A Single Blood Test May Soon Replace Your Annual Physical
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
The measurement of proteins in one blood test could provide a comprehensive snapshot of a person's health in the near future.
For all the excitement over "personalized medicine" in the last two decades, its promise has not fully come to pass. Consider your standard annual physical.
Scientists have measured thousands of proteins from a single blood test to assess many individualized health conditions at once.
Your doctor still does a blood test to check your cholesterol and gauge your risk for heart disease by considering traditional risk factors (like smoking, diabetes, blood pressure) — an evaluation that has not changed in decades.
But a high-risk number alone is not enough to tell accurately whether you will suffer from heart disease. It just reflects your risk compared to population-level averages. In other words, not every person with elevated "bad" cholesterol will have a heart attack, so how can doctors determine who truly needs to give up the cheeseburgers and who doesn't?
Now, an emerging area of research may unlock some real-time answers. For the first time, as reported in the journal Nature Medicine last week, scientists have measured thousands of proteins from a single blood test to assess many individualized health conditions at once, including liver and kidney function, diabetes risk, body fat, cardiopulmonary fitness, and even smoking and alcohol consumption. Proteins can give a clear snapshot of how your body is faring at any given moment, as well as a sneak preview at what diseases may be lurking under the surface.
"Years from now," says study co-author Peter Ganz of UCSF, "we will probably be looking back on this paper as a milestone in personalized medicine."
We spoke to Ganz about the significance of this milestone. Our interview has been edited and condensed.
Is this the first study of its kind?
Yes, it is. This is a study where we measured 5,000 proteins at once to look for patterns that could either predict the risk of future diseases or inform the current state of health. Previous to this, people have measured typically one protein at a time, and some of these individual proteins have made it into clinical practice.
An example would be a protein called C-reactive protein, which is a measure of inflammation and is used sometimes in cardiology to predict the risk of future heart attacks. But what's really new is this scale. We wanted to get away from just focusing on one problem that the patient may have at a time, whether it's heart disease or kidney disease, and by measuring a much greater number of proteins, the hope is that we could inform the health of ultimately just about every organ in the body or every tissue. It's a step forward for what I would call "a one-stop shop."
"I'm very excited about personalized medicine through proteins as opposed to genes because you get both the nature and nurture."
Three things get me excited about this. One is the convenience for the patient of a single test to determine many different diseases. The second thing is the healthcare cost savings. We estimated what the cost would be to get these 11 healthcare measures that we reported on using traditional testing and the cost was upwards of 3,000 British pounds. And even though I don't know for sure what the cost of the protein tests would ultimately be, [it could come down to about $50 to $100].
The last thing is that the measurement of proteins is part of what people have called personalized medicine or precision medicine. If you look at risk factors across the population, it may not apply to individuals. In contrast, proteins are downstream of risk factors. So proteins actually tell us whether the traditional risk factors have set in motion the necessary machinery to cause disease. Proteins are the worker bees that regulate what the human body does, and so if you can find some anomalies in the proteins, that may inform us if a disease is likely to be ongoing even in its earliest stages.
Does protein testing have advantages over genetic testing for predicting future health risks?
The problem with genomics is that genes usually don't take care of the environment. It's a blueprint, but your blueprint has no idea what you will be exposed to during your lifetime in terms of the environment and lifestyle that you may choose and medications that you may be on. These are things that proteins can account for. I'm very excited about personalized medicine through proteins as opposed to genes because you get both the nature and nurture as opposed to genomics, which only gives you nature but doesn't account for anything else.
Proteins can also be tracked over time and that's not something you can do with genes. So if your behavior improves, your genes won't change, but your proteins will.
Could this new test become a regular feature of your annual physical?
That's the idea. This would be basically almost a standalone test that you could have done every year. And hopefully you wouldn't need other tests to complement this. This could be your yearly physical.
How much more does it need to be validated before it can enter the clinic and patients can trust the results?
This was a proof-of concept study. To really make this useful, we need to expand from 11 measures of health to a hundred or more health insights, to cover the whole body. And we need to expand this to all racial groups. Three of the five centers in the study were European – all Caucasian – so it's one of our high priorities to find groups of patients with better representation of minorities.
When do you expect doctors to be routinely giving this test to patients?
Much closer to five years than 20 years. We're scaling up from 11 disease states to 100, and many of those studies are underway. Results should be done within three to five years.
Do you think insurance will cover it?
