Good Friday Morning!
Quick note before getting started. This post was originally written for Aging Successfully. Aging Successfully is a joint effort between me, my sister and her husband (Laura and Matt). Matt and Laura are family doctors focused on metabolic health, obesity medicine, and using lifestyle changes as THE first line of treatment for a range of chronic conditions and wherever else possible.
Every so often I might write a post for that Substack which feels like it could also fit on 01Core and vice versa. This is one such post. As you can see in the screenshot below most posts on that Substack will be health focused, please check it out if you’re interested!
There are a growing number of people who subscribe to both (thank you!!!) - and I apologize in advance if you have already seen this and are getting your inbox spammed.
Now on with the post.
Healthcare has always felt like a mess - just ask George Washington (see below).
Today, dealing with insurance is a nightmare (for both patients and doctors). Doctors have to keep multiple employees on staff just to handle claims. A CT scan at a hospital might cost $900 if you’re paying out of pocket but $4,000 if the hospital gets to charge an insurance company. In countries with single payer systems you can wait months just to get an appointment.
Chronic conditions are on the rise and have been for decades, despite the fact that we have more knowledge of what causes them now than ever. No one (it sometimes feels) seems to be interested in doing things to prevent sickness in the first place…
Worse yet, at a time when the world is richer than it has ever been, medical expenses are still the second most frequently cited cause of bankruptcy in the United States.
But…things used to be a lot worse. For one, most treatments used to be total bunk that made things worse more often than they made things better. Take bloodletting for example.
Blood letting was invented around 3,000 years ago, and its use became widespread between 2,500 and 2,000 years ago.
The logic behind bloodletting was first described by Hippocrates. Existence was represented by the four basic elements - earth, air, fire, and water - which in humans were related to the four basic humors: blood, phlegm, black bile, yellow bile.
The idea was that if you were ill it was because of an imbalance between the humors, and bleeding would restore balance.
Obviously bloodletting didn’t work. Our first president George Washington was actually bled to death in an attempt to cure whatever was ailing him (his illness is still debated to this day). Imagine that, the President of the United States of America, was treated with bloodletting…
In 1828 Pierre Charles Alexandre Louis was one of the first physicians to openly criticize it, but it wasn’t until the late 19th century that it was widely discredited. Talk about a ridiculously long run. If you don’t count the use of alcohol, opium and other naturally derived substances to treat pain, bloodletting probably takes the crown for the longest used medical treatment.
You don’t have to go back that far though to find things that would seem outrageous (and dangerous, awful, horrific, scammy, etc)…
Here are three examples pulled from the Library of Congress) of treatments that took place up until the early 20th century.
Milk Transfusions. “In the late 19th century, milk was believed to be the perfect substitute for blood, and the fatty/oily qualities would become white blood cells.”
Using cigarettes to treat asthma. Here’s an advertisement promoting cigarettes as a cure, shown in the Indianapolis Times in 1923.
Soothing Syrup. For babies of course…A remedy for everything from teething to diarrhea. Naturally, the key ingredients were alcohol and morphine. At least we know why it got the babies to stop fussing so much… This ad was printed in 1907.
One last tidbit I ran across in my research that I thought was worth sharing.
The opiate epidemic we are currently going through is actually the second one our country has experienced. The first started during the Civil War, when 10 million opium pills and 2.8 million ounces of opium powders were given to soldiers. It got even worse when the war was over and doctors were trying to treat wounded soldiers after they returned home. Opiates made up 15 percent of all prescriptions dispensed in Boston in 1888.
Healthcare is improving exponentially
Before diving into the rest of this post I want to introduce the concept of exponential growth. Exponential growth is important to understand because healthcare is advancing exponentially, but if you don’t intuitively understand what that means then you won’t be as optimistic about where we might be going over the next 10-20 years as you should be.
Let’s assume that 1,000 years ago we had “1 unit of knowledge” about healthcare. Each year we learn 1% more than we knew the year before. The vertical axis is “knowledge of healthcare” and the horizontal axis is “time”.
