- 4 weeks ago
Highlights groundbreaking advances in fertility treatments and shows how science is helping to improve fetal development and raise healthier babies....
育治疗领域的科学进展，探讨相关技术如何改善胎儿生命质量及婴幼儿养育过程 ...
育治疗领域的科学进展，探讨相关技术如何改善胎儿生命质量及婴幼儿养育过程 ...
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00:11Human beings have long been intrigued by the mysteries of our origins and the mechanics
00:17of our minds and bodies. As we continue to tease apart our biological makeup, we hope
00:26to achieve our ultimate potential. Scientists are uncovering the secrets of
00:32staying healthy, performing optimally and living longer. In the past few decades
00:39our progress towards these goals has been breathtaking. What have we discovered
00:47about getting smarter, beating disease and our bionic future? This is our
00:55extraordinary journey, our search for superhuman. Just over 40 years ago the
01:03moment of conception was brought from the womb to the lab. Is it changing the
01:10nature of our species? In some European societies up to 10% of the population are
01:16being generated by IVF. Have scientists unlocked the secret to staying fertile
01:21into older age. This intervention can potentially extend reproductive lifespan.
01:28And what have we learnt about the developing brain? If you can't wake your
01:33teenagers up in the morning, that's a good reason. They're not lazy. They are doing
01:38what their genetic development is telling you to actually do. In this episode we
01:44look back on the big discoveries in reproductive science that are
01:48revolutionising our understanding of life, birth, and human development.
02:04Over the last 60 years humanity has been going through one of the most fundamental changes in history.
02:13Globally our species has got itself into a very interesting place. All over the world we are
02:19seeing declining rates of fertility. As living standards and life expectancy have improved,
02:27instead of having more children we're having less. Since the 1960s global fertility rates have halved.
02:38They're now so low that many industrialised countries are facing a baby bust. With less than two children
02:47being born per couple. That's below replacement rates.
02:54As you become more affluent, it's more likely that the female population within any given nation will become educated.
03:01And as they become educated, they quite rightly want to pursue their own career objectives before they start having a
03:08family.
03:09And there's a very precipitous decline in female fertility between the ages of 30 and 40.
03:15So the longer you leave it, the more likely it is that age dependent infertility will become a factor in
03:21defining the fertility of a population.
03:26But infertility is not just a female issue. Male fertility has also been plummeting.
03:34And it's not just older dads. Male infertility is extremely common and seems to be getting even more common.
03:43There's a lot of concern over declining sperm counts, particularly in China where sperm counts have halved in the last
03:4950 years.
03:51We need to try to understand why this is happening. And in that way, treat the male rather than his
03:57female partner.
04:01Ironically, fertility problems today may be partly traced back to scientific breakthroughs
04:07that saved the lives of billions of babies and brought the spark of life into the laboratory.
04:20Wind the clock back to the mid-19th century. Families were much bigger. There were lots of children
04:28being born and a lot of children dying. It was the era before vaccines and antibiotics.
04:37The average family size in Victorian London was 11. But why did Victorian women in London need 11 children?
04:45Well, the reason was that there were high rates of infant mortality. Most of those children were going
04:50to die before they reached maturity and had the chance of passing genes on into the next generation.
04:57If you were only able to have one child in the 19th century, chances are your bloodline would come to
05:05an end.
05:06You had to be very fertile in order for your genotype to make it into the next generation.
05:11Now, not so much. So this lack of selection pressure automatically means that we will have less and
05:18less high fertility genes in the population. Today, a one-child family is perfectly ordinary.
05:27In Australia, for example, the average woman has 1.7 children and we can pretty much guarantee,
05:33because of the excellent primary health care we have in this country, that those 1.7 children will survive
05:38and have a chance to reproduce and pass the genes on into the next generation.
05:47There are a lot of reasons why large families are becoming a thing of the past. Contraception became
05:54widely available. Education became compulsory, so we can't send kids off to the factories anymore. And
06:01raising children has become much more expensive. Today, if we have poor fertility genes, they're likely to get
06:09passed down to the next generation. But for almost every fertility hurdle, there's been an amazing
06:15discovery to overcome it. And that's not necessarily sending our species in the right direction.
06:27Today, couples who find it difficult to conceive naturally are able to create a family thanks to
06:35amazing discoveries in reproductive science. In vitro fertilisation was developed in the 1970s
06:43by British scientist Sir Robert Edwards. The creation of human life was once an awesome mystery. But these
06:51days, human beings are being created in test tubes. The original idea was to help women with blocked
06:59fallopian tubes get pregnant. At the time, there was little understanding how it would change the world.
