Limitless: DNA Science’s Brave New World

The Past, Present, and Future of DNA symposium.The Past, Present, and Future of DNA symposium.
By Jillian Lokere

Students, academics, and practitioners gathered at Radcliffe to hear how research using DNA has expanded our knowledge of the past, shapes the world we live in today, and points toward synthetic DNA.

Since 1953, when James Watson and Francis Crick proposed the double-helical structure of DNA, our fascination with our own genetic code has seemed nearly limitless. From gene therapy to personalized medicine, cloning to genetically modified food, forensic science to genetic disease risk, DNA science has been at the forefront of our national discourse, both professional and popular. Yet so often the discussion is fragmented among academic institutions. The law school might discuss forensic DNA science, while the medical school focuses on breakthrough treatments for genetic disease. This year, the Radcliffe Institute’s annual science symposium, “The Past, Present, and Future of DNA,” took an entirely different approach. Led by researchers from all walks of DNA science, the symposium, held on October 2, 2015, at the Knafel Center, looked across the entire continuum of DNA science, emphasizing the common goals, hopes, and fears. With participation from a packed and rapt audience, the symposium highlighted the powers we can harness by understanding our own genes and those of organisms around us, but did not neglect a fearless examination of the ethics of our brave new world.

The Past: New Secrets from Old Bones

George Church, John Hawks, Beth Shapiro, and Spencer Wells on the panel "Mammoths, Nanderthals, and Your Ancestors."George Church, John Hawks, Beth Shapiro, and Spencer Wells on the panel "Mammoths, Nanderthals, and Your Ancestors."

Although analyzing the degraded DNA present in many ancient bone fossils proved elusive to scientists for decades, recent breakthroughs now allow useful genetic data to be gathered even from samples in which the DNA is heavily fragmented. According to John Hawks, the Vilas-Borghesi Distinguished Achievement Professor of Anthropology at the University of Wisconsin–Madison, this new technology is allowing ancient hominid fossils to reveal new secrets. “It turns out that human evolution is much less linear than previously believed,” said Hawks. About 3 percent to 4 percent of the DNA of modern European and Asian peoples is shared with Neanderthals, and 3 percent to 5 percent of the DNA of modern Melanesians and Aboriginal Australians is shared with ancient Asian hominids called Denisovans. “Some ancient gene variants are still beneficial today,” noted Hawks, “such as a Denisovan vascular gene variant that allows for improved fetal growth at high altitudes. This gene variant is prevalent among the modern Tibetan population.”

An attendee examines a model of the enzyme Cas9, brought to the symposium by presenter Jacob Corn.An attendee examines a model of the enzyme Cas9, brought to the symposium by presenter Jacob Corn.Using similar technology, Beth Shapiro, an associate professor of ecology and evolutionary biology at the University of California, Santa Cruz, has gathered and analyzed hundreds of ancient DNA samples in the Arctic from the bones of species present in the last Ice Age that are now either surviving or extinct. She has found that as a species population declined toward extinction, the genetic distance between individuals increased. “As a species’ habitat became more and more patchy, the populations of those patches became isolated and declined simultaneously,” said Shapiro. These findings are helping to inform strategies for conserving threatened species.

The Present: Linking Families and Solving Crimes

Phil Grayson at the student poster session held during the event.Phil Grayson at the student poster session held during the event.Modern humans differ from one another, on average, at about 1 in every 1,000 of the chemical letters, called nucleotides, that make up DNA. When a certain characteristic change in a section of DNA nucleotides is shared among people, those people have a common ancestor. Such a section is called a DNA marker. Spencer Wells, former explorer-in-residence and director of the Genographic Project at National Geographic, and his team use these markers to construct large-scale human family trees that broadly encompass every modern human being. “To date, the project has analyzed markers of descent in nearly 800,000 people from 140 countries,” said Wells. “Thanks to public enthusiasm, the number of volunteer human genomes analyzed continues to grow exponentially.”

DNA markers can also be used to solve crimes by matching a sample of DNA found at a crime scene with a known DNA sample in a criminal database. According to Greg Hampikian, a professor of biological sciences and of criminal justice and the director of the Idaho Innocence Project at Boise State University, this technology is a double-edged sword. Forensic DNA science faces widespread problems, including sample contamination and mix-ups during testing. These are all known to have led to false convictions. Misleading statistical language is also a problem. “If the chance that a sample does not match the suspect is 1 in 10,000, then there are about 64 other people in the city of Boston for whom that is also true,” Hampikian noted. “But juries have trouble with that idea.” Samples with DNA mixtures are also difficult to analyze and have been incorrectly used to convict suspects. Not all is lost, however. As the cost of DNA sequencing continues to fall, forensic scientists will be able to affordably sequence larger sections of DNA, which will make matching a sample with a suspect less prone to errors.

