And you thought this was old...

What do you own that is 600 million years old? Your old suit? That little league baseball glove? Your cologne? In fact, every man possesses something that old, and believe it or not, it’s a gene. Not the clothing kind, but the kind you keep in your genome, in your chromosomes. We’ve talked about the Y chromosome in this space but lets take a moment to focus on a single tiny gene.

Tucked away in every cell of your body is a gene called Boule, a piece of DNA critical for sperm production. A colleague of mine just announced that the Boule gene is present in every organism from insects like fruit flies, to sea urchins, roosters, fish and man. It is in invertebrates and vertebrates alike. That is, this tiny bit of DNA has remained essential for making sperm through 600 million years of evolution. Surely the oldest treasure you own.

But what’s really impressive about the Boule gene is that is has not changed over time. And change is the rule with every other known gene involved with reproduction in every species. In fact, evolution of reproductive traits is how a species diverges from other species. It gives each species its identity. And this change can be very rapid: in some fish, reproductive traits are observed to change in fewer than a dozen generations. So why would this one gene stay the same?

We think that the Boule gene has remained true over 600 million years because it is essential for reproduction. Boule is a “quality control” gene that ensures all goes well as sperm are made. Just as you would want your new car to be well inspected so it is safe to drive when you buy it, you want your sperm to be reproductively fit. In fact, if the Boule gene is removed, sperm production stops entirely. Not a single sperm is made in its absence. Now that’s control.

What’s also impressive about the Boule gene is that since it is linked to sperm production, it means that sperm are very, very ancient cells. Seems that nature sticks with what is tried and true and feels no need to experiment with magic potions or fairy dust to get the job done. Reminds me of what Einstein once said while reflecting on relativity and physics: “God does not play dice.” When it comes to reproduction, the Boule gene phenomenon suggests that he may take even fewer chances.

The beauty of a balsa wood board.

Up at dawn, and while waiting for a perfect, crumbling long board wave at Waikiki this past week, I recalled that Hawaiians live longer than the rest of Americans and wondered why. For some reason, life expectancy at birth in Hawaii is among the longest in the nation. Indeed, people born in Hawaii have a life expectancy of almost 81 years, at least three years longer than the US average. Why is this?

While watching rainbows appear and fade as early morning showers give way to the rising sun over Waikiki, I thought that it must be the fabulous and consistent climate. Then, as I saw surfers stream out to the break that I was tending before their workday started, I figured it must be that “island fitness” that pervades the tropics. Taking a large breath, I was reminded of the lack of air pollution and the sweet smell of jasmine, orchid and hibiscus flowers that blossom everywhere on the island. Could this be their secret?

A relaxing evening luau with soothing traditional aloha music and dancing accompanied by light, aromatic, almost Mediterranean dinner fare suggested that reducing stress and eating well and in moderation may also have something to do with it. Witnessing the deep respect held for family elders, for the community at large, and for the beauty and health of their island must also contribute in some way to longevity.

And then it hit me. Balance. The backbone of many older cultures is that they have found and maintain a seemingly harmonious balance as a civilization. They are aligned with others as individuals, with nature and with their place as a society on this good earth. The stress of extremes is present but not pervasive in such self-realized cultures and this is obvious in the genuinely large smiles that greet you at every corner of the island. So, let me propose a formula for staying healthy: realize that it is not life’s moments themselves that define you, but how you choose to live them.

The spine: OK for shivers and tingling, but that's it.

I have a lot of patients in my practice who have broken their backs. Not figuratively by working so hard, but literally, by having spinal cord injuries. Some have been crushed by rolling logs, fallen from tall heights, been victims of shooting, dived into shallow pools or took an untoward jump while skiing or skateboarding. As a group, these men are impressive: imbibed with fortitude, perseverance, decisiveness and joie de vivre, they take nothing in life for granted. Live it hard, wring it dry, no regrets.

