Bone cancer reunites identical twin brothers separated by their careers and thousands of kilometres. The prognosis: so far so good
My brother, Gene Berthelsen, was born at 5:13 pm on October 4, 1937. I was born 20 minutes later at 5:33, although it could have been the other way round. We can’t be sure.
That is because when our mother brought us home from what was then Siskiyou County Hospital in Yreka, California, and bathed us for the first time, she took off the hospital-supplied identification bracelets. Once finished, she told us decades later, she discovered we were so identical that she couldn't figure out who was who. One of us arbitrarily became Gene and the other John, she said, which was disconcerting.
Even though we were separated only by minutes, as we grew up in the remote mountain town of Etna, near the Oregon border, we developed an older brother-younger brother relationship—he steadier and more responsible, I more rebellious and immature. He has lived his life in California, I have spent much of mine in Asia. He is also one of northern California's most prominent traditional jazz musicians. I play CDs on the stereo.
We are monozygotic, or mirror twins. I am left-handed, he is right-handed, a sign that we originated from the same ovum. Because we have suffered almost exactly the same diseases at nearly identical times, when he was stricken with bone marrow cancer last year I was filled with dread. The multiple myeloma he contracted became a foe we both would fight. Our remarkable similarity, we hope, appears to be a key to prolonging my brother's life. This is thus both a story of our unique advantage in battling cancer and the very real danger that what happens to one could happen to the other. It is a story of hope and pain and depression. Since I live on one side of the planet, he on the other, the fact that we share the same DNA has brought us into more intimate contact with each other than we have known for decades.
In the face of vastly differing diets, climates and lifestyles, our body weight has usually been within a pound of each other. When we are in the same country, people often mistake us for each other. Despite the fact that our careers have separated us by a third of the globe, we remained largely identical for many years—enough so that once, rounding a corner and unexpectedly encountering a full-length mirror, he asked it what I was doing there. Even after we broke our noses in separate childhood accidents, his curved slightly to the right, mine slightly to the left—and we maintained the mirror image. We once had moles on opposing temples, although they have disappeared with age. On meeting us together for the first time, his oncologist, Dr Ginna G. Laport, did a double-take and asked which of us was which, despite the fact that at that point he had lost most of his hair and I am bearded.
In February, I flew from Hong Kong, where I live, to the United States to donate adult stem cells to be injected into him in an attempt to restart his bone marrow production and recreate my immune system in his body. Interestingly, it is also expected to give him any allergies I might have acquired over the years. Thus, whatever physical divergences we have undergone over almost seven decades and wide geographic separation are about to end. Because of the transplant, we are about to become one again.
The story began on May 27, 2005 when, after complaining for several weeks of what he thought was a severe charley horse from a skiing trip, my brother received a chilling diagnosis: multiple myeloma, or cancer of the plasma cells. As the cancer grows, it tends to clump up within the marrow and eat away the bone. He required the immediate insertion of a titanium rod in his left femur, the major bone in his thigh, within hours. If the operation hadn't taken place, his doctors said, the bone could have disintegrated in an instant simply from walking. Later, cancer also would be discovered in the marrow of his pelvis and rib.
Until fairly recently, a diagnosis of multiple myeloma was the equivalent of a death sentence. Even today the survival rate for those afflicted with the disease is only three to four years, according to the American Society of Hematology. That was enough to send my own blood racing, not only out of concern for my lifelong Doppelganger, but because our medical histories are so similar. In 2002, for instance, when I entered hospital for a triple bypass operation to clear blocked arteries, he was operated on just three weeks later for the same problem. Could cancer be an inevitable part of my future?
Dr Laport, an oncologist at Stanford University Medical Center Bone Marrow Transplantation Program, who moved with her parents from the Philippines to the United States when she was a year old, says nobody really knows today how much of a role genetics plays.
Certainly there is an obvious genetic predisposition among siblings, especially among those who share identical DNA. But, Dr Laport said, unidentified environmental factors play an equally vital role, an irony for us since my brother spent his entire life in the relatively clean surroundings of northern California while I have spent much of the last three decades in several environmentally degraded Asian countries as a newspaper and magazine correspondent and editor.
Fortunately, as a career official in Sacramento with the California Department of Transportation, my brother is a member of Kaiser Permanente, one of the biggest health maintenance insurance plans in the United States. Despite controversies over limitations of care to some patients in other areas, Kaiser was willing to pour vast and expensive resources into his care.
