"WHAT ARE YOU OPTIMISTIC ABOUT?"

BEATRICE GOLOMB, MD, PhD
Professor of Medicine, University of California, San Diego


Reforming Scientific and Medical Publishing Via the Internet

I am optimistic that the ascendance of open access postings of articles to the internet will transform scientific and medical publishing; and that a number of profound problems—some particular to medical publishing—will be assuaged as a result.

Currently, it can be impossible to gauge the true balance of risks and benefits of medical treatments from a reading of the literature. Frighteningly, this is true too for those doctors who ground their clinical decisions upon a reading of it. I will review some aspects of the problem; and then relay grounds for possible optimism.

First, as is probably true in all fields, bias occurs in favor of existing orthodoxy. This is arguably more troubling in medicine since the orthodoxy is in turn influenced, as has been learned, by the profusion of articles favorable to their products that are ghostwritten by the pharmaceutical industry, or by the for-profit MECCs (Medical Education and Communication Companies) that industry hires for this purpose. These companies in turn pay physicians and pharmacists—including favorably disposed "thought leaders" whom they seek to succor —to be the listed authors, extinguishing any appearance of connection to industry for the favorable views propounded. This provides the appearance that many independent parties are in agreement in their favorable representations of the evidence. Crisply said, advertising is published as though it were science.

These problems are exacerbated by bias arising from direct conflict of interest. Conflict of interest is endemic in medical research; and articles about a class of drug have been shown to be dramatically more likely to be favorable when authored by persons with ties to industry than when authored by persons without such conflicts. Conflicts for authors thus appear to foster submission of industry-favorable articles. Conflicts for reviewers may also foster rejection of industry-unfavorable ones. (As elsewhere, reviewers are drawn from the pool of authors.) Moreover, reviewers are seldom tasked to disclose conflicts, and they remain anonymous, precluding repercussions for biased reviews.

These factors are aggravated, possibly dwarfed, by pharmaceutical company influence on medical publishing—further aligning medical publishing with medical advertising. Medical journals are not the independent arbiters of article quality one might wish. They are businesses and derive their revenue from pharmaceutical company advertising, and from sales to industry of glossy reprints of industry-favorable articles, at inflated prices. For some medical journals, profits reportedly number in the millions, providing high stakes.

At least three former Editors in Chief of major US and British medical journals have penned books decrying the inimical impact of industry influence on medicine. One has to ask why, in medical journals, advertising is accepted (just because it is available for the taking); and whether the journal's bottom line is a proper consideration in dictating what is published, in settings where lives are on the line.

So, whence the optimism? One means to propel optimism is to suggest a tactic that might enable its fruition. Briefly, I suggest that papers be published on the Internet, reviews be submitted by named reviewers; and that others rate (and review) the reviews. Both papers and reviewers receive ratings that are updated on an ongoing basis. While this won't protect against biased submissions, it will protect against biased rejections—and at least enable a voice for original or contrary perspectives.

It is probable that more bad science will be released. However the system provides a means for improving poor quality work; and avoiding having to view what remains substandard.

More importantly, more good science may be published—and perhaps, more great science. As Nobelist Sydney Brenner (who famously authored an article entitled "Moron peer review") has observed, many of his co-Nobelists' prize winning work was initially rejected through the review process.

Transformative work by its nature may defy conventional wisdom. One might be drawn to wonder: is there other work that would have revolutionized science and merited a Prize, that languishes unpublished? And that does so because authors at some point ceased to persevere in submission efforts after some number of rejections, or finally deemed the effort to publish futile?

Hark back to the many great discoveries of which we have heard that were initially ridiculed: H. pylori as a contributor to ulcers; handwashing as a means to reduce puerperal fever; the sun as the center around which the earth revolves, to name a few. What might this imply for the possibility that major discoveries may be pilloried into nonpublication by peer review? There is no means to estimate the fraction of Nobel-caliber efforts that achieve publication, as the denominator remains unknowable.

