To Lead, First Master Your Unconscious

FORBES.COM, July 14, 2010, by Cleve W. Stevens  —  John Doe, the chief executive of a multinational corporation, is in the middle of a meeting with his board of directors when the board’s chairman, Bob Roe, directs an innocent, even affectionate joke at him. Jack hears not amiability but a veiled attack on his leadership and his regime. He completely misreads his boss’ intent, his mind clouds, his temperature rises, and he hears little else for the rest of the meeting. He thinks to himself, “I’ve just got to get through this meeting and get out of here.”

Jack is unwittingly at war with himself, unaware that he is creating his own misery. It’s all unconscious. The automatic, instantaneous psychological filtering and response system we all have has kicked in for him, and it, not his conscious mind, is now running the show. In this state he may further exacerbate the problem with glibness or by getting smart-alecky, or maybe by turning fawning and obsequious, thus diminishing his stature with the board and its chairman.

We don’t know–and most likely Jack doesn’t know–what kind of experiences in his past might have set him up to so mishear a remark and lose his control of a meeting. Most people have little idea of the extent to which we are all prey to our own unconscious. Yet it is estimated that anywhere from 80% to 95% of our cognitive activity happens at an unconscious level. The vast majority of the problems that occur in human interactions, and therefore within all organizations, are exacerbated–if not caused–by unresolved, unconscious conflicts within individuals.

As Sigmund Freud so rightly observed, “Only a good for nothing is not interested in his past”

In companies this problem starts at the top, with the CEO and how the CEO relates to his or her direct reports, and it cascades on down through the organization. Over the past two decades, working with executives and their companies as a transformational leadership consultant, I have found that when senior executives begin to address their unconscious leadership issues and in the process become conscious of the degree to which they, like all of us, are unconscious, amazing things begin to happen.

First, they begin to find a new level of personal and leadership power. Second, they learn how to create real teams, leadership bodies that are honest, united and focused on a bigger game. Third–and for many the most surprising–they begin to understand that being genuinely committed to your people and their growth is not in conflict with producing extraordinary results. In fact, the opposite is true. What has become increasingly clear to me, working with organizations around the world, is that when leaders become fiercely and wisely committed to their peoples’ development, employee satisfaction, including that of the leadership, invariably (and I mean invariably) goes way up; customer satisfaction follows; and the top and bottom lines soar. I’ve seen it time and time again, without fail.

It isn’t easy to implement the sort of a systemic cultural shift this represents. It takes a courageous commitment, a genuine willingness on the part of leadership to take itself and its people on. How do we do it?

The starting point is always with the CEO and his or her leadership team. Initially, they are brought together off site for two to three days to be challenged to face up to who they are as leaders and as people, and to consider who they can yet become as individuals and as a team. It is not an easy or comfortable process. It is confrontational and demanding. One client told me it was a “self-awareness boot camp, the most intellectually and emotionally challenging and exhilarating three days of my adult life.”

That first gathering initiates a yearlong process in which each leader is challenged to do deep, honest introspective work with himself (or herself), taking to heart Socrates’ 2,500-year-old admonition that “the unexamined life is not worth living.” In the process he begins to come to grips with some of his limiting, false, largely unconscious self-beliefs. There are four steps that help him identify and move past the problematic beliefs, steps that liberate his leadership power and move him toward the formation of collaborative teams that achieve breakthrough results.

The steps are simple, but they are not easy. We call them ARRC. They are first, Acknowledgement–facing up (becoming conscious of the fact that we are largely unconscious creatures); second, Responsibility–accepting our causality (accepting the simple fact that we are, like it or not, the causal agents in our lives and in the organizations we lead); third, Recognition–seeing our unique false beliefs (acknowledging our unconscious programming, the subterranean beliefs and judgments that drive our behaviors and limit our authentic power and fulfillment); and, fourth, Changing our brains–and thus our minds (intentionally creating new, accurate beliefs at the deepest levels of mind, and establishing new and more genuinely powerful ways of being).

The third and fourth steps, which truly change people’s lives, are by far the most demanding. You may have noticed that the third step seems, at least at first blush, logically impossible. If our false beliefs are unconscious, how are we supposed to see them with our conscious minds? Through guided group interactions and feedback, and, more important, through a rigorous process of deductive reasoning and self-honesty, these deeply embedded beliefs begin to give up the ghost, so to speak, and reveal themselves. Leaders examine past experiences, old and recent, and the past results they have generated in their lives, and they look for specific circumstantial patterns or consequences in their personal as well as leadership lives. Once recognized, these patterns, such as chronic issues with certain types of employees or bosses or people in general, or recurring difficulties with certain types of business challenges or opportunities, open the door toward understanding basic beliefs about worth, talent, intelligence, goodness, personal power and confidence.