For several months, Kaiser doctors sought to control his cancer through chemotherapy, with mixed results. Then, in December, they were elated to discover that he had a twin brother whose DNA was identical. Unfortunately, that brother—me—was 7,000 miles away. Exhaustive physical examinations ensued in Hong Kong, including the drawing of 12 vials of blood to test for such afflictions as AIDS, syphilis and others. I emerged clean and ready for California.
Until relatively recently, close siblings and those who shared identical DNA underwent bone marrow transplants rather than stem cell transplants. Fortunately, that is no longer necessary. Bone marrow donations involve excruciating pain. The donor is anesthetized while holes are drilled in the back of the pelvic saddle for the extraction of marrow. That pain has largely been eliminated through the substitution of transplanted stem cells for bone marrow.
The common misperception is that stem cells are only found in the nuclei of human ova. The stem cells found in the human ovum are embryonic stem cells, which are even more immature and less differentiated than hematopoietic stem cells, which promote the formation of blood cells. They have provoked a bitter fight between pro- and anti-abortion forces in the United States, with anti-abortion forces claiming the harvesting of stem cells from unused ova are the equivalent of murdering unborn children. In fact, hematopoetic stem cells are found in the bone marrow of all humans.
Over the past 15 years, doctors have discovered that they can increase the production of immature hematopoietic cells by the injection of a hormone called granulocyte colony stimulating factor, known commercially as Neupogen.
If no independent donor can be found, cancer patients donate their own stem cells, which can be manipulated and processed to remove cancer cells via various methods and then transplanted back into the patient. But, according to Stanford Blood and Bone Marrow Center Nurse Adele Ullner, it is difficult to remove all the cancer cells from a stricken patient's cells. Having an independent donor with identical (but cancer-free) DNA is far preferable and gives the patient a far better chance for longer remission.
They also have a relatively cheap donor. Finding an independent donor with similar DNA costs about $300,000, about triple the cost of that from an identical twin. The cost for the remainder of his oncological care, including the removal and replacement of his femur, probably ran to another $100,000, an illustration of why medical costs have soared out of control in the United States. This is an ethical dilemma. Should doctors save a 68-year-old retiree at that cost when simple vaccines and clean water could save thousands of third-world babies for the same amount? Maybe not. But then again, I don't want my brother to die.
Our medical situation is certainly unusual, although we are not particularly rare, since about four of each 1,000 live births result in identical twins, a pattern that seems to have held steady across different ethnic groups for ages. But Stanford's cancer program, Ullner said, has been doing marrow transplants for 16 years. To her knowledge, this is the first time an identical twin has been found as a donor.
Neupogen injections to stimulate stem cell production are no picnic. Although often they are generally painless, at odd times they involve pain so acute, Ullner said, that some receiving the shots call the hospital in the belief that they are having heart attacks.
These pains strike at odd times. For me, I was lying in bed watching television. I got up momentarily to discover that every single heartbeat was sending what seemed to be a pulsating electric shock through my body. I was reminded of a time when I was a child on our father's dairy farm and on a dare I touched an electrified fence. Painkillers like Vicodin help, but there are times when even Vicodin doesn't slow those electric shocks. One possible side effect is an enlarged spleen. (Indeed, those injected with Neupogen are warned not to fly for at least three days after the process is completed because one patient who didn't wait suffered a ruptured spleen while in the air. The 14-1/2 hour flight back to Hong Kong was no place to experiment to see if that was true.)
At the end of the five days comes ''apheresis,'' the harvesting of those stimulated cells. It is mainly boring: sitting in what vaguely resembles a dentist's chair, a tube in the left arm draining off blood, which then runs through a centrifuge that separates out the needed cells before the remainder of the blood is returned through the right wrist. About nine ounces of blood is outside one's body at any given time. The blood is chilled before being returned, which for some odd reason makes your nose itch. Over about four hours, the 4,750 cubic centimeters of blood in my body circulated through the centrifuge more than three times, passing 15,045 cc through the machine to produce what my brother needed.
I was surprised and shocked to discover how much the process had weakened me, however. On my first trip back to the elliptical trainer, where I usually exercise for an hour to burn off about 850 calories, I only lasted 15 minutes before I staggered off. It would be weeks back in Hong Kong before I found myself fully recovered.
