An Interview with Professor Manuel Varela: Leroy Hood and the Human Genome

Oct 1, 2019 by

Michael F. Shaughnessy –

1) One name that seems to be synonymous with the Human Genome Project is Leroy Hood. Where was he born and where did he go to school?

Dr. Leroy (Lee) Hood was born in the city of Missoula, Montana, in the U.S., on the 10th day in the month of October, in the year 1938, to parents Myrtle Evylan Wadsworth and Thomas Edward Hood. Hood’s father, an alcoholic, was an engineer working for Mountain States Telephone Company, and his mother held a bachelor’s degree in home economics.

Hood would later say that his tenacity was due to his mother’s upbringing, encouraging Hood and his three younger siblings, Doral, Myron, and Glen, to stand up to their challenges, to do their very best, never to quit when times became difficult, and to figure out their own solutions to their problems. The Hood family, because of his father’s occupation, often moved, and as a child, Hood was consequently raised in several Montana-based cities like Ramsey and Butte, finally settling in the city of Shelby, MT.

Hood first attended Prescott elementary school in Missoula, and all three Hood children were known to have academically excelled in school. The young Hood learned to play the piano and clarinet. Later in high school at Shelby, Hood played sports, especially football in which at some point in his high school career the team took the state championship, with Hood as its quarterback. Hood flourished academically in high school, even becoming class president and being voted Best-all-Around in his class yearbook.

He later attributed his successes to several of his teachers. One such teacher was Mr. Cliff Olson, Hood’s teacher in science. Olson encouraged Hood and his doubtful parents to apply for admittance to the California Institute of Technology, commonly called Caltech. The Hood family had been leaning more towards Carleton College or Montana State University. Another high school teacher of note, Ms. Corlie Dunster, provided needed advice about the rigors of Caltech, which Hood appreciated only later on. Hood graduated from his Shelby-based high school as its valedictorian, in 1956.

Hood was accepted into Caltech with a scholarship funded by the General Motors Foundation despite not having had a course in calculus while in high school. Hood majored in Biology. He later speculated that his interest in human biology stemmed from his youngest brother, Glen, who had been born with Down syndrome. After much debate between his parents, Glen had been institutionalized. The experience had an influence on Hood’s choice of major at Caltech. Additionally, two Caltech faculty played a role in Hood’s choice of major. Drs. James Bonner, a biochemist who studied plants, and Ray Owen, a professor of immunology, both scientists of whom shared their enthusiasm for the biological sciences with their students.

At the time, Caltech was already famous for its students and faculty. Prominent scientists who were associated with Caltech included Drs. Richard Feynman, Murray Gell-Mann, Linus Pauling, Thomas Hunt Morgan, Max Delbrück, and George Beadle.

A biographer has noted that at Caltech Hood studied many long hours, taking courses such as Chemistry, Physics, and Math, in addition to his Biology courses. The foundation was to solidify his later entry into the arena of molecular biology. Hood also managed to join the Glee Club, play college football, and even do volunteer work giving guest lectures to high school students at the local YMCA. During his junior year, he took a trip abroad participating in a European tour with his brother, Myron, and his roommate, Eric Adelberger, who would become Hood’s life-long friend and physics professor in later years. In June of 1960, Hood took his undergraduate degree, his B.S. in Biology, with high academic honors.

After his college graduation, Hood moved to Baltimore, Maryland, in the U.S. to attend medical school at the prestigious Johns Hopkins School of Medicine, having turned down Harvard Medical School. An influential professor in medical school was a microbiologist, Dr. William Wood, Jr., who imparted the importance of the immune system upon his students. However, Hood became more interested in biomedical research, rather than in clinical medicine. Interestingly, Hood had been intrigued by technology, after having spent some research time in a laboratory at Johns Hopkins devoted to the study of neurophysiology, with its sophisticated equipment for measuring nerve conduction. Dr. Leroy Hood took his M.D. degree from Johns Hopkins in 1964.

