Another Review!

“Embryologenesis Explained is a pleasure to read, presenting difficult concepts clearly and effectively. It carries deep biological thought, and whether one agrees with the differentiation waves theory or not, it is inspiring and stimulating.”

Biol Theory
DOI 10.1007/s13752-017-0260-z

BOOK REVIEW

Mechanistic Development

Natalie K. Gordon and Richard Gordon: Embryogenesis Explained; World Scienti c, Singapore, 2016, 784 pp., £164 hbk, ISBN 978-981-4350-48-8

Jean-Jacques Kupiec1

© Konrad Lorenz Institute for Evolution and Cognition Research 2017

 

Excerpts:

“Overall, Embryogenesis Explained is a very interesting book. Although it is primarily intended to be theoreti- cal, it provides a large overview of the data collected on various subjects of developmental biology and could thus also be used as a complementary textbook. Of course, it raises a number of questions. The main question concerns the di erentiation waves theory itself. I am typically one of those biologists referred to by the authors who usually does not put the cytoskeleton and mechanical forces at the forefront for understanding development. So, was I con- vinced that the cell state splitter is the driver of develop- ment? The theory is certainly coherent. It is based on data and it suggests testable hypotheses. In this regard it should be accepted, and its research program should be developed. Natalie and Richard Gordon undoubtedly point to some- thing very important, and molecular biologists focused on gene expression will bene t from reading this book.”

“Am I entirely convinced, however? When reading this book, a question will inevitably arise in the mind of any reader: could it be that simple? In the preface, the authors argue that a theory of embryogenesis has to be simple. But, I am perplexed. Although I agree that the physics of biology has not been su ciently taken into account, and this is why Embryogenesis Explained is valuable, I have some reservations about the purely mechanical theory proposed here and the broader holistic philosophy in which it is inserted. First, the di erentiation waves theory is totally deterministic, whereas the stochastic aspects of cellular physiology, notably in gene expression, are amply docu- mented now. Integrating the randomness of cells into the picture will produce a radical change. Because of this inherent stochasticity in cellular behavior, cell fate cannot be determined exclusively by the cell state splitter as described here in a purely deterministic way. I would rather see the physics of biology as imposing constraints that give a direction to cells but not as acting as their rst causal mover. Second, I am not at ease either with the holistic philosophy the authors wrap their theory in. I even nd it to be paradoxical. Mechanism is philosophically associated with reductionism. There is no doubt that if Descartes were alive today he would enthusiastically approve and applaud the authors’ mechanistic theory. But, I think there is a widespread confusion among a number of biologists today. Because they reject genetic reduction- ism they tend to reject reductionism in general and adopt a holistic perspective. However, there are different forms of reductionism. Natalie and Richard Gordon’s theory is physicalist, and physicalism is an even more radical form of reductionism than genetic reductionism. In my mind this is not an infamy. Historically reductionism has been (and still is) the prima philosophy and methodology of science. It is beyond the scope of this review to analyze these issues in depth. I mention them only to show possible further discussions. It does not diminish the merit of Natalie and Richard Gordon. Clearly, they are successful writers, and I enthusiastically recommend their book. Embryology Explained is a pleasure to read, presenting difficult concepts clearly and effectively. It carries deep biological thought, and whether one agrees with the differentiation waves theory or not, it is inspiring and stimulating.”

Embryogenesis and the G-d Factor.

Many years ago Dick and I reached am impasse on our research on the waves. We had the image of the wave on the top part of the ectoderm but we couldn’t actually see the bottom half. Our engineer collaborator said the wave must cover all the ectoderm and therefore could not be THE differentiation and organizing signal. I said our engineer was wrong. I had observed enough embryos that I just knew the wave did not go all the way around the embryo. I was absolutely certain I was right.

We had an argument over it. It started at work and it continued after we got home and the kids were in bed. Now normally we never argue. We have these very rational easy going discussions about everything from laundry to dishes. This time we ended up shouting at each other into the wee hours of the morning. Neither one would back down. In the end we concluded that the only thing to do was more research. We  did top and bottom pictures simultaneously and it turned out I was right. End of story.

