By Ian Halim

In 1979, Dr. Linda Laubenstein began seeing patients in New York City with a rare cancer called Kaposi’s sarcoma. Because the cancer was so rare, she knew there had to be an explanation for the growing cluster of cases with their telltale purple skin lesions.

Her first patient with Kaposi’s was a 33-year-old schoolteacher who had noticed raised purple lesions behind his ears. A biopsy of a skin lesion revealed the normally-rare cancer. The lesions spread and multiplied until he had 75 on his “head, neck, trunk, and arms.” At first, he responded to anti-cancer chemotherapy agents. Then his disease came roaring back. Four different chemotherapy agents failed to control the infection. 18 months after his first lesions had appeared, he died.

Laubenstein became known for her dedication to New Yorkers with Kaposi’s sarcoma. Other doctors hesitated, out of fear of the new infection, or out of prejudice. Laubenstein did not. She predicted a terrible epidemic. And Kaposi’s sarcoma came to be known as a manifestation of AIDS. But why do people with AIDS develop Kaposi’s sarcoma? The aim of this essay is to explain that, and to honor Laubenstein’s role in the early response to the crisis.

Laubenstein published papers on the new disease and developed new treatments. She made house calls. She invited patients to her home. After her untimely death in 1992, her colleague, Dr. Jeffrey Greene, described her as, “the ultimate AIDS physician.” The AIDS activist and writer Larry Kramer penned a play about the early days of the AIDS crisis in New York, The Normal Heart. The physician character was based on Laubenstein.

The key to why AIDS causes Kaposi’s sarcoma is a special group of cells known as T-cells. The human immunodeficiency virus – better known as HIV – attacks these cells. T-cells are white blood cells, and like other white blood cells, they are part of our immune system. It’s the job of T-cells to protect the human body against infectious diseases and cancers. So when HIV attacks these cells, it’s breaking down the immune system.

HIV causes AIDS, but HIV and AIDS are different. HIV is the virus. AIDS – the acquired immunodeficiency syndrome – is the disease caused by the virus. AIDS arises when HIV infects a person and replicates out of control, killing off that person’s T-cells. As the T-cell numbers drop, a key prong of the immune system gets knocked out, and opportunistic diseases—like Kaposi’s sarcoma with its purple lesions – emerge.

The T-cells are so crucial to the body’s immune system that clinicians use the T-cell count from a blood sample to rank the severity of AIDS. The fewer the T-cells in a sample, the weaker the immune system, and the more vulnerable the body becomes to infection. A healthy immune system would knock out opportunistic bacteria or viruses before an infection could take hold, but in a person with AIDS, there are too few T-cells to do this.

Through the 1980’s, Dr. Laubenstein and her colleague Dr. Jeffrey Greene saw first-hand how patients with AIDS suffered, often stricken with a kind of double-injury – first by the illness, and then by those who discriminated against them for having it. At the time, homophobia was even more widespread than it is today.

In 1982 and 1984, when questioned about AIDS, President Ronald Reagan’s White House Press Secretary Larry Speakes laughed, teased the reporter, and appeared to regard the questions as a joke. Laubenstein’s colleague and friend Jeffrey Greene later recalled that he was, “advised by many of my fellow physicians not to become known as an AIDS doctor.” He ignored the advice.

Greene took care of a man who had a case of AIDS pneumonia (another opportunistic infection) that seemed mild. He learned that his patient had a good job in the fashion industry. He expected him to recover.

But after getting a pink slip delivered to his hospital room, the man became depressed and soon died. Laubenstein blamed his death on the employer who had sent the pink slip. Greene and Laubenstein then teamed up and co-founded an organization called Multitasking in 1989, helping to find work for people with HIV.

Behind HIV and AIDS lies an intricate biology. The T-cells, whose destruction by HIV causes AIDS, are part of our adaptive immune system. This means that when our body encounters a new infectious agent like a virus or bacteria, the T-cells learn to recognize it. Each pathogen has a kind of unique three-dimensional key that acts as a kind of fingerprint, allowing the adaptive immune system to learn to recognize that specific pathogen. This key is known as an antigen. And once the body learns to recognize that antigen, it can defend against the virus, bacteria, or other infectious agent that has that unique antigen.

T-cells are an important part of this learned defense. A T-cell develops a specialized receptor akin to a lock or keyhole that matches the key-like antigen of a specific infectious agent. When a human cell is infected, the infected cell displays the key-like antigen of whatever has infected it. When a cell in the liver is infected with the hepatitis B virus, for instance, the infected cell displays a key-like antigen that is unique to the hepatitis B virus. That “key” projects from the infected cell’s surface, like a beacon.

