Here are updates on the HPV and Measles vaccines:
HPV:
"While common and generally not life-threatening, HPV
also can trigger a host of cancers, and rates are rising: 43,371
cancers were associated with the virus in the United States in 2015, up
from 30,115 in 1999, according to a report in August by the U.S. Centers for Disease Control and Prevention." See https://www.bridgemi.com/michigan-health-watch/hpv-cancer-rates-are-yet-many-michigan-doctors-wont-talk-about-it
Most of the US population of reproductive age is infected with HPV, which means that all in this age range are likely to get exposed unless vaccine use increases dramatically. Don't pretend you can avoid it by being "careful." That assumes that everyone communicates honesty and accurately about their histories, and that you are only exposed to people who themselves were never exposed or were vaccinated and developed antibodies.
For more information on how HPV causes cervical, head & neck and skin cancer, see page 20 of my December 2017 paper at http://www.natpernick.com/HowCancerArises.pdf.
Measles:
Yes, measles kills healthy people. See https://www.cnn.com/2019/08/13/health/israeli-flight-attendant-measles-death. When physicians give our opinions on medical matters, we put our reputation and license on the line. We cannot easily just state our opinion because we feel like it. We also have extensive training and experience. Of course, we could be wrong, and there are "bad apples" in the medical profession, but it is usually obvious that they are "outliers." This is not the case with those who write anonymous flyers.
Monday, September 9, 2019
Tuesday, September 3, 2019
3 September 2019: Be Optimistic to Live Longer (or does it only seem longer?)
Good
news for the cheery: A Boston study published this month suggests
people who tend to be optimistic are likelier than others to live to be
85 years old or more.
Click here.
Click here.
Friday, July 26, 2019
26 July 2019: How Cancer Arises based on Complexity Theory, 2019 update
I have updated this paper, originally published in December 2017, see http://www.natpernick.com/HowCancerArises.pdf. I plan to present it at a cancer research conference in Spring 2020. The Abstract and Executive Summary are below. I am happy to answer questions about this paper or cancer in general, but cannot answer patient specific questions.
Abstract
Background: The War on Cancer has failed, due in part to its reliance on reductionist thinking to understand how cancer arises.
Methods: We reviewed prominent cancer risk factors at major sites and categorized them based on a complexity theory approach that focuses on early changes to network behavior instead of later changes to oncogenes.
Results: Cancer is caused by nine sources of chronic cellular stress that often interact to provide the multiple “hits” that produce malignancy. They are: chronic inflammation (due to infection, infestation, autoimmune disorders, trauma, overweight, diabetes and other causes); exposure to carcinogens; reproductive hormones; Western diet (high fat, low fiber, vegetable and fruit consumption); aging; radiation; immune system dysfunction; germ line changes and random chronic stress or bad luck.
Conclusions: Cancer is an inevitable tradeoff of human biologic design that will always be with us, particularly as life expectancy increases. However, we can often prevent it, we can detect it earlier and we can treat it more effectively. Most cancer is caused by chronic cellular stress that disturbs the delicate balance of our interconnected biologic networks. Malignancy arises due to a buildup of dysfunctional hierarchical structures, in which combination of agents (biomarkers and networks) at one level become agents at the next level. These dysfunctional structures are identifiable by patterns of network changes, molecular changes or possibly histologic changes. New treatment approaches include targeting multiple tumor features to overcome tumor heterogeneity, targeting the chaotic nature of some tumors, moving tumor cells into less lethal network states by emulating physiologic mechanisms and reducing chronic stressors.
Executive summary
1. Cancer is an inevitable tradeoff of human biologic design. It will always be with us, particularly as life expectancy increases. However, we can often prevent it, we can detect it earlier and we can treat it more effectively.
2. Most cancer is caused by chronic cellular stress, which disturbs the delicate balance that exists in our interconnected biologic networks. In the correct microenvironment, it pushes susceptible stem or progenitor cells into increasingly dysregulated and unstable network trajectories that are ultimately associated with uncontrolled cell growth. It is foreseeable that some chronic cellular stressors will cause cancer but which stressors will be important, where the cancers will arise and what their molecular and histologic features will be is not predictable due to the nonlinear nature of complex systems.