07:06Bob Edwards, who was the inventor of IVF, if you like, had this very simple solution. It was a kind
07:13of
07:13mechanical solution. We would just remove eggs from the ovary, fertilise them in glass, in vitro,
07:22develop the embryo until it's still invisible to the naked eye, just a small dot, and then transfer it back
07:28into the uterine environment. I remember at that time, learned people saying that IVF would never work.
07:36And even if it did work, nobody would want it.
07:40As the technique began to look promising, one revered scientist predicted that all hell would
07:46break loose, politically and morally, if IVF was allowed to continue.
07:52We're being divided up into our eggs and our uteruses. And we're saying we are more than that. We are
07:59whole
07:59human beings. How can we control or how do we know that this particular child is actually conceived or
08:10that the ovum of the womb of the womb was fertilised and sperm of her husband? How do we know?
08:17In those days, IVF was really very controversial. Early attempts at IVF were blocked very often by
08:25administrators of the hospitals on the grounds of unethical actions. Then, in 1978, the first
08:34test tube baby, Louise Brown, was born, causing a sensation. Medical researchers believe that IVF
08:43families are the ideal situation and many couples are expected to have more than one child as the
08:49procedure continues to be streamlined. More than eight million children have now been born as a result
08:56of IVF. In 2010, Bob Edwards was finally awarded the Nobel Prize for Medicine for his part in developing
09:04this revolutionary technology. IVF, this wonderful reproductive technology that we've now introduced,
09:12a lot of years, means that in our society, 5%, in some European societies, up to 10% of the
09:18population
09:18are being generated by IVF. A few years ago, these children would have caused a sensation.
09:25Now there's nothing remarkable about them at all. They're just two of the hundreds of IVF babies that
09:31have been born in Australia.
09:38Since its invention, IVF has advanced in great leaps, from how eggs are harvested to how they're preserved.
09:48Initially, women had to have surgery just to obtain one egg.
09:53So what happened originally was that you would have to do surgery to obtain a mature egg from a natural
10:01menstrual cycle, fertilize it, and they tried multiple times before they finally managed to
10:07attain pregnancy from it. One of the biggest breakthroughs was that gonadotrophins were used,
10:13which are hormones from women after menopause. Urine from menopausal women was collected,
10:20and proteins containing those hormones were concentrated and then given to patients.
10:25And this allowed not one follicle to grow, but 5 or 10 or 15 follicles to develop at the same
10:31time.
10:32This was a major, major advance. By stimulating multiple follicles, many viable eggs could be
10:40collected at once. A big step forward in achieving a successful pregnancy. But this created its own set of
10:49problems. The biggest issue was that we were very bad at freezing embryos. So the only reasonable chance
10:59of attaining pregnancy would be from transferring fresh embryo within the first three days of retrieval
11:05of the eggs. Success from single embryo transfer would be in the range of few percent only. So to give
11:14a patient reasonable chance of success, people would transfer three, four, five, six or even more
11:20embryos hoping that one of them would take. On occasion, all embryos would become babies and then you
11:27had those triples, quadruples and so on. Multiple pregnancies were not always considered a blessing.
11:36They're high risk, often proving deadly to babies. What doctors needed was a reliable way to preserve
11:44embryos for later implantation. The first successful frozen embryo birth was in Australia in 1984,
11:53using a slow freezing technique. The first authenticated birth using the freeze-thaw method
12:00resulted in the birth of Zoe in March this year. Three other women are now pregnant,
12:04one due in August. But there were risks. Slow freezing led to the formation of ice crystals which could
12:13damage the embryo. One of the biggest breakthroughs in the last 10-15 years was the ability to freeze
12:23the embryo safely, do genetic testing when appropriate and then transfer single embryo back.
12:31So, for example, in our center we almost never transfer two embryos and our rate of twins is minimal.
12:39Twins are considered generally safe, but people don't realize that even twins have six times higher
12:46chance of dying within the first year. In our center we consider twins as failure.
13:02In the four decades since the birth of Louise Brown, IVF has brought hope and joy to couples all over
13:09the world.
13:11It was less than birthday weather, but the kids didn't seem to mind. Kids who just wouldn't exist
13:18without the in vitro fertilization program. But there's also been a downside. It's one more factor
13:26reducing evolutionary pressure on our species to remain fertile, particularly the men.
