What did you find? I asked Jeff as he walked into the doctors’ lounge.
Not much. Just looked like guts to me, Jeff replied. I thought cancer or a ruptured appendix might explain the pain, he added, but as far as I could tell there was nothing in that boy’s belly but normal bowel. Maybe you’ll find something in the bone marrow--all I know for sure is that he is sicker than a dog that’s been wormed.
Our patient, J. J. Walker, had recently been hospitalized because of excruciating abdominal pain. Jeff had just completed a laparotomy--a surgical exploration of the abdomen. He had made an incision from Mr. Walker’s navel to his pubis, then looked at the organs closely, feeling for any abnormalities in the bowels, liver, stomach, and spleen. But he had come up empty-handed. There was nothing apparent to the naked eye or the soft touch of the gloved hand to explain why Mr. Walker was in such pain. As a pathologist, I would have the job of hunting for clues in the bone marrow.
Jeff and I work at a hospital in Columbus, Ohio, but Mr. Walker’s story had begun over 200 miles away in a small town tucked away in the hollows of the foothills of the Appalachian Mountains. He had woken up three days earlier, on November 11, with a pain deep in his belly. It was a Sunday morning. For the next four hours he had remained at the commode, vomiting. Finally he asked his wife to take him to a nearby hospital in Shepherd, Ohio.
Providence Hospital is a small, old facility that serves one of the state’s most impoverished counties. The land there is tough and poor, and the people reflect their geography. They are craggy, stoic, and nearly unbreakable. I’m asked to visit the hospital from time to time, and the biggest tumors I’ve seen--some the size of a rat--come out of those hollows. When a man from a hollow yelps, I know he’s not crying wolf.
When Mr. Walker arrived in the emergency room, the laboratory technicians drew blood for standard tests and took a urine sample for a routine drug screen. The most common cause of intense abdominal pain in a 24-year-old man is acute appendicitis, and that was the working diagnosis until the test results came back.
Mr. Walker’s urine test was normal, showing no trace of drug use or infection. But his blood count was extremely low for all three kinds of blood cells: the red cells that carry oxygen, the white cells that fight infection, and the platelets that help blood clot. J. J. Walker had bad blood, but no one knew why. My colleague Ed Bains, a blood specialist, was called down to Shepherd from the hospital in Columbus where we work.
On Monday afternoon Ed examined Mr. Walker for the first time. Tall, angular, and a bit abrupt, Ed is like many hematologist-oncologists I have known who every day have to deliver to perfectly lovely people the perfectly awful news of blood disorders or cancer.
Mr. Walker’s belly was as taut as a drum--often a sign that the bowel is about to burst. Ed couldn’t tell what was going wrong, but he had a hunch. Belly pain and bad blood are common signs of lymphoma, a cancer of the white blood cells. The primary targets in patients with lymphoma are the lymph nodes--bits of tissue scattered about the body where white blood cells and other immune cells exchange the signals that promote healthy immune function. Attacks on the numerous lymph nodes that line the bowel could have been the source of Mr. Walker’s belly pain. In addition, renegade white blood cells could have been taking over Mr. Walker’s bone marrow, disturbing the normal production of blood cells. The only way to know for sure would be to look for abnormalities in Mr. Walker’s bowel and bone marrow.
Ed explained the need for exploratory surgery to Mr. Walker and his wife and recommended that Mr. Walker be transferred to our hospital in Columbus. A CT scanner there could detect any enlarged lymph nodes. After a four-hour ambulance ride through the hills and onto the flats of central Ohio, Mr. Walker arrived at our hospital on Monday evening.
The next day’s efforts were dead ends. Nothing showed up on the CT scan, and Jeff found nothing wrong in Mr. Walker’s belly. Ed then extracted a bit of Mr. Walker’s bone marrow for me to examine.
On Wednesday morning I slid the sample under the microscope and twisted the knob to bring the blood cells into focus. Buried so deep within us, the marrow is the very soul of the blood, and what cruel and extraordinary tales it can tell. But Mr. Walker’s marrow was strangely silent. His red blood cells were a bit swollen, or megaloblastic, and stippled with tiny clumps of hemoglobin and iron. Those scattered clumps, called basophilic stippling, are a very general sign that the red blood cells aren’t making hemoglobin properly. It occurs in disorders as diverse as anemia, malaria, and vitamin deficiencies.
But I saw nothing that could explain why Mr. Walker’s bone marrow wasn’t releasing normal amounts of blood cells. The proportion of red blood cells, white blood cells, and cells that become platelets was just about right. There was no sign of murderously multiplying cancer cells. So far I had turned up nothing in Mr. Walker’s bone marrow to link the blood and the belly.
I called Ed. Close, but no cigar. Just some fat red blood cells and some stippling. What do you think?
Well, I’ll check for a vitamin deficiency, but I don’t think it means much.
On Friday, Mr. Walker’s fifth day in the hospital, his condition took a turn for the worse. His feet began to tingle. By the next Wednesday he couldn’t move his toes, and by the following Friday his lower legs were nearly paralyzed. Now we had three conditions--abdominal pain, failing blood, and nerve damage--and no causes. After nearly two weeks of work, Ed and I were going nowhere. Mr. Walker was receiving fluids and other supportive care, but he was slipping from our grasp. In desperation I went up to Mr. Walker’s ward and carefully reviewed his chart.
Until he was admitted to the hospital, J. J. Walker had been in perfect health. He came in for belly pain with no visible cause. His blood cell counts were low, but his bone marrow was normal. Now, two weeks after he was admitted, his muscles and nerves were beginning to fail.