Indeed, the benefits of a new, Internet-based approach may be particularly great for the most important work: work that challenges existing orthodoxy; work that defines a new field and fits no existing journal; work that crosses boundaries to other disciplines—with their own often arbitrary conventions and in-groups; or that demands knowledge from two or more disciplines; science that is ahead of its time, that entails many advances at once or that founds new work on an understanding of relevant material that others do not yet have. Or, too, work that runs counter to vested interest groups—particularly but hardly exclusively in the arena of medicine, where the potent impact of industry influence on information has been the subject of increasing alarm—and where disparities between literature and truth may cost patients' lives.

An instance from mathematics supports the premise that current convention, requiring articles to be published in peer-reviewed journal venues, may inhibit promulgation of at least some of the very most important work. The Poincaré conjecture—a holy grail in mathematics—was recently proved by a Russian mathematician who posted his work on the Internet but refused the bother of submitting his work to a journal. Other cases can be adduced favoring the proposition that some among persons capable of propelling major advances—which often entails rejecting conventions in science—are also constitutionally inclined to reject the conventions, petty obstacles and distractions that attend the current model of scientific publishing. And perhaps they do so with justifiable contempt.

Surely many will defend the current system—not least those who fare well within it, and who benefit disproportionately from it. And surely there will be problems to overcome in the new system. Orthodoxy, in-groups, and interest groups will continue to influence the literature. Those who serve these masters will likely submit negative reviews of articles (and of reviewers) who do not toe the respective party lines. But at least now the contrarian positions will achieve release, reviewers can be held accountable for biased reviews, and unacknowledged conflicts can be exposed in instances when others know of them.

In short, I am optimistic that online publishing, with a review-the-reviewer system akin to that proposed here, will provide more voice and venue for science that may now have the highest need—and the lowest prospect—of being aired.

PAUL STEINHARDT
Physicist; Albert Einstein Professor of Science, Princeton University; Coauthor, Endless Universe: A New History of the Cosmos

Bullish on Cosmology

I am optimistic that there will be a historic breakthrough in our understanding of the universe in the next five years that will be remembered as one of the most significant of the millennium. I would also give better-than-even odds that there will be more than one discovery of this magnitude.

My optimism is sparked by a remarkable coincidence: the simultaneous maturing of several unrelated technologies, each of which could open a new window on the cosmos. Historically, every new technology is a harbinger of great discovery. Consider, then, that at least a handful of major advances will occur within just five years:

• Directly detecting of dark matter:

After decades of gradual progress, physicists will finally build the first detectors sensitive enough to detect dark matter particles directly, if they consist of weakly interacting massive particles (WIMPs), as many physicists suspect. 

• Discovering the nature of dark energy:

Although their names sound similar, the only quality dark matter and dark energy have in common is that they are both invisible. Dark matter consists of massive particles that gravitationally attract one another and clump into clouds that seed the formation of galaxies.

Dark energy is gravitationally self-repulsive, so it tends to smooth itself out. When it is the dominant form of energy, as it is today, dark energy causes the expansion of the universe to speed up.The composition of dark energy is one of the great mysteries of science, with profound implications for both fundamental physics and cosmology. 

Over the next five years, arrays of novel wide-field telescopes will be constructed that are programmed to rapidly scan large fractions of the sky to search for astronomical phenomena that vary rapidly with time. The arrays will be used to search for distant supernovae (exploding stars), whose brightness and colors can be used to judge the distance and recessional speed of their host galaxies. From these measurements, astronomers can measure precisely the accelerated expansion of the universe, a primary means of distinguishing different theories of dark energy.

At the same time, in the laboratory, physicists will be trying to detect changes in the gravitational force when masses are placed at close proximity or tiny changes in the strength of the electromagnetic force with time, other effects predicted by some theories of dark energy. These measurements will significantly narrow the candidates for dark energy, perhaps identifying a unique possibility.

• Exploring the big bang and the origin of the large-scale structure of the universe:

The conventional wisdom is that the universe sprang into existence 14 billion years ago in a big bang and that a period of exponentially rapid inflationary expansion accounts for its large-scale structure. However, the last decade has seen the emergence of alternative possibilities, such as the cyclic model of the universe. 

