New technologies promise to help us discover more cancers in time to treat them. But they also risk ushering even the well into an all-encompassing kingdom of the ill.

"In the summer of 2005, I met a woman, Laura M., whose life had been upended by cancer. She wasn't sick: What haunted her was anxiety about cancer in her future.

Three years earlier, Laura had been diagnosed with a primary tumor in her breast that was small and localized. She had surgery, radiation and chemotherapy -- the standard protocol -- and then came to see me, an oncologist, to help manage her future care. I suggested doing nothing: She had likely been cured.

But in the wake of her treatment, she became obsessed by the possibility of a relapse. She scoured her family history and discovered a distant aunt who had died of breast cancer at age seventy. Her own mother had died at a young age from a car accident, but Laura became convinced that had her mother lived, she would have been diagnosed with breast cancer.

Laura's visits to the clinic were shadowed by a sense of doom. She often brought sheaves of printouts from the internet, detailing "occult metastases" in patients who, like her, were thought to be at low risk. She repeatedly asked me to confirm that she had been given the most aggressive possible chemotherapy. We checked her for genetic susceptibilities but found none. Nonetheless, she asked if she and her daughter could undergo "the most intensive form of cancer surveillance" to detect early abnormalities.

In recent weeks, panic over the latest turn in a contagion has been spreading like, well, a contagion. Yet even in today's pandemic world, cancer holds a special place in the anxious imagination. Its advance is often stealthy, its prognosis potentially frightening and its treatments damaging and life-altering. Once its shadow falls on us, we fear it will never go away -- that there will always be another relapse and a return to harsh therapies that subsume our lives.

Cancer is appropriately perceived as a disease of risk: genetic or heritable risks, lifestyle risks and the unknown risks of chance. Modern medical science has begun to quantify these hazards for patients even before they get cancer. The new modes of detection improve or expand on the old screening methods, of which colonoscopies and pap smears, followed at a distance by mammography, are among the only few that have really led to significant drops in mortality. (Cancer prevention is another matter: Campaigns against smoking and a vaccine for Human Papilloma Virus have both been remarkably effective).

The hope is for the new, more powerful means of pre-screening and early detection to identify a wider array of cancers at stages when tumors can be surgically removed and cured, even avoiding chemotherapy in some cases.

But the state of the art in cancer surveillance and detection also risks unleashing a pervasive anxiety -- a state of "feeling under siege from the future," as one patient describes it. A strange new term, "previvor," has emerged to designate a person who has not yet experienced an illness she is predisposed to have. For Laura M., survivorship of one breast cancer turned overnight, it seemed, to previvorship of another.

The borders of "Cancerland" -- a term the oncologist David Scadden coined with the title of his 2018 memoir -- begin to feel all-encompassing. In the past, entry was reserved for those with a diagnosis of cancer. Today everyone, in one way or another, slowly becomes a citizen.

Two kinds of technology are radically altering the landscape of cancer risk and screening. The first involves genetic surveillance -- the attempt to quantify an individual's inherited predisposition for cancer. The second is physiological surveillance, which seeks to detect chemical markers of incipient cancers in blood. These techniques hold out the hope of making minimally invasive, life-saving therapies available to people who might not otherwise have known of their cancers until much later.

But they are not yet as precise as we might hope, and they come at a cost: By pulling increasing numbers of people into the domain of surveillance and screening, they encourage people without current cancer, but with the prospect of future cancer, to become citizens or permanent residents of Cancerland. Settling into this domain can be life-distorting: As the shadow of future illness dilates and magnifies, so too do the shadows of anxiety and dread.

For decades, perhaps centuries, we have known of families in which some form of cancer (usually breast or pancreatic) manifests in multiple people across generations. Until recently, our capacity to identify the culprit genes -- or, more actionably, to identify the members of the family who carried the heightened risk -- was limited to inherited single-gene mutations. These included mutations in such genes as BRCA1, BRCA2 and MLH1 that, if inherited from parents, increase the likelihood of breast, colon and other cancers severalfold.

