Exposing the Student Body: Stanford Joins U.C. Berkeley in Controversial Genetic Testing of Students
This week, the University of California, Berkeley will mail saliva sample kits to every incoming freshman and transfer student. Students can choose to use the kits to submit their DNA for genetic analysis, as part of an orientation program on the topic of personalized medicine. But U.C. Berkeley isn't the only university offering its students genetic testing. Stanford University's summer session started two weeks ago, including a class on personal genomics that gives medical and graduate students the chance to sequence their genotypes and study the results.
The idea behind the two novel projects is that students will learn about optimizing treatment based on one's genetic profile most effectively if they are studying their own DNA–an idea that has met with both praise for educational innovation and criticism centering on potential ethical issues.
"The concerns did not revolve around whether students should be taught about genetic testing–everyone agreed about that," says Gilbert Chu, a Stanford professor of medicine and biochemistry. "The concerns surround allowing students to undergo genetic tests themselves. I don't think it's been an easy road to get to this, and I don't think we know whether it's going to be successful."
George Annas, a bioethicist at the Boston University School of Public Health, worries that the projects are premature. "This potentially is a model that other schools will copy. I think it's an innovative idea that can get students engaged, but from my perspective they are facing a very steep learning curve about how to do this. I don't think they're ready."
Stanford and Berkeley faced the same essential ethical dilemmas in creating their programs: avoiding coercion, protecting students' privacy and adequately preparing students to interpret the results of their tests. But the two universities took markedly different approaches to designing and executing their respective projects
Outsourcing vs. testing on campus
Berkeley's project is essentially a modified version of the summer homework many colleges assign to new students in an attempt to foster intellectual discussion and class cohesion. This year, instead of asking students to read the same book or watch the same movie for later debate on campus, Berkeley sent approximately 5,500 incoming freshmen and transfer students DNA sampling kits. The hope is to spark discussion during orientation on how genetic testing works, the results of the students' tests and their decisions on whether or not to participate. The "Bring Your Genes to Cal" program is the first mass genetic testing project by any national university. Although the program is entirely voluntary and confidential it has alarmed some bioethics watchers, who cite concerns about privacy, student health and the ambiguous nature of the project.
"This year we decided to take on the topic of personalized medicine, which in the future will allow doctors to tailor their treatments," explains Mark Schlissel, dean of biological sciences at Berkeley and one of the program's organizers. "We wanted to provide an actual genetic test of the type that will become routine in the future and provoke very personal thought processes."
After difficulty finding an affordable outside company that would agree to complete the genetic testing, Berkeley settled on a genetics laboratory in its School of Public Health. The Berkeley lab will test students' DNA for three specific gene variants that affect how the body metabolizes and uses alcohol, folic acid (vitamin B9) and lactose.
Any student choosing to participate uses the provided kit to collect their saliva in the provided container and mail the sample to Berkeley with a unique bar code attached–a duplicate of which the student keeps. Reportedly, test results will not be linked with any names–they will only be tied to the confidential bar codes that students use to identify their results online. All participating students must provide informed consent and minors must obtain additional permission from their parents.
Stanford's project, in contrast, is only open to medical and graduate students in the form of an eight-week elective summer class called "Genetics 210: Genomics and Personalized Medicine," in which about 50 students have enrolled, with a dozen more auditing. Students in the class can choose to have their genotype analyzed by Navigenics or 23andMe–personal genomics companies that provide individualized risks for various health conditions and sensitivity to drugs (23andMe also provides additional information about ancestry). The results of their tests will be incorporated into the class curriculum, although students can also opt to study publicly available genetic data in lieu of analyzing their own. Professors will not know what decision the students make. The idea behind the class is to prepare a new generation of physicians and scientists with the understanding that they need to properly analyze and interpret genetic data.
"When individuals want expert advice on their genetic test results they are going to turn to physicians or professors, so it's particularly important for these individuals to be adequately prepared," says Keyan Salari, a sixth-year MD/PhD student who originally proposed the course and is now its director.
Stuart Kim, a Stanford professor of developmental biology and genetics who served as Salari's faculty sponsor, says the goal is to make sure Stanford students are prepared to handle the future of personalized medicine. "The students are going to need extensive training," he adds.