13:33I think it's inevitable that the more we use assisted conception in one generation,
13:39the more we're going to need it in the next. Even if men have low sperm counts or poor swimmers,
13:46they now have a high chance of fathering children thanks to a technique developed in the 1990s.
13:54It practically guarantees fertilization as long as the egg is viable. It's known as ICSI.
14:04When I first started in this field in the 1970s and early 80s, there was a lot of interest in
14:10male
14:11infertility, not just for our species, but for domestic animals as well. But everything changed
14:17with the advent of ICSI. ICSI stands for intracytoplasmic sperm injection, and it's an amazing technical feat.
14:26If you can find one spermatozoom in a human ejaculate or even in a testicular biopsy,
14:34you can take that single spermatozoom and inject it directly into an egg.
14:39And so it doesn't matter what's wrong with the sperm, as long as you can find one.
14:45But the drop in male fertility over a short space of time is so dramatic that it can't be explained
14:51just by a lack of selection of good genes. John Aitken has been at the forefront of the
14:59international search to discover what's going on. We've been very active in trying to understand what
15:05the causes of male infertility are. The particular cause which we've identified
15:11is one due to oxidative stress. And there are many ways to create oxidative stress in the male
15:18reproductive tract. Some involve infection. Many involve exposure to environmental chemicals.
15:30In the late 80s, John uncovered one of the major contributors to male infertility.
15:36He found that molecules generated by smoking, known as free radicals, can damage DNA in sperm.
15:44But when men smoke, they're doing damage to their germline.
15:49More recent evidence is suggesting other chemicals in the environment are also contributing to the
15:55problem. We still don't have a good handle on what environmental toxicants are causing changes in
16:02male reproductive function. But there does seem to be a relationship there.
16:08In the laboratory, a number of different chemicals that are commonly found in the home
16:14have been shown to damage sperm.
16:20One example, which is parabens, used extensively in cosmetics. And when you expose permatozoa to
16:27parabens, they certainly suffer a lot of oxidative stress. One of the consequences of that oxidative
16:35stress is not just that the cell becomes less able to fertilize the egg, but you damage the DNA in
16:43the
16:43sperm cell. There is a risk that if fertilization occurs, there will be developmental defects in the offspring.
16:53Many trials over recent decades have attempted to reverse oxidative stress in sperm.
16:59But so far, there's been no proven way to turn the tide on male infertility.
17:12For females, the major issue with fertility is a matter of timing.
17:18Eggs decline in quality with age. And that's something IVF techniques have not been able to solve.
17:27It's got nothing to do with sperm meeting egg, which is all IVF was ever designed to do.
17:33The live birth rate with IVF declines at exactly the same rate as live birth rate with natural conception.
17:41So women who've left it to their late 30s to start their families,
17:47in the belief that IVF can solve that problem for them,
17:50are under a misconception, literally.
17:57As a woman gets older, her eggs are less likely to be genetically normal.
18:02And even with help in the lab, abnormal eggs are unlikely to achieve fertilization.
18:10But two decades ago, scientists finally provided women with a way to outsmart their biological clock.
18:20Eggs have a high water content, and scientists struggled for decades to find ways to slow freeze them
18:26without destruction from ice crystal formation.
18:31But in 1999, vitrification, the same snap freezing technique that improved embryo survival rates,
18:39changed everything.
18:42Vitrification involves stripping eggs of their protective layer using a special enzyme,
18:48the same one used by sperm when they burrow into the egg.
18:53The eggs are then loaded onto a small hook, which is touched onto the surface of an incredibly cold metal
19:00block, the same temperature as liquid nitrogen.
19:03The egg instantly solidifies like glass, without crystals forming.
19:13We improve chances of future fertility, but there is no guarantee.
19:17You need to obtain a lot of eggs to have a reasonable chance of having just one pregnancy.
19:27If you freeze embryos, the success is around 90 to 80 percent.
19:32If you freeze an egg, success is 75 to 80 percent.
19:36So a very large proportion of eggs don't survive.
19:39If the egg has to be fertilized, around 75 to 80 percent of the time you can attain fertilization.
19:47If you freeze eggs from a patient who is 40 years old, two-thirds of the embryos will be abnormal.
19:53Putting young eggs on ice still remains the best hope for women wanting to have a family later in life.
20:01Today, it's become so popular that companies like Apple and Facebook are covering the cost
20:07of egg freezing to attract young employees.
20:11It is a very big deal now, and I would say probably 20 to 30 percent of my patients
20:16now come for fertility preservation.