Over the first 544 years (the red box) we go from having 1 unit of knowledge to 222 units of knowledge. Impressive, but still in the grand scheme of things the rise in total knowledge is barely recognizable.
The yellow box is half the size of the red box. So in half the time it took us to go from 1 to 222 units of knowledge, we acquired 3,274 units of knowledge! (3,496-222).
But the green box is where it really gets crazy. Just like with the yellow box, the green box is half the size. So, in half the time it took to gain 3,274 units of knowledge, we gained 10,167 units of knowledge.
The reality is we’re learning a hell of a lot more than 1% compared to what we knew previously. This makes sense.
Each year we graduate new scientists and doctors, each year the tools we have to work with improve, each year we have more money being invested. Consider the fact that there were only 2 billion people on earth at the turn of the last century (1900) and most of them were illiterate. Now we have almost 8 billion people…
The number of doctors, scientists and engineers we have working on solutions is tens of thousands of times greater vs. 1900, and the tools they have to work with are incomparable even to the tools we had 30 years ago.
Now we’re going to take a (relatively) brief walk through the history of medicine. The main takeaway I want you to keep an eye out for is how rapidly progress has been made, and how rapidly the rate of progress is increasing. We’ll finish the post off with some incredibly exciting things happening today that paint a picture of a very bright future, and thankfully, one that isn’t too far away.
By the end of this post I hope to have convinced you to do everything in your power to be as healthy as possible to make sure that you will still be around when real “miracle treatments” start to become commonplace.
58,000 BC through 500 BC
In the beginning…Everything was discovered by accident, in the exact same way that hunter-gatherers discovered which nuts, berries, grasses and animals were good to eat.
Archeologists found evidence for the use of herbal remedies dating back to 58,000 BC. 27,000 years later humans figured out that if some part of a body is wounded, it was often best to just cut that part off. Archeologists in Indonesia just this year discovered evidence of the first amputation that dated to 29,000 BC. They can tell from the fossil that the young hunter-gather on whom it was performed survived. Mind you, these surgeries were done without anesthesia. Opium wasn’t discovered for another 24,000 years (see below), and even if they had figured out the chemical properties of opium they would not have been able to process it into the concentrations that are possible today.
Fermented beverages (alcohol) were likely discovered around 10,000 BC, and the first people to cultivate opium started around 3,400 BC. Both of these substances were widely used to dull pain and have been ever since. Humans began using honey at least 8,000 years ago, though we don’t know when they started using it to treat coughs - it was likely not long after.
Around 3,000 years ago, someone in India discovered that if you took a piece of clothing or something that had touched someone with smallpox, you could introduce a less severe version of the illness to healthy children and adults, thereby reducing the likelihood that they would catch it too. This technique is known as Variolation.
500 BC to 1800
By the mid 400s BC it was widely known in communities that had dealt with smallpox that survivors were the best people to care for the ill.
In 1590 the microscope was invented by a Dutch lens grinder named Zacharius Jannssen. By 1670 the technology had improved to the point at which blood cells and microorganisms became visible. This marked the beginning of people realizing that our health could be impacted by things we couldn’t see with the naked eye.
In 1796, a British Physician named Edward Jenner noticed that milkmaids who had gotten cowpox were protected from smallpox. He invented the first vaccine, which involved injecting pus from a cowpox blister into a healthy person.
Let’s pause here for a moment. If you discount opiates, alcohol and other sense-dulling drugs, it took sixty thousand years to go from herbal remedies to the first thing resembling modern medical treatment (the smallpox vaccine).
Here’s a graphic that makes this easier to digest. Each X represents 100 years.
1800 to 1941
Now for the real progress.
The stethoscope was invented by Rene Laennec in 1816.
In 1818 James Blundell completed the first successful blood transfusion to treat postpartum hemorrhage, and in 1840 the first successful transfusion was used to treat hemophilia.