But many human traits do not track with single-gene mutations. Height, for example, is highly heritable -- we know that tall parents tend to produce tall children, and shorter parents bear shorter children -- but early attempts to pin this trait down to single-gene variations or mutations revealed only a smattering of candidates. Geneticists described the conundrum as the "missing heritability" of height. We could infer from the pattern of inheritance that height-determining genes must exist in the human genome, but their precise identity and number remained unknown.

By similar logic, the inherited risk of cancer might be carried by mutations or variations in not one but multiple genes, which act together to increase risk. Today's computational technology can help with this problem. Algorithms can scan millions of fully sequenced human genomes and dissect how variations in thousands of genes, each exerting a small effect, might ultimately add up to the heightened risk of an illness.

One machine-learning algorithm has learned to predict human height as the consequence of variations in a thousand-odd genes. (Take a moment to digest this startling fact: Such an algorithm might soon predict your actual height, or the future height of your unborn child, based on your genetic sequence alone.) Another program can predict the risk of future cardiovascular disease; yet another, the future risk of obesity. Notably, some of these genetic markers are independent of previously known risk factors, such as cholesterol levels in the case of cardiovascular disease.

Such algorithms might soon identify those of us at highest genetic risk for future cancers. They may even be able to account for the role that chance and the environment play in the development of many cancers, including the ones that run in families. It is not hard to imagine a world in which we are sorted into those who do and those who do not require screening for particular cancers based on both inherited risk and potential exposures.

Other machines, meanwhile, would seek to identify chemical signals of current cancer in our blood or other organs. Called a liquid biopsy, or liquid surveillance, such procedures look for minuscule amounts of the products that cancer cells shed -- shards of DNA, proteins and other substances -- into the blood or other circulating tissues. By scouring the body to find ovarian, lung and prostate cancers, for instance, before these become clinically manifest, we might enable earlier or better treatment.

Liquid biopsies will further expand the pool of people who must be surveyed and screened for cancer. They may also heighten the risk of overdiagnosis. What if someone is found to carry a liquid marker for ovarian cancer, say, but the cancer never takes root in her body? Cancer cells, we now know, can exist in a body, or a site within the body, without becoming manifest as clinical disease or a detectable metastasis. Most likely, this is because the "soil" of a particular organ does not allow the "seed" of a cancer to sprout. And some of the markers may turn out to overlap with benign diseases, thereby increasing the risk of false positive results.

Perhaps most concerning, the markers that liquid biopsies identify can tell us that a cancer may be growing somewhere in the body, but they usually don't tell us where, nor do they reveal the stage of the cancer's development (although these puzzles are being tackled). A patient with troubling markers on a liquid biopsy would likely then undergo a raft of screenings, some of them invasive, in search of a cancer that might not actually need to be treated or that would otherwise make itself known in good time. Some liquid biopsy start-up companies, daunted by these complexities, have begun to focus on the early detection of relapses -- a much more tractable challenge.

The promise of detecting cancer in its earliest stages, together with that of identifying those at genetic risk for future cancer, is powerfully alluring. And yet the prospect of farther-reaching surveillance for this elusive long-term illness also warrants caution. In the 1950s, the sociologist Erving Goffman coined the term "total institution" for a community in which "a great number of similarly situated people, cut off from the wider community for a considerable time, together lead an enclosed, formally administered round of life."

Total institutions, such as mental hospitals, prisons and even boarding schools, have rituals of entry and exit. They inculcate belonging. They invent their own vocabulary and codes of behavior; they have an internal logic, impenetrable to others. They encourage surveillance and create anxiety: Members are united by a common sense of purpose, by the feeling of being chosen or marked. Those who are expelled may feel a sense of betrayal, while those who remain can be consumed by the guilt of survivorship.

In this new era of cancer treatment, I wonder whether we unwittingly, but insidiously, intensify the totality of the "cancer institution" for patients. When I once asked a woman with a rare sarcoma about her life outside the hospital, she observed, "I am in the hospital even when I am outside the hospital."

