Yogi Berra was right when he said, “Prediction is very hard, especially when it's about the future." Difficult or not, that hasn't stopped a flood of predictions about how the knowledge gained from the first survey of the entire human genome will affect life in the 21st century and beyond. Ranging from dire to downright delightful, these predictions are nothing if not sci-fi fantastic — and for the first time ever, quite realistic.
Tony J. Beugelsdijk '71 was already imagining the enthralling possibilities lying coiled in the landmark achievement more than a decade before the historic June 26 announcement from British Prime Minister Tony Blair and President Bill Clinton: that the international Human Genome Project and Celera Genomics Corp. had both completed an initial sequencing of the genetic blueprint for human beings.
As the leader of a team of scientists and engineers who built the U.S. Department of Energy's Los Alamos National Laboratory's cutting-edge robotics and automation program, Beugelsdijk was approached in the mid-1980s to develop robotic systems to support the Human Genome Project. It is his team's laboratory robotics that were, and are, used extensively in the mapping of human chromosomes.
"Basically, I've always been interested in building tools that can unlock the potential of science — to build tools that can help us generate vast amounts of data that are fundamentally important to humankind," Beugelsdijk says.
And what could be more fundamental to human beings than deciphering the human genetic code? But the undertaking was almost inconceivable. Think for a minute — or at least until your brain cells start squirming — about the complexities and the astronomically large number of infinitesimally small bits of information genetic decoders must deal with. Recall from Biology 101 that most of the body's 37 or so trillion cells contain a nucleus with 46 chromosomes, each one made up of a long, coiled-up strand of DNA (deoxyribonucleic acid). Thousands of sections along every strand represent genes, which are coded instructions for making the proteins needed to construct a complete human organism. The human genome boasts 100,000 genes — and there are billions of DNA letters, or base pairs, in the human genetic code. [Editor's 2019 note: The estimate of the number of human genes has been repeatedly revised down from initial predictions of 100,000 or more as genome-sequence quality and gene finding methods have improved. In 2019, the estimate is 20,000-25,000 human protein-coding genes.] How would you go about deciphering that?
“Mapping the human genome was considered a 'holy grail' in biology," says Beugelsdijk, who graduated summa cum laude from WSU with a bachelor's degree in chemistry. He went on to earn a master's degree in analytical chemistry and a doctorate in inorganic chemistry from the University of Illinois, as well as a master's degree in business administration from the University of New Mexico. Then, he continues, “about 15 years ago the DOE realized that much of the instrumentation and technology was available to begin mapping the human genome."
After exciting discussions in Santa Fe, N.M., Washington, D.C., and other locales about the looming possibilities, the international Human Genome Project was born. Beugelsdijk and his team at the Los Alamos lab were charged with building tools not then in existence to complement existing technologies that could be used together to chart the human genome and characterize its biochemical nature — in other words, to crack the code.
The scale of the enterprise was huge. More than 1,000 individual scientists at more than a dozen research institutions in the United States, Great Britain, Germany, France, Japan and China turned their combined energies to the landmark project. Funding came from grants from government agencies and public charities in the various countries. Agencies funding the HGP in the U.S. are the DOE and the National Institutes of Health, which anted up roughly half of the approximate $300 million world-wide cost.
Impressively, all HGP participants agreed to quality standards and to a daily data release policy, ensuring that information from the public project would be continuously, immediately and freely released to the world.
“Initial meetings,” Beugelsdijk recalls, "dealt primarily with what it would take to handle the job, which was divided into two phases: mapping, for which there was very little equipment ready for use, and sequencing, for which technology was available that could be developed further, relatively easily.” Beginning hands-on work in 1988 and taking about two years, Beugelsdijk's team created a number of the necessary tools and procedures to map the cods, thus laying the foundation for the completion of phase one. This mapping phase entailed placing large fragments of DNA in the proper order to cover all of the human chromosomes. "The process is like putting toether a jigsaw puzzle," Beugelsdijk explains. "But you can't see any of the pieces, and when you put them together, you still can't see any of them."
At this point, since the technologies for the second phase in the project — the DNA sequencer — had already been developed, the HGP work of the team at the Los Alamos was complete. But the overall project was not yet realized. So, while Beugelsdijk began to focus on new frontiers, HGP scientists entered phase two: sequencing. Sequencing means determining the exact order of DNA's base pairs. Human chromosomes, which range in size from about 30 million to 300 million base pairs, are comprised of four different chemical bases: adenine, thymine, guanine and cytosine, or, for brevity's sake, A, T, G, and C. Essentially, two strings of these bases compose the double helix structure of DNA.
This June, after more than 22.1 billion bases of raw sequence data had been accumulated, the first working draft of the human genome was complete. And, it seems, nearly that number of predictions about what this major milestone will mean for the future were unleashed.