The Stanford blood and bone marrow center itself, where the procedure took place, is a remarkable institution, which pays as much attention to your emotional and spiritual needs as their physical ones. Patients are provided with voluminous information about their afflictions, with complete descriptions of the emotional issues they face both prior to and after recovery, of sadness and depression two to three months after the transplant is completed. Extensive counseling services are provided both to recipients and donors. The facility itself is a tranquil, light-filled oasis, often filled with the sounds of artists playing quiet solos on either the piano or guitar—or a harp, which, given its heavenly connotations, might not be such a good idea.
Gene's doctors at the facility set out to destroy the cancer cells in his bone marrow, and along with them, the entire marrow itself as well as his immune system. In the early years of the program, cancer patients were sequestered in sterile rooms a la the famed ''boy in the bubble'' for a full 100 days, since any contact with any kind of virus would kill them, before regenerated bone marrow cells were injected back into their bodies.
That thankfully is no longer necessary. Massive doses of antibiotics allow patients to live relatively normal lives, although they must wear inhalators when outside. Nonetheless, it is a horrific process. For months, Gene underwent chemotherapy that cost him his hair and much of his vitality. He was required to drink three litres of water a day to flush out his liver and kidneys. If he didn't, the chemicals could destroy his vital organs.
Then, starting on March 15, the process of destroying the cancer cells accelerated drastically when a cocktail of virulent drugs was injected through a catheter in the center of the chest. The drug also delivered immediate side effects including nausea, vomiting, decreased appetite, diarrhea, fatigue, sores in the mouth and throat and decreased blood cell counts. Later possible side effects could include sterility, cataracts, hypothyroidism, scarring of the lungs and second malignancies.
High-dose therapy, as it is known, kills all cells that form newly reproducing elements of the body—not only bone marrow but hair, fingernails, semen, saliva and blood cells that reproduce to fight disease. It results in infertility because of the permanent damage to sperm cells in men and ova in women. Women treated before the age of 50 enter menopause. In other words, the medical process comes as close as possible to killing the patient in an effort to eradicate the cancer cells.
On March 23, the process continued with the transplant of my DNA into my brother's body to seek to re-create his bone marrow and his immune system. The chemotherapy that he had undergone now made him dreadfully sick, ultimately requiring hospitalization for continuous vomiting and diarrhea as well as painful mouth and throat sores and other debilitating conditions. The toxicity of the chemotherapy was now so high that he required the constant injection of fluid through a catheter to keep the poisons from destroying his vital organs.
Would he make it? One could only hope. In the cold language of the disclosure statement of the Stanford University Medical Consent Form, if both my DNA and the cells he donated himself as a backup failed to grow, ''then this complication would be expected to result in death.
He ultimately grew so ill that the Stanford doctors became concerned that his body was rejecting my cells. He lost 26 pounds in two weeks, or nearly 15 percent of his body weight. But finally, on April 7, after virtually nonstop vomiting and diarrhea, his white blood cell count started to rise. ''Engraftment,'' as his doctors called it, had begun. My cells had been transplanted, prompting a weak joke from him that he had suddenly become left-handed, as I am.
On April 21, he was finally able to return to his Sacramento home, weak, debilitated and raspy-voiced but on the mend. Along with everything else, the chemotherapy had destroyed his ability to produce saliva, making him sound like he had aged 20 years in a matter of weeks. He said he looked more like Uncle Fester of the Munsters than Yul Brynner.
Now, however, he is recovering his old vitality—along with his hair, which oddly is coming back in different colors. He has regained 13 pounds, although he has continuing neuropathy—numbness in his hands and feet—and he is dizzy when he stands too quickly. But tests in mid-July showed that levels of IG(g) protein, an indication of his kidney' function in battling myeloma, had fallen to healthy levels, meaning he is now cancer-free.
Ultimately, the process, according to Dr Laport, should dramatically extend his time in remission, at which time other therapies should come into play.
On Sunday, April 30, two weeks after the final process was completed, Gene was able to return to the musical stage at a jazz festival in Jackson and once again pick up his cornet and front the Catsnjammer Jazz Band, as they have been called for nearly 30 years. He didn't play long, but he played. After all, in the 1920s, jazz cornetist Joe "King" Oliver wrote this song:
Hello central, give me doctor jazz
He's got the thing for me, I'll say he has
So when I'm in trouble and when I've got the blues
He's one who makes me put on both my dancin' shoes.
John Berthelsen (email@example.com) is the editor of the Asia Sentinel. This story appeared in slightly different form in the San Francisco Chronicle and the Standard of Hong Kong.