Blood Money: Paying for Convalescent Plasma to Treat COVID-19
A bag of plasma that Tom Hanks donated back in April 2020 after his coronavirus infection. (He was not paid to donate.)
Convalescent plasma – first used to treat diphtheria in 1890 – has been dusted off the shelf to treat COVID-19. Does it work? Should we rely strictly on the altruism of donors or should people be paid for it?
The biologic theory is that a person who has recovered from a disease has chemicals in their blood, most likely antibodies, that contributed to their recovery, and transferring those to a person who is sick might aid their recovery. Whole blood won't work because there are too few antibodies in a single unit of blood and the body can hold only so much of it.
Plasma comprises about 55 percent of whole blood and is what's left once you take out the red blood cells that carry oxygen and the white blood cells of the immune system. Most of it is water but the rest is a complex mix of fats, salts, signaling molecules and proteins produced by the immune system, including antibodies.
A process called apheresis circulates the donors' blood through a machine that separates out the desired parts of blood and returns the rest to the donor. It takes several times the length of a regular whole blood donation to cycle through enough blood for the process. The end product is a yellowish concentration called convalescent plasma.
Recent History
It was used extensively during the great influenza epidemic off 1918 but fell out of favor with the development of antibiotics. Still, whenever a new disease emerges – SARS, MERS, Ebola, even antibiotic-resistant bacteria – doctors turn to convalescent plasma, often as a stopgap until more effective antibiotic and antiviral drugs are developed. The process is certainly safe when standard procedures for handling blood products are followed, and historically it does seem to be beneficial in at least some patients if administered early enough in the disease.
With few good treatment options for COVID-19, doctors have given convalescent plasma to more than a hundred thousand Americans and tens of thousand of people elsewhere, to mixed results. Placebo-controlled trials could give a clearer picture of plasma's value but it is difficult to enroll patients facing possible death when the flip of a coin will determine who will receive a saline solution or plasma.
And the plasma itself isn't some uniform pill stamped out in a factory, it's a natural product that is shaped by the immune history of the donor's body and its encounter not just with SARS-CoV-2 but a lifetime of exposure to different pathogens.
Researchers believe antibodies in plasma are a key factor in directly fighting the virus. But the variety and quantity of antibodies vary from donor to donor, and even over time from the same donor because once the immune system has cleared the virus from the body, it stops putting out antibodies to fight the virus. Often the quality and quantity of antibodies being given to a patient are not measured, making it somewhat hit or miss, which is why several companies have recently developed monoclonal antibodies, a single type of antibody found in blood that is effective against SARS-CoV-2 and that is multiplied in the lab for use as therapy.
Plasma may also contain other unknown factors that contribute to fighting disease, say perhaps signaling molecules that affect gene expression, which might affect the movement of immune cells, their production of antiviral molecules, or the regulation of inflammation. The complexity and lack of standardization makes it difficult to evaluate what might be working or not with a convalescent plasma treatment. Thus researchers are left with few clues about how to make it more effective.
Industrializing Plasma
Many Americans living along the border with Mexico regularly head south to purchase prescription drugs at a significant discount. Less known is the medical traffic the other way, Mexicans who regularly head north to be paid for plasma donations, which are prohibited in their country; the U.S. allows payment for plasma donations but not whole blood. A typical payment is about $35 for a donation but the sudden demand for convalescent plasma from people who have recovered from COVID-19 commands a premium price, sometimes as high as $200. These donors are part of a fast-growing plasma industry that surpassed $25 billion in 2018. The U.S. supplies about three-quarters of the world's needs for plasma.
Payment for whole blood donation in the U.S. is prohibited, and while payment for plasma is allowed, there is a stigma attached to payment and much plasma is donated for free.
The pharmaceutical industry has shied away from natural products they cannot patent but they have identified simpler components from plasma, such as clotting factors and immunoglobulins, that have been turned into useful drugs from this raw material of plasma. While some companies have retooled to provide convalescent plasma to treat COVID-19, often paying those donors who have recovered a premium of several times the normal rate, most convalescent plasma has come as donations through traditional blood centers.
In April the Mayo Clinic, in cooperation with the FDA, created an expanded access program for convalescent plasma to treat COVID-19. It was meant to reduce the paperwork associated with gaining access to a treatment not yet approved by the FDA for that disease. Initially it was supposed to be for 5000 units but it quickly grew to more than twenty times that size. Michael Joyner, the head of the program, discussed that experience in an extended interview in September.