In the cyclic model, the big bang is not the beginning but, rather, an event that has been repeating every trillion years, extending far into the past. Borrowing ideas from string theory, the cyclic model proposes that each bang is a collision between our three-dimensional world and another three-dimensional world along an extra spatial dimension. Each bang creates new hot matter and radiation that begins a new perio of expansion, cooling, galaxy formation and life, but space and time exist before and after the bang.

The large-scale structure of the universe and the pattern of galaxies are set by events that occurred about a cycle ago, before the bang, just as events occurring today are setting the structure for the cycle to come. Although the inflationary and cyclic pictures predict distributions of galaxies, matter and radiation that are indistinguishable, their predictions for the production of gravitational waves in the early universe are exponentially different.

Gravitational waves are ripples in space produced during inflation or near the beginning of a new cycle that propagate through the universe and distort space like undulations traveling through jello. These cosmic gravitational waves are too weak to be detected directly, but experimental cosmologists throughout the world are mounting ground- and balloon-based experiments to search for their imprint on the polarization pattern of cosmic microwave background radiation produced in the first 380,000 years after the bang. 

The results will not only affect our view of our cosmic origin, but our future as well. The conventional big bang inflationary theory predicts our universe is headed towards the cold oblivion of eternal expansion—a whimper—but the cyclic model predicts a new hot big bang.

• Direct detecting gravitational waves:

The first window on the universe using something other than electromagnetic waves could be open within the next five years. After decades of developments, the LIGO (Laser Interferometer Gravitational Wave Observatory), with one detector in Livingston, Louisiana, and one in Hanford, Washington, has a plausible chance of directly detecting gravitational waves, beginning a new era in astronomy. 

The observatory is designed to detect stronger gravitational waves than those produced in the early universe, such as waves generated by the violent collision of neutron stars and black holes in our own galaxy. However, this frontier is so fresh and unexplored that there could well be unanticipated cosmic sources of strong gravitational waves to be discovered that could cause us to reassess our understanding of the universe. 

• Breakthroughs in fundamental physics and direct production of dark matter: 

The Large Hadron Collider at the Center for European Research (CERN) in Geneva, Switzerland, is set to begin operation this year. This facility consists of a powerful particle accelerator that will reproduce collisions of the type that occurred within the first pico-second after the big bang, carrying the investigation of fundamental physics over an important energy threshold where new phenomena are anticipated. For example, physicists hope to discover a spectrum of new "supersymmetric" particles, confirming a key prediction of string theory, and also WIMPs that may comprise the dark matter.  

The impact will  be profound.  As we enter 2007, we understand the composition of less than five percent of the universe; we do not understand how space, time, matter and energy were created; and we cannot predict where the universe is headed. In the next five years, we may witness the historic resolution of one or more of these issues. I have my personal bet on what the individual outcomes will be; but the only prediction I will reveal here is that, with the opening of so many new windows on the cosmos, we are sure to discover something unanticipated and astonishing. 

ROBERT SAPOLSKY
Neuroscientist, Stanford University, Author, A Primate's Memoir

With The Right Sort Of Priorities And Human Engineering (Whatever That Phrase Means), We Can Be Biased Towards Making Us/Them Dichotomies Far More Benign

A truly discouraging thing to me is how easily humans see the world as dichotomized between Us and Them. This comes through in all sorts of ways —social anthropology, lord of the flies, prison experiments, linguistics (all those cultures where the word for the members of that culture translates into "People," thus making a contrast with the non-people living in the next valley).

As a neurobiologist, I'm particularly impressed with and discouraged by one finding relevant to this. There's a part of the brain called the amygdala that has lots to do with fear and anxiety and aggression. Functional brain imaging studies of humans show that the amygdala becomes metabolically active when we look at a scary face (even when the face is flashed up so quickly that we aren't consciously aware of seeing it). And some recent work—solid, done by top people, independently replicated — suggests that the amygdala can become activated when we view the face of someone from another race. The Them as scary, and the Them being someone whose skin color is real different from our own.

