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| Volume 49, Number 2, Summer 2000 |
by Ricki Lewis
I knew, back in March, that I was taking a gamble. The fourth edition of my human genetics textbook would be published in July, and judging from the rate of genomes being sequenced, it looked like Homo sapiens might join the list come summer. Unless the new edition assumed that the project was completed, my book would be obsolete before it was printed. So, I e-mailed the great and powerful J. Craig Venter, president of Celera Genomics Corp. in Rockville, MD, to ask about the timetable.
Despite his image as Darth Vader-softened perhaps since the joint announcement of June 26-Venter has always been exceptionally courteous to reporters. In my case, I had to do some rephrasing reminiscent of Woodward and Bernstein in All the President's Men to get him to admit that if a student were to read in late July that the human genome project was a fait accompli, it wouldn't be science fiction. That was good enough for me, and I managed to keep from blabbing this news and investing immediately in Celera.
As I began rewriting, I quickly realized that "genomics" is not just a new buzzword, but an entirely different way of thinking about biology. Genetics is no longer based on a one gene-one enzyme, or even a this-mutation-causes-that-disease paradigm. Instead, we now view a genome as a dynamic entity, a vast storehouse whose information is accessed in a staggeringly complex panoply of expression exquisitely controlled in time and place throughout a life.
I also realized that the four editions of my textbook, targeted to nonscience majors, chronicle the evolution of genetics to genomics.
I first suggested writing a human genetics textbook in 1980, while at my first faculty appointment and vulnerable to the seasonal influx of acquisitions editors. No, said they, the market was saturated and there wasn't much interest in genetics. With visions of Genentech dancing in my head, I disagreed, but was sidetracked into other projects.
Then circa 1992, I convinced a well-placed editor to let me write the book, composing the table of contents on a dinner napkin. That napkin became a makeshift contract, and the first edition of Human Genetics: Concepts and Applications was published in 1994 (translation: August 1993). Because the publishing powers-that-be still thought that human genetics was not of much interest to non-science majors, they let me write what and how I wanted to. Example: in contrast to the boxed readings in other books that highlighted the researchers, I instead found real people, such as a teen with spina bifida, to share their stories. Not everyone liked this approach. One critic accused me of "writing like a woman," an odd comment since I am of the XX persuasion. Like others, he was confused by my name.
When I align all four editions of my text, the changes are most striking in the first and last chapters, and these are the changes that mirror the field most closely. Much of the interior hasn't changed, such as Mendel's laws, Hardy-Weinberg equilibrium, and how the genetic code oversees protein synthesis-current headlines about "cracking the human genetic code" to the contrary. The genetic code-the correspondence between nucleic acid and protein sequence-was of course "cracked" in the 1960s, and were it not universal, biotechnology as we know it would not exist.
The first edition opened with the story of phenylketonuria (PKU), chosen because it is a curable single-gene disease-in contrast to the tales of doom that opened other texts. Still, the chapter presented the dark side of genetics, entitled "Portrait of an Inborn Error of Metabolism."
Mention of the human genome project in the opening chapter was fleeting and vague, but I brought it up again in the final chapter, "Maps, Markers, and the Human Genome Project." That chapter addressed the goals and priorities of genome sequencing, but was festooned with the technotalk of the time: chromosome walking and jumping, contigs, and RFLPs, YACs, and cDNAs. The focus was on positional cloning, using conventional gene and chromosome maps to identify candidate genes. I used the search for the Huntington disease (HD) gene to describe these approaches, a backdrop chosen for its long time frame and, more practically speaking, the fact that a student of mine was the very first person to realize that a marker had been identified. She'd kept me posted.
The first chapter of the second edition, published in 1997, instead took a newsy approach, thanks largely to O.J. Simpson's role in publicizing DNA fingerprinting. Other topics included BRCA1 testing; agbiotech, along with a cartoon of a Frankensteinesque tomato, and nine-color photos showing skin colors. Less obvious was a shift in focus from abnormal to normal variation, and from single genes to multifactorial traits. The opening disease scenario was jettisoned, replaced by the more lasting "A Look Ahead." Circa 1997, that meant considering a pregnant woman in 2001 undergoing embryo biopsy for preimplantation genetic diagnosis; testing for various single gene disorders and colon cancer susceptibility; and cord blood set aside at birth. A bit optimistic.