Clearly something was knocking out Mr. Walker’s gut, blood, and nerves that we couldn’t see with our eyes or a microscope. It had to be something even smaller than a single cell. Most likely it was a molecule-- perhaps some kind of poison.
Mr. Walker’s drug test had been negative, but it had screened only for the most commonly abused drugs. There are thousands upon thousands of poisons. It could be a heavy metal. It could be a snake venom. It could be an overdose of a prescription drug or an over-the-counter medication. It could be toxic fumes from a manufacturing plant. Each poison requires a specific test to detect it. Unless I had a hunch, I would be ordering tests in the dark.
Then, as I was closing the chart, I noticed Mr. Walker’s occupation: plumber. Could this be lead poisoning? If Mr. Walker had welded pipes with lead solder, he might have accidentally inhaled lead as it vaporized.
I called Ed. What about lead poisoning? I asked. That would explain the abdominal pain, the problems in the blood, and even the nerve damage.
Good idea, but lead would cause paralysis without tingling. It only affects the nerves that supply muscle, not the sensory nerves.
I know, but it’s still a possibility.
Okay. I’ll order a screen for heavy metals.
That screen would test for metals with high atomic mass, such as lead, mercury, and platinum. A device called an atomic absorption spectrometer detects the presence of heavy metals in a patient’s urine sample. Each metal absorbs at its own particular wavelength--254 nanometers for mercury, 283 for lead, and so on. By bombarding the sample with radiation and observing which wavelengths were being absorbed, we could tell whether a heavy metal was poisoning Mr. Walker.
Two days later I reviewed the results. They were positive, but not for what I thought. What was killing Mr. Walker wasn’t lead but something far more poisonous. It was arsenic, a molecule so reactive that it can bind to nearly every cell in the body, with protean and devastating effects.
In its most common form, arsenic is nearly tasteless, and once ingested, it quickly produces intense abdominal pain. First the gut absorbs the poison. Then the arsenic enters the bloodstream and is carried from head to toe and to every organ in between. If enough poison is ingested, arsenic kills instantly. If not, the poisoning gradually disrupts the body’s normal functions. Blood cell production in the bone marrow will falter, and two to three weeks after the initial poisoning, the tingling and paralysis of the hands and feet begin.
I called Ed with the news.
We finally nailed it, he exclaimed. We’ve finally found something to unite what’s happening in Mr. Walker’s gut, blood, and nerves.
Now we’ve got to find out how it happened.
This time Ed had a few hunches. Mr. Walker might have been exposed to arsenic accidentally, possibly at work. He might even have attempted suicide. Or he might have been intentionally poisoned.
While Ed headed off to question Mr. Walker, I returned to the lab and began my own investigation. Arsenic kills by attaching to sulfhydryl groups, highly reactive molecules that are required for the function of many energy-producing enzymes. Because hair and nails are rich in sulfhydryl groups and grow at known rates, I would be able to tell when Mr. Walker was poisoned by locating exactly where arsenic showed up on a shaft of his hair.
When I asked Ed to get a lock of Mr. Walker’s hair, he learned that Mr. Walker’s wife had recently cut her husband’s hair and nails very short. I then asked Ed to get a sample of what was left and to mark clearly which end had been closest to the head.
Ed sent me an inch-long sample, bound with a red rubber band at one end. Hair grows about .37 millimeters a day, so the sample would provide a record of 60 days’ growth. I divided the shaft into portions 3 millimeters long, each portion reflecting about one week’s growth. Then I began the tests for arsenic.
I had a feeling some things in this case didn’t add up.
When J. J. Walker arrived at the ER in Shepherd, his blood cell count was already extremely low. If the poisoning was recent, that shouldn’t have happened for another day or two. What’s more, nerve damage showed up within 5 days, not the usual 14 to 21 days.
Two days later, on November 23, my analysis was complete. J. J. Walker had had a whopping dose of arsenic about two weeks earlier. That would correspond with his admission to the hospital on November 11. A week before that, he had had a little dose of arsenic. And three weeks earlier, sometime in the last week of October, Mr. Walker had had another big dose. I called Ed and told him what I’d found.
When Ed explained the results to Mr. Walker, he learned that Mr. Walker had had a bout of flu around Halloween--about three weeks earlier.
Ed asked investigators from the Occupational Safety and Health Administration to inspect Mr. Walker’s home and workplaces, but no trace of arsenic was found. Ed even had Mr. Walker evaluated by a psychiatrist, who informed us that he wasn’t suicidal. Then the Bureau of Criminal Investigation set to work on the case. They began by closely questioning Mr. Walker’s wife. But no arsenic was ever found and no admissions were made.
During the next two months, Mr. Walker got worse, despite continuous treatment with a drug that binds up arsenic. The paralysis crept up his legs toward his chest until he needed a respirator to breathe. Then slowly, a cell at a time it seemed, the nerves began to fire again and the paralysis receded like a poisonous tide.
Over the course of his hospitalization, Mr. Walker learned that his wife was having an affair with his best friend. The Walkers divorced, and she moved in with the friend. Finally, months after he was first admitted, he hobbled out of the hospital and headed home alone, a cane in either hand.
J. J. Walker still lives in Shepherd, just about 100 yards from the Ohio River. Occasionally his mother lays a warm mustard poultice across his legs, hoping to draw out the poison. On a good day he says he can make it down to the river and back in about an hour. With time the nerves in his legs are recovering, but I doubt they will ever be the same. And I suspect that even the poultice of time cannot erase the scars on J. J. Walker’s heart.