Once unconscious falsehoods are revealed and recognized, the fourth step, an equally challenging one, is implemented. How do we change our deepest ways of thinking? There are two main ways. First, leaders take specifically chosen, repeatable actions that they otherwise would likely avoid, thus allowing themselves to begin to experience life more expansively, again and again. Second and simultaneously, leaders who are truly committed to changing their minds establish a brief daily practice of focused, disciplined, rigorous thinking, specifically tailored to address their limiting beliefs and to strengthen their more accurate self-understanding. Despite how it may sound, there is nothing fluffy or New Age in this. It is about strong, no-nonsense declarative assertions of the truth as it actually is.

When committed human beings take themselves on in this manner and do so within a leadership team environment that demands honesty and accountability, amazing things begin to happen. True team spirit begins to emerge. My message to a CEO and his leadership team is one of courageous and demanding possibility, of affirmation that there is a way out of inertia. It declares that we can all grow and change, and thereby accomplish more and make more money.

If you find this all a little hard to believe, I ask you to briefly suspend your disbelief and consider the following. There’s an explanation for how we drove our economy to the edge of the abyss, and it starts with the fact that an old paradigm for business leadership simply no longer works in a world as transparent and instantaneous as ours. That paradigm is the transactional approach to leadership. It says that as a leader, I have something you want–money–and as a follower, you have something I want–labor. So we make an exchange, a transaction. That is the tacit agreement we all make when we go to work for or hire anyone.

As that type of leader, I care about your growth and development only inasmuch as it helps my bottom line. This is not necessarily a good or bad approach, as far as it goes, but when you throw in a healthy dose of “Greed is good” what you end up with is Goldman Sachs, Massey Energy, BP and a world economy in a shambles.

The new paradigm says something fundamentally different about the leader’s job. The new leader is not transactional but transformational. He says, “My fundamental job is to grow my people, really grow them, and to grow myself in the process.” The results will and do follow because in this model demand and expectations go up, not down, and accountability becomes more vivid, not less. Productivity is the organic outcome.

If I systematically challenge my people to become clearer, more conscious, stronger, smarter, more powerful employees and human beings, if I push them to contribute, and in a meaningful way, if I demand (yes, demand) that they care about themselves and their colleagues in a way that leads to professional and personal expansion, and if I hold them to account at ever higher levels because of all this, does it not follow that they will produce better, smarter, more lasting success?

If you doubt it, take a look at Starbucks or Whole Foods or PeopleSoft (before it was consumed by Oracle) or Costco or Southwest Airlines or countless other organizations where they have figured out that intelligent commitment to your people leads to a much better bottom line. The transformational approach is the furthest thing from naive idealism. It is as pragmatic as the day is bright, while it is also a humane approach to business, a humane capitalism whose time has come. It seems to me we’d better wake up, and soon. The edge of the cliff we have pulled back from is still but a few steps away.

And, yes, this approach all begins with getting the top people of the business world to step back and consider who they really are, and consider what really runs them and summon their yet unrealized promise. It is simple, but it’s anything but easy.

Cleve W. Stevens, a transformational leadership consultant to business leaders, is the founder and president of Owl Sight Intentions, in Los Angeles. E-mail him at

Healing the heart: Inhibiting microRNAs reduces the buildup of dangerous collagen (shown in red) typical of cardiac fibrosis, an abnormal thickening of the heart valves that can lead to heart failure. The bottom image shows cells that have been treated with an anti-microRNA agent.    Credit: Regulus Therapeutics

Drugmakers place big bets on the emerging science of microRNA

MIT Technology Review, July 14, 2010, by Arlene Weintraub  —  San Diego startup Regulus, founded in 2007, has quietly been working on a new way to target RNA for drug development. The company has been studying a subset of RNA molecules called microRNAs, or miRNAs. First discovered in the 1990s, misbehaving miRNAs have been linked to several diseases, including cancer and heart failure. Drug developers hope these molecules will prove to be particularly effective drug targets because manipulating just one seems to suppress several disease-linked proteins–whereas most biotech drugs only target individual proteins.

Regulus is co-owned by Alnylam and Isis, leaders in RNA-based drug development. While it is just one of a handful of startups developing miRNA therapeutics, it has attracted significant attention from big pharmaceutical companies. Last month, French pharmaceutical giant Sanofi-Aventis announced a research alliance with the company. Sanofi has pledged up to $750 million in payments, including $35 million up front to Regulus–an unusually large investment in such early-stage science. Sanofi and Regulus will work together to target fibrosis, an excessive buildup of hard collagen that can wreak havoc on the heart, kidneys, and other organs. Regulus already has a multimillion-dollar alliance with GlaxoSmithKline to codevelop drugs to treat immune diseases and a hepatitis C treatment.

