T h e  S i x t h             S  e  n  s e

Ryan McVay/Photodisc/Getty Images

How could the patient have seen and heard them when she was clinically dead?

by Allan J. Hamilton

Arizona Health Sciences Center, Harvard Medicine, (TUCSON) By any clinical measure Sarah was dead. Her body had cooled, her heart had stopped, her brain waves had disappeared. During her seventeen minutes as a corpse, a surgical team worked quickly yet carefully to seal off her brain aneurysm.

In a planned cardiac arrest, a cardiopulmonary bypass machine replaces the heart’s vital pumping function. Surgery for Sarah’s basilar aneurysm required blood flow to stop completely, however, so her surgeons cooled her brain to allow it to tolerate this cessation.

During Sarah’s suspended animation, a microphone picked up several murmured conversations. In one, the surgeon asked the perfusionist whether the bypass machine was ready to be restarted; the perfusionist replied that he needed to “blow” it first—to fire it up to ensure any bubbles in the system would clear. In another exchange, a nurse recounted her marriage proposal the night before: the posh restaurant, the oneand-a-half-carat diamond ring, the swain on bended knee, the waiter who tripped over him and fell into the wine case.

When the pump cleared, the perfusionist said, “Thar she blows, captain.” The bypass machine churned, and Sarah’s blood began flowing again. Her body was gently warmed, and her heart resumed beating. Within minutes, a normal, healthy brainwave pattern reappeared on the EEG. The operation had proceeded flawlessly.

After several hours in the intensive care unit, Sarah’s head cleared. When she sat up to greet her surgeon, she asked whether her aneurysm had blown. He reassured her that the surgery had been “textbook perfect.”

“Well, I thought I remembered hearing something ‘blow,’” Sarah said. “I thought someone said, ‘Thar she blows.’ Like in Moby Dick.”

Her surgeon paled. After explaining his conversation with the perfusionist, he asked whether she had remembered anything else. Not realizing the sheer impossibility of what she had just said, Sarah went on to describe the nurse’s proposal, recounting the anecdote nearly word for word, right down to the restaurant’s name, the diamond’s carat weight, and the waiter’s stumble and fall.

It was utterly impossible, from a biochemical, metabolic, or physiologic point of view, for Sarah to have created any memories during her moments of suspended animation. Her brain had been devoid of any discernible electrical activity. Yet she had stored and recalled not only accurate auditory memories, but visual ones as well. She was able to describe the perfusionist’s beard, the blonde tendril escaping from the cap of the newly betrothed nurse, and the bypass machine’s location in the operating suite—even though the unit had been wheeled in after she had been under general anesthesia for more than two hours.

I was one of many doctors and researchers who soon flocked to Scottsdale, Arizona, to interview Sarah. We pored over the records, listened to the audio track, and watched the video footage of the surgery. Sarah was the equivalent of a valuable archeological find, and we wanted to leave the site fully explored, yet undisturbed. Not only were OR personnel interviewed independent of one another, but they were not allowed contact with Sarah, who was interviewed and videotaped separately.

We began our inquiry with a vague, almost smug, scientific curiosity, confident we’d find an explanation for this mystery. But as rational explanations faded one by one, we began to wonder whether we had encountered something unique, wondrous even. Could we be looking at the neurophysiologic equivalent of the Holy Grail?

According to one theory, Sarah’s brain—and the conscious mind it produced—had traveled beyond its physical and physiological confines. A group of physics researchers posited another notion, as radical as the first: that the OR conversations had survived as discrete quanta of energy, available for later plucking as memories.

No matter how we sought to explain it, Sarah’s experience seemed to suggest that the mind, the essential repository of consciousness, could separate from the very brain that created it and live without neuronal support, like a light bulb illuminated without any source of power.

What, I wondered, should those of us in the medical field do with such unsettling disturbances, such seeming ripples of the supernatural? Ignore them? Or should we declare them simply to be a puzzling mixture of science and spirit? Can we not allow ourselves to entertain the possibility that the supernatural, the divine, and the magical may all underlie our physical world? Can we not admit that we yearn to glimpse the mystery of the spirit?

I’m reminded of a carved angel perched near the top of the spire of the Notre Dame Cathedral in Paris. Turned away from the cross just above her, she is shielding her eyes with her arm, as if fearful of being struck blind while witnessing the glory of God. Perhaps Sarah’s experience offers a glimpse into the mysteries of our minds, but one that upends our world of scientific convention and constraints.

Like the cautious angel, we must content ourselves with oblique glimpses and trust that as much as we can withstand has been revealed. We cannot grasp the mystery. Or measure it. Or map it. But maybe that has to suffice for now.