The Centers for Medicare and Medicaid Services (CMS) also created associated reimbursement codes, which became permanent in August.
Mayo published an analysis of the first 35,000 patients as a preprint in August. It concluded, "The relationships between mortality and both time to plasma transfusion, and antibody levels provide a signature that is consistent with efficacy for the use of convalescent plasma in the treatment of hospitalized COVID-19 patients."
It seemed to work best when given early in infection and in larger doses; a similar pattern has been seen in studies of monoclonal antibodies. A revised version will soon be published in a major medical journal. Some criticized the findings as not being from a randomized clinical trial.
Convalescent plasma is not the only intervention that seems to work better when used earlier in the course of disease. Recently the pharmaceutical company Eli Lilly stopped a clinical trial of a monoclonal antibody in hospitalized COVID-19 patients when it became apparent it wasn't helping. It is continuing trials for patients who are less sick and begin treatment earlier, as well as in persons who have been exposed to the virus but not yet diagnosed as infected, to see if it might prevent infection. In November the FDA eased access to this drug outside of clinical trials, though it is not yet approved for sale.
Show Me the Money
The antibodies that seem to give plasma its curative powers are fragile proteins that the body produces to fight the virus. Production shuts down once the virus is cleared and the remaining antibodies survive only for a few weeks before the levels fade. [Vaccines are used to train immune cells to produce antibodies and other defenses to respond to exposure to future pathogens.] So they can be usefully harvested from a recovered patient for only a few short weeks or months before they decline precipitously. The question becomes, how does one mobilize this resource in that short window of opportunity?
The program run by the Mayo Clinic explains the process and criteria for donating convalescent plasma for COVID-19, as well as links to local blood centers equipped to handle those free donations. Commercial plasma centers also are advertising and paying for donations.
A majority of countries prohibit paying donors for blood or blood products, including India. But an investigation by India Today touted a black market of people willing to donate convalescent plasma for the equivalent of several hundred dollars. Officials vowed to prosecute, saying donations should be selfless.
But that enforcement threat seemed to be undercut when the health minister of the state of Assam declared "plasma donors will get preference in several government schemes including the government job interview." It appeared to be a form of compensation that far surpassed simple cash.
The small city of Rexburg, Idaho, with a population a bit over 50,000, overwhelmingly Mormon and home to a campus of Brigham Young University, at one point had one of the highest per capita rates of COVID-19 in the current wave of infection. Rumors circulated that some students were intentionally trying to become infected so they could later sell their plasma for top dollar, potentially as much as $200 a visit.
Troubled university officials investigated the allegations but could come up with nothing definitive; how does one prove intentionality with such an omnipresent yet elusive virus? They chalked it up to idle chatter, perhaps an urban legend, which might be associated with alcohol use on some other campus.
Doctors, hospitals, and drug companies are all rightly praised for their altruism in the fight against COVID-19, but they also get paid. Payment for whole blood donation in the U.S. is prohibited, and while payment for plasma is allowed, there is a stigma attached to payment and much plasma is donated for free. "Why do we expect the donors [of convalescent plasma] to be the only uncompensated people in the process? It really makes no sense," argues Mark Yarborough, an ethicist at the UC Davis School of Medicine in Sacramento.
"When I was in grad school, two of my closest friends, at least once a week they went and gave plasma. That was their weekend spending money," Yarborough recalls. He says upper and middle-income people may have the luxury of donating blood products but prohibiting people from selling their plasma is a bit paternalistic and doesn't do anything to improve the economic status of poor people.
"Asking people to dedicate two hours a week for an entire year in exchange for cookies and milk is demonstrably asking too much," says Peter Jaworski, an ethicist who teaches at Georgetown University.
He notes that companies that pay plasma donors have much lower total costs than do operations that rely solely on uncompensated donations. The companies have to spend less to recruit and retain donors because they increase payments to encourage regular repeat donations. They are able to more rationally schedule visits to maximize use of expensive apheresis equipment and medical personnel used for the collection.
It seems that COVID-19 has been with us forever, but in reality it is less than a year. We have learned much over that short time, can now better manage the disease, and have lower mortality rates to prove it. Just how much convalescent plasma may have contributed to that remains an open question. Access to vaccines is months away for many people, and even then some people will continue to get sick. Given the lack of proven treatments, it makes sense to keep plasma as part of the mix, and not close the door to any legitimate means to obtain it.
