hi everyone welcome to our channel today we will discuss how to treat yeast infection. Is your furry mate in constant discomfort,
licking, and gnawing at its feet? Or have its ears turned gunky and it just
can�t stop scratching them? Also, if you can pick a foul and musty smell
from the coat, take it as a final confirmation that your poor pooch has been infested by
yeasts, an infection also known as yeast dermatitis. It is a common �pet peeve,� especially
in a hot and humid climate. Yeast is a type of fungus that is found both
on the skin and in the gut of every healthy pet or cat. Your pet�s natural defense keeps the number
of yeasts in check. However, at times, a stressed immune system
can lead to an abnormal growth of the fungus, giving way to a yeast infection. While it is important to take your pet to
the vet as soon as you notice the symptoms, a number of adjunct home remedies can also
be used in to speed up the recovery. Here are the few safe home remedies you can
use to treat yeast infection in pets. Home Remedy # 1: Yogurt Increasing the good bacteria in your pooch�s
gut will help raise its natural defense to counter infections. Add � cup of probiotic yogurt to your pet�s
food. Increase the quantity to 1/2 cup for a larger
pet. Feed the appropriate quantity of yogurt once
daily for 3 to 4 days. Home Remedy # 2: Apple Cider Vinegar Similar to white vinegar, the anti-fungal
content of apple cider vinegar can also kill the fungi causing yeast infection in your
pet. Take a small spray bottle half-filled with
water. Fill the remaining half with raw and unfiltered
apple cider vinegar. Shake well and spray it on all the itchy areas
of your pet. Let it air dry. Use it 2 to 3 times every day for 4 to 5 days
to get rid of the yeast infection. Home Remedy # 3: White Vinegar White vinegar works as a powerful disinfectant
to clean the infected site and soothe the red and inflamed skin. Mix � cup of white vinegar in � cup of
water. soak a cotton ball in the solution and apply
it on the affected surface. Use white vinegar 3 times a day for 1 or 2
days. Home Remedy # 4: Tea Tree Tea tree oil is a powerful antifungal agent
that has proven its worth to treat various skin maladies in humans. Add 1 or 2 drops of tea tree oil to 1 teaspoon
of olive oil. Blend well and massage it onto the affected
skin of your pet. Home Remedy # 5: Coconut Oil As coconut oil is anti-bacterial and anti
fungal in nature, to get rid of the yeast infection. Take some extra virgin coconut oil and rub
it on the affected skin patches of your pet. The oil is pretty light and will absorb quickly
into the skin. Home Remedy # 6: Colloidal Silver Colloidal silver is also a powerful anti-microbial
compound that blocks cellular respiration in the pathogenic cells present in your pet�s
body, and thus suffocates and kills them. Mix 5 to 10 drops of colloidal silver to your
pet�s wet food or drinking water. Repeat 2 or 3 times every day for 1 week to
get rid of the yeast infection. Home Remedy # 7: Zymox Solution with Hydrocortisone Zymox is a broad spectrum anti-microbial solution
that is especially beneficial in treating ear infection in pets. Put 10 drops of the Zymox solution in both
the ears of your pet. Close the ear flap and rub the ears for 10
to 20 seconds. Allow your pet to shake off excess fluid. Repeat this once every day for 1 week. While it is important to take your pet to
the vet as soon as you notice the symptoms, a number of adjunct home remedies can also
be used in to speed up the recovery. so apply these home remedies to get rid of
yeast infection in pets.
Good day, Eric Bakker, another FAQ here. This
question is from Paul in Sydney, Australia. Erik, how long does it take for me to cure
Candida? How long does it take for me to get well? Well, there’s no real answer to this question,
Paul. You know, I generally find many people with a yeast infection take on average between
four to six months to get well. But in saying that, it could take 8 months, 9 months, or
even 12 months. Some patients can take two years or more to get well. So to answer your question; my reply to you
would be what are you going to do to do what it takes to get well? Are you going to eat
the right foods? Live the right kind of lifestyle? Are you going to rest plenty? Are you going
to have a good balance between work and play? It’s a good question you’re asking me, but
my reply would be you need to have a balanced lifestyle, eat the right kind of foods, and
keep working on that yeast infection for as long as it takes to get well. In my situation, it took about a year to get
well when I was in my 20s. I had a rather extreme case of Candida. If you’ve got a Candida
infection in the gut or perhaps in the groin region or in the foot region or if you’re
a female with a vaginal yeast infection, it depends on whether it’s acute or chronic.
It depends on whether you’ve taken antibiotics or not. So there are many variables to answering
this question. But generally a yeast infection when you’re on to it, you’re doing the right
things, on average you can account for about six months to get well. But if you’ve had
a yeast infection for 10 years, it may take you 1 year get well. There’s no real clear cut way to answer that
question, Paul. If you’ve got any more questions, I would say go and have a look at my YouTube
channel. You’ll find lots of different questions there and responses to questions. If you can’t
find the question you’re looking for, please contact me on Candidacrusher.com and ask me
the question, and I’ll reply to it. Subscribe to my channel. There are many questions
on my YouTube channel and there are many more coming. And the third thing is please do my
survey on yeastinfection.org. I’ve designed this survey after quite a long time for men,
women, and children, and it will show you the severity of your yeast infection. Thank you.
Greetings. It’s New Zealand naturopath, Eric
Bakker, author of Candida Crusher and formulator of the Canxida range of dietary supplements.
Thanks for tuning in today. I’ve been asked by many people in several
countries to do a video on how to do a Candida cleanse. What’s the best way to rid my body
of a yeast infection? How can I clean up my system? How can I get rid of bacteria and
parasites? How can I get rid of Candida? That’s what we’re going to talk about today. I’m
going to put quite a few elements together for this video, and I think you’re going to
find it quite informative. It will be a video you may want to watch once or twice because
there will be quite a lot of information here for you to take in.
There are essentially three elements to a Candida cleanse. If you want to do it properly,
there are three main categories that we’re going to talk about. Category 1 is the diet,
what to eat, what to avoid and special foods. Category 2 is the lifestyle, and Category
3 is what are the best kind of supplements to take. Let’s just go through that step by
step and explain to you a little bit about what I think is the best kind of Candida cleanse
to do. You may be familiar with my website, yeastinfection.org.
If not, please go and have a look at that website. And if you haven’t already done my
online questionnaire, I would urge you to do that to see what kind of level of Candida
you’ve got. If you’ve got mild, moderate or severe. Thousands of people have already completed
this online quiz, and I could easily say it’s the world’s best online quiz for yeast infection.
It cost me a hell of a lot of time and investment to create this quiz, and I think it’s the
best one around. So if you haven’t already completed it, please go to yeastinfection.org
and complete that quiz. Let’s talk about the diet as being the first
step. Before we go into taking you off of all kinds of foods and saying, “You can’t
do this and you can’t do that,” the first thing I like to do is to put a person on a
really basic Candida cleanse. Usually for the first 14 days, I get people to clean up
their act, for want of a better word. And that 14-day period, I call it the “warm turkey”
period. Cold turkey means you take everything away from people, but warm turkey means you
have a softer approach. For 14 days, we’re going to get you to be aware of everything
you’re eating and drinking. And in that 14-day period, I want you to stop all alcohol. I
want you to cut caffeine down to one or two cups per day max, and generally, a cup of
coffee or tea in the morning is okay, providing you don’t put sugar in it. Those sorts of
drinks are usually okay. In that 14-day period, you’re going to have
a good look at what kind of takeaway or junk food you eat. What kind of processed foods
you eat. You’re going to look into your refrigerator and try to get rid of all those bottles and
jars with different sauces. Often they contain sugars, molds, and all kinds of crap in them.
Many people I know have got containers in their cupboard or refrigerator. There could
be jars of jam in there or all sorts of sauces, shrimp sauce, chili sauce, tomato sauce. They
all need to go. Because on a Candida diet, they’re not really good foods to have. That
14-day period is when you’re going to make the switch from eating the not-so-good foods
to eating a better kind of food, and I think it makes a lot of sense. In my experience,
it’s not good just to plunge people into an average, standard diet and then into a Candida
diet. You need to have a transition period. That’s the two-week period. You’ll be able
to read more about that at yeastinfection.org about that transition period that is very
important to do. Once you’ve gone through that transition period,
it’s time to look at what I call the MEVY diet. The MEVY diet has been around for a
long time now, probably about 40 years. In fact, these sorts of diets have been around
before the word “paleo” diet was invented. These are high protein diets. Candida loves
sugar, so of course, the big thing that we want to do is take sugar out of the diet.
Yeast need sugar to thrive, and the Paleo/MEVY kind of approach doesn’t really have sugar
in it. The MEVY diet is an acronym for meat, eggs, vegetables, and yogurt. That’s how you
basically form your diet. Lots of good quality lean proteins. My favorite protein is fresh
fish, free-range chicken, free-range eggs. If you’re a vegan, there are plenty of other
options you’ve got. There are plenty of legumes you can eat. There are nuts, seeds, beans,
and all sorts of things you can eat. If you are, however, a non-vegan or you are a meat
eater and want to go more into the legume kind of diet, be aware that the bacteria in
your digestive system will not be used to processing those kind of foods yet, and there
could be a lot of flatulence going on and bloating, as you have to let your gut get
used to these kinds of foods. Making any kind of quick diet switch is not really a good
idea because you could get a lot of digestive upsets. Whether you’re a vegetarian going
to start eating more meat or whether you’re a meat eater going to start eating more vegetarian,
you need to make the approach very slowly and gently over a period of one to two months.
The MEVY approach is very important because it basically starves the Candida. It stops
the Candida from feeding on the kind of foods it loves to have. In that MEVY diet approach,
I often get asked, “How long do I need to do that? Is it a week? Is it a month?” There
are no real guidelines here. I generally like to keep people on the MEVY for anything from
one month up to three months, but I mean that’s up to you. You could do it for four, six,
or eight weeks if you want. Once you’ve gotten used to eating this kind of diet, and again,
you can read more on yeastinfection.org or in my book, Candida Crusher.
Once you’re used to this kind of dietary approach, we start moving you into what we call the
low allergy diet. At this stage, we’re going to take out the most allergy forming of all
foods like the dairy products, especially cow’s milk. I take out bananas. I take out
oranges. I make sure that there is no chocolate in the diet, even dark chocolate, 70 percent
cocoa or whatever it is, that’s got to go for a while. We take peanuts out. And then
we tidy the diet up even a little bit more. We take out some more foods that potentially
could affect your digestive system. My book contains quite a large page on the hypoallergenic
diet. The books are available through Candidacrusher.com. I think I’ve written the most comprehensive
information anywhere on the internet regarding food and yeast infection.
The low allergy diet is very smart because what we’ve done initially. We’ve cleaned you
up, we put you into a protein diet with plenty of fiber in there and starches for the good
bacteria to feed on. Now, we’re stripping away the potentially allergenic foods. This
is a very smart move because a lot of people with Candida have got food allergies and food
intolerances. They will have one or two key foods that are creating immune dysfunction
because nearly all patients I see with Candida have got leaky gut. But taking out the potentially
allergenic foods are going to stop the immune system from reacting.
After this low allergy approach, and again, that can last anywhere from 4 weeks up to
about 12 weeks, depending on how you improve. You’re going to start reintroducing foods.
That’s the third stage of the diet. Before we go into the food reintroduction, it’s important
to also tell you that you need to eat foods that are going to help fight Candida. And
again, I’ve written quite a lot of articles and done YouTube videos on the anti-Candida
foods. We’ve talked about garlic extensively, oregano, coconut oil, clove. There are many
different kinds of foods you can consume that actually fight Candida that the Candida hates.
These foods also discourage bad bacteria like Citrobacter freundii. They get rid of things
like Blastocystis, pseudomonas, all these kinds of bacteria and parasites. They don’t
really like this kind of diet approach. This diet approach is very favorable toward encouraging
the beneficial bacteria. When we look at the special foods for Candida,
we’ve got the anti-Candida special foods. And then we’ve got the prebiotic special foods,
so there are two separate categories of foods that I think you should learn to incorporate
into your diet as you’re going through a Candida cleanse. Foods that discourage Candida and
bad bacteria and foods that encourage the good bacteria. We call those the FOS and GOS
foods. I’ve written a whole article on that at EricBakker.com. I think it’s Part 4 of
my “Alternatives to Antibiotics,” but I’ll explain a little bit about those FOS and GOS
foods right now. These are special kind of foods that contain
sugars called oligosaccharides. Not all sugars are bad for Candida. Oligosaccharides, in
fact, are what we call “prebiotic” foods. And these foods encourage the growth of lactobacillus
acidophilus and bifida bacteria. It’s very important for you to understand that you need
a lot of these beneficial bacteria to fight Candida. These beneficial bacteria themselves
produce lots of different types of antibiotics in their own right that counter the bad bacteria.
Acidophilus is also responsible for the production, particularly bifida bacteria, for B vitamins
and Vitamin K and even folate, folic acid gets produced by these beneficial bacteria.
These beneficial bacteria are responsible for powering up your immune system, making
you feel very good. I see countless stool reports from Candida patients that show very
low levels of beneficial bacteria. Let’s look at some of the FOS and GOS foods.
There are plenty of them. Foods like Jerusalem artichokes, asparagus, sweet potato, particularly
the darker colored vegetables, like the red ones and the black ones. You can get these
dark potatoes in New Zealand called Mallory potatoes or like purple potatoes. You might
be able to get them in your country, purple colored potatoes. Dark colored carrots, red
carrots, or even purple carrots. Purple cabbage is quite a good one to have. Purple grapes,
all these sorts of foods. Before you start saying, “Hang on a minute.