Good question. I have been approached by an insurance company that wanted to understand the product better – a major insurer, with the possibility that this could actually be cost saving.
I have to ask you a curveball -- do you think that the downfall of Theranos will make consumers hesitant to trust a new technology that relies on using a single blood sample to screen for multiple health risks?
[Laughs] You're not the first person to ask me that today. I actually got a call from Elizabeth Holmes [in 2008 when I was at Harvard]. I met with her for an afternoon and met her team two more times. I gave them advice that they completely disregarded.
In many ways, what we do is diametrically opposite to Theranos. They had a culture of secrecy, and what we do is about openness. We publish, like this paper in Nature Medicine, to show the scientific details. Our supplement is much longer than the typical academic paper. We reveal everything we know. A lot of the research we do is funded by [the National Institutes of Health], and they have strict expectations about data sharing. So we agree to make the data available on a public website. If there is something we haven't done with the data, others can do it.
So you're saying that this is not another Theranos.
No, God forbid. We hope to be the opposite.
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
Catching colds may help protect kids from Covid
A new study shows that the immune system's response to colds can help prepare it to defend against COVID-19 - but only in the very young.
A common cold virus causes the immune system to produce T cells that also provide protection against SARS-CoV-2, according to new research. The study, published last month in PNAS, shows that this effect is most pronounced in young children. The finding may help explain why most young people who have been exposed to the cold-causing coronavirus have not developed serious cases of COVID-19.
One curiosity stood out in the early days of the COVID-19 pandemic – why were so few kids getting sick. Generally young children and the elderly are the most vulnerable to disease outbreaks, particularly viral infections, either because their immune systems are not fully developed or they are starting to fail.
But solid information on the new infection was so scarce that many public health officials acted on the precautionary principle, assumed a worst-case scenario, and applied the broadest, most restrictive policies to all people to try to contain the coronavirus SARS-CoV-2.
One early thought was that lockdowns worked and kids (ages 6 months to 17 years) simply were not being exposed to the virus. So it was a shock when data started to come in showing that well over half of them carried antibodies to the virus, indicating exposure without getting sick. That trend grew over time and the latest tracking data from the CDC shows that 96.3 percent of kids in the U.S. now carry those antibodies.
Antibodies are relatively quick and easy to measure, but some scientists are exploring whether the reactions of T cells could serve as a more useful measure of immune protection.
But that couldn't be the whole story because antibody protection fades, sometimes as early as a month after exposure and usually within a year. Additionally, SARS-CoV-2 has been spewing out waves of different variants that were more resistant to antibodies generated by their predecessors. The resistance was so significant that over time the FDA withdrew its emergency use authorization for a handful of monoclonal antibodies with earlier approval to treat the infection because they no longer worked.
Antibodies got most of the attention early on because they are part of the first line response of the immune system. Antibodies can bind to viruses and neutralize them, preventing infection. They are relatively quick and easy to measure and even manufacture, but as SARS-CoV-2 showed us, often viruses can quickly evolve to become more resistant to them. Some scientists are exploring whether the reactions of T cells could serve as a more useful measure of immune protection.
Kids, colds and T cells
T cells are part of the immune system that deals with cells once they have become infected. But working with T cells is much more difficult, takes longer, and is more expensive than working with antibodies. So studies often lags behind on this part of the immune system.
A group of researchers led by Annika Karlsson at the Karolinska Institute in Sweden focuses on T cells targeting virus-infected cells and, unsurprisingly, saw that they can play a role in SARS-CoV-2 infection. Other labs have shown that vaccination and natural exposure to the virus generates different patterns of T cell responses.
The Swedes also looked at another member of the coronavirus family, OC43, which circulates widely and is one of several causes of the common cold. The molecular structure of OC43 is similar to its more deadly cousin SARS-CoV-2. Sometimes a T cell response to one virus can produce a cross-reactive response to a similar protein structure in another virus, meaning that T cells will identify and respond to the two viruses in much the same way. Karlsson looked to see if T cells for OC43 from a wide age range of patients were cross-reactive to SARS-CoV-2.
And that is what they found, as reported in the PNAS study last month; there was cross-reactive activity, but it depended on a person’s age. A subset of a certain type of T cells, called mCD4+,, that recognized various protein parts of the cold-causing virus, OC43, expressed on the surface of an infected cell – also recognized those same protein parts from SARS-CoV-2. The T cell response was lower than that generated by natural exposure to SARS-CoV-2, but it was functional and thus could help limit the severity of COVID-19.