Two approaches to anticipated controversy
Despite enthusiasm from many Stanford students and professors, the course did not receive approval without significant deliberation. "This is all new waters," Kim says. "I didn't think there would be such a controversy over writing this course, but it turned into a big debate."
In fact, after Salari originally proposed the class last fall, a Stanford task force of about 30 basic scientists, clinical scientists, genetic professors, genetics counselors, bioethicists, legal counselors and students spent several months working through the various ethical issues and establishing safeguards to protect students. In contrast, the organizers of Berkeley's project incurred criticism because they spent hardly any time considering the potential reaction to their new orientation program.
Kimberly Tallbear, a professor of science, technology and environmental policy at Berkeley, explains that neither Mark Schlissel nor any of the project's other organizers consulted with Berkeley's bioethics community. "Schlissel said several times they were surprised about the controversy," Tallbear says. "I said to him, 'Well doesn't that tell you that you needed input from us? Because we could have told you about the controversy and debate.'"
In response, Schlissel says that Berkeley does "not organize educational programs by inviting all 1,500 professors to participate in the design." The project was approved by Berkeley's Committee for Protection of Human Subjects Institutional Review Board, which included bioethicists of its own, Schlissel adds.
Three bioethics issues
Apart from the preparation–or lack thereof–that shaped the new programs, three main issues concern critics in the bioethics community: The manner in which universities are asking for genetic data from students; what will happen to that information; and how students will understand and respond to the results of their tests.
Berkeley is offering genetic testing to its students free of charge, a decision that could persuade students to participate, many bioethicists argue, because many may jump at the opportunity to obtain for free what is usually costly.
Furthermore, some argue that the assignment borders on coercion. Any pressure from peers or the university to participate in the program should not be overlooked, say critics like Arthur Caplan, a bioethicist at the University of Pennsylvania (Penn). There's already considerable excitement about the program on Facebook, according to Joanna Maltbaek, an incoming Berkeley freshman from Mountain View, Calif., who says she will most likely participate in the "Bring Your Genes to Cal" program. "I like that it's a way for incoming freshmen to get involved in something important," Maltbaek says. "I can already see people wanting to go to campus and discuss it, and I think people might feel pressured, especially because Berkeley isn't offering an alternative [to the class-wide summer assignment]."
Students enrolled in Stanford's elective must pay a $99 fee to have their genotypes analyzed by 23andMe or Navigenics. "These tests are normally offered to the general public at $500 or $600," Chu says. "If students could get the testing for free there was some concern that it would encourage students to neglect all the risks involved." When Salari pointed out that 23andMe recently advertised their genetic testing package for $99–a promotional offer for DNA Day on April 23–the course's organizers decided that would be an appropriate fee to request of students, just as many must pay for the materials they use in laboratory classes.
Beyond the incentives and pressures students might feel to participate in genetic testing, critics have called attention to a second kind of ethical dilemma: the question of how the universities will use the resulting data.
In Berkeley's case, the matter is complicated by conflicting statements about exactly what kind of project the university is organizing. The program's founders insist it is not a research or medical project, but the informed consent document all participating students must sign explicitly characterizes the project as "a medical research study in the area of personalized medicine…providing free of charge information on three of your genes in which variants are common in the human population and which affect aspects of your health that you can address by simple, safe and effective dietary means."
"If you look at the language in the informed consent, it looks like it's a study," Tallbear says. "I don't understand–it's not clear at all. If it's unclear to us who deal with consent forms all the time, how will it look to 18-year-olds?"
Although all DNA samples collected by Berkeley will be incinerated after testing is complete, the results of those tests will be preserved as data sets on computers. But the tests results will not be useful for research purposes, says Michael Eisen, a Berkeley biologist who has defended the "Bring Your Genes to Cal" program on his blog. "It's such a small sample of alleles that are not of significant research interest. I could probably tell you in two seconds what the results are likely to be–it's completely predictable."
Schlissel says the data from the Berkeley tests will only be used for educational purposes, explaining that Jasper Rine–the Berkeley professor of genetics heading the project–will aggregate the test results for a presentation during orientation. "If we provoke the kind of interest and discussion that we hope, we might write about it as an educational project," Schlissel adds, "but not as a scientific study."