I can’t eat grapes. I can’t eat sweet potato. I can’t eat this.” You can eat these foods,
but they have to be introduced at the right time. Grapes are not a food you’re going to
have in the first several months of a yeast infection. But over time, you’ll be able to
eat a couple of grapes. And when I say a couple, I’m talking three or four. I’m not talking
about handfuls of grapes. Any large amount of food regardless of what kind of sugars
they’ve got in them are going to upset your digestive system until you can get used to
them. When it comes to the FOS and GOS foods, you have to introduce them slowly. A lot of
vegetables contain FOS and GOS. Even the root vegetables like sweet potatoes contain them.
I don’t generally always take out pumpkin and sweet potatoes, squash, sweet corn and
peas from somebody’s diet in the MEVY stage. I only do that if they’ve got a seriously
bad Candida infection. If they’ve had it for years. They’ve had years of antibiotics. They’ve
had years of brain fog. If they’re a Category 3 patient, like a really bad patient, then
I may take out these starchy vegetables for the first two or three weeks, but then I slowly
reintroduce them. It’s not good to take people off all starches and grains because they get
bored with their diet and they lose too much weight, and I’m not a fan of anti-gluten,
anti-wheat, anti-rye, anti-oats, anti-everything. I don’t like being the food police to my patients.
I was in the first several years of my practice and I found that it pissed off too many people,
and a lot of people didn’t come back. A lot of patients will end up gravitating toward
their own diet down the track anyway regardless of what you say. Remember the special foods.
The FOS and the GOS foods. You can read a bit more about that on EricBakker.com.
That constitutes the diet. The diet is the easy part of the Candida approach. The hard
part is the lifestyle, and that’s something you’re not going to read about on a lot of
websites. The Candida Diet website, for example, doesn’t talk about how important lifestyle
changes are. Most yeast infection sites I’ve seen talk very little about lifestyle. And
this is the missing link because three quarters of your recovery from Candida is about lifestyle.
Because lifestyle affects your immune system. It affects your endocrine system, your hormone
system. It all gets affected by lifestyle. So what’s the point in eating really good
foods if you’re going to bed at one o’clock in the morning and looking at your iPad? Waste
of time. What good is there in eating a lot of good foods if you’re living in a situation
with bad relationships or a lot of stress hanging over your head? High mortgage stress
or something like that. Waste of time eating good food.
Let’s look at some lifestyle points here. The work/life balance is very important. Many
people today have got blurred boundaries. They work for too long, too many hours. They
don’t take enough time out. I’ve spoken about this at length on other videos, too. That
people will often go from one screen to another screen. They’ll go from their work computer,
they’ll go home, and they’ll spend more time on their mobile phone or on their electronic
device or on their computer right up until when they go to bed. When they go to bed,
they take the device to bed with them. There is no balance there. You need a clear demarcation
between working and not working. You need what’s called “leisure time” or “relaxation
time,” and that’s really missing today. Leisure time empowers the parasympathetic nervous
system. This is the nervous system that helps to rebuild the body. It helps the body to
rest and digest. The activating system or the sympathetic nervous system is a system
we use during the day, and this empowers us and gets us up off our feet doing things and
thinking about things. That’s the sympathetic nervous system. It activates all our organs.
The parasympathetic helps to calm and slow down and rebuild. And as I said, it’s rest
and digest. That system activates predominantly when you’re sleeping.
Sleep is a big problem. Forty percent of people in my country have got sleeping issues. If
you’re in the US, I would say over half of the patients I see have got a sleeping dysfunction.
What’s the point in having a premium diet with quinoa and salmon, organically grass
fed beef and all this sort of stuff if you’re not sleeping properly? What a load of crap.
You just can’t expect a really good health and recovery if there is a poor sleep level.
You need to sleep very, very well. If you’ve got a sleeping issue and you’re watching this,
that is probably one of the primary things you need to fix up. Work out why you’re not
sleeping and fix that up. Exercise. You’ve heard all about it. You’ve
probably seen lots of videos and read lots of blogs and thought, “Yeah, I’ll get around
to it one day.” Regular walking or exercise is paramount for recovery from Candida. Everything
improves when you exercise regularly. If you’re not doing it now, you need to start doing
it. This could be one of reasons why you’re not recovering. If you’ve been sick for years
and you’re doing everything right, but you’re not recovering, get off your butt and do some
exercise. Join the gym or find an activity that you like, whether it’s cycling or swimming
or walking, you need to be active if you want good health. And again, if you can’t understand
that concept, you’re probably wasting your time watching this video because you’re not
going to cure Candida with supplements and diet alone. In some cases, but in chronic
cases, you won’t. You need to look at the whole picture.
Attitudes. Attitudes are very important, too. It’s very important for you to cultivate a
positive frame of mind, and always believe in a full recovery. That you’re going to really
recover from Candida one day. The patients I see that have been sick for years that recover,
they understand that health is in their own hands and they have to make those calls on
what they can and can’t eat. If they’re going to get off their butt to go out for a walk,
if they say “no” to an alcoholic beverage. They know that it’s all up to them. And the
attitude is very important to have a very positive attitude and to watch out for negative
people, and to watch out for really negative things on the internet. Because there is a
lot of junk on the internet. I want you to think carefully about the lifestyle.
There are many articles I’ve written on yeastinfection.org on lifestyle and attitudes on how to be happy,
for example. Understanding the things that predominate the parasympathetic nervous system
or the healing part of the nervous system. Laughing a lot more. Chewing food properly.
These are very important concepts for you to bear in mind. Sleeping, resting, because
this allows digesting. These are important concepts and you need to really get a good
grip on those, in my opinion, even more so than the diet to aid a full recovery.
And the last point we’re going to talk about will be the dietary supplements. I’ve created
a range of products that you can find on Canxida.com. The Canxida supplements were created because
I’ve been using supplements for patients now for over 20 years in my clinic and realize
that there are a lot of problems with many of these dietary supplements. They weren’t
performing the way I like them to. And many patients were aggravating on all kinds of
supplements that I use. So I thought it’s time to make my own products and to make them
to my standards. I used the best quality raw materials in the exact proportions. So far,
two products have been created. One is called Canxida Remove and the other one is called
Canxida Restore. Canxida Remove has proven to be a difficult product to manufacture.
It’s not easy. And nothing really good is easy to achieve, I’ve discovered.
Our first batch sold out very, very quickly, and we had incredibly good feedback on it.
Our second batch is almost produced now, but we’re waiting for one of the raw materials.
Canxida Remove, in my opinion, is the premium antifungal/anti-bacterial/anti-parasite product
made yet. You won’t find anything like this anywhere else on the internet. It’s quite
a unique product in that I’ve tried to select the best herbal medicines that really target
Candida, but also ones that quite specifically target many different kinds of parasites and
bacteria. So it’s a very broad-spectrum product that really helps to cleanse the bacteria
and fungus from the mouth right through the back passage. It cleans everything up. It’s
also made in a sustained release form, so the tablet takes about three to four hours
to breakdown in the gut. What you’re going to find by taking this product two to three
times per day is you’re going to have a long kill range, so it’s going to be able to wipe
out bugs over a prolonged period of time. And that product should always be taken with
food and preferably for anywhere from one up to six months. And it works perfectly fine
at any stage of the Candida Crusher protocol. It will work quite well.
The second product I created is called Canxida Restore. Canxida Restore is a probiotic/enzyme
combination. It contains seven different enzymes and six probiotics. I didn’t put any fructooligosaccharides
or inulin in this product, so there are no prebiotics in there, and I did that for a
very specific reason. I’ve used too many products in the past with prebiotics and had aggravations
from patients. Spaced out people, sick people, they developed bloating, gas, headaches, all
kinds of things. And I can tell you I’ve used every darn product out there for Candida that
I could find. All the professional products. All the retail products. I know all the brands.
I’ve used them all. And after using so many different products, I started to discover
that most of them in these combinations with enzymes and probiotics contain prebiotics.
And I thought, “What the hell is that all about? Why don’t I just get people to eat
foods that contain prebiotics and then they can eat more or less as they see fit, but
keep that separate from the supplement?” So the Canxida Restore was very carefully made
to use the best possible enzymes for people going into the MEVY diet. If you’re on a Paleo
kind of approach or a high protein diet, this is a perfect supplement for you to eat. If
you suffer from food intolerances or food allergies, this is the perfect supplement
to take along with that. I’ve created the Restore to be used as a stand-alone
probiotic or a stand-alone digestive enzyme for any kind of gut related problem, constipation,
diarrhea, irritable bowel, inflammatory bowel, food allergy, food intolerance, any of those
kind of conditions you’re going to get benefit from the Restore. Now, the Restore also contains
a systemic enzyme in it called serapeptase. And this enzyme is very expensive. People
look at my supplements and say, “Oh, you put a bit of a premium on that product.” I can
tell you now, I’ve used the best possible enzymes from the top manufacturer in the world
in that product in a very special capsule, a time release capsule, that only opens up
in the small intestine. The probiotics are in a spore form, so they take time to really
get warm, open up, and activate. And also, there are about 15 to 20 percent more probiotics
in that product than is stated on the bottle. You’re going to definitely get these beneficial
bugs into the system. The Canxida Restore is best taken one in the morning with breakfast
and one before bed at night. Two per day is usually good, so that’s going to give you
a whole month on one bottle. The Canxida Remove, you take one of those
with breakfast, one with lunch, one with dinner or you can take one twice per day. Two or
three times per day, that’s up to you. Take the Remove with food and take the Restore
one with food in the morning and one before bed at night. And that protocol is an amazing
protocol and I guarantee that you’re going to get outstanding effect on that. Those products
are available through Canxida.com. Don’t forget to please do my online quiz at
yeastinfection.org. It’s important for you to do that to get a feel for where you are
right now. And then once you’ve treated yourself with these products, again within a month
or two, you can do the quiz again to see where you are, what the ballpark is. A good thing
for you to do. Please subscribe to my Candida Crusher channel. I’ve got many subscribers
now, and I intend to make many more high quality videos for you to enjoy. Please keep emailing
your questions through, so I can respond to those questions as well.
Thank you so much for the comments I’ve been receiving. It’s been fantastic. I hope this
has been an informative video today as I’ve covered most of the points. Thank you very
Greetings, Erik Bakker from New Zealand, the
naturopath. I have another question here from a subscriber. I feel that most of my symptoms from Candida
have gone away in the last three years, since I have treated it with a variety of herbs,
example, oil of oregano, berberi, grapefruit seed, etc., an oral thrush persists despite
coconut oil, oregano oil pulling, tongue scraping, Pittman oil, but I also wonder if the fluoride
in toothpaste kills good bacteria, which could be harmful to oral health. Well, I would like to see what kind of diet
you’ve got, what you’re eating on a daily basis but I’d also like to see what your adrenal
health is like, what your overall eating patterns are like, energy patterns, sleeping patterns
all those kinds of things are very important. It’s not just about what you eat and how you
treat, it’s about how you live your life, so a whole other effectors make up for digestive
health. The state of your autonomic nervous system,
do you feel more stressed and relaxed, do you spend enough time relaxing, exercising,
doing things apart from work especially if you are a computer-based person. So there’s lots of commentary about treatment,
oil pulling and all the things that you’re doing, brushing, scraping all this stuff. There’s a lot of oral based stuff that you’re
doing, but what about other things in your life that you may not be doing for example,
okay, it’s very important. Fluoride in toothpaste kills good bacteria. I don’t know about that, I know many people
who use toothpaste with fluoride in it, they don’t have any problems at all. I’m not going to get into political debates
about fluoride, pro or con things like that. I prefer to drink water without chlorine or
fluoride in it with a water filter and I recommend everybody do that. Each to their own. I know that many people who do drink water
with chlorine and fluoride with it and they don’t have any health problems. And I know many other people who say they
do get health problems so that’s up to the individual. I would tend to use more natural kinds of
toothpaste like with baking soda in it, not the commercial ones, I wouldn’t recommend
you buy the commercial toothpaste anyway. I don’t like all that names of chemicals you
can’t even pronounce, I don’t think it’s a good idea. I’d also say what are you doing in terms of
cultured and fermented foods. Are you putting any of these in your diet,
like yogurt or kefir, sauerkraut, what are you doing there? Are you eating foods that are conducive towards
building good bacterial health in the gut. I just did a video on prebiotic foods, for
example, are you eating all of these? Are you chewing foods properly? Have you got good dental health? What are your cortisol levels like? What is your immune function like? Do you get sore throats? Do you get any other kind of health issues
at all? So it’s not just about the persistent oral
yeast it’s about your overall health. There’s a picture here that we need to look
at. So maybe I’m not as helpful as I could be
with this question but if you give me some more information maybe I could be. Thanks for the question, anyway
Hey guys, Dr. Axe here. I want to talk about
the many benefits of vitamin D as well as vitamin D deficiency. So many people are struggling
with vitamin D deficiency. In fact, according to a lot of medical studies today, they’re
showing that quite possibly the top deficiency we have in America is a vitamin D deficiency,
and for a lot of us there are several reasons for that. But let me talk about the symptoms
of vitamin D deficiency. I’m then going to get into what’s causing vitamin D deficiency,
then go over the best foods, supplements and things you can do to correct this type of
issue. But first and foremost, the big thing that
can cause or the big symptoms you might have with a vitamin D deficiency are immune issues.
If you have a weakened immune system, that could be correlated with a vitamin D deficiency.
If you have candida or bacterial overgrowth, it can be caused from a vitamin D deficiency.
If you struggle with let’s say emotional ups and downs, like depression and anxiety, that
can be a cause. Hormone imbalance, major cause of vitamin D deficiency. If you have trouble
putting on muscle or losing weight, those are all correlated with a vitamin D deficiency.