“One of the most politicized aspects of our pandemic response was not accepting that children are so much less at risk for severe disease with COVID-19,” because usually young children are among the most vulnerable to pathogens, says Monica Gandhi, professor of medicine at the University of California San Francisco.
“The cross-reactivity peaked at age six when more than half the people tested have a cross-reactive immune response,” says Karlsson, though their sample is too small to say if this finding applies more broadly across the population. The vast majority of children as young as two years had OC43-specific mCD4+ T cell responses. In adulthood, the functionality of both the OC43-specific and the cross-reactive T cells wane significantly, especially with advanced age.
“Considering that the mortality rate in children is the lowest from ages five to nine, and higher in younger children, our results imply that cross-reactive mCD4+ T cells may have a role in the control of SARS-CoV-2 infection in children,” the authors wrote in their paper.
“One of the most politicized aspects of our pandemic response was not accepting that children are so much less at risk for severe disease with COVID-19,” because usually young children are among the most vulnerable to pathogens, says Monica Gandhi, professor of medicine at the University of California San Francisco and author of the book, Endemic: A Post-Pandemic Playbook, to be released by the Mayo Clinic Press this summer. The immune response of kids to SARS-CoV-2 stood our expectations on their head. “We just haven't seen this before, so knowing the mechanism of protection is really important.”
Why the T cell immune response can fade with age is largely unknown. With some viruses such as measles, a single vaccination or infection generates life-long protection. But respiratory tract infections, like SARS-CoV-2, cause a localized infection - specific to certain organs - and that response tends to be shorter lived than systemic infections that affect the entire body. Karlsson suspects the elderly might be exposed to these localized types of viruses less often. Also, frequent continued exposure to a virus that results in reactivation of the memory T cell pool might eventually result in “a kind of immunosenescence or immune exhaustion that is associated with aging,” Karlsson says. https://leaps.org/scientists-just-started-testing-a-new-class-of-drugs-to-slow-and-even-reverse-aging/particle-3 This fading protection is why older people need to be repeatedly vaccinated against SARS-CoV-2.
Policy implications
Following the numbers on COVID-19 infections and severity over the last three years have shown us that healthy young people without risk factors are not likely to develop serious disease. This latest study points to a mechanism that helps explain why. But the inertia of existing policies remains. How should we adjust policy recommendations based on what we know today?
The World Health Organization (WHO) updated their COVID-19 vaccination guidance on March 28. It calls for a focus on vaccinating and boosting those at risk for developing serious disease. The guidance basically shrugged its shoulders when it came to healthy children and young adults receiving vaccinations and boosters against COVID-19. It said the priority should be to administer the “traditional essential vaccines for children,” such as those that protect against measles, rubella, and mumps.
“As an immunologist and a mother, I think that catching a cold or two when you are a kid and otherwise healthy is not that bad for you. Children have a much lower risk of becoming severely ill with SARS-CoV-2,” says Karlsson. She has followed public health guidance in Sweden, which means that her young children have not been vaccinated, but being older, she has received the vaccine and boosters. Gandhi and her children have been vaccinated, but they do not plan on additional boosters.
The WHO got it right in “concentrating on what matters,” which is getting traditional childhood immunizations back on track after their dramatic decline over the last three years, says Gandhi. Nor is there a need for masking in schools, according to a study from the Catalonia region of Spain. It found “no difference in masking and spread in schools,” particularly since tracking data indicate that nearly all young people have been exposed to SARS-CoV-2.
Both researchers lament that public discussion has overemphasized the quickly fading antibody part of the immune response to SARS-CoV-2 compared with the more durable T cell component. They say developing an efficient measure of T cell response for doctors to use in the clinic would help to monitor immunity in people at risk for severe cases of COVID-19 compared with the current method of toting up potential risk factors.
In this week's Friday Five: The eyes are the windows to the soul - and biological aging?
Plus, what bean genes mean for health and the planet, a breathing practice that could lower levels of tau proteins in the brain, AI beats humans at assessing heart health, and the benefits of "nature prescriptions"
The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on new scientific theories and progress to give you a therapeutic dose of inspiration headed into the weekend.
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Here are the stories covered this week:
- The eyes are the windows to the soul - and biological aging?
- What bean genes mean for health and the planet
- This breathing practice could lower levels of tau proteins
- AI beats humans at assessing heart health
- Should you get a nature prescription?