Friday, July 24, 2009
How to deal with scientists who cheat
What do you do when a scientists (PI, post-doc, graduate student) is caught falsifying data? Should they be expelled from the community, fired from their job, or given a slap on the wrist and rehabilitated?
This isn't an easy question as Janet Stemwedel demonstrates in Tempering justice with mercy: the question of youthful offenders in the tribe of science. I hate it when she does that. It would be so easy to conclude that cheating scientists should be drummed out of the profession but then along comes Janet to confuse me.
She's right, of course. There ought to be a range of punishments that fit the wide range of crimes and motives.
Cody Cobb's Visit
We had a fun visit with Cody Cobb the other day when he flew up to Toronto for a free lunch [Lunch with a winner].
I mentioned that Cody was a blogger but I didn't link to his blog because I wasn't sure if he wanted to be identified as the author of 90% True. Well, apparently he doesn't care, 'cause he's posted two articles about his visit to Toronto.
In Canadian Lunch he reviews a lot of the things we talked about, including our lunch debates with Alex Palazzo. In Science Blogging he covers the discussion about the value and purpose of science blogging. They're both excellent reads—pay him a visit.
Thursday, July 23, 2009
The Richard Dawkins Award Goes to Bill Maher
Atheist Alliance International is an organization that gives out The Richard Dawkins Award each year. The criteria, according to Wikipedia are ...The Richard Dawkins Award will be given every year to honor an outstanding atheist whose contributions raise public awareness of the nontheist life stance; who through writings, media, the arts, film, and/or the stage advocates increased scientific knowledge; who through work or by example teaches acceptance of the nontheist philosophy; and whose public posture mirrors the uncompromising nontheist life stance of Dr. Richard Dawkins.This year the award goes to Bill Maher. One assumes that he is the man who best exemplifies the criteria for the award.
Does Bill Maher advocate increased scientific knowledge and does his public posture resemble that of Richard Dawkins?
Not bloody likely. As Orac and others have pointed out, Maher believes in all sorts of kooky ideas including the idea that vaccinations don't work [Bill Maher gets the Richard Dawkins Award? That's like Jenny McCarthy getting an award for public health].
Bill Maher may be a good atheist but he sure ain't a good scientist.
So what does PZ Myers think of this? [Put Maher in the hot seat]
However, let's be clear about the obvious. He is being given this award for making a movie this year that clearly promotes atheism and mocks religion, and that's all that is being endorsed.Nope, sorry PZ but you seem to be wrong about that. Unless, of course, the criteria for the award as described in the Wikipedia article are wrong.
You need to be much more that a good little religion-bashing atheist to meet the criteria and it's as plain as the nose on your face that Bill Maher doesn't qualify.
BTW, like PZ, I was not a big fan of Religulous. Thus, I don't even agree that Bill Maher was in the same league as Richard Dawkins and his Root of all Evil series.
Dawkins, Tyson, Druyan, Stenger
This panel discussion took place
The thing that troubles me most about this discussion is the general agreement that "science" is nothing more than learning about physics, astronomy, chemistry, geology and biology. I think "science" is a way of knowing that includes absolutely everything; english, history, music, sociology and whatever. Real knowledge ("truth") in any of these subjects can only come from applying scientific methodology based on evidence and rationality coupled to a healthy degree of skepticism.
The discussion about whether science should confront religion is particularly interesting. Ann Druyan was the wife of Carl Sagan and she helped produce Cosmos. She claims that science has a wonderful story of its own to tell and there's no need to criticize religion. In fact, it's counter-productive to do so.
Ms. Druyan suggests that Sagan's description of science in Cosmos is the best way to sell science to the general public. She says that the TV series is still being shown frequently on television even though it was made in 1980.
To me that raises an obvious question. Thinking scientifically, I can't help but ask the obvious question. If this was such an effective way to communicate science how come after 29 years it hasn't had much effect on science literacy in the USA? Shouldn't we be basing our claims about science education on evidence and not on wishful thinking?
The Problem with Science Journalism
There are many problems with science journalism these days. One of the most important problems is that their sources (scientists) are highly unreliable as we witnessed in the recent Darwinius Affair.