20:28So far, there's no intervention that can make old eggs young again, at least not in humans.
20:40But what was once thought impossible, now appears to have been achieved in mice.
20:46One of the most fundamental things we see when an egg cell loses its quality
20:50is its ability to separate chromosomes accurately.
20:53So every cell in our body has 46 chromosomes, and during this process of meiosis,
20:58when an egg cell matures, it needs to essentially get rid of exactly 23 of them.
21:03Now, during aging, what we see is the egg cell loses its ability to accurately
21:07separate those 46 into 23. And so what you end up with is an egg cell that has too many
21:12or too few chromosomes. This can be a cause of early embryonic failure, spontaneous abortions,
21:19and we believe accounts for the fact that there is an increased rate of chromosomal disorders
21:23in children born from mothers of increased maternal age.
21:29In the last few years, researchers in Australia discovered a way to wind the biological clock
21:36backwards in mature female mice, just by adding a supplement to their drinking water.
21:44The ingredient helps the body make a common molecule called NAD.
21:51NAD is one of these cofactors or vitamins that's present inside every cell in our body.
21:56It's used by about 40% of every biochemical reaction that happens inside your body.
22:01So what that means is you need it everywhere.
22:04So the fact that the levels of this metabolite or this vitamin decline so much with age is a serious
22:10concern.
22:12The decline of NAD is thought to contribute to the ageing process itself.
22:18And the molecule has attracted big attention.
22:23Potentially it's one of the reasons for cell death and ageing.
22:28What the whole field is working on is trying to identify ways of increasing NAD through these
22:33metabolites and translating these into clinical trials.
22:38It's one of the most important things that we have in the world.
22:39When researchers at the University of New South Wales raised levels of NAD in mature female mice,
22:45their egg cells completely transformed to look and behave just like much younger eggs.
22:54Essentially in these animal studies we see that they maintain the ability to accurately
22:58separate those chromosomes and they have the regular number of chromosomes needed for a live birth.
23:12So what we see is that in terms of ageing we can give it to older animals and at least
23:16in our
23:17mouse studies they become pregnant, which is something that we're really excited about.
23:22It's not yet proven that raising NAD levels has the same effects in humans,
23:27but the ability to extend our fertility to superhuman extremes may just be around the corner.
23:39As reproductive technologies revolutionised the way humans can achieve pregnancy,
23:45they also delivered new ways to monitor and protect the life of the unborn.
23:50In the last few decades, new genetic technologies have emerged that can take these investigations to
23:57the next level. But they're also giving scientists new insights into how the outside world drives
24:03development within the womb. From the embryo to the newborn, science has been unlocking the secrets
24:10of our first chapter of life. Throughout history, human development in the womb of the expectant mother
24:22remained hidden from view. The sex, health and even the number of the unborn was a mystery until birth.
24:30Then, in the middle of last century, ultrasound opened a magical new window into the beginnings of life.
24:38From the 1950s onward, a range of different tests to screen for birth defects began to home in on genetic
24:46abnormalities. And by 2011, a foetus with Down syndrome could be detected in just a drop of maternal blood.
24:57You can get fetal DNA from maternal blood and that was a huge breakthrough, which has really transformed
25:05the landscape of prenatal genetic testing as well. So far, both pre- and postnatal screenings
25:14have targeted specific conditions. Most Western industrialised and other countries
25:21do a newborn screening routinely, but it's only for a very small number of conditions,
25:27and we have set up over the last three decades really, really firm rules about which conditions
25:34we screen for. It's basically a biochemical test, not a genetic test, but it's for genetic disease.
25:42With the cost of DNA sequencing dropping dramatically, companies have now begun to market a much more
25:49comprehensive type of screening. One that can provide a readout of the entire genome of the newborn,
25:57like a kind of DNA crystal ball highlighting future health and disease risks. Some researchers say
26:05this could allow a lifetime of personalised medical care. Others say it offers needless worry and little certainty.
26:18When and how to use genetic testing is one of the hardest and most difficult challenges that come
26:25from the success of the Human Genome Project. Some people think it just seems intuitive. Well,
26:31why don't we just get all of their genes at birth and then we would have like a magic path
26:36to everything
26:37that would happen to them during their life. But it turns out it's much more complicated than that.
26:42The big problem with making predictions from whole genome sequencing is that genes
26:47don't necessarily equal destiny. We started out with this idea that genetics was extremely
26:55deterministic. A gene yielded a behaviour or a disease, but we now know that genes are actually
27:02not that deterministic. The Human Genome Project pioneered the sequencing of the entire human genetic code
27:13and ran through the 90s and early 2000s. It turned out to be just part of our understanding of the
27:21blueprint for life as scientists began to appreciate just how differently identical genes can be expressed.