Their numbers are not insignificant either. Roughly 5,000-10,000 individuals experience spinal cord injury annually in the U.S. alone. And although you may think that cars have plenty of safety measures, they don’t, as the biggest cause of cord injury is motor vehicle accidents. Violence, recreational activities and workplace-related injuries round out the top four causes. And, of course, single, reproductive age men (ages 20-34 years old) are by far the most commonly affected.

I am reminded of these patients after a good friend, Dr. Stephen Seager, came over for dinner last week. A true Irish gentleman (“blended scotch before dinner and single malt after, no ice”) and world famous veterinarian, Dr. Seager invented the rectal probe electroejaculator in the early 1980s. I will leave it up to your imagination to wonder how this device works. But realize that this one doctor, through his invention and its popularization worldwide among male fertility specialists, has touched every spinal cord injured father from around the world over the past 30 years.

Seriously, the Seager Electroejaculator has revolutionized our ability to help men with spinal cord injury to conceive and become fathers. It takes advantage of the fact that ejaculation is governed by a spinal reflex (like sneezing) and it stimulates that reflex to happen. In fact, probably the only biological function that is not seriously affected in men who have broken their necks and cannot move any of their limbs (quadriplegic) is reproduction as this reflex generally remains intact.

By his innovative thinking, Dr. Seager brings hope to every spinal cord injured patient who dreams of being a father. Personally, seeing my patients with their little children running around their wheelchairs, and the wide, grateful smiles on their faces is easily one of the most satisfying experiences I have had in my medical career.

China: 5000 years old and on the move.

Just got back from China, from Beijing and Hong Kong to be exact. I lectured to several medical and academic institutions on where I believe men’s health is headed in the future. What I found was an audience eager to push the research frontiers in this field, however I also a sensed a lack of sufficient infrastructure to do this at the highest level. I paused for a moment to think about what was possible, since a monumental tidal wave of increased industrial productivity and change is occurring in China. For example, there are 1000 new cars being put on the road daily in Beijing alone! I sensed that when the might of China’s intellectual potential directs its energy toward medical research and innovation, the world will stand in utter awe at the prodigious output that will result.

Despite the fact that China’s culture is endowed with 5000 years of evolution and is responsible for helping to define human civilization, one thing really surprised me: its decision in 1979 to control its population by mandating a “One Child Only” policy. In the rest of the world, human reproduction is a basic right and for the most part, entirely unregulated. Under China law, families are allowed to have one child. After that, a vasectomy is performed on the male partner. Like it or not.

In addition to great control of population growth, the “One Child Only” policy has also led to the development of the wildly successful “No Scalpel Vasectomy” procedure. Now relatively common in the U.S., the “No Scalpel Vasectomy” is a quicker (10 minute), cleaner, less invasive and more comfortable innovation on a 100-year old American procedure.

But the curse of the “No Scalpel Vasectomy” is now being felt in China. Currently, it is difficult to find enough youth to fill jobs in urban areas within the massive and burgeoning Chinese economy. As a consequence, there has been a softening of the law such that couples that are both products of “one child” parents can now have two children. So can farmers, handicapped couples, and couples who work in “high risk” occupations like coal mining, heavy equipment operations and the like.

Even more fascinating is that infertile couples have a real reproductive edge over fertile couples under this law. How? Well, if they need assisted reproduction to help them conceive and they happen to have twins or triplets as a result (a 30-40% chance), they are not penalized for bearing “extra” children. Can’t help but think that this little known fact may partly contribute to the size of the massive, bustling IVF clinics that I visited in China last week. many of which are 4-10 times the size of U.S. clinics.

Estrogens and the manly man.

There must be something in the air… or water. The Bolivian President Evo Morales recently asserted publicly that hormones found in mass-produced foods are “feminizing” men. Speaking about chicken in Bolivia, which he believes are “loaded with feminine hormones,” he suggested that when men eat chicken “they are diverted from their nature as men.” So, is this how metrosexuals came to be?