One of the other problems is that science journalists have been very reluctant to criticize each other and maintain certain minimal standards of reporting. They are much more interested in giving each other awards for good writing than they are in evaluating good science.
Carl Zimmer has become an exception to the rule.1 He has taken on the role of defending his profession against those science journalists who would abuse science for the sake of a high profile publication [George Will’s Crack Fact-Checkers Continue Their Nap]. We need more journalists like Carl Zimmer and we need more scientists who will chastise their less-than-scientific colleagues when they step out of line.
1. Chris Mooney is another.
Shona Holmes and Canadian Health Care
Shona Holmes is a Canadian citizen. She suffered from a number of symptoms including dizziness and loss of vision. Her family doctor in Canada sent her for an MRI and the results suggested a brain tumor. Homes might have to wait months before seeing a neurologist for further tests. (This hasn't been confirmed, to my knowledge.)
Shona Holmes decided to fly to the the Mayo Clinic in Scottsdale Arizona. There she was eventually diagnosed as having a Rathke's cleft cyst (RCC) in her brain. This is not a tumor and it is not life-threatening. It does, however, threaten her vision, which was already impaired.
Eventually, after more tests and at least one further visit to Scottsdale, the cyst was removed. It's not clear how long it took from making the first appointment at the clinic to the actual surgery but the article on the Mayo Clinic website suggests it was about a month. Incidentally, this article has been removed from the Mayo Clinic website but it is cached here.
The bottom line is that Holmes suffered from a non-life-threatening cyst that affected her vision and could have eventually led to blindness. She choose not to wait for treatment in Canada but to pay for treatment in Arizona.
Shona Holmes is suing the Government of Ontario in order to force it to revise and/or dismantle public health care. The suit [Lindsay McCreith and Shona Holmes/The Attorney General for the Province of Ontario] is being supported by the Canadian Constitution Foundation, a right-wing group that's described here.
To summarize, we have a patient with a non-life-threatening brain cyst who may or may not have had to wait a long time for treatment in Canada but choose to go to an American clinic where she was operated on after about a month. This patient is sufficiently opposed to Canada's health care system that she has collaborated with a right-wing group to sue the Government of Ontario for allegedly violating her rights.
Oh yes, one more little bit of information, this is the same Shona Holmes you see in this video warning Americans about the dangers of universal health care. This Shona Holmes was going to die of a brain tumor if she had stayed in Canada.
It's pretty clear that Holmes is not telling the truth in the TV ad. The only question is whether she "misinformed" the group Patients United Now or whether they pressured her into making untrue statements in the TV add. Canadian Cynic wants to know [Shona Holmes: Useful idiot or puppetmaster?].
Wednesday, July 22, 2009
The Positive Case for Intelligent Design Creationism?
In biology, when you encounter something that has the superficial appearance of design there are two possible explanations. Either it evolved by entirely natural processes or God did it.
In the Intelligent Design Creationist literature, 99% of the effort is spent on trying to prove that evolution cannot produce the appearance of design.1 They have to focus on the anti-evolution argument because if they admit that evolution can do the job then there's no reason to invoke the supernatural.
The frequent criticism of this negative anti-science rhetoric is an embarrassment to many Intelligent Design Creationists so they often make up stories about the "positive" argument for design.
Sometimes it's fun to watch them twist and turn. Here's Casey Luskin performing: How James Carville’s New Book, 40 More Years Misrepresents Intelligent Design.
1. The remaining 1% is uninterpretable gibberish.
Who goes in the sack?
Dara Ó Briain tells us who he would put in a big sack and what he would do with them ...
[Hat Tip: Pharyngula]
Lunch with a winner
Cody Cobb was the winner of Monday's Molecule #129. He lives in New Jersey where he is about to start graduate school at Rutgers. If you live in New Jersey you look forward to traveling, so Cody decided to fly up to Toronto for the day to collect his lunch. Because this was his first time in Canada, I decided to splurge and take him to a restaurant with white table cloths.
Cody has been blogging for many years—much longer than me. We had a good time talking about blogs and their
Of course no first time visit to Canada would be complete without ...