Beugelsdijk, for one, is excited. "The ramifications for health care alone are profound," he says. Since alterations in genes are responsible for an estimated 5,000 clearly hereditary diseases and influence the development of thousands of other health problems, decoding the human genome is sure to lead to myriad new ways of preventing, diagnosing, treating and curing disease.
Already here is the limited ability to alert certain patients who carry particular genetic markers that they are at risk for certain diseases. On the near horizon is the development of gene therapies for hemophilia, heart disease and some cancers. Further away, but some experts say as early as 2010, are DNA chips that analyze your personal genetic makeup. By 2015 medicine may be tailored to an individual's genetic makeup, allowing for more effective treatment of many diseases, including cancer. In 2025, doctors may be correcting defective genes, thereby curing illnesses such as sickle-cell anemia.
So far, so good. But looking a little further down the road of henomics progress, things get morally murky, fast. Spiraling into view are such science fiction visions as human beings using test tubes to reproduce "designer babies" or to clone themselves and tinker with their genes, not to mention the genes of every other DNA-based life form on earth, present and past. And so sci fi — think Blade Runner, Jurassic Park, Mary Shelley's Franenstein and, for good measure, the myth of Pandora's box — takes shape as reality.
A little knowledge is indeed a dangerous thing. And, as Elvera Skokan, WSU's biology lab coordinator and assistant chair, biological sciences, somewhat more gently puts it: "As with all research, more questions than answers result. In this case, the most difficult questions, involving ethical and social impacts, will need to be dealt with by the disciplines of humanities and social sciences, rather than the natural sciences."
On the legislative front, answers to at least one genetics-driven question is being pounded out in Washington: Will genetic information be allowed to be used to discriminate against those with "defective" genes? Last winter, President Clinton signed an executive order that prohibits medical information gleaned from genetic tests from being used against Federal employees in hiring or promotion actions. The Genetic Nondiscrimination in Health Insurance and Employment Act of 1999, if passed into law, will extend those protections to the private sector and help guarantee that individuals purchasing health insurance will not lose or be denied coverage because of their genetic makeup.
Aware of the darker implications of genetic research, Beugelsdijk is nevertheless optimistic that there's time for the right paths to be pondered out and taken. After all, designer babies and armies of genetically manipulated mutant warriors are not yet imminent. Mapping and sequencing the human genome are only the first steps toward understanding it; most of the genes and their specific functions are yet to be deciphered. But, he says, "science doesn't slow down because of our fears. However, my confidence is that as a society we will adapt to the challenges and come up with the right answers."
Like Beugelsdijk, David McDonald, WSU chair of biological sciences, looks forward to the unfolding possibilities, yet sees the potential for misadventure. "The progress of characterizing the human genome is exciting and not just for scientific reasons," he notes. "It is also exciting because it will ultimately impact all human beings. It will be our challenge to use what we find to serve as a positive force rather than a negative one. There is much good work that can be done based upon what we can learn about a person from their genome. Hoever, this same information could be misused. The choice will be ours as a whole to make."
As DNA deciphering continues, Beugelsdijk, who in 1996 was awarded the Los Alamos Distinguished Performance Award for his contributions to HGP at Los Alamos and who in 1997 edited the book Automation Technologies for Genome Characterization, certainly keeps up with decoding progress, but other work has become center stage for him.
This past March, he was appointed project leader for the Los Alamos Research Park project, a joint effort by Los Alamos County, the private sector, nonprofit economic development organizations and LANL. When completed, the park is expected to house 1,500 researchers in a laboratory and office complex, adjacent to LANL's administrative area. "The first of five building is being built now," Beugelsdijk relates. "Companies will be able to come and experiment with high speed computers, for instance, and work on research and development challenges unique to each company. It's like a mall, in a way, with Motorola as an anchor. The park will be of use to companies from start-up outfits to Fortune 500 corporations."
Beugelsdijk's fascination with science and research began early. After immigrating with his parents, younger sister and twin brother, Henry '71, to the United States from Holland in 1954 and enrolling at WSU in the late 1960s, his intention was to study physics, but he learned he preferred the discipline of chemistry. "I fell in love with chemistry," he says, "especially the experimental side of it. In not too many areas of study can you learn something in the classroom, then go to the lab to test the validity of it in such an immediate way. I enjoyed that."
He sees his experiences at Wichita State as solid preparation for his later studies and work. "As an undergrad," he notes, "I really benefited from the small classes and the personal attention of the faculty." Together, he adds, those faculty members helped "take the mystery out of difficult concepts."
Yet Beugelsdijk — showing that all-too-human trait of curiosity — remains attracted to the mystery of the unknown and the attempt to unravel it. Today, he's excited about a new venture: creating tools and materials by manipulating matter on the nanometer length scale. "Nanoscience is the next big thing," he explains. "Basically, that means controlling individual atoms and molecules. We'll be able to design new materials, elementally. That will have impacts on health, industry — nearly everything." Even over the phone, his sense of wonder is clear.
The sense of wonder: You can't help but wonder on just what DNA strand the basis for that is encoded.