3. There are nine important sources of chronic cellular stress that cause cancer and often interact to provide the multiple “hits” (genetic or network aberrations) that produce malignancy:
* Chronic inflammation (due to infection, infestation, autoimmune disorders, trauma, overweight, diabetes and other causes)
* Exposure to carcinogens
* Reproductive hormones
* Western diet (high fat, low fiber, vegetable and fruit consumption)
* Aging
* Radiation
* Immune system dysfunction
* Germ line changes
* Random chronic stress or bad luck
These chronic stressors typically create a field effect; i.e., large areas are affected by a single aberration.
4. Complexity theory helps us better understand how cancer arises:
A. To understand cancer, it is important to think about how life arose from cellular networks because the same principles guide the pathophysiology of cancer. Focusing too much on specific details of the networks, such as characteristics of individual molecules in the network, ignores the overriding theme that the emergence and disturbance of generic network features is independent of these details.
B. Living systems require fine tuning of cellular networks to enable rapid transitions during fertilization, embryogenesis and repair of external or internal damage via inflammation, as well as slower transitions during fetal growth, childhood growth, puberty and response to environmental changes. Living systems must also have enough flexibility to promote and tolerate evolutionary change. Robust control mechanisms prevent these transitions from being activated inappropriately, but the chronic stressors may disrupt these control mechanisms.
C. Malignancy arises due to a build up of hierarchical structures, in which combination of agents (biomarkers and networks) at one level become agents at the next level. Hierarchical structures may be identifiable by patterns of network changes, molecular changes or histologic changes.
D. We can acquire new insights about malignancy by analyzing patterns of network behavior (such as the creation of new hierarchical structures or increasing instability) that are more uniform than changes to downstream oncogenes.
E. Self-organized criticality describes how enormous transformations (“catastrophes”) occur in living and nonliving systems. Similarly, malignant change does not occur through gradualism but by bursts of activity.
5. Treatment approaches based on complexity theory focus on interacting cellular networks, not just killing tumor cells where they exist. Curative treatment must combine multiple strategies that target existing tumors, prevent future tumors from arising and optimize the overall health of the patient:
* Cytotoxic cancer therapy should kill as many tumor cells as possible.
* Curative treatment for adult tumors must address tumor heterogeneity to a greater extent than curable childhood tumors.
* It may be useful to move cancer networks into less lethal states using biomolecules that influence malignant-type behavior or that alter pathways that promote malignant-type behavior.
* Reducing the chronic stressors is important because current knowledge is often inadequate to reverse network changes caused by even the simplest carcinogens.
* Novel treatments may take advantage of the sophistication present in physiologic cells but lost in the somewhat chaotic cells of advanced and aggressive cancers.
* Targeting the microenvironment that nurtures the tumor cells may have therapeutic value.
* More effective screening is important, both for premalignant and malignant lesions.
* Promoting rational medical care is important at the individual and societal level to more easily detect signs and symptoms associated with malignancy and to increase the range of possible treatments.
- End of post -
Abstract
Background: The War on Cancer has failed, due in part to its reliance on reductionist thinking to understand how cancer arises.
Methods: We reviewed prominent cancer risk factors at major sites and categorized them based on a complexity theory approach that focuses on early changes to network behavior instead of later changes to oncogenes.
Results: Cancer is caused by nine sources of chronic cellular stress that often interact to provide the multiple “hits” that produce malignancy. They are: chronic inflammation (due to infection, infestation, autoimmune disorders, trauma, overweight, diabetes and other causes); exposure to carcinogens; reproductive hormones; Western diet (high fat, low fiber, vegetable and fruit consumption); aging; radiation; immune system dysfunction; germ line changes and random chronic stress or bad luck.