Next, Dr. Hood moved back to Caltech to enter graduate school for the pursuit of the Ph.D. Living back in Pasadena, CA, Dr. Hood studied in the laboratory of newly minted faculty member Dr. William J. Dreyer, who would later become a world-famous immunologist, having formulated a ground-breaking notion for somatic recombination of genes involved in encoding antibodies. In 1963, Dr. Hood would become prof. Dreyer’s first Ph.D. student.

It was about this time, the 14th of December, in 1963, that Dr. Hood married his longtime girlfriend, Valerie Logan, who was a secondary school teacher.

Studying again at Caltech in the Dreyer laboratory as a graduate student, Dr. Hood was to recount in later years that he was given the sound advice of conducting research at the leading edge of science and, if possible, try inventing a new technological system. Prof. Dreyer had adopted a hands-off approach to his lab management policies, a policy that Dr. Hood would later adopt as well when he later became the head of his own laboratory.

Dr. Hood’s first project for his graduate thesis involved an essential problem regarding antibodies, called at the time as the Bence-Jones proteins. The proteins were strongly believed to be mostly responsible for conferring an immune-based protection from pathogens and cancer. The problem involved determining how the antibody managed to harbor vast diversity to recognize antigens and how it somehow maintained a consistency in neutralizing and destroying these antigens.

New ideas were emerging about these antibodies, the Bence-Jones proteins, and their ability to consistently destroy an incredibly diverse array of pathogens. One idea held that the diversity and constancy of antibodies was performed by the joining together of separate genes, one gene of which accounted for the diversity, called a variable region, and the other gene, called a constant region, accounting for the constancy in effecting antigen destruction. The hypothesis became known as the somatic recombination mechanism.

Towards this, Dr. Hood needed to isolate the proteins and determine their amino acid sequences. Though the protein isolation work was labor-intensive, Dr. Hood had managed somehow to purify a sparse few milligrams of the Bence-Jones antibody proteins.

Then, a life-changing incident occurred for Dr. Hood regarding the Bence-Jones project. His graduate thesis advisor, Dr. Dreyer, walked into the laboratory and announced that Dr. Hood was taken off of the project.

Prof. Dreyer felt that, as a graduate student, the somatic recombination hypothesis was too risky for him to examine. It was a controversial idea. There were two huge problems with the somatic recombination hypothesis. First, it violated the so-called “one-gene leads to one protein” notion of Drs. George Beadle and Edward Tatum. It was a Nobel Prize-winning notion, after all. Second, the somatic recombination idea went totally against the widespread belief that in all somatic cells of an organism, the DNA should be the same; that is, the DNA is unchanged in non-sex cells.

An established postdoctoral fellow, Dr. J. Claude Bennett, who was working in Dr. Bennett’s laboratory, was given the project. Together, Drs. Bennett and Dreyer set out to test the so-called Dreyer-Bennett hypothesis of somatic recombination leading to antibody diversity. The new work was published in 1965, leaving out Dr. Hood as a co-author.

Although, on the one hand, Dr. Hood never really forgave Dr. Dreyer for the slight, it nevertheless spared Dr. Hood from the onslaught that was to come to Drs. Bennett and Dreyer—the work was widely and quite harshly criticized from all scientific circles. Yet, despite being spared from the forefront of the controversy, Dr. Hood regretted the omission for many years.

Dr. Hood’s new graduate thesis work was relegated to the protein purification of the Bence-Jones proteins and in simply providing further supporting evidence for the somatic recombination model of antibody diversity, a hypothesis that was initially formulated by Drs. Bennett and Dreyer. Thus, when Dr. Hood completed his Ph.D. project, the significance of the findings had been somewhat diluted. Consequently, he had neglected to write up the final version of his thesis for a while, leaving instead for a new post, in 1967, as a senior investigator, at the National Institutes of Health (NIH), in order to satisfy a public service activity required by the draft board in lieu of serving time in the ongoing Vietnam War. Nevertheless, at NIH, Dr. Hood managed to find the time to complete the thesis write-up and defend it, officially taking his Ph.D. from Caltech in 1968.