27:29If you look just at the gene, it might be that you end up with a child who can express
27:35a little bit of the protein
27:37that's needed and so doesn't have a problem, but the genes still suggest that they have a disease.
27:45Genetic expression can be changed by chemical tags that either ramp them up or turn them down,
27:51effectively silencing them. Which is like all these different coloured highlighter pens underlining old
27:59italics, which dictates whether genes are turned on more or off.
28:08This coating of chemical markers across our 20,000 genes are collectively known as the epigenome.
28:16It acts like the software program for the DNA hardware to follow.
28:23It's absolutely crucial because as the embryo grows from this fertilised egg,
28:29that same genome can specify a different cell, a brain cell versus a heart cell versus a liver cell,
28:36in order for the cell to know what it is and what it's going to become.
28:41That's dictated by epigenetics as well during development.
28:52Receiving the wrong chemical cues during this critical phase can be catastrophic.
28:59It's one of the reasons why the mother's diet is of critical importance as the fetus develops.
29:06Epigenetics is the study of how our genes learn from experience.
29:11Probably the best example is one of the most important from a public health perspective,
29:16which is it is essential for women who want to become pregnant to take a vitamin, folic acid.
29:22If they do that, and if they take a daily supplement of folate throughout pregnancy,
29:27their child has a dramatically lowered risk of a particular birth abnormality.
29:33Two large randomised trials in the 1990s provided convincing evidence
29:38that folic acid in the mother's diet could prevent neural tube defects.
29:46Neural tube defects can occur before women even realise they're pregnant.
29:53In the first month, a tube forms in the developing embryo that will later become the baby's brain,
29:59spinal cord and backbone. When this tube doesn't close properly, it can result in severe
30:06and lifelong disabilities like spina bifida.
30:14Believe it or not, this has not to do with the DNA, but with this makeup that the DNA acquires
30:20as the fetus develops into a baby.
30:24Folate is part of the vitamin B group and is found in leafy green vegetables,
30:30legumes, fruits and other foods. For cells, it's an important source of methyl groups,
30:37one of the most common chemical compounds that tag DNA and change its expression.
30:44This tagging is thought to be one of the primary ways folate helps prevent neural tube defects.
30:52Today, more than 50 countries fortify food products like breads, pasta and flour with folic acid.
31:00In the US alone, it's been estimated this intervention saves around 1300 babies a year
31:07from lifelong disabilities. More recently, researchers have been discovering the profound effects that
31:21man-made chemicals can have on fetal development. Some of these changes are not immediately apparent
31:28in the newborn, but cause damage that manifests later in life.
31:33One of the ways you see this manifest is in the rising incidence of testicular cancer.
31:38In the 1940s and 50s, and certainly when I was growing up, nobody knew anybody who had
31:44testicular cancer. Now everybody knows somebody who had testicular cancer.
31:49And the actual prevalence of this disease is increasing.
31:54Testicular cancer rates have doubled since the 1960s in many Western countries.
32:00It affects young men at their peak, but has its beginnings much earlier.
32:11The thought is that it has its origins in fetal life. The environmental chemicals that women are
32:18exposed to when they're pregnant, if they're carrying a male baby, those chemicals will influence the
32:24differentiation of the testis and cause changes that ultimately lead to testicular cancer.
32:32The peak instance is around the age of 31 and 32.
32:37This developmental disruption is one of the many factors that can also affect male fertility.
32:45And that will affect his fertility for a variety of reasons, but mostly the germ cells,
32:50the fundamental cells that develop into sperm, they've been impacted by this change.
32:54So it's not that men with testicular cancer are infertile, but frequently subfertile.
33:08There are a multitude of different environmental chemicals that can interfere with the body's hormone
33:14system. They're known as endocrine disruptors and can epigenetically reprogram cells with long-lasting effects.
33:24Which one leads to testicular cancer is not yet known.
33:30The hunt is on for what is that environmental chemical. One thought is that compounds which
33:35are used in the plastics industry can impact the adult male and have a direct influence on its fertility.
33:41The hunt is on for what is that energy.
33:43Today, there are nearly 1,000 man-made chemicals in the environment which are known endocrine disruptors.
33:52We know that there are an enormous number of man-made chemicals in the environment,
33:59and we don't entirely know what their effects are, and this requires a lot more research as well.