If you have weak bones or teeth, osteoporosis or osteopenia, those are warning signs you
have a vitamin D deficiency. So again, you can see there are a lot of things
— and I didn’t even get into certain other things like cancer and diabetes and heart
disease — but those are all warning signs you could have a vitamin D deficiency. Vitamin D is responsible for really supporting
a healthy immune response, digestive health, hormone balance, and here’s a key thing to
remember. Vitamin D is not just a vitamin. It’s also a pro hormone. So it’s responsible
for so many hormone producing reactions within your body. You’ve got to have vitamin D. Now here are the biggest causes of vitamin
D deficiency. Number one is not getting enough sunlight. The sun should be your number one
source of vitamin D. We live in a world today where we live inside, especially if you’re
in the northern states, whether it be in Canada or northern US or northern Europe. But if
you are not getting outside enough and not getting enough direct sunlight on your skin,
that will create a vitamin D deficiency. So starting off, the majority of people are vitamin
D deficient because we don’t get outside enough. And the other thing can be certain chemicals,
especially things that are plastic in nature, those can block vitamin D absorption. So if
you’re drinking out of plastic bottles that have something called BPA, that’s bisphenol
A, that can cause vitamin D deficiency and really affect the way vitamin D is absorbed
and utilized and created by your liver in your body. The other thing is toxicity. If you’re exposed
to toxins on a regular basis, that affects the liver. Your liver is actually responsible
for producing and creating vitamin D within your body. So again, toxicity another major
cause of vitamin D deficiency. So if you want to start to correct vitamin
D deficiency and see improvements in your immune function, in your metabolism, in your
hormones and things like your thyroid and your adrenal glands and improving your overall
mood and bone strength, you’ve got to get more vitamin D. Again, your number one source by far is sunlight.
I recommend getting outside 20 minutes to 30 minutes every single day. Even if it’s
cold outside, getting a little bit of sun on your face and hands, it’s so important
for getting Vitamin D. So again, number one is get sunlight 20 to 30 minutes a day. Now, apart from that, certain foods will contain
small amounts of vitamin D. Number one source will be wild caught salmon or fish, so again
getting wild caught fish on a regular basis. Also, raw fermented milk, like a goat’s milk
yogurt, may have small amounts of vitamin D, as will mushrooms and eggs. But again,
you’re going to get very small amount in diet. Those foods are good. But again, it’s only
small amounts of vitamin D. Then the next thing would be take a high quality
vitamin D supplement. You don’t want to take vitamin D2. You do want to start taking vitamin
D3, and there are many forms of this. There are several good brands out there today. But
again, you can actually take it in a capsule form. You can actually get it in a spray bottle
form. But again, vitamin D is essential to take as a supplement. For most adults, 2000
to 5000 IUs a day is what’s recommended. Now if you have a severe deficiency and you’ve
gone and got a vitamin D test done, in that case for 1 to 2 months, you might take 5000
IUs 2 times a day. But again, for the days that you’re not in the sun, I recommend 2000
to 5000 IUs of vitamin D3 daily. Here’s one last important thing to remember.
When you are supplementing with vitamin D3, you want to take it with some fat because
it’s a fat soluble vitamin. So take it with a teaspoon of coconut oil or take it with
a fish oil supplement. But when you are taking vitamin D, you want to take it with some healthy
fat like coconut, avocado, or an almond butter. You’ll want to get it with some healthy fat
because it actually improves and increases absorption there as well. So again, make sure
you’re getting your vitamin D. It is crucial for immune function, bone health, emotional
health, and balanced hormones. So again, remember vitamin D, it’s not only
a vitamin. It’s a hormone. It’s an immune boosting nutrient that you’ve got to have.
Hey, if you’ve enjoyed this video, make sure you subscribe to our other YouTube videos
on our YouTube video page as well as our newsletter here on DrAxe.com. We’ve got some great information
coming out as well on other vitamins and nutrients that can help take your health to the next
Here’s a question. Will a male yeast infection
go away on its own? It can. In fact, it is possible if it’s a very slight yeast infection
and not much is done about it. Particularly, if the guy makes a few changes to his diet
and lifestyle and starts to realize that he’s really gone off track and makes a few changes
and then the body will pick up; the immune system will get on top of it. But in most
cases, it will not go away unless the guy makes a significant change or starts using
some kind of cream or pill to suppress the symptom, but those treatments are only temporary,
and they can harm your body in the long term because you’re still doing the things that
maintain the Candida and now you’re taking a drug, whether it’s topical or oral, to try
to get rid of the problem. I’ve always been a great believer in identifying
the cause and treating the cause, and if you understand that with Candida we’ve usually
got an exciting cause or something that starts the yeast infection and then we’ve got a maintaining
cause, something that keeps it going. For example, you may have had an antibiotic for
an illness or an infection and that could’ve started your jock itch like it did with me.
I had a chest infection. I worked in a flourmill as a young guy doing rotating shifts, I got
very sick and developed a bad bronchial infection and the doctor gave me antibiotics. And I
went on a few rounds of them and then I started getting itchy skin and the jock itch and it
didn’t go away. And how did I maintain it? Well, I was drinking
beer like all guys do. We all drink beer. And I drank stupid things like Coca-Cola and
I had a poor diet back in those days. I lived in a house that was quite moldy. It was in
a low-lying area and when it rained I used to get sometimes water in my bedroom. There
was even like a black mold on the walls, so I was sleeping in a moldy environment. I was
eating poor foods. I was living in a high stress sort of job with rotating shifts, midnight,
working days, and the midnights and crazy hours, so all these stresses on the body maintained
the jock itch. These are the sort of things that you’ve got
to look at. You won’t get rid of this problem unless you make major changes, so I got rid
of my job, just got rid of it. I moved out of that house, moved away, and I saw a naturopath,
which was the start of my naturopathic career. The naturopath helped me to understand that
all that Candida was was a combination of all of these factors that I had to make changes.
And when I made the changes, the jock itch slowly went away after about a year. So this is what you need to do. Identify what
caused it and what’s maintaining it and deal with this problem correctly. When you do that,
you’ll put an end to this nightmare. That’s how you get rid of it. It won’t go away on
its own accord. You need to make those changes. Check on my other videos and do the yeast
infection quiz, the world’s best one, on yeastinfection.org you’ll find links to that or CandidaCrusher.com
will take you directly to my quiz. Thanks for tuning in.
Thanks for checking out my video. I’m going
to be doing a series of case histories over the next few weeks, which may be of use to
you. In my book, Candida Crusher, there’s about 25 case histories in here out of the
many thousands of people I’ve seen, so I’ve written a few of them up in here. I’m going
to go through a lot of these case studies. I’ll read some text out of my book and then
I’ll elaborate on these cases and explain a bit more as they go along. I think you might
find this of a lot of use. Our first case history is a 19-year-old lady
called Kirsty. This is out of chapter two of Candida Crusher. Kirsty’s a young female
student who came to my clinic about two years ago complaining of chronic fatigue. She was
absolutely exhausted and found it hard to concentrate at the university. Kirsty was
falling asleep during the afternoon lectures and becoming anxious at her inability to concentrate.
Her main complaints were foggy thinking, anxiety and depression, occasional vaginal yeast infection,
intermittent pains in her tummy, nausea and small white spots on her body.
Her mother had been a patient of my practice for some time, so she referred Kirsty to see
me. When I questioned about her daughter’s diet and lifestyle, so I gave her a call.
I remember calling this lady up. Sometimes I get very good information from relations
of patients regarding the patient’s behavior or desires, their diet, and sometimes people
are a bit embarrassed to give that information away.
I practice in a small village her in New Zealand. Not that many people and many people know
people. And for that reason, I often get a lot of inside information on people. It’s
surprising how often I go shopping and someone will say, “Oh, I’ve got to send my daughter
to you,” or “I’ve got to send my husband” or things like that. “And by the way, he drinks
too much.” Things like that, so you’ll get information.
In Kirsty’s case, her mom told me that Kirsty likes to drink quite a lot of alcohol on Friday
and Saturday night, a lot of white wine, and she smokes a few cigarettes, but likes to
drink. And, of course, when I saw Kirsty, she said she didn’t drink much at all. But
according to her mom, she’s drinking like a bottle of wine a night on the weekends and
eating a lot of stuff that typical university students eat like two-minute noodles and a
lot of take away food. What I’ve written here, Kirsty showed me her
arms and I immediately identified a fungal skin complaint that I’ve commonly seen on
arms, legs, and torsos of chronic Candida patients for many years. I knew this was another
chronic Candida sufferer, and her doctor ran all the tests and found nothing wrong. The
skin scraping was sent to the lab, which was inconclusive. I’ve seen similar skin rashes
before and sometimes the doctors quickly say, “Oh, it’s eczema. It’s psoriasis. It’s dermatitis.”
It’s blah, blah, blah, some weird name. Sometimes they’ll get referred to a dermatologist that
comes up with a name like this long. “I’ve just diagnosed this condition and we’ve got
this wonderful cream for this condition.” I tend to call dermatologists “cream specialists”
because all they do is give creams all day. How depressing is that? We had a few consultations.
I can remember working with Kirsty for some time, two or three consultations and a few
Skype consultations. The big thing with young girls at that age
is usually they’ve moved out of home. They’ve just started university or college. They miss
their parents. Sometimes if they haven’t been introduced to alcohol, they’ll cut loose and
go crazy with booze. My daughter when she was 17 or 18 would have a glass of wine here
at home sometimes, so she got used to alcohol at a young age and she didn’t go crazy with
it. Many times when they’re flatting or move into
an apartment by themselves, with a girlfriend, or with their boyfriend, they’ll often have
crappy diets. They’ll eat two-minute noodles. They’ll have pizzas. They won’t look after
themselves properly. They’ll be under high stress, study stress, financial stress, emotional
stress; they’re on the Pill, all these sorts of things. They’re basically a sitting duck
for a yeast infection. Many of them get digestive problems. It’s easy for them to eat at weird
hours and get heartburn or bloating or constipation. Many of these girls also get urinary tract
infections. These are some of the core issues that I tend to look at with patients.
The main thing really that needed doing in Kirsty’s case was the diet needed changing.
The lifestyle needed changing. And these are things I spent time talking to her about.
About the need for eating quality proteins, cutting out the sweet foods, cutting the booze
right back, and of course, we had a fantastic outcome with this patient like we do when
patients comply. Patients say to me, “I’m looking for a good doctor.” And I say to them,
“Well, that’s funny because I’m looking for a good patient.” When we find good patients
that comply, the outcome is usually satisfactory. That’s just a bit about Kirsty in case number
one regarding her skin infection. Her skin is perfect now. We’ve had no more problems
with her. That’s case number one. Thanks for tuning in.
Greetings. It’s Eric Bakker, naturopath from
New Zealand. Author of Candida Crusher and the formulator of the Canxida range of dietary
supplements. Thanks for checking out my video today. I’m making this video because over
the years, I’ve had patients on and off that I notice end up with severe aggravations when
they’re on the Candida cleanse. Regardless whether they’re on a Candida diet or the Candida
Crusher diet or whatever kind of a Candida cleansing approach, some people end up with
a severe aggravation and severe die off. Now, this is one patient in particular whom
I had yesterday on Skype. Of course, I won’t mention her name, the country, or any details
about her, but she was quite happy to discuss her case anonymously with the public. This
lady still has got quite a major yeast infection, vaginal yeast infection, intestinal yeast
infection, probably systemic yeast infection, and for many years, she’s been treated by
different practitioners and she’s been taking fluconazole on and off for a long time. Recently,
she’s been on a strict diet, and then occasionally, she’ll break out of the diet. So then, she
approached me. My recommendations were for her to go nice and easy on the treatment and
gradually build treatment up. And what this poor lady did is she dropped
the treatment she was doing entirely and went on a very powerful cleansing regime. She started
to take right off the bat, 60 drops of grapefruit seed extract per day, 6 capsules of oregano
oil per day, one liter of a very strong anti-fungal tea, different kinds of tea she was drinking,
5 tablespoons of coconut oil, and a very strict diet. All carbs were gone. It was like a meat
diet with some eggs in it. Literally within a couple of days, she felt unwell, but she
kept the treatment going and pushing and pushing. She ended up in the emergency room. She thought
she was dying of a heart attack. She had chest pains, she had facial pains, and she couldn’t
sleep. I think it lasted almost two weeks this headache. It was a severe headache on
one side of the face. She thought her head was going to explode. She was vomiting. She
couldn’t sleep. She had severe aggravations. Well, these things can come about when you
do a 360, when you do an about turn, and do a very abrupt stop of everything you’re doing
and a very abrupt start of everything new and in particular in high dosages. You can
cause a serious aggravation. This is not what I want people to do. And in my book, I’ve
written about this on many occasions that you’re better off to slowly wind down, especially
if you’re eating a poor diet, just slowly take your diet down over a two or three week
period and gently introduce new foods. And at that time, it’s probably not a good idea
to put antifungal treatment in right from day one. You’re better off cleaning yourself
up a little bit in terms of diet and lifestyle and then putting an antifungal approach in
there. And when you do, you start on a low dose if you have severe Candida, then you
gradually build up. It may take two or three weeks before you can start taking even a reasonable
amount of antifungal. I’ve had this same thing with people taking
my Canxida Remove and Canxida Restore products. Some people will start, they take 12 straightaway,
so they’ll get the bottle, and they’ll take three tablets, 2 hours later another three,
then another three. Some people seem to think that if you take a huge amount of something,
you’re going to hurry up and quickly get the cleanse over and done with. You’re going to
kill all the Candida in your body. This is a stupid way of thinking. If you want to feel
really sick and get bad aggravations, go ahead, take lots and lots of things. Make lots and
lots of changes abruptly. It’s not a good idea.
For example, if you’re going to join a gym or going to get fit, you’re not going to go
to the gym on day one and do three hours of weights and then go out and do 50 miles on
a bike, and then a week later, you won’t be able to walk for a month. No. You don’t do
that. You go very slowly into exercise. Very slowly and get a reasonable level of fitness,
then build that fitness up gradually until you become increasingly fit. And who knows,
in six months, you may be able to do a quarter or half marathon. You can’t do a half marathon
in Candida the first week that you start a Candida cleanse. It doesn’t work like that.