2) Apparently, he did not work alone- but he and his co-workers developed a type of DNA gene sequencer and synthesizer- what exactly is this and why is it important?

Both machines invoked automation. The DNA gene sequencer (sometimes called a DNA sequenator) was designed to determine the nucleotide sequences along a DNA chain for the purpose of knowing what gene products, i.e., proteins, the genes encoded. The DNA sequences could then be compared, and the evolution and relationships of groups of organisms could be examined more closely. The DNA synthesizer machine was invented for the purpose of making stretches of DNA of desired sequences, which may be used, for example, to make DNA probes, for diagnostics, cloning, or mutagenesis. The making of DNA with known and desired nucleotide sequences allowed biomedical scientists to progress in their individual fields of study.

To sequence or synthesize DNA by conventional means, it necessitated hands-on, labor-intensive laboratory work. Every aspect of each task had to be performed by hand. The toil was slow, cumbersome, and tedious. The automation in the machines provided the everyday laboratory work that had been required to sequence or synthesize DNA. The automation could replace the laborious effort.

One of the key figures who participated in the development of an automated DNA sequencer included Mike Hunkapiller, who in 1978 had been a postdoctoral fellow in Dr. Hood’s laboratory at Caltech where he (Hood) had already been a faculty and investigator. Hunkapiller had already proven his acumen in the development of the protein sequencer. He had had expertise both in chemistry and engineering, skills which would aid significantly in enhancing automation of DNA sequencing.

Another key figure was Mike’s brother, Tim Hunkapiller, who joined the Hood laboratory at Caltech as a graduate student, also in 1978. Shortly after his arrival at Pasadena, Tim Hunkapiller had formulated an innovative idea. His brainstorm took the form of a modification of the Frederick Sanger method for DNA sequencing. In Dr. Sanger’s original technique, it involved detecting the DNA fragments using radioactively labeled nucleotides. Tim Hunkapiller’s idea was instead to use fluorescently-labeled nucleotides to accomplish the needed DNA fragment detection. The Hunkapiller brothers worked together to realize Tim’s idea. The new modification permitted the sequencing to be performed with more than one sample at a time.

A new prominent figure in the push to automate DNA sequencing in Dr. Hood’s laboratory was Dr. Lloyd Smith, who had taken his Ph.D. from Stanford, CA, in the area of biophysics and had expertise in computer programing, optics of lasers, and physical chemistry. These elements would all be needed to design the automated DNA sequencer in an efficacious manner.

Dr. Smith hired a team of personnel devoted to the task of working up the chemistry. The team included Chris Dodd, Peter Hughes, Robert Kaiser, and Jane Sanders. They helped to sort out the fine-tuning needed to get accurate fluorescent signatures for each of the nucleotides along the DNA chain.

An additional person on the Hood team was Kip Connell, who had previously been an engineer at Hewlett-Packard and was at ABI, which had formerly been Applied Biosystems, Inc. Connell had developed a critical optic device for the detection of one remaining fluorescent dye in the DNA sequencer machine.

Unfortunately, when the groundbreaking work was published in June of 1986, Connell was left out of the co-authorship on their seminal Nature paper. It was considered a glaring slight. To make matters worse, Dr. Hood never mentioned by name any of the others on the team during a press conference about the discovery. The rift upended the relationship between Hood and the others on his team. It paved the way, thus, for other investigators take the lead in pursuing automated DNA sequencing.

3) Then aligned with the above is the protein sequencer and synthesizer- how do all these work together?

Together, with the DNA synthesizer and the DNA sequencer mentioned above, the protein synthesizer and protein sequencer constitute a quartet of biomedically necessary scientific research instruments. Dr. Hood was influential in contributing to each of these advancements.