Human genome project coverage in the 1997 edition was more in-depth, including a section on "interim information" as the maps were being assembled. But already researchers were realizing that gene density is uneven and unpredictable, the chapter pointed out. The HD story and positional cloning remained.
The third edition arose for marketing reasons. Not a whole lot happened in human genomics between 1997 and 1999, but a competing book appeared in a new edition. And so it was deemed time for me to change only a few chapters to one-up the competition in the newest edition stakes. Ever the perfectionist, I changed nearly every chapter, much to the frustration of my editors.
The opening chapter for the edition pushed the date of "A Look Ahead" to 2003, but kept the tests the same. New forensic examples replaced the stale O.J., a shot of Tiger Woods stood in for the nine human hues, but the killer tomato stayed. Emphasis continued to swing to the multifactorial. Human genome project coverage remained the same from the last edition.
If not much happened between 1997
and 1999, perhaps it was just the calm before the storm of what
would transpire as genetics became genomics from 1999 to 2001.
As the field changed drastically, so did my book.
Gone from chapter one were PKU and even O.J., replaced by two college students undergoing DNA microarray tests to predict future health problems and addictive tendencies. Emphasis is clearly on multifactorial traits and a genome-view of the organism. For the applications section of the introductory chapter, I just couldn't choose among the many new examples. The DNA fingerprinting discussion considers reversing criminal convictions, Thomas Jefferson and Sally Hemings, Jewish priests, and wine ancestry. The first recipient of gene therapy for hemophilia tells his story in one boxed reading, and another box addresses the Icelandic database. I retained the scary tomato, now accompanied by a photo of transgenic rice gloriously yellowed with beta-carotene.
Although the GM tomato remained a fixture, the field of ag biotech itself has resonated with a resounding sense of deja vu. So too my coverage. After the first edition, several instructors asked that I drop the agricultural and environmental biotechnology chapter, because it wasn't human. I stubbornly refused. Interestingly, the chapter in the fourth edition isn't changed much in content, but it is in trappings, the more specific and accurate term "transgenic" sometimes accompanied by "GM" just because it is more familiar. But new examples abound-rhizosecretion, low lignin wood, mercury bioremediation, and plants and bacteria that detect buried munitions.
The saddest change over the four editions concerns gene therapy, whose chapter until now began with a section called "The Evolution of a Cure," which happily chronicled the children who pioneered successful gene therapy for ADA deficiency. Although I've tried to preserve that optimism, the fourth edition rendition opens with "Gene Therapy Successes and Setbacks," beginning with the story of Jesse Gelsinger, to whom the book is dedicated.
The final chapter is now called simply "Genomics." Much of the earlier versions are condensed into a short introductory section, and positional cloning placed in a box so that instructors can delete it if it becomes not much more than a historical footnote, an irony considering how difficult it is to do and how brilliant it is in conception. After detailing the history of the genome project, the chapter gets into the nitty-gritty of DNA microarrays, including applications such as functional genomics, pharmacogenomics, and toxicogenomics.
The final section of the final chapter of this book that I first conceived two decades ago ends with the section "Genome Information Answers and Raises Questions." But this isn't a new idea. In thumbing through my old editions, I found that the end of the first chapter of the first edition states: "It seems that the more we learn about the genetic material, the more we realize there is to know."
So we're still learning. And I can hardly imagine what future editions will bring!
Keeping Up: Genetics to Genomics in Four Editions by Ricki Lewis, The Scientist, July 22, 2000. Reprinted with permission.
(Ricki Lewis is a freelance based in Scotia, NY. She is a contributing editor of The Scientist and a medical/biotech editor of Biophotonics International.)