While many RNAs encode proteins, miRNAs instead regulate the expression of multiple genes by preventing protein-coding RNAs from fulfilling their function. That, in turn, controls everything from metabolism to immune response to muscle development. About 700 miRNAs have been identified so far.

“The analogy we like to use is that miRNA is the maestro conducting the orchestra–the entire biological network,” says Zak Zimmerman, Regulus’s director of business development. “If something goes wrong with the maestro, the orchestra starts to play off-key.”

Regulus has synthesized several compounds that block or modify “oligonucleotides”–the chains of nucleotides that comprise miRNAs. In 2008, the company demonstrated that it could inhibit a particular miRNA in mouse hearts, reversing a fibrotic condition that causes heart failure. Regulus is also researching potential remedies for renal fibrosis, a major cause of kidney failure and common complication among transplant patients. Sanofi had a team of scientists researching miRNA for quite some time, but they lacked the chemistry know-how to transform their discoveries into drugs.

Despite their promise, translating miRNA targeting compounds into safe drugs is likely to prove challenging. MiRNAs control many bodily processes, so altering them can cause unwanted side effects. “They’re promiscuous–they affect multiple downstream components,” says Sumit Chanda, associate professor at the Sandford Burnham Medical Research Institute in La Jolla, CA. “The more targets you take out, the more toxicities there can be.”

Regulus’s scientists acknowledge that they’ll have to perform extensive toxicity testing before they identify molecules that are safe for testing in people. Funding from Sanofi and GSK will help move that testing forward. The company expects to choose its first drug candidate for clinical trials by the end of this year. 

A new test is transforming the way some doctors diagnose and treat their patients.

MIT Technology Review, July 14, 2010, by Lauren Gravitz  —  As a genre, personalized medicine has yet to deliver many individualized treatments. But progress has been more tangible on the diagnostics side.

Some of that progress has come from Tethys Bioscience, a startup in Emeryville, CA, that is working on tests for some of the country’s most prevalent diseases. Their first diagnostic, a blood test called PreDx, determines a person’s risk of developing diabetes over a five-year period. The test is already changing the way some physicians diagnose and treat their patients.

People with prediabetes don’t regulate blood sugar the way they should; of the 57 million or so people in the U.S. with this syndrome, only about 10 to 15 percent develop the full-blown disease. With proper diet and exercise, the trajectory toward diabetes can be slowed or even reversed. But the current standard for identifying diabetes risk, the fasting blood-glucose test, can’t determine which 10 to 15 percent are most likely to get the disease. As a result, doctors can’t easily figure out which patients to concentrate on.

There are a few tests to determine which patients are high-risk, but these tend to be expensive, resource-intensive, time-consuming, or all three. Tethys’s simple $250 blood test can be almost as accurate.

“The PreDx risk score allows a physician to determine which subjects to focus their interventions on,” says Tethys president R. Michael Richey. Suddenly, a patient who might have once been told that his lab results indicate he’s on the verge of diabetes could be told the likelihood of disease progression as a percent. Someone else with similar fasting blood-glucose results might be told that if she doesn’t lose weight and start exercising, her risk of developing diabetes is quite high.

Richey and his colleagues at Tethys developed this “risk stratification” approach by hunting down blood-sample banks from long-term studies of large groups of patients with known health outcomes. The researchers tested these blood samples for as many potential diabetes markers as they could. Then they looked for protein combinations that differentiated those who developed full-blown diabetes from those who didn’t. “We ran them through complex algorithms and found the smallest number of markers that, when taken together, would accurately predict incidence of diabetes,” Richey says.

The resulting algorithm is based on seven proteins and metabolites present in blood. Tethys has tested this approach in two more large study groups with known diabetes outcomes, including a multi-ethnic U.S. population, and found the results to be just as accurate.

Such an advance in diagnostics is due to a convergence of new technology and disease-prevention research. “It’s a result of our understanding the human genome and better understanding the biology that leads to these metabolic disorders, as well as an enormous amount of research published that allowed us to understand which markers we need to look at,” he says. Tethys began marketing the test to physicians in 2008, and it’s been used at least 12,000 times since.

Patients receive their PreDx results in the form of a color-coded bar chart, with their risk level highlighted as green (low), yellow (moderate), or red (high), and a number between one and 10 (the higher the number, the greater their chance of developing diabetes). “The critical thing about the test is that you don’t need to be a rocket scientist to understand it, and that means that patients understand it and get motivated to really make changes,” says Ed Kersh, the chief of cardiology at St. Luke’s Hospital in San Francisco and a clinical professor of medicine at the University of California, San Francisco.

