Q+A: In New Book, George Annas Explores Legal and Ethical Issues in Evolving Science of Genetics.

With the deciphering of the human genome, people are now able to know more about themselves than ever before, in the most minute and exacting detail. But unlocking that information, and the subsequent ability to edit and rearrange genes to potentially change essential characteristics of what makes us who we are, has spawned a host of critical questions about ethics, consent, and personal privacy.

In his latest book, Genomic Messages: How the Evolving Science of Genetics Affects Our Health, Families, and Future, George Annas, director of the Center for Health Law, Ethics & Human Rights, explores these issues with the aim of presenting them to a general audience, many of whom may only have a surface understanding of the fundamental changes currently underway.

Annas says he and co-author Sherman Elias, the late obstetrician-gynecologist geneticist, wrote the book because the rapidly expanding field of genetics is beginning to be applied in many different clinical aspects. The average person, whether as a patient or a consumer, does not know enough to decide whether they want to get their genome screened, Annas said, nor do they have enough information on how to use information about whether they are carrying a mutation that might have a major medical impact on them or their family.

As a William Fairfield Warren Distinguished Professor and a health law professor for more than 30 years, Annas is a noted thought leader in the areas of genetic privacy and genetics in medical practice. Some genetic screening is relatively common in the US and other developed countries, Annas says. Historically, fetuses have been screened for Down’s syndrome, spina bifida, cystic fibrosis, Tay-Sachs disease, and other conditions that cause chromosomal abnormalities or other genetic triggers. But these, Annas warns, are relatively big problems.

New techniques can detect fetal DNA in the mother’s blood, allowing genetic testing of the fetus without amniocentesis, chorionic villus sampling, or other invasive tests. The relative ease, speed, and declining cost will likely  open the door to testing for any number of conditions. This is an entirely new area, Annas says, and one that will require serious thought on both societal and individual levels. Would widespread fetal genomic screenings have value as public health tools that outweigh serious privacy concerns? Should parents do broad genomic testing on a fetus? And if so, what should be done with that information?

Q: Why do you discourage testing newborns for cancer, Alzheimer’s, and other diseases that usually do not show any onset until people are in their 50s, 60s, or beyond?

A: All you can do with diseases that do not have treatments is to label your child, stigmatize your child, and discriminate against your child. There is nothing that can be done. Hopefully, by the time the child is 50, say 50 years from now, we may have some cures. Then it would make sense for the child to know about it. Other than that, you are trying to look at the future and say, “This is what I want to concentrate on, this disease.” We do not know the future. We do not know the influence of the environment. We do not know if we might survive, or die of something else. It seems to be a false waste of time.

Q: Why are there so many more false-positive newborn screening results compared to true-positive results?

A: It is the basics of statistics. Whenever you are looking for a disease that does not occur very often, you are going to get false positives. That is almost all of the genetic diseases. Most of us do not have genetic diseases or we would not be alive, or they are not important, or they would have significant impacts on our health. It is true that most of the time when we are looking for genetic conditions, they are rare.

That’s one reason that President Obama has recommended that we have a giant gene bank with a million genomes from a million people, because with a million-member group, you may be able to find a few of those rare diseases. But it may turn out that you are going to need 10 million.

Q: What are some of the privacy issues that might concern consumers, clinicians, and people who will be in charge of that gene bank?

A: For Dr. Elias and I, the two big issues in genomics are the effects on privacy, and the impact on the doctor/patient relationship and informed consent. Privacy is simply having other people find out information about you that you consider private. It’s information that has always been considered private, that might be embarrassing, or cause you to be discriminated against. Genomic information—what is in your genome that is not evident by looking at you—is classic private information. In fact, we even call it genetic privacy, a special kind of privacy, and we do not think that anyone should have their genome sequenced, or stored in a public bank, or even a private bank, without their informed consent. That is the key. There is no problem doing all of this with consent, but it is hard to know whether you can give informed consent unless you know something about genomics and what they might find, and how it could be used—not just for you, but against you and your family.

Q: What would be the difference between having that informed consent and having the presumed consent or community consent of being part of a big organization like a gene bank?

A: We are debating that right now. There are two levels of this, one is everybody agrees we have to consent to have your genome put in the Obama Bank, or the Precision Medicine Bank. But the debate now is about, once we have this bank made up of these million people, a million genomes, and we want to do research with this genome, do you have to go back and ask every time you come up with a new research project, you would have to say, “Can I do this research on cancer? Can I do this research on mental illness? Can I do this research on…?”

The current thought is that if the people going in know what the bank is for, and know a menu of different types of research we are thinking of doing now, that they could give what is called “broad consent.” I can say, “I consent to have you hold my DNA and do research like this on it without you coming back and getting an additional consent from me.” Surprisingly, to a lot of people, Dr. Elias thought that is okay. As long as it is spelled out, as long as you retain the right to withdraw your sample from the project, altogether, if you become uncomfortable with what is going on.

Q: In the book you make several key pop culture references, one being the movie Gattaca, where parents use various means of testing their embryos, to either figure out the genetic makeup of the child, or even to influence it. Do you think that type of screening is in the future?

A: Right now, this only happens when you are using in vitro fertilization, and you have the embryo outside of the woman. When it is in the laboratory, right now, we can screen it for genetic diseases, we can screen it for gender, you can decide whether to have a boy or girl. What we cannot do that is done in Gattaca, which goes a step beyond screening, is changing the embryo. You may remember in Gattaca, the doctor said, “We have eliminated premature baldness, alcoholism, aggression…” We may never be able to understand the genetic basis of any of those things, but since the book was published, there is a new gene editing technique that has been used on embryos. These are not embryos that are destined to become fetuses, but embryos in the laboratory, and researchers are able to make genetic alterations.

The international debate now is whether that research should go forward with humans or whether that should be limited to animals. Gattaca, even though it seems weird and out there, is an excellent vehicle to spur that discussion. I do not think any individual doctor should be able to decide that. I think we have to decide as a society, whether we want to even go in that direction at all.

Q: Can you explain the differences between post-humans and trans-humans?

A: Post-humans/trans-humans are a name for a similar phenomenon, which is for humans to move beyond the current species limitations, as people would say, and to transcend them. [Inventor and futurist] Ray Kurzweil, who now works for Google, came up with the notion of “the Singularity,” which is when machines get smarter than humans, and run humans. At some measure, either the machines will destroy humanity, or in his view, machines will merge with humanity, and we will become immortal as part of a machine, or as part of a computer inside a machine.

There is another basic view, that instead of becoming immortal by merging with machines, we will be able to figure out a way to dump the contents of your brain into a computer chip, and put that computer ship into a robot body. Theoretically, if you think that is you, live forever, replacing the body anytime whenever it wears out with your chip from your brain. People are looking forward to that. I think that is a little creepy. I do not know what kind of a human you are, if you are a computer chip.

Q: In the book, you highlight the similarity between personalized medicine and what you argue may be best called stratified medicine. 

A: Personalized medicine is a funny term, it has almost been discouraged now. It is synonymous with genomic medicine, which is really what it is. Now the NIH and the President use the term ‘precision medicine.’ They are different words for the same thing, but personalized is misleading, because that says we are going to make medicine just for you. Everybody’s genome is unique, that is true, but the notion that it is so unique that no medicines that exist are good for you, that we need our own medicine … that is silly. The real thought is that people do have different clusters of genes, different types of genes, and that is the stratification. If you carry X or Y gene, for example, you are not the only one that has got that gene. You and a million other people have it. That is the strata; we may do a drug that is for that particular gene, or that particular sequence of bases. That is what we are looking at and the point is it is precise to that gene, not to that one person that has that gene, but to the group of people that have that gene.

Q: So, how can we take advantage of the coming flood of genomic data without getting drowned in information? In the book, you have a great quote from [health policy investigator] Gil Welch, saying that we know so much and have so much information, yet the healthiest populations may be those who know nothing about their DNA.

A: Gil’s point—and I think that he may be right—is that there is a big difference between information and data. What we have is a whole lot of data, and whether it is useful data or not, we do not know. That is what we are doing research on right now, to know when it matters that you know your DNA, and your possible future. It only matters if there is something you can do about it. If it is a bad thing, like if you are pre-diabetic. Half the country is pre-diabetic now. That is useful information only if there is something you can do about it. Right now, we have diet and exercise, that is fine. Americans don’t want to do diet and exercise, we want to take a pill. If there is a pill, that is fine, but if not, then all you can do is worry about it.

That is what Gil is thinking of: people are running around worried, they are not sick. They might become sick in the future, but we all know that we are all going to die in the future, but that does not seem to bother us that much. But once we know that we are going to get sick, then we are going to fixate on it. That is going to make us sick. We were not sick before, but now we have this information about our genome, instead of looking at the healthy parts, we look at the parts that might give us trouble. That is very American—you always look for trouble. It is true of the annual physical exam, are we getting too much information now is the question. The information is making us sick. That is a great question; it is part of the whole over-diagnosis movement in the country now. To say, maybe there is some things that you do not want to get diagnosed, that are likely to never have caused problems.

Prostate cancer is a classic for men, right? Almost every man who dies has prostate cancer, but most of them never knew about it. But once you know about it, and it is diagnosed, it is a rare guy who can say “I can live with it, let us watch it and see what happens.” Most say “Take it out, get rid of it. I am not walking around with my prostate cancer.”

Q: You discuss the value of using genetic information for diagnosis versus the value of using genetic information for screening, and how they may have the same outcome, but different results in the way people feel. Can you explain about the “Angelina Jolie effect” and why you discourage people from adopting it?

A: I do not second guess Angelina—she is probably one of the most informed patients in the United States, and she can certainly afford any treatment she wants—but nobody should have a treatment just because a celebrity had it. That is not a good reason. It is controversial. It is not that you have the breast cancer gene, all the data that we have is about people who have breast cancer and ovarian cancer that run in their family. You have two or more family members who also had this. Again, most people as far as we know, with these genetic mutations even BRCA1 and BRCA2 are not going to develop breast cancer, but if you have it in your family, then you are more likely to develop breast cancer. Even then, you may not.

Some women may be more than willing to watch carefully and they have themselves screened every year, see if it develops or not. Others do not want to think about it, they are obsessed with it. Angelina said she was, that she could not think about it. Remember, she did not have breast cancer, she had the likelihood of developing breast cancer sometime in the future, but not a 100 percent certainty that she would. It is paradoxical that you would do a much more aggressive operation, a bilateral mastectomy, on a patient who did not have breast cancer, than you would do on a patient who did have breast cancer where you would likely do a lumpectomy, not a radical mastectomy.

Q: Do you think reproductive counseling before this level of genetic testing is important?

A: I think counseling before testing is critically important. There has been some debate in the genetics community about whether we should go ahead, whenever we are doing genetic testing…. The screening we are going to see most of is going to be done in embryos and fetuses. Then, after that, in children that have diseases that we cannot diagnose. Finally, in patients with cancer, screening their tumors more than screening them specifically, to see if we can treat the specific route to treat the tumor. That is where most of the action is—we are way too premature to do routine screening of adults.

I think we should not even be talking about doing routine screening of newborns yet, even though it is a big-time public health thing. We do not do whole genome screening yet and I do not think we ever will, but we might. That debate is going to be on the horizon soon.

Q: So, if that debate carries forward, then what will be the most immediate effects?

A: We are going to come up with more treatments. Whether they are any good or not, we can argue about, but a lot of the new cancer treatments, for example, give you an extra two or three months of life—for $100,000. Those treatments are not genetic necessarily, but you can see similar things happening in genomics. Especially with stratified populations, we are going to have groups who are going to become expensive to treat. At some point soon, we are going to have to have a rational discussion about rationing, which we have never done in this country. We think we can have everything, no limits. Yes, there are limits, and I think the Genome Project is going to make that clear to everybody, at some point.