Allan J. Hamilton ’82 is a professor of neurosurgery and a clinical professor in the radiation oncology, psychology, and computer and electrical engineering departments at the Arizona Health Sciences Center in Tucson. This essay was excerpted and adapted from The Scalpel and the Soul: Encounters with Surgery, the Supernatural, and the Healing Power of Hope, by arrangement with Jeremy P. Tarcher, a member of Penguin Group (USA) Inc., ©2008. This article appeared in the Spring 2010 issue of Harvard Medicine.

Biomedicine


Early warning: Cancer cells contain high concentrations of repetitive stretches of RNA known as satellites (the dark stain indicated by an arrow in the bottom image), while healthy cells (top) do not.
Credit: Science/AAAS

Repetitive stretches of RNA are found in high concentrations in cancer cells

MIT Technology Review, January 19, 2011, by Emily Singer  —  Compared with their healthy cousins, cancer cells are a chaotic mess, often having extra chromosomes, abnormal shapes, and other odd attributes. Now scientists have discovered a strange feature that appears to be unique to cancer cells: long stretches of repetitive RNA, known as satellites. Preliminary research suggests that the satellites appear early in the development of cancer, a finding that may ultimately aid early detection.

“It’s a very interesting and provocative finding,” says Stuart Orkin, chairman of pediatric oncology at the Dana-Farber Cancer Institute, who was not involved in the research. “It suggests wholesale changes in gene expression in cancer cells that was previously unrecognized. It hints at how chromatin [the mass of DNA and proteins that make up chromosomes] and gene expression in cancer cells are deranged in a global fashion.”

David Ting, Daniel Haber, and collaborators at Massachusetts General Hospital discovered the markers by accident while Ting was studying RNA from tumor cells. The DNA that codes for genes is normally transcribed into RNA, which is then translated into proteins. Ting was puzzled by the appearance of RNA molecules whose sequence didn’t correspond to genes. He found that the sequences corresponded instead to satellites, stretches of repetitive DNA that are transcribed into RNA but never translated into proteins.

“We were surprised to find [the satellites] are expressed in abundant amounts in tumor tissue compared to normal tissue,” says Ting. Follow-up testing in both mouse and human cancer tissue revealed high levels of satellites in different types of tumors, including lung, kidney, ovarian, prostate, and pancreatic cancers.

“This is a fascinating finding because there is no precedent for finding a single class of [DNA] that is uniformly overexpressed in different types of cancer,” says Bert Vogelstein, professor of oncology and pathology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University. “It appears to be true in virtually every cancer they looked at.”

While scientists have known about the existence of satellite repeats in the genome for years—they make up about five percent of the genome—the role they play in healthy cells is still unclear. “For a long time, people have ignored it, thinking it was residual DNA,” says Ting. In fact, most software used to analyze DNA sequences is designed to eliminate these stretches from their analysis, he says.

Scientists do know that satellites are expressed during fetal development, and they are thought to help chromosomes to divide normally. That similarity between cancer cells and embryonic cells—both can proliferate extensively—may hint at the role satellites play in cancer. “Somehow cancer has found a way to go backwards, to hijack a program from early in development for malicious use,” says Ting.

However, researchers don’t yet know whether satellites play a central role in the development of cancer or merely reflect some other malignant process. It might be analogous to, for example, prostate-specific antigen (PSA), which is found in high levels in prostate-cancer cells but doesn’t play a role in cancer. Either way, they hope the repetitive sequences will provide a new biomarker for diagnosing cancer.

If scientists confirm that satellite expression is highly concentrated only in cancer cells in adult tissue, they may be able to diagnose cancer accurately from very small amounts of tissue, such as the cells collected during needle biopsies. Ting’s team has already done some initial testing on cells collected in needle biopsies of pancreatic cancer. With a fluorescent molecular probe designed to bind to the satellites, “you can see cancer cells light up, while non-cancer cells do not,” says Ting. Currently, pathologists analyze cells based mainly on their appearance under the microscope, and their assessment can vary widely.

Ting’s team also found high concentrations of satellites in a type of precancerous cell that precedes pancreatic cancer. “That implies satellites are turned on relatively early in cancer development,” says Ting. If so, he hopes they can be used to detect cancer early. “Now we are trying to get a sense of the landscape. For what percentage of other cancers does this phenomenon occur? It seems to be prevalent, but we don’t have numbers.”

Researchers say they were able to make this discovery in part because of the type of sequencer they used—one from Helicos Biosciences that reads single molecules of DNA and RNA allowed scientists to count the number of RNA molecules present in the samples. Most other sequencers on the market have to replicate the RNA or DNA molecules under study before sequencing them.

Ting says he hopes other scientists will start to look for satellites in their own samples. “We think this is an initial step towards a new area of research for cancer,” he says.