Damn, that's an upsetting finding.

But right on the heels of those studies are follow-ups showing that the picture is more complicated. The "Other skin color = scared activated amygdala = the Other" can be modified by experience. "Experience," can be how diverse of a world you grew up in. More diversity, and the amygdala is likely to become activated in that circumstance. And also, "experience," can be whether, shortly before your amygdala is put through the brain imaging paces, you are subtly biased to think about people categorically or as individuals. If you're cued towards individuating, your amygdala doesn't light up.

Thus, it seems quite plausible to me that we are hard-wired towards making Us/Them distinctions and not being all that nice to the Them. But what is anything but hard-wired is who counts as an Us and as a Them —we are so easily manipulated into changing those categories.

So, I'm optimistic that with the right sort of priorities and human engineering (whatever that phrase means), we can be biased towards making Us/Them dichotomies far more benign than they tend to be now. Say, by making all of us collectively feel like an Us with Them being the space aliens that may attack us some day. Or making the Them to be mean, shitty, intolerant people without compassion.

But, I'm sure not optimistic that we'll soon be having political, religious or cultural leaders likely to move us effectively in that direction. Just to deflate that optimism.

ALISON GOPNIK
Psychologist, UC-Berkeley; Coauthor, The Scientist In the Crib

New Children Will Be Born

New children will be born. This may seem rather mundane compared to some of the technological breakthroughs that other scientists have focused on. After all, children have been born for as long as the species has been around. But for human beings children are linked to optimism in a way that runs deeper than just the biological continuation of the species.

Optimism, after all, isn't essentially a matter of the rational assessment of the future—it's an attitude rather than a judgment. And it's the most characteristically human attitude, the one that's built into our DNA. The greatest human evolutionary advantage is our innate ability to imagine better alternatives to the current world—possible universes that could exist in the future—and to figure out how to make them real. It's the ability we see in its earliest form in the fantastic pretend play of even the youngest children.

But, in fact, everything in the room I write in now—not only the computer and the electric light but the right-angled wall and the ceramic cup and the woven cloth was once imaginary—no more than an optimistic pipe dream. And I myself, a scientist, a writer, and woman literally could not have existed in the evolutionary Pleistocene past, or even in the only slightly less neolithic atmosphere of the universities of fifty years ago.

This ability to change the physical and social world in unprecedented and unpredictable ways is deeply bound up with our characteristically extended human childhood—that long period of protected immaturity. The radical changes that have transformed human lives for the better never could have been accomplished in a single lifetime.

We change the world bit by bit, generation by generation. We pass on our own innovations and the new worlds they create to our children—who imagine new alternatives themselves. We work to imagine alternatives that will make our lives better, but, even more impressively, over generations we can revise what we mean by leading a better life. Our moral lives are no more determined by our evolutionary past than our physical or social lives. 

I can see only small glimpses of the future and they are all heavily rooted in the past. But it's a good rational induction that my children and their children and all the new children to be born will see the world in new ways, discover new possibilities and find new ways to make them real, in ways that I literally can't imagine now. 

ROGER BINGHAM
Cofounder and Director, The Science Network; Neuroscience Researcher, Center for Brain and Cognition, UCSD; Coauthor, The Origin of Minds; Creator PBS Science Programs

The Women of the 110th Congress

I am optimistic about the record number of women who will come to Washington in January 2007 as members of the 110th Congress —16 Senators and 71 Representatives. Only 20 years ago, there were just two female Senators and 23 Representatives. Now, the Speaker of the House is a woman, second in the line of succession to the Presidency. Why do I think this Ascent of Women is cause for optimism? Because I believe we need a lot more social smarts—particularly empathy—in the corridors of power and the brains of our political leaders; and current evidence indicates that, in general, the female brain is intrinsically a more proficient empathizing device.