But wait, the Vatican commented on this issue a year earlier, although they blamed female hormones from birth control pills for the increased estrogens in ground water. Pedro Castellvi, writing in the Vatican newspaper L’Osservatore Romano in 2009, stated: “we have sufficient data to affirm that one of the reasons for the not insignificant rise in male infertility in the west, is the environmental contamination caused by the pill.” Actually, it’s not the birth control pill itself but the urine from women taking the pill.

In fact, to date, the urine of women taking birth control pills has been blamed for worsening sperm counts in men, the growth of female sex organs in male fish, breast growth in young men and the early onset of puberty in young girls. What next?

Can I add a little balance to this discussion? First of all, exactly what is happening to men in Bolivia such that the President is not happy with them? Are they more civilized and less disruptive? Second, male infertility is not necessarily increasing in the western world; it may even be true that men have lower sperm counts now than a generation ago not because they are less fertile but because women are more fertile. Third, estrogens are found everywhere in the environment including in many plants (phytoestrogens) such as soy and legumes, and are not produced exclusively from the urine of women. Fourth, the intersex conditions that have been reported in many animal species tend to be caused by a very specific exposure at a very specific time point during fetal development and have been linked to pesticides, bisphenol A, dioxins and other environmental contaminants (xenoestrogens). Fifth, did we somehow forget about the worldwide obesity epidemic in humans and the fact that fat converts male hormones to female hormones? Lastly, there is little evidence that substantially increasing a man’s estrogen levels as an adult will dramatically alter anything, except maybe waist size and color preferences. Where the truth lies in all of this is currently unknown, but it is hard for me as a urologist to see how women’s urine could be blamed for so much.

Caetano Veloso, a masterful, otherworldly voice and an eye on the potential of youth

Had a wonderful evening out with my wife last night at a Caetano Veloso concert at Masonic Hall on Nob Hill in San Francisco. Caetano Veloso is Brazil’s equivalent of Frank Sinatra and is endowed with an absolutely otherworldly voice and reigns from Bahia. He is an historically important figure having led the Bossa Nova and Tropicalia movements in the late 1960’s. He plays it all: Jazz, pop, world beat, folk and ballad styles with an Ellingtonian understanding of harmonic richness.

As the Rolling Stone once said: “He’s a sublime and seductive melodist, a curious musician capable of taking sharp left turns, a historian whose compositions tie past and present together…at once upholding tradition and transcending it.” I have been a fan of his since the mid-1990’s, having seen him perform both in Brazil and in San Francisco. He is now 67 years old, and was simply outstanding again last night.

So how does one get this good? I think I discovered his secret last night, listening to him for the umpteenth time. In addition to his obvious musical gifts, he is at once historically grounded and very modern. And he is a fan of youth. His following remains a generation or two younger than he, and time and again he connects them to their past and to the future. It’s really a form of wisdom that he brings to music.

It is precisely this balance that I seek to achieve in the field of men’s health. Lets forget the stylistic aspects of Caetano Veloso that would be pretty difficult to match. But, bringing the wisdom of old fashioned medicine into the modern age has a certain timeless value. Making it a point not to forget that what has mattered in the doctor-patient relationship since the beginning of time, including trust, communication and empathy also still counts.  And leading the way with original and creative ideas that result in more innovative, efficient and personalized care is undoubtedly “modern.”

Caetano Veloso’s band is always filled with youthful musicians, all in their 20s or 30s. Surely he knows that youth have their ears to the ground and possess an uncanny sense of future…of their future.  Youth holds creativity, brilliance and fire, all forces strong enough to move mountains. Youths take paths that are characteristically unchartered, often “left turns,” and make decisions untainted and undaunted by experience. This all fits in nicely with my philosophy about taking care of men: “Want to take great care of men? Just listen to them.” I move with them just as I move with Caetano.

Did Warhol know about the "cola limit?"

How much coffee or tea do you consume everyday? Since many of us buy Slurpee sized cups of coffee in the morning, you should break those down into units of 8 ounce cups. How about cans of soda and in particular colas? Might be a good idea to keep track of this for a moment, as a recent study of 2,554 young Danish man has suggested that excessive cola intake could lead to lower sperm counts.