The New Seven Wonders of Nature
There are 28 finalists in the running for the New 7 Wonders of Nature. You can see the list here.Guess who didn't make the cut? Niagara Falls wasn't even on the list of possible wonders because the Americans in New York State didn't want to spend money to promote the Falls as a legitmate contender. (I assume the Canadians didn't want to foot the entire bill themselves.)
If you're Canadian you can vote for the Bay of Fundy and if you're American you can vote for the Grand Canyon. Australians, Germans, Irish, South Africans and Italians can all vote for a 7th wonder form their own country. Even the Swiss have an entry.
If you're from the United Kingdom, you are out of luck. Apparently there's nothing wonderful in the UK.
[Photo Credit: The Eire Hiker]
Tuesday, July 21, 2009
Direction and Purpose in Evolution
If you put two people together who believe that natural selection is the only important mechanism of evolution and that humans are the only, and best, end product of evolution, then this is what you get.
Watch Robert Wright and Daniel Dennet discuss direction and purpose in evolution.
Now imagine what the discussion would look like if they really understood the important role of chance and accident in evolution and, instead of humans, they used lobsters, ginkgo trees, shiitake mushrooms, rotifers, and cyanobacteria as examples of modern evolved species with three billion years worth of ancestors.
Even worse, think about the octopus. Is there any sane person who would point to the existence of those eight-legged slimeballs as evidence that evolution must have a direction and a purpose?
[Hat Tip: Robert Wright]
Monday's Molecule #130: Winner?
The "molecule" is Rous Sarcoma Virus or RSV. It's a retrovirus, specifically an alpharetrovirus. Other types of retrovirus include Lentivirus (e.g. HIV).
Unless you're an expert, you really can't tell from the diagram whether this is an alpharetrovirus or some other type of retrovirus. That's why I provided some clues linking this virus to last week's molecule and Nobel Laureates.
The Nobel Laureate is Peyton Rous.
Bill Chaney was the only person who got the right answer and he isn't eligible. There is no winner this week. Most of you guessed that it was HIV. One person—who shall not be named—guessed RSV and HIV with a total of five possible Nobel Laureates. That's only worth part marks. I'm expecting this person to be a winner real soon!
I thought last week's molecule would be a challenge but Sandwalk readers came up with the correct answer even in the middle of summer in the Northern hemisphere. Considering how well you did last week, following up with this week's "molecule" should be a gift.Identify the thing shown here and relate it to a Nobel Laureate.
The first person to identify the "molecule" and the Nobel Laureate(s), wins a free lunch. Previous winners are ineligible for six weeks from the time they first won the prize.
There are six ineligible candidates for this week's reward: Bill Chaney of the University of Nebraska, Ian Clarke of New England Biolabs Canada in Pickering ON, Canada. Dima Klenchin of the University of Wisconsin at Madison, Dara Gilbert of the University of Waterloo, Anne Johnson of Ryerson University, and Cody Cobb, soon to be a graduate student at Rutgers University in New Jersey.
I have an extra free lunch for a deserving undergraduate so I'm going to continue to award an additional prize to the first undergraduate student who can accept it. Please indicate in your email message whether you are an undergraduate and whether you can make it for lunch.
THEME:
Nobel Laureates
Send your guess to Sandwalk (sandwalk (at) bioinfo.med.utoronto.ca) and I'll pick the first email message that correctly identifies the molecule(s) and names the Nobel Laureate(s). Note that I'm not going to repeat Nobel Prizes so you might want to check the list of previous Sandwalk postings by clicking on the link in the theme box.
Correct responses will be posted tomorrow.
The image is from Butan et al. (2008) [doi: 10.1016/j.jmb.2007.12.003]
What Is Accommodationism?
Are you uninterested in the debate about accommodationism but secretly want to know what it's all about? Here's a brief summary that will get you up to speed without having to wade through all the rhetoric [What is accommodationism?].
It comes with cartoons.
