory connotations for algeny. Indeed, already by 1967, he was happily back-pedaling, claiming that algeny was coming faster than even he had thought.  Rifkin’s verbal piracy must have stung.

In retrospect, he left himself open. It is hard to imagine how his ultra-rational mind neglected the pitfalls of linking an unproven field of medicine to a branch of science whose standing depended on hype.

Tags: algeny, euphenics, gene therapy, genetic medicine, joshua lederberg, personalized medicine