Here's how one doctor overcame extraordinary odds to help create the birth control pill
Dr. Percy Julian had so many personal and professional obstacles throughout his life, it’s amazing he was able to accomplish anything at all. But this hidden figure not only overcame these incredible obstacles, he also laid the foundation for the creation of the birth control pill.
Julian’s first obstacle was growing up in the Jim Crow-era south in the early part of the twentieth century, where racial segregation kept many African-Americans out of schools, libraries, parks, restaurants, and more. Despite limited opportunities and education, Julian was accepted to DePauw University in Indiana, where he majored in chemistry. But in college, Julian encountered another obstacle: he wasn’t allowed to stay in DePauw’s student housing because of segregation. Julian found lodging in an off-campus boarding house that refused to serve him meals. To pay for his room, board, and food, Julian waited tables and fired furnaces while he studied chemistry full-time. Incredibly, he graduated in 1920 as valedictorian of his class.
After graduation, Julian landed a fellowship at Harvard University to study chemistry—but here, Julian ran into yet another obstacle. Harvard thought that white students would resent being taught by Julian, an African-American man, so they withdrew his teaching assistantship. Julian instead decided to complete his PhD at the University of Vienna in Austria. When he did, he became one of the first African Americans to ever receive a PhD in chemistry.
Julian received offers for professorships, fellowships, and jobs throughout the 1930s, due to his impressive qualifications—but these offers were almost always revoked when schools or potential employers found out Julian was black. In one instance, Julian was offered a job at the Institute of Paper Chemistory in Appleton, Wisconsin—but Appleton, like many cities in the United States at the time, was known as a “sundown town,” which meant that black people weren’t allowed to be there after dark. As a result, Julian lost the job.
During this time, Julian became an expert at synthesis, which is the process of turning one substance into another through a series of planned chemical reactions. Julian synthesized a plant compound called physostigmine, which would later become a treatment for an eye disease called glaucoma.
In 1936, Julian was finally able to land—and keep—a job at Glidden, and there he found a way to extract soybean protein. This was used to produce a fire-retardant foam used in fire extinguishers to smother oil and gasoline fires aboard ships and aircraft carriers, and it ended up saving the lives of thousands of soldiers during World War II.
At Glidden, Julian found a way to synthesize human sex hormones such as progesterone, estrogen, and testosterone, from plants. This was a hugely profitable discovery for his company—but it also meant that clinicians now had huge quantities of these hormones, making hormone therapy cheaper and easier to come by. His work also laid the foundation for the creation of hormonal birth control: Without the ability to synthesize these hormones, hormonal birth control would not exist.
Julian left Glidden in the 1950s and formed his own company, called Julian Laboratories, outside of Chicago, where he manufactured steroids and conducted his own research. The company turned profitable within a year, but even so Julian’s obstacles weren’t over. In 1950 and 1951, Julian’s home was firebombed and attacked with dynamite, with his family inside. Julian often had to sit out on the front porch of his home with a shotgun to protect his family from violence.
But despite years of racism and violence, Julian’s story has a happy ending. Julian’s family was eventually welcomed into the neighborhood and protected from future attacks (Julian’s daughter lives there to this day). Julian then became one of the country’s first black millionaires when he sold his company in the 1960s.
When Julian passed away at the age of 76, he had more than 130 chemical patents to his name and left behind a body of work that benefits people to this day.
Therapies for Healthy Aging with Dr. Alexandra Bause
My guest today is Dr. Alexandra Bause, a biologist who has dedicated her career to advancing health, medicine and healthier human lifespans. Dr. Bause co-founded a company called Apollo Health Ventures in 2017. Currently a venture partner at Apollo, she's immersed in the discoveries underway in Apollo’s Venture Lab while the company focuses on assembling a team of investors to support progress. Dr. Bause and Apollo Health Ventures say that biotech is at “an inflection point” and is set to become a driver of important change and economic value.
Previously, Dr. Bause worked at the Boston Consulting Group in its healthcare practice specializing in biopharma strategy, among other priorities
She did her PhD studies at Harvard Medical School focusing on molecular mechanisms that contribute to cellular aging, and she’s also a trained pharmacist
In the episode, we talk about the present and future of therapeutics that could increase people’s spans of health, the benefits of certain lifestyle practice, the best use of electronic wearables for these purposes, and much more.
Dr. Bause is at the forefront of developing interventions that target the aging process with the aim of ensuring that all of us can have healthier, more productive lifespans.