The protein synthesizer is also an automated machine that will chemically connect amino acids together to form polypeptide chains of varying lengths. Early on in its history of development, the number of amino acids that could be made was relatively low, but with time, as improvements were incorporated into the early prototypes, the amino acid numbers were enhanced. In more modern times, about 100 amino acids can be chemically connected to each other. Furthermore, new advancements have been made in which chemically-made peptides can be connected to each other to produce even larger polypeptides and complete proteins.

These short peptide could be used for various purposes. For instance, a short synthetic peptide could be used as a probe to recognize and bind a desired protein. Alternatively, new peptides could be made in order to occupy the binding site of a deleterious enzyme and inactivate it for potential therapeutic purposes. Biochemists can also study more closely the catalytic behaviors of synthetic enzymes. Furthermore, biomedical investigators may choose to design new stretches of amino acids along a protein chain in which the newly synthesized chain can fold into a three-dimensional shape that contains certain desired activities. The types of biomedical research projects that could be enhanced by the availability of proteins with desired amino acid sequences seem endless.

A proper context of protein-synthesizing technology is important to consider here. Although investigators may be able to make proteins artificially in which the end-products have about 100 or more amino acids, the laboratory process may take days, if all works well, of course. On the other hand, microbes, e.g., bacteria or yeast come to mind, have the ability to biosynthesize similarly sized proteins in only a few seconds! Thus, protein chemists still have a long way to go in order to catch up with our microbial friends.

The protein sequencer, also known as a sequenator, permitted biomedical scientists, such as protein biochemists and even cell biologists or molecular biologists, to determine the sequences of amino acids along a protein chain. With about 20 well-known amino acids in our existing repertoire and the varying degrees of chain lengths, the sequences and types of proteins can become extremely diverse.

New technologies for determining protein sequences of amino acids that were developed prior to automation relied on brute force chemical and biochemical methods. The work was laborious, and the lengths of the amino acids was relatively short, and perhaps only a handful of amino acids could be sequenced. Early on in its history of development, perhaps as many as 20 amino acids could be sequenced.

Automation permitted more amino acids to be sequenced along a given polypeptide chain. Additionally, much less protein was needed to conduct the automated analyses, compared with earlier conventional methods. Today, about 100 amino acids can be directly sequenced with newer technologies, such as mass spectrometry.

With their new protein sequenator in hand, Dr. Hood and his colleagues were able to show early on, in 1980, how proteins from various species of organisms could be studied, from mice to humans. One of the first proteins they sequenced was interferon, a short protein known to fight viral infections and cancer. Knowledge of the amino acid sequence was then used to elucidate the genetic element, i.e., the gene that was responsible for encoding the interferon protein. Molecular biologists could then use the gene to produce large quantities of interferon in biotechnology labs and to purify the artificially made proteins.

A more efficient method of deducing protein sequences, however, relies first on determining the DNA sequences of the gene that encode the proteins. This is where DNA sequenators can significantly help in the effort. The ability to determine DNA sequences has been tremendously enhanced by many orders of magnitude. In fact, biomedical scientists have moved from determining DNA sequences for individual genes to those of entire genomes to those of entire collections of genomes (metagenomics) that are found in various niches.

With the aid of a computer, the information gleaned from the DNA sequences of genes and of genomes can be easily used to translate into protein sequences. Whether one gains the protein sequences directly by protein sequencers or indirectly by DNA sequences first, the process can delineate a vast wealth of information.

For example, knowledge of protein sequences can be used to formulate structures of proteins, which can then be used to study the protein functions. We can learn where a protein resides in a cell or a tissue, depending on whether the protein has location-based sequences, i.e., amino acid sequences that specify where a protein is to be delivered. We may learn how a protein has evolved using its sequence and comparing it to those sequences of all other known proteins. Along these lines, if a new protein of unknown function is discovered, then we may use its amino acid sequence to evaluate its evolutionary history, comparing its sequence with those sequences contained within vast protein sequence databases in order to find its function.

Furthermore, by studying the evolutionary relationships of proteins, biomedical investigators may discover specific sequences that are shared with seemingly unrelated proteins. Such shared sequences are considered conserved by evolution, i.e., homologous, shedding light on the potential mechanisms of protein action. We may then test the functions predicted by these shared conserved amino acid sequence motifs. We may even be able to coax the proteins to enhance their functional efficiencies or to conduct new desired functions, such as for disease preventive chemotherapy or biotechnology.