For comparison, the average young Danish military recruit consumes about 1 cup of coffee and 1 can of soda daily. This is in addition to about a half of cup of tea and 2 small chocolate bars (why not, Danish chocolate is yummy). This intake was associated with normal semen quality. However, the semen quality of young Danish men who consume more than 2 liters (2.1 quarts) of fizzy colas daily had a 30% less ejaculated sperm than men who drank no colas.

Interestingly, although colas are a weak source of caffeine (ounce for ounce, colas have 65% of the caffeine in coffee) there were no strong correlations between any amount of caffeine intake (even up to 7 cups of coffee a day!) and semen quality in these men. So, it is not likely that caffeine is the issue.

So what is the issue among those men who drink colas in excess? Well, the same issue as those who drink almost anything in excess—they have unhealthier lifestyles than those who consume in moderation. More burgers, more smoking, more alcohol, and fatter.

So, does drinking cola make men infertile? I doubt it, as the average sperm counts in men from all different levels of cola intake in the study were all normal by established fertility standards. Plus, fertility was not actually studied in these men, only a single semen sample. And even a good man can have a bad day.

There is a deeper truth running through this though. And you have heard this from me before. To be the best that you can be reproductively (and in life), do all things in moderation and treat your body like a temple.

Patients can handle the truth...try them.

How would you react to a doctor who, instead of explaining the entirety of your medical options, simply said “trust me, this is the right choice.” Maybe that style of “care” worked a generation or two back, but today’s patients have access to any piece of medical information that their doctors do. Patients want to know as much as they can so they can make the best choices for themselves or their loved ones.

Why do I bring this up? Well, because I got a call the other day from a patient who was seeking for more information about his options for fatherhood after vasectomy. He had an older vasectomy, 25 years or so, and a wife who was 40 years old. He met with two doctors in other cities and asked them about vasectomy reversal and sperm retrieval with assisted reproduction. Both of these are options for vasectomized men. Both urologists said, “forget it!” The patient was stunned. He just wanted information to help him decide how he was going to approach the family building issue. Instead, he received no information, and, without asking, he was told what he should do. Forget it.

Two things are still true after visiting these two doctors:

1. He still wants a family.

2. He knows no more than he did before about how to achieve this goal.

Now what is wrong with this picture? Patients do not necessarily depend on doctors for information; they can get that almost anywhere on the Web. However, they do depend on doctors for wisdom and knowledge–the interpretation of information as it applies to the patient. I believe that life is a journey, one that involves many forks in many roads. Some are chosen and others are not. In the end, there is a story, a memory, of the path that was taken. Making decisions about medical care is also part of the journey that we all take. As doctors, we are obliged to use our experience and wisdom to help patients face decisions and choices that affect their health, their budgets and often their very lives. A patient’s “trust” is earned and is not gifted to doctors. Be their trusted consultant, someone who they can rely on for good solid information and wisdom. Unlike what Col. Nathan R. Jessep says in A Few Good Men, patients can handle the truth.

In my discussion with this patient, I gave him the facts about each choice. Older vasectomies are less successful at being reversed than younger ones, but the results are still very respectable in the right hands. His wife’s age could influence his decision either way, especially if she has limited time left to have children. Pregnancies after reversals of older vasectomies occur later than those after younger vasectomies. Sperm retrieval and assisted reproduction

can be a faster, albeit more expensive, way to conceive. If more than one child is desired, then assisted reproduction can get very expensive compared to vasectomy reversal. No value judgments, just the facts. There are lots of ways to build families and patients armed with good informaton can decide which way is best for them.

It has always been my philosophy as a physician and surgeon to walk the walk with the patient. Even stepping into their shoes and taking the journey with them. This makes good sense in situations in which outcomes cannot be guaranteed. Sure, I will offer an opinion if they ask, “what would you do?” However, in my brief stay on this good earth, I have found that the educated consumer always makes the best choices.