Kersh started using the test about a year ago, and he says the approach has led to healthy changes in weight and blood-glucose levels in over 90 percent of his high-risk patients. “Creating lifestyle change in patients is a very difficult thing–the success rate for diet, exercise, and smoking cessation is down around 10 percent unless they’re confronted with significant data,” he says.

One physician was so convinced by the PreDx methodology that he developed an entire weight-loss clinic around the concept of the PreDx test. Michael Abou Assaly directs the Health Living Clinic at the Great River Medical Center in Burlington, IA, and has used the test on about 750 patients. He’s seen significant lifestyle changes in about three-quarters of his high-risk patients (about 30 percent, he says). “It’s been like nothing I’ve ever seen, as far as a motivating tool,” Abou Assaly says.

Richard Bergman, a professor of physiology and biophysics at the Keck School of Medicine at the University of Southern California, specializes in diabetes risk prediction and has developed a clinical method that can measure that risk. But the PreDx test, he says, “is better than anything else you can do without a clinical test,” which requires time and money. “The fact that it can be measured from a blood sample and is much less labor-intensive means that it can be used routinely in a doctor’s office,” says Bergman, who is on the Tethy’s scientific advisory board.

Tethys hopes to submit its PreDx research to the FDA for approval sometime in 2011. (Such diagnostic tests don’t require FDA regulation, which is how the company has been able to market it so broadly.) In the meantime, they’re also working to create similar risk-profile tests for cardiovascular disease and osteoporosis and hope to have the first one, a test for heart-attack risk, ready for market within the next two years.

The FDA plans to overhaul its regulation of the increasingly common diagnostic tests.

MIT Technology Review, July 14, 2010, by Emily Singer  —  In a prelude to overhauling its regulatory oversight of genetic diagnostic testing, the U.S. Food and Drug Administration will convene a public meeting next week to gather input from test makers and others.

The event reflects a turning point in genetic testing, a cornerstone of personalized medicine. Once mainly the domain of rare diseases, scientists have discovered a growing number of genetic variations linked to both the risk of more common disease and patients’ response to drugs. The number of genetic diagnostic tests has expanded rapidly, and tests have become increasingly complex, making it more challenging to interpret and act on the results.

“We don’t think physicians are going to be able to interpret the results; they are relying on the labs that make them,” says Alberto Gutierrez, director of the Office of In Vitro Diagnostic Device Evaluation and Safety at the FDA. “So we think a third party should assess these devices.”

The early generation of genetic tests was relatively simple, testing for a single cancer-linked gene, for example. The possible treatment decisions or other responses were well-defined. But in the last few years, these tests have incorporated more genes and tackled more complex and common diseases. “The scope of these tests and how they can be used is growing rapidly,” says Alexis Borisy, chief executive officer of Foundation Medicine, a startup based in Cambridge, MA, that is developing genetic tests to predict the most effective drugs for cancer patients. More than 2,000 genetic tests are now available through clinical laboratories.

However, tests developed and performed in a single laboratory today face little federal regulation other than that they be performed in a certified laboratory. (Some states, such as New York and California, have stricter laws, such as requiring that a physician order clinical tests.) For these “laboratory developed” tests, physicians collect a sample from patients and then send them to a specific lab. So-called test kits, which are sold to hospitals and other labs so that they can perform the tests themselves, are subject more extensive regulation.

The FDA has made several moves toward more extensive regulation in recent years, but the regulatory issue came to a head in May when Pathway Genomics announced plans to sell its genetic tests in drugstores. Those plans were halted when the agency sent Pathway and other genetics testing companies a letter questioning whether the tests could be sold without the agency’s approval. A month later, the agency issued a statement describing its intent to rethink its approach to all laboratory-developed tests.

“These tests, which are becoming more complex and high risk, are playing an increasingly important role in clinical decision-making. As a result, LDTs [laboratory developed tests] that have not been properly validated put patients at risk, such as for missed diagnosis, wrong diagnosis, and failure to receive appropriate treatment,” the agency explained in the statement. Because of the lack of existing regulation, little data exists on error rates or misinterpretation of the tests.

“The primary concern was once just analytic validity; does it accurately measure what it says it does?” says Daniel Vorhaus, an attorney at Robinson, Bradshaw & Hinson, in Charlotte, NC, and editor of the firm’s Genomics and Life Sciences blog. “That’s still very important, but now there are other issues as well. How are people using the information? Is the interpretation of information accurate? What do I do with the information?” For example, if a test predicts that someone is at greater risk for diabetes, a physician could suggest diet and exercise or a more aggressive approach involving drugs.

The agency says it plans to take a risk-based approach, meaning that tests linked to major medical decisions will be more tightly regulated than those that might predict a minor increase in risk for disease.