There was one tiny issue. The next morning after our huge argument our neighbour came over for coffee with the wife of the newly wed couple who had just moved in next door. As soon as Dick left and she asked me if I was all right. Was I injured? Had he hit me? We had been yelling so loudly we had awakened her. She was so worried about me! How embarrassing. I had to assure her we were only arguing over data interpretation and we had concluded the way to settle the argument was to do more experimental work. She left, somewhat reassured but still dubious, and we made a decision to be certain the windows were closed if we ever needed to fight over data interpretation like that again. We never did have such an argument because we both learned an important lesson. The embryo is always right and when you have a disagreement you must always go back to the embryo to settle it. (I only occasionally rub it in that I was right.)

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From our giddy newlywed days and our only really ferocious argument.

The second worst debate we ever had was over the G-d factor in our book. Dick is an avowed atheist although he does occasionally stray off that stance and exhibits more of an agnostic position. Although I am no biblical literalist,  I am a religious person and I deeply and absolutely accept the idea of a higher power I call ‘The Master of the Universe’ according to my beliefs. In preparing our book I really wanted to make sure we acknowledged the Master of the Universe.

I wrote the first draft of Chapter 1 and every time Dick did his round and he removed the G-d factor. I would review his work and put the G-d factor back in. This went round and round quite a few times. He argued there is no place for a G-d factor in a purely scientific book. He is right but this is also MY book and we were gong to have that G-d factor. One reason I was so intent on having it in there is I am not alone in being both a scientist and being a religious person and I often feel the lack of acknowledgement of the Master of the Universe in science. It’s like one can’t be both religious and scientific which is obviously untrue. I have a lot of company.

My first mentor in embryology was Hans Laale and he was also a deeply religious man. On his desk was a picture of his parents and a rosary bead hung on that. he kept his religious beliefs out of the classroom but he did acknowledge them once. About half way through his course, when I was having  deep philosophical discussion, he complained how hard the problem of embryology was and he said he wondered if the problem would ever be solved. Maybe there were just some things that we weren’t meant to know.

I disagree. G-d has created this universe with a set of rules and regulations, constants and laws. They may be hard for us to understand but as we grow and learn as a species I see absolutely no reason we should not be able to figure out exactly how the Master of Universe did it. Nor would figuring it out in any way diminish the glory of His creation. In fact I think greater understanding will only serve to increase our appreciation for Him.

We talked a lot about the problem over the years together. I like to think that at least in part, Dick agreed to co-edit a book where creationists and scientists debated the origin of life because of my influence. There is an interesting story he references there which we first heard from a rabbi. It is about a scientist who has been climbing the mountain of ignorance seeking answers to how the universe works. He arrives on the mountain top to find a lovely flat spot. And there, sitting around a fire discussing the problem, is a group of theologians (Jastrow, 1992). Dick’s book ended up creating more questions than answers but at least they got to questioning.

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From this process Dick acquired enough respect for theology that although he maintains his personal firm stance as an atheist, he was nonetheless ready to compromise with me and eventually allow me to keep the G-d factor in the book.

Dick and I added the following paragraph we could both agree on;

“The religious among us who nonetheless embrace the overwhelming evidence for evolution often see the finger of G-d as stirring that primordial goo: yes, life did start out as goo somewhere in the universe, maybe more than once, but it could only have done so because G-d did it. … And if one must invoke G-d, then we can at the very least, expect to figure out exactly how He does it.”

And that is the how and why of the brief appearance of the G-d factor in Embryogenesis Explained.

Stadium Waves and Embryogenesis.

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I (Natalie) was at a southern barbecue eating good food and enjoying good company when our book came up in conversation. With it came a request to explain the waves in simple terms. Being surrounded by a bunch of really keen American football fans I invoked the stadium wave.

The stadium wave (also called the Mexican wave) is great fun phenomena where someone starts a “wave” that is made by people in the stands leaping up and putting their arms in air. The wave will travel around the stadium. The differentiation waves are much the same. A sheet of cells is ready to participate in the wave but each cell doesn’t actually stand up and wave its arms until the cell next to it does it first. If you look at the stadium way, the people can watch what other people are doing. A cell has no eyes and no brain. So instead of watching for the wave and watching it as it passes, the cell has its bistable organelle on top to sense if a wave is coming its way. When the cell next to it “waves” it gets its signal to do its thing.