34:12The influence of the environment continues well after the baby leaves the womb, but it goes way beyond chemicals.
34:20Scientists have uncovered fascinating ways that childhood experiences can shape everything from
34:27the immune system to the developing brain. These discoveries reveal how simple choices that parents
34:33make could dramatically alter the course of their children's lives.
34:40The nature versus nurture. It's never one or the other.
34:46In the journey from foetus to newborn, through childhood to adolescence,
34:52the environment exerts a profound and lifelong impact on health and well-being.
34:58But for the past 30 years, scientists have made some surprising new discoveries that have changed
35:05what we understand about the optimal childhood environment. One of the most startling is how
35:12their first microbial contact can shape health for many years to come.
35:20As the fully formed human prepares to greet the world outside the womb, there's another important
35:27group of organisms getting ready to inhabit their new home.
35:34During pregnancy, your gut microbiome reshapes and also your vaginal microbiome reshapes into a new state.
35:41And one thing that's really exciting is the possibility that this might be an adaptation
35:46to coat the baby with the right kinds of microbes.
35:50As the baby is thrust into its new life, it makes first contact with many bacteria, fungi and viruses.
36:00One of the great discoveries from the last two decades of research into the human microbiome,
36:06has been how important these first few moments are to a baby's future health.
36:17If you're delivered the regular way, then all of the microbes all over your body, including in your gut,
36:22are going to be seeded from your mother, primarily in a microbiome that looks like the vaginal microbial community.
36:29Whereas in contrast, if you're delivered by C-section, you just don't get any of those microbes.
36:36And instead what you do is you pick up microbes from dust and from people touching you.
36:41And so the microbes all over your body and inside your body look much more like a skin microbiome.
36:47We're just starting to see some of the impacts that has on long-term health
36:50in a study with the Norwegian Institute of Public Health.
36:54Rob Knight's team have been analysing the microbiomes from babies born 12 years ago
37:01by C-section or natural birth and comparing it to their health today.
37:07And those first microbiomes within the first month of life have a huge impact on how children develop
37:13later on. And in particular, the combination of C-section and antibiotics has a particularly
37:19helpful effect on your microbiome and on your later development. Although one thing that's exciting
37:24is that we're seeing that breast milk erases a lot of those early differences.
37:33At the turn of the last century, it was observed that babies fed breast milk had a much higher survival
37:40rate than bottle-fed babies. In the 1920s, scientists discovered the bifidus factor,
37:47the presence of healthy, protective, beneficial bacteria in breast milk. Studies across the decades
37:55have since identified many more factors. By the year 2000, more than 100 had been discovered.
38:04Breast milk has a lot of things that are probably good, including microbes, but also including
38:08antibodies that confer resistance to particular diseases, but may also help reshape the microbiome.
38:15And then what are called HMOs or human milk oligosaccharides, which are special kinds of sugars that
38:20your own genes and your own enzymes can't digest, but they feed the right kinds of bacteria for your developing
38:27gut.
38:38Once babies are populated with a diverse and healthy microbiome, the choices parents make
38:45in those first early years can either trash or enhance this important microbial population.
38:53Some of the things there are fairly obvious, like not feeding your child too many chips,
38:57not too many sugary drinks, but some of the things are less obvious. So for example,
39:02one thing we're finding has a huge impact on the microbiome is how many different kinds of plants
39:07you eat. And that seems to be a lot more important than, for example, whether you're vegan or whether you
39:12also eat meat. The other thing that's really important is antibiotic use.
39:18A 2010 study in the US revealed the average two-year-old has already received three courses
39:25of antibiotics, jumping to 10 courses by the age of 10.
39:31A lot of the reason why antibiotics are handed out like candy to children
39:35is that usually the assumption that it's not going to do any harm.
39:40But we're now starting to understand that it may not just be harming your child,
39:43but your grandchildren and their grandchildren by depleting the microbiomes in their gut and in
39:49the rest of their body so that they're losing species they need to maintain their overall health
39:54over a lifetime. The use of antibiotics in childhood has been linked to an increased risk of obesity,
40:01asthma, inflammatory bowel disease, allergies and diabetes.
40:13For many decades, scientists have tried to understand the reason for rising inflammatory diseases.