And if you do that, you’ll get severe aggravations. So take it easy. You’ve got plenty of time.
You’ve been to 50 doctors or practitioners already; you’ve gotten nowhere. Why would
you think that you could push things through in a hurry and get somewhere? If you’re going
to do it properly, take your time. Do it properly. Because I want you to also learn and become
educated in the correct lifestyle habits as well as diet habits. Remember, a lot of products
you can take can be very powerful if taken in dosages way too high. I mean 60 drops of
grapefruit seed extract on day one is not a good approach. You can get very sick doing
that. Have a think about that suggestion. I thought
it might be worthwhile doing a video on this topic. Go slow. Go low. Take it easy and gradually
build. Work under the threshold of discomfort. You don’t want to push yourself to the point
where you’re vomiting and you have to go to the hospital. That’s not really a good idea.
Thanks for tuning into my video.
– Dude, I swear to God,
I saw Andrew Dice Clay. He stopped in a comedy club
and he’s doing a bit. He’s like, “Women don’t–
women shave their assholes. “Back in my day, they used
to hide their assholes with hair like Helen Keller in the attic.”
– Oh, no. – And everyone’s like laughing
that he made this mistake and he picked up on the laughter
and he goes, “Yeah, yeah. Like Helen Keller in the attic.”
– Oh, no. – Like he doubled down. And it’s so funny
to imagine these things. – Oh, that’s so embarrassing.
– There’s a blind and deaf woman hiding in an attic like,
“Where is everyone?” (laughter)
You know. ♪♪ – What a great show today. We have Ian Fidance in studio
as we do every Thursday. – That’s right.
Hi. – Hi, walkin’ on sunshine.
– Uh-huh. – Brendan Sagalow is also here.
– Hi. – First time on the show?
– I’m having so much fun. – There might be a second.
We don’t know. – Whoo!
– Yeah, I think it’s in your future.
– Every Thursday? – Mmm…
– Get him out of fucking here? – Listen, I’m open to it.
(Brendan laughing) – I’m open to anything
at this point. – Dumpster?
– Yeah, yeah. And now in studio
we have Seth Green. Seth, how’s it going?
– It’s good, Nikki. How are you? – I’m so good. Seth has a new movie out, his writing
and directorial debut. It’s called “Changeland.”
“Change-land”? “Change Land”? – “Changeland.”
– “Changeland.” – Yeah.
– “Changeland,” it’s in select theaters
and video-on-demand. I watched this film last night.
I loved it. It’s beautiful. – Oh, thanks.
– It’s funny. It’s captivating.
It’s all those things. – I– I really appreciate that.
I’m so glad you dug it. – I feel like
I went on vacation with you. – Yes, it is definitely designed
to be a cinematic vacation that you can take from
a movie theater or your house. – Cool.
– Oh, hell yeah. – That is how I…
Because my producer Noah had watched it
before I watched it and said, um, “I just watched
Seth’s movie and now I have
to go to Thailand.” – Oh, good.
– And, um… And– and I was like,
“Oh, haven’t you known that Thailand’s great any…?”
But you’re right. I’ve been to Thailand before
and this made me wanna go again. I mean, you really do a service
to the country to show how fun it is there.
– Well, thanks. – And how cool and beautiful. – I was really inspired
by the place itself and all of the things that
the characters do in the movie are something that you can
go do in real life. In each instance,
it was something I had done and thought, oh, I’m living
in a movie. And so I just constructed
a narrative that would support being able to visit
all those places. – That’s so…
So you had already– you had vacationed there
for a while? – Yeah, my buddy Dan and I
went on vacation in Thailand, and everywhere we went,
people assumed we were a romantic
honeymooning couple. And so they went
out of their way to give us like a beautiful
romantic experience. – That’s great.
– You know, drinks with two straws in it and…
– Champagne? – All of it.
– Free champagne? – Our beds littered
with rose petals and just everyone going like,
“We just want you to be in love today.”
– That’s so nice. – We’re just friends, so… – That’s gotta be so annoying
after a while. The third rose petal on the bed,
you’re like, “All right,
get off, get off!” – It– it honestly just–
it got– And we even–
we even do it in the movie, just get to the point
where you’re like, yeah, fine, whatever.
Thank you. Thank you, I appreciate
the– the way that this was intended.
– Yeah. – Yeah, so you decided to–
while you were there, were you like, I’m gonna
come back here and shoot a film, or did it come after?
– I did. No, it was while we were there.
Everything that was happening was so cinematic,
just the backgrounds and the experience,
the characters that we met, the night that we had. I was like, all of this
actually feels like an incredible narrative
for a movie. So I just– I came up
with all of the emotional disposition of it, right?
– Yeah. – ‘Cause none of that was–
actually existed. I had just started dating, uh,
the actress in the movie, Clare Grant. I had just started
dating her when… – Which one, which one
did she play? – She plays Dory, the girl that
Breckin Meyer winds up… – Oh, yeah, she’s great.
Is she your– She’s your girlfriend now?
– Oh, Breckin Meyer’s in it? – Yeah, we’ve been married
almost ten years, actually. – Wait, you’re married to…?
– Yeah. – She was awesome.
– I thought so, too. That was why I cast her
in the role. – Oh, my God, I love that.
(laughter) – In each one of these cases, I wrote the part
for a particular actor and then was, you know,
grateful that they said “yes.” – That’s so cool. Okay, I didn’t know
that you had been married for ten years.
– Even better. – That’s– Okay.
So, yeah, the casting in this is fantastic, too.
– Oh, thanks. – So you got to make a movie
with your friends and family. – Yeah, yeah, exactly, yeah.
– What a dream. – Well, I got– I got
all of my first picks for all of the performers. Like as a director,
all you hope is that you can cast people
who are gonna be organically believable
in the roles and then really great at it. But because we’re making this
tiny independent movie on small islands and boats, you need people
that are professional and really good at the job and gonna give it to you
in like one or two takes. – Yeah.
– And not be concerned that there isn’t
a triple-stack trailer for them to change their clothes in. Everybody had to be kinda
cool about it. – Yeah.
– Yeah. – So I-I felt like I’d made
all the conditions as perfect as I could, but man,
I was glad when it worked. – Ha-ha.
– Was this so fun to make? – It was.
– It looked like a really fun film to make.
– It was, it was a lot of fun. And I think that you can see
the years of familiarity and chemistry amongst
all the performers. – That’s awesome.
– You definitely can. – That’s great.
– Um, when did…? So this is the first film
you’ve ever written? – Yeah.
– How do you even go about doing that? I mean, did you just come home and just open your laptop
at a Starbucks and start typing?
I mean, what did you do? – Not at a Starbucks,
but pretty much. – Coffee Bean.
– It took about– Yeah, exactly. It was at a Peet’s.
It– it– it took about eight years to–
from the time I went on this trip to the time we were
actually making the movie. And I completely rewrote
the script six times where I still knew
all the set pieces but I needed
a more compelling story or I wanted a better take
on the characters. And different things
just sort of happened to me in that time that–
that made me understand a little more clearly
what I wanted to say and what– what characters
could be highlighted how. – Yeah.
– Jesus. – When– when you were actually
on this trip and you were like, oh, this
might actually be kinda cool, were you like taking notes
while you were like… – Yeah.
– …hanging out? – Kind of. I mean, I joked
that I was essentially location scouting
while I was on my vacation. But I did. I made notes
about different people that we met or the way
that something felt or… just an environment,
a sequence of events that, because it happened
that way… it just felt a specific way. And so my whole goal was
to present that to an audience and translate it in a way that people would feel
the same thing I felt. – Right.
– Again, Seth Green is with us. His movie is “Changeland.” It’s in theaters
and on video-on-demand. I really recommend this film. It is, from the get-go,
so compelling and so visually stunning
and funny and quirky. My favorite–
The opening is so good. You just, uh, just despondent
traveling. There’s like the opening shots
of you just staring into the abyss
kind of depressed. ‘Cause it’s a guy going through
a hard time in his relationship which kinda is the impetus
for him going abroad with his friend
which is supposed to be like a honeymoon with your… Not a honeymoon, but a romantic
vacation with your wife. – It’s like a prepaid
second honeymoon that was gonna be a surprise
for my character’s wife. And on the eve
of surprising her, he discovers she’s been
having an affair. And so, instead
of confronting her, he gathers his old best friend, which you come to realize
he’s a little estranged from. And they go
on this trip together to figure out what to do.
– Oh, that’s great. – And so, from my character’s
perspective, he’s cowardly running away
from the confrontation. And from his best friend’s
perspective, it’s a badass move to like
ditch town on your anniversary without even a word
to your wife. – Yeah.
– Yeah. When you’re directing yourself,
how do you check…? Do you just go back and…? I mean, I know
this is like a– How do you– how do you
make sure you look good? – Do you yell “action”
and then run into the…? (laughter)
– You have to be standing there. “Action,” and then get
right into your… – I…
– …dialogue. – No, I, uh, it…
(stammering) I had an A.D. that would call
“action” for me, especially if I was in a scene. If I was behind the camera,
I’d call “action.” – Right.
– But it’s a little challenging. It took a lot
of compartmentalizing and a ton of preparation. I just had to be really prepared
in each– in each category. So I had to be really prepared
as an actor so that I didn’t have
to ask myself questions or so that I could make
minimal adjustments, and I had to be incredibly
prepared as a director so that I could multitask. But also, it took having
awesome people around me. You know, if I’m in a scene
with Breckin and– and I’m not the best
in it, he’d be like, “Hey, you could do that better.”
– Yeah. – The next take, I’d be like,
“Oh, tell me what.” – That would crush me.
– Yeah, any kinda criticism. If he was like, “Yeah, you could
do that better,” I’d be like, “Fuck you, man.”
– But I think that’s good to push you.
– I’m just not… – Yes.
– Yeah, the– the– the point of surrounding yourself
with friends or– or professionals that
you really trust the opinion of is that they will
give you the goods and no one’s gonna let you
screw up like that. – Right.
– No one’s gonna leave you hanging out there.
– Of course. – You know what I mean?
– Yeah. – That’s great they believe
enough in the project to like not just show up to act, but to show up
to make it better, to enhance everything
that they’re in. – Absolutely.
That’s the– I really, you know,
it sounds smart after the fact, but I just stacked the deck
in my favor to– to make it go well
any way that I could. I knew there were people
that I could depend on. – That’s great. – I’m gonna go see it
this weekend. My girlfriend like loves you and quotes “Robot Chicken”
to her whole family. And I’m gonna take her
and she’s gonna be so excited. – It’s so good and it’s just–
it’s a visually stunning movie and the music is so good.
– Hell yeah. – Oh, thanks.
– The acting– I mean, the acting is…
you– you look at the… – Mm-hmm.
– …the cast, you know what you’re gonna get.
It’s fantastic. And it’s really funny,
but it’s just real. Like the conversations,
I feel like aren’t– It didn’t feel too scripted.
It just– You did a really great job…
– (chuckles) Thanks. – …for your debut
as a director and writer. I mean, this is going to lead
to many more opportunities for you in those fields.
– Oh, thanks. – Do you feel
like that’s something you wanna keep on doing? – I love making stuff.
– You’re good at it. – And making movies
is something that I’ve done my whole life, so it– it–
it feels a little like cheating ’cause I’ve gotten to work
on so many films with so many people.
– Mm-hmm. – And so, before I ever
attempted to do it myself, I felt like I’d gone to several
college courses about how to do it right
or how to do it wrong. I’m– I’m glad you mentioned
the soundtrack. That was something
I put a lot of work into. – It was awesome.
– In most cases, the… the music was selected
or a scene was written around a particular song.
– Yes. – And so I had to go out to each
of these artists personally and say, “Hey, say ‘yes,’
’cause if you don’t, I’m totally fucked.”
– Right. – That’s like the running theme
with this movie. You’re like, I need
this specific actor. – Yeah. Yeah.
– I need this specific song. If it doesn’t work out,
it won’t work out in my head. – It’s– it’s chemistry,
you know. It’s a kind of alchemy
that if you get all the right elements together, the end result is a movie
that’s watchable. I mean, I don’t– I don’t know if this’ll be people’s
favorite movie. I don’t expect it
to make a ton of money. But I hope that anybody
that watches it feels what we set out
to give them. – That’s great, I love–
– Every time a song would start, I’d be like, how much
did this cost? Oh, and then
what about this one? I mean, I was looking to music
for my special, and it’s like any song that you
even have maybe heard of a little bit
is so expensive. But you have so many
great tracks from so many great artists.
Like the soundtrack is– Is there gonna be
a soundtrack to this movie? – Yeah, there’s a playlist
on Spotify now, and I’m– I’m putting
a vinyl together. – Great.
– Because Patrick Stump, who’s the lead singer
of Fall Out Boy, he wrote all of our composition and even did like orchestral
score for the movie. And it’s– it’s beautiful,
all his work. And then we got
all this licensed music from Otis Redding
to The xx. – Yes.
– No shit. – And I wanna put them
on a vinyl that people can… – Dude, music makes a movie.
– That’s amazing. – That is so awesome.
– Totally agree. – You can find
the Spotify playlist by searching “Changeland”
on Spotify? – Yeah, yeah.
– Okay, I’m definitely going to add that to my…
– It doesn’t… – ‘Cause it is great.
– Thank you. I think that– that list
is just missing the Coldplay, um, and there’s like
one other song that’s not on the Spotify list,
but it’s everything else. – There’s a Lorde song
you had in there that I was like,
God, that’s a good pick. I mean, just…
– Cool. – But it all just– It was like a series
of music videos with these amazing… I just– I really loved it
and what– what– How long were you
over there shooting? – We shot for about four weeks,
like 24 days. – Wow. Damn.
– So it was six-day weeks. But I was over there almost
three months this go. I had five weeks of prep
and then two weeks of wrap down. – Damn.
