Monday, July 28, 2014

How many genes do we have and what happened to the orphans?

How many genes in the human genome? There's only one correct answer to that question and that's "we don't know."

The main problem is counting the number of genes that produce functional RNA molecules. The latest Ensembl results are based on build CRch37 from February 2009 and the GENCODE annotation from last year (GENCODE 19) [see Human assembly and gene annotation and Harrow et al., 2014]

The most recent estimates are 20,807 protein-encoding genes, 9,096 genes for short RNAs, and 13,870 genes for long RNAs. This gives 43,773 genes. Nobody knows for sure how many of the putative genes for RNAs actually exist. They may only be a few thousand functional genes in this category.

It's a lot easier to figure out whether a gene really encodes a functional protein so most of the annotation effort is focused on those genes. I want to draw your attention to a recent paper by Ezkurdia et al. (2014) that discusses this issue. The authors begin with a bit of history ...

Transcription Initiation Sites: Do You Think This Is Reasonable? (revisited)

I'm curious about how different people read the scientific literature. My way of thinking about science is to mentally construct a model of how I think things work. The more I know about a subject, the more sophisticated the model becomes.

When I read a new paper I immediately test it against my model of how things are supposed to work. If the conclusions of the paper don't fit with my views, I tend to be very skeptical of the paper. Of course I realize that my model could be wrong and I'm always on the lookout for new results that challenge the current dogma, but, in most cases, if the paper conflicts with current ideas then it's probably flawed.

This is what people mean when they talk about making sense of biology. The ENCODE papers don't make sense, according to my model of how genomes work so I was immediately skeptical of the reported claims. The arseniclife paper conflicted with my understanding of the structure of DNA and how it evolved so I knew it was wrong even before Rosie Redfield pointed out the flaws in the methodology.

Finding the "perfect" enzyme

I got an email message yesterday from a student who is taking a summer course in biochemistry. His professor asked the class to find "most efficient enzyme known to man." The professor gave them a hint by telling them that the enzyme had something to do with nucleotide biosynthesis. The student contacted me because some of my blog posts popped up on Goggle. He (the student) was a bit confused about how to define the "perfect" enzyme.

There are two different ways of defining the "perfect" enzyme and both of them are wrong because there's no such thing. The common textbook definition picks up on the idea that the "perfect" enzyme catalyzes a reaction every time it encounters a substrate(s). These enzyme rates are referred to as "diffusion-controlled" rates since the rate is limited only by the rate at which substrate diffuses into the reaction site on the enzyme. Some enzymes can even catalyze reactions that are slightly faster than the diffusion-controlled limit.

Here's what Voet & Voet (4th edition) say (page 490) ...

Friday, July 25, 2014

The Central Dogma according to Riken

You may never have heard of Riken. Here's what they say on their website [Riken] ...
RIKEN is Japan's largest comprehensive research institution renowned for high-quality research in a diverse range of scientific disciplines. Founded in 1917 as a private research foundation in Tokyo, RIKEN has grown rapidly in size and scope, today encompassing a network of world-class research centers and institutes across Japan.
They've published a video on the Central Dogma. Here's how they describe it ...
The 'Central Dogma' of molecular biology is that 'DNA makes RNA makes protein'. This anime shows how molecular machines transcribe the genes in the DNA of every cell into portable RNA messages, how those messenger RNA are modified and exported from the nucleus, and finally how the RNA code is read to build proteins.

The video was made by RIKEN Omics Science Center (RIKEN OSC) for the exhibition titled 'Beyond DNA' held at National Science Museum of Japan. RIKEN OSC has published in Nature Genetics on the regulation of RNA expression in human cancer cells.
Most of you know that I have a different view of The Central Dogma of Molecular Biology but that's not what I want to discuss here. Watch the video. Do you think it's a good idea to show this process as well-designed little machines and ships? It sure gets the IDiots excited {RIKEN’s 10-minute antidote to atheism: see for yourself].



Wednesday, July 02, 2014

Carnival of Evolution #73: World Cup Edition

This month's Carnival of Evolution is hosted by none other than the King of the Carnival, Bjørn Østman Pleiotropy . Read it at 73rd Carnival of Evolution: World Cup Edition .
Welcome to the 2014 Carnival of Evolution World Cup of evolution blog posts.

We have an exciting post ahead of us today where we will find the winner of the inaugural CoE World Cup. Entered posts will be scored based on several parameters, and matches will be determined probabilistically.