People like Laura M. certainly experience a "cancer world" in that way. They are in either treatment, remission, surveillance, maintenance or re-surveillance. Mavens of early detection are working on algorithms that will pick up cancerous lesions on patients' imaging results and classify them as malignant, using criteria that seem to defy even the most acute human eye. The German computer scientist Sebastian Thrun imagines a world in which even the daily instruments of our normal lives morph into weapons of diagnostic surveillance -- a bathtub that scans your body to detect abnormal masses that might require investigation; a mirror that could check your body for precancerous moles; a computer program that (with your consent) would scour your Instagram or Facebook page while you slept at night, evaluating changes in your photographs that might signal signs of cancer.

In the most optimistic scenario of such a future -- one in which every person had to be genetically annotated, subjected to surveillance and treated if a tumor was found -- many lives would be saved by early diagnosis, but the costs would be astronomical. Issues of over-diagnosis and overtreatment would have to be addressed. We would have to devise careful guidelines about when not to act and whom not to treat.

Laura M.'s experience presages a strange new world of constant diagnostic surveillance; of dealing with the anxiety of relapse and maintenance; of that peculiar desolation of the shuttle from clinical trial to clinical trial, and from hospital to hospital, as she tries to keep one step ahead in the chess game against cancer; and of watching doctors pit their will, wit and imagination against a formidable enemy that keeps changing its shape.

This world has its own internal vocabulary. A "haircut party" is a celebration thrown in honor of a person about to enter the cancer world as a sign of solidarity, even if the patient is spared hair-loss-inducing chemo. "No Exit chemo," as a patient of mine put it, describes the fact that a unique personalized chemo regimen for a patient produces unique toxicities, like the personal hell assigned in Sartre's play.

"A world in which cancer is normalized as a manageable chronic condition would be a wonderful thing," medical historian Steven Shapin wrote in 2010. "But a risk-factor world in which we all think of ourselves as precancerous would not," he continued. "It might decrease the incidence of some forms of malignancy while hugely increasing the numbers of healthy people under medical treatment. It would be a strange victory in which the price to be paid for checking the spread of cancer through the body is its uncontrolled spread through the culture."

One could argue that routine surveillance for other formerly fatal conditions has become woven into our lives with little or no ill consequence: No scientist bemoans the cultural and medical surveillance of cardiac disease, for example. We do not suffer over much from automobile safety having dramatically altered our driving habits, either. Yet perhaps precisely because cancer encompasses so many different cancers, the cultural shift feels totalizing, unstoppable.

The borders of Cancerland are changing and, with them, how Americans collectively conceive of illness and health. What shape will we give the surveillance of cancer in the years ahead? Will it be a great civil project, in which all Americans partake -- a project of justice? Or will the most vulnerable among us see their health insurance curtailed as we increase genomic surveillance and curtail privacy laws, all while the elites bemoan the inability of "disadvantaged populations" to curtail their smoking or overeating? Will we allow anxiety to dominate our cultural attitude toward risk, or will we find a balance between curative therapies and the condition of being mortal?

To date, Laura M. has not suffered from a relapse of breast cancer. Nor, fortunately, has she had a new cancer anywhere in her body. But strange victory over her body has not spared her mind. She remains haunted by the future prospect of illness.

The novelist and critic Susan Sontag once wrote of a passport between the kingdom of the well and the kingdom of the ill, imagining a bidirectional passage: Men and women might pass into illness, but some would return to wellness. In inventing cancer's new surveillance culture, I fear that we have closed the borders of the kingdoms. I fear that we now possess one-way passports into the realm of illness. What we will find there is up to us." [1]

1. REVIEW --- Will We All Soon Live in Cancerland? --- New technologies promise to help us discover more cancers in time to treat them. But they also risk ushering even the well into an all-encompassing kingdom of the ill.
Mukherjee, Siddhartha. Wall Street Journal, Eastern edition; New York, N.Y. [New York, N.Y]. 18 Dec 2021: C.1.