40:21One of the most popular concepts put forward in 1989 was the hygiene hypothesis, that by keeping our
40:29environments too sterile, we were robbing children of the necessary infections needed to develop their
40:35immune system. Since then, the old friends theory has gained ground, that we're missing beneficial bacteria
40:43that we've evolved with for millennia. For example, in studies of farm communities like the Amish and the Hutterites,
40:52children who go on the farm have much lower rates of asthma and allergies than children who are sequestered
40:57at home and kept away from the farm animals. That seems to be due to changes in their microbial exposures
41:02early in life.
41:07Nature has been shown to foster beneficial changes, not just in the human microbiome,
41:14but in the developing brain as well.
41:25From the moment they're born, children seek interaction with the world around them in order to learn.
41:31It's also known for children. A large part of this development occurs during play.
41:37Around 15 years ago, Kathleen Baggett set out to study how children perceived their school
41:43playgrounds and how play affects cognitive performance and mood.
41:49What I found was that children found playgrounds that were greener or had more natural elements.
41:55They found them to be more restorative. That was associated with how green the playground was.
42:00And what that then did was translated to their behaviour back in the classroom.
42:06Kathleen also discovered that children in greener playgrounds scored significantly higher in maths
42:13and English tests than those in less green playgrounds.
42:18So I was in a number of different socio-economic areas and we controlled for that within the analyses as
42:26well.
42:27The higher the amount of vegetation in the playground, the stronger association with academic outcomes.
42:41In 2012, a large Spanish study also looked at the relationship between green spaces and mental
42:49development in more than two and a half thousand primary school students.
42:56The researchers found that each degree of increase in surrounding greenness corresponded to a five percent
43:03improvement in the development of short-term or working memory over the year.
43:10The overarching theory is that because we evolved in a more natural environment,
43:17then our bodies and minds are more attuned to be functioning well in those types of environments.
43:23People are studying the brain and looking at brain waves and what they're finding is that
43:27there's differences in the brain waves if people are looking at a natural scene versus a more built or
43:33more urban scene. And what they're proposing is that the brain takes less effort to actually process
43:40green spaces or natural spaces and therefore when you spend time in those greener spaces your brain
43:47isn't working as hard to process what it can see and what's going on.
43:52And therefore your capacity to pay attention improves, your mood can improve, if you can feel more
44:00restored and more refreshed after time in a green space than after time in an urban space.
44:06Natural spaces incite engagement, risk-taking, discovery and creativity which are all thought to
44:14enhance mental development in children.
44:18In natural spaces there is more unstructured play typically is able to take place.
44:25So for example there was a playground where they had a cut-off tree trunk.
44:29Sometimes it was a rocket ship, sometimes it was a boat, sometimes it was a home, sometimes it was a
44:35tent.
44:35So they were able to use their own imagination with this one element and come up with all sorts of
44:41different things and then unstructured play would come from that.
44:47Brain development in the early years is marked by an extensive change in architecture,
44:52as children build their repertoire of experience and learning.
44:56But over the last two decades it's also been discovered that chronic stress during this time
45:02can leave lasting chemical marks on the brain.
45:07These epigenetic tags can evoke changes like altered hormone production, increasing the likelihood of a major depressive illness.
45:18child abuse of any kind and trauma early on actually left this epigenetic memory
45:25in the brain that could be measured and that's absolutely growing in understanding the whole of
45:32psychiatry and mental health that your environment throughout your life including critical periods
45:37of development this trauma can be carried through life. Adolescence is also a critical period of development
45:47as a rush of hormones is triggering changes in every aspect of the developing child
45:52from body organs to personality. The genes of puberty are extremely important. The genes related to whether you're a girl
46:01or a boy,
46:01so the hormonal influences you're under are extremely important in these particular areas
46:05and genes are operative at different developmental phases. You might have noticed that your teenagers
46:10change body shape. Guess what? Their brain changes. So also does their sleep-wake cycle.
46:20For parents, the sudden arrival of a teenager who goes to bed late at night and can't get up in
46:26the morning
46:26can be disturbing. The sleep-wake cycle goes through a developmental period. Primary school,
46:32pre-pubertal children, they get up when the sun gets up and they go to bed and the sun goes
46:37down.
46:38Teenage comes along, it messes with it. Since the early 90s, scientists began to suspect that this
46:45common pattern could be a biological shift associated with puberty. Studies since have confirmed it
46:53occurs in many other adolescent mammals. So if you can't wake your teenagers up in the morning,
47:00that's a good reason they're not lazy. The science suggests that allowing this natural
47:05sleep pattern in teenagers is vital for their development, especially when it comes to their
47:11mental health. My colleagues in the United States have demonstrated you go wake teenagers too early,
47:17you make them more depressed, you increase their suicidal behaviour, you make them worse because
47:21you're waking them at the wrong period. Good morning.