– And when did you shoot this? – It was in the end of summer
of ’17. – Okay. Wow.
– Yeah. – And then, have you
know Breckin for a while? – Yeah, Breckin and I met
when we were teenagers and we really connected young.
– What film? – We– we met ’cause
we both auditioned for all the same stuff.
– Yeah, yeah. – And then I’ve told
the story before… – So have you ever been
in a film together like before? – Yeah, we did, um,
“Rat Race” together. He’s in…
– All right. – We got to do “Josie
and the Pussycats” together. – Okay.
– He cameos in “Can’t Hardly Wait.”
– That’s right. – Jesus, man.
– We’ve been collaborating on “Robot Chicken”
for the last 15 years. – Oh, yeah, okay. – You just named
so many good movies. – Oh, thanks.
– I know. – And then Breckin created
a show called “Men at Work.” I played a homeless guy on that.
– Oh, that’s right. (laughter)
– That’s so fun to make a film with
your best friend. – Any time, any time Breckin
and I can work together, I know it’s going to go well. He– he and I have such
excellent chemistry together and such a trusting confidence
with one another. That was– There really was
no one else for this part. – Can we talk about
“Can’t Hardly Wait”? – Sure.
– Um, like… – Talk about a soundtrack.
– Maybe my… I know. No kidding.
– Oh, yeah. Holy shit. – Whoo!
– I was so obsessed with that movie
in middle school, high school. I mean, it defined, uh…
(stammering) “Clueless” and that movie
are my two favorite movies to this day, I mean…
– Breckin’s in that, too. – I know! I know!
(laughter) – Yeah!
– I can’t even– I can’t get over–
And your role… – That seems to be
the through line in all the things you like.
– You and Breckin. – You got a crush on Breckin… – I think I have
a Breckin thing. – Yeah.
– Um, uh… – You’re a Breckin baby. – I saw him
at a restaurant once. And yeah, and it was
very exciting for me. – Yeah, he eats out a lot.
– Nice. – I’m glad it checks out.
– That’s why she likes him. – Yeah.
(laughter) – That guy’s always
at restaurants. He’s a classy guy.
(laughter) He doesn’t have some
crumpled-up takeout bag on the corner of the sofa. That guy’s sitting
in a proper chair. – I knew it.
I knew it. – Some paid professional
is handing him food. – Um, when you did
“Can’t Hardly Wait,” how old were you
when you did that role? I mean, you were supposed
to play a high-schooler. – Yeah, I was probably 22.
– Yeah. Yeah. – I think I was 22 or 23.
That was ’98, I think. – Yeah…
– ’97– end of ’97 when we filmed it.
– Yeah. Was it, um, was it a party
filming it? Did it feel like that on set?
– It was, we were– we were filming in a set
that– that was the entire interior of a house. And so you could move
from room to room, but it was on a soundstage. And not all of the kids shot
on the same days. There were only a couple of days
when the whole cast was… in a scene together. So we were passing each other
and I joked that Love Hewitt and I were like
the characters in “Ladyhawke,” only passing in the nighttime.
– Yeah, yeah. – That one hour of twilight.
– Ships in the night. – ‘Cause we never had
any scenes together. But it was an awesome time. The only thing is, you know,
making a movie takes a long time and so extras kept
falling asleep on set. ‘Cause you’d have like an hour
in between lighting setups, and everyone just had
to stay on set. So any time an extra
would fall asleep on set, we would take Polaroids
like hanging out around their prone body.
– Oh, that’s great, yeah. – And a couple times
we started taping caution tape over them or like binding them
to whatever chair. – Oh, my God.
(laughter) – And then like yelling
real loud, “We need you on set!
We need you on set!” And then they kinda like
struggle like this. Just stupid pranks.
– Oh, man, that– that– that movie I remember looking
at the extras in the background. Like I feel like those extras,
you got to know them if you watch the movie enough.
– Just like dancing… – Were there any extras
that were like, “I fuckin’ hate being
on this movie set. “They keep putting
caution tape on me. I’m here for eight hours.”
– I don’t know. I think people felt
like they had been acknowledged. If they fell asleep and then
got taped to their chair, they were like, “Oh, thank–
For me? Thanks, guys.” – And there was a lot of
like couch sitting around. – “Does this mean I’m SAG?”
– Yeah, yeah. – You could at least,
as an extra, be on a couch… – “Does this count as like
a waiver? Can I get my SAG card?” – But then you had to–
a lot of your scenes in that movie
were in a bathroom. – It’s true.
– So you and Lauren Ambrose just hooking up in a bathroom.
– Yeah. – I mean, that was such
a good story line of you being this guy who’s
trying to be something he’s not. She’s this girl that
doesn’t fit in. You end up falling in love
by the end of it and having sex
for the first time. You’re projecting like
you’re this like Lothario… – That was so relatable.
– …who’s had so much sex. – Yes, like all the condoms
and being like, “I’m gonna fuck.” And then it’s like,
“I’ve never touched a woman like in my life.”
(laughter) – So good.
– Yeah, yeah. – I love– I love those kinds
of characters, you know, that are– that are complicated
and deeply human no matter what it is
that they’re projecting. Deep down, all people
are the same. – Oh, yeah, completely.
– I love being able to find that– that element
to any character. – Now, did they–
did that character come out– Did they ask you to behave
that way, to talk that way? – Yeah, yeah, the character was
written as a guy who– It’s like Michael Rapaport
in “Zebrahead,” you know? – Yeah, yeah.
– It’s literally this guy, and it was such a product
of that time where all these young
white kids desperately wanted a– a– a new Jan Brady persona and they kinda reinvented
themselves as, you know, Busta Rhymes…
– That was me. – It never felt exactly true. It always felt like
a little bit of a put-on no matter how authentically
you projected it just because
of your circumstance. That was not a time when anyone
was gonna be like, “Oh, yeah, you should
have a rap career.” – Dude, I used to say “you know
what I’m saying” after… Like it wasn’t natural. I’d be like, okay, now I have to
say “you know what I’m saying?” – You were his character.
– Yeah, I was. – He dyed his hair blonde
and would rap in his garage. – Oh, yeah. Oh, yeah.
And I’d talk and be like… – You’d follow your dream, man.
– Like, “Oh, man, math sucks. You know what I’m saying?”
Like I would talk like that. And I’m like, you gotta throw
the “you know what I’m saying?” – In math class?
– You’re saying it too much. Stop– Hold it back.
I would wear do-rags, do-rags. – Yeah.
– With like a hat on. – Yeah, I made some pretty
aggressive fashion choices in my youth.
– Oh, yeah, yeah. – JNCOs were a big part
of my life. – God, you’re just
like searching for any kind of identity.
– Yes. – Did you, Brendan,
did you also pretend like you had been laid
like a ton? – Yeah, definitely. I remember I was getting
a haircut and this was when
I was still a virgin, and the guy cutting my hair
was like, “How’d you lose your virginity?”
He asked me. And I made it up.
I just went, “I was in a car with a girl.” I hadn’t–
I had no idea. I didn’t have sex at all,
so I was just making it… He was like,
“What did she look like?” I made up a girl.
I was like, “Oh, blonde hair,” like…
– (laughs) – Yeah, but at least it’s that
and not you’re like, “I took my penis out
of my pants…” – Yeah, yeah, yeah.
– “…and with my fingers, “I put it into her vagina, and we– we had the sex
together.” – “Great.
She was all creamy…” – I was at wrestling camp and…
(laughter) – “…she got so creamy
and stinky.” Isn’t that what it is?
– Isn’t that, right? – What is that when he says,
“The 40-Year-Old Virgin,” when he– when he says,
“Oh, yeah, they’re like balloons of sand.”
– Yeah. – “That’s what the boobs
feel like in person when you touch them
with your hands.” – I mean, I couldn’t believe
with penises, like if you would’ve asked me, if I would’ve had to come up
with like what a penis is like before I had had sex,
like I didn’t know that they could go
any more than a right angle. Like I didn’t know they could go
all the way up. That still mystifies me.
– Yeah, like an inch from the tummy.
(laughter) – I remember hearing guys
would tuck it into their pants. – Belt, yeah, the boner tuck.
– Into their belt. And I’d be like,
“How could you do that?” – Yeah.
– But you can do a lot of things with dicks I didn’t understand.
– Oh, yeah. – And also that when you’re–
when you’re young and desperately trying to hide
the fact that you have no control over your body…
– Oh, man. – Your body is constantly
selling you out. – Oh, yeah.
– Oh, yeah. – I mean, popping boners
in middle s– in like– Does it happen
in high school, too? – Yeah. Yeah, you gotta
put a book bag over your crotch
in first period. – When does it stop?
– I have a boner right now. – It was– it was def…
– It’s all creamy. (laughter)
– It smells. – It’s all stinky.
– Stinky and creamy. – I got a stinky dick.
(laughter) – When do you stop
getting random boners? When can you start
trusting your body? – Eh…
– Uh, when you… – When does that happen exactly? – I think you just have
to go with it. ‘Cause when
you’re in high school, you’re like, “Stop!” And now I’m like,
“Live your life, dude. Fuckin’ get a boner.”
– Do you– do you get random boners now, Brendan?
– Sometimes. – Like in public?
– Not as many as… – Oh, that’s a NRB–
no-reason boner. – Oh, a no-reason boner.
– Yeah. – I have to like…
– Just a boner for no reason. – There’s gotta be an NRPB, like a no-reason
public boner, too. – Mm-hmm.
– Yeah, yeah, yeah. – ‘Cause in the privacy
of your own space… – If I’m wearing like sweatpants
or like mesh shorts or something and I walk out,
I’ll think like, I hope I don’t get a boner. And then my brain will go,
what gives you a boner? Oh, boobs and blah-blah,
and then I’ll start… – Then you’ll start
getting a boner. – …getting a boner, yeah.
– God, yeah. I guess it’s the same
as if you get like aroused as a woman,
like sometimes you get wet during the day, I guess.
– Yeah, like riding a horse. – Yeah, but sometimes it’s–
it has nothing to do with anything.
– Yeah. – Sometimes you have
a yeast infection. – General friction, you know?
– Just kidding. (laughter)
Is that wet? (laughter) No, but that– it is true
’cause like sometimes I’d– If– Yeah, if we had to–
as women, if we had boner– like that would be really hard
to deal with. If we get wet, we’re just like,
“Oh, I guess I’m wet.” And then you go to the–
you go pee later on and you wipe and you’re like, “Whoa, who was I
thinking about before?” – Mmm…
– It’s a little slicker down there, you know
what I mean? – Yeah, but also if you’re
getting a boner in public, you gotta like really be aware of the public company
you’re keeping. – Yeah, I mean, it’s…
it would be horrifying. – If you’re at like
a softball game… – That’s that belt tuck. That’s where the belt tuck
comes in handy. – Yeah.
– Always wear a belt. That’s what I’ve learned.
– That’s the theme. – “Always wear a belt.” – Then what if it pokes
out the top? – You know, most people
are not looking. And so you really–
you can just be… – And you’re not wearing
a crop top, I guess. – Yeah, yeah, yeah.
– Just by being calm, you can usually conceal it.
– Yeah. – (Nikki) Oh, God!
– Yeah. – I just noticed
your RADIO8BALL shirt. Do you know Andras?
– Yeah! – That’s so cool.
– Yeah. – We made a movie together
called “The Attic Expeditions.” – No way!
– Yeah, when I was like 21. – Oh, wow.
– I don’t know if anyone’s ever seen that.
– Oh, that’s awesome. Yeah, our friend Anya Marina
did a web series, and he had us all
on for it, and then made us these
t-shirts for it. My name’s on it.
I should cover it up. – That’s so fun.
– But, uh, yeah. I love this t-shirt!
It’s so great. – It’s so cool, yeah.
– That’s awesome. – It is cool.
– Yeah. Andras is awesome.
– Agreed. – Okay, we’ve got
four minutes left. What do I want to get to.
Seth, wh– wh– You started acting
at what age? – Seven.
– Seven. Is that something… – Whoo!
– Wow. – …that you were
begging to do? Like begging your parents
to– to do? – Yeah.
– …or was it something, they were like you’re good,
you should try this. – No, they wanted
nothing to do with it. – Yeah.
– My parents were like lower middle-class teachers
in Philadelphia. – Yeah?
– And I was this obnoxiously, oddly driven kid
who knew from a young age that I was supposed to be
doing this, and just relentlessly
pursued it. – And do you look back
on yourself then and you’re like, where did this
confidence come from? Like, what– this bold kid,
because I feel like– Do you still feel
like you’re that kid? Or do you not– do you relate
to him still? – I still feel like
this is what I’m meant to do. I never feel more like myself
than when I’m performing. And I still
feel most at home amongst the artists
and performers. That’s– that’s what makes
the most sense to me. – Yeah.
– Everything else is just something that I’ve learned
along the way, like how to not go crazy
or spend all my time desperately insecure
or deeply depressed. – Mm.
– Yeah. Yeah. – Yeah.
– I really like how eclectic your choices for performing
and… have always been– I mean, you’ve been in
so many different things. We– I was so excited to be
a part of something you were in, which is the “Historical–
Historical Roasts.” – Oh, it was so good.
– Which you crushed, by the way. You were so funny in that.
– Thank you. Likewise, man. Like, you raised the bar that
day in terms of performance. Y-You played David Bowie.
I played Kurt Cobain. It was the roast
of Freddie Mercury. – Amazing.
– It’s on Netflix now. “Historical Roasts.”
– So fuckin’ good. – Thanks, man.
– Yeah, the show was awesome. – That day–
– That show is awesome. – It’s awesome.
– I’ve seen a bunch of episodes of it now.
I’m so proud of Jeff. – And it’s educational too.
– Yeah, me too. – It really is.
– You’re like learning things. – (laughing)
– Yeah. – It’s fantastic.