[Hat Tip: John Wilkins]
Questioning the Tree of Life
I'm going to Halifax NS (Canada) next week to attend a very exciting conference with a catchy title: Questioning the Tree of life. This is legitimate scientific debate about the tree of life metaphor and its validity in light of massive horizontal gene transfers (HGT, also known as lateral gene transfers - LGT) during the early evolution of single cell organisms. It brings together scientists and philosophers who share an interest in this problem. Should be a blast!I'm supposed to report the meeting on my blog but I don't know where I'll find the time. Here are the main speakers.
W. Ford Doolittle
Tree of Life, Tree of Cells, LUCA and other questionable entities
Jan Sapp
Thinking laterally on the tree of life: An historical overview
Olivier Rieppel
The series, the network, and the tree: Changing metaphors of order in nature
Gordon McOuat
The origins and politics of trees and non-hierarchical taxonomic systems
Rob Beiko
The impact of different LGT scenarios on simulated genome evolution
Laura Franklin-Hall
Scientific models and the history of life: Deep disagreement or mere misunderstanding?
Peter Gogarten
The indistinguishability of patterns created through gene transfer between preferred partners and patterns created through shared ancestry
Joel Velasco
Inferring phylogenetic networks
Sina Adl
Specimen choice and the implications of modern technology in tree construction
Jeffrey Lawrence
Fragmented speciation in bacteria: The failure of a coalescent model
Greg Morgan
Defining biodiversity in a world with horizontal gene transfer
Yan Boucher
Evolutionary units: Breaking down species concepts
Dick Burian
Conceptual revisions deriving from the loss of the Tree
Maureen O’Malley
Philosophy of biology, Ernst Mayr, and the Tree of Life
Eric Bapteste
Lateral thinking about trees
Lisa Gannett
Trees, trellises, and the Garden of Eden
Andrew Hamilton
TOL issues in macrobes as they relate to taxonomic practice
James Mallet
Was Darwin wrong about the nature of species and speciation?
James McInerney
LUCA and LECA: Gene genesis in the genome of Eden
Chris. Malaterre
On the roots of the tree of life
Bill Martin
Endosymbiosis and gene transfers from endosymbionts, the most glaring insult to the tree
John Archibald
Genic and genomic threads in the tapestry of photosynthetic life: Implications for ‘tree thinking’
Fréd. Bouchard
Endosymbiosis in light of reflections on symbiosis and the superorganism
Rob Wilson
On arguments over the tree of life
Andrew Roger
Deconstructing deconstructions of the Tree of Life: Why a tree of microbes might be realizable, meaningful and useful
John Dupré
Analysing analyses of Tree of Life arguments: A commentary on Wilson and Roger
Susan Spath
Cultural politics and the Tree of Life
Monday, July 20, 2009
Nobel Laureates: J. Michael Bishop and Harold Varmus
The Nobel Prize in Physiology or Medicine 1989
"for their discovery of the cellular origin of retroviral oncogenes"
J. Michael Bishop (1936 - ) and Harold E. Varmus (1939 - ) won the Noble Prize in 1989 for proving that viruses contain a cancer-causing gene derived from the genome of the organism they infect. Specifically, they showed that chicken Rous Sarcoma Virus (RSV) carried an oncogene called v-src and this gene was an intronless version of a normal chicken gene called c-src.The discovery had tremendous implications in many fields. Not only did it explain the origins of a particular chicken cancer but it also suggested that there where many other oncogenes in other well-known retroviruses. This turned out to be correct and several dozen such oncogenes have been discovered (e.g. abl, fos, jun, and erb among others).
The discovery also ignited a burst of activity in signaling because the c-src gene encodes a tyrosine kinase. This is an enzyme that adds phosphate groups to proteins thereby affecting their activity. Such enzymes belong to pathways triggered by specific signals leading to the regulation of growth and cell division.
The discovery lent support to the idea that small changes in regulatory pathways could have large effects—in this case converting a normal cell to a cancer cell. This idea fit nicely with the work of developmental biologists who were showing that single genes could regulate entire developmental pathways. It meant that large-scale changes in morphology during evolution could be effected by small changes (mutations) in the genome.