47:28Have a seat. I'll be in in just a second. I'll get you unplugged, okay?
47:32They're not being lazy and naughty. They are doing what their genetic development is telling them to
47:38actually do. It's one of the reasons why in 2014, the American Academy of Pediatrics endorsed a start
47:51time of 8.30am or later across schools in the US. But if the teenage clock shifts too far in
48:02the wrong
48:02direction, it may be a red flag for trouble ahead. Those who are at risk and the ones we study
48:09in
48:10particular called atypical depression, they almost become nocturnal. They're in a lot of trouble. They
48:15often actually don't get up actually in daylight hours and then they're up all night. And they're
48:20at very severe risk of developing major mood disorders. Even though the brain reaches its full
48:26size by puberty, MRI studies have revealed that it's still undergoing prolific change. The teenage
48:34years in particular are marked by a profound pruning phase where the brain shapes its most efficient and
48:40useful networks and cuts back others. So the baby brain actually has many, many more connections
48:48than the adult brain will have. They're not as myelinated, they're not as large and they haven't
48:52really established themselves yet as strong connections. But everything is kind of hyper
48:56connected to some degree in the baby brain. And as you progress through your childhood and
49:02adolescent and teenage years, there's a sculpting in which particular circuits and synapses are
49:07built up and reinforced and other ones are removed. Taking risks at this age, especially chemical ones,
49:15can have damaging lifelong effects on brain architecture and mental health.
49:22For depression, for example, only 30% of the risk is explained by genes. But genes are just one of
49:30the factors. What turns a gene on or off often lies in the environment. You may have the genes that
49:37expose
49:37you to develop psychosis if you smoke a lot of cannabis or take a lot of drugs. But if you
49:41never take
49:42them, you aren't getting it. You know, so in our area, genes are not illnesses.
49:48The ongoing Dunedin study, which has been following more than 1000 New Zealanders born in the early 70s,
49:55found that teenagers who smoked cannabis by the age of 15 were four times as likely to have
50:01schizophrenia by age 26 than those who didn't smoke.
50:07I think it's fair to say that because the teenage and adolescent brain is so fragile and is still
50:14developing, that things that really change the neurochemical environment, like recreational drugs,
50:21are potentially very hazardous, especially at that age. And I'm not here as an anti-drug crusader. I'm a
50:28neuroscientist. But you want to let the biology take hold. You want natural, healthy learning and
50:33experience to take hold. And that chemical intervention is potentially very hazardous.
50:39They hold such great potential to harm the developing brain.
50:44Studies around the world indicate that mental illnesses like depression, anxiety and bipolar disorders
50:51have risen significantly over the last 70 years. Although some studies blame social media for depression
50:59in teenagers, Ian Hickey says the evidence is not there. There are dangers in new social media.
51:08It is not the cause of the change. In fact, what young people did with social media,
51:16in fact, increases social connection between people. Because we're humans, we relate to each other.
51:22Social media can increase connection. I've worked with kids with autism and kids who were withdrawn
51:27and kids who are transgender and these kids stay connected to others they would have never connected to.
51:32The facts are clear. Suicide rates were higher in the late 1990s before Facebook was invented.
51:44Across that time frame, there's been a larger change happening in society,
51:50which brings us back to the unusual phenomenon of shrinking families.
51:57If you look at post-World War II, a number of things that happened, drug and alcohol use being important.
52:03But the loss of connection between us as humans, ways families have changed,
52:07ways communities have changed, is a much bigger risk factor.
52:12Wired into our human DNA is a need for connection that is perhaps as vital for our health and survival
52:19as water, food and shelter. The desire to communicate, to form a loving and secure relationship is apparent
52:30almost from the moment of birth. So adolescents who are lost, who are disconnected, who don't have big
52:37families, not parts of communities, who are alone, feel there's nowhere to go, that's a much bigger risk factor.
52:42And social media, like many things, we must monitor the risk, but we should also seize potential.
52:51Although our nature is written in our genes, it's the nurture we receive that shapes the superhuman
52:58version of us all. From a fertilised cell, all the way to adulthood, the way we are conceived,
53:08the lifestyles of our parents as we develop in the womb, our first contact with microbes,
53:15the early steps we make through our natural environment and who we interact with. Even the
53:22rhythms of our sleep make an indelible impression on our health, wellbeing and personality for the term of
53:31our natural lives.
53:32So
53:38so