The scoring system works like this:

+1 for mentioning "evolution" or "evolve"
+1 for posts about biological evolution
-1 for saying "develop" or "development" when meaning "evolve" or "evolution"
-1 for being very short
-2 for being very long
0 to +5 points based on the interest of the referee (the CoE host)
+2 for posts about peer-reviewed articles
+4 for posts whose authors clearly present opinions of their own
+1 per picture (up to three) included in the post
+1 for attracting any comments
+1 extra for each original picture (max 3)
+3 for showing videos
+25 for reports on rabbit fossils from the Cambrian
-5 for any hint of panadaptationism
-2 for each logical fallacy
-4 for any mention of aquatic ape theory
-7 for agreeing with Lynn Margulis that everything is endosymbiosis
-3 if talking about the work of others without citation
-5 to -1 for any wrong statements about evolution - See more at: http://pleiotropy.fieldofscience.com/2014/07/73rd-carnival-of-evolution-world-cup.html#sthash.75w1XHA6.dpuf
It was a tough battle. My own entry, The Function Wars: Part I, had a fairly low score but managed to squeak out a victory in the early rounds in spite of the fact that it had a severe disadvantage (too long).

My post beat out Was Fisher (W)right? in the semi-final thanks to an own goal in extra time. In the final, Function Wars was up against a better post Of Population Structure and the Adaptive Landscapes but Function Wars won on penalty kicks. Yeah!!!!

If you want to host a Carnival of Evolution please contact Bjørn Østman. Bjørn is always looking for someone to host the Carnival of Evolution. He would prefer someone who has not hosted before but repeat hosts are more than welcome right now! Bjørn is threatening to name YOU as host even if you don't volunteer! Contact him at the Carnival of Evolution blog. You can send articles directly to him or you can submit your articles at Carnival of Evolution although you now have to register to post a submission. Please alert Bjørn or the upcoming host if you see an article that should be included in next month's. You don't have to be the author to nominate a post.

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Tuesday, July 01, 2014

The Function Wars: Part II

This is Part II of several "Function Wars"1 posts. The first one is on Quibbling about the meaning of the word "function" [The Function Wars: Part I].

The ENCODE legacy

I addressed the meaning of "function" in Part I It is apparent that philosophers and scientists are a long way from agreeing on an acceptable definition. There has been a mini-explosion of papers on this topic in the past few years, stimulated by the ENCODE Consortium publicity campaign where the ENCODE leaders clearly picked a silly definition of "function" in order to attract attention.

Unfortunately, the responses to this mistake have not clarified the issue at all. Indeed, some philosophers have even defended the ENCODE Consortium definition (Germain et al., 2014). Some have opposed the ENCODE definition but come under attack from other scientists and philosophers for using the wrong definition (see Elliott et al, 2014). The net effect has been to lend credence to the ENCODE Consortium’s definition, if only because it becomes one of many viable alternatives.

Saturday, June 28, 2014

Ann Gauger's old facts

Some of you are probably watching Saturday morning cartoons but for those of you looking for other forms of entertainment I offer a list of six "old facts" that Ann Gauger says have been proven to be wrong [Why Does Biology Still Have the Ability to Surprise Us?].

Since I'm at least as old as Ann Gauger, I offer my own interpretation under each one. If you want to see how she interprets them you'll have to go to the IDiot website.

1. Old fact: DNA is stable and genes don't hop around.
I suppose there was a time when scientists might have thought that "DNA was stable." I was taught about "jumping genes" in my second year genetics class in 1965. I think that's before many of you were born so it's a pretty old fact.
2. New "old" fact: Mobile genetic elements are selfish DNA that replicate themselves without benefit to the organism, thus cluttering the genome with garbage.
That's still pretty much true today.
3. Old fact: A gene is an uninterrupted stretch of DNA that encodes a single protein. Genes are arranged like beads on a string.
I learned in 1965 that some genes produced tRNA and ribosomal RNA. I learned in 1975 that some protein-encoding genes had introns. (That one was a surprise.) I still think that genes are lined up one-after-another on their chromosomes although there are some minor exceptions. I learned about overlapping genes, for example, when the φX174 genome was sequenced in 1978. That's how old her facts are.
4. Old fact: There are only 3 forms of RNA: messenger RNA, transfer RNA, and ribosomal RNA.
Scientists have known about RNA viruses for at least 70 years. That's long before the discovery of messenger RNA and tRNA. It wasn't until the early 1970s that molecular biologists became aware of regulatory RNAs, RNA primers on Okazaki fragments, and antisense RNAs. This was followed quickly by the discovery of many other types of RNAs. Ann Gauger says these are "new" discoveries. I guess that depends on whether something that's been known for forty years (or seventy years) counts as "new."
5. Old fact: Pseudogenes are useless broken remnants of former genes.
Still true today. The fact that some of the sequence of one-in-a-million pseudogenes may have secondarily acquired another function doesn't change the fact that it is a pseudogene.
6. Old fact: The genome is full of junk, the remnants of wasteful evolutionary processes and selfish DNA (see #1, #2 and #5 above).
Still a fact in the 21st century.

Friday, June 27, 2014

This is my little boy playing in the mud

My son, Gordon, ran in a 19km race at Whistler (British Columbia) last weekend. There were lots of obstacles and a 10,000 volt electric shock at the end. He said it was "Super fun!"

I remember when playing in the mud meant something a lot different.


UPDATE Ms. Sandwalk has posted more pictures, and more words at: Oh My Goodness.


Wednesday, June 25, 2014

The Function Wars: Part I

This is Part I of two “Function Wars” posts. The second one is on Quibbling about the meaning of the word “junk”.1

Quibbling about the meaning of the word “function”

The world is not inhabited exclusively by fools and when a subject arouses intense interest and debate, as this one has, something other than semantics is usually at stake.
Stephan Jay Gould (1982)
The ENCODE Consortium tried to redefine the word “function” to include any biological activity that they could detect using their genome-wide assays. This was not helpful since it included a huge number of sites and sequences that result from spurious (nonfunctional) binding of transcription factors or accidental transcription of random DNA sequences to make junk RNA [see What did the ENCODE Consortium say in 2012?]..

I believe that this strange way of redefining biological function was a deliberate attempt to discredit junk DNA. It was quite successful since much of the popular press interpreted the ENCODE results as refuting or disproving junk DNA. I believe that the leaders of the ENCODE Consortium knew what they were doing when they decided to hype their results by announcing that 80% of the human genome is functional [see The Story of You: Encode and the human genome – video, Science Writes Eulogy for Junk DNA]..

The ENCODE Project, today, announces that most of what was previously considered as 'junk DNA' in the human genome is actually functional. The ENCODE Project has found that 80 per cent of the human genome sequence is linked to biological function.

[Google Earth of Biomedical Research]

Monday, June 16, 2014

A bun bargain

We were at our local supermarket yesterday and I wanted to buy some large Kaiser rolls. Unfortunately, the bins were empty.

I guess the customers couldn't resist the bargain if they bought half-a-dozen buns.


Friday, June 13, 2014

Ontario elects a Liberal government under Kathleen Wynne

The people of Ontario (Canada) voted in a provincial election yesterday and the Liberal Party won a majority of the seats. The leader of the party is Kathleeen Wynne and she becomes the first woman to be elected Premier of Ontario. (She has been Premier for the past sixteen months since she became leader of the Liberal Party.) Not only is she the first woman, she is the first openly gay politican to be elected Premier of any province in Canada. (According to Wikipedia, she is the first openly gay head of any government in the Commonwealth.)

The results are:

Liberals: 59 seats, 39% of the vote
Progressive Conservatives: 27 seats, 31%
New Democratic Party: 21 seats, 24%
Green Party: 0 seats, 5%.

The results are going to be poured over with a fine-tooth comb in the next few weeks but it's clear that the Tea-Party agenda of the Progressive Conservatives did not work. (He hired American Republican strategists to help with his campaign.) They should have won the election handily after 11 years of Liberal government plagued by scandal but, instead, they lost 10 seats and their leader Tim Hudak resigned last night when the results became clear.




Friday, June 06, 2014

June 6, 1944

Today is the 70th anniversary of D-Day—the day British, Canadian, and American troops landed on the beaches of Normandy.1

For baby boomers it means a day of special significance for our parents. In my case, it was my father who took part in the invasions. That's him on the right as he looked in 1944. He was an RAF pilot flying rocket firing typhoons in close support of the ground troops. During the initial days his missions were limited to quick strikes and reconnaissance since Normandy was at the limit of their range from southern England. During the second week of the invasion (June 14th) his squadron landed in Crepon, Normandy and things became very hectic from then on with several close support missions every day.

I have my father's log book and here (below) are the pages from June 1944. The red letters on June 6 say "DER TAG." It was his way of announcing D-Day. On the right it says "Followed SQN across channel. Saw hundreds of ships ... jumped by 190s. LONG AWAITED 2nd FRONT IS HERE." Later that day they shot up German vehicles south-east of Caen where there was heavy fighting by British and Canadian troops. The next few weeks saw several sorties over the allied lines. These were attack missions using rockets to shoot up German tanks, vehicles, and trains.


The photograph on the right shows a crew loading rockets onto a typhoon based just a few kilometers from the landing beaches in Normandy. You can see from the newspaper clipping in my father's log book that his squadron was especially interested in destroying German headquarter units and they almost got Rommel. It was another RAF squadron that wounded Rommel on July 17th.

The log book entry (above) for June 10th says, "Wizard show. Recco area at 2000' south west of Caen F/S Moore and self destroyed 2 flak trucks, 2 arm'd trucks, and i arm'd command vehicle, Every vehicle left burning but one. Must have been a divisional headquarters? No casualties."

Here's another description of that rocket-firing typhoon raid [Air Power Over the Normandy Beaches and Beyond].
Intelligence information from ULTRA set up a particularly effective air strike on June 10. German message traffic had given away the location of the headquarters of Panzergruppe West on June 9, and the next evening a mixed force of forty rocket-armed Typhoons and sixty-one Mitchells from 2 TAF struck at the headquarters, located in the Chateau of La Caine, killing the unit's chief of staff and many of its personnel and destroying fully 75 percent of its communications equipment as well as numerous vehicles. At a most critical point in the Normandy battle, then, the Panzer group, which served as a vital nexus between operating armored forces, was knocked out of the command, control, and communications loop; indeed, it had to return to Paris to be reconstituted before resuming its duties a month later.

My father was awarded the Distinguished Flying Cross (DFC) for his efforts during the war.



1. The British landed at Sword Beach and Gold Beache, the Canadians at Juno Beach, and American troops landed at Omaha and Utah Beaches.

Wednesday, June 04, 2014

Do you really "get" evolution?

Stephanie Keep is the new editor of Reports of the National Center for Science Education at NCSE (National Center for Science Education).

She tells an interesting story in her first post on the Science Laegue of Amercia blog [A New Finger in the Pie].
An editor friend of mine asked me the other day to read an activity she’s developing for middle school, one of the soon-to-be plethora of activities aligned to the Next Generation Science Standards. This particular one was about evolution, and asked kids to look for variation in a number of human traits and then infer adaptive explanations. For example, they could measure finger lengths and then come up with a reason that longer fingers are more adaptive than shorter ones. What followed was a half-hour conversation in which I tried my best to explain why that was a terrible idea for an activity. And here’s the thing—this friend of mine, she’s super-smart and has an advanced degree in biology from Harvard University. Now, she completely understood, once we discussed it, why that kind of activity will reinforce misconceptions about evolution (that every feature is adaptive, that you can infer a structure’s adaptive value from its current function, etc.), but we still had to have the discussion.

I have worked for the past decade-plus with scientists, science writers, and science educators, all of whom have the best intentions in the world, all of whom would have no problem declaring their allegiance to the cause of an authentic science education grounded in evolution. But—and I don’t want to point fingers at anybody here—many of them would have not batted an eye if that activity had come across their desks. And this, I believe, is one of the most important truths we have to face: many of us don’t really get evolution. It’s such a beautiful, simple, and powerful idea, but it’s also finicky, demanding vigilant attention to detail to be properly explained and explored.
Most of you will be familiar with this idea since I've been complaining about adaptationism for decades. In order to "get" evolution, you need to know about Neutral Theory and random genetic drift—and that's just for starters. We need to work much harder to dispel misconceptions about evolution.

Lot's of people don't really "get" evolution but, in fairness, they don't study it either. But if you are going to write about evolution—or teach it—then you'd better make sure you understand it. Unfortunately, there are far too many people like Stephanie Keep's friend. We have to fix that.

There's one group that spends an extraordinary amount of time "studying" evolution without ever "getting" it. I'm referring to creationists, especially the Intelligent Design Creationists, otherwise known as IDiots. They've been told time and time again that there's much more to evolution than just adaptation. Recently, some of them actually seemed to "get" the ideas of Neutral Theory and random genetic drift although that turned out to be an illusion. They still don't get evolution.

In any case, one of the creationists (Donald McLaughlin1) has blogged about Stephanie Keep's story [see A New Hire at the National Center for Science Education Admits "Many of Us Don't Really Get Evolution"]. Here's part of what McLaughlin says,
Bear in mind, too, that the very educators who don't get evolution are also the ones who fuss and complain whenever a state legislator or science standards committee member proposes language about "teaching the strengths and weaknesses" of evolution. From the way they kvetch, you would think there are no weaknesses in evolutionary theory. But if many of them don't get evolution in the first place, how would they know?

Keep says that evolution is a "beautiful, simple, and powerful idea, but it's also finicky, demanding vigilant attention to detail to be properly explained and explored." Perhaps Keep could provide a helpful list of exactly what those details are so educators like her Harvard-trained friend can stay on the straight and narrow Darwinian path, lest they join the chorus calling for a new theory of evolution.
This is ironic and confused on so many levels that I'm not even going to try and point them out. I just post it here for your amusement.


1. Here's his profile on the Discovery Institute website.
Donald McLaughlin joined Discovery Institute in August 2013, as a Development Officer and Regional Representative in the upper Midwest and Northeast regions. His areas of responsibility include cultivating and stewarding major gifts, and planned giving. Donald has had a successful career in development, including 8 years as a Regional Director of Advancement for Prison Fellowship Ministries, 2 years as National Director of Major Gifts for Teen Mania Ministries and 5 years as Regional Director of Advancement for Taylor University.

Donald is a 1975 graduate of Taylor University where he earned his BA in Speech and Drama. In 1977, he earned an MA in Clinical Audiology from Ball State University in Muncie, IN. While at Prison Fellowship, Donald also participated in the Centurions Program. Prior to his work in Development, Donald spent more than twenty years in financial services with both AG Edwards and Merrill Lynch. Donald lives in Granger Indiana, near South Bend, with his wife of 35 years, Elizabeth, who is Chair of the Communications Department at Bethel College in Mishawaka, IN. Donald enjoys reading, traveling, and music.
He also has a religious profile at: Donald McLaughlin.

Monday, June 02, 2014

"Flipping the classroom": what does that mean?

The latest issues of ASBMB Today contains an article by Brent R. Stockwell and Michael Cennamo with a provocative title: Reimagining the undergraduate science course.

It describes an undergraduate course in biochemistry at Columbia University. Apparently, this course used to be taught in a way that's similar to many biochemistry courses. The lecture consisted of PowerPoint slides and a description of basic facts such as metabolic pathways. Stockwell and Cennamo want to redesign the course to allow more time in the classroom for debate and discussion. This is an admirable goal.

They decided to "flip the classroom."
What does it mean to flip the classroom?

When we say we flipped the classroom, we mean that we had students watch recorded videos before class, freeing classroom time for discussion, group work and solving problems. But this is not something you can do overnight.

We took time to define our goals: Obviously, we wanted the students to be better prepared for each class, allowing them to engage more fully in class discussion. But we also wanted to have students put lecture material into action by tackling practical biochemistry problems.

Last summer, we had a number of meetings to design a new course that not only would get students thinking and problem solving in a new way but would provide instant feedback on how well they understood the material.
What they did was to create a video with their PowerPoint slides and a recording of the lecturer explaining what's on the slides. The students were supposed to watch the video before class and, to ensure that they did, there was a quiz at the end of the video presentation. For example, at the end of the lecture on amino acid metabolism, the students were asked to identify the product of the deamination of alanine.1

Here's the part I don't understand. What's the value of having students watch a video presentation when they have a textbook? (The recommended textbook is Lehninger, Principles of Biochemistry by David Nelson and Michael Cox (6th edition, 2013)).

Why not just assign readings from the textbook? I assume that most lecturers are not very knowledgeable about the content of most lectures in an introductory biochemistry course so they probably rely on a textbook anyway.

And what are the students supposed to do when they watch the video? In the new version of the course, students are divided into groups and they deal with problems that "required students to synthesize and apply the information from the textbook, videos and class discussion" (i.e. "problem-based learning," according to the authors). One of the question is ....
If glucose labeled with 14C at C-1 were the starting material for amino acid biosynthesis, the product(s) that would be readily formed is/are:

A. Serine labelled at alpha carbon
B. None of these
C. All of these
D. Serine labelled at the carboxyl carbon
E. Serine labelled at the R-group carbon2
I assume that the students would have to take notes while watching the video and/or download the PowerPoint slides in order to answer this question during class. Or, they could bring their textbook to class.

Do PowerPoint video presentations add anything to the course that can't be found in the textbook?

1. Pyruvate and glutamate?
2. I assume the instructors are thinking about organisms that regularly utilize glucose as a carbon source so that amino acids like serine are mostly derived from intermediates in glycolysis (e.g. humans). In that case, the students have to understand the distribution of carbon atoms in the aldolase reaction. I had to look this up to determine that the correct answer is "E." I hope I'm right. For species that use the pentose-phosphate pathway, I think the correct answer is "B." (This doesn't seem to me like a fundamental principle or concept based on an evolutionary approach to biochemistry.)

Saturday, May 31, 2014

The Third Fourth? Way

Back in 1997, James Shapiro wrote an article for the Boston Review entitled "A Third Way." It was a very confusing article. His main point seemed to be that conventional neo-Darwinism wasn't a complete picture of modern evolutionary theory.

That part wasn't news since by 1997 the ideas of Neutral Theory and random genetic drift had been around for thirty years. Apparently, Shapiro was three decades behind in his understanding of evolution.

Shapiro doesn't demonstrate that he understands population genetics and random genetic drift. This just one (of many) criticisms that I mentioned in my review of Shapiro's book Evolution: A View from the 21st Century in NCSE Reports [Evolution: A View from the 21st Century]. Shapiro responded to my review at: Reply to Laurence A Moran’s review of Evolution: A View from the 21st Century] and I discussed his response on my blog [James Shapiro Responds to My Review of His Book].

The "third" way, according to Shapiro's 1997 article, is not classic Darwinism and it's not creationism. Instead, it's a new way of looking at evolution.
What significance does an emerging interface between biology and information science hold for thinking about evolution? It opens up the possibility of addressing scientifically rather than ideologically the central issue so hotly contested by fundamentalists on both sides of the Creationist-Darwinist debate: Is there any guiding intelligence at work in the origin of species displaying exquisite adaptations that range from lambda prophage repression and the Krebs cycle through the mitotic apparatus and the eye to the immune system, mimicry, and social organization? Borrowing concepts from information science, new schools of evolutionists can begin to rephrase virtually intractable global questions in terms amenable to computer modelling and experimentation. We can speculate what some of these more manageable questions might be: How can molecular control circuits be combined to direct the expression of novel traits? Do genomes display characteristic system architectures that allow us to predict phenotypic consequences when we rearrange DNA sequence components? Do signal transduction networks contribute functional information as they regulate the action of natural genetic engineering hardware?

Questions like those above will certainly prove to be naive because we are just on the threshold of a new way of thinking about living organisms and their variations. Nonetheless, these questions serve to illustrate the potential for addressing the deep issues of evolution from a radically different scientific perspective. Novel ways of looking at longstanding problems have historically been the chief motors of scientific progress. However, the potential for new science is hard to find in the Creationist-Darwinist debate. Both sides appear to have a common interest in presenting a static view of the scientific enterprise. This is to be expected from the Creationists, who naturally refuse to recognize science's remarkable record of making more and more seemingly miraculous aspects of our world comprehensible to our understanding and accessible to our technology. But the neo-Darwinian advocates claim to be scientists, and we can legitimately expect of them a more open spirit of inquiry. Instead, they assume a defensive posture of outraged orthodoxy and assert an unassailable claim to truth, which only serves to validate the Creationists' criticism that Darwinism has become more of a faith than a science.
Now Shapiro has joined forces with some other "revolutionaries" and started a new website called "The Third Way." It has grandiose goals ....
The vast majority of people believe that there are only two alternative ways to explain the origins of biological diversity. One way is Creationism that depends upon supernatural intervention by a divine Creator. The other way is Neo-Darwinism, which has elevated Natural Selection into a unique creative force that solves all the difficult evolutionary problems. Both views are inconsistent with significant bodies of empirical evidence and have evolved into hard-line ideologies. There is a need for a more open “third way” of discussing evolutionary change based on empirical observations.
There's only one problem. I'm familiar with Shapiro's ideas and with the ideas of most of the other people listed on the website and I don't think any of them (except Eugene Koonin) have anything significant to say about evolutionary theory. Futhermore, most of them don't seem to understand that there's already been a revolution and population genetics, Neutral Theory, etc. won the day. They seem to have completely missed that revolution.

They are advocating a fourth way that skips right from adaptationism to something else.

They are like a group of would-be revolutionaries marching up Rue de Lyon in Paris only to discover that the Bastille has been replaced by an open square and an opera house.

Note: There aren't many biologists that are interested in this "Third Way" but the creationists are lapping it up [A Group of Darwin-Skeptical Scientists Seeking a "Third Way" in Biology Have Launched a New Website; Welcome to Them!].