When I was a little girl in Brownies we attended a huge event in honour of Canada’s 100th birthday in 1967. The Montreal Arena was absolutely packed full of little Brownies all in uniform and we each had a cushion. My cushion was yellow on one side and brown on the other. All those in my pack had the same cushion. All the packs sitting in my section had the same colour. Other packs in other sections had other cushions, with different pairs of colours but always light and dark. I recall being absolutely fascinated by how the person directing from the floor was able to make incredible patterns across the stadium by the simple act of saying things like “Everyone on the south side hold up their cushion with the dark side out.” The arena became a brown sea. “Now everyone turn your cushion over!” and suddenly the area erupted in gigantic patches of bright colours.

Imagine a bunch of little girls in their cute little Brownie uniforms but instead of one cushion each Brownie has five cushions. The cushions are numbered 1 through 5. The Brownies are all in their seat and they follow instructions to take out cushion number one and be ready. Cushion number 1 is red on one side and white on the other. Now the leader gives instructions. Everyone on this row, turn your cushions to white. In the row beside them everyone turn their cushions to red. Now “go”.  In embryonic terms, the cell is ready with a “cushion” that is the bistable organelle, the cell state splitter. The cell state splitter can either expand or contract in response to an outside mechanical signal or to what the cell next to it can do. Red cushion is analogous to contraction, white to expansion.

The result would be a moving wave of white in one direction and red in the other other that would move around the stadium until the red and white meet on the opposite side and then the wave would stop. We would now have the stadium neatly divided into half red and half white. This is exactly what happens during the embryonic stage in mammals known as compaction. A ball of cells is neatly divided into two parts, the inner cells mass and the outer trophoblast. Instead of red and white we have contraction of the inner cell mass and expansion of the outer trophoblast. The contraction action actually moves the contracted cells into the inside. The expansion results in an outer sphere of cells. The balls of cells of the recently fertilized egg undergoes it first differentiation. The inner cell mass will become the future mammal. The outer sphere will come the placenta, and amniotic sack and other supportive tissue which is later discarded at birth.

What part do “genes” play? Go back to our little Brownies. Now once the first wave has gone by the leader says to the Brownies “Check your cushion for instructions!” The white side of the cushion has printed on it “Put the red and white cushion away and put cushion number 2 (brown and orange) away with it and take out cushion number 3 (green and yellow). The red side of the cushion has the instructions “Put the red and white cushion away and take out cushion number 2 (brown and orange) and put cushion number 3 (green and yellow) aside with the red and white cushion. Now repeat the entire event but this time the two start rows are not at one end of the stadium but instead are started in the middle. Two rows in the middle of the white section are instructed to have one row wave green and the other row wave yellow. Meantime in red section the two rows are to use their brown or orange side respectively. The result of triggering the waves again is the division of the stadium into four sections, brown, orange, green and yellow.

The only “outside” information required to do this division of Brownies in a stadium is to watch the girl next to you and do what she does except for the ones in the start row. This is how the differentiation waves work. The only information a cell has is what the cell next to it does. The response is inherent in the colour of the cushions the child is carrying and the directions on those cushions which is analogous to the genetic code each cell carries. The code includes instructions of which part of the code (cushion) each girl is to use next. The code also contains instructions for which genes (cushions) to put away and not use.

This response to the wave, reading the cushion instructions, is the embryonic process of “determination”. If we wanted to carry the analogy even further, imagine that each little girl has brought a suitcase of clothing along, separated in five numbered bags that match the cushion colors. After she participates in the red wave, the instruction on the cushion include the directive to take out and change into the clothing in one of the bags. Eventually all the girls are wearing a new outfit corresponding to which waves she participated in. This changing of clothing would be analogous to “differentiation” where cells stop producing one set of proteins and change to another set of proteins and in doing so become a new type of cell. The genetic code carries not just the instruction on the cushion (which are signal transduction to the nucleus i.e. determination) but the instructions for how to make the clothing in the suitcases (differentiation). Each different cell uses some of the code but not everything in the code (some cushions nut not others) depending on where the cell is and what sequence of waves it has participated in.