Finally, the work of Bishop and Varmus helped change our view of the genome. Not only do retrovirus sequences pop in and out of the genome but they can also capture cellular genes by converting them to retrogenes. The work confirmed the idea that genomes were dynamic—a idea that began with transposons. Not only that, the discovery of the retrogene, v-src, showed us that introns were almost certainly not an essential component of a gene.
In my opinion, this is one of the most significant scientific advances of the 2oth century. There aren't many achievements that really count as breakthroughs because either the work was done in many labs and came out piecemeal, or the result wasn't very significant. This is one achievement that truly was a big step forward in biology.
By 1989, the press releases from the Karolinska Institute were becoming excellent educational tools for the scientifically literate general public. In this case, the press release explains how oncogenes cause cancer. I'm going to include the entire Press Release (below) because it's so good.
THEME:
Nobel Laureates
Summary
The discovery awarded with this year's Nobel Prize in Physiology or Medicine concerns the identification of a large family of genes which control the normal growth and division of cells. Disturbances in one or some of these so-called oncogenes (Gk ónco(s) bulk, mass) can lead to transformation of a normal cell into a tumor cell and result in cancer.
Michael Bishop and Harold Varmus used an oncogenic retrovirus to identify the growth-controlling oncogenes in normal cells. In 1976 they published the remarkable conclusion that the oncogene in the virus did not represent a true viral gene but instead was a normal cellular gene, which the virus had acquired during replication in the host cell and thereafter carried along.
Bishop's and Varmus' discovery of the cellular origin of retroviral oncogenes has had an extensive influence on the development of our knowledge about mechanisms for tumor development. Until now more than 40 different oncogenes have been demonstrated. The discovery has also widened our insight into the complicated signal systems which govern the normal growth of cells.
Cellular Oncogenes Discovered by the Use of Retrovirus
The term oncogene was introduced in the middle of the 1960s to denote special parts of the genetic material of certain viruses. It was believed that this part of the genetic material could direct the transformation of a normal cell into a tumor cell under the influence of other parts of the viral genetic material, alternatively via chemical or physical effects. The favourite theory of the time was that virus-mediated cell-to-cell transmittance of oncogenes was the origin of all forms of cancer. This view was later proven to be incorrect.
The original discovery of an oncogenic virus was made in 1916 by Peyton Rous working at the Rockefeller Institute in New York. Fifty years later Rous received the Nobel Prize in Physiology or Medicine. Rous virus, as the infectious agent later was named, is a member of a large virus family named retroviruses. The genetic material of these viruses is RNA (ribonucleic acid). This RNA can be transcribed into DNA (deoxyribonucleic acid) by a unique enzyme in the virus, reverse transcriptase. The 1975 Nobel Prize in Physiology or Medicine was awarded to David Baltimore, Renato Dulbecco and Howard Temin partly for the discovery of this enzyme.
Reverse transcription of the genetic material of the virus into DNA has the important consequence that it can become integrated into the chromosomal DNA in the cells. It was through investigations of Rous virus that this year's laureates Michael Bishop and Harold Varmus in 1975 could demonstrate the true origin of oncogenes. They used one variant of Rous virus which contained an oncogenic gene (Figure 1) and another variant which lacked this gene. By use of these viruses they managed to construct a nucleic acid probe which selectively identified the oncogene. This probe was used to search for the corresponding genetic material in DNA from different cells. It was then found that oncogene-like material could be detected in different species throughout the animal kingdom, in fact even in simple organisms comprising only a few cells. Furthermore, it was shown that the gene had a fixed position in the chromosomes of a certain species, and that the gene, when it constituted part of the cellular genetic material, was divided into fragments (a mosaic gene) (Figure 1).Figure 1. The difference between an oncogene in a virus and in a cell. In retroviruses causing tumors there is a separate segment of transforming nucleic acid which has been derived from a cell. The cellular gene is split (a mosaic gene) whereas the oncogene in the virus is continuous.These findings led to the remarkable conclusion that the oncogene in the virus did not represent a true viral gene but a cellular gene which the virus had picked up far back during its replication in cells and carried along. This cellular gene was found to have a central function in the cells. It controlled their growth and division.