– He made a really funny point. He said, you know,
modern audiences don’t know the difference between
Anne Frank and Helen Keller, so if nothing else, this is going to provide
some context for it. – ♪ I’m an alligator boy ♪ – Oh, God.
– ♪ I’m an alligator boy ♪ ♪ I’m an alligator boy
I’m an alligator boy ♪ ♪ I ain’t no crocodile kid ♪ ♪ I ain’t no crocodile kid
I ain’t no crocodile kid ♪ ♪ I ain’t no crocodile kid
I’m an alligator boy ♪ ♪ I’m an alligator boy
I’m an alligator boy ♪ ♪ I’m an alligator boy ♪♪ (off-camera chuckling) – Okay, that’s an original song
that Andrew wrote that he sang for my parents, um,
and I thought it would– They liked him so much
that I thought that, oh, I can’t wait till
he sings “Alligator Boy.” That will infuriate my dad
in so many ways because it’s not a song,
it’s not good, his singing is terrible,
there’s two lyrics– – But it comes from
a place of honesty and truth and realness, and that’s what
I think E.J. likes about me, ’cause I’m not fake, and I’m–
and I’m– and I’m– I’m open. And through “Alligator Boy,”
he sees that in me. – No, everything else
about you is true. “Alligator Boy,”
there’s no truth in that song. What– No one’s ever described
you as an alligator boy or a crocodi–
– I’m from Florida. – Okay, but that’s not truth.
– And I ain’t no crocodile kid. ♪♪ – So generally,
my dad hates bad singers. – Okay.
– Like, cannot tolerate them. When– Especially someone who
like thinks they might be good, which, you think you’re good
and you’re not. – That’s– I don’t think I–
think I’m really good. – Well, I think that you… – I give my all.
Well, you did karaoke. – Okay, when you do karaoke,
you give your all. You don’t have any
kind of like embarrassment about how bad you are.
– Okay. – And usually when there’s
someone that’s a bad singer that– that has
a lot of um… – Gravitas?
– Confi– confidence. – Yeah.
– “Confi-tas.” – Yeah.
(chuckles) – To combine both
of what we were saying. – Yeah.
(laughing) Go on.
– (off-camera laughing) – Um, he could get–
he usually generally gets like really irritated by them
and can’t stand that they don’t know
that they’re bad singers. – (laughing)
– I don’t like any of this. (laughter)
What– It looks like you’re just
trying to like hold in a poop. – Be Jiminy Glick kind of.
– Oh, yeah, Jiminy Glick! – You know, Jiminy Glick
would always go… (silly Glick voice)
– (laughing) – (silly Glick voice) (laughing, gibbering
in silly voice) – We can’t– we can’t do
an impression of our– of an obscure show
that no one remembers. – Yup. (chuckles)
– Uh, okay. – So, yeah– so, the singing.
But there’s– Your mom said something to me.
She goes– she didn’t really
want me to do another song. She– Your mother…
– My mom is– – …was a little hammered. -Yeah.
– Got a little loose. – A little hammered is not
the way people describe it. Lilyhammer is where
the Olympics were, but little–
a little hammered, um… you’re either hammered
or you’re just a… you’re a little drunk
or you’re hammered. – Yeah. Yeah.
– So which one was she? – I think– I don’t think
she was hammered. – No, she wasn’t.
– I think that– Yeah. I mean, you– I’m sure
you’ve seen her more loose. – Yeah. Yeah.
– Yeah. – Yeah, I– You saw my mom drunk
for the first time ever. I think.
– Yeah. – Yeah and, uh– but–
and the next day you were like, your mom was drunk.
And I was like oh, that was… ♪ Nothing ♪
– Yeah. I can see that. (twinkles)
– Cool mom. – Cool mom. – But, um, no,
but my mom gets– she told you not to
sing anymore? – Yeah.
– ‘Cause you– you are not good. – I know, but if you’re
doing karaoke, first of all,
there’s five of us in a room. No one likes doing karaoke
where it feels like the other four people are being judgmental
of their karaoke singing. Karaoke is all about
bad singing. – I agree.
– It’s not about going in and being the best and on-key. And it’s like,
okay, you know what? Take that on-key bullshit–
It’s like– First of all, you all
don’t even sing that great. – No, we’re not.
I’m not– I’m a terrible singer. And that’s why I, um…
that’s why as a kid, my dad’s judgment, based on
like if you’re not good– – Yeah. But you’re–
you could be– if you were–
okay, you have a voice… – Yes, but I– but I–
– …that I hate. – But… (sighs)
– (off-camera laughing) – No, no, no, no, no, no.
You really do have a good voi– like if you trained your voice,
you could– – If I trained my voice
I would be good. If I– I also have
musical ability, like guitar-wise.
Like I could play an instrument, but because my dad can’t
tolerate any kind of, uh, bad– like, uh…
– He didn’t let you get to even the first–
past the first stage. – Yeah, if you–
if you make a flaw, he’s just like,
why’d you do it like that? And then I would just give up
and I’d go, well, then, I don’t want
to learn this at all. So– And all
he’s ever wanted me to do is sing and play guitar
with him. But because he’s been
so judgmental, when I tried to do
those things and I failed, because you have to fail when
you first start to try, I never got good
at any of it. So he holds this over my head
my whole life of like, you never play guitar with me.
You never sing with me. And I’m like, because
you are so mean about it. And– But that’s why
I was so angry when after you sang terribly,
my dad was just like, oh, it was really fun.
And I’m like, you– So you weren’t annoyed
with Andrew’s… like the fact that he sings
everything, uh, too fast? – Yeah, but this is why–
This is what I think it is. – You’re always singing
one lyric ahead so you can prove to everyone
that you know the lyric, which we know you know it because it’s on the screen.
Everyone knows it. So you’re always
singing one lyric ahead and you’re off-key
and you’re loud. It’s like everything that
my dad generally hates, it was happening
in that room. And he still liked you,
and it annoyed me. – Remember I asked
for your hand in marriage? – Yes. It was so like mean
to do to me, ’cause no one
will ever do that to me. And the one time I get it
is a joke. From Andrew Collin?
– In front of her parents. – In front of my parents.
– (off-camera laughing) – (sighs)
– I go, Nikki… – Don’t you do it again!
Don’t do this now! – Just hold my hand.
Just hold my hand. (laughing) – No!
– Please be my boss. – Oh, yeah.
– Forever. (laughter) Please employ me till October.
– Till July? – Ju– September.
– September? – The 17th.
– 17th! That’s when I get
to bring out a new opener? – (laughing)
No, not until 2028. – That’s too far. I’m not gonna–
– ’27. Your hands are cold.
(laughing) 2026. ’25. 2024. Just give me
a fucking job. – I can give you till the end
of the summer, this summer. – I’ll take it.
– But then you’re on your own. Start a podcast.
Get your own fans. – She said “no.”
– (laughing) You just saw a clip from
“You Up? With Nikki Glaser.” Check here every Tuesday
for a new clip from my radio show,
“You Up? With Nikki Glaser.” – From our radio show, with “You Up?
With Andrew and Nikki.” – Never.
– Andrew Collins’ radio show, who happens to have Nikki
on sometimes. – Okay, we all know
that’s not true.
Good afternoon, and welcome
to the 47th annual James R. Killian, Jr. Faculty
Achievement Award lecture. I’m Susan Silbey, chair
of the MIT faculty. Before we begin, I will
ask that you please silence your electronic devices. And also, I invite, though
I don’t see too many, those at the edge of the room– there aren’t many seats
left to move to the middle, just in case few
stragglers come in, and we can accommodate them. The James R. Killian, Jr.
Faculty Achievement Award was established in
the spring of 1971 as a permanent tribute to
Dr. James R. Killian, Jr., president of MIT
from 1948 to 1959 and chairman of the
corporation from ’59 to ’71. The purpose of the Killian Award
is to recognize and celebrate extraordinary achievement
by MIT faculty members and to communicate their
accomplishments to members of the institute community. The title of Killian
lecturer is the highest honor that the MIT faculty may
bestow on a colleague. It is our privilege today to
be addressed by Gerald Fink, Margaret and Herman
Sokol professor in biomedical research, American
Cancer Society professor of genetics, and a member
of the Whitehead Institute for Biomedical Research. As noted by our colleagues on
the Killian Award Committee, which was chaired by
Professor Michael Strano, Professor Fink is among
the very few scientists who can be singularly credited
with fundamentally changing the way we approach
biomedical problems. He has made numerous
seminal contributions to understanding
the fundamentals of all nucleated
life on the planet, significantly
advancing our knowledge of many cellular
processes critical to life systems and human diseases. His research, which
includes understanding infectious disease,
how cells divide, and how genes are
controlled, has proved critical to modern biology. Professor Fink’s overarching
scientific achievement has been the development of
baker’s or brewer’s yeast into the premier model
for understanding the biology of
eukaryotes, that is, organisms whose cells have
a nuclei, which includes all known animals and plants. Yeast transformation
advanced the field of biology by making it possible
to do gene editing and targeting in yeast similar
to contemporary CRISPR, but– an importantly but–
approximately 40 years earlier. The ability to gene edit
yeast spurred many scientists to take a yeast
molecular biology course that Professor
Fink taught for 17 years at Cold Spring
Harbor Laboratory. Former students in that course
include three Nobel laureates and 28 members of the
National Academy of Sciences. Professor Fink’s discovery of
transposable elements in yeast laid the groundwork
for future studies of transposable elements. A later discovery of
filamentation in yeast uncovered a genetic mechanism
by which disease-causing fungi switch from a benign
to an infectious form and invade human tissues. This has led to a
better understanding of how Candida albicans, a
persistent human pathogen, can overpower the immune
system, offering clues that may lead to the development of
life-saving antifungal drugs. Professor Fink joined the
MIT faculty and the Whitehead Institute in 1982. He served as director of
the Whitehead Institute from 1990 to 2001,
establishing during this time the Whitehead MIT Genome
Center, which in 2003 became the cornerstone facility of the
newly launched Broad Institute. MIT’s premier place in the
world of biological research is due in no small part to
Professor Fink’s selfless, tireless, and generally
unheralded work in creating and nurturing
these institutions. Professor Fink’s
scientific accomplishments have been heralded and
recognized by many awards, including the National Academy
of Sciences Award in Molecular Biology, the George W. Beadle
Award from the Genetics Society of America, and
the Gruber International Prize in Genetics. He has served as president of
both the American Association for the Advancement of
Science and the Genetics Society of America, and he is
an elected member, or fellow, of the National
Academy of Sciences, the American Academy
of Arts and Sciences, the Institute of Medicine,
and the American Philosophical Society. He chaired a National
Research Council committee that produced a highly
influential report entitled Biotechnology Research
in an Age of Terrorism: Confronting the
Dual Use Dilemma. This report recommended
policies and practices that would allow
the continuation of legitimate research while
preventing the destructive use of biotechnology. In addition,
throughout this time, Professor Fink mentored more
than 100 graduate students and postdoctoral fellows and
is approaching the publication of his 300th paper. This is an extraordinary career. Jerry, will you join
me up here, please? [APPLAUSE] Gerald Fink, it is my privilege
to represent the MIT faculty in honoring you with James
R. Killian, Jr. Faculty Achievement Award. We recognize your
pioneering contributions to the genetics and engineering
of eukaryote systems and your scientific and
educational leadership in the biological sciences. Congratulations. [APPLAUSE] Thank you, Professor Silbey,
for your generous introduction and the committee for choosing
me as the Killian lecturer. I consider it a
tremendous honor, especially because it’s an award
coming from my peers, family, rather than from outsiders, who
often know your achievements, but don’t know your
contribution to your institution and colleagues. As I look out on
this audience, I realize what an amazing
group of talented scientists we have here at MIT
and how fortunate I am to be a member
of this community. I’d also like to thank
the institute affairs office for saturating the
campus with posters of me. [LAUGHTER] As I walk along Main
Street, strangers now stare at me as if I were someone
they must have seen before, but can’t quite recognize. [LAUGHTER] Now, I’m a real American. On my father’s side, my
grandfather came from Scotland. And on my mother’s
side, my grandfather came to America from
Lithuania through Brazil. I grew up in Freeport, New
York, a complacent suburb on the south shore
of Long Island, notable only for its easy
access to New York City and for its access to
Jones Beach State Park. The high school was
sleepy and uninspiring. Its heroes were the athletes
and their admiring cheerleaders. The successful launching
of the Russian satellite Sputnik in October 1957
awakened this sleepy town, electrified the
nation, and changed the course of American
science and my future. And I can still remember
the thrill one dark fall evening in 1957 when I
went out in our backyard and was hypnotized by
the new star in the sky as Sputnik slowly raced
towards the horizon. Overnight, science became
a national priority energized by the dread
of Soviet technology and technological superiority. Local engineers from Grumman
and Republic Aviation came to our high school and
taught math courses pro bono. Not only did this improve
my science education, but perhaps, equally
important for a teenager, the cheerleaders suddenly took
an interest in the smart kids. [LAUGHTER] I came to MIT in 1982 after 15
years as a professor at Cornell as the first appointed professor
at the Whitehead Institute. Now, probably, looking out here,
most of you probably cannot recall, but the idea of an
independent Whitehead Institute associated with MIT was
considered a radical experiment at the time. MIT was not sure it
wanted to take the leap. Concern among the
faculty spawned articles in The New York Times. The third and perhaps last time
the faculty in Massachusetts will convene to try to
resolve one of the most divisive conflicts– I think there’s a bit
of hyperbole here. [LAUGHTER] But it was a difficult time. Now, while still at Cornell, I
was on the visiting committee for the biology department
when the faculty was debating the wisdom of having
this separate institute. Now, as you know, the visiting
committees here at MIT are taken extremely seriously. At the committee meeting,
we sat around in a circle with the faculty, and there was
heated discussion, pro and con, about the possibility
of the Whitehead. I was fortuitously sitting next
to the president of MIT, Howard Johnson, who whispered
to me, do you think this would
be a good thing? I whispered back, absolutely
wonderful opportunity. Two weeks later, after I
had this whispering exchange with President Johnson, MIT
agreed to the Whitehead, and I was immediately offered
a position at the new Whitehead Institute. [LAUGHTER] Let me assure you
there was no collusion. [LAUGHTER] As we now know, MIT
made the right decision. Whitehead turned out to be a
successful pioneer, a pioneer experiment that
led, in my opinion, to the blossoming of
the Kendall Square area. And we should not
forget that Whitehead was the home of the
Human Genome Project and the model for the
many other institutes that have grown up
here now at MIT. Moreover, three previous
Killian awardees were Whitehead faculty. I came to MIT with
some trepidation. I was told by the chairman