In our cell sheets, the start of the wave is signalled by some mechanical force in the cell sheet instead an announcer/leader. If we take the ectoderm contraction wave as an example, the underlying invagination of mesoderm touching the underside of the sheet of cells is the signal. This mechanical signal is passed from cell to cell the pushing and tugging of neighbours.

The ectoderm contraction wave actually goes through more than one tissue. It starts in tissue that will eventually become notochord then passes through tissue that will become tailbud mesoderm and then finally through to the ectoderm. In early embryogenesis, many of the waves go through more than one tissue. However, if the cell in that tissue has been previously subdivided by earlier waves, the result is simply that the wave passing through more than one tissue type will create a pattern duet each cell having a different set of instructions (or a different cushion). If you look at the “Best Wave” sequence, the audience has previously been divided by being given different cushions. The wave in the stadium simply exposes a preexisting difference in a spectacular fashion. Note how once the wave has created the beer glass pattern, there is another wave inside just the beer glass that empties it visually. A second wave (or third or fourth or fifth) on one section of an embryo but not another allows refinements of the pattern of embryogenesis.  In our model, the people who make the beer glass drain would be a tissue type that once triggered is primed to be trigger again even though the people around it stay quiet. Repeat waves are also very common in embryogenesis in development of the early brain, for example.

One other little bit of embryological jargon. A cell can only participate in a wave if it is “competent” as in ready to go. In the case of the beer commercial below, it is like the people waiting, cushions ready, like the people at the beginning to the video.

 

 

It is hard to explain the waves of embryogenesis in few sentences in a break between barbecued steak and key lime pie to a group of people whose sole common interest, aside from being related, is that we have all watch football. But the stadium wave, and my experience as a Brown back in 1967, served as an excellent analogy where everyone seemed to “get it”. Yes, “the genes” do it but waves explain why genes only “do it” in the right place at the right time.

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Lil Girl Released to the Sea.

Yesterday we attended the release of a loggerhead sea turtle named Lil Girl. Lil Girl had been a resident of Gulf Specimen Marine Lab since she failed as a test subject on a turtle exclusion device. She was one of several hatchlings who were taken from Florida, transferred to Galveston Texas where she was raised by NOAA until she was the perfect age and size to stand in as a Kemp’s Ridley sea turtle in experiments on mandatory equipment used by shrimp fishermen that allow turtles to be excluded instead of drowned.

Turtle exclusion devices are, in my opinion, the very best of humanity in action. Instead of simply railing at the evil of humans who accidentally kill turtles as by-catch a constructive solution was researched, developed and then tested. The problem is solved in a rational and practical way that still allows humans to eat shrimp. This wonderful and incredibly valuable work is still on going at NOAA’s Fisheries Service Sea Turtle Facility which Dick got a tour of during our Galvaston trip.

Lil Girl was originally raised in this facility. After she flunked the TED test she got sent to Gulf Specimen Marine Lab to be used as a teaching animal until she reached adult size. As a young adult capable of breeding, and therefore extremely valuable to the wild loggerhead population, Lil Girl was deemed ready to go this December.

Lil Girl was a long time favourite at GSML. She arrived as a tiny turtle in 2008 at 13.6 inches long (32cm) and weighing 12.5 lbs (5.7kg) and at the time of her release she had gown to an astonishing 27.7 inches  (70.4cm) and 81.6 lb (37kg). Every year when we arrived back at GSML we looked forward to seeing Lil Girl again and see how much she had grown. An estimated 180,000 people have come to GSML and have seen Lil Girl. She has been a wonderful Ambassador for her species. The picture above is Lil Girl in 2014 and then two years later in 2016 and you can see how her shell is not only bigger but grew longer as she grew. Dr. Robbin N. Trindell of the Florida Wildlife Services decided it was time for Lil Girl to have her chance to make it on her own out in the big wild ocean. Dr. Trindell was on hand for the release and to reassure the public this was the right thing to do.

Lil Girl arrived in the GSML truck and staff gathered to say goodbye. More than one was in tears because Lil Girl had become something of everyone’s favourite pet at GSML. The guest of honour seemed to be very nonchalant and relaxed about the entire thing.