How damaged is your genetic sheet metal?

Imaging parking your car at home after work and all the nicks and scratches are removed while you sleep, before heading to work the next day. All shiny and new, polished even, while you sleep. Believe it or not, this is normally what happens to your genes and chromosomes on a minute-to-minute basis. DNA mismatch repair is a constant and vigilant process, occurring in all cells of the body. Why the biologic vigilance?  Well, It keeps us whole, healthy and cancer free.

About 11 years ago, we published a paper showing for the first time that infertile men can’t repair the errors normally encountered in their DNA as well as normal men. This was startling news in part because it implied that infertile men may be more likely to develop other problems later in life, including cancer. Why cancer? Because the development of cancer has been associated with the inability to normally repair the frequent daily errors that occur to one’s DNA as the body’s cells divide and renew.

Today, however, we know much more. We know that testis cancer is 3-fold more likely to occur in previously infertile men than in fertile men as they age. And our latest research has shown that prostate cancer, thought to be a disease exclusive to older men, occurs more seriously and more commonly in previously infertile men.

So what does this mean? Is male infertility the first sign of a larger problem in our species? It is the ultimate medical problem of a species trying to reproduce?  Well, honestly it isn’t entirely clear. However, to me it indicates that male infertility should certainly be considered an insurable and real medical condition that should be taken as seriously as a heart attack. Even more worrisome is the issue of whether the use of sperm from severely infertile men is putting their offspring at even higher risk of medical issues than that experienced by their fathers.

So do not ignore the infertility issue when it strikes and get that male partner evaluated by a specialist. Teach him to perform testicular self-examination, a simple maneuver performed once monthly in the shower that has far more potential to extend his life than even exercising or weight control. Educate him about prostate cancer so that he does not ignore the powerful screening tools available to find it early. The age of innocence is over. The warning signs are now clear; get men the care that they deserve.

A stem cell in a dish is worth a hundred different therapies.

Not all stem cells are alike. News to you? Maybe not, but it has hit researchers pretty hard over the past several weeks. As you may have garnered from prior essays on this blog, stem cells are potentially capable of morphing into many different tissues, such nerves, heart or liver, and are the next wave in medical therapy for all kinds of diseases affecting both the young and the old. The medical treatment that they will bring to the table is called “personalized, cell based therapy.”

One huge problem is that the best kind of stem cell, the one that can do the most, is created from embryos. The embryonic stem cell has many “issues” though: derived from embryos, retrieval ethics, not patient specific, created by cloning, inefficient to produce and the like. Because of this, research has focused on alternatives like transformed adult stem cells or our very own untransformed testicular stem cells. The news today concerns the quality of adult-type stem cells that are “reprogrammed” and transformed into embryonic-like stem cells, also termed induced pluripotency stem (iPS) cells.

Well, there appear to be growing pains for the iPS cell, an embryonic stem cell alternative. Developed in 2006 from adult skin cells, researchers genetically manipulated a specialized adult cell, transforming it back to an unspecialized state. Since then, hundreds of labs have leaped into the burgeoning adult stem cell field.

The ideal stem cell is like a blank slate. It is capable of becoming any other tissue, and is immortal. True embryonic stem cells are like this, but, according to several recent publications, many iPS cell lines are not really blank slates. Also, it appears that nerve and blood cells made from iPS cells grow poorly and age quickly and may even “remember” what cell from whence they came. Some even conclude that iPS cells may not even be considered a practical choice for cell-based therapy down the line.

The realization that iPS cells are not exactly like the gold standard embryonic stem cells has slowed the field down a bit, but it is an important observation. Like people or even wine, stem cells are a bit different from one another, each with their own personality, temperament and potential. Some do this better than that, and others do that better than this. It suggests that stem cell-based therapy may eventually involve tapping into a mixture of different stem cells to cure the problem. Now that’s an old fashioned idea: a little of this and a little of that…