Conclusions: Cancer is an inevitable tradeoff of human biologic design that will always be with us, particularly as life expectancy increases. However, we can often prevent it, we can detect it earlier and we can treat it more effectively. Most cancer is caused by chronic cellular stress that disturbs the delicate balance of our interconnected biologic networks. Malignancy arises due to a buildup of dysfunctional hierarchical structures, in which combination of agents (biomarkers and networks) at one level become agents at the next level. These dysfunctional structures are identifiable by patterns of network changes, molecular changes or possibly histologic changes. New treatment approaches include targeting multiple tumor features to overcome tumor heterogeneity, targeting the chaotic nature of some tumors, moving tumor cells into less lethal network states by emulating physiologic mechanisms and reducing chronic stressors.
Executive summary
1. Cancer is an inevitable tradeoff of human biologic design. It will always be with us, particularly as life expectancy increases. However, we can often prevent it, we can detect it earlier and we can treat it more effectively.
2. Most cancer is caused by chronic cellular stress, which disturbs the delicate balance that exists in our interconnected biologic networks. In the correct microenvironment, it pushes susceptible stem or progenitor cells into increasingly dysregulated and unstable network trajectories that are ultimately associated with uncontrolled cell growth. It is foreseeable that some chronic cellular stressors will cause cancer but which stressors will be important, where the cancers will arise and what their molecular and histologic features will be is not predictable due to the nonlinear nature of complex systems.
3. There are nine important sources of chronic cellular stress that cause cancer and often interact to provide the multiple “hits” (genetic or network aberrations) that produce malignancy:
* Chronic inflammation (due to infection, infestation, autoimmune disorders, trauma, overweight, diabetes and other causes)
* Exposure to carcinogens
* Reproductive hormones
* Western diet (high fat, low fiber, vegetable and fruit consumption)
* Aging
* Radiation
* Immune system dysfunction
* Germ line changes
* Random chronic stress or bad luck
These chronic stressors typically create a field effect; i.e., large areas are affected by a single aberration.
4. Complexity theory helps us better understand how cancer arises:
A. To understand cancer, it is important to think about how life arose from cellular networks because the same principles guide the pathophysiology of cancer. Focusing too much on specific details of the networks, such as characteristics of individual molecules in the network, ignores the overriding theme that the emergence and disturbance of generic network features is independent of these details.
B. Living systems require fine tuning of cellular networks to enable rapid transitions during fertilization, embryogenesis and repair of external or internal damage via inflammation, as well as slower transitions during fetal growth, childhood growth, puberty and response to environmental changes. Living systems must also have enough flexibility to promote and tolerate evolutionary change. Robust control mechanisms prevent these transitions from being activated inappropriately, but the chronic stressors may disrupt these control mechanisms.
C. Malignancy arises due to a build up of hierarchical structures, in which combination of agents (biomarkers and networks) at one level become agents at the next level. Hierarchical structures may be identifiable by patterns of network changes, molecular changes or histologic changes.
D. We can acquire new insights about malignancy by analyzing patterns of network behavior (such as the creation of new hierarchical structures or increasing instability) that are more uniform than changes to downstream oncogenes.
E. Self-organized criticality describes how enormous transformations (“catastrophes”) occur in living and nonliving systems. Similarly, malignant change does not occur through gradualism but by bursts of activity.
5. Treatment approaches based on complexity theory focus on interacting cellular networks, not just killing tumor cells where they exist. Curative treatment must combine multiple strategies that target existing tumors, prevent future tumors from arising and optimize the overall health of the patient:
* Cytotoxic cancer therapy should kill as many tumor cells as possible.
* Curative treatment for adult tumors must address tumor heterogeneity to a greater extent than curable childhood tumors.
* It may be useful to move cancer networks into less lethal states using biomolecules that influence malignant-type behavior or that alter pathways that promote malignant-type behavior.
* Reducing the chronic stressors is important because current knowledge is often inadequate to reverse network changes caused by even the simplest carcinogens.
* Novel treatments may take advantage of the sophistication present in physiologic cells but lost in the somewhat chaotic cells of advanced and aggressive cancers.