The Future: Editing Our Own DNA

Scientists have become experts at reading the chemical letters in DNA from every kind of organism. Jacob Corn, the managing director and scientific director of the Innovative Genomics Initiative at the University of California, Berkeley, is working on the next step—editing our own DNA. He described an enzyme-based system isolated from bacteria that can be used to edit DNA with unprecedented accuracy in nearly every organism tested. “One near-future application of the technology is editing cells ex vivo for use as made-to-order bone marrow transplant therapies for hematopoietic diseases. In the long term, it may be applied to produce personalized in vivo correction of genetic diseases,” said Corn.

Students, professors, scientists, and others attended the daylong symposium.Students, professors, scientists, and others attended the daylong symposium.Floyd Romesberg, a professor of chemistry at The Scripps Research Institute, is taking DNA editing one step further by adding new chemical letters to the DNA alphabet. His team is synthesizing a third pair of DNA nucleotides that can pair specifically and be replicated faithfully. His goal is to eventually create a semisynthetic cell that can produce proteins containing amino acids that do not occur naturally in humans. “Protein therapeutics are a big deal in medicine today,” said Romesberg. “If we could expand the scope of what types of proteins could be made via unnatural amino acids, we might develop protein therapeutics that could revolutionize medicine.”

The Ethical Frontier of DNA Science

No discussion of DNA science would be complete without considering the ethical implications. Arthur Caplan, the Drs. William F. and Virginia Connolly Mitty Professor of Bioethics at NYU School of Medicine, noted that in the near future, genetic tests for many neurological differences among humans, such as addiction, ADHD, depression, and autism, are likely to become available. He used Down syndrome as an example of the complex ethics surrounding such testing. Today, approximately 70 percent to 80 percent of pregnancies in which the fetus is found to have trisomy 21 are terminated. “The Down syndrome experience is very predictive for some of the ethical challenges that are in store,” said Caplan. These include questions of who provides genetic counseling, what information is provided, and how that information is presented to families.

Alison Murdoch, a professor of reproductive medicine at Newcastle University (United Kingdom), participated in the panel "The Future Utility of DNA Science."Alison Murdoch, a professor of reproductive medicine at Newcastle University (United Kingdom), participated in the panel "The Future Utility of DNA Science."Alison Murdoch, a professor of reproductive medicine at Newcastle University (United Kingdom), discussed the ethics of mitochondrial donation as a reproductive treatment for individuals with mitochondrial disease. Mitochondria, the “energy factories” in our cells, contain their own DNA, which is inherited only from the mother. This DNA is distinct from the 23 pairs of chromosomes in the cell nucleus, which are inherited from both. When a mother’s mitochondrial DNA has a mutation, it can result in devastating mitochondrial disease in her children. To circumvent this problem, both a healthy donor egg and an egg from a woman with mitochondrial disease are fertilized with her partner’s sperm. The nuclear DNA from both fertilized eggs is removed. Then the nuclear DNA from the woman with the mitochondrial disease is placed in the donor egg. “The result is a healthy embryo that contains normal mitochondria plus normal nuclear DNA from the woman with mitochondrial disease and her partner,” said Murdoch. This technique will soon be available in the United Kingdom. Murdoch focused mainly on the ethical issues of mitochondrial donation, including the rights of the unborn child and the parental status of the mitochondrial donor.

Janet Rich-Edwards '84, SD '95, faculty codirector of the science program at Radcliffe, organized the symposium.Janet Rich-Edwards '84, SD '95, faculty codirector of the science program at Radcliffe, organized the symposium.Janet Rich-Edwards ’84, SD ’95—a faculty codirector of the science program at the Radcliffe Institute, an associate professor of medicine at Harvard Medical School, and an associate professor of epidemiology at the Harvard T.H. Chan School of Public Health—closed the symposium by pointing out that humanity is the first species that can edit its own evolution. “What we have learned today is that we have a fantastic, brand-new toolbox to work with in DNA science, and all of us, not just the scientists and researchers, have a responsibility to consider how we want to use it,” she said. “Let’s just be sure that our intelligence doesn’t outrun our wisdom.”

Jillian Lokere is an independent medical and science writer.

Photos by Jessica Scranton

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