There was a thunderstorm in the area at release time and the big moment was delayed while this small twister passed by and eventually formed a small water spout over the bay before the weather cleared and the sun came out. To everyone’s delight a group of three dolphins swam by, coming close to shore to check out the fuss as the water spout moved out of sight.

Members of the public took advantage of the delay to get one last close up look at Lil Girl.

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Very special guest of honour was little Kai Rudloe with his Mom April. Will Kai Rudloe grow up to come the third generation of Rudloes to work in a third generation at Gulf Specimen Marine Laboratory? Only time will tell but he did get a great start today.

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So Lil Girl was removed from the vehicle and loaded up into the transfer sling for her walk down to the beach. More than one staff member was fighting tears.

It was hard to let her go. And she didn’t seem all that keen to be off herself. Unlike Allie who was straining to be free again at her release, Lil Girl looked all around and blinked her eyes obviously very puzzled about what was going on. She has always been in the care of humans and she trusts us completely and something was up she didn’t understand. In the end, she needed some shoving by Cypress Rudloe before she finally headed off into the great ocean she had never seen or swam in before.

 

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This fabulous picture was taken by Nic Christie, a professional photographer who does a lot of great work for GSML. It is not our picture though I sure wish it was! A great place to see more of his work is on the GSML Facebook Page.

When the waves began hitting her in the face, her bewilderment passed and she seemed to know what to do. She finally moved into the water and swam off. She paused briefly to lift up her head and take a breath and then she was gone.

As she swam off I found myself humming the old Cat Stevens song

Oh baby baby it’s a wild world
It’s hard to get by just upon a smile
Oh baby baby it’s a wild world
And I’ll always remember you like a child, girl

I’ll always remember you like a child, girl
You know I’ve seen a lot of what the world can do
And it’s breaking my heart in two
‘Cause I never want to see you sad girl
Don’t be a bad girl
But if you want to leave take good care
Hope you make a lot of nice friends out there
But just remember there’s a lot of bad and beware
Beware

Part of me is afraid you got only a few miles from shore and some shark, a creature you never knew, swam up and ate you or you’ll go seeking people you knew who fed you and get hurt by a boat or hooked on a fishing dock. Being a reptile, and therefore mostly programmed by instinct and not so much by learning, you should be all right. There are records of turtles like you turning up, healthy and fine, years after release and having adapted well. I take the presence of dolphins as good sign. Good luck Lil Girl. I hope you get to make baby loggerheads and swim the sea for many years.

Day 2 of the International Disability Rights Affirmation Conference

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Day 2 of the International Disability Rights Conference opened with a talk about L’Arche. The speaker was Melanie Saxon, Community Leader / Executive Director of L’Arche Jacksonville (FL). She shared some of L’Arche’s history and mission through the use of short videos  and her own words. I must admit I had never heard of them before and I am kind of ashamed of myself for that since they appear to do wonderful things.

Virtual Ability member Mook Wheeler has created a number of displays and exhibits on Healthinfo Island about l’Arche, Jean Vanier, and the concept of community for persons with disabilities. If you are in Second Life, please visit them.

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The second talk was Dr. Margaret Nosek, Professor of Physical Medicine and Rehabilitation at Baylor College of Medicine (Houston, TX, US) and two co-presenters, Stephanie Silveira and Rachel Markley. She got some group chat going about how our avatars interact and how they affect us. Having an avatar to go to a conference or get out and about to a support group makes life much easier for people with disabilities because they don’t have to leave home. It is especially important for people in rural areas or those who are isolated. We discussed a lot about safety on line and finding a community in Second Life. Members really wanted to have support and SL allowed people to find it while not leaving home. People also often want to represent themselves accurately and in SL you have to work at finding wheelchairs and canes. Also in SL architecture means you don’t need to have ramps and such for accessibility but many people feel it is an important political and educational statement to have them built in. Overall a fascinating and amusing talk. I have actually published on this topic.

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Our second speaker has been “in world” since 1994 and the in world experience in the early days consisted of IM style chat rooms of the era. He also talked about Mike from NYC who would not share anything personal but provided widespread and great support in a Parkinson’s group. Seven years later Mike from New York turned out to be Michael J Fox! Our speaker then told a third story was about a platform where people could use emoticons. And the ones that loved it the most were people with mobius syndrome, people who were unable to show facial expressions. In his fourth story he talked about how people with autism and aspergers practiced in SL (Brigadoon Island) to work on RL situations. Scary in Real Life became manageable in Second Life eventually making Real Life more manageable.