* Targeting the microenvironment that nurtures the tumor cells may have therapeutic value.
* More effective screening is important, both for premalignant and malignant lesions.
* Promoting rational medical care is important at the individual and societal level to more easily detect signs and symptoms associated with malignancy and to increase the range of possible treatments.
- End of post -
Friday, May 3, 2019
3 May 2019: Vaccines
Vaccines
by Nat Pernick, M.D.
I was happy to learn that my measles titer blood test
(technically, Measles Antibody, IgG) was positive at 4.6 Elisa units (1). This
means I have antibodies to the measles virus and do not need to get the MMR
vaccine. With a record number of measles cases in the US, including in
Southeast Michigan where I live, I wanted to ensure I was protected (2).
However, I had been told by physicians in the past to NOT get the MMR vaccine
due to my medical history, because it uses a live but weakened virus, which meant
I might be in a similar situation to newborns that were unprotected but unable
to be vaccinated (3).
In late 1983, while a first semester law student in Ann Arbor, I
felt a large, rock hard mass in my abdomen. I was diagnosed with Hodgkin
lymphoma and treated with radiotherapy.
Hodgkin lymphoma is a relatively common cancer, typically of young
adults (4), first described by Sir Thomas Hodgkin in 1832 (5). It previously
was called Hodgkin’s disease because its cause was unknown. However, we now
know that it is arises from post germinal center B lymphocytes (a type of white
blood cell) with "crippling" mutations of the IgH variable region
segment. B lymphocytes are a type of white blood cell that respond to
microorganisms by producing a large variety and number of antibodies. After
these cells are stimulated by exposure to microorganisms, they multiply and
cluster in the region of lymph nodes known as the germinal center. Then, they
multiply and mature into a plasma cell, which produces antibodies (6). Rarely,
B lymphocytes acquire crippling mutations that prevent their maturation (7).
Antibodies have a heavy chain, referred to as IgH, with constant
and variable regions, as well as a light chain. The diversity of the heavy and
light chains creates millions of antibodies that can bind to different
substances. B lymphocytes tend to be relatively unstable, which makes sense
given their physiologic function of rapidly producing millions of “daughter”
cells. To counter the inherent risk of B lymphocytes and other cells
reproducing out of control, multicellular organisms have evolved a
sophisticated process of “cell suicide,” also called apoptosis, that
intentionally destroys these cells and recycles their contents. When apoptosis
is hindered, cancer may occur.
Why Hodgkin lymphoma arises is unknown. In a paper I am finalizing
on How Cancer Arises Based on Complexity Theory (8), I propose that Hodgkin
lymphoma may be due to a “runaway” immune system, which couples the inherent
instability of activated B lymphocytes with defects in apoptosis and other
immune system control mechanisms, either congenital or acquired. The immune
system has a delicate balance between activating and dampening forces, which I
speculate occasionally undergoes major disruption by seemingly trivial events,
based on features of complex systems.
In Hodgkin lymphoma, the tumor cells, called Hodgkin
Reed-Sternberg cells after Dorothy Reed Mendenhall (9) and Carl Sternberg (10),
constitute a very small amount of the tumor mass. These cells secrete cytokines
(biologically active molecules) that recruit normal cells to the area and
change their properties to produce a mass that destroys organs and may cause
death. Remarkably, when the Hodgkin Reed-Sternberg cells are killed by
radiotherapy or chemotherapy, the normal cells revert to normal (11). Today,
Hodgkin lymphoma has a high (80-90%) cure rate, but this was not always true.
One of my high school classmates had an older sister who died of this disease.
After my diagnosis, my oncologist told me that I was immunocompromised
and should not get live vaccines. Thus, when working as a physician in a
hospital that required the MMR (for protection against rubella, or German
measles, which can cause congenital rubella syndrome (12)), I was given an
exemption. However, at age 61, after living a lifetime with better health than
almost anyone I know, I questioned if I was really immunocompromised and could
safely get the vaccine. My internist did not have an opinion. So I had the
measles test to help with the decision process (if positive, I would not need
it). As it turns out, the current MMR recommendations are to avoid the vaccine
only if “severely immunocompromised,” which clearly does not apply to me.