4) Dr. Hood’s research seemed to focus on cancer biology–prostate, ovarian, breast and liver cancer—why these specific areas?

Dr. Hood’s interest in cancer stems from his early days as a graduate student, focusing on so-called myeloma cells, which were a form of bone marrow cancer. He had used these cancer cells to isolate the Bence-Jones proteins, also known as a type of antibody. These particular type of cancer cells had been fused with specific antibody-producing cells, called plasma cells, which were derived from B-lymphocytes. The fused cells were now immortal and could be used for studying the antibodies. His interest in immunology is closely related to cancer, as the immune system is a critical defense mechanism in the fight against cancer.

Dr. Hood’s determination of the amino acid sequence for several members of the interferon family, in 1980, garnered a significant amount of attention, not only amongst his biomedical scientist colleagues but also amongst members of the press and then potential benefactors. Dr. Hood’s fame among the public was an opportunity for him to have an influence on the direction of research. He gave compelling public speeches in which members of the audience were eager entrepreneurs, venture capitalists, and wealthy bankers. He spoke of the remarkable potential for biotechnology, making sure to mention, among other ailments, promising avenues for treating cancer.

In 1983, Dr. Hood, working with Dr. Hunkapiller, used their protein sequenator to find the amino acid sequence for a protein called platelet-derived growth factor (PDGF). They then showed that the PDGF was somehow connected to an oncogene, that is, a cancer-causing gene! The discovery started in a new field of cancer biology, a field that is still a hot topic even to this day.

The advent of DNA sequencing on a massive scale, i.e., high-throughput sequencing, opened a new area of focus, namely, that of genome sequencing and its potential promise for cancer treatments. This is where cancers like those involving the prostate, the ovary, the breast or of the liver came into play with the putative benefactors. One such benefactor was Michael Milken, a wealthy Wall Street magnate and a past survivor of prostate cancer. In the mid-1990s, Milken and Dr. Hood hit it off, finding that they had common interests and personalities.

The collaboration between benefactor Milken and scientist Dr. Hood, however promising, proved to be contentious. It was short-lived, with only a few publications coming out of the massive effort and with no treatment for prostate cancer discovered after three years of work. The reasons for collaborative derailment are unclear. Perhaps the unmatched application of the business model to a scientific endeavor, however worthy a cause, cancer, resulted in the clash. The business model required set schedules for specific accomplishments, and scientific arena dealt with the unknown frontiers of science. Another reason that has been put forth is that the consortium itself lacked robust management. Whatever the reasons were, the collaboration was at an end, in 1998.

In the years since the consortium terminated, great strides have been made in all of these areas of cancer biology, cancers of the prostate, the breast, the liver, and the ovary. Dr. Hood’s approach, namely, examine the oncogenes encoded in the DNA and their expressed protein products in these and other cancer tissues was an insightful one. In more modern times, biomedical scientists have gained an understanding regarding the failures of cell cycle growth checkpoints, from both molecular and cellular standpoints. Nevertheless, since cancer includes a vast constellation of specific diseases, depending on the type of cell, tissue, or organ involved, much work remains to be completed before clinicians and researchers can get a handle on these terrible illnesses.

5) What is meant by “prion disease in mice”? And why is this important?

The term prion is derived from their characterization. It is short for proteinaceous infectious agent. Discovered by Dr. Stanley Prusiner, Nobel Laureate, the prions were known to consist primarily, if not wholly, of protein, and they were infectious all on their own, without the help of any sort of nucleic acids, such as RNA or DNA. In mice, the prions caused a form of the disease characterized by a constellation of holes in their brains. The infected brains took the form of a sponge-like consistency. These pathological conditions in mice was vital because they served as useful model systems for study in higher organisms.