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The final speaker of the day was Shayla the Super Geeko who spoke about Persons With Disabilities and what happened to them on September 11. Over 200 PWDs died that day. Most did not survive because they could not evacuate. She then extended the concept to PWDs during disasters in general. We had a lot of talk about how PWDs have to make their own plans to be sure they get out in a disaster because depending on others will not work.

And so it was overall a fun, interesting and eye opening two day conference. I am very happy I was able to play a small part in the organization of the conference by finding introducers. Well done everyone involved!

International Disability Rights Affirmation Conference Day 1

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I (meaning Natalie) spend time in the virtual word of Second Life doing a variety of things both serious and work related and just plain fun. Today I am attending and have the honor of being an introducer in the International Rights Disability Conference hosted in Second Life by Virtual Ability.

Virtual Ability is a great place designed to provide support and community for people with disabilities. Each year they host a conference designed to promote rights for people with disabilities and to encourage fuller participation of people with disabilities in their own community.

I have been providing very occasional and small consultative help to Virtual Ability almost since they started in Second Life. It has been astounding to me to see how this have taken off and grown from a tiny single plot in Second Life to an entire huge multi-sim island in Second Life with a large and vibrant community.

Entry into the virtual world  can be a bit intimidating and since different people come into Second Life with different aims and desires, there can be difficulties while newbies are adjusting. Virtual Ability provides a gentler and much more supportive environment for newbies.

idrc-conference_003In Second Life we get to pick what we look like and here you can see me, right foreground in my “professional” av. I am sitting with a cowboy, a geeko and turtle and another human. I have all kinds of other avatars for less serious events.

The conference covered a wide range of topics.

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We began with Caroline Pavis of Johnson and Johnson who talked about their HealthEVoices disability bloggers conference. Their next conference is in 2017 in Chicago and they hope to encourage interaction between various disability and health advocacy and support groups across a wide variety of people from those living with HIV to those with intellectual and emotional disabilities. She talked about the benefits of the conference and after we had a lively discussion about how Second Life, and other Virtual World media could be integrated into their setting.

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Our second set of speakers were from South Africa. This is one of the nice things about a Second Life conference. You can have people come from all over the world and yet all feel together.Theresa Lorenzo and Siphokazi Sompeta of the University of Cape Town, South Africa, spoke about their research on ways to make disability-inclusive services available in rural areas of South Africa, Botswana and Malawi. She described problems like lack of local transportation and lack of practical skills for dealing with people with disabilities. For example, they taught taxi drivers how to better transport people with disabilities. Ms. Sompeta described being in Second Life as like being in a spiritual world, a lovely and apt metaphor.

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I was introducer for the next session which was a panel of presenters from the Chronic Pain Anonymous group. styled after Alcoholics Anonymous but geared entirely to people who live with chronic pain due to many different health conditions, the group provides a supportive environment without advocating any specific treatment or protocols. Rather it helps people to live well and at peace with themselves even though they also live in chronic pain. By coincidence, I had attended a group session as a family member of someone living with chronic pain. So I got to experience the reality of the support available.

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The next speaker for today was Dr. Margaret Nosek and her colleagues. They presented on “Women with mobility impairments in community weight loss programs: Exploring new venues in virtual worlds.” Obesity and being overweight is really a problem for people with mobility impairments. Over 50% of people with mobility impairments are obese. Yet exercise, the major tool for effective weight loss is not something easily available to those with limited mobility. The talk centered on things that can be done.

The final speaker was Maggie Sheets with the Disability Policy Consortium of Massachusetts. She explained the importance of including people with disability in policy making.

So we had the conference and there were many side conversations and instant messages as well as group chat going on during the conference so it was fun and stimulating and I felt really connected. I also didn’t have to fight airports, a strange bed with a room full of strange scents that make me wheeze, worrying about food when I have so many allergies and all the usual stresses of going to a conference. It was a great experience.

The conference continues tomorrow.