If the body is already familiar with the infectious agent, the specially-trained T-cell receptor will interlock with the antigen, like two puzzle pieces snapping together, or like a keyhole fitting a key. It can then kill off the infected cell, helping control the progress of the infection.

This allows the body to stave off many infections. But HIV evades T-cells’ powers of surveillance by covering its antigen or “key” with sugar-like molecules–masking itself and making it harder to find. And HIV not only hides from T-cells, it also attacks them, infects them, and destroys them (as described earlier).

Once inside a T-cell, HIV hijacks the cellular machinery, using each T-cell to make more HIV virions. These virions then spill out, ready to attack and infect the next cell. Without treatment, HIV progressively destroys more and more T-cells, leaving our immune defense weakened and ripe for opportunistic diseases–like Kaposi’s.

In 1981, Laubenstein co-authored a case series describing eight men with Kaposi’s sarcoma – a cluster that already seemed too large to be random for such a normally-rare cancer. These eight cases were all men who had sex with men. Early on, Laubenstein and her co-authors suspected some form of sexual transmission – although they weren’t certain and also considered other possible explanations.

HIV isn’t just a disease that affects men who have sex with men, of course. In the years following these cases, it eventually became clear that HIV can be transmitted through vaginal sex, anal sex, or blood-to-blood transmission.

Bloodborne transmission includes infection by injecting drugs with a shared syringe. If someone who is infected with HIV injects drugs, the needle can become contaminated with residual virus from that person’s blood, making it a dangerous vector of infection for the next person who injects with it. Before the first commercial HIV test became available in 1985, those with bleeding disorders known as hemophilia, or who lost blood in surgery or needed transfusion for another reason, were also at risk of infection from blood transfusion with donor blood that sometimes harbored HIV.

In 1984, Linda Laubenstein co-organized a conference about AIDS and Kaposi’s sarcoma, and co-edited a volume of collected papers based upon that conference. She also helped develop one of the first therapies to treat Kaposi’s in patients with AIDS. That therapy was a cocktail of anti-cancer chemotherapy drugs more potent than any single drug on its own.

Kaposi’s sarcoma is a cancer, often occurring in people with AIDS, but it’s actually itself caused by a virus called human herpesvirus 8 (HHV8). Certain viruses—like HHV8—damage the cells they infect, and make those cells more prone to become cancers–-like Kaposi’s sarcoma. AIDS impairs the immune system’s ability both to control HHV8 and Kaposi’s sarcoma itself.

Today, a combination of different drugs targeting HIV can prevent or reverse the immune suppression found in AIDS, limiting viral replication, protecting our T-cells, and preventing Kaposi’s sarcoma before it appears. So the purple lesions that alarmed Laubenstein in 1979 are much rarer now in the United States. But not everyone is tested for HIV, has health insurance, or can manage taking medications regularly.

When Laubenstein was a child, she was infected with polio and became paralyzed in her legs. She was thereafter unable to walk and used a wheelchair throughout most of her childhood and all of her adult life. Larry Kramer—who wrote The Normal Heart—said that he modeled the physician character in his play after Laubenstein because her paraplegia would create a parallel between her bravery and that of the men he depicted facing AIDS.

In other contexts, some with disabilities have objected to being called brave, as a kind of condescension that treats any achievement by a person with a disability as surprising and exceptional. It’s not clear what Laubenstein thought, but she never saw the play, even when the producer offered to send a limousine.

Later, in 1990, Laubenstein had a serious illness and had to go to the intensive care unit. She was placed in an iron lung to help her breathe, a device that encases the entire body, leaving just the head poking out. The iron lung respirator sucks air into the lungs by lowering the pressure within the chamber that surrounds the body. She had used an iron lung as a child as well, for many months, when she was first affected by polio.

In 1992, Laubenstein died unexpectedly of heart disease. Later, Julia Roberts would play the doctor character inspired by her in the film version of The Normal Heart, which premiered on HBO in 2014.

The writer Hallie Ephron, who attended Barnard College with Laubenstein, later recalled first meeting her in 1965, and finding her: “…attractive and slim with straight brown hair cut in bangs, and big features- large, expressive brown eyes and a toothy smile that took over her face.”

After she died, Dr. Linda Laubenstein’s colleague and fellow AIDS-physician Dr. Jeffrey Greene took care of many of her patients with AIDS, finding they had, “trouble speaking of her care for them without breaking down in tears of admiration and loss.” A patient of hers named Bill wrote that she gave him, “a sense of security with my own HIV status that will never be equaled.”

Physician-scribe and Bagel-Bard-at-large Ian Halim writes essays that aim to make medicine accessible to the widest possible audience – drawing on storytelling, history, and connections with everything from ethics to botany. Ian earned his PhD in Greek & Latin literature and his MD, both at Columbia University in The City of New York. He now lives in Pittsburgh.