Other such higher organisms that were susceptible to the prions included cows (mad cow), deer, and humans. It was found that in these and other types of hosts, the prion proteins would fold-up in an improper manner, causing them to produce more abnormal prions and somehow result in the holes called plaques within their brains.

Dr. Hood’s involvement, starting in the early 1980s, was that he and his colleagues used the protein sequenator to elucidate the entire amino acid sequence of the prion protein, which had been purified first. Dr. Prusiner’s laboratory collaborated with that of Dr. Hood’s, and together they published the new work.

They then used the protein sequence to search for the corresponding gene DNA, and they cloned the relevant gene. They found that the prion gene was present in the genomes of their hosts. Next, they determined that the pathological version of the prion protein, called scrapie, was distinct than the regular version of the same protein. Surprisingly, they found that the sequences were virtually identical! The primary difference was that the scrapie and the healthy protein were structurally dissimilar.

They even managed to examine how sugars would bind to the prion proteins, a biochemical process called glycosylation. They learned which amino acids of the prion protein were attached to by the sugars. They purified prion proteins from a variety of animal hosts, and they used antibodies to delineate the structural differences between the regular cellular versions from the abnormal scrapie versions. Using traditional biochemical methodology, they learned of new proteins that were making bonds with the prion proteins. These types of studies went into the 1990s. At some point, Dr. Hood grew weary of the work. He was a type of scientist who was continually coming up with new ideas about disparate fields of study, and he did not wish to become fastened with prion biology for the remainder of his career. While the progress of the prion work was fascinating, if not groundbreaking, he felt the needed to move onto other areas of study.

6) Now, he apparently worked with “hematopoietic stem cells.” Can you describe these and why they are important?

The so-called hematopoietic stem cells are of tremendous importance. One of the biggest reason for their relevance is because they are pluripotent. That is, they have the potential to develop into functionally specialized cells.

For example, they may give rise to brain cells, or liver, or kidney, whatever cell one desires or needs. Much work is still being conducted in this area to take stem cells and coax them to become heart cells, bone cells, pancreatic cells, etc.

Dr. Hood started his work with pluripotent hematopoietic stem cells in the early 2000s. They searched for genes that were expressed in specialized adult mice cells and compared with those expressed in the stem cells. They wanted to know the gene expression programs involved in the cellular development of a stem cell to a more specialized neuronal cell. They then cloned the genes that had shown expression during their cellular developments. One of the critical organs that Dr. Hood’s laboratory and those of his collaborators focused on was the kidney. They examined how the hematopoietic stem cells differentiated into kidney cells while delineating the genes and their corresponding proteins that were responsible for the differentiation.

The work proved to be fruitful throughout the 2000s. The hematopoietic stem cell studies were focused on cancer. In so doing, a new field of study emerged—systems biology. Dr. Hood has been credited with starting the new branch of biomedical sciences.

The new discipline, systems biology, seeks to integrate the various components inherent in living organisms with each other. Basically, biomedical scientists want to know how organs, tissues, pathways, genes, and molecules, etc., are connected to each other. It represents a holistic view, as opposed to a reductionist approach in which individual components are separated from the rest of the body’s systems for study. The methodological approaches include bioinformatics, mathematics, molecular biology, biochemistry, physiology, and cell biology. Stems cells, with their undifferentiated states with no specialization to them and their great potential to develop into differentiated, specialized states (pluripotency) can be at the very center of the systems biology field.

Recently, in 2018, pluripotent hematopoietic stem cells were used to produce cells that secreted the hormone insulin. The new pancreatic cells were then cultured and implanted into diabetic mice, and their diabetes condition was alleviated. The mice had reacquired normal levels of blood glucose! The field of stem cell biology may, in the future, show even more promising avenues for treatment of biomedical diseases.

7) Blood proteins and nanotechnology- how are these interlinked?