Stanford cannot use the students' physical DNA samples for research because 23andMe destroys DNA samples after testing, and Navigenics–although it may preserve the sample for a year–eventually does the same (also giving customers the option to request earlier destruction). The tests results, however, will be maintained on computer servers at the respective personal genomics companies. The creators of Stanford's new genetics class also claim their project is educational, and that students' test results will not be used in research. Stanford will, however, survey student attitudes to learn whether or not analyzing their own DNA facilitated learning about personalized medicine, says Charles Prober, senior associate dean for medical education. "We'll be conducting an educational study," Prober says. "If you choose to have your own genotyping done, will that make the information [one learns] stick more? That's what we want to know."
The third main ethical issue raised by bioethicists is how students will react to the results of their genetic tests. Specifically, critics are concerned students will lack the proper context and knowledge to interpret their results and might make unwise lifestyle decisions.
One of the gene variants Berkeley's project identifies, called aldehyde dehydrogenase 2 (ALDH2), codes for an enzyme crucial to breaking down alcohol in the body. People with this particular variant may experience facial blushing and nausea when they drink. "If they learn they don't have the gene [variant] that makes them flush, they might think they can drink more," Annas says. Others argue that most Berkeley students will already know what their genetic tests tell them, because the conditions in question–like facial blushing and lactose intolerance–are so common and noticeable. "First of all, it's hardly like they need an excuse to binge drink," Eisen says. "Probably most people are already aware of their condition."
To help students understand their test results, Berkeley is relying on a series of lectures and discussions during freshmen orientation. But critics say that is not enough. "I worry students won't understand or would easily misconstrue the information they are being presented," Caplan says. "A meeting in an auditorium is not the way to discuss genetic testing at this point in its evolution." Instead, critics argue that Berkeley must provide one-on-one genetic counseling to all participating students.
According to Schlissel, students will have the option to meet one-on-one with himself, Rine or a genetic counselor–but there is no mention of genetic counselors on the program's official Web site or in the informed consent form. "They say Rine would be available for counseling–that's like insane," Annas says. "The students are going to tell their professor? It's supposed to be confidential."
Meanwhile, before students in Stanford's summer class can choose to participate in genetic testing, they will attend two class sessions intended to provide them with adequate background on the potential risks as well as the relevant ethical and legal issues. Once the results are in, students will have the option of one-on-one confidential genetic counseling offered by both Navigenics and 23andMe at no extra charge. Still under negotiation is whether Stanford's own genetic counseling program will offer additional services. Alan Schatzberg, a Stanford psychiatrist on the original task force, also offered to counsel students.
Stanford v. Berkeley
Another big distinction between Stanford and Berkeley's projects are the respective student populations involved, emphasizes Salari, the grad student who originally proposed the Stanford summer course and attended Berkeley as an undergraduate. "The Berkeley population is 17 to 20 years old. At Stanford they are all in graduate or medical school. They are a generally older, more mature population. I'm proud of my alma mater for organizing their program. I think it's a good idea, but it's very different from what we are doing."
Not everyone at Stanford agrees that graduate and medical students are better able to interpret genetic data, however. "I don't like the idea of subsidized genotyping for students," says Hank Greely, director of the Center for Law and the Biosciences at Stanford Law School. "I think it's less concerning when the students are medical students and PhD students than when they are freshmen, but the fact you are smart and know something about the Krebs cycle doesn't necessarily mean you know genetic risk very well."
"Those of us on the task force who opposed it are strong supporters of genetics, just genetics done carefully," Greely adds. "I think it's telling that all the ethics and policy people were largely against it but the basic science people were the most supportive."
Most critics of both university programs applaud innovation in teaching personalized medicine and genetics, even if they think the projects are poorly designed and full of ethical pitfalls. "I agree with the idea of looking for more hands-on experiences," Berkeley's Tallbear says. "They just collectively seem to be unaware of the controversial nature."
Penn's Caplan called the Berkeley approach "a clever class project, but I think they could have done it in a manner that was more sensitive to flaws in genetic testing."
Greely says that neither project is reckless or grossly foolish, but he advises against them. "There's been the assertion that students will be more engaged if they are studying their own DNA," he says, "but I haven't seen any empirical evidence for that. How significant of an improvement would that even be? I think it's a mistake."