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Brain Boosters

How should we deal with cognitive-enhancing drugs?

Courtesy Henry Greely

GREELY: Enhancement is no dirty word.

Here's a good way to stir people up: publish a commentary in a prominent science journal supporting the use—with safeguards—of prescription drugs such as Ritalin and Adderall as a way for healthy adults to improve brain functions, including concentration and memory. (Those two drugs are central nervous system stimulants commonly prescribed for attention deficit and hyperactivity disorders.)

Law School professor Henry Greely was first author among the seven professors and scientists who collaborated on the article for Nature. He has gotten an earful since its December appearance, and he sat down with STANFORD for a question-and-answer follow-up. An abridged version of this Q&A appeared in the print version of the magazine.

You’ve provoked quite a bit of attention. What’s your take on the overall reaction so far?

Part of me thinks that any attention is good attention, because we think this is a really important issue. I have to admit I also sort of cringe sometimes when I look at my e-mail. The two most common reactions I’ve gotten are: “How much crack were you were smoking when you wrote this?” and “How much money did your friends in the pharma industry pay you to write this?”

But at the same time, I’ve gotten some very thoughtful responses, including some pretty negative responses, from a couple of my friends and colleagues here at the University. It’s an issue that people care about. One of the reasons that we wrote this piece is we think people care about it more than they’ve thought about it. The other big reason is we think there’s more and more of this coming down the road, and we’re just not prepared as a society yet for how we should deal with good, safe, cognitively enhancing drugs that will almost certainly be available in the next 10 to 20 years.

You acknowledge that a great deal is unknown about the benefits and the risks of cognitive-enhancing drugs, so why advocate for their wider use before more research is done?

One of the things that has troubled me most about the reaction is that so many people have read that article as saying, “Let’s freely use Adderall and Ritalin.” That’s not our goal, that’s not our position, that’s not what we want. We do think that safety is a major issue, and particularly Adderall and Ritalin are not benign drugs. They may be useful; they are useful to people with certain illnesses. But they’ve got really dangerous side effects. One of the things we think most important is further research on what the effects of these kinds of drugs will be.

And an important regulatory note here: the FDA rules drugs as safe and effective, so Adderall, Ritalin, Provigil (Modafinil) have all been declared by the FDA safe and effective. But it’s safe and effective for a particular use. So Adderall and Ritalin are safe and effective for whatever the FDA has approved them for—say ADHD—but the FDA has never said they’re safe and effective for various off-label uses. Yet once a drug is approved by the FDA for one use, a physician can prescribe it for any use whatsoever. If you’re talking about enhancement uses, you really want a better safety profile than if you’re talking about a drug being used for a serious disease.

So, for example, metastatic pancreatic cancer, about the most serious disease you can have: 99 percent of people with that diagnosis are dead within a year. If we came up with a drug that killed half of them instantly and cured the other half, that’s a miracle drug. That’s safe and effective. If it also cures teenage acne, it’s not a safe and effective drug for teenage acne. If it improves your memory, it’s not a safe and effective drug for improving your memory. So, our regulatory system isn’t set up to look at or think about the enhancement uses of drugs that are approved for medical conditions. We think there needs to be more research and more work on safety.

More drugs are going to come along, and some of them will have the characteristic that they not only make sick people better but they make healthy people still better. These drugs will be there, we need to think about how we should deal with them. One strong reaction is a knee-jerk “We should ban them”: that they’re cheating, that they’re unnatural, that they’re somehow wrong. The main point of this article is that we don’t agree with that. Enhancement is not a dirty word. I’m a teacher—my job is to enhance people. I’m a parent—my job, until they became teenagers, was to enhance my kids.

We do enhancement all the time. Education is enhancement. And as a law professor, I’m not only teaching my students facts that are important to them, but ways of manipulating those facts, ways of dealing with them. That’s cognitive enhancement. And it only works if I actually change their brains. If you remember tomorrow anything I’ve said today, it will be because I’ve made physical or electro-chemical changes in the cells of your brain. It’s kind of a weird thought, but true. So why is it that we do enhancement by so many other ways, but if you start talking about doing it through drugs, suddenly it becomes evil?

Well, I think part of it is, drug is a dirty word. Somebody’s talked about our pharmacological Puritanism. It’s a very love-hate relationship, as all of us who enjoy a glass of wine know. I mean, our society is probably one of the biggest users of drugs that change mental states, and also one of the most negative toward them in this odd sort of way. Well, there’s some good reasons to be worried about drugs, and we’ve laid some of them out, particularly enhancing drugs: safeness, coercion and fairness. And those are appropriate concerns, but they’re not knee-jerk concerns. They’re not, “All enhancing drugs are bad in all circumstances at all times.” Right now, to the extent the public has thought about this issue at all, it’s kind of the knee-jerk “drugs are bad, enhancement is bad, let’s ignore it.” Not a good solution.

And we have a pretty good idea that at Stanford, as at other universities, we’ve got kids out there who are buying, borrowing or stealing Adderall or Ritalin and using it to study. We’re largely ignoring that. What we should do about it is a tricky, difficult issue, which is in part why we’re ignoring it. But as more and more of these drugs come along, the ostrich strategy is going to be worse and worse.