Handwashing was discovered in 1848 when professor of biology Ignaz Semmelweis was trying to figure out why there were far more deaths in a doctor-led maternity ward than in a midwife’s clinic. He determined that the cause was doctors interacting with dead bodies in the morgue and getting bad “particles” on their hands - something the midwifes never did. It took 20 years for there to be widespread recognition by surgeons that they needed to scrub, but it wasn’t for another 100 years that the United States issued their first “national hand hygiene guidelines”.
Louis Pasteur discovered Germ Theory in 1861. Until then most people believed that sickness was either a spiritual phenomenon or the result of foul odors.
X-rays were discovered by accident by German physicist Wilhelm Rontgen in 1895.
The creation of the smallpox vaccine kicked off a race to create other vaccines against common diseases. Between 1796 and 1941 vaccines were invented for:
cholera
anthrax
rabies
tetanus
diphtheria
typhoid fever
the plague
pertussis (whooping cough)
tuberculosis
yellow fever
typhus
1941 to 1990
Penicillin was discovered in 1928 by Dr. Alexander Fleming, who realized that mold in his petri dish could kill bacteria. It took until 1941 to figure out how to turn penicillin into an at-scale deliverable drug, and thanks to WWII the market was massive and government funded.
Penicillin really kicked off the the modern era of healthcare. Companies saw the potential market size for treatments and began to industrialize the discovery process, increasing the amount of money spent on R&D by many orders of magnitude.
Here’s a brief list of innovations and things we learned between 1941 and 1990:
Antipsychotics were invented
The double helix of DNA was discovered
Immunology
Vaccines for measles, flu, meningitis, chicken pox and pneumonia
Valium
First kidney, liver, lung and heart transplants
Pacemakers
Artificial insemination
Limb reattachments
CAT scans and MRIs
Statins
Surgical robots
Laser cataract surgery
HIV is discovered
Telomeres
Hepatitis A, B, and C vaccinations
Radiosurgery
Use of cameras on a “smart pill” to diagnose gastrointestinal issues
Viagra
Intravenous catheters
Gamow bag
Protease inhibitors
Stem cell therapy
Where we are today
In 1990 the humane genome project kicked off. It took thousands of scientists 13 years to complete and cost $3 billion. Today we can scan a genome for $1,000. Even better, because we have built machines capable of doing the majority of the work, a single scientist can scan multiple genomes simultaneously if they have the machines for it. A lot more progress than 1% per year eh?
That finished in 2003, but where are we now?
Today, gene therapies have become a reality.
In my post called The most important things to know about aging I wrote the following about gene therapies, which serves as a perfect closing note for this post:
Gene therapies attempt to do one of four things:
replace missing genes
put in new genes
delete genes
turn genes on/off
Gene therapies already exist. Zolgensma is one such therapy used to treat spinal muscular atrophy (SMA) - one of the most debilitating diseases on the planet. It works by replacing missing or non-functional SMN1 genes at a cost of $2m. Interestingly, as George Church explains in this interview, the technology used to deliver Zolgensma is very similar to that used to deliver the Covid-19 mRNA vaccine, the implication being that costs will come down over time ($2 is the estimated delivery cost of an mRNA vaccine for Covid) as the number of people receiving treatment grows and the R&D dollars can be amortized over a larger population.
In-vivo (performed inside a living organism) gene therapies are essentially the same thing as re-writing the “computer code” our bodies are made of. While the first gene therapy took place in 1990, it wasn’t until the 2010s that we started getting good at controlling them. The following excerpt comes from Boston Children’s Hospital:
Scientists developed better viral vectors which can more precisely target expressions of genes in specific cell types, don’t go stray in the body, and don’t trigger the immune system. Some deliver genes meant to work for a short while and then inactivate themselves. Others carry genes that remain active long-term and pass to daughter cells as the cells divide.
Unfortunately our bodies are more complex than computers (go figure). Imagine how chaotic your smartphone would be if every time you loaded a new app it started making all of the other apps work differently, or stop working all together. You download Google Maps, and suddenly your email stops working, or you lose the ability to text, or your phone starts taking pictures non-stop and fills up all of the storage space. It would be an unmitigated disaster and would render your phone completely unusable. This is the danger that comes with doing anything in-vivo. Unlike computers which can store programs in such a way that they don’t contaminate the other software - inside our bodies everything is connected.