of the biology department not to go across Main
Street after dark. It was too dangerous. Well, there was really nothing
on this side of Main Street, either, except MIT. So this is what it looked
like when the Whitehead was being constructed. Here’s Main Street. No Novartis. Back here, I think,
was a building that store popcorn and
beer for Fenway Park. OK. [LAUGHTER] There was only one
restaurant, the F&T Diner. I didn’t know– oh, yes. This was construction
of the Whitehead. This was the first
director, David Baltimore. This is Jack Whitehead, who
engendered this New York Times article. And you may not believe
it, but that’s me. [LAUGHTER] I didn’t know what it
would be like to leave the rustic, pastoral
countryside of Ithaca to come to the big
city, but my confidence was buoyed, as it
has always been, by my family, my wife, Rosalie,
and my two daughters, Julia and Jennifer. But MIT turned out to be much
better than I had imagined. It’s a real community
of scholars, and I was welcomed
into this community. Perhaps no better
indication of what I mean by a
community of scholars is to note the wonderful
people with whom I have collaborated in
research and published papers over the years. They were not only from
biology, this group on the left, but also from a number
of other departments. Alex van Oudenaarden when he was
in physics, Greg Stephanopoulos and Bob Langer in chemical
engineering, and David Gifford from EECS, all co-authors
of papers with me since I’ve been here. This is unique to
many institutions. Furthermore, it wasn’t
just in research. Another sense of
community is the number of compelling colleagues
who taught courses together with me. This group on the left taught
undergraduate courses with me. And the group on the right
taught graduate seminars together with me and
some graduate courses. Bob Horvitz probably
doesn’t remember that we taught a course
a number of years ago. So in this lecture, I would like
to address the question that has intrigued me and geneticists
throughout my career– what is a gene? In the lecture,
I hope to live up to a charge given to the
speaker for the Killian lecture. According to the terms
of the award, I quote, “these lectures
are intended to be at a level that will make them
understandable to a majority of the faculty and
students at MIT.” So you may ask, why
waste time on this question when the gene, what
it is, is common knowledge? You hear it all the time. It should be a simple task. It’s integrated into
our daily language. Everybody seems to
know what it is. A book has been
written about it. And PBS is planning a
special on the gene. The author of this book won a
Pulitzer Prize for this book, which many you may
have read, The Emperor of All Maladies, where
they get most things right. They also wrote a
book called The Gene, where much is incorrect. [LAUGHTER] And after reading it–
it’s 600 pages long. Not a real page turner. [LAUGHTER] I was completely confused
about what the gene was. [LAUGHTER] But you can’t avoid it. Gene talk is everywhere. I hear workers behind
the counter in Starbucks talking about their genes,
no doubt because companies like 23andMe or AncestryDNA– I’m not partisan here– look at your DNA and
promise to provide you not only with your ancestry,
but your potential health or why don’t you feel
chipper every morning. A little saliva is all it takes. You spit into a tube, and
you send it off to them. Well, I was teaching 703, and I
kind of poopooed this 23andMe. And several undergraduates
walked up to me and said, did I do it? They said, you’re a geneticist. Aren’t you interested? So I did it. And I got back this email. Here, Gerald Fink. [LAUGHTER] Our laboratory attempted
analysis of your saliva. I don’t have any DNA in my– I have no DNA. But I don’t need to worry. [LAUGHTER] I spit again. It worked. It worked the second time. Now, geneticists have struggled
with the definition of a gene since genetics
began as a science at the dawn of the 20th century. It’s a young science. And it may seem strange
that in his Nobel talk, one of the great geneticists,
T.H. Morgan, said, what are genes? Now that we locate them
in the chromosomes, are we justified in regarding
them as material units, as chemical bodies of a
higher order than molecules? And here’s the kicker. Frankly, these are questions
with which the working geneticist has not much
to concern himself, except now and then to
speculate as to the nature of the postulated elements. The discovery that DNA
is the genetic chemical body of heredity,
coupled with the ability to sequence the DNA
of whole genomes, requires the definition
of a gene for reasons that T.H. Morgan could
not have anticipated. The DNA sequence of a
genome yields a string of billions of nuclear bases
that are incomprehensible without the aid of a computer. But the computer, shown here,
is helpless in its search for genes within this
vast sea of nucleobases without an explicit
definition of a gene. You can’t tell the
computer, I don’t have a definition of the gene. If you try, the
computer says, hey, you just fed me three
billion base pairs and want to know how many
genes are in the genome. How about a definition? So 20th century
scientists must have a definition of the gene
that is computer compatible. And arriving at a computer
compatible definition of the gene took an
enormous amount of work and resulted in
four Nobel prizes. A current definition of the gene
used to program the computer is the sequence of bases
in DNA sufficient to encode a single polypeptide. This comes from
the central dogma that I think they teach
now in grade school. DNA makes RNA makes protein. And so what does a gene
look like to the computer? There’s a string of bases. And what the computer sees
is, oh, there’s an ATG. That’s like a capital
letter in a sentence. And then, it reads
along in frames of three these bases until it sees
the period in the sentence. In the decoding process,
each successive triplet code specifies the next
amino acid to be added to the polypeptide chain. So what about the code? Well, you can read it
right off this table. So if you look at
AUG, methionine, that would be the beginning of the
protein that it specified. And you go along
this whole chain by threes until you get
to one of these stop words, the period. So for the computer, a gene is
defined as this segment of DNA that’s translated into proteins
starting with a triplet, ATG, and ending with a period. So what does the genome
of protein coding genes look like to the computer? You can see the
smile on its face. It’s happy. Here’s gene one. Makes an RNA. Then, RNA translated
into a protein. Gene two. Gene three. Gene four. So when you read
in the newspaper that humans have
about 20,000 genes and the yeast genome
has about 5,500, that’s what they’re
talking about, these protein coding genes. Now, the question
of what is a gene became more pressing
for me in my own lab when we discovered how to
transform yeast with DNA because the ability
to transform yeast meant we could insert
any gene into yeast and express the protein. So what protein? Well, it could be whatever
your favorite gene was, but you had to know what
the code was for that gene. Let’s say you wanted to
express insulin, for example. You had to know what the
code for insulin was. You could get that
gene from human tissue, put it into yeast,
and now, yeast would decode it and
make human insulin. Indeed, half of all human
insulin is now made in yeast. Knowing what a gene is in terms
of the protein coding gene is really important. In fact, all of these proteins
are made now commercially in yeast. Hepatitis B, which
is eliminating hepatitis B in mainland China– the vaccine is made. Gardasil against
human cervical cancer. I mentioned insulin and
all the rest of these. So it spawned an industry
that continues today. Yeast is easy to grow not
only to make beer and wine, but to make all of these
medicinal products. But I think that what may
have the most profound effect on economics and
society in general is what I read in New
York Times on Tuesday. And that is “Behold the
Beefless Impossible Whopper.” Burger King is
introducing a Whopper made with a vegetarian
patty from the start up Impossible Foods. I have no stock in
Impossible Foods. [LAUGHTER] So this is a– you should know the
background to this, which is that a highly
respected scientist at Stanford University, Pat Brown– me and my colleagues know. Very imaginative guy. Got tired of academia. He’s a vegan. But he was forced
to taste a hamburger and realized as much as
he liked veggie burgers, they don’t taste the same. I’ve tried. If you put enough ketchup
on, they taste like ketchup. [LAUGHTER] And so he started– he left Stanford and started
a company, Impossible Foods. And he then did taste tests. What is it that
makes a hamburger taste like a hamburger? And it turns out that
it is the hemoglobin in the blood of the meat that
you’re eating from cattle. It’s this iron
containing protein. This is a true story. So what gave hamburgers
their distinctive taste was the cow’s blood,
specifically hemoglobin protein. Now, it turns out
that soybeans have a heme protein that mimics the
taste of hemoglobin in the cow. Legumes make like hemoglobin. So what did he do? He cloned the like
hemoglobin gene into yeast and produced tons of it
and made hamburger patties without any cows. The head of tasting
at Burger King said, quote, “employees
were not able to tell the difference between the old
meaty Whopper and the new one. People on my team who know
the Whopper inside and out– and I’m sure they do– they try it, and they
struggle to differentiate which one is which.” I think this is
fundamentally going to change agriculture and
farming and many other things. I will point out a
farm of 3,000 cattle produces the amount of
manure of a city of 500,000. That’s Sacramento or Atlanta. This is game-changing. Now, also, Professor
Silbey mentioned that I like yeast, which I do. I want to point out that when
you’re pumping gas in your car, 40% of the corn that’s
grown in the United States goes to feed yeast
to make ethanol. Right, Greg? And so this is not to feed
livestock, but to feed yeast. So, together with
Greg Stephanopoulos, we’ve used gene editing, whose
modern incarnation is CRISPR, to modify the yeast genome. And we tried to make any
little improvement you make when you’re dealing with– the US is aiming for 15
billion gallons of ethanol per year made by this process. Any little bit that you change
is, of course, transformative. So having a
definition of the gene has clearly been a benefit
for both basic research and human health. And you might want to
know not about yeast. How does a human genome
look to the computer? If you look at four
people’s genomes– these are past presidents. This is the current
president, in case you didn’t recognize it. The important thing to note is
how conservative evolution is. They all have the same
genes in the same order. Evolution is very conservative
with the protein coding genes. Now, this little
gene over here shows that there might
be spelling changes between Abraham Lincoln’s
genes and [INAUDIBLE] genes. Lincoln was thought to
have Marfan syndrome, so he might have a
coding difference because that gene encodes
a protein, fibrillin-1. And if he did,
that might account for his description of
him as tall and thin with long arms and legs. But the genes are all
in the same order. there’s no change in that. In fact, the remarkable
thing to me as a geneticist is how conservative
evolution is. If you look at these
protein coding genes in humans and the mouse,
much of the gene order is the same, even though
they had a common ancestor 75 million years ago. Why didn’t it all
get scrambled up? Something is keeping
these things in the order. So these are two
chromosomes, and this is the alignment of genes
on those two chromosomes that have been saved
over the millennia. It’s quite remarkable. It accounts for the
fact that if you don’t– why is a mouse such a
popular organism to work on? Well, if you don’t know
what a gene does in humans and you figure it
out in the mouse and you know where it is
on the human chromosome, there’s a pretty good chance
it has a similar function in the mouse. So the definition of a
gene as a DNA sequence that codes for a protein
coupled with the sequencing of the human genome
I think has– everybody does– revolutionized
molecular medicine. It’s been a
remarkable milestone. Genome sequencing, along
with computational power to compare and analyze genomes,
has led to important insights into basic science and disease. As an example, we
know the genetic basis for literally thousands of
inherited diseases caused by those spelling changes
I showed for Abe Lincoln in protein coding genes. Sickle cell disease,
which afflicts about 100,000
Americans roughly, it’s one of the earliest
molecular diseases identified where a component of hemoglobin
normally has the codeword CAG. Gluten codes for
this– amino acid glutamate, you have a
normal red blood cell. In sickle cells, there’s
been a change in the code to make valine instead
of glutamic acid, and so red cells sickle. These sickling cells
cause periodic episodes of pain called crises. And pain develops when
the sickle red blood cells block blood flow through
the tiny vessels to the chest, abdomen, and joints. Now, when I used this example
of a molecular disease to teach 703, an
MIT undergraduate came up to me at
the end and said, oh, just reverse the arrow. Then, you can cure the disease. It’s easy in PowerPoint. Very easy in PowerPoint. Unfortunately, the student asked
the question about reversal more than 10 years
ago at a time we didn’t know enough about how
red blood cells differentiate from bone marrow stem cells,
and we didn’t know enough about stem cells. And there was no CRISPR to edit
the gene and reverse the arrow. But now, armed with CRISPR
and really deep knowledge about stem cells, it
seems feasible to make the correction in
patient’s own stem cells use a gene editing by CRISPR,
coupled with knowledge about the bone marrow. Normally, in a bone marrow
transplant recipient, you have to get rid
of their stem cells, get stem cells from someone
who’s a compatible donor, and then, hopefully, they’ll
take home in the patient and regenerate good
red blood cells. But often, there are
immunological problems because the two people
are not the same person. But with this new
technology, you could reverse the sickle
cell trait in the bone marrow stem cells of this
person and populate them with their own cells,
not donor cells. This is not the germline
editing of embryos to make genetically modified
children, for which scientists have called a moratorium. This is similar to bone marrow
transplants used widely today to treat hematopoietic
diseases, and not the germline. You’d be your own donor,
populating your bone marrow with your own genetically
modified cells, but your eggs and sperm
would be unchanged. The protein coding gene makes
cures just around the corner is my title. And there are articles popping
up in The New York Times frequently because
I think it is true. We are close. I predict this type
of gene therapy will be one of the great
successes of modern medicine in the 21st century and is a
wonderful benefit of science achieved in our time, not only
the sequencing of the genomes, but the definition of a gene
as encoding for a protein. Now, with this
evangelical prediction, if this were a TED Talk, which
[INAUDIBLE] calls God talks, I could end the lecture here. As a recent TED
speaker ended her talk, my talk should get
your testosterone up and get your cortisol down. However, the sobering fact
is that these protein coding genes constitute only 2% of
all the DNA in your cells. What does your DNA really
look like to the computer? Well, here are the genes
we’ve been talking about. But 98% of it is
outside of these genes. And the computer is