Last week, by coincidence, a Ukrainian pathologist sent me
microscopic images of the appendix of his 40 year old patient with measles
appendicitis (13). The measles virus induces the formation of Warthin-Finkeldey
cells, which are multinucleated cells containing the measles virus, in the
appendix and lymph nodes. They indicate the presence of measles virus, but have no other known significance.
This past week I also decided to get the Shingrix vaccine against
shingles, which is recommended for healthy adults age 60 or older (14).
Although in short supply, the vaccine was available at Maple Pharmacy in West
Bloomfield. Amazingly, even with my high deductible HAP insurance, there was no
charge, but the list price is about $200 per shot. A second dose is recommended
after 2-6 months. Shingles is a very painful disease due to the chicken pox
virus which features a prominent rash and can cause encephalitis (15).
References:
1. ELISA stands for Enzyme Linked ImmunoSorbent Assay. This
laboratory method detects a “target” molecule by attaching a sample that may
contain the target to a solid substance, then adding an antibody to the target
which is linked to an enzyme. In this case, the target is the measles antibody,
so the method uses an antibody to an antibody. Then the antibody-enzyme is
washed away, but it persists if it has bound to the target, which, in this
case, means the measles antibody is present. Finally, the presence of the
enzyme (and thus the target) is detected by adding a substance which typically
changes color in the presence of the enzyme, see https://en.wikipedia.org/wiki/ELISA
3. https://www.cdc.gov/vaccines/vpd/mmr/public/index.html, https://www.nytimes.com/2019/05/02/us/measles-babies-vaccine.html
11. This is one mechanism in which dysfunctional cells influence
normal cells. They can also confer toxic properties on normal cells that are
not reversed by removal of the original cells, as described by prion proteins (https://www.cdc.gov/prions/index.html).
Tuesday, February 26, 2019
26 February 2019: Suicide prevention
I had an experience with someone I know that I want to share. I’ll call this person “Pat” and use male pronouns. I have changed many details to protect Pat’s privacy.
My take home points are: (1) make sure you know the physical address of people you care about, particularly if they are having significant problems, (2) if you are worried about someone and cannot physically visit them, call the local police to have them check. That is why you need the physical address. The police may not be excited about trying to track someone down from their cell phone number.
Pat had been declining for years due to losing a job, relationship issues and health problems. Some time ago, he called me to tell me that “this was the end”, and he was going to harm himself. He had the number of a suicide center but would not call. I had no idea what to do – I didn’t know any of his friends or family who might help. I wondered if he had any other close friends. His significant other appeared to have left him. A physician friend of mine suggested I call the local police, but I didn’t know exactly where he lived. I made my best guess, and spent a fair amount of time getting transferred around and explaining what I knew, which was not that much. Since I was not sure this police department was going to do anything, I called Pat again, and surprisingly he gave me his address. I called the correct police department, who was at his place in 2 minutes.
The police asked some questions, and ultimately took Pat to a hospital with a psychiatric department. Within a day, Pat was released home and to the significant other, who was now back in Pat’s life to some extent. I have called Pat several times since. He was mad at me at first. Didn’t I know he wasn’t serious? But eventually he “forgave” me for calling the police. I actually thought it would be much worse.
There is no great ending. Pat is not suicidal, but still seems pretty miserable. His significant other is back, at least for now. I am a little more grateful for my life, which seems pretty good in comparison. I also feel a stronger obligation to help those whose life is not so good.
Sunday, February 17, 2019
17 February 2019: Living without a car in Detroit's suburbs - an update
Living without a car in Detroit’s suburbs, an update
17Feb19
It has now been almost 2 years since I gave up driving (technically I just gave my car to one of my kids; I can drive if I want). There were several reasons: to reduce my carbon footprint (i.e. take action against climate change), to get more exercise and to see what it would be like. I was also worried about driving after a stressful day. I had no accidents, but was not as attentive as I thought I should be.