One example. About a year ago, Tania Singer (then at University College London, now at the University of Zurich) published a study on the neural processes underlying empathy. As one rather lurid headline described the work: "Revenge Replaces Empathy in Male Brain. Watching bad guys suffer lights up the mind's reward centers for men." The experiment involved imaging the brains of a group of male and female volunteers while they played a monetary investment game based on trust. A few of the players were actors, planted to play fairly or unfairly.

Subsequently, the actors were zapped with a mild electric shock, while the other players watched. When an actor who had played fair was shocked, both female and male volunteers felt their pain: fMRI images showed empathic activation of pain-related areas of their brains—specifically in the insular and anterior cingulate cortices. But when the unfair actor was shocked, the sexes reacted differently. The females still showed a surge of empathy; the males didn't. Instead, their reward areas lit up. The German word for this feeling—schadenfreude—roughly translates as taking pleasure in the misery of others. The researchers' conclusion, based on the scanning and on the comments from post-experiment questionnaires, was that "men expressed a stronger desire for revenge than women".

Twenty years ago, in a PBS program called The Sexual Brain, I explored male-female differences. It was quite clear then (and has since become even more evident) that anatomically, chemically and functionally the brains of men and women have some significant differences. To what extent these variations drive or map on to differences in cognition and behavior remains controversial (ask Larry Summers). But we know, for example, that men have a proportionally larger amygdala than women  and women have a proportionally larger prefrontal cortex.

There's evidence, too, that women have a proportionally larger anterior cingulate cortex (ACC) and insula than men. From quite recent brain imaging studies, we now know that these areas are important components of the circuitry that underpins our ability to process complex social emotions, ‘read' the faces and minds of the people we encounter as we navigate through social space, understand and predict their behavior, make moral judgments and empathize. (Of course, everything I am saying should have the usual scientific safety net of caveats—the differences exist at the level of populations, not individuals; cultural factors play an important role; etc.)

So what does this have to do with my optimism about the women of the 110th Congress? Would women govern differently than men?

That's exactly the question that Geneva Overholser posed in The New York Times in 1987 just after Margaret Thatcher won a new term as British Prime Minister. Overholser noted that Thatcher —like the few other women who were national leaders—operated in a male-dominated political arena and basically behaved no differently in office from men.

"Would that be true," Overholser asked, "if the number of women in high office better reflected their share of the population? Would they then govern differently, feeling more comfortable and secure as women?" She turned to the example of Norway, where the Prime Minister—Gro Harlem Brundtland—was a woman (and, incidentally, a physician). Of 17 Cabinet ministers, seven were women. And the consequences were dramatic. One example: Despite huge spending cuts, the Norwegian government actually increased child care subsidies and paid parental leave. In Norway's case, the answer to Overholser's question was: "Probably, if enough came to power."

In The Sexual Brain, I asked: "Is it wise for males to confront each other across an arms control negotiating table? Is global security enhanced in an atmosphere charged with testosterone?" Today, more women have had seats at that negotiating table—think of Madeleine Albright and Condoleeza Rice in the United States, Margaret Beckett (first female Foreign Secretary) in the United Kingdom, Angela Merkel (first female Chancellor and, incidentally, a physicist) in Germany. But the questions remain. Is it inherently bad that males experience schadenfreude—or is a taste for revenge a valuable prerequisite for dispensing justice?  Is it admirable that females have more empathy for a cheater in pain  —or a regrettable sign of weakness? Kinder maybe. Gentler maybe. But the best way to run a country?

I am optimistic that the answer to questions like these will eventually emerge from the synergy of science and society. Our relatively recent ability to image activity inside the human brain is a giant step forward and will allow us to better understand individual differences. I view a science of empathy as a realistic prospect: data will replace simplistic slogans (like Men are from Mars; Women are from Venus) as a basis for making social decisions. And I am optimistic that the social sophistication that a larger number of female legislators can bring to the 110th US Congress can help create "a more perfect union, insure domestic tranquility and secure the blessings of liberty for ourselves and our posterity".