frowning because they are invisible to the computer. The computer doesn’t like this. Now, what do you
do when you have a good definition that the
computer likes and gives you results, but can’t
explain 98% of the data? Do you know what happens? I don’t care what
field you’re in. It happens in all fields. You could ignore it, or
you could given a name that defies a definition. Geneticists could
call it dark matter. [LAUGHTER] But that name is already taken. [LAUGHTER] You could call it
garbage or junk DNA. Well, it ended up
being called junk DNA. According to Sydney
Brenner, you need to distinguish between
garbage and junk. Garbage, you throw out. Junk, you keep. [LAUGHTER] Right after I arrived
at MIT, my lab obtained results
suggesting the junk DNA was not just an uninteresting,
inert wasteland. We found that yeast
had jumping genes, genes that leapt from one
place on the chromosome to another by a process
of retrotransposition. And where did they end up? In the supposed junk DNA. So here, gene one, gene two. Here is the supposed junk. But these jumping genes
would jump around. And if you look at the DNA now,
not of the conserved protein coding genes, but
in this interstellar space in between them– Rafael has one here. Susan has one here. President Obama has one here. Abe had one there. They’re all in different places. And furthermore, instead
of DNA, RNA, protein, they just went DNA, RNA. They didn’t make protein. And furthermore, if
they tended to land near one of the protein coding
genes, as shown here for Abe, they affected the
expression of that gene. So here, we have
a real conundrum, which is they didn’t have the
classical DNA, RNA, protein, just DNA, RNA, but
they had a function. And they landed all in this
wild world of junk DNA. This alerted me and
many others to the fact that lots of junk DNA might be
making RNA, but not proteins. What was needed was a technique,
a very sensitive technique, to assess the total RNA
output of the genome from protein and
non-protein coding DNA. And a very sensitive method
was devised, not by me, to sequence all the RNAs
in a cell, called RNA-seq. And when you looked at the
total RNA output of the genome, you saw an amazing
collection of RNAs, not only those that made
proteins, but those that had no protein coding capacity. That is, they want DNA
to RNA, but no protein. No ATG and no open
reading frame. No capital letter and
no open reading frame. When I discussed this initially
with a computer biologist– a computational biologist. Excuse me. He’s a well-known
one here on campus. He told me, don’t worry. These RNAs from the
junk DNA are noise. But they turned
out not to be noise because these RNAs
have functions. And you know they have some
functions because they now have names. [LAUGHTER] MicroRNAs. LncRNAs. Long non-coding
RNAs is the acronym. RAN RNAs. And the list can go on. So these are, in
other words, what’s coming from
interstellar space here, is lots of non-protein
coding RNAs. And are they noise? No. OK, they’re not noise because
over the last 15 years or so, it turns out
these microRNAs are critical for controlling
gene expression of those protein coding genes. And the long non-coding
RNAs are critical, as well. These are so wild, I
won’t discuss them. And they’re antisense RNAs. So what is the
function of these RNAs? The image is just emerging. But, of course, they’re
invisible to the computer because we don’t have an
algorithm to identify them in the DNA or what they do. They’re in this vast
genome interstate. So while many scientists
sleep at night and sleep well at night without
a definition of the gene that includes DNA that codes
for these non-protein coding RNAs, which constitute
a huge percentage [INAUDIBLE],, more than the protein
coding, that we call genes, geneticists sleep like a baby. They wake up every
two hours crying. [LAUGHTER] But these RNAs are not
just recreational or noise. They’re regulatory, like
these microRNAs and lncRNAs depicted here, turning on or
off the protein coding genes. And only now are we
beginning to visualize the importance of this formerly
invisible part of the genome. As an example, I’ll focus on the
best known of one of these lnc, or non-coding, RNAs, which has
an important role in silencing genes, but only in females. As you know, females
have two X chromosomes, one they got from mom,
one they got from dad. And this lncRNA actually codes
one of the two X chromosomes, either the one
from mom or the one from dad randomly,
and shuts it off. That’s weird. Men are uninteresting. They get only their X
chromosome from their mother. And so that’s quite different
from females, who have two. Now, why would you
have this mechanism? Well, there’s a dosage problem. If women get two X chromosomes,
they should have twice as much of all those protein coding
gene products as the men. But they don’t. They have exactly
the same amount. It turns out that
this lncRNA shuts down most of the genes on one
of the two X chromosomes. Remember, she got one
of her X chromosomes– all you ladies got one
of your X chromosomes from your mother and the
other from your father, here shown as pink and green. This RNA shuts off
one or the other, and it does it early
in development. So men, for any cell that you
look at, all of their genes come from one X chromosome,
and they’re all one color. You can imagine color
blindness, for example. They’d be all one color. They would see or not see,
depending what gene they got from their mother. But women are much
more interesting. They have this polka dot
pattern because one of their X chromosomes, the one they
got from their father, from their dad, is
shut off and is now expressing only the
genes from the mother, or the other is only expressing
the one in the father. Now, if you look at this in a
mouse in a real experiment– and what we’re
looking at here, this was an experiment done at
Johns Hopkins in the laboratory of Jeremy Nathans. We’re looking at
individual neurons in the brain of the mouse. And you see for
individual neurons, some are expressing mom’s,
and some are expressing– I don’t know whether you
call mice mom and dad. One is expressing mom,
and one is expressing dad. And even to me, more remarkably,
this left-right asymmetry in some of the neurons– some neurons on the
left side of the brain are expressing one X
chromosome, and some, the other. And so this left-right
asymmetry is not seen in males. They’re either red or green. This is all due to this
long non-coding RNA, again, which would be
invisible to the computer. This is, to me, remarkable
results and, I think, to people in the field, suggests
that X chromosome mosaicism in the human central
nervous system caused by one of these strange
lncRNAs could generate female-specific
functional diversity that does not exist in males. And the similarities in
early brain development across mammals suggests that the
observations made in the mouse may apply to humans. In fact, there’s
already data suggesting inhomogeneities in human
female X chromosome mosaicism. And a question that
might arise in your mind is, does this variability
caused by this non-coding lncRNA lead to behavioral
differences, even among genetically
identical individuals? So these lncRNAs have
an important function, so important they now
have their own blog, and journals are now full of
what used to be called junk. I like the other side here– extremely volatile. Because they’re much
more evolutionarily mutable than the
protein coding genes. They’ve even got their
own blog, lncRNA blog. They do everything. Long intergenic
non-coding RNA promotes colorectal cancer, HIV
infection, [INAUDIBLE] kidney cancer. The literature is flooded
with that used to be noise. So I’ve been referring
to non-protein coding RNAs that don’t make proteins. There’s even junk in
protein coding genes that confuses the computer. Many protein coding genes
are discontinuous genes. That is, you go along. There’s an ATG. You see some coding. And then, there’s
some junk, which is called an intron, in
the middle of the gene. And then, the gene again. And then, this is
spliced out, as shown by Phil Sharpe in his
Nobel Prize-winning work. These genes are
mosaics, small pieces of coding sequences interrupted
by non-coding sequences here. The computer doesn’t recognize. It can’t tell when they come. These junk genes
here, which would be very nice to recognize
because then, you’d say, oh, there’s an
interrupted gene– but the computer can’t– they’re not consistent
enough for the computer to recognize them. People here have worked
trying to find those signals, but can’t find them. What’s even worse–
some of these genes– the intervening
sequences, the junk, is bigger than the gene
itself, the protein coding, or there are many
small coding sequences camouflaged by introns. So the computer goes along and
then suddenly has to start. It can’t find one
of these genes. So I point out, what
happened to this junk? It’s supposed to be
discarded, chewed up. Well, it turns out the
intron is not junk. Oh, my god. So together with Dave Bartell,
we just published a paper showing that excised linear
introns regulate growth in yeast. Namely, this piece of non-coding
RNA now has a function. These have no obvious
sequence conservation. They do have some
size constraints. I just want to emphasize
again that your genome is full of these protein coding
genes that were thought to be junk, but this paper shows
they have valuable information. Now, this paper
reincarnating the intron as genetic information
with function generally received a
rather complimentary, though I have to say,
surprised response from the readers of the paper. There are those that cannot
deal with this continued attack on the definition of the gene. It made them very anxious. Soon after publication,
I received this email from a highly regarded
biochemistry professor at Berkeley. “Just wild. Now, I have to
pay more attention to all that splicing crap.” OK. [LAUGHTER] So, as [INAUDIBLE] explained,
the current definition of a gene used to program the
computer, the sequence of bases and DNA sufficient to
code a single polypeptide, is inadequate to embrace all the
different informational units of the genome. The existence of these diverse
classes of RNAs, microRNAs, lncRNAs, antisense RNAs,
enhancer RNAs, intron RNAs, and many others
that are cropping up that don’t encode proteins
but are transcribed from distinct
sequences of DNA are evidence that there is no single
physical and functional unit heredity that we
can call the gene. Rather, the genome contains
many different categories of informational units, each of
which may be considered a gene. And the definition
I think that is compatible with
current knowledge is a DNA sequence that’s
transcribed into an RNA molecule with a function. This RNA centric
definition would permit a number of
categories of gene, each one denoted by an
adjective that describes the transcription unit. So there would not only
be protein coding genes, but lncRNA, intron, et cetera. Really, this is not radical. The terminology is
already becoming part of the vernacular. It’s part of the literature. The majority of
these RNA only units would currently be invisible
to a computer program to uncover only genes
that encode proteins. But progress is being made. For some RNA only genes, like
transfer RNA and ribosomal RNA, they’re so evolutionarily
conserved, the computer can easily spot those
signature sequences in the DNA. For micro RNAs,
progress is being made in identifying
secondary RNA folding structures that conserve
signatures for microRNAs. But so far, the lncRNAs and
other non-protein coding RNAs have not identified unified
identifying signatures that enable the computer
to see all of them in the vast sea of nucleotides. But I believe that the
importance of these genes for non-coding RNAs and the
flurry of activity around them– definitions that will work
for the computer will emerge. And I think as this attempt
to identify definition for these genes, the
computer will work together and be an indispensable ally of
the lab bench scientists trying to figure out function. So in genetics, we’ve
lost a simple definition of a gene, a definition
that lasted over 50 years. But loss of the definition
has spawned whole new fields trying to understand
the unknown, information in non-protein coding
junk DNA, which is, after all, 98%
of the information. As scientists
witnessing the unknown creates that intense moment
of exhilaration as a new vista unfolds, whether it’s, in your
field, discovering a new planet or unraveling the role
of unanticipated RNAs, it evokes an emotion that
I have personally found difficult to express in words. Perhaps, it’s best
expressed in music. [MUSIC PLAYING] To go where no one
has gone before and to see what no
one has seen before, this lure of these
unexpected voyages is what drew us all to
science in the first place. I look forward to enjoying
these voyages with you. Thank you. [APPLAUSE] Will you take questions? If you want me to. [APPLAUSE] Thank you, Jerry. At this time,
Professor Fink will answer one or two, maybe
three, questions about his work or the lecture. And so I will ask those who
want to pose the questions, as you’re forming the queue and
thinking about your questions, to let you also
know that afterward, I invite you all to a
reception downstairs in the lobby of building 13. Do we have any questions? I was about to ask one, but the
microphone is quite far away. OK. [INAUDIBLE] speak loudly. Go ahead. Jerry. Hi. Truly, truly congratulations. This is such a
well-deserved award. I’ve known you since
I was very small, and you’ve been always such a
wonderful mentor to all of us, all of your students,
and extended groups. So thank you very much,
and congratulations. I want to go to that
last point that you made that maybe our computers
will be our friends one day and sort of be happy
about the signal. And I want to challenge
that a little bit because I work on the computer. And we’ve looked a
lot for these signals, and they’re simply not there. I mean, basically,
it’s not that we haven’t looked for a code
for these non-coding RNAs. Coding genes have a code. [INAUDIBLE] they have
codons, et cetera. If you look evolutionarily,
you look transcriptionally, if you look at [INAUDIBLE],, if
you look in all kinds of ways, there doesn’t seem
to be a single code. So my question to you is, what
do you mean by that statement? Do you mean that we simply
haven’t found the code yet, or is it that we have to
think about it differently in some way? Is Dave Bartel here? [LAUGHTER] He should really answer. Because– [LAUGHTER] He should answer it
because for the microRNAs, there are signatures of the
microRNAs, which he has– And we’ve worked together
with Dave [INAUDIBLE] [LAUGHTER] So why are you asking me? [LAUGHTER] My question’s about
the lncRNAs and– The lncRNA. I don’t have an answer to that,
although there are some lncRNAs that are conserved. [INAUDIBLE] You’re younger than I am. You should solve this problem. [LAUGHTER] I was hoping you were
going to guide me. You’ve been doing
that my whole career. I have a simple question. Why do the microbiologists
go to sleep at night, and they sleep right
through the night because the DNA going to
RNA going to protein holds? It’s only in the eukaryotic
cells with nuclei that you have the
problem or the– how should I say it– the joy of searching
for these RNAs. Actually, bacteria have them. They don’t. They don’t have them. They have some small RNAs. Yeah. If you take a bacterium
like E. coli, 99% of it is either coding or
ribosomes or tRNA. And then, there’s a small
smattering of small RNAs. Now, there’s no such
thing as lncs or microRNAs that our equivalent. So there is something going
on in the eukaryotic cell, the cell that you study, that
is totally different than what’s going on in bacteria. And the question is, why? [LAUGHTER] I don’t know. [LAUGHTER] End it now? That’s it. Again. Would you all please
thank Professor Fink? [APPLAUSE]