After two years, I can confidently proclaim that I am not going back.
I never realized how much stress was connected with driving - I just assumed it was part of life. But when I listen to other people, I now realize how much easier and less stressful my life is because I don’t drive. This is what I don’t worry about - moving cars around in the garage or driveway, shoveling the driveway, warming up the car in the morning, flat tires, cars that don’t start, dodging cars when leaving my house, driving in bad weather, driving when tired or sick, slow traffic, bad drivers, getting lost, parking, car maintenance, car insurance, car payments, tickets, accidents, getting a tow, getting a rental car and buying / leasing a replacement car.
There are problems with not driving, but they seem minor. In the warm weather I bike, and sometimes I get caught in the rain or get a flat tire. It’s annoying, but not that bad. Rarely I fall, but at least to date, I have only had some bruises. Sometimes I take the SMART bus, which involves some waiting. Once the bus hit a car and went “off line” until a supervisor came. I got a ride from someone else, rather than wait. If I am worried that the bus is not showing up, I can use Uber / Lyft as a backup.
In the cold weather, I use Uber and Lyft. For the past 2-3 weeks, in the morning, Uber does not seem to work for me. No cars are available, although once I tried the “upgrade” of Uber XL, which did work, but cost an extra $5. Fortunately, Lyft cars have been available. I use both and check the best price - often there is a dramatic difference. The drivers are typically interesting and pleasant. I like talking to most of them about their lives. Some are not the friendliest, but none are hostile or threatening, unlike the taxi drivers in my past.
My life is now simpler. I don’t spend the weekend running around doing errands. I bundle trips, shop online, and avoid doing things that really are not important. If I am meeting someone and there is a supermarket nearby, I will try to go there afterwards. This also introduces me to different places to shop.
What about the cost? I estimate that ride sharing costs me more in the winter than car ownership, but less in the warm weather when I bike. Even if it does cost more overall, it is worth it to me to have my own personal driver, so that I can work or sleep or socialize with the driver, instead of anxiously watching the road. In addition, I get dropped off and picked up right at the door of my office or wherever I am going. The down side is waiting, typically 5-20 minutes, for the driver to arrive, but I just read or use the computer. Every once in a while I have to go back and forth between the Uber and Lyft apps for a few minutes until I get a decent rate.
Living without a car works for me, but I am not preaching - everyone has to figure out how to optimize their own life. But you should know that not having a car is a possibility, even for someone with an active life.
Prior articles about living without a car:
Saturday, January 12, 2019
12 January 2019: The decline of mental inhibition
The New York Times recently published an article about the acclaimed scientist, James Watson, co-discoverer of DNA, and his bizarre thoughts about differences in IQ between ethnic groups, click here. The article can best be summed up by the statement of Dr. Michael Wigler, a scientist at Cold Spring Harbor Laboratory in New York, which revoked some of the honors it had bestowed upon Dr. Watson:
It is not news when a ninety year old man who has lost cognitive inhibition, and has drifted that way for decades as he aged, speaks from his present mind,” Dr. Wigler wrote in an email. “It is not a moment for reflection. It is merely a peek into a corner of this nation’s subconscious, and a strong whiff of its not-well-shrouded past secrets.”
Detroiters may recall a similar situation when veteran White House reporter Helen Thomas started spouting anti-Semitic views, click here. Wayne State University ultimately revoked an award in her name, click here.
I suggest that family and friends of public figures need to protect their legacy by keeping them away from situations that will be harmful. All of us have evil thoughts, but our intact intellect keeps us from making them public. But when we lose that inhibition under the influence of alcohol or when suffering from dementia or other mental decline, it is not surprising that we will say terrible things. Of course, this is true for those who are not public figures, but their friends and family know their true nature, and that this is part of their condition.
In addition, I suggest that the awards should not be revoked. These individuals did great things, and their statements, although terrible, were made when their minds were damaged. We should not hold that against them.
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