These potential interactions are one of the things that make gene therapies so complex. But, we’re getting better at them very quickly. Today, the most cutting edge research taking place is around something called base editing, which involves combining tools like CRISPR/Cas 9 with enzymes to actually re-write, letter for letter, Cs, Ts, As and Gs (the equivalent of 0s and 1s for computers). CTAG are the four types of bases found in a DNA molecule, which is why they call it base editing.
From the same Boston Children’s Hospital article:
These small changes (to ACTG), can correct a “spelling error” mutation, silence a disease-causing gene, or help activate a specific gene…they offer the promise of more precision, efficiency, and safety.
Take a moment to consider how absolutely mind-blowingly incredible it is that humans are actually able to re-write our own software TODAY!
I literally feel like I need to stand up just to let some energy out when I start thinking about what this means for the future.
Now, let me get you excited about what’s coming. Here’s another excerpt from my post on aging:
Studies like this aim to figure out which genes are associated with extreme longevity (living past 100). Two things impact our lifespans: genes and experiences (nature and nurture). Obviously healthy living isn’t enough to get to 110 years old or more people would make it. Genes are playing a role. Once we figure out what those genes are (or aren’t) we’ll have everything we need to start gene therapy trials to TREAT AGING. The first treatments won’t be cures but they will buy us time.
George Church, a Harvard and MIT professor recognized by Time Magazine as one of the 100 most influential people in the world and widely considered to be the “Founding Father of Genomics”, believes that these treatments are coming in the 2030s.
My belief is that we are at an inflection point known as the knee of the exponential curve. I think of the knee of the curve as being the point at which change over the course of one year becomes noticeable to the savvy eye. To put it in practical terms, the knee of the curve is the point where every single year we hear of game-changing break throughs.
One of the coolest breakthroughs I’ve read about recently just happened this year, and it’s a drug called Tirzepatide created by Eli Lilly. Tirzepatide gives your body back a hormone that becomes low with obesity, thus greatly improving hunger and satiety (another type of re-programming!). There are no major side effects.
Tirzepatide is more like using testosterone or estrogen replacement therapy than taking a serious pharmaceutical with a bajillion side effects. In a high quality, double blind/randomized study, patients taking 15 mg of Tirzepatide per week lost 21% of their total bodyweight!
This drug is already being used to treat type two diabetes and will likely be approved later this year for general weight loss. Unfortunately, it’s insanely expensive and not covered by most insurance. But, remember that this drug will eventually come off patent. Even better, now that scientists know such a thing is possible, you can bet your last dollar enormous amounts of additional money will be pouring into innovation over the coming years, and competition means lower prices.
I’m not alone in being optimistic. In fact, just this year a company called Altos Labs was formed.
Altos Labs is the newest and highest profile presence on the “aging is curable” scene. They just broke records by raising a $3billion seed round (seed means money to get started). Hal Barron is the CEO and a co-founder. Prior to Altos he was President and Chief Scientific Officer of R&D at GSK, a $57billion biotech company. The rest of the executive and scientific leadership reads likes a “Who’s Who” of biotech, pharma and academia. The funny thing about disease is that it mostly hits us when we’re old. Here’s a chart showing the likelihood of getting cancer by age:
Here’s another chart showing the likelihood of getting dementia by age:
Obviously, aging is the underlying cause of most diseases, and now we have companies with billions of dollars trying to attack the root cause of the problem rather than working on how to treat the symptoms.
Over the next couple of decades it is increasingly likely that we will figure out how to start curing diseases outright or, better yet, prevent them in the first place.
The good news is, if I’m right - we don’t have to wait very long to find out.
Let me re-iterate the takeaway: we’re getting damn close to solving a lot of problems and dramatically increasing the amount of HEALTHY LIFE each of us has. Make sure you do everything in your power to stay healthy long enough for you to benefit when these miraculous innovations arrive.