The nanotechnology discipline emerged from the systems biology field, in which the seemingly disparate components that constitute a living being are connected to each other via molecular interactions. It can also be used for the purpose of detection of elements involved in connecting the various cellular and molecular systems. Another application of nanotechnology is to visualize pathological states within the context of healthy tissue. The nanotechnology field also seeks to provide targeted treatment of diseases by focusing on the precise components that are involved in the illnesses and providing a nano-based therapy delivery scheme.

As your question above alludes, nanotechnology can be used to measure levels of specific proteins in the blood. Such approaches have been referred to as sensor systems. The sensors may take the form of probes consisting of elements (e.g., DNA, proteins, antibodies, etc.) which specifically bind the desired proteins and which are connected to nano-sized wires that are strewn across a glass slide. A sample of blood will be passed through the glass slide containing the probe with the nanowires. If the desired blood protein is detected by the probe, the nanowire sends an electrical signal, thus announcing the presence of the desired protein.

The announcement of the desired protein’s presence can take the form of an image. The probe that’s attached to a nano-based cantilever will alter its orientation. The altered cantilever can be visualized, and the signal will be sent to the observer.

Nanotechnology can be used to highlight cancer within the context of healthy animal tissue, lighting up the cancerous tissue within the host. Nanocrystals called quantum dots that are made up of detectable metals like cadmium, or even mercury will fluoresce distinctly, depending on whether a cancer-specific molecule, like an anti-cancer antibody, thus, allowing visualization of cancerous tissue inside an intact animal host.

Lastly, nanotechnology can be used to deliver specific chemotherapy in a targeted fashion. Individual nano-sized containers harboring a therapeutic agent can be connected to individual probes that are specific to the tumor, or to the pathological tissue within a host. The delivery system will specifically recognize the target and bind to it and release the therapeutic agent.

8) Apparently Dr. Hood was also interested in Diabetes-specifically Type 1–for the uninitiated- what is the difference between Type 1 and Type 2, and what did Dr. Hood find in his research?

As you indicated, there are two main categories of diabetes, Type 1 and Type 2. Type 1 diabetes is also called insulin-dependent diabetes mellitus (IDDM). It often manifests itself in children. It is autoimmune in nature. Auto-antigens may include insulin itself or other seemingly unrelated proteins, such as glutamate decarboxylase or peripherin, for example. Type 2 diabetes is also called adult-onset or non-insulin-dependent diabetes mellitus (NIDDM). Type 2 is often correlated with obesity, diet, or genetic inheritance. Recently, type 2 was associated with inflammation due to infection with the bacterium Staphylococcus aureus.

Dr. Hood’s involvement with diabetes started in the early 1990s. The research group examined the repertoire of so-called beta chains along the T-lymphocyte receptors in patients with type 1 IDDM, and disappointingly found no differences between these patients and individuals without the IDDM. Next, in 2002, Dr. Hood participated in a large consortium in which they examined type 1 diabetics for the presence of specific genes believed to place individuals at risk for diabetes and for the presence of specific autoantibodies to autoantigens. The findings revealed certain molecular genetic markers for type 1 diabetes. Expanding on these genetic markers, the group focused on an immune system component, the major histocompatibility complex (MHC) in mice, known as human leukocyte antigen (HLA) in humans, and one of its autoantigen targets called the inositol triphosphate receptor gene, publishing the work in 2006. More recent work has focused on particular metabolite markers in the human gut microbiome that are somehow linked to diabetes. As of this writing work in this critical area is still being actively pursued.

9) What have I neglected to ask about this fascinating scientist?

Dr. Hood has proposed a vision for the future of medical practices, namely that of P4 medicine. The four Ps include medicine that (1) makes predictions, (2) advocates prevention, (3) invokes personalized medicine and proposes (4) participatory practices amongst patients and physicians alike. Towards this effort, he has helped to establish an entire institute devoted to the implementation of the P4 mode of practicing this type of medicine.

Interestingly, while Dr. Hood, at over 80 years old, has garnered numerous awards and accoalades for his significant biomedical science contributions, such as the preamble to the Nobel, the Albert Lasker Award, to date, the coveted Nobel has, nevertheless, eluded him.

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