Through these studies of the abnormal, i.e. the diseased state, it was possible to elucidate critical normal cellular functions - a not uncommon situation in biomedical research. The original discovery of a cellular oncogene led to an intensive search for further similar genes. The explosive development of this field of research has led to the identification of more than 40 different oncogenes which direct different events in the complex signal systems that regulate the growth and division of cells. Changes in any one or more of these oncogenes may lead to cancer.
Balanced Cellular Interactions - A Biological Wonder
Symmetrical and asymmetrical, multicellular structures develop from the fertilized ovum by a process of differentiation about which only limited knowledge is available. In the fully developed individual carefully balanced conditions prevail. Damage of an organ elicits sophisticated repair processes which lead to restitution of the original condition of the organ. However, if a single cell escapes the network of growth control the result may be an abnormal local proliferation of cells or in the worst case a cancer implying the dissemination of cells running amok.
The development of a cancer is a complicated process involving several consecutive changes of the genetic material. Studies of cellular genes (proto-oncogenes) corresponding to the viral oncogenes, has started to shed light on the intricate systems which control normal cellular growth and division.
Cellular Oncogene Products Constitute Links in Signal Chains which Regulate Growth and Division of Cells
The regulation of growth and division of cells has turned out to be much more complicated than originally believed. Cellular oncogene products with different properties act in different positions of elaborate signal systems (Figure 2). In order to transmit signals from one cell to the other or from one cell to itself there are growth factors. These factors appear in the fluids surrounding cells. There are examples of oncogene products, viz. proteins produced in the cytoplasm, which can act as growth factors. Thus, it was found that the product of the sis1) gene was closely related to a previously identified growth factor PDGF (Platelet Derived Growth Factor).Figure 2. Oncogene products are links in signal chains that stretch from the cell surface to the genetic material in the cell nucleus. This chain is composed of (1) growth factors, (2) growth factor receptors, (3) signal transducing proteins in cell membranes, (4) phosphokinases in the cytoplasm and (5) proteins transported from the cytoplasm into the nucleus where they bind to DNA. The localization of different oncogene products (Sis, ErbB, Ras, Src, Myc) is schematically indicated.In order for a growth factor to be able to interact with a cell there has to be membrane structures, receptors, to which they can bind. There are several oncogene products which represent receptors in the cytoplasmic membrane of the cells, e.g. ErbA, Fms, Kit. These receptors have a unique enzymatic activity. They are so-called kinases with a capacity to phosphorylate (=add a phosphate group) the amino acid tyrosine. There are two more groups of oncogene products with phosphokinase activity; firstly tyrosine/phosphokinase which lack receptor function and is located at the inside of the cytoplasmic membrane, and secondly serine/threonine phosphokinase which is found in the cytoplasm.
Thus, oncogene products function as links in signal chains stretching from the surface of the cell to the genetic material in the nucleus. In the cytoplasm there is one more group of oncogene products. These are called Ras and are related to important cellular signal factors called G-proteins.
Finally, there is a large number of oncogene products which are located in the nucleus of the cell, i.e. Myc, Myb, Fos, ErbA and others. These products direct the transcription of DNA into RNA and therefore play a critical role in the selection of proteins to be synthesized by the cell.
Cancer - A Complex, Biological Sequence of Events
Changes in the genetic material constitute the basis for the development of all cancer. Generally there are several consecutive such changes which influence different steps in the signal chains described above. Therefore, one should à priori not expect to find one single clue to the mechanism of origin of cancer. However, application of the expanding knowledge in the oncogene field allows us to start comprehending the disharmonic orchestration behind abnormal cellular growth.
It is conceptually incorrect to speak about "cancer genes". However, historical circumstances explain why the oncogene terminology was introduced before a designation of the corresponding normal cellular genes was proposed. From the point of view of cancer the important matter is to compare oncogenes in normal cells and in tumor cells.
Oncogenes as a Cause of Cancer
The majority of oncogenes have been discovered in experimental studies using retroviruses. However, in a few cases oncogenes were identified by the use of an alternative technique, i.e. genetic material was isolated from tumor cells of non-viral origin and transferred (transfected) to other cells prapagated in culture. The cells receiving the DNA changed growth pattern, and further characterization of the transfected genetic material revealed the presence of oncogenes.