What sparked your initial interest in this topic and what have you been doing to investigate it?

I’ve been working on ethical, legal and social issues in biosciences since about 1991, 92, starting with genetics. (I) started doing neuroscience work in 2002, and that’s where I plan to spend most of the rest of my career. I think it’s really fascinating, really hard, not going to be figured out in my lifetime and more important than genetics. Once I started doing neuroscience work, I started thinking about enhancement as one of the important issues. And I should note with the neuroscience side of things, there are really two different, icky, knee-jerk-producing kinds of enhancements. Drugs is one. The other one is neuroelectronic interfaces—plugging your brains into computers. Which I think has equally eerie, and maybe in the long run, bigger implications in terms of enhancement in the brain than the drugs do.

You’re arguing that cognitive-enhancing drug use can’t be judged by the same standards as physically or sports-enhancing drug use. But won’t the concerns overlap and wouldn’t cognitive drugs substantially benefit many athletes?

That’s a really good question that nobody else has ever asked. So what drug has been most abused—apart from alcohol—for the longest period of time in major league baseball? Yes, amphetamines. And that is mainly a mental thing, not mainly a physical thing at all.

We didn’t want to get into the sports issue in part because we didn’t want to deal with all that baggage in this article. My own view is that sports enhancement should be looked at pretty much the same way I think cognitive enhancement should be looked at. There are issues of fairness, safety and coercion. These people who go on about the integrity of the game—you know, God didn’t say the bases are going to be 90 feet apart. These are rules; we change the rules from time to time.

I’m old enough to remember when the pitching mound was lowered because the pitchers were too good. Carl Yastrzemski had the lowest league-leading batting average in history at .301. Same year that Bob Gibson had the lowest all-time ERA. And then they lowered the pitching mound. And in recent years they’ve brought in the fences. There’s not a platonic ideal despite what true lovers of baseball might believe about what baseball is. Look at the old gloves. Fielding is much better, in part because they’ve got better equipment. We enhance bats. We have rules about what you can enhance and what you can’t. And I think it is cheating to violate the rules—at least more than whatever the standards of the game are about how much you’re allowed to violate the rules. Holding happens on every play in football. Water polo apparently is incredibly dirty under the water. Baseball pitchers will do what they can.

But I’m not advocating violating the rules. The reaction against drug-related enhancement in sports is strong and deep. I think it’s not entirely rational. It threatens to color the reaction to cognitive enhancement. Cognitive enhancement is different in a way that we state in the article. The world isn’t particularly better off if the weightlifting record is 402 kilograms instead of 400 kilograms. Or if the Turk wins the gold medal instead of the Iranian. Maybe it’s an academic bias, but we like to think that if people are smarter and working better—their brains are working better—the world will be a better place. We tried to avoid the analogy with sports because we don’t want people’s views of this to be so strongly colored by their views of sports. But I do think one can distinguish between the two in a number of different ways, the most important being that there’s the potential for real personal and social benefits from cognitive enhancement that is much, much weaker in terms of sports enhancement.

As you weighed the pros and cons of your recommendations, what was most persuasive to you about the potential individual or social advantages?

For me personally it’s the sense of inevitability. We’re going to have to confront this issue, and we haven’t even begun to think about it.

In terms of the drugs themselves, I personally have a bit of this drug Puritanism. And yet, if this can help people do their job or lives their lives better, it’s very hard for me to see why we should try to stop them. We’ve got these scary scenarios out there—people using them so that they can be 24-7 machines. There’s also the possibility of the person who’s struggling in school, who has always wanted to graduate or always wanted to be a doctor, always wanted to be something else, who maybe wasn’t born with as much talent, or didn’t grow up with a family that strongly supported education or had to work early in addition to schooling. And we should be very reluctant, I think, to condemn without good reason people’s efforts to improve themselves, even if they involve drugs.

The legal obstacles to implementing your recommendations are formidable, yes?

Law’s a very practical subject. It really eschews seeking the best and is in reality a practice of muddling through and making do. And we could, I think, with fairly minor adjustments to the food and drug laws, muddle through dealing with enhancements. I think the FDA would have to modify its approach in drug approvals. I’d like to see some increased safety requirements and regulatory requirements for safety evidence. I think in an ideal world the main changes would be to the drug approval laws and to the scheduled substance laws.

The second part makes it very complicated because the first part’s only federal. The second part is not just federal but every state’s laws, as we see with the continuing medical marijuana problems. California says it’s good, and the Feds say it’s bad. So, if given free rein, I would rewrite the regulatory regime in a way to make the regulation of these kinds of drugs, when used for enhancing purposes, more rational. It’s always a lot easier to get an administrative agency to change its regulations than to get Congress to change a statute.

But I do think that some changes will be needed. I’m ultimately not pessimistic about whether we’ll get those changes. I certainly don’t believe we’ll get the legal changes we need as soon as we need them in perfect form. But we’re pretty good at muddling through, and if in fact—and this is of course the big if behind the whole subject—we produce drugs that have a significant cognitive-enhancing effect, we won’t be able to ignore these issues. And then the laws will have to adapt to them one way or the other. It is an article of faith more than anything proven by experience that we’re likely to adapt better the more we’ve talked about it and thought about it.

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