Two principally different forms of activation of oncogenes can be distinguished. Firstly, the normal cellular oncogene is hyperactive, and secondly the oncogene product is altered so that it can no longer be regulated in a normal way. There are several examples of these types of activation of oncogenes.
The discovery of oncogenes was as mentioned originally made by the use of retroviruses. This infers that genetic control elements in the virus itself can be responsible for the abnormal expression of the oncogene. However, in many cases it was found that alterations of the transferred oncogene contributed to its accentuated expression.
There are retroviruses which lack oncogenes but still can induce cancer. This is due to the fact that the virus has inserted its genetic material (in the form of DNA) very close to a normally occurring oncogene in the genetic material of the cell. This may result in an increased turn-over of the oncogene which may lead to abnormal cellular growth. The corresponding phenomenon can also occur in the absence of retroviruses. In this case there is a reorganization of the genetic material in the cell. Such a reorganization may occur within a single chromosome or by exchange of material between chromosomes. Repeated copying of a normal oncogene can lead to its amplification in the chromosome and consequently to increased amounts of the oncogene product. In certain brain tumors, glioblastomas, an amplified erbB-gene has been found, and a correspondingly increased neu-gene activity was shown in some forms of breast cancer.
The same effect can be seen when there is a reciprocal exchange of segments between chromosomes (translocation). Thus the normal myc-gene on chromosome 8 has been translocated to chromosome 14 in many patients with Burkitt's lymphomas (Figure 3). The insertion of the myc-gene containing chromosome segment is such that it becomes located close to hyperactive genes directing the synthesis of antibody protein. As a consequence the myc-gene becomes activated. Chromosome translocations occur in many different tumors. Chromosome analysis can therefore be of considerable value for localization of genetic changes in the genome critical for tumor development.Figure 3. Chromosome translocation in Burkitt's lymphoma. Segments have been exchanged between chromosomes 8 and 14 which has activated the oncogene myc.Oncogenes with point mutations have been observed in many tumors. These mutations may cause alterations in the amino acid composition of the gene product. A well-known example of such a modification is the exchange of amino acid 12 from glycine to valine in the ras gene product which has been observed in human tumor material. The mutation may also be somewhat more extensive leading to the absence of part of the protein (deletion). Different examples of modified oncogenes in human tumor material are given in Table I.The Importance of Viruses for Cancer in Man
Cancer is not a contagious disease. However, infectious agents like viruses can contribute to the origin of cancer. Thus, it is by use of retroviruses that most oncogenes were identified, the starting materials in such investigations often being highly specialized, experimentally derived tumors. It seems likely that retroviruses play a relatively limited role for the development of cancer under natural conditions. The only known example in man in which a retrovirus infection contributes to the origin of cancer is the HTLV-1 associated lymphomas which occur in Japan.
However, there are other kinds of viruses which can contribute to the development of tumors in man. All these viruses have DNA as their genetic material. As examples can be mentioned papillome (wart) viruses and Epstein-Barr virus, a type of herpes virus. Certain types of papillome viruses play a role for the development of cervical cancer in the genital tract, while Epstein-Barr virus is an important factor for the development of Burkitt's lymphomas in Africa and nasopharyngeal cancer in Asia. However, in all these cases factors in addition to the virus infections are required for the cancer to develop.
References
J.M. Bishop: Oncogenes. Scientific American, 1982, 246, 68-78.
T. Hunter: The Proteins of Oncogenes. Scientific American, 1984, 251, 60-69.
C-H. Heldin & B. Westermark: Tillväxtfaktorer och onkgener. Läkartidningen 1988, 85, 497-499.
E. Norrby: I: Våra virus. Virus och cancer. Allmänna Förlaget, 1987, sid. 66-74.
1) All oncogenes are identified by the use of three letter abbreviations. In addition cellular and viral oncogenes are sometimes distinguished by c- and v- prefixes, respectively, e.g. c-src and v-src.
[Photo Credit: UCSF]
The images of the Nobel Prize medals are registered trademarks of the Nobel Foundation (© The Nobel Foundation). They